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January 12, 2007: Jennifer Strange died after drinking nearly 2 gallons (7.6 liters) of water in an attempt to win a Nintendo Wii. The KDND radio stations morning show, the Morning Rave, held an on-air contest entitled "Hold Your Wee for a Wii," in which contestants were asked to drink as much water as they could without urinating. The DJs were made aware of the dangers but did not inform the contestants. KDNDs parent company, Entercom Sacramento LLC, was subsequently ordered to pay $16,577,118 in damages to Stranges family. March 11, 2020: Zachary Sabin, an 11-year-old child, died after being forced to drink almost three liters of water in just four hours by his parents. They thought his urine was too dark, so they made him drink water until he threw up. See also
== References == | These eruptions wear down the lava dome holding the magma down, and it disintegrates, leading to much more quiet and continuous eruptions. Thus an early sign of future Vulcanian activity is lava dome growth, and its collapse generates an outpouring of pyroclastic material down the volcanos slope. Deposits near the source vent consist of large volcanic blocks and bombs, with so-called "bread-crust bombs" being especially common. These deeply cracked volcanic chunks form when the exterior of ejected lava cools quickly into a glassy or fine-grained shell, but the inside continues to cool and vesiculate. The center of the fragment expands, cracking the exterior. However the bulk of Vulcanian deposits are fine grained ash. The ash is only moderately dispersed, and its abundance indicates a high degree of fragmentation, the result of high gas contents within the magma. In some cases these have been found to be the result of interaction with meteoric water, suggesting that Vulcanian eruptions are partially hydrovolcanic.Volcanoes that have exhibited Vulcanian activity include:
Sakurajima, Japan has been the site of Vulcanian activity near-continuously since 1955. Tavurvur, Papua New Guinea, one of several volcanoes in the Rabaul Caldera. Irazú Volcano in Costa Rica exhibited Vulcanian activity in its 1965 eruption. Anak Krakatoa, Indonesia, repeated vulcanian activities since its rise in 1930 until the present time.Vulcanian eruptions are estimated to make up at least half of all known Holocene eruptions. | 0-1
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The remaining variation is attributed to the environment and other genes that modify the mechanism of HD. About 36 to 39 repeats result in a reduced-penetrance form of the disease, with a much later onset and slower progression of symptoms. In some cases, the onset may be so late that symptoms are never noticed. With very large repeat counts (more than 60), HD onset can occur below the age of 20, known as juvenile HD. Juvenile HD is typically of the Westphal variant that is characterised by slowness of movement, rigidity, and tremors. This accounts for about 7% of HD carriers. Inheritance
Huntingtons disease has autosomal dominant inheritance, meaning that an affected individual typically inherits one copy of the gene with an expanded trinucleotide repeat (the mutant allele) from an affected parent. Since the penetrance of the mutation is very high, those who have a mutated copy of the gene will have the disease. In this type of inheritance pattern, each offspring of an affected individual has a 50% risk of inheriting the mutant allele, so are affected with the disorder (see figure). This probability is sex-independent.Trinucleotide CAG repeats numbering over 28 are unstable during replication, and this instability increases with the number of repeats present. This usually leads to new expansions as generations pass (dynamic mutations) instead of reproducing an exact copy of the trinucleotide repeat. | A Bakers cyst, also known as a popliteal cyst, is a type of fluid collection behind the knee. Often there are no symptoms. If symptoms do occur these may include swelling and pain behind the knee, or knee stiffness. If the cyst breaks open, pain may significantly increase with swelling of the calf. Rarely complications such as deep vein thrombosis, peripheral neuropathy, ischemia, or compartment syndrome may occur.Risk factors include other knee problems such as osteoarthritis, meniscal tears, or rheumatoid arthritis. The underlying mechanism involves the flow of synovial fluid from the knee joint to the gastrocnemio-semimembranosus bursa, resulting in its expansion. The diagnosis may be confirmed with ultrasound or magnetic resonance imaging (MRI).Treatment is initially with supportive care. If this is not effective aspiration and steroid injection or surgical removal may be carried out. Around 20% of people have a Bakers cyst. They occur most commonly in those 35 to 70 years old. It is named after the surgeon who first described it, William Morrant Baker (1838–1896). Signs and symptoms
Symptoms may include swelling behind the knee, stiffness, and pain. If the cyst breaks open, pain may increase, and there may be swelling of the calf. Rupture of a Bakers cyst may also cause bruising below the medial malleolus of the ankle (Crescent sign). Cause
In adults, Bakers cysts usually arise from almost any form of knee arthritis (e.g., rheumatoid arthritis) or cartilage (particularly a meniscus) tear. Bakers cysts in children do not point to underlying joint disease. | 0-1
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Because taste disorders can have detrimental effects on a patients quality of life, more research needs to be conducted concerning possible treatments such as zinc supplementation. Altering drug therapy
The effects of drug-related dysgeusia can often be reversed by stopping the patients regimen of the taste altering medication. In one case, a forty-eight-year-old woman who had hypertension was being treated with valsartan. Due to this drugs inability to treat her condition, she began taking a regimen of eprosartan, an angiotensin II receptor antagonist. Within three weeks, she began experiencing a metallic taste and a burning sensation in her mouth that ceased when she stopped taking the medication. When she began taking eprosartan on a second occasion, her dysgeusia returned. In a second case, a fifty-nine-year-old man was prescribed amlodipine in order to treat his hypertension. After eight years of taking the drug, he developed a loss of taste sensation and numbness in his tongue. When he ran out of his medication, he decided not to obtain a refill and stopped taking amlodipine. Following this self-removal, he reported experiencing a return of his taste sensation. Once he refilled his prescription and began taking amlodipine a second time, his taste disturbance reoccurred. These two cases suggest that there is an association between these drugs and taste disorders. This link is supported by the "de-challenge" and "re-challenge" that took place in both instances. It appears that drug-induced dysgeusia can be alleviated by reducing the drugs dose or by substituting a second drug from the same class. | The LIN28 gene also plays a role in wound healing. It is dormant in most mammals. Also, the proteins MG53 and TGF beta 1 play important roles in wound healing. Wound healing
In response to an incision or wound, a wound healing cascade is unleashed. This cascade takes place in four phases: clot formation, inflammation, proliferation, and maturation. Clotting phase
Healing of a wound begins with clot formation to stop bleeding and to reduce infection by bacteria, viruses and fungi. Clotting is followed by neutrophil invasion three to 24 hours after the wound has been incurred, with mitoses beginning in epithelial cells after 24 to 48 hours. Inflammation phase
In the inflammatory phase, macrophages and other phagocytic cells kill bacteria, debride damaged tissue and release chemical factors such as growth hormones that encourage fibroblasts, epithelial cells and endothelial cells which make new capillaries to migrate to the area and divide. Proliferative phase
In the proliferative phase, immature granulation tissue containing plump, active fibroblasts forms. Fibroblasts quickly produce abundant type III collagen, which fills the defect left by an open wound. Granulation tissue moves, as a wave, from the border of the injury towards the center.As granulation tissue matures, the fibroblasts produce less collagen and become more spindly in appearance. They begin to produce the much stronger type I collagen. Some of the fibroblasts mature into myofibroblasts which contain the same type of actin found in smooth muscle, which enables them to contract and reduce the size of the wound. | 0-1
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The impairment of mitochondrial electron transport can result in higher levels of oxidative stress and release of reactive oxygen species.Glutamine is known to be excitotoxic when present in large amounts, that can cause damage to numerous cellular structures. Excessive glutamine is not found in HD, but the interactions of the altered huntingtin protein with numerous proteins in neurons lead to an increased vulnerability to glutamine. The increased vulnerability is thought to result in excitotoxic effects from normal glutamine levels. Macroscopic changes
Initially, damage to the brain is regionally specific with the dorsal striatum in the subcortical basal ganglia being primarily affected, followed later by cortical involvement in all areas. Other areas of the basal ganglia affected include the substantia nigra; cortical involvement includes cortical layers 3, 5, and 6; also evident is involvement of the hippocampus, Purkinje cells in the cerebellum, lateral tuberal nuclei of the hypothalamus and parts of the thalamus. These areas are affected according to their structure and the types of neurons they contain, reducing in size as they lose cells. Striatal medium spiny neurons are the most vulnerable, particularly ones with projections towards the external globus pallidus, with interneurons and spiny cells projecting to the internal globus pallidus being less affected. HD also causes an abnormal increase in astrocytes and activation of the brains immune cells, microglia.The basal ganglia play a key role in movement and behavior control. Their functions are not fully understood, but theories propose that they are part of the cognitive executive system and the motor circuit. | Nicardipine (Cardene) is a medication used to treat high blood pressure and angina. It belongs to the dihydropyridine class of calcium channel blockers. It is also used for Raynauds phenomenon. It is available in by mouth and intravenous formulations. It has been used in percutaneous coronary intervention. Nicardipine has been used as an alternative to sodium nitroprusside, especially because sodium nitroprusside is light sensitive and a fresh solution must be prepared. Its mechanism of action and clinical effects closely resemble those of nifedipine and the other dihydropyridines (amlodipine, felodipine), except that nicardipine is more selective for cerebral and coronary blood vessels. Nicardipine also has a longer half-life than nifedipine. Nicardipine was approved by the FDA in December 1988. The patent for both Cardene and Cardene SR expired in October 1995.It was patented in 1973 and approved for medical use in 1981. See also
Calcium channel blocker toxicity
== References == | 0-1
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The pain associated with the inflamed appendages is located in the left and sometimes in the right lower abdominal quadrant. Diagnosis of epiploic appendagitis can be challenging due to its infrequency. Diagnosis
Epiploic appendagitis is more common in patients older than 40 years of age; however, it can occur at any age. "The reported ages range from 12 to 82 years. Men are slightly more affected than woman." Patients with epiploic appendicitis describe having a localized, strong, non-migratory sharp pain after eating. Patients generally have tender abdomens as a symptom. Symptoms do not include fever, vomiting, or leukocytosis. The pain is typically located in the right or left lower abdominal quadrant. When there is pain in the right lower quadrant, it can mimic appendicitis; however, it more commonly mimics diverticulitis, with pain present on the left side. Differential diagnosis
There are several conditions that mimic the symptoms of epiploic appendicitis. Omental infarction: Omental infarction is uncommon reason for acute abdomen. It is similar to acute appendicitis. The pain is of a few days duration centering in the right lower or upper quadrant. Imaging is required to obtain an accurate diagnosis due to the common misdiagnosis of omental infarction as appendicitis or cholecystitis. Omental infarction occurs commonly in pediatric patients approximately 15 percent of cases. The most frequent cause of non- torsion related omental infarction is due to trauma as well as thrombosis or the omental veins. The predisposition for omental infarction includes obesity, strenuous activity, congestive heart failure, digitalis administration, recent abdominal surgery and trauma. | Mexiletine (INN) (sold under the brand names Mexitil and Namuscla) is a medication used to treat abnormal heart rhythms, chronic pain, and some causes of muscle stiffness. Common side effects include abdominal pain, chest discomfort, drowsiness, headache, and nausea. It works as a non-selective voltage-gated sodium channel blocker and belongs to the Class IB group of anti-arrhythmic medications. Medical uses
Mexiletine has several uses including the treatment of abnormal heart rhythms or arrhythmias, chronic pain, and myotonia. In general when treating arrhythmias, mexiletine is reserved for use in dangerous heart rhythm disturbances such as ventricular tachycardia. It is of particular use when treating arrhythmias caused by long QT syndrome. The LQT3 form of long QT syndrome is amenable to treatment with mexiletine as this form is caused by defective sodium channels that continue to release a sustained current rather than fully inactivating, however other forms of long QT syndrome can also be treated with this medication.Mexiletine has been used to treat chronic pain and may also be used to treat muscle stiffness resulting from myotonic dystrophy (Steinerts disease) or nondystrophic myotonias such as myotonia congenita (Thomsen syndrome or Becker syndrome). Adverse effects
Common side effects of mexiletine include abdominal pain, chest discomfort, drowsiness, headache, nausea and skin reactions. Uncommon or rare side effects include seizures and liver dysfunction. Pharmacology
Mexiletine is an oral analogue of lidocaine. It is a class IB antiarrhythmic which shorten the refractory period and action potential duration (APD). Decrease in APD more than that of ERP so there is increase ERP/APD ratio. | 0-1
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In particular, people with Williams syndrome experience challenges in visual-motor skills and visuospatial construction. Most affected people are unable to spatially orient themselves and many experience difficulty when given a task that requires even the most basic visual problem-solving. Many adults with Williams syndrome cannot complete a simple six-piece puzzle designed for young children, for example. These visuospatial deficits may be related to damage to the dorsal cortical pathway for visual processing.Despite their physical and cognitive deficits, people with Williams syndrome exhibit impressive social and verbal abilities. Williams patients can be highly verbal relative to their IQ. When children with Williams syndrome are asked to name an array of animals, they may well list a wild assortment of creatures such as a koala, saber-toothed cat, vulture, unicorn, sea lion, yak, ibex and Brontosaurus, a far greater verbal array than would be expected of children with IQs in the 60s. Some other strengths that have been associated with Williams syndrome are auditory short-term memory and facial recognition skills. The language used by people with Williams syndrome differs notably from unaffected populations, including people matched for IQ. People with Williams syndrome tend to use speech that is rich in emotional descriptors, high in prosody (exaggerated rhythm and emotional intensity), and features unusual terms and strange idioms.Among the hallmark traits of people with Williams syndrome is an apparent lack of social inhibition. | Life expectancy is less than that of the general population, mostly due to the increased rates of heart disease. Signs and symptoms
The most common symptoms of Williams syndrome are heart defects and unusual facial features. Other symptoms include failure to gain weight appropriately in infancy (failure to thrive) and low muscle tone. People with WS tend to have widely spaced teeth, a long philtrum, and a flattened nasal bridge.Most people with WS are highly verbal relative to their intelligence, and are often very sociable, having what has been described as a "cocktail party"-type personality. People with Williams syndrome hyperfocus on the eyes of others in social engagements. Physical
People with WS experience many cardiac problems, commonly heart murmurs and the narrowing of major blood vessels, as well as supravalvular aortic stenosis. Other symptoms may include gastrointestinal problems, such as severe or prolonged colic, abdominal pain and diverticulitis, nocturnal enuresis (bed wetting) and urinary difficulties, dental irregularities and defective tooth enamel, and hormone problems, the most common being hypercalcemia. Hypothyroidism has been reported to occur in children, although no proof has been found of it occurring in adults; adults with WS have a higher risk of developing type-2 diabetes, with some cases apparent as young as 21 years old.People with WS often have hyperacusia and phonophobia, which resembles noise-induced hearing loss, but this may be due to a malfunctioning auditory nerve. People with WS can also tend to demonstrate a love of music, and they appear significantly more likely to possess absolute pitch. | 11
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The adducted vocal folds do not close completely but instead remain partially open. The narrow opening between the folds is referred to as the glottis. As air moves through the glottis, it causes a distortion of the air particles which sets the vocal folds into vibratory motion. It is this vibratory motion that produces phonation or voice. In dysphonia, there is an impairment in the ability to produce an appropriate level of phonation. More specifically, it results from an impairment in vocal fold vibration or the nerve supply of the larynx. Diagnosis
The assessment and diagnosis of a dysphonic voice is completed by a multidisciplinary team, such as an otolaryngologist (ear, nose and throat doctor) and Speech-Language Pathologist, involving the use of both objective and subjective measures to evaluate the quality of the voice as well as the condition of the vocal fold tissue and vibration patterns. Definition
Dysphonia is a broad clinical term which refers to abnormal functioning of the voice. More specifically, a voice can be classified as "dysphonic" when there are abnormalities or impairments in one or more of the following parameters of voice: pitch, loudness, quality, and variability. For example, abnormal pitch can be characterized by a voice that is too high or low whereas abnormal loudness can be characterized by a voice that is too quiet or loud. Similarly, a voice that has frequent, inappropriate breaks characterizes abnormal quality while a voice that is monotone (i.e., very flat) or inappropriately fluctuates characterizes abnormal variability. | There are a number of potential treatments that are currently being tested or have just undergone testing including magnesium, etidronate, PPi, and tissue-nonspecific alkaline phosphatase inhibitors.Given that ABCC6 heterozygous mutations result in few symptoms of PXE, this disease is a candidate for gene therapy. Some initial proof-of-principle experiments have been done in mice that have relieved some of symptoms of PXE, but as with all gene therapy treatments, there are many hurdles that must be over come including insuring that the treatment will be long-lasting and reducing the risk of insertional mutagenesis and severe immune reactions. Epidemiology
The reported prevalence of pseudoxanthoma elasticum is about 1:25,000. Females are twice as likely to be affected as males. The disease occurs in all ethnicities, but Afrikaners are more likely to have PXE as a result of a founder effect (i.e., higher prevalence in the small group of people from whom Afrikaners descend). History
The first description of PXE that distinguished it from other xanthoma conditions was by Dr Ferdinand-Jean Darrier in 1896. The eponym "Grönblad-Strandberg syndrome" is used in older literature, after two physicians who made further discoveries in the disease manifestations.PXE has the distinction of being the only disease for which a layperson is the discover of the mutated gene. The ABCC6 gene mutation was discovered simultaneously by four research teams, all of which published at the same time. The principal investigators were (in order of the date of publication): Jouni Uitto, Arthur Bergen, Charles Boyd, and Klaus Lindpainter. | 0-1
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However, CMS is also considered an adaptation of pulmonary and heart disease to life under chronic hypoxia at altitude.Consensus for clinical diagnosis of CMS use laboratory values: haemoglobin in Males ≥ 21 g/dL; Females ≥ 19 g/dL, haematocrit > 65%, and arterial oxygen saturation (SaO2) < 85% in both genders. Treatment
Migration to low altitude is curative, though not immediate, as the body adapts to the normal oxygen level near sea-level and the haematocrit normalises. Alternatively, bloodletting (phlebotomy) can be performed to lower the haematocrit temporarily; when combined with volume replacement with fluids this can have a longer effect.Medication with acetazolamide, a carbonic anhydrase inhibitor, has been shown to improve chronic mountain sickness by reducing erythropoietin and the resulting polycythaemia, which results in better arterial oxygenation and a lower heart rate.Oxygen therapy and training in slow breathing techniques has been shown to reduce symptoms through increasing blood oxygenation. Epidemiology
Although CMS generally affects people native to altitudes higher than 3,000 metres (9,800 ft), it does not affect populations around the world equally. A 2013 study reviewed CMS prevalence rates around the world and found the highest rates were found in Andean countries of South America and the lowest rates in people native to the East African Mountains of Ethiopia. | CMS prevalence rates reported from the study are summarised below:
Ethiopia [3600–4100 m]: 0%
Tibetan Plateau (Tibetans): 0.91–1.2%
Indian Himalayas [3000–4200 m]: 4–7%
Kyrgyzstan [3000–4200 m]: 4.6%
Tibetan Plateau (Han Chinese): 5.6%
La Paz, Bolivia [3600 m]: 6% to 8%
Bolivia: 8–10%
Cerro de Pasco, Peru [4300 m]: 14.8–18.2%
References
External links
^ Online calculator illustrating blood oxygen carrying capacity at altitude | 11
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Treatment
Supervised exercise programs have been shown in small studies to improve exercise capacity by several measures.Oral sucrose treatment (for example a sports drink with 75 grams of sucrose in 660 ml.) taken 30 minutes prior to exercise has been shown to help improve exercise tolerance including a lower heart rate and lower perceived level of exertion compared with placebo.A low dosage treatment with creatine showed a significant improvement of muscle problems compared to placebo in a small clinical study. History
The deficiency was the first metabolic myopathy to be recognized, when Dr. McArdle described the first case in a 30-year-old man who always experienced pain and weakness after exercise. Dr. McArdle noticed this patients cramps were electrically silent and his venous lactate levels failed to increase upon ischemic exercise. (The ischemic exercise consists of the patient squeezing a hand dynamometer at maximal strength for a specific period of time, usually a minute, with a blood pressure cuff, which is placed on the upper arm and set at 250 mmHg, blocking blood flow to the exercising arm.) Notably, this is the same phenomenon that occurs when muscle is poisoned by iodoacetate, a substance that blocks breakdown of glycogen into glucose and prevents the formation of lactate. Dr. McArdle accurately concluded that the patient had a disorder of glycogen breakdown that specifically affected skeletal muscle. The associated enzyme deficiency was discovered in 1959 by W. F. H. M. Mommaerts et al. | This renders eight possible categories, six of which Mellor was able to find multiple criminal offenders to exemplify:
This typology is compatible with the necrophilia typology, producing hybrid categories which help to understand the totality of the offenders paraphilic desires. See also
Sexual masochism disorder
Biastophilia
Lust murder
Marquis de Sade, after whom sadism is named
Sadistic personality disorder
References
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Metreleptin (MYALEPT) is a recombinant human leptin analog and was approved by FDA in 2014 for generalized lipodystrophy as an adjunct therapy to diet to treat the complication of leptin deficiency. It is the only drug option approved for generalized lipodystrophy-related symptoms and is not intended to use for patients with HIV-related lipodystrophy or complications of partial lipodystrophy. Although it is a recombinant human leptin analog, it is not completely the same as natural leptin as it is produced in e. coli and has added methionine residues at is amino terminus. It works by binding to the human leptin receptor, ObR, and activates the receptor. The receptor belongs to the Class I cytokine family and signals the JAK/STAT pathway. It is available as 11.3 mg powder in a vial for subcutaneous injection upon reconstitution and needs to be protected from the light. For treatment, patients and their doctors need to be enrolled and certified in the Myalept Risk Evaluation and Mitigation Strategy (REMS) Program because people on this treatment has a risk of developing anti-metreleptin antibodies that decrease the effectiveness of metreleptin, and increased risk of lymphoma. | Adoxa is the type genus of flowering plants in the family Adoxaceae. It contains at least 2 species of flowering plant, including the moschatel, for which the family is named. Adoxa moschatellina L.
Adoxa xizangensis G.Yao
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The eponym Gee-Herter disease was sometimes used to acknowledge both contributions. Sidney V. Haas, an American paediatrician, reported positive effects of a diet of bananas in 1924. This diet remained in vogue until the actual cause of coeliac disease was determined.While a role for carbohydrates had been suspected, the link with wheat was not made until the 1940s by the Dutch paediatrician Dr Willem Karel Dicke. It is likely that clinical improvement of his patients during the Dutch famine of 1944 (during which flour was scarce) may have contributed to his discovery. Dicke noticed that the shortage of bread led to a significant drop in the death rate among children affected by coeliac disease from greater than 35% to essentially zero. He also reported that once wheat was again available after the conflict, the mortality rate soared to previous levels. The link with the gluten component of wheat was made in 1952 by a team from Birmingham, England. Villous atrophy was described by British physician John W. Paulley in 1954 on samples taken at surgery. This paved the way for biopsy samples taken by endoscopy.Throughout the 1960s, other features of coeliac disease were elucidated. Its hereditary character was recognised in 1965. In 1966, dermatitis herpetiformis was linked to gluten sensitivity. Social and culture
May has been designated as "Coeliac Awareness Month" by several coeliac organisations. Christian churches and the Eucharist
Speaking generally, the various denominations of Christians celebrate a Eucharist in which a wafer or small piece of sacramental bread from wheat bread is blessed and then eaten. | A typical wafer weighs about half a gram. Wheat flour contains around 10 to 13% gluten, so a single communion wafer may have more than 50 mg of gluten, an amount that harms many people with coeliac, especially if consumed every day (see Diet above). Many Christian churches offer their communicants gluten-free alternatives, usually in the form of a rice-based cracker or gluten-free bread. These include the United Methodist, Christian Reformed, Episcopal, the Anglican Church (Church of England, UK) and Lutheran. Catholics may receive from the Chalice alone, or ask for gluten-reduced hosts; gluten-free ones however are not considered to still be wheat bread and hence invalid matter. Roman Catholic position
Roman Catholic doctrine states that for a valid Eucharist, the bread to be used at Mass must be made from wheat. Low-gluten hosts meet all of the Catholic Churchs requirements, but they are not entirely gluten free. Requests to use rice wafers have been denied.The issue is more complex for priests. As a celebrant, a priest is, for the fullness of the sacrifice of the Mass, absolutely required to receive under both species. On 24 July 2003, the Congregation for the Doctrine of the Faith stated, "Given the centrality of the celebration of the Eucharist in the life of a priest, one must proceed with great caution before admitting to Holy Orders those candidates unable to ingest gluten or alcohol without serious harm. "By January 2004, extremely low-gluten Church-approved hosts had become available in the United States, Italy and Australia. | 11
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The initial fever is usually followed in a few days by a single, short rise but there may be many relapses between periods without fever. The most constant symptom is pain in the legs. Recovery takes a month or more. Lethal cases are rare, but in a few cases "the persistent fever might lead to heart failure". Aftereffects may include neurasthenia, cardiac disturbances and myalgia. Pathophysiology
Bartonella quintana is transmitted by contamination of a skin abrasion or louse-bite wound with the faeces of an infected body louse (Pediculus humanus corporis). There have also been reports of an infected louse bite passing on the infection. Diagnosis
Serological testing is typically used to obtain a definitive diagnosis. Most serological tests would succeed only after a certain period of time past the symptom onset (usually a week). The differential diagnosis list includes typhus, ehrlichiosis, leptospirosis, Lyme disease, and virus-caused exanthema (measles or rubella). Treatment
The treatment of trench fever can vary from case to case, as the human body has the ability to rid itself of the disease without medical intervention. Some patients will require treatment, and others will not. For those who do require treatment, the best treatment comes by way of doxycycline in combination with gentamicin. Chloramphenicol is an alternative medication recommended under circumstances that render use of tetracycline derivates undesirable, such as severe liver disease, kidney dysfunction, in children under nine years and in pregnant women. The medication is administered for seven to ten days. | Most males have mild symptoms such as hypertelorism and a broad nasal base with bifid nose, but can also be a carrier of the mutation yet stay clinically unaffected. Genetics
CFND is a very rare X-linked malformation syndrome caused by mutations in the ephrin-B1 gene (EFNB1). The EFNB1 gene codes for a membrane-anchored ligand which can bind to an ephrin tyrosine-kinase receptor. This ephrin receptor is, amongst other things, responsible for the regulation of embryonic tissue-border formation, and is important for skeletal and craniofacial development. As the ephrin receptor and its EFNB1 ligand are both bound to the (trans)membrane of the cell its cascade is activated through cell-cell interactions. These cell-cell interactions are disturbed due to the presence of cells with the mutant EFNB1 gene, as a result causing incomplete tissue-border formation.Paradoxical to other X-linked conditions, with CFND the females are more severely affected than males. This is due to the process of X-inactivation in females, where at random either the maternal or paternal X-chromosome is inactivated in a cell. Due to this process, the body’s tissues contain either cells with normal EFNB1 or the mutated EFNB1. This is called a mosaic pattern. This mosaic pattern of cells interferes with the functionality of the cell-cell interactions, as a result causing the severe physical malformations in females.As with all X-linked conditions CFND has a preset chance of being passed down from parents to their offspring. Females have two X-chromosomes and males have one X-chromosome. | 0-1
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A small proportion, however, have persistently raised hormone levels six months after treatment has started, thought to be autonomous production of hormone by the glands and loss of feedback mechanisms. In this situation surgical parathyroidectomy may be required, especially if calcium and phosphate levels remain elevated, there is calcium deposition in the wall of blood vessels (calciphylaxis in severe cases) or there is worsening bone disease. In people on dialysis, parathyroidectomy can improve their survival. It does appear that the procedure may be underused. Procedure
The operation requires a general anesthetic (unconscious and pain free) or a local anesthetic (pain free). The surgeon makes an incision around an inch long in the neck just under the larynx (Adams apple), and locates the offending parathyroid glands. Preoperative testing using sestamibi scanning can help identify the location of glands. It can also be used to limit the extent of surgical exploration when used in conjunction with intraoperative PTH hormone monitoring. The particular problem or disease process will determine how many of the parathyroid glands are removed. Some parathyroid tissue must be left in place to help prevent hypoparathyroidism. Recovery after the operation tends to be swift. The PTH level is back to normal within 10–15 minutes, and can be confirmed by intraoperative rapid assessment during the operation. However, the remaining parathyroid glands may take hours to several weeks to return to their normal functioning levels (as they may have become dormant). | 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. | 0-1
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When CD4+ T cell numbers decline below a critical level, cell-mediated immunity is lost, and the body becomes progressively more susceptible to opportunistic infections, leading to the development of AIDS. Virology
Classification
HIV is a member of the genus Lentivirus, part of the family Retroviridae. Lentiviruses have many morphologies and biological properties in common. Many species are infected by lentiviruses, which are characteristically responsible for long-duration illnesses with a long incubation period. Lentiviruses are transmitted as single-stranded, positive-sense, enveloped RNA viruses. Upon entry into the target cell, the viral RNA genome is converted (reverse transcribed) into double-stranded DNA by a virally encoded enzyme, reverse transcriptase, that is transported along with the viral genome in the virus particle. The resulting viral DNA is then imported into the cell nucleus and integrated into the cellular DNA by a virally encoded enzyme, integrase, and host co-factors. Once integrated, the virus may become latent, allowing the virus and its host cell to avoid detection by the immune system, for an indeterminate amount of time. The HIV virus can remain dormant in the human body for up to ten years after primary infection; during this period the virus does not cause symptoms. Alternatively, the integrated viral DNA may be transcribed, producing new RNA genomes and viral proteins, using host cell resources, that are packaged and released from the cell as new virus particles that will begin the replication cycle anew. Two types of HIV have been characterized: HIV-1 and HIV-2. | In addition, Hu and Temin suggested that recombination is an adaptation for repair of damage in the RNA genomes. Strand switching (copy-choice recombination) by reverse transcriptase could generate an undamaged copy of genomic DNA from two damaged single-stranded RNA genome copies. This view of the adaptive benefit of recombination in HIV could explain why each HIV particle contains two complete genomes, rather than one. Furthermore, the view that recombination is a repair process implies that the benefit of repair can occur at each replication cycle, and that this benefit can be realized whether or not the two genomes differ genetically. On the view that recombination in HIV is a repair process, the generation of recombinational variation would be a consequence, but not the cause of, the evolution of template switching.HIV-1 infection causes chronic inflammation and production of reactive oxygen species. Thus, the HIV genome may be vulnerable to oxidative damage, including breaks in the single-stranded RNA. For HIV, as well as for viruses in general, successful infection depends on overcoming host defense strategies that often include production of genome-damaging reactive oxygen species. Thus, Michod et al. suggested that recombination by viruses is an adaptation for repair of genome damage, and that recombinational variation is a byproduct that may provide a separate benefit. Assembly and release
The final step of the viral cycle, assembly of new HIV-1 virions, begins at the plasma membrane of the host cell. | 11
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Interactions
If diazepam is administered concomitantly with other drugs, attention should be paid to the possible pharmacological interactions. Particular care should be taken with drugs that potentiate the effects of diazepam, such as barbiturates, phenothiazines, opioids, and antidepressants.Diazepam does not increase or decrease hepatic enzyme activity, and does not alter the metabolism of other compounds. No evidence would suggest diazepam alters its own metabolism with chronic administration.Agents with an effect on hepatic cytochrome P450 pathways or conjugation can alter the rate of diazepam metabolism. These interactions would be expected to be most significant with long-term diazepam therapy, and their clinical significance is variable. Diazepam increases the central depressive effects of alcohol, other hypnotics/sedatives (e.g., barbiturates), other muscle relaxants, certain antidepressants, sedative antihistamines, opioids, and antipsychotics, as well as anticonvulsants such as phenobarbital, phenytoin, and carbamazepine. The euphoriant effects of opioids may be increased, leading to increased risk of psychological dependence. Cimetidine, omeprazole, oxcarbazepine, ticlopidine, topiramate, ketoconazole, itraconazole, disulfiram, fluvoxamine, isoniazid, erythromycin, probenecid, propranolol, imipramine, ciprofloxacin, fluoxetine, and valproic acid prolong the action of diazepam by inhibiting its elimination. Alcohol in combination with diazepam may cause a synergistic enhancement of the hypotensive properties of benzodiazepines and alcohol. Oral contraceptives significantly decrease the elimination of desmethyldiazepam, a major metabolite of diazepam. Rifampin, phenytoin, carbamazepine, and phenobarbital increase the metabolism of diazepam, thus decreasing drug levels and effects. Dexamethasone and St Johns wort also increase the metabolism of diazepam. Diazepam increases the serum levels of phenobarbital. Nefazodone can cause increased blood levels of benzodiazepines. | Readers are also referred to the commentary “Motherisk and Canadian Family Physician” in the January 2017 issue of Canadian Family Physician." [Ed: bolding to help summarize information, note please follow link to article to see the footnotes from this article]
Society and culture
From a legal perspective, the case through Daubert v. Merrell Dow Pharmaceuticals, 509 U.S. 579 (1993) set a new standard for admitting expert testimony in federal courts in lieu of the Frye standard. See also
Daubert v. Merrell Dow Pharmaceuticals
Daubert standard
References
External links
FDA FederalRegister/Vol. 64, No. 152/August 9,1999/Determination That Bendectin Was Not Withdrawn From Sale for Reasons of Safety or Effectiveness
FDA approves Diclegis for pregnant women experiencing nausea and vomiting, April 8, 2013
About Morning Sickness from MOTHERISK at the Hospital for Sick Children in Toronto | 0-1
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Oral spelling for these individuals is normal, and their finger tapping speed is below normal. This shows that there are problems within the fine motor skills of these individuals. People with developmental coordination disorder may be dysgraphic and motor-dysgraphia may serve as a marker of dyspraxia. Motor-dysgraphics struggle with proper finger grip and writing is often slanted due to holding a pen or pencil incorrectly. Average writing speed is slower than that of non-dysgrapic individuals, but this seems to improve with age. Motor skill deficits appears to be a common cause of dysgraphia; 78% of children with the disorder present kinematic difficulties, while 58% of them display issues with pressure skills. Spatial
A person with spatial dysgraphia has a defect in the understanding of space. This impaired spatial perception causes illegible spontaneously written work, illegible copied work, abnormal spacing between letters and majorly impaired drawing abilities. They have normal oral spelling and normal finger tapping speed, suggesting that this subtype is not fine motor based. Symptoms in actuality may vary in presentation from what is listed here. Spatial dysgraphia may develop in individuals with lesions on the right hemisphere of the brain. Miscellaneous
Other subtypes and informal classification systems have been proposed by researchers; this includes but is not limited to phonological dysgraphia, deep dysgraphia and surface dysgraphia. Signs and symptoms
The symptoms to dysgraphia are often overlooked or attributed to the student being lazy, unmotivated, careless or anxious. The condition may also be dismissed as simply being an expression of attention deficiency or having delayed visual-motor processing. | Keratolysis exfoliativa (also known as "lamellar dyshidrosis", "recurrent focal palmar peeling", "recurrent palmar peeling": 212 ) is a sometimes harmless, sometimes painful skin condition that can affect the focal surface of the fingers and/or the palm or soles of the feet. It is often misdiagnosed as chronic contact dermatitis or psoriasis. It is characterized by dry skin and superficial, air-filled blisters. These blisters can be peeled off very easily and will leave reddish, tender areas. The loss of this corneal layer of the skin, which protects the underlying layers, leaves the skin more vulnerable to dryness and cracking. Causes
Keratolysis exfoliativa normally appears during warm weather. Due to excessive sweating and friction, in for example athletic shoes, the skin can start to exfoliate. Other factors that can cause exfoliation are detergents and solvents. Another very common cause has been reported from salt water fishermen, who often suffer from these symptoms. It is not sure whether it is from the salt water or whether it is from some bacteria from fish. Treatment
Normally, exfoliation is restricted to a particular area and normal skin will replace the exfoliated parts, so no treatment is needed. Since keratolysis exfoliativa is caused by friction, detergents, and solvents, these factors should be avoided. Creams, especially those with silicone and lactic acid are also helpful. In severe cases, photochemotherapy is an option. Prognosis
In most cases exfoliation resolves spontaneously and no lasting damage is seen. However, some patients experience cracking and even bleeding in extreme cases. See also
Acrokeratoelastoidosis of Costa
Peeling skin syndrome
List of cutaneous conditions
References
External links
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Common mild side-effects include an elevated heart rate, muscle cramps, and gastric upset (including heartburn and diarrhea).Symptoms of overdose in particular include: collapse into a seizure; chest pain (possible precursor of a heart attack); fast, pounding heartbeat, which may cause raised blood pressure (hypertension); irregular heartbeat (cardiac arrhythmia), which may cause paradoxical lowered blood pressure (hypotension); nervousness and tremor; headache; dizziness and nausea/vomiting; weakness or exhaustion (medical fatigue); dry mouth; and insomnia.Rarer side effects may indicate a dangerous allergic reaction. These include: paradoxical bronchospasm (shortness of breath and difficulty breathing); skin itching, rash, or hives (urticaria); swelling (angioedema) of any part of the face or throat (which can lead to voice hoarseness), or swelling of the extremities. Pharmacology
Mechanism of action
Activation of β2 adrenergic receptors on airway smooth muscle leads to the activation of adenylate cyclase and to an increase in the intracellular concentration of 3,5-cyclic adenosine monophosphate (cyclic AMP). The increase in cyclic AMP is associated with the activation of protein kinase A, which in turn, inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in muscle relaxation. Levosalbutamol relaxes the smooth muscles of all airways, from the trachea to the terminal bronchioles. Increased cyclic AMP concentrations are also associated with the inhibition of the release of mediators from mast cells in the airways. Levosalbutamol acts as a functional agonist that relaxes the airway irrespective of the spasmogen involved, thereby protecting against all bronchoconstrictor challenges. | Levosalbutamol, also known as levalbuterol, is a short-acting β2 adrenergic receptor agonist used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). Evidence is inconclusive regarding the efficacy of levosalbutamol versus salbutamol or salbutamol-levosalbutamol combinations, however levosalbutamol is believed to have a better safety profile due to its more selective binding to β2 receptors (primarily in the lungs) versus β1 (primarily in heart muscle).The drug is the (R)-(−)-enantiomer of its prototype drug salbutamol. It is available in some countries in generic formulations from pharmaceutical companies including Cipla, Teva, and Dey, among others. Medical use
Levosalbutamols bronchodilator properties give it indications in treatment of COPD (chronic obstructive pulmonary disease, also known as chronic obstructive lung disease) and asthma. Like other bronchodilators, it acts by relaxing smooth muscle in the bronchial tubes, and thus shortening or reversing an acute "attack" of shortness of breath or difficulty breathing. Unlike some slower-acting bronchodilators, it is not indicated as a preventative of chronic bronchial constriction. Comparison to salbutamol
A 2013 systematic review of the drugs use as a treatment for acute asthma found that it "was not superior to albuterol regarding efficacy and safety in subjects with acute asthma." The review concluded: "We suggest that levalbuterol should not be used over albuterol for acute asthma." Levalbuterol is notably more costly. Adverse effects
Generally, levosalbutamol is well tolerated. | 11
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The intussusceptum itself may mechanically obstruct the rectoanal lumen, creating a blockage that straining, anismus and colonic dysmotility exacerbate.Some believe that internal rectal intussusception represents the initial form of a progressive spectrum of disorders the extreme of which is external rectal prolapse. The intermediary stages would be gradually increasing sizes of intussusception. However, internal intussusception rarely progresses to external rectal prolapse. The factors that result in a patient progressing from internal intussusception to a full thickness rectal prolapse remain unknown. Defecography studies demonstrated that degrees of internal intussusception are present in 40% of asymptomatic subjects, raising the possibility that it represents a normal variant in some, and may predispose patients to develop symptoms, or exacerbate other problems. Treatment
Conservative
Surgery is thought to be the only option to potentially cure a complete rectal prolapse. For people with medical problems that make them unfit for surgery, and those who have minimal symptoms, conservative measures may be beneficial. Dietary adjustments, including increasing dietary fiber may be beneficial to reduce constipation, and thereby reduce straining. A bulk forming agent (e.g. psyllium) or stool softener can also reduce constipation. Surgical
Surgery is often required to prevent further damage to the anal sphincters. The goals of surgery are to restore the normal anatomy and to minimize symptoms. There is no globally agreed consensus as to which procedures are more effective, and there have been over 50 different operations described.Surgical approaches in rectal prolapse can be either perineal or abdominal. | Symptoms of internal intussusception overlap with those of rectocele, indeed the 2 conditions can occur together.Patients with solitary rectal ulcer syndrome combined with internal intussusception (as 94% of SRUS patients have) were shown to have altered rectal wall biomechanics compared to patients with internal intussusception alone. The presumed mechanism of the obstructed defecation is by telescoping of the intussusceptum, occluding the rectal lumen during attempted defecation. One study analysed resected rectal wall specimens in patients with obstructed defecation associated with rectal intussusception undergoing stapled trans-anal rectal resection. They reported abnormalities of the enteric nervous system and estrogen receptors. One study concluded that intussusception of the anterior rectal wall shares the same cause as rectocele, namely deficient recto-vaginal ligamentous support. Comorbidities and complications
The following conditions occur more commonly in patients with internal rectal intussusception than in the general population:
Rectocele
Solitary rectal ulcer syndrome. Diagnosis
Unlike external rectal prolapse, internal rectal intussusception is not visible externally, but it may still be diagnosed by digital rectal examination, while the patient strains as if to defecate. Imaging such as a defecating proctogram or dynamic MRI defecography can demonstrate the abnormal folding of the rectal wall. Some have advocated the use of anorectal physiology testing (anorectal manometry). Treatment
Non surgical measures to treat internal intussusception include pelvic floor retraining, a bulking agent (e.g. psyllium), suppositories or enemas to relieve constipation and straining. If there is incontinence (fecal leakage or more severe FI), or paradoxical contraction of the pelvic floor (anismus), then biofeedback retraining is indicated. | 11
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This means that if the result is positive (indicating that the group A strep antigen was detected and therefore confirming that the person has a group A strep pharyngitis), then it is appropriate to treat the people with scarlet fever with antibiotics. But, if the rapid antigen detection test is negative (indicating that they do not have group A strep pharyngitis), then a throat culture is required to confirm, as the first test could have yielded a false negative result. In the early 21st century, the throat culture is the current "gold standard" for diagnosis.Serologic testing seeks evidence of the antibodies that the body produces against the streptococcal infection, including antistreptolysin-O and antideoxyribonuclease B. It takes the body 2–3 weeks to make these antibodies, so this type of testing is not useful for diagnosing a current infection. But, it is useful when assessing a person who may have one of the complications from a previous streptococcal infection.Throat cultures done after antibiotic therapy can show if the infection has been removed. These throat swabs, however, are not indicated, because up to 25% of properly treated individuals can continue to carry the streptococcal infection while being asymptomatic. Differential diagnosis
Viral exanthem: Viral infections are often accompanied by a rash which can be described as morbilliform or maculopapular. This type of rash is accompanied by a prodromal period of cough and runny nose in addition to a fever, indicative of a viral process. | Allergic or contact dermatitis: The erythematous appearance of the skin will be in a more localized distribution rather than the diffuse and generalized rash seen in scarlet fever. Drug eruption: These are potential side effects of taking certain drugs such as penicillin. The reddened maculopapular rash which results can be itchy and be accompanied by a fever. Kawasaki disease: Children with this disease also present a strawberry tongue and undergo a desquamative process on their palms and soles. However, these children tend to be younger than 5 years old, their fever lasts longer (at least five days), and they have additional clinical criteria (including signs such as conjunctival redness and cracked lips), which can help distinguish this from scarlet fever. Toxic shock syndrome: Both streptococcal and staphylococcal bacteria can cause this syndrome. Clinical manifestations include diffuse rash and desquamation of the palms and soles. It can be distinguished from scarlet fever by low blood pressure, lack of sandpaper texture for the rash, and multi-organ system involvement. Staphylococcal scalded skin syndrome: This is a disease that occurs primarily in young children due to a toxin-producing strain of the bacteria Staphylococcus aureus. The abrupt start of the fever and diffused sunburned appearance of the rash can resemble scarlet fever. However, this rash is associated with tenderness and large blister formation. These blisters easily pop, followed by causing the skin to peel. Staphylococcal scarlet fever: The rash is identical to the streptococcal scarlet fever in distribution and texture, but the skin affected by the rash will be tender. | 11
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Bolton developed a method to calculate the ratio between the mesiodistal width of maxillary and mandibular teeth and stated that a correct and harmonious occlusion is possible only with adequate proportionality of tooth sizes. Boltons formula concludes that if in the anterior portion the ratio is less than 77.2% the lower teeth are too narrow, the upper teeth are too wide or there is a combination of both. If the ratio is higher than 77.2% either the lower teeth are too wide, the upper teeth are too narrow or there is a combination of both. Other conditions
Other kinds of malocclusions can be due to or horizontal, vertical, or transverse skeletal discrepancies, including skeletal asymmetries. Increased vertical growth causes a long facial profile and commonly leads to an open bite malocclusion, while decreased vertical facial growth causes a short facial profile and is commonly associated with a deep bite malocclusion. However, there are many other more common causes for open bites (such as tongue thrusting and thumb sucking) and likewise for deep bites.The upper or lower jaw can be overgrown (macrognathia) or undergrown (micrognathia). It has been reported that patients with micrognathia are also affected by retrognathia (abnormal posterior positioning of the mandible or maxilla relative to the facial structure). These patients are majorly predisposed to a class II malocclusion. Mandibular macrognathia results in prognathism and predisposes patients to a class III malocclusion.Most malocclusion studies to date have focused on Class III malocclusions. Genetic studies for Class II and Class I malocclusion are more rare. | For example, the Asp816Phe and Asp816Val mutations (the aspartate normally at position 816 in the c-kit protein has been replaced with phenylalanine or valine respectively) have been associated with early manifestation of the disease (mean age of onset: 1.3 and 5.9 months respectively). The c-kit gene is encoded on the q12 locus of chromosome 4. Irritants
Several factors can worsen the symptoms of urticaria pigmentosa:
Emotional stress
Physical stimuli such as heat, friction, and excessive exercise
Bacterial toxins
Venom
Eye drops containing dextran
NSAIDs
Alcohol
MorphineThe classification of NSAIDs can be disputed. Aspirin, for example, causes the mast cells to degranulate, releasing histamines and causing symptoms to flare. However, daily intake of 81 mg aspirin may keep the mast cells degranulated. Thus, while symptoms may be worsened at first, they can get better as the mast cells are unable to recharge with histamine. Diagnosis
The disease is most often diagnosed as an infant, when parents take their baby in for what appears to be bug bites. The bug bites are actually the clumps of mast cells. Doctors can confirm the presence of mast cells by rubbing the babys skin. If hives appear, it most likely signifies the presence of urticaria pigmentosa. Treatments
There are no permanent cures for urticaria pigmentosa. However, treatments are possible. Most treatments for mastocytosis can be used to treat urticaria pigmentosa. | 0-1
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There is no single chemotherapy regimen which is universally used, and enrollment in clinical trials is often recommended when possible. Chemotherapy agents used to treat cholangiocarcinoma include 5-fluorouracil with leucovorin, gemcitabine as a single agent, or gemcitabine plus cisplatin, irinotecan, or capecitabine. A small pilot study suggested possible benefit from the tyrosine kinase inhibitor erlotinib in people with advanced cholangiocarcinoma. Radiation therapy appears to prolong survival in people with resected extrahepatic cholangiocarcinoma, and the few reports of its use in unresectable cholangiocarcinoma appear to show improved survival, but numbers are small.Infigratinib (Truseltiq) is a tyrosine kinase inhibitor of fibroblast growth factor receptor (FGFR) that was approved for medical use in the United States in May 2021. It is indicated for the treatment of people with previously treated locally advanced or metastatic cholangiocarcinoma harboring an FGFR2 fusion or rearrangement.Pemigatinib (Pemazyre) is a kinase inhibitor of fibroblast growth factor receptor 2 (FGFR2) that was approved for medical use in the United States in April 2020. It is indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test. Ivodesinib (Tibsovo) is a small molecule inhibitor of isocitrate dehydrogenase 1. | It cleaves angiotensinogen to angiotensin I, which is in turn converted by angiotensin-converting enzyme (ACE) to angiotensin II. Angiotensin II has both direct and indirect effects on blood pressure. It directly causes arterial smooth muscle to contract, leading to vasoconstriction and increased blood pressure. Angiotensin II also stimulates the production of aldosterone from the adrenal cortex, which causes the tubules of the kidneys to increase reabsorption of sodium, with water following, thereby increasing plasma volume, and thus blood pressure. Aliskiren binds to the S3bp binding site of renin, essential for its activity. Binding to this pocket prevents the conversion of angiotensinogen to angiotensin I.
Aliskiren is also available as combination therapy with hydrochlorothiazide. Chemistry
The chemical name for aliskiren is (2 S,4S,5S,7S)-5-amino-N-(2-carbamoyl-2-methylpropyl)-4-hydroxy-2-isopropyl-7-[ 4-methoxy-3-(3-methoxypropoxy)benzyl]-8-methylnonanamide. Rationale for design
Many drugs control blood pressure by interfering with angiotensin or aldosterone. However, when these drugs are used chronically, the body increases renin production, which drives blood pressure up again. Therefore, pharmacologists have been looking for a drug to inhibit renin directly. Aliskiren is the first drug to do so. References
External links
"Aliskiren". Drug Information Portal. U.S. National Library of Medicine. Aliskiren at the US National Library of Medicine Medical Subject Headings (MeSH) | 0-1
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GABA is the principal inhibitory neurotransmitter in the mammalian central nervous system (CNS). Barbiturates bind to the GABAA receptor at multiple homologous transmembrane pockets located at subunit interfaces, which are binding sites distinct from GABA itself and also distinct from the benzodiazepine binding site. Like benzodiazepines, barbiturates potentiate the effect of GABA at this receptor. In addition to this GABAergic effect, barbiturates also block AMPA and kainate receptors, subtypes of ionotropic glutamate receptor. Glutamate is the principal excitatory neurotransmitter in the mammalian CNS. Taken together, the findings that barbiturates potentiate inhibitory GABAA receptors and inhibit excitatory AMPA receptors can explain the superior CNS-depressant effects of these agents to alternative GABA potentiating agents such as benzodiazepines and quinazolinones. At higher concentration, they inhibit the Ca2+-dependent release of neurotransmitters such as glutamate via an effect on P/Q-type voltage-dependent calcium channels. Barbiturates produce their pharmacological effects by increasing the duration of chloride ion channel opening at the GABAA receptor (pharmacodynamics: This increases the efficacy of GABA), whereas benzodiazepines increase the frequency of the chloride ion channel opening at the GABAA receptor (pharmacodynamics: This increases the potency of GABA). The direct gating or opening of the chloride ion channel is the reason for the increased toxicity of barbiturates compared to benzodiazepines in overdose.Further, barbiturates are relatively non-selective compounds that bind to an entire superfamily of ligand-gated ion channels, of which the GABAA receptor channel is only one of several representatives. | Counseling is the professional guidance of the individual by utilizing psychological methods especially in collecting case history data, using various techniques of the personal interview, and testing interests and aptitudes.This is a list of counseling topics. Therapeutic modalities
Common areas
See also
List of psychotherapies
Outline of communication
Outline of psychology
Outline of sociology
Subfields of sociology
Outline of self
Psychopharmacology
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The consequences of vessel and airway obstruction include chylous fluid accumulations, hemoptysis, airflow obstruction and pneumothorax. The typical disease course displays progressive dyspnea on exertion, spaced by recurrent pneumothoraces and in some patients, chylous pleural effusions or ascites.Most people have dyspnea on exertion with daily activities by 10 years after symptom onset. Many patients require supplemental oxygen over that interval. Genetics
LAM occurs in two settings: in the disease tuberous sclerosis complex (TSC-LAM) and in a sporadic form, in women who do not have TSC (sporadic LAM). In both settings, genetic evidence indicates that LAM is caused by inactivating or “loss of function” mutations in the TSC1 or TSC2 genes, which were cloned in 1997 and 1993 respectively. The TSC1 gene is located on the long arm of chromosome 9 (9q34) and the TSC2 gene is located on the short arm of chromosome 16 (16p13). TSC-LAM occurs in women who have germline mutations in either the TSC1 or the TSC2 gene.Sporadic LAM is primarily associated with somatic TSC2 gene mutations. Germline and somatic mutations in LAM include many types of mutations spread across the genes, with no clear “hot spots,” including missense changes, in-frame deletions and nonsense mutations. Because of the large size of the genes (together they have more than 60 exons) and because mutations can be located virtually anywhere within the genes, mutation detection is often challenging.On a cellular basis, LAM cells carry bi-allelic inactivation of the TSC2 genes, consistent with the “two-hit” tumor suppressor gene model. | Epidemiology
It is slightly more common in multiple births, in infants with chromosome anomalies, and in girls than in boys. References
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Idiopathic pure sudomotor failure (IPSF) is the most common cause of a rare disorder known as acquired idiopathic generalized anhidrosis (AIGA), a clinical syndrome characterized by generalized decrease or absence of sweating without other autonomic and somatic nervous dysfunctions and without persistent organic cutaneous lesions.The term IPSF was first introduced in 1994 after researchers at Saitama Medical School speculated the primary lesion sites in patients were within cholinergic receptors of the sweat glands. The term IPSF represent a distinct subgroup of AIGA without sudomotor neuropathy or sweat gland failure. Clinical features
Early onset in life
Acute or sudden onset
Concomitant sharp pain or cholinergic urticaria over the entire body
Absence of other autonomic dysfunction
Elevated serum IgE levels
Marked response to glucocorticoids
Preserved apocrine sweating (adrenergic innervation)
Pathology
Intracutaneous injection of pilocarpine (sweat gland stimulant) is known to evoke no sweat response, indicating that lesions are on the post-synaptic side of the nerve-sweat gland junction.The proposed pathomechanisms of idiopathic pure sudomotor failure include:
A deficit within muscarinic cholinergic receptors of the eccrine sweat glands. Interference in acetylcholine transmission to cholinergic receptors. A cross-reactive immune response which interferes with cholinergic transmission in the eccrine glands. Components of an immediate-type allergy (based on the dramatic resumption of axon reflex sweating following glucocorticoid treatment). Diagnosis
Management
Treatment of AIGA almost always consists of steroid pulse therapy or high-dose oral steroids and is not consistently effective. Much remains unclear regarding the reasons for recurrent anhidrosis. | 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
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Anti-vibration gloves in many cases amplify the vibrations at frequencies lower than those mentioned in the text above. Reactive monitoring
A simpler system, known as re-active monitoring, may be used by, for example, monitoring rates of usage of consumable items. Such a system was introduced by Carl West at a fabrication workshop in Rotherham, England. In this system, the vibration levels of the angle grinding tools in use was measured, as was the average life of a grinding disk. Thus by recording numbers of grinding disks used, vibration exposure may be calculated. History
The symptoms were first described by Professor Giovanni Loriga in Italy in 1911, although the link was not made between the symptoms and vibrating hand tools until a study undertaken by Alice Hamilton MD in 1918. She formed her theory through following the symptoms reported by quarry cutters and carvers in Bedford, Indiana. She also discovered the link between an increase in HAV symptoms and cold weather as 1918 was a particularly harsh winter.The first scale for assessing the condition, the Taylor-Pelmear scale, was published in 1975, but it was not listed as a prescribed disease in the United Kingdom until 1985, and the Stockholm scale was introduced in 1987. In 1997, the UK High Court awarded £127,000 in compensation to seven coal miners for vibration white finger. A UK government fund set up to cover subsequent claims by ex-coalminers had exceeded £100 million in payments by 2004. See also
List of cutaneous conditions
Hypothenar hammer syndrome
References
External links
BBC News article on coal miners claims
"Noise and vibration". | The second form of bone marrow suppression is bone marrow aplasia, which is associated with being late into toxicity and cannot be reversed in some cases. Chloramphenicol is contraindicated in persons who are breastfeeding due to the risk of toxic effects in the baby, but if maternal use of chloramphenicol cannot be avoided, close monitoring of the babys symptoms such as feeding difficulties, and blood work is recommended. Treatment
Chloramphenicol therapy should be stopped immediately if objective or subjective signs of gray baby syndrome are suspected since gray baby syndrome can be fatal for the infant if it is not diagnosed early on as it can lead to anemia, shock, and end-organ damage. After discontinuing the antibiotic, the side effects caused by the toxicity should be treated. This includes treating hypoglycemia to help prevent hemodynamic instability, as well as increasing the temperature of the infant if they have developed hypothermia. Since symptoms of gray baby syndrome are correlated with elevated serum chloramphenicol concentrations, exchange transfusion may be required to remove the drug, charcoal column hemoperfusion is a type of transfusion that has shown significant effects but is associated with numerous side effects. The associated side effects isnt the only reason why this method of treatment is not a first line therapy. According to the American Journal of Kidney Diseases, elevated cartridge prices and viable lifespan of the product are deterring factors to consider. | 0-1
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Angulation of tooth
Most commonly used classification system with respect to treatment planning. Depending on the angulation the tooth might be classified as:
Mesioangular
Horizontal
Vertical
Distoangular
Palatal
Buccal
Lingual
Relationship of tooth to anterior border of ramus
This type of classification is based on the amount of impacted tooth that is covered with the mandibular ramus. It is known as the Pell and Gregory classification, classes 1, 2, and 3. Relationship of tooth to occlusal plane
The depth of the impacted tooth compared with the adjacent second molar gives the basis for this type of classification. This was also given by Pell and Gregory and is called as Pell and Gregory A, B and C classification. Relationship to occlusal plane Class A-C
Complications
Erupted teeth that are adjacent to impacted teeth are predisposed to periodontal disease. Since the most difficult tooth surface to be cleaned is the distal surface of the last tooth, in the presence of an impacted tooth there is always gingival inflammation around the second molar that is invariably present. Even this minor amount of inflammation can provide bacteria access to a larger portion of the root surface that results in early formation of periodontitis compromising the tooth. Even in situations in which no obvious communication exists between the mouth and the impacted third molar there may be enough communication to initiate dental caries (tooth decay). Pericoronitis
Pericoronitis is an infection of the soft tissue that covers the crown of an impacted tooth and is usually caused by the normal oral microbiota. | An impacted tooth is one that fails to erupt into the dental arch within the expected developmental window. Because impacted teeth do not erupt, they are retained throughout the individuals lifetime unless extracted or exposed surgically. Teeth may become impacted because of adjacent teeth, dense overlying bone, excessive soft tissue or a genetic abnormality. Most often, the cause of impaction is inadequate arch length and space in which to erupt. That is the total length of the alveolar arch is smaller than the tooth arch (the combined mesiodistal width of each tooth). The wisdom teeth (third molars) are frequently impacted because they are the last teeth to erupt in the oral cavity. Mandibular third molars are more commonly impacted than their maxillary counterparts. Some dentists believe that impacted teeth should be removed except, in certain cases, canine teeth: canines may just remain buried and give no further problems, thus not requiring surgical intervention. However, removal of asymptomatic, pathology-free, impacted teeth isnt a medical consensus: watchful monitoring may be a more prudent and cost-effective strategy and make the future placement of a dental implant through such impacted tooth a feasible approach. Classification
Classifications enable the oral surgeon to determine the difficulty in removal of the impacted tooth. The primary factor determining the difficulty is accessibility, which is determined by adjacent teeth or other structures that impair access or delivery pathway. The majority of classification schemes are based on analysis on a radiograph. The most frequently considered factors are discussed below. | 11
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Shorter episodes of occlusion can lead to what is referred to as silent myocardial ischemia due to its asymptomatic nature. These episodes can also be accompanied by arrhythmias. Longer episodes of occlusion can lead to stable or unstable angina, myocardial infarction, and sudden cardiac death. Risk factors
Unlike classical angina pectoris, traditional cardiovascular risk factors are not thought to be significantly associated with coronary vasospasm. The exception to this is with smoking, which is known to be a modifiable risk factor for vasospastic angina.There are several risk factors that are thought to precipitate, or trigger, episodes of coronary vasospasm. Many of these factors work by exerting effects on the autonomic nervous system. One of the mechanisms through which this occurs is via increasing sympathetic nervous system activity. The resulting increased sympathetic outflow leads to vasoconstrictive effects on blood vessels. For example, cocaine use can trigger vasospasm in coronary arteries through its actions on adrenergic receptors causing vasoconstriction. Exercise, cold weather, physical activity or exertion, mental stress, hyperventilation are additional precipitating factors. Pathophysiology
The exact pathophysiology behind coronary vasospasm has not been elucidated. Instead, a combination of different factors has been proposed to contribute to coronary vasospasm. In general, it is thought that an abnormality within a coronary artery causes it to become hyperreactive to vasoconstrictor stimuli. This abnormality can be located in one segment of the coronary artery, or it may be diffuse and present throughout the entire artery. If and when vasoconstrictor stimuli act upon the hyperreactive segment of the artery, then vasospasm can result. | Critical illness polyneuropathy (CIP) and critical illness myopathy (CIM) are overlapping syndromes of diffuse, symmetric, flaccid muscle weakness occurring in critically ill patients and involving all extremities and the diaphragm with relative sparing of the cranial nerves. CIP and CIM have similar symptoms and presentations and are often distinguished largely on the basis of specialized electrophysiologic testing or muscle and nerve biopsy. The causes of CIP and CIM are unknown, though they are thought to be a possible neurological manifestation of systemic inflammatory response syndrome. Corticosteroids and neuromuscular blocking agents, which are widely used in intensive care, may contribute to the development of CIP and CIM, as may elevations in blood sugar, which frequently occur in critically ill patients.CIP was first described by Charles F. Bolton in a series of five patients.Combined CIP and CIM was first described by Nicola Latronico in a series of 24 patients. Signs and symptoms
People with CIP/CIM have diffuse, symmetric, flaccid muscle weakness. CIP/CIM typically develops in the setting of a critical illness and immobilization, so patients with CIP/CIM are often receiving treatment in the intensive care unit (ICU).Weakness (motor deficits) occurs in generalized fashion, rather than beginning in one region of the body and spreading. Limb and respiratory (diaphragm) muscles are especially affected. | 0-1
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People reporting MCS-like symptoms may have other health issues, ranging from common conditions, such as depression or asthma, to less common circumstances, such a documented chemical exposure during a work accident. These other conditions may or may not have any relationship to MCS symptoms, but they should be diagnosed and treated appropriately, whenever the patient history, physical examination, or routine medical tests indicates their presence. The differential diagnosis list includes solvent exposure, occupational asthma, and allergies. Definitions
Different researchers and proponents use different definitions, which complicates research and can affect diagnosis. For example, the 1987 definition that requires symptoms to begin suddenly after an identifiable, documented exposure to a chemical, but the 1996 definition by the WHO/ICPS says that the cause can be anything, including other medical conditions or psychological factors.In 1996, an expert panel at WHO/ICPS was set up to examine MCS. | It may depend on whether the bleeding is regarded as marking the menstrual period (favoring the term "irregular cycles") or being separate from it (favoring the term "metrorrhagia"). Oligomenorrhea generally refers to infrequent menstruation, More strictly, it is menstrual periods occurring at intervals of greater than 35 days, with only four to nine periods in a year. Menstrual periods should have been regularly established before the development of infrequent flow and often (but not always) involves irregular intervals. In contrast to "irregular cycles", the interval between one cycle and the next may be consistent but can be regarded as "irregular" compared to the cycle length of a female without oligomenorrhea. Women with oligomenorrhea often have irregular cycles as well. Polymenorrhea is the medical term for cycles with intervals of 21 days or fewer. It can be regarded as the opposite of oligomenorrhea. References
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In 1953 Dr Saxtorph, medical advisor to the Greenland department (part of the Danish government), wrote that the Greenlanders do not like outsiders to see or discuss these birthmarks; "they doubtless feel as a reminiscence of the time when they lived on a low cultural level".The presence or absence of the slate grey nevus was used by racial theorists such as Joseph Deniker (1852-1918), the French anthropologist.The Journal of Cutaneous Diseases Including Syphilis, Volume 23 contained several accounts of the slate grey nevus on children in the Americas:
Holm ("Ethnological Sketch. Communications on Greenland," X., Copenhagen, 1887) announced the presence of the spot in the east part of Greenland. Bartels ("The So-Called Mongolian Spots on Infants of Esquimaux," Ethnologic Review, 1903) received letters regarding it from East Greenland and also from Esquimaux of Alaska. In half-breed European-Esquimaux, Hansen says he has encountered it. Among Indians of North Vancouver, British Columbia, there are observations made by Baelz as well as by Tenkate (secondhand). In the Mayas of Central America, Starrs (Data on the Ethnography of Western Mexico, Part H., 1902) facts are corroborated by Herman (Aparecimiento de la Mancha Mongolica. Revista de Ethnologia, 1904). He cites A. F. Chamberlain (Pigmentary Spots, American Anthropologist, 1902,) and Starr (Sacral Spots of Mayan Indians, Science, New Series, xvii., 1903). In Central America, according to these authorities, the spot is called Uits, "pan," and it is an insult to speak of it. It disappears in the tenth month. It is bluish-reddish (in these Native people), and is remarkable by its small size. | Collagen disease is a term previously used to describe systemic autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue.The term "collagen disease" was coined by Dr. Alvin F. Coburn in 1932, on his quest to discover streptococcal infection as the cause for rheumatic fever. See also
Collagenopathy, types II and XI
Connective tissue disease
References
External links
Collagen disease entry in the public domain NCI Dictionary of Cancer Terms
This article incorporates public domain material from the U.S. National Cancer Institute document: "Dictionary of Cancer Terms". | 0-1
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Pelvic congestion syndrome, also known as pelvic vein incompetence, is a long term condition believed to be due to enlarged veins in the lower abdomen. The condition may cause chronic pain, such as a constant dull ache, which can be worsened by standing or sex. Pain in the legs or lower back may also occur.While the condition is believed to be due to blood flowing back into pelvic veins as a result of faulty valves in the veins, this hypothesis is not certain. The condition may occur or worsen during pregnancy. The presence of estrogen is believed to be involved in the mechanism. Diagnosis may be supported by ultrasound, CT scan, MRI, or laparoscopy.Early treatment options include medroxyprogesterone or nonsteroidal anti-inflammatory drugs (NSAIDs). Surgery to block the varicose veins may also be done. About 30% of women of reproductive age are affected. It is believed to be the cause of about a third of chronic pelvic pain cases. While pelvic venous insufficiency was identified in the 1850s it was only linked with pelvic pain in the 1940s. Signs and symptoms
Women with this condition experience a constant pain that may be dull and aching, but is occasionally more acute. The pain is worse at the end of the day and after long periods of standing, and those affected get relief when they lie down. | The pain is worse during or after sexual intercourse, and can be worse just before the onset of the menstrual period.Women with pelvic congestion syndrome have a larger uterus and a thicker endometrium. 56% of women manifest cystic changes to the ovaries, and many report other symptoms, such as dysmenorrhea, back pain, vaginal discharge, abdominal bloating, mood swings or depression, and fatigue. Causes
Local pelvic hormonal milieu
Venous outflow obstruction, such as May-Thurner syndrome, Nutcracker syndrome, Budd-Chiari syndrome, or left renal vein thrombosis
External compression due to tumor (including fibroids, endometriosis), or scarring
Diagnosis
Diagnosis can be made using ultrasound or laparoscopy testing. The condition can also be diagnosed with a venogram, CT scan, or an MRI. Ultrasound is the diagnostic tool most commonly used. Some research has suggested that transvaginal duplex ultrasound is the best test for pelvic venous reflux. Treatment
Early treatment options include pain medication using nonsteroidal anti-inflammatory drugs, and suppression of ovarian function.More advanced treatment includes a minimally invasive procedure performed by an Interventional Radiologist. This minimally invasive procedure involves stopping blood within the pelvic varicose veins using a minimally invasive procedure called a catheter directed embolization. The procedure rarely requires an overnight stay in hospital and is usually performed as an outpatient procedure, and is done using local anesthetic and moderate sedation. Patients report an 80% success rate, as measured by the amount of pain reduction experienced. See also
Ovarian vein syndrome
Nutcracker syndrome
References
== External links == | 11
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Cholesterol is a major component of cell plasma membranes, which define the cell as a whole and its organelles. It is also the basic building block of steroid hormones, including neurosteroids. In Niemann–Pick type C, large amounts of free or unesterified cholesterol accumulate in lysosomes, and leads to relative deficiency of this molecule in multiple membranes and for steroid synthesis. The accumulation of glycosphingolipids in the nervous system has been linked to structural changes, namely ectopic dendritogenesis and meganeurite formation, and has been targeted therapeutically.Several theories have attempted to link the accumulation of cholesterol and glycolipids in the lysosomes with the malfunction of the NPC-1 protein. Neufeld et al. hypothesized that the accumulation of mannose 6-phosphate receptors (MPRs) in the late endosome signals failure of retrograde trafficking of cholesterol via the trans Golgi network. Another theory suggests that the blockage of retrograde cholesterol breakdown in the late endosome is due to decreased membrane elasticity and thus the return vesicles of cholesterol to the trans Golgi Network cannot bud and form. Iouannou, et al. have described similarities between the NPC1 protein and members of the resistance-nodulation-division (RND) family of prokaryotic permeases, suggesting a pumping function for NPC1. Recent 2008 evidence indicates that NPC-1 may play an important role in calcium regulation. Diagnosis
Niemann–Pick type C is diagnosed by assaying cultured fibroblasts for cholesterol esterification and staining for unesterified cholesterol with filipin. The fibroblasts are grown from a small skin biopsy taken from a patient with suspected NPC. | The pregnane X receptor has been identified as a potential target.Neural stem cells have also been investigated in an animal model, and clear evidence of life extension in the mouse model has been shown.Low cholesterol diets are often used, but there is no evidence of efficacy.Gene therapy is being used clinically to treat genetic diseases including haemophilia and spinal muscular atrophy. It has been used preclinically, in a mouse model of Niemann-Pick type C, using an adeno-associated virus derived viral vector has been shown to extend lifespan following injection into the lateral ventricles of the neonatal brain. In a separate proof-of-concept study a similar vector, but with a modified capsid capable of delivering genes to the central nervous system following intravenous injection, was given to Niemann-Pick type C mice at around four weeks of age; this resulted in extended lifespan and improved weight gain. Prognosis
The lifespan of patients with NPC is usually related to the age of onset. Children with antenatal or infantile onset usually succumb in the first few months or years of life, whereas adolescent and adult onset forms of Niemann–Pick type C have a more insidious onset and slower progression, and affected individuals may survive to the seventh decade. Adult cases of NPC are being recognized with increasing frequency. It is suspected that many patients affected by NPC are undiagnosed, owing to lack of awareness of the disease and the absence of readily available screening or diagnostic tests. For the same reasons the diagnosis is often delayed by many years. | 11
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This lower-boiling ternary azeotrope is removed preferentially, leading to water-free ethanol. Molecular sieves and desiccants
Apart from distillation, ethanol may be dried by addition of a desiccant, such as molecular sieves, cellulose, or cornmeal. The desiccants can be dried and reused. Molecular sieves can be used to selectively absorb the water from the 95.6% ethanol solution. Molecular sieves of pore-size 3 Ångstrom, a type of zeolite, effectively sequester water molecules while excluding ethanol molecules. Heating the wet sieves drives out the water, allowing regeneration of their dessicant capability. Membranes and reverse osmosis
Membranes can also be used to separate ethanol and water. Membrane-based separations are not subject to the limitations of the water-ethanol azeotrope because the separations are not based on vapor-liquid equilibria. Membranes are often used in the so-called hybrid membrane distillation process. This process uses a pre-concentration distillation column as the first separating step. The further separation is then accomplished with a membrane operated either in vapor permeation or pervaporation mode. Vapor permeation uses a vapor membrane feed and pervaporation uses a liquid membrane feed. Other techniques
A variety of other techniques have been discussed, including the following:
Salting using potassium carbonate to exploit its insolubility will cause a phase separation with ethanol and water. This offers a very small potassium carbonate impurity to the alcohol that can be removed by distillation. This method is very useful in purification of ethanol by distillation, as ethanol forms an azeotrope with water. | These include aminoglycosides such as streptomycin and gentamicin, tetracyclines (especially doxycycline), and the fluoroquinolone ciprofloxacin. Mortality associated with treated cases of bubonic plague is about 1–15%, compared to a mortality of 40–60% in untreated cases.People potentially infected with the plague need immediate treatment and should be given antibiotics within 24 hours of the first symptoms to prevent death. Other treatments include oxygen, intravenous fluids, and respiratory support. People who have had contact with anyone infected by pneumonic plague are given prophylactic antibiotics. Using the broad-based antibiotic streptomycin has proven to be dramatically successful against the bubonic plague within 12 hours of infection. Epidemiology
Globally between 2010 and 2015, there were 3,248 documented cases, which resulted in 584 deaths. The countries with the greatest number of cases are the Democratic Republic of the Congo, Madagascar, and Peru.For over a decade since 2001, Zambia, India, Malawi, Algeria, China, Peru, and the Democratic Republic of the Congo had the most plague cases with over 1,100 cases in the Democratic Republic of the Congo alone. From 1,000 to 2,000 cases are conservatively reported per year to the WHO. From 2012 to 2017, reflecting political unrest and poor hygienic conditions, Madagascar began to host regular epidemics.Between 1900 and 2015, the United States had 1,036 human plague cases with an average of 9 cases per year. In 2015, 16 people in the Western United States developed plague, including 2 cases in Yosemite National Park. | 0-1
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A dream is a succession of images, ideas, emotions, and sensations that usually occur involuntarily in the mind during certain stages of sleep. Humans spend about two hours dreaming per night, and each dream lasts around 5 to 20 minutes, although the dreamer may perceive the dream as being much longer than this.The content and function of dreams have been topics of scientific, philosophical and religious interest throughout recorded history. Dream interpretation, practiced by the Babylonians in the third millennium BCE and even earlier by the ancient Sumerians, figures prominently in religious texts in several traditions, and has played a lead role in psychotherapy. The scientific study of dreams is called oneirology. Most modern dream study focuses on the neurophysiology of dreams and on proposing and testing hypotheses regarding dream function. It is not known where in the brain dreams originate, if there is a single origin for dreams or if multiple regions of the brain are involved, or what the purpose of dreaming is for the body or mind. The human dream experience and what to make of it has undergone sizable shifts over the course of history. Long ago, according to writings from Mesopotamia and Ancient Egypt, dreams dictated post-dream behaviors to an extent sharply reduced in later millennia. These ancient writings about dreams highlight visitation dreams, where a dream figure, usually a deity or a prominent forebear, commands the dreamer to take specific actions and may predict future events. | Ischemic optic neuropathy (ION) is the loss of structure and function of a portion of the optic nerve due to obstruction of blood flow to the nerve (i.e. ischemia). Ischemic forms of optic neuropathy are typically classified as either anterior ischemic optic neuropathy or posterior ischemic optic neuropathy according to the part of the optic nerve that is affected. People affected will often complain of a loss of visual acuity and a visual field, the latter of which is usually in the superior or inferior field.When ION occurs in patients below the age of 50 years old, other causes should be considered, such as juvenile diabetes mellitus, antiphospholipid antibody-associated clotting disorders, collagen-vascular disease, and migraines. Rarely, complications of intraocular surgery or acute blood loss may cause an ischemic event in the optic nerve. Presentation
Anterior ION presents with sudden, painless visual loss, developing over hours to days. Diagnosis
Examination findings usually include decreased visual acuity, a visual field defect, color vision loss, a relative afferent pupillary defect, and a swollen optic nerve head. Posterior ION occurs arteritic, nonarteritic, and surgical settings. It is characterized by acute vision loss without initial disc edema, but with subsequent optic disc atrophy. Management
Although there is no recognized treatment that can reverse the visual loss, upon recent reports, optic nerve health decompression may be beneficial for a select group of patients with a gradual decline in vision due to ION. See also
Ocular ischemic syndrome
References
Dictionary of Eye Terminology, Triad Publishing Company, 1990. | 0-1
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The emergence of the mcr-9 gene is quite remarkable.Use of colistin to treat Acinetobacter baumannii infections has led to the development of resistant bacterial strains. They have also developed resistance to the antimicrobial compounds LL-37 and lysozyme, produced by the human immune system. This cross-resistance is caused by gain-of-function mutations to the pmrB gene, a phosphoethanolamine transferase (similar to mcr-1) located on the bacterial chromosome.Not all resistance to colistin and some other antibiotics is due to the presence of resistance genes. Heteroresistance, the phenomenon wherein apparently genetically identical microbes exhibit a range of resistance to an antibiotic, has been observed in some species of Enterobacter since at least 2016 and was observed in some strains of Klebsiella pneumoniae in 2017–2018. In some cases this phenomenon has significant clinical consequences. Inherently resistant
Variable resistance
Aeromonas
Vibrio
Prevotella
Fusobacterium
Escherichia coli
Adverse reactions
The main toxicities described with intravenous treatment are nephrotoxicity (damage to the kidneys) and neurotoxicity (damage to the nerves), but this may reflect the very high doses given, which are much higher than the doses currently recommended by any manufacturer and for which no adjustment was made for pre-existing renal disease. Neuro- and nephrotoxic effects appear to be transient and subside on discontinuation of therapy or reduction in dose.At a dose of 160 mg colistimethate IV every eight hours, very little nephrotoxicity is seen. Indeed, colistin appears to have less toxicity than the aminoglycosides that subsequently replaced it, and it has been used for extended periods up to six months with no ill effects. | As multi-drug resistant bacteria became more prevalent in the 1990s, colistin started to get a second look as an emergency solution, in spite of toxicity.Colistin has also been used in agriculture, particularly in China from the 1980s onwards. Chinese production for agriculture exceeded 2700 tons in 2015. China banned colistin use for livestock growth promotion in 2016. Biosynthesis
The biosynthesis of colistin requires the use of three amino acids: threonine, leucine, and 2,4-diaminobutryic acid. The linear form of colistin is synthesized before cycliziation. Non-ribosomal peptide biosynthesis begins with a loading module and then the addition of each subsequent amino acid. The subsequent amino acids are added with the help of an adenylation domain (A), a peptidyl carrier protein domain (PCP), an epimerization domain (E), and a condensation domain (C). Cyclization is accomplished by a thioesterase. The first step is to have a loading domain, 6-methylheptanoic acid, associate with the A and PCP domains. Now with a C, A, and PCP domain that is associated with 2,4-diaminobutryic acid. This continues with each amino acid until the linear peptide chain is completed. The last module will have a thioesterase to complete the cyclization and form the product colistin. References
Further reading
Reardon S (December 2015). "Spread of antibiotic-resistance gene does not spell bacterial apocalypse — yet". Nature. doi:10.1038/nature.2015.19037. External links
"Colistimethate sodium". Drug Information Portal. U.S. National Library of Medicine. "Colistin sulfate". Drug Information Portal. U.S. National Library of Medicine. "Colistin topics page (bibliography)". Science.gov. | 11
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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. | In advanced cystic kidney disease with renal failure, renal transplant or dialysis may ultimately be necessary. Prognosis
By late 70s, 50-75% of patients with CKD require renal replacement therapy, either dialysis or kidney transplant. The number and size of cysts and kidney volume are predictors for the progression of CKD and end-stage renal disease. PKD does not increase the risk for the development of renal cancer, but if such develops, it is more likely to be bilateral. The most probable cause of death is heart disease, ruptured cerebral aneurysm, or disseminated infection. Some factors that can affect life expectancy are mutated gene type, gender, the age of onset, high blood pressure, proteinuria, hematuria, UTI, hormones, pregnancies, and size of cysts. If risk factors are controlled and the disease is stabilized then the patients life expectancy can be prolonged greatly. References
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This is because remifentanil will be rapidly eliminated from the blood plasma on termination of the remifentanil infusion, hence the effects of the drug will quickly dissipate even after very long infusions. Owing to synergism between remifentanil and hypnotic drugs (such as propofol) the dose of the hypnotic can be substantially reduced. This leads often to more hemodynamic stability during surgery and a quicker post-operative recovery time. Side-effects
Remifentanil is a specific μ-receptor agonist. Hence, it causes a reduction in sympathetic nervous system tone, respiratory depression and analgesia. The drugs effects include a dose-dependent decrease in heart rate and arterial pressure and respiratory rate and tidal volume. Muscle rigidity is sometimes noted. The most common side effects reported by patients receiving this medication are a sense of extreme "dizziness" (often short lived, a common side effect of other fast-acting synthetic phenylpiperidine narcotics such as fentanyl and alfentanil) and intense itching (pruritus), often around the face. These side effects are often controlled by either altering the administered dose (decreasing or in some cases, increasing the dose) or by administering other sedatives that allow the patient to tolerate or lose awareness of the side effect. Because pruritus is due to excessive serum histamine levels, antihistamines such as diphenhydramine (Benadryl) are often co-administered. This is done with care, however, as excessive sedation may occur. Nausea can occur as a side effect of remifentanil, however, it is usually transient in nature due to the drugs short half-life which rapidly removes it from the patients circulation once the infusion is terminated. | Leg before wicket (LBW)
a way of dismissing the batsman. In brief, the batsman is out if, in the opinion of the umpire, the ball hits any part of the batsmans body (usually the leg) before hitting or missing the bat and would have gone on to hit the stumps. Leg break
a spin bowling delivery which turns from the leg side to the off side of a right-handed batsman. The stock delivery of a leg spin bowler. Leg bye
Extras taken after a delivery hits any part of the body of the batsman other than the bat or the gloved hand that holds the bat. If the batsman makes no attempt to play the ball with the bat or evade the ball that hits them, leg byes may not be scored. Leg cutter
A break delivery bowled by a fast or medium-pace bowler with similar action to a spin bowler, but at a faster pace. The ball breaks from the leg side to the off side of the batsman. Leg glance
A delicate shot played at a ball aimed slightly on the leg side, using the bat to flick the ball as it passes the batsman, deflecting towards the square leg or fine leg area. Leg side
the half of the field to the rear of the batsman as they take strike (also known as the on side). Leg slip
a fielding position equivalent to a slip, but on the leg side. Leg spin
the style of spin bowling produced by right-handed wrist spin. | 0-1
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Activity: Many people with hepatitis prefer bed rest, though it is not necessary to avoid all physical activity while recovering. Diet: A high-calorie diet is recommended. Many people develop nausea and cannot tolerate food later in the day, so the bulk of intake may be concentrated in the earlier part of the day. In the acute phase of the disease, intravenous feeding may be needed if patients cannot tolerate food and have poor oral intake subsequent to nausea and vomiting. Drugs: People with hepatitis should avoid taking drugs metabolized by the liver. Glucocorticoids are not recommended as a treatment option for acute viral hepatitis and may even cause harm, such as development of chronic hepatitis. Precautions: Universal precautions should be observed. Isolation is usually not needed, except in cases of hepatitis A and E who have fecal incontinence, and in cases of hepatitis B and C who have uncontrolled bleeding. Hepatitis A
Hepatitis A usually does not progress to a chronic state, and rarely requires hospitalization. Treatment is supportive and includes such measures as providing intravenous (IV) hydration and maintaining adequate nutrition.Rarely, people with the hepatitis A virus can rapidly develop liver failure, termed fulminant hepatic failure, especially the elderly and those who had a pre-existing liver disease, especially hepatitis C. Mortality risk factors include greater age and chronic hepatitis C. In these cases, more aggressive supportive therapy and liver transplant may be necessary. Hepatitis B
Acute
In healthy patients, 95–99% recover with no long-lasting effects, and antiviral treatment is not warranted. | After conducting its investigation, the CDC attributed the source of the outbreak to the use of contaminated raw green onion. The restaurant was purchasing its green onion stock from farms in Mexico at the time. It is believed that the green onions may have been contaminated through the use of contaminated water for crop irrigation, rinsing, or icing or by handling of the vegetables by infected people. Green onion had caused similar outbreaks of hepatitis A in the southern United States prior to this, but not to the same magnitude. The CDC believes that the restaurants use of a large communal bucket for chopped raw green onion allowed non-contaminated plants to be mixed with contaminated ones, increasing the number of vectors of infection and amplifying the outbreak. The restaurant was closed once it was discovered to be the source, and over 9,000 people were given hepatitis A immune globulin because they had either eaten at the restaurant or had been in close contact with someone who had. Special populations
HIV co-infection
Persons infected with HIV have a particularly high burden of HIV-HCV co-infection. In a recent study by the WHO, the likelihood of being infected with hepatitis C virus was six times greater in those who also had HIV. The prevalence of HIV-HCV co-infection worldwide was estimated to be 6.2% representing more than 2.2 million people. Intravenous drug use was an independent risk factor for HCV infection. | 11
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Lebers hereditary optic neuropathy (LHON) is a mitochondrially inherited (transmitted from mother to offspring) degeneration of retinal ganglion cells (RGCs) and their axons that leads to an acute or subacute loss of central vision; it predominantly affects young adult males. LHON is transmitted only through the mother, as it is primarily due to mutations in the mitochondrial (not nuclear) genome, and only the egg contributes mitochondria to the embryo. LHON is usually due to one of three pathogenic mitochondrial DNA (mtDNA) point mutations. These mutations are at nucleotide positions 11778 G to A, 3460 G to A and 14484 T to C, respectively in the ND4, ND1 and ND6 subunit genes of complex I of the oxidative phosphorylation chain in mitochondria. Men cannot pass on the disease to their offspring. Signs and symptoms
Clinically, there is an acute onset of visual loss, first in one eye, and then a few weeks to months later in the other. Onset is usually young adulthood, but age range at onset from 7-75 is reported. The age of onset is slightly higher in females (range 19–55 years: mean 31.3 years) than males (range 15–53 years: mean 24.3). The male-to-female ratio varies between mutations: 3:1 for 3460 G>A, 6:1 for 11778 G>A and 8:1 for 14484 T>C.This typically evolves to very severe optic atrophy and a permanent decrease of visual acuity. Both eyes become affected either simultaneously (25% of cases) or sequentially (75% of cases) with a median inter-eye delay of 8 weeks. Rarely, only one eye is affected. | In the acute stage, lasting a few weeks, the affected eye demonstrates an oedematous appearance of the nerve fiber layer, especially in the arcuate bundles and enlarged or telangiectatic and tortuous peripapillary vessels (microangiopathy). The main features are seen on fundus examination, just before or after the onset of visual loss. A pupillary defect may be visible in the acute stage as well. Examination reveals decreased visual acuity, loss of color vision and a cecocentral scotoma on visual field examination. LHON with demyelinating lesions or LHON Plus
LHON Plus is a rare variant of the disorder with eye disease together with other conditions. Its symptoms include loss of the brains ability to control the movement of muscles, tremors, and cardiac arrhythmia. Many cases of LHON plus have been compared to multiple sclerosis because of the lack of muscular control and the presence of demyelinating lesions in the CNS. It is therefore a subtype of MS, according to McDonalds definition. Genetics
Leber hereditary optic neuropathy is a condition related to changes in mitochondrial DNA. Although most DNA is packaged in chromosomes within the nucleus, mitochondria have a distinct mitochondrial genome composed of mtDNA.Mutations in the MT-ND1, MT-ND4, MT-ND4L, and MT-ND6 genes cause Leber hereditary optic neuropathy. These genes code for the NADH dehydrogenase protein involved in the normal mitochondrial function of oxidative phosphorylation. Oxidative phosphorylation uses a series of four large multienzyme complexes, all embedded in the inner mitochondrial membrane, to convert oxygen and simple sugars to energy. | 11
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: 705 One antidote for cyanide poisoning, nitrite (i.e. via amyl nitrite), works by converting ferrohemoglobin to ferrihemoglobin, which can then compete with COX for free cyanide (as the cyanide will bind to the iron in its heme groups instead). Ferrihemoglobin cannot carry oxygen, but the amount of ferrihemoglobin that can be formed without impairing oxygen transport is much greater than the amount of COX in the body. : 1475 Cyanide is a broad-spectrum poison because the reaction it inhibits is essential to aerobic metabolism; COX is found in many forms of life. However, susceptibility to cyanide is far from uniform across affected species; for instance, plants have an alternative electron transfer pathway available that passes electrons directly from ubiquinone to O2, which confers cyanide resistance by bypassing COX. : 704
Diagnosis
Lactate is produced by anaerobic glycolysis when oxygen concentration becomes too low for the normal aerobic respiration pathway. Cyanide poisoning inhibits aerobic respiration and therefore increases anaerobic glycolysis which causes a rise of lactate in the plasma. A lactate concentration above 10 mmol per liter is an indicator of cyanide poisoning, as defined by the presence of a blood cyanide concentration above 40 µmol per liter. Lactate levels greater than 6 mmol/L after reported or strongly suspected pure cyanide poisoning, such as cyanide-containing smoke exposure, suggests significant cyanide exposure.Methods of detection include colorimetric assays such as the Prussian blue test, the pyridine-barbiturate assay, also known as the "Conway diffusion method" and the taurine fluorescence-HPLC but like all colorimetric assays these are prone to false positives. | Lipid peroxidation resulting in "TBARS," an artifact of heart attack produces dialdehydes that cross-react with the pyridine-barbiturate assay. Meanwhile, the taurine-fluorescence-HPLC assay used for cyanide detection is identical to the assay used to detect glutathione in spinal fluid. Cyanide and thiocyanate assays have been run with mass spectrometry (LC/MS/MS), which are considered specific tests. Since cyanide has a short half-life, the main metabolite, thiocyanate is typically measured to determine exposure. Other methods of detection include the identification of plasma lactate. Treatment
Decontamination
Decontamination of people exposed to hydrogen cyanide gas only requires removal of the outer clothing and the washing of their hair. Those exposed to liquids or powders generally require full decontamination. Antidote
The International Programme on Chemical Safety issued a survey (IPCS/CEC Evaluation of Antidotes Series) that lists the following antidotal agents and their effects: oxygen, sodium thiosulfate, amyl nitrite, sodium nitrite, 4-dimethylaminophenol, hydroxocobalamin, and dicobalt edetate (Kelocyanor), as well as several others. Other commonly-recommended antidotes are solutions A and B (a solution of ferrous sulfate in aqueous citric acid, and aqueous sodium carbonate, respectively) and amyl nitrite. The United States standard cyanide antidote kit first uses a small inhaled dose of amyl nitrite, followed by intravenous sodium nitrite, followed by intravenous sodium thiosulfate. Hydroxocobalamin was approved for use in the US in late 2006 and is available in Cyanokit antidote kits. Sulfanegen TEA, which could be delivered to the body through an intra-muscular (IM) injection, detoxifies cyanide and converts the cyanide into thiocyanate, a less toxic substance. | 11
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A two-day CPET cannot be used to rule out chronic fatigue syndrome. : 216
Definitions
Notable definitions include:
Centers for Disease Control and Prevention (CDC) definition (1994), the most widely used clinical and research description of CFS, is also called the Fukuda definition and is a revision of the Holmes or CDC 1988 scoring system. The 1994 criteria require the presence of four or more symptoms beyond fatigue, while the 1988 criteria require six to eight. The ME/CFS 2003 Canadian Clinical working definition states: "A patient with ME/CFS will meet the criteria for fatigue, post-exertional malaise and/or fatigue, sleep dysfunction, and pain; have two or more neurological/cognitive manifestations and one or more symptoms from two of the categories of autonomic, neuroendocrine, and immune manifestations; and the illness persists for at least 6 months". The Myalgic Encephalomyelitis International Consensus Criteria (ICC) published in 2011 is based on the Canadian working definition and has an accompanying primer for clinicians The ICC does not have a six months waiting time for diagnosis. The ICC requires post-exertional neuroimmune exhaustion (PENE) which has similarities with post-exertional malaise, plus at least three neurological symptoms, at least one immune or gastrointestinal or genitourinary symptom, and at least one energy metabolism or ion transportation symptom. Unrefreshing sleep or sleep dysfunction, headaches or other pain, and problems with thinking or memory, and sensory or movement symptoms are all required under the neurological symptoms criterion. According to the ICC, patients with post-exertional neuroimmune exhaustion but only partially meet the criteria should be given the diagnosis of atypical myalgic encephalomyelitis. | In February 2010, the All-Party Parliamentary Group on ME (APPG on ME) produced a legacy paper, which welcomed the recent MRC initiative, but felt that far too much emphasis in the past had been on psychological research, with insufficient attention to biomedical research, and that further biomedical research must be undertaken to help discover a cause and more effective forms of management for this disease.Controversy surrounds psychologically oriented models of the disease and behavioral treatments conducted in the UK. United States
In 1998, $13 million for CFS research was found to have been redirected or improperly accounted for by the United States CDC, and officials at the agency misled Congress about the irregularities. The agency stated that they needed the funds to respond to other public-health emergencies. The director of a US national patient advocacy group charged the CDC had a bias against studying the disease. The CDC pledged to improve their practices and to restore the $13 million to CFS research over three years.On 29 October 2015, the National Institutes of Health declared its intent to increase research on ME/CFS. The NIH Clinical Center was to study individuals with ME/CFS, and the National Institute of Neurological Disorders and Stroke would lead the Trans-NIH ME/CFS Research Working Group as part of a multi-institute research effort. | 11
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Camptocormia, also known as bent spine syndrome (BSS), is a symptom of a multitude of diseases that is most commonly seen in the elderly. It is identified by an abnormal thoracolumbar spinal flexion, which is a forward bending of the lower joints of the spine, occurring in a standing position. In order to be classified as BSS, the anterior flexion (the lower back bending) must be of 45 degrees anteriorly. This classification differentiates it from a similar syndrome known as kyphosis. Although camptocormia is a symptom of many diseases, there are two common origins: neurological and muscular. Camptocormia is treated by alleviating the underlying condition causing it through therapeutic measures or lifestyle changes. History and society
Camptocormia comes from two Greek words, meaning "to bend" (κάμπτω, kamptō) and "trunk" (κόρμος, kormos), and was coined by Alexandre-Achille Souques and B. Rosanoff-Saloff. These two men also created the definition of the disease that is widely accepted today.When the disorder was first clinically studied around the time of First World War, it was believed to be a psychogenic conversion disorder that resulted from the severe trauma of war. Souques and others treated patients with psychological therapy and early versions of electrotherapy. Samuel A. Sandler used a similar approach to treat soldiers during the Second World War. The view of BSS as a conversion disorder led to a lack of awareness about the conditions and few diagnoses by physicians. As time progressed and advances were made in knowledge of neuroscience and physiology, biological mechanisms behind the irregular bending were identified. | In addition, patients with camptocormia often experience low back pain as a result of the condition. BSS often appears in individuals with Parkinsons disease, muscular dystrophies, endocrine disorders, inflammatory conditions (myositis), or mitochondrial myopathies. As previously mentioned, the disease is more common in older individuals. Pathology
When initially identified, camptocormia was classified as a psychogenic disease. Although the condition is sometimes a psychogenic manifestation, camptocormia typically originates from either muscular or neurological diseases. However, due to the wide variety of pathologies resulting in camptocormia, there is no singular cause that is most influential for the condition. Muscular origin
Myopathic origin BSS can be secondary to various muscular disorders or occur as a primary idiopathy. These etiologies are termed secondary and primary BSS respectively. Idiopathic primary BSS is a late-onset myopathy with progressive muscular weakness that is detected on the spinal extensor muscles in elderly patients and is more predominant in females. The pathogenesis of primary BSS is typically related to fibrosis and fatty infiltration of muscular tissues and to mitochondrial changes due to the aging process. Specifically, weakening occurs in the paravertebral muscles of patients. | 11
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Further reading
Palacios, Druce, Du, Tran, Birch, Briese, Conlan, Quan, Hui, Marshall, Simons, Egholm, Paddock, Shieh, Goldsmith, Zaki, Catton, Lipkin (2008). "A New Arenavirus in a Cluster of Fatal Transplant-Associated Diseases". The New England Journal of Medicine. 358 (10): 991–998. doi:10.1056/NEJMoa073785. PMID 18256387. {{cite journal}}: CS1 maint: multiple names: authors list (link)
External links
Virus Pathogen Database and Analysis Resource (ViPR): Arenaviridae | When the mutation is present, there is no signal for B cells to undergo class switching, so there is an excess of IgM and little to no other immunoglobulin types produced. Type 4
Immunodeficiency with hyper IgM type 4 is poorly characterized. All that is known is that there is an excess of IgM in the blood, with normal levels of the other immunoglobulins. The exact cause is yet to be determined. Type 5
Immunodeficiency with hyper IgM type 5 is caused by a mutation in the Uracil-DNA glycosylase (UNG) gene, which, like AICDA, is located on chromosome 12. This codes for Uracil DNA Glycosylase, which is responsible for excising previous uracil bases that are due to cytosine deamination, or previous uracil misincorporation from double-stranded previous DNA substrates. This enzyme is also responsible for helping with gene conversion during somatic recombination in B cells. The mutation in the gene causes an enzyme that does not function properly, thus gene conversion does not proceed and class switching cannot occur. See also
Monoclonal gammopathy of undetermined significance
References
== External links == | 0-1
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The leaves were dried for half a day, then chopped into small pieces with a string trimmer and sprinkled with a small amount of powdered cement (replacing sodium carbonate from former times). Several hundred pounds of this mixture were soaked in 50 US gallons (190 L) of gasoline for a day, then the gasoline was removed and the leaves were pressed for the remaining liquid, after which they could be discarded. Then battery acid (weak sulfuric acid) was used, one bucket per 55 lb (25 kg) of leaves, to create a phase separation in which the cocaine free base in the gasoline was acidified and extracted into a few buckets of "murky-looking smelly liquid". Once powdered caustic soda was added to this, the cocaine precipitated and could be removed by filtration through a cloth. The resulting material, when dried, was termed pasta and sold by the farmer. The 3750 pound yearly harvest of leaves from a hectare produced 6 lb (2.5 kg) of pasta, approximately 40–60% cocaine. Repeated recrystallization from solvents, producing pasta lavada and eventually crystalline cocaine were performed at specialized laboratories after the sale.Attempts to eradicate coca fields through the use of defoliants have devastated part of the farming economy in some coca-growing regions of Colombia, and strains appear to have been developed that are more resistant or immune to their use. Whether these strains are natural mutations or the product of human tampering is unclear. | Its actual effectiveness has never been systematically studied.In 1986 an article in the Journal of the American Medical Association revealed that U.S. health food stores were selling dried coca leaves to be prepared as an infusion as "Health Inca Tea". While the packaging claimed it had been "decocainized", no such process had actually taken place. The article stated that drinking two cups of the tea per day gave a mild stimulation, increased heart rate, and mood elevation, and the tea was essentially harmless. Insufflation
Nasal insufflation (known colloquially as "snorting", "sniffing", or "blowing") is a common method of ingestion of recreational powdered cocaine. The drug coats and is absorbed through the mucous membranes lining the nasal passages. Cocaines desired euphoric effects are delayed when snorted through the nose by about five minutes. This occurs because cocaines absorption is slowed by its constricting effect on the blood vessels of the nose. Insufflation of cocaine also leads to the longest duration of its effects (60–90 minutes). When insufflating cocaine, absorption through the nasal membranes is approximately 30–60%In a study of cocaine users, the average time taken to reach peak subjective effects was 14.6 minutes. Any damage to the inside of the nose is because cocaine highly constricts blood vessels – and therefore blood and oxygen/nutrient flow – to that area. Rolled up banknotes, hollowed-out pens, cut straws, pointed ends of keys, specialized spoons, long fingernails, and (clean) tampon applicators are often used to insufflate cocaine. | 11
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Public concern over the safety of generic drugs was further exacerbated by a Congressional investigation into bribery at the FDA by generics companies that found pervasive corruption; the investigation had been spurred by the generics company Mylan, which had hired private investigators based on its beliefs that competitors were getting unfair advantages in getting their generics approved.Mylan itself developed a version of a triamterene/hydrochlorothiazide combination drug after the Dyazide patent expired, and used a different, more stable formulation as well as different dosages of each active ingredient (50 mg hydrochlorothiazide and 75 mg triamterene, compared with Dyazides 25 mg hydrochlorothiazide and 50 mg triamterene) so it had to get approval as a new drug, as opposed to a generic; their product was called Maxzide and was approved in 1984. The higher dose allowed once per day dosing, which Mylan and its marketing partner, Lederle, believed would help it compete against Dyazide, which had $210M in sales in 1983.Mylans patents on the drug were declared invalid in court, and its marketing exclusivity expired in 1987, prompting a rush of generic competition and litigation by two of them, American Therapeutics Inc. and Vitarine Pharmaceuticals, with the FDA. Vitarine, along with Par Pharmaceutical, were two of the companies that Mylan had targeted in its investigation into corruption and it turned out that Par and Vitarine had each used Mylans Maxzide to obtain its bioequivalence data, leading both companies to withdraw its generic competitor to Mylans product. Generics eventually entered the market. | These Vaccine Court awards often come with language stating that the Court denies that the specific vaccine "caused petitioner to suffer CIDP or any other injury. Nevertheless, the parties agree to the joint stipulation, attached hereto as Appendix A. The undersigned finds said stipulation reasonable and adopts it as the decision of the Court in awarding damages, on the terms set forth therein." A keyword search on the Court of Federal Claims "Opinions/Orders" database for the term "CIDP" returns 202 opinions related to CIDP and vaccine injury compensation. See also
Autoimmune disease
Neurology
References
External links
CIDP at NINDS
CIDP at GBS|CIDP Foundation International | 0-1
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Elapegademase, sold under the brand name Revcovi, is a medication for the treatment of the rare disease adenosine deaminase deficiency-SCID in children and adults.It is a recombinant enzyme that is administered weekly by intramuscular injection.Elapegademase may interact with PEGylated drugs.Elapegademase-lvlr was approved by the U.S. Food and Drug Administration (FDA) in 2018. Leadiant Biosciences was awarded a priority review voucher for its development under the pediatric rare diseases program. References
External links
"Elapegademase". Drug Information Portal. U.S. National Library of Medicine. | Transdermal dosing results in significantly higher exposure to selegiline and lower exposure to all metabolites when compared to oral dosing; this is due to the extensive first-pass metabolism of the pill form and low first-pass metabolism of the patch form. The site of application is not a significant factor in how the drug is distributed. In humans, selegiline does not accumulate in the skin, nor is it metabolized there. Chemistry
Selegiline belongs to the phenethylamine and amphetamine chemical families. It is also known as L-deprenyl, as well as (R)-(–)-N,α-dimethyl-N-(2-propynyl)phenethylamine or (R)-(–)-N-methyl-N-2-propynylamphetamine. The compound is a derivative of levomethamphetamine (L-methamphetamine) with a propargyl group attached to the nitrogen atom. This detail is borrowed from pargyline, an older MAO-B inhibitor of the phenylalkylamine group. Selegiline is the levorotatory enantiomer of the racemic mixture deprenyl. Selegiline is synthesized by the alkylation of (–)-methamphetamine using propargyl bromide.Another clinically used MAOI of the amphetamine class is tranylcypromine. History
Following the discovery that the tuberculosis drug iproniazid elevated the mood of people taking it, and the subsequent discovery that the effect was likely due to inhibition of MAO, many people and companies started trying to discover MAO inhibitors to use as antidepressants. Selegiline was discovered by Zoltan Ecseri at the Hungarian drug company, Chinoin (part of Sanofi since 1993), which they called E-250. | 0-1
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According to the U.S. National Institutes of Health (NIH), a blood glucose level below 70 mg/dL (3.9 mmol/L) at the time of symptoms followed by relief after eating confirms a diagnosis for reactive hypoglycemia. Signs and symptoms
Symptoms vary according to individuals hydration level and sensitivity to the rate and/or magnitude of decline of their blood glucose concentration.A crash is usually felt within four hours of heavy carbohydrate consumption. Along with the symptoms of hypoglycemia, symptoms of reactive hypoglycemia include:
The majority of these symptoms, often correlated with feelings of hunger, mimic the effect of inadequate sugar intake as the biology of a crash is similar in itself to the bodys response to low blood sugar levels following periods of glucose deficiency. Causes
The NIH states: "The causes of most cases of reactive hypoglycemia are still open to debate. Some researchers suggest that certain people may be more sensitive to the body’s normal release of the hormone epinephrine, which causes many of the symptoms of hypoglycemia. Others believe deficiencies in glucagon secretion might lead to reactive hypoglycemia.Several other hormones are responsible for modulating the bodys response to insulin, including cortisol, growth hormone and sex hormones. Untreated or under-treated hormonal disorders such as adrenal insufficiency (see also Addisons disease) or growth hormone deficiency can therefore sometimes cause insulin hypersensitivity, and reactive hypoglycemia. Stomach bypass surgery or hereditary fructose intolerance are believed to be causes, albeit uncommon, of reactive hypoglycemia. | Another cause might be hysteresis effect of insulin action, i.e., the effect of insulin is still prominent even if both plasma glucose and insulin levels were already low, causing a plasma glucose level eventually much lower than the baseline level.Sugar crashes are not to be confused with the after-effects of consuming large amounts of protein, which produces fatigue akin to a sugar crash, but are instead the result of the body prioritising the digestion of ingested food.The prevalence of this condition is difficult to ascertain because a number of stricter or looser definitions have been used. It is recommended that the term reactive hypoglycemia be reserved for the pattern of postprandial hypoglycemia which meets the Whipple criteria (symptoms correspond to measurably low glucose and are relieved by raising the glucose), and that the term idiopathic postprandial syndrome be used for similar patterns of symptoms where abnormally low glucose levels at the time of symptoms cannot be documented. To assist in diagnosis, a doctor may order an HbA1c test, which measures the blood sugar average over the two or three months before the test. The more specific 6-hour glucose tolerance test can be used to chart changes in the patients blood sugar levels before ingestion of a special glucose drink and at regular intervals during the six hours following to see if an unusual rise or drop in blood glucose levels occurs. | 11
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A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinsons disease, Alzheimers disease, Huntingtons disease, multiple system atrophy, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies (like proteinopathy) and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well. Within neurodegenerative diseases, it is estimated that 55 million people worldwide had dementia in 2019, and that by 2050 this figure will increase to 139 million people. Specific disorders
Alzheimers disease
Alzheimers disease (AD) is a chronic neurodegenerative disease that results in the loss of neurons and synapses in the cerebral cortex and certain subcortical structures, resulting in gross atrophy of the temporal lobe, parietal lobe, and parts of the frontal cortex and cingulate gyrus. It is the most common neurodegenerative disease. Even with billions of dollars being used to find a treatment for Alzheimers disease, no effective treatments have been found. | The weaker signals from subthalamic nuclei thus cause reduced initiation and modulation of movement, resulting in the characteristic movements of the disorder, notably chorea. Huntingtons disease presents itself later in life even though the proteins that cause the disease works towards manifestation from their early stages in the humans affected by the proteins. Along with being a neurodegenerative disorder, HD has links to problems with neurodevelopment.HD is caused by polyglutamine tract expansion in the huntingtin gene, resulting in the mutant huntingtin. Aggregates of mutant huntingtin form as inclusion bodies in neurons, and may be directly toxic. Additionally, they may damage molecular motors and microtubules to interfere with normal axonal transport, leading to impaired transport of important cargoes such as BDNF. Huntingtons disease currently has no effective treatments that would modify the disease. Multiple sclerosis
Multiple sclerosis (MS) is a chronic debilitating demyelinating disease of the central nervous system, caused by an autoimmune attack resulting in the progressive loss of myelin sheath on neuronal axons. The resultant decrease in the speed of signal transduction leads to a loss of functionality that includes both cognitive and motor impairment depending on the location of the lesion. The progression of MS occurs due to episodes of increasing inflammation, which is proposed to be due to the release of antigens such as myelin oligodendrocyte glycoprotein, myelin basic protein, and proteolipid protein, causing an autoimmune response. | 11
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A BBC investigation in June 2008 found that this advice was being widely ignored by British doctors. Evidence suggested that the elderly are more likely to experience weight gain on olanzapine compared to aripiprazole and risperidone. Adverse effects
The principal side effect of olanzapine is weight gain, which may be profound in some cases and/or associated with derangement in blood-lipid and blood-sugar profiles (see section metabolic effects). A 2013 meta-analysis of the efficacy and tolerance of 15 antipsychotic drugs (APDs) found that it had the highest propensity for causing weight gain out of the 15 APDs compared with an SMD of 0.74. Extrapyramidal side effects, although potentially serious, are infrequent to rare from olanzapine, but may include tremors and muscle rigidity. Aripiprazole, asenapine, clozapine, quetiapine and olanzapine, in comparison to other antipsychotic drugs, are less frequently associated with hyperprolactinaemia. Although these drugs can cause transient or sustained hyperprolactinaemia, the risk is much lower. Owing to its partial dopaminergic agonist effect, aripiprazole is likely to reduce prolactin levels and, in some patients, can cause hypoprolactinaemia. Although olanzapine causes an early dose-related rise in prolactin, this is less frequent and less marked than that seen with haloperidol, and is usually transient. | Olanzapine was effective for treating the prodromal symptoms, but was associated with significant weight gain. References
External links
"Olanzapine". Drug Information Portal. U.S. National Library of Medicine. Alex B (5 January 2007). "Lilly Settles With 18,000 Over Zyprexa". The New York Times. | 11
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Angiogenic factors are crucial for vascular growth in the placenta. An FLT1 soluble isoform caused by a splice variant is sFLT1, which works as an antiangiogenic factor, reducing vascular growth in the placenta. A healthy, normotensive pregnancy is characterized by a balance between these factors. However, upregulation of this variant and overexpression of sFL1 can contribute to endothelial dysfunction. Reduced vascular growth and endothelial dysfunction manifest primarily in maternal symptoms such as renal failure, edema, and seizures. However, these factors can also lead to inadequate oxygen, nutrient, or blood supply to the fetus. Furthermore, in this loci region, several single-nucleotide polymorphisms (SNPs) have been observed to impact the overexpression of sFL1. Specifically, SNPs rs12050029 and rs4769613s risk alleles are linked with low red blood cell counts and carry an increased risk of late-onset pre-eclampsia. Patau syndrome, or Trisomy 13, is also associated with the upregulation of sFLT1 due to the extra copy of the 13th chromosome. Because of this upregulation of an antiangiogenic factor, women with trisomy 13 pregnancies often experience reduced placental vascularization and are at higher risk for developing pre-eclampsia.Beyond fetal loci, there have been some maternal loci identified as effectors of pre-eclampsia. Alpha-ketoglutarate-dependent hydroxylase expression on chromosome 16 in the q12 region is also associated with pre-eclampsia. Specifically, allele rs1421085 heightens the risk of not just pre-eclampsia but also an increase in BMI and hypertension. This pleiotropy is one of the reasons why these traits are considered to be a risk factor. | In November 2006 the American Dental Association published information stating that water fluoridation is safe, effective and healthy; that enamel fluorosis, usually mild and difficult for anyone except a dental health care professional to see, can result from ingesting more than optimal amounts of fluoride in early childhood; that it is safe to use fluoridated water to mix infant formula; and that the probability of babies developing fluorosis can be reduced by using ready-to-feed infant formula or using water that is either free of fluoride or low in fluoride to prepare powdered or liquid concentrate formula. They go on to say that the way to get the benefits of fluoride but minimize the risk of fluorosis for a child is to get the right amount of fluoride, not too much and not too little. "Your dentist, pediatrician or family physician can help you determine how to optimize your childs fluoride intake." Prevention
Dental fluorosis can be prevented by lowering the amount of fluoride intake to below the tolerable upper limit. This can be achieved by consuming de-fluorinated water and improving the general nutritional status of the people. History
In ancient times, Galen describes what is thought to be dental fluorosis. However, it was not until the early 20th century that dental fluorosis became increasingly recognized and scientifically studied. In 1901 Eager published the first description of the "mottled enamel" of immigrants from a small village near Naples, Italy. | 0-1
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Several disease that are frequently used for differential diagnoses include Binswangers disease, CADASIL, Nasu-Hakula disease, and chronic progressive multiple sclerosis. Treatment
There is currently no treatment or cure for CARASIL. Most frequently, a combination of supportive care and medications to prevent the occurrence of stroke are recommended. Counseling or other forms of emotional support may be beneficial to both patients and family members. Medications or therapies may be used to treat specific symptoms of the disease. Tizanidine and baclofen may be used to treat the spasticity of the limbs. A walker or cane may be used to assist individuals with gait disturbances. Anxiolytics may be prescribed for mood changes. Prognosis
The prognosis for individuals with CARASIL is progressive neurological decline over the course of 10–20 years after the onset of symptoms, ultimately ending in death. CARASIL is a degenerative disease, and most patients live only 10 years past symptom onset, although some may live for 20–30 more years. Epidemiology
Of the approximately 50 cases worldwide, the majority were found in Japan, with a few cases in China, Spain, Portugal, and Romania. CARASIL appears to affect males more often than females. A ratio of 7.5 males to 1 female was observed in Japan. Research
Research consists primarily of case studies reporting observed cases of CARASIL, one study suggests that a possible future treatment option may be inhibition of TGF-β signaling by an angiotensin I receptor agonist, due to the fact that an excess of TGF-β signaling is involved in causing CARASIL. | A large number of toxic plants may also cause symptoms.Some agents are more specific to a certain species. Transmissible gastroenteritis coronavirus (TGEV) occurs in pigs resulting in vomiting, diarrhea, and dehydration. It is believed to be introduced to pigs by wild birds and there is no specific treatment available. It is not transmissible to humans. See also
Enterocolitis
References
Notes
Dolin, Raphael; Mandell, Gerald L.; Bennett, John E., eds. (2010). Mandell, Douglas, and Bennetts principles and practice of infectious diseases (7th ed.). Philadelphia: Churchill Livingstone/Elsevier. ISBN 978-0-443-06839-3. External links
Diarrhoea and Vomiting Caused by Gastroenteritis: Diagnosis, Assessment and Management in Children Younger than 5 Years – NICE Clinical Guidelines, No. 84. "Gastroenteritis". MedlinePlus. U.S. National Library of Medicine. | 0-1
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A World Health Organization study estimated that between 70 and 90% of head injuries that receive treatment are mild, and a US study found that moderate and severe injuries each account for 10% of TBIs, with the rest mild.The incidence of TBI varies by age, gender, region and other factors. Findings of incidence and prevalence in epidemiological studies vary based on such factors as which grades of severity are included, whether deaths are included, whether the study is restricted to hospitalized people, and the studys location. The annual incidence of mild TBI is difficult to determine but may be 100–600 people per 100,000. Mortality
In the US, the case fatality rate is estimated to be 21% by 30 days after TBI. A study on Iraq War soldiers found that severe TBI carries a mortality of 30–50%. Deaths have declined due to improved treatments and systems for managing trauma in societies wealthy enough to provide modern emergency and neurosurgical services. The fraction of those who die after being hospitalized with TBI fell from almost half in the 1970s to about a quarter at the beginning of the 21st century. This decline in mortality has led to a concomitant increase in the number of people living with disabilities that result from TBI.Biological, clinical, and demographic factors contribute to the likelihood that an injury will be fatal. In addition, outcome depends heavily on the cause of head injury. In the US, patients with fall-related TBIs have an 89% survival rate, while only 9% of patients with firearm-related TBIs survive. | Weisse found that 13% of 121 patients had endocarditis. Marantz also found a prevalence of endocarditis of 13% among such patients in the emergency department with fever. Samet found a 6% incidence among 283 such patients, but after excluding patients with initially apparent major illness to explain the fever (including 11 cases of manifest endocarditis), there was a 7% prevalence of endocarditis.Among people with staphylococcal bacteremia (SAB), one study found a 29% prevalence of endocarditis in community-acquired SAB versus 5% in nosocomial SAB. However, only 2% of strains were resistant to methicillin and so these numbers may be low in areas of higher resistance. Prevention
Not all people with heart disease require antibiotics to prevent infective endocarditis. Heart diseases have been classified into high, medium and low risk of developing IE. Those falling into high risk category require IE prophylaxis before endoscopies and urinary tract procedures. Diseases listed under high risk include:
Prior endocarditis
Unrepaired cyanotic congenital heart diseases
Completely repaired congenital heart disease in their first 6 months
Prosthetic heart valves
Incompletely repaired congenital heart diseases
Cardiac transplant valvulopathyFollowing are the antibiotic regimens recommended by the American Heart Association for antibiotic prophylaxis:
Oral amoxicillin one hour before the procedure
Intravenous or intramuscular ampicillin one hour before the procedure
In patients allergic to penicillins
Azithromycin or clarithromycin orally one hour before the procedure
Cephalexin orally one hour before the procedure
Clindamycin orally one hour before the procedureIn the UK, NICE clinical guidelines no longer advise prophylaxis because there is no clinical evidence that it reduces the incidence of IE and there are negative effects (e.g. | 0-1
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Hyperoxaluria is an excessive urinary excretion of oxalate. Individuals with hyperoxaluria often have calcium oxalate kidney stones. It is sometimes called Birds disease, after Golding Bird, who first described the condition. Causes
Hyperoxaluria can be primary (as a result of a genetic defect) or secondary to another disease process. Type I primary hyperoxaluria (PH1) is associated mutations in the gene encoding AGXT, a key enzyme involved in oxalate metabolism. PH1 is an example of a protein mistargeting disease, wherein AGXT shows a trafficking defect. Instead of being trafficked to peroxisomes, it is targeted to mitochondria, where it is metabolically deficient despite being catalytically active. Type II is associated with GRHPR.Secondary hyperoxaluria can occur as a complication of jejunoileal bypass, or in a patient who has lost much of the ileum with an intact colon. In these cases, hyperoxaluria is caused by excessive gastrointestinal oxalate absorption.Excessive intake of oxalate-containing food, such as rhubarb, may also be a cause in rare cases. Diagnosis
Types
Primary hyperoxaluria
Enteric hyperoxaluria
Idiopathic hyperoxaluria
Oxalate poisoning
Treatment
The main therapeutic approach to primary hyperoxaluria is still restricted to symptomatic treatment, i.e. kidney transplantation once the disease has already reached mature or terminal stages. However, through genomics and proteomics approaches, efforts are currently being made to elucidate the kinetics of AGXT folding which has a direct bearing on its targeting to appropriate subcellular localization. Secondary hyperoxaluria is much more common than primary hyperoxaluria, and should be treated by limiting dietary oxalate and providing calcium supplementation. A child with primary hyperoxaluria was treated with a liver and kidney transplant. | A favorable outcome is more likely if a kidney transplant is complemented by a liver transplant, given the disease originates in the liver. Controversy
Perhaps the key difficulty in understanding pathogenesis of primary hyperoxaluria, or more specifically, why AGXT ends up in mitochondria instead of peroxisomes, stems from AGXTs somewhat peculiar evolution. Namely, prior to its current peroxysomal destiny, AGXT indeed used to be bound to mitochondria. AGXTs peroxisomal targeting sequence is uniquely specific for mammalian species, suggesting the presence of additional peroxisomal targeting information elsewhere in the AGT molecule. As AGXT was redirected to peroxisomes over the course of evolution, it is plausible that its current aberrant localization to mitochondria owes to some hidden molecular signature in AGXTs spatial configuration unmasked by PH1 mutations affecting the AGXT gene. References
External links
GeneReviews/NIH/NCBI/UW entry on Primary Hyperoxaluria Type 1 | 11
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Diagnosis
LGL syndrome is diagnosed in a person who has experienced episodes of abnormal heart racing (arrhythmias) who has a PR interval less than or equal to 0.12 second (120 ms) with normal QRS complex configuration and duration on their resting ECG. A short PR interval found incidentally on an ECG without episodes of tachycardia is simply a benign ECG variant.LGL can be distinguished from WPW syndrome because the delta waves seen in WPW syndrome are not seen in LGL syndrome. The QRS complex will also be narrow in LGL syndrome, as opposed to WPW, because ventricular conduction is via the His-Purkinje system. Lown–Ganong–Levine syndrome is a clinical diagnosis that came about before the advent of electrophysiology studies. It is important to be aware that not all WPW ECGs have a delta wave; the absence of a delta wave does not conclusively rule out WPW. Prognosis
Individuals with LGL syndrome do not carry an increased risk of sudden death. The only morbidity associated with the syndrome is the occurrence of paroxysmal episodes of tachycardia which may be of several types, including sinus tachycardia, atrioventricular nodal re-entrant tachycardia, atrial fibrillation, or atrial flutter. See also
Cardiac electrophysiology
Electrocardiogram
Electrophysiology study
Premature ventricular contraction
Wolff–Parkinson–White syndrome
References
== External links == | Cytoreductive therapy
In cases of advanced systemic mastocytosis or rare cases with indolent systemic mastocytosis with very troublesome symptoms, cytoreductive therapy can be indicated. ɑ-interferon. Given as subcutaneous injections. Side effects include fatigue and influenza-like symptoms
Cladribine (CdA). Chemotherapy which is given as subcutaneous injections. Side effects include immunodeficiency and infections. Tyrosine kinase inhibitors (TKI)
Midostaurin. TKI acting on many different tyrosine kinases, approved by FDA and EMA for advanced mastocytosis
Imatinib. Can have effect in rare cases without mutation in KIT(D816V)
Masitinib. Is being tested in trials. Not approved. Midostaurin - 60% respond. Avapritinib in trials; currently being tested but showing promise in reduction of tryptase levels.Allogeneic stem cell transplantation has been used in rare cases with aggressive systemic mastocytosis in patients deemed to be fit for the procedure. Other
Treatment with ultraviolet light can relieve skin symptoms, but may increase the risk of skin cancer. Prognosis
Patients with indolent systemic mastocytosis have a normal life expectancy. The prognosis for patients with advanced systemic mastocytosis differs depending on type of disease with MCL being the most serious form with short survival. Epidemiology
The true incidence and prevalence of mastocytosis is unknown, but mastocytosis generally has been considered to be an "orphan disease"; orphan diseases affect 200,000 or fewer people in the United States. Mastocytosis, however, often may be misdiagnosed, as it typically occurs secondary to another condition, and thus may occur more frequently than assumed. | 0-1
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In his paper, Jung introduced the non-psychotic version of the illness with the statement, "I would like to publish a number of cases whose peculiarity consists in chronic hypomanic behavior" where "it is not a question of real mania at all but of a hypomanic state which cannot be regarded as psychotic." Jung illustrated the hypomanic variation with five case histories, each involving hypomanic behavior, occasional bouts of depression, and mixed mood states, which involved personal and interpersonal upheaval for each patient.In 1975, Jungs original distinction between mania and hypomania gained support. Fieve and Dunner published an article recognizing that only individuals in a manic state require hospitalization. It was proposed that the presentation of either the one state or the other differentiates two distinct diseases; the proposition was initially met with skepticism. However, studies since confirm that BP-II is a phenomenologically distinct disorder.Empirical evidence, combined with treatment considerations, led the DSM-IV Mood Disorders Work Group to add BP-II as its own entity in the 1994 publication. Only one other mood disorder was added to this edition, indicating the conservative nature of the DSM-IV work group. In May 2013, the DSM-5 was released. Two revisions to the existing BP-II criteria are anticipated. The first expected change will reduce the required duration of a hypomanic state from four to two days. The second change will allow hypomania to be diagnosed without the manifestation of elevated mood; that is, increased energy/activity will be sufficient. | Different patterns of muscle weakness or hyperactivity can occur based on the location of the lesion, causing a multitude of neurological symptoms, including spasticity, rigidity, or dystonia.Spastic hypertonia involves uncontrollable muscle spasms, stiffening or straightening out of muscles, shock-like contractions of all or part of a group of muscles, and abnormal muscle tone. It is seen in disorders such as cerebral palsy, stroke, and spinal cord injury. Rigidity is a severe state of hypertonia where muscle resistance occurs throughout the entire range of motion of the affected joint independent of velocity. It is frequently associated with lesions of the basal ganglia. Individuals with rigidity present with stiffness, decreased range of motion and loss of motor control. Dystonic hypertonia refers to muscle resistance to passive stretching (in which a therapist gently stretches the inactive contracted muscle to a comfortable length at very low speeds of movement) and a tendency of a limb to return to a fixed involuntary (and sometimes abnormal) posture following movement. Management
Therapeutic interventions are best individualized to particular patients.Basic principles of treatment for hypertonia are to avoid noxious stimuli and provide frequent range of motion exercise. Physical interventions
Physiotherapy has been shown to be effective in controlling hypertonia through the use of stretching aimed to reduce motor neuron excitability. The aim of a physical therapy session could be to inhibit excessive tone as far as possible, give the patient a sensation of normal position and movement, and to facilitate normal movement patterns. | 0-1
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Combined oral contraceptive
Noretynodrel (and norethisterone) were subsequently discovered to be contaminated with a small percentage of the estrogen mestranol (an intermediate in their synthesis), with the noretynodrel in Rocks 1954–5 study containing 4–7% mestranol. When further purifying noretynodrel to contain less than 1% mestranol led to breakthrough bleeding, it was decided to intentionally incorporate 2.2% mestranol, a percentage that was not associated with breakthrough bleeding, in the first contraceptive trials in women in 1956. The noretynodrel and mestranol combination was given the proprietary name Enovid.The first contraceptive trial of Enovid led by Celso-Ramón García and Edris Rice-Wray began in April 1956 in Río Piedras, Puerto Rico. A second contraceptive trial of Enovid (and norethisterone) led by Edward T. Tyler began in June 1956 in Los Angeles. On January 23, 1957, Searle held a symposium reviewing gynecologic and contraceptive research on Enovid through 1956 and concluded Enovids estrogen content could be reduced by 33% to lower the incidence of estrogenic gastrointestinal side effects without significantly increasing the incidence of breakthrough bleeding.While these large-scale trials contributed to the initial understanding of the pill formulations clinical effects, the ethical implications of the trials generated significant controversy. Of note is the apparent lack of both autonomy and informed consent among participants in the Puerto Rican cohort prior to the trials. Many of these participants hailed from impoverished, working-class backgrounds. | Also in 1957, the FPA established a Council for the Investigation of Fertility Control (CIFC) to test and monitor oral contraceptives which began animal testing of oral contraceptives and in 1960 and 1961 began three large clinical trials in Birmingham, Slough, and London.In March 1960, the Birmingham FPA began trials of noretynodrel 2.5 mg + mestranol 50 µg, but a high pregnancy rate initially occurred when the pills accidentally contained only 36 µg of mestranol—the trials were continued with noretynodrel 5 mg + mestranol 75 µg (Conovid in the UK, Enovid 5 mg in the U.S.). In August 1960, the Slough FPA began trials of noretynodrel 2.5 mg + mestranol 100 µg (Conovid-E in the UK, Enovid-E in the U.S.). In May 1961, the London FPA began trials of Scherings Anovlar.In October 1961, at the recommendation of the Medical Advisory Council of its CIFC, the FPA added Searles Conovid to its Approved List of Contraceptives. On December 4, 1961, Enoch Powell, then Minister of Health, announced that the oral contraceptive pill Conovid could be prescribed through the NHS at a subsidized price of 2s per month. In 1962, Scherings Anovlar and Searles Conovid-E were added to the FPAs Approved List of Contraceptives. France
On December 28, 1967, the Neuwirth Law legalized contraception in France, including the pill. The pill is the most popular form of contraception in France, especially among young women. It accounts for 60% of the birth control used in France. The abortion rate has remained stable since the introduction of the pill. | 11
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Assuming the pressure difference between the two sides of the barrier is much smaller than
P
a
v
g
{\displaystyle P_{\rm {avg}}}
, the average absolute pressure in the system (i.e. | Δ
P
≪
P
a
v
g
{\displaystyle \Delta P\ll P_{\rm {avg}}}
), it is possible to express effusion flow as a volumetric flow rate as follows:
Φ
V
=
Δ
P
d
2
P
a
v
g
π
k
B
T
32
m
{\displaystyle \Phi _{V}={\frac {\Delta Pd^{2}}{P_{\rm {avg}}}}{\sqrt {\frac {\pi k_{B}T}{32m}}}}
or
Φ
V
=
Δ
P
d
2
P
a
v
g
π
R
T
32
M
{\displaystyle \Phi _{V}={\frac {\Delta Pd^{2}}{P_{\rm {avg}}}}{\sqrt {\frac {\pi RT}{32M}}}}
where
Φ
V
{\displaystyle \Phi _{V}}
is the volumetric flow rate of the gas,
P
a
v
g
{\displaystyle P_{\rm {avg}}}
is the average pressure on either side of the orifice, and
d
{\displaystyle d}
is the hole diameter. | 11
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Bannayan–Riley–Ruvalcaba syndrome (BRRS) is a rare overgrowth syndrome and hamartomatous disorder with occurrence of multiple subcutaneous lipomas, macrocephaly and hemangiomas. The disease is inherited in an autosomal dominant manner. The disease belongs to a family of hamartomatous polyposis syndromes, which also includes Peutz–Jeghers syndrome, juvenile polyposis and Cowden syndrome. Mutation of the PTEN gene underlies this syndrome, as well as Cowden syndrome, Proteus syndrome, and Proteus-like syndrome, these four syndromes are referred to as PTEN Hamartoma-Tumor Syndromes. Signs and symptoms
Bannayan–Riley–Ruvalcaba syndrome is associated with enlarged head and benign mesodermal hamartomas (multiple hemangiomas, and intestinal polyps). Dysmorphy as well as delayed neuropsychomotor development can also be present. The head enlargement does not cause widening of the ventricles or raised intracranial pressure; these individuals have a higher risk of developing tumors, as the gene involved in BRRs is phosphatase and tensin homologue.Some individuals have thyroid issues consistent with multinodular goiter, thyroid adenoma, differentiated non-medullary thyroid cancer,
most lesions are slowly growing. Visceral as well as intracranial involvement may occur in some cases, and can cause bleeding and symptomatic mechanical compression
Genetics
The genetics of the Bannayan–Riley–Ruvalcaba syndrome is determined, in the majority of cases, via the PTEN gene which presents about 30 mutations in this condition. This gene which regulates cell growth, when not working properly can lead to hamartomas. PTEN chromosomal location is 10q23.31, while the molecular location is 87,863,438 to 87,971,930 There are many syndromes that are linked to PTEN aside from Bannayan–Riley–Ruvalcaba Syndrome.The syndrome combines Bannayan–Zonana syndrome, Riley–Smith syndrome, and Ruvalcaba–Myhre–Smith syndrome. | Aminocaproic acid (also known as ε-aminocaproic acid, ε-Ahx, or 6-aminohexanoic acid) is a derivative and analogue of the amino acid lysine, which makes it an effective inhibitor for enzymes that bind that particular residue. Such enzymes include proteolytic enzymes like plasmin, the enzyme responsible for fibrinolysis. For this reason it is effective in treatment of certain bleeding disorders, and it is sold under the brand name Amicar. Aminocaproic acid is also an intermediate in the polymerization of Nylon-6, where it is formed by ring-opening hydrolysis of caprolactam. The crystal structure determination showed that the 6-aminohexanoic acid is present as a salt, at least in the solid state. Medical use
Aminocaproic acid (Amicar) is FDA-approved for use in the treatment of acute bleeding due to elevated fibrinolytic activity. It also carries an orphan drug designation from the FDA for the prevention of recurrent hemorrhage in patients with traumatic hyphema. In clinical practice, aminocaproic acid is frequently used off-label for control of bleeding in patients with severe thrombocytopenia, control of oral bleeding in patients with congenital and acquired coagulation disorders, control of perioperative bleeding associated with cardiac surgery, prevention of excessive bleeding in patients on anticoagulation therapy undergoing invasive dental procedures, and reduction of the risk of catastrophic hemorrhage in patients with acute promyelocytic leukemia. References
Further reading
Alkjaersig N, Fletcher AP, Sherry S (April 1959). "xi-Aminocaproic acid: an inhibitor of plasminogen activation". The Journal of Biological Chemistry. 234 (4): 832–7. doi:10.1016/S0021-9258(18)70185-3. PMID 13654273. Kang Y, Lewis JH, Navalgund A, Russell MW, Bontempo FA, Niren LS, Starzl TE (June 1987). | 0-1
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Other bird species have been known to develop rabies antibodies, a sign of infection, after feeding on rabies-infected mammals.The virus has also adapted to grow in cells of cold-blooded vertebrates. Most animals can be infected by the virus and can transmit the disease to humans. Worldwide, about 99% of human rabies cases come from domestic dogs. Other sources of rabies in humans include bats, monkeys, raccoons, foxes, skunks, cattle, wolves, coyotes, cats, and mongooses (normally either the small Asian mongoose or the yellow mongoose).Rabies may also spread through exposure to infected bears, domestic farm animals, groundhogs, weasels, and other wild carnivorans. However, lagomorphs, such as hares and rabbits, and small rodents, such as chipmunks, gerbils, guinea pigs, hamsters, mice, rats, and squirrels, are almost never found to be infected with rabies and are not known to transmit rabies to humans. Bites from mice, rats, or squirrels rarely require rabies prevention because these rodents are typically killed by any encounter with a larger, rabid animal, and would, therefore, not be carriers. The Virginia opossum (a marsupial, unlike the other mammals named in this paragraph, which are all eutherians/placental), has a lower internal body temperature than the rabies virus prefers and therefore is resistant but not immune to rabies. Marsupials, along with monotremes (platypuses and echidnas), typically have lower body temperatures than similarly sized eutherians.The virus is usually present in the nerves and saliva of a symptomatic rabid animal. The route of infection is usually, but not always, by a bite. | Boniva may refer to:
Boniva, a company acquired by software company SSA Global Technologies in August 2005
Ibandronic acid (marketed as Boniva), a potent bisphosphonate drug used in the prevention and treatment of osteoporosis | 0-1
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This treatment alone is not wholly effective, and many people still experience other symptoms such as lung disease and noninfectious inflammatory symptoms. This treatment replenishes Ig subtypes that the person lacks and is given at frequent intervals for life, and is thought to help reduce bacterial infections and boost immune function. Before therapy begins, plasma donations are tested for known blood-borne pathogens, then pooled and processed to obtain concentrated IgG samples. Infusions can be administered in three different forms: intravenously (IVIg), subcutaneously (SCIg), and intramuscularly (IMIg). The administration of intravenous immunoglobulins requires the insertion of a cannula or needle in a vein, usually in the arms or hands. Because highly concentrated product is used, IVIg infusions take place every 3 to 4 weeks. Subcutaneous infusions slowly release the Ig serum underneath the skin, again through a needle, and takes place every week. Intramuscular infusions are no longer widely used, as they can be painful and are more likely to cause reactions. People often experience adverse side effects to immunoglobulin infusions, including:
swelling at the insertion site (common in SCIG)
chills
headache
nausea (common in IVIG)
fatigue (common in IVIG)
muscle aches and pain, or joint pain
fever (common in IVIG and rare in SCIG)
hives (rare)
thrombotic events (rare)
aseptic meningitis (rare, more common in people with SLE)
anaphylactic shock (very rare)In addition to Ig replacement therapy, treatment may also involve immune suppressants, to control autoimmune symptoms of the disease, and high dose steroids like corticosteroids. In some cases, antibiotics are used to fight chronic lung disease resulting from CVID. | Differential diagnosis
Despite many distinguishing features, the clinical spectrums of following diseases may overlap with chancroid:
Primary syphilis
Genital herpesPractical clinical approach for this STI as Genital Ulcer Disease is to rule out top differential diagnosis of Syphilis and Herpes and consider empirical treatment for Chancroid as testing is not commonly done for the latter. Comparison with syphilis
There are many differences and similarities between the conditions syphilitic chancre and chancroid:
SimilaritiesBoth originate as pustules at the site of inoculation, and progress to ulcerated lesions
Both lesions are typically 1–2 cm in diameter
Both lesions are caused by sexually transmissible organisms
Both lesions typically appear on the genitals of infected individuals
Both lesions can be present at multiple sites and with multiple lesionsDifferencesChancre is a lesion typical of infection with the bacterium that causes syphilis, Treponema pallidum
Chancroid is a lesion typical of infection with the bacterium Haemophilus ducreyi
Chancres are typically painless, whereas chancroid are typically painful
Chancres are typically non-exudative, whereas chancroid typically have a grey or yellow purulent exudate
Chancres have a hard (indurated) edge, whereas chancroid have a soft edge
Chancres heal spontaneously within three to six weeks, even in the absence of treatment
Chancres can occur in the pharynx as well as on the genitals
Prevention
Chancroid spreads in populations with high sexual activity, such as prostitutes. Use of condom, prophylaxis by azithromycin, syndromic management of genital ulcers, treating patients with reactive syphilis serology are some of the strategies successfully tried in Thailand. | 0-1
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However, long-term observational studies are desperately needed to guide the development of evidence-based surveillance algorithms designed to detect late tumor progression." Also (see Medical and Gene Therapies, above): "Basic science and identification of genes, molecular pathways, and networks related to tumor growth are likely to change our approach to treatment including conservative management." Incidence of Sporadic VS
The U.S. National Institutes of Health (NIH) consensus statement for Acoustic Neuroma in 1991 estimated that 2–3,000 cases of VS were diagnosed in the U.S. annually—an incidence rate of about 10 per million of population per year. In 2015, researchers at the Cleveland Clinic in Ohio used population-based data of the Central Brain Tumor Registry of the U.S. to calculate an incidence of 10.9 per million of population, or about 3,300 cases of VS per year. A higher incidence up to 29.3 per million of population was found for the 65-74 year-old age group. There was no significant difference in incidence by gender. Incidence was higher in Asian Pacific Islanders, and lower in African Americans and Hispanics. The annual number of diagnosed VS increased significantly worldwide by the early 1990s with the introduction of magnetic resonance imaging (MRI). Notably, epidemiologists in Denmark (population of 5.7 million in 2015) reported 193 cases of VS for 2015—an incidence of 34 per million of population per year. The first MRI scanner in Denmark was functional in 1989, and by 2015 the number increased to approximately 100. | Complications
Infection
Repeated trauma
Bursting and reformation
Dysphagia (in the case of a large ranula)
Causes
Minor trauma to the floor of the mouth is thought to damage the delicate ducts that drain saliva from the sublingual gland into the oral cavity. The lesion is a mucous extravasation cyst (mucocele) of the floor of mouth, although a ranula is often larger than other mucoceles (mainly because the overlying mucosa is thicker). They can grow so large that they fill the mouth. The most usual source of the mucin spillage is the sublingual salivary gland, but ranulae may also arise from the submandibular duct or the minor salivary glands in the floor of the mouth. A cervical ranula occurs when the spilled mucin dissects its way through the mylohyoid muscle, which separates the sublingual space from the submandibular space, and creates a swelling in the neck. It may occur following rupture of a simple ranula. Rarely, ranulae may extend backwards into the parapharyngeal space. Mechanism
The fluid within a ranula has the viscous, jellylike consistency of egg white. Diagnosis
The histologic appearance is similar to mucoceles from other locations. The spilled mucin causes a granulation tissue to form, which usually contains foamy histiocytes. Ultrasound and magnetic resonance imaging may be useful to image the lesion. A small squamous cell carcinoma obstructing the Wharton duct may require clinical examination to be distinguished from a ranula. Criteria
Mostly seen in young children and adolescents, both sexes are equally affected. Swelling in floor of mouth, which may be painful. Mostly unilateral, on one side of frenulum. | 0-1
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Gastrinomas are neuroendocrine tumors (NETs), usually located in the duodenum or pancreas, that secrete gastrin and cause a clinical syndrome known as Zollinger–Ellison syndrome (ZES). A large number of gastrinomas develop in the pancreas or duodenum, with near-equal frequency, and approximately 10% arise as primary neoplasms in lymph nodes of the pancreaticoduodenal region (gastrinoma triangle).Most gastrinomas are sporadic (75–80%), whereas approximately 20–25% are associated with multiple endocrine neoplasia type 1 (MEN-1). Over 50% of gastrinomas are malignant and can metastasize to regional lymph nodes and liver. One fourth of gastrinomas are related to multiple endocrine neoplasia type 1, Zollinger–Ellison syndrome, peptic ulcer disease. Signs and symptoms
Gastrinoma in the early stages will have signs and symptoms of indigestion or similar to irritable bowel disease (IBD) such as:
Hypergastrinemia
Refractory or recurrent peptic ulcers involving duodenum
Chronic diarrhea
Generalized cancer symptoms
Abdominal pain
Gastrointestinal bleeding
Obstruction of intestine
Weight loss/poor appetite
Anemia (Due to vitamin B12 malabsorption, and bleeding)
Hematemesis
Gastroesophageal reflux disease
Esophageal complications (Barretts esophagus, esophagitis, stricture formation)
Vomiting
Steatorrhea
Pathophysiology
Gastrin is secreted by the G cells. G cells are primarily found in the pyloric antrum but can also be found in the duodenum and the pancreas. The primary function of gastrin is to induce the release of hydrochloric acid (HCl) from the parietal cells located in the fundus of the stomach. Parietal cells are responsible for hydrochloric (HCl) secretion along with intrinsic factor that binds to vitamin B12 and helps with its uptake in the terminal ileum. Other functions of gastrin include stimulating the growth of gastric mucosa and gastric motility and promoting gastric emptying. | Obstruction may refer to:
Places
Obstruction Island, in Washington state
Obstruction Islands, east of New Guinea
Medicine
Obstructive jaundice
Obstructive sleep apnea
Airway obstruction, a respiratory problem
Recurrent airway obstruction
Bowel obstruction, a blockage of the intestines. Gastric outlet obstruction
Distal intestinal obstruction syndrome
Congenital lacrimal duct obstruction
Bladder outlet obstruction
Politics and law
Obstruction of justice, the crime of interfering with law enforcement
Obstructionism, the practice of deliberately delaying or preventing a process or change, especially in politics
Emergency Workers (Obstruction) Act 2006
Science and mathematics
Obstruction set in forbidden graph characterizations, in the study of graph minors in graph theory
Obstruction theory, in mathematics
Propagation path obstruction
Single Vegetative Obstruction Model
Sports
Obstruction (baseball), when a fielder illegally hinders a baserunner
Obstructing the field
See also
The Five Obstructions, a 2003 film
USS Obstructor, an American minelayer ship used in World War II | 0-1
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In general, the mortality rate for infected AIDS patients is based on CD4+ marker counts. Patients with CD4+ counts over 180 cells/mm³ recover with supportive hospital care and medication; but, in patients with CD4+ counts below 50 cells/mm³, the effects are usually fatal within 3 to 6 months. During the Milwaukee cryptosporidiosis epidemic (the largest of its kind), 73% of AIDS patients with CD4+ counts lower than 50 cells/mm³ and 36% of those with counts between 50 and 200 cells/mm³ died within the first year of contracting the infection.The best treatment approach is to improve the immune status in immunodeficient individuals using highly active antiretroviral therapy that includes an HIV protease inhibitor along with continued use of antiparasitic medication. Antiparasitic drug treatment for immunocompromised individuals usually involves the combination of nitazoxanide, paromomycin, and azithromycin together; these drugs are only partially active in HIV/AIDS patients compared to their effect in immunocompetent persons. A Cochrane Collaboration review recommended that nitazoxanide be considered for use in treatment despite its reduced effectiveness in immunocompromised individuals.Currently, research is being done in molecular-based immunotherapy. For example, synthetic isoflavone derivates have been shown to fight off Cryptosporidium parvum both in vitro and in animal studies. Derivates of nitazoxanide, known as thiazolides, have also shown promising results in vitro. rifaximin is also sometimes used for immunocompromised patients/patients with severe disease. Epidemiology
Cryptosporidiosis is found worldwide. It causes 50.8% of water-borne diseases that are attributed to parasites. In developing countries, 8–19% of diarrheal diseases can be attributed to Cryptosporidium. | The source of the Cryptosporidium is believed to be overflow from the Milwaukee area combined sanitary and storm sewer system into Lake Michigan, which was then taken into the Howard Avenue Water Purification Plant and distributed to an estimated 880,000 residents (of the 1.61 million residents in the Milwaukee area who receive their drinking water from Lake Michigan). These residents, who receive their drinking water from Lake Michigan, were told to boil their water before drinking it. More people were affected in this one outbreak than the combined number of people affected in every cryptosporidiosis outbreak in the 24 years since then. An estimated 69 people died during the outbreak, according to the CDC. The UKs biggest outbreak occurred in Torbay in Devon in 1995. In the summer of 1996, Cryptosporidium affected approximately 2,000 people in Cranbrook, British Columbia, Canada. Weeks later, a separate incident occurred in Kelowna, British Columbia, where 10,000 to 15,000 people got sick. 2001–2009
In April 2001, an outbreak occurred in the city of North Battleford, Saskatchewan, Canada. Between 5800 and 7100 people had diarrheal illness, and 1907 cases of cryptosporidiosis were confirmed. Equipment failures at the citys antiquated water filtration plant following maintenance were found to have caused the outbreak. In the summer of 2005, after numerous reports by patrons of gastrointestinal upset, a water park at Seneca Lake State Park, in the Finger Lakes region of upstate New York was found to have two water storage tanks infected with Cryptosporidium. | 11
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The media influences eating disorders whether shown in a positive or negative light, it then has a responsibility to use caution when promoting images that projects an ideal that many turn to eating disorders to attain.To try to address unhealthy body image in the fashion world, in 2015, France passed a law requiring models to be declared healthy by a doctor to participate in fashion shows. It also requires re-touched images to be marked as such in magazines.There is a relationship between "thin ideal" social media content and body dissatisfaction and eating disorders among young adult women, especially in the Western hemisphere. New research points to an "internalization" of distorted images online, as well as negative comparisons among young adult women. Most studies have been based in the U.S, the U.K, and Australia, these are places where the thin ideal is strong among women, as well as the strive for the "perfect" body.In addition to mere media exposure, there is an online "pro-eating disorder" community. Through personal blogs and Twitter, this community promotes eating disorders as a "lifestyle", and continuously posts pictures of emaciated bodies, and tips on how to stay thin. The hashtag "#proana" (pro-anorexia), is a product of this community, as well as images promoting weight loss, tagged with the term "thinspiration". | Psychopathology
The psychopathology of eating disorders centers around body image disturbance, such as concerns with weight and shape; self-worth being too dependent on weight and shape; fear of gaining weight even when underweight; denial of how severe the symptoms are and a distortion in the way the body is experienced.The main psychopathological features of anorexia were outlined in 1982 as problems in body perception, emotion processing and interpersonal relationships. Women with eating disorders have greater body dissatisfaction. This impairment of body perception involves vision, proprioception, interoception and tactile perception. There is an alteration in integration of signals in which body parts are experienced as dissociated from the body as a whole. Bruch once theorized that difficult early relationships were related to the cause of anorexia and how primary caregivers can contribute to the onset of the illness.A prominent feature of bulimia is dissatisfaction with body shape. However, dissatisfaction with body shape is not of diagnostic significance as it is sometimes present in individuals with no eating disorder. This highly labile feature can fluctuate depending on changes in shape and weight, the degree of control over eating and mood. In contrast, a necessary diagnostic feature for anorexia nervosa and bulimia nervosa is having overvalued ideas about shape and weight are relatively stable and partially related to the patients low self-esteem. Pro-ana subculture
Pro-ana refers to the promotion of behaviors related to the eating disorder anorexia nervosa. Several websites promote eating disorders, and can provide a means for individuals to communicate in order to maintain eating disorders. | 11
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The laparoscopic method requires longer operating time but a shorter recovery period with a smaller and less prominent surgical scar. If it is unnecessary to remove the entire spleen a partial splenectomy may occur; this method preserves some of the immune function while reducing the probability of hypersplenism. Those undergoing splenectomy should receive an appropriate pneumococcal vaccine at least one week (preferably three weeks) before the surgery. Therapeutic
Long-term transfusion therapy (in those with transfusion dependent beta thalassemia) is a treatment used to maintain hemoglobin levels at a target pre-transfusion hemoglobin level of 9–10.5 g/dL (11-12 g/dL in those with concomitant heart disease). To ensure quality blood transfusions, the packed red blood cells should be leucoreduced. By having leucoreduced blood packets, the patient is at a lower risk to develop adverse reactions by contaminated white cells and preventing platelet alloimmunisation. Patients with allergic transfusion reactions or unusual red cell antibodies must receive washed red cells or cryopreserved red cells. Washed red cells have been removed of plasma proteins that would have become a target of the patients antibodies allowing the transfusion to be carried out safely. Cryopreserved red cells are used to maintain a supply of rare donor units for patients with unusual red cell antibodies or missing common red cell antigens. These regular transfusions promote normal growth, physical activities and suppress bone marrow hyperactivity. Pharmaceutical
During normal iron homeostasis the circulating iron is bound to transferrin. | This test is used to investigate deletions and mutations in the alpha- and beta-globin-producing genes. Family studies can be done to evaluate carrier status and the types of mutations present in other family members. DNA testing is not routine, but can help diagnose thalassemia and determine carrier status. In most cases the treating physician uses a clinical prediagnosis assessing anemia symptoms: fatigue, breathlessness and poor exercise tolerance. Further genetic analysis may include HPLC should routine electrophoresis prove difficult. Prevention
Beta thalassemia is a hereditary disease allowing for a preventative treatment by carrier screening and prenatal diagnosis. It can be prevented if one parent has normal genes, giving rise to screenings that empower carriers to select partners with normal hemoglobin. A study aimed at detecting the genes that could give rise to offspring with sickle cell disease. Patients diagnosed with beta thalassemia have MCH ≤ 26 pg and an RDW < 19. Of 10,148 patients, 1,739 patients had a hemoglobin phenotype and RDW consistent with beta thalassemia. After the narrowing of patients, the HbA2 levels were tested presenting 77 patients with beta thalassemia. This screening procedure proved insensitive in populations of West African ancestry because of the indicators has high prevalence of alpha thalassemia. Countries have programs distributing information about the reproductive risks associated with carriers of haemoglobinopathies. Thalassemia carrier screening programs have educational programs in schools, armed forces, and through mass media as well as providing counseling to carriers and carrier couples. | 11
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The disease which is often also associated with gigantism, is difficult to diagnose in the early stages and is frequently missed for many years, until changes in external features, especially of the face, become noticeable with the median time from the development of initial symptoms to diagnosis being twelve years. Cushings syndrome is a hormonal disorder that causes hypercortisolism, which is elevated levels of cortisol in the blood. Cushings disease (CD) is the most frequent cause of Cushings syndrome, responsible for approximately 70% of cases. CD results when a pituitary adenoma causes excessive secretion of adrenocorticotropic hormone (ACTH) that stimulates the adrenal glands to produce excessive amounts of cortisol.Cushings disease may cause fatigue, weight gain, fatty deposits around the abdomen and lower back (truncal obesity) and face ("moon face"), stretch marks (striae) on the skin of the abdomen, thighs, breasts, and arms, hypertension, glucose intolerance, and various infections. In women, it may cause excessive growth of facial hair (hirsutism) and in men erectile dysfunction. Psychiatric manifestations may include depression, anxiety, easy irritability, and emotional instability. It may also result in various cognitive difficulties.Hyperpituitarism is a disease of the anterior lobe of the pituitary gland which is usually caused by a functional pituitary adenoma and results in hypersecretion of adenohypophyseal hormones such as growth hormone; prolactin; thyrotropin; luteinizing hormone; follicle-stimulating hormone; and adrenocorticotropic hormone. | A fetish (derived from the French fétiche, which comes from the Portuguese feitiço, and this in turn from Latin facticius, artificial and facere, to make) is an object believed to have supernatural powers, or in particular, a human-made object that has power over others. Essentially, fetishism is the attribution of inherent value, or powers, to an object. Historiography
The term fetish has evolved from an idiom used to describe a type of object created in the interaction between European travelers and Africans in the early modern period to an analytical term that played a central role in the perception and study of non-Western art in general and African art in particular. William Pietz, who, in 1994, conducted an extensive ethno-historical study of the fetish, argues that the term originated in the coast of West Africa during the sixteenth and seventeenth centuries. Pietz distinguishes between, on the one hand, actual African objects that may be called fetishes in Europe, together with the indigenous theories of them, and on the other hand, "fetish", an idea, and an idea of a kind of object, to which the term above applies.According to Pietz, the post-colonial concept of "fetish" emerged from the encounter between Europeans and Africans in a very specific historical context and in response to African material culture. | 0-1
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The next step was shown by Robert Thomson Leiper, who described in a 1907 paper that monkeys fed D. medinensis-infected Cyclops developed mature guinea worms, while monkeys directly fed D. medinensis larvae did not.In the 19th and 20th centuries, dracunculiasis was widespread across nearly all of Africa and South Asia, though we lack exact case counts from the pre-eradication era. In a 1947 article in the Journal of Parasitology, Norman R. Stoll used rough estimates of populations in endemic areas to suggest that there could be as many as 48 million cases of dracunculiasis per year. In 1976, the WHO estimated the global burden at 10 million cases per year. Ten years later, as the eradication effort was beginning, the WHO estimated 3.5 million cases per year worldwide. Etymology
Dracunculiasis Latin name, Dracunculus medinensis ("little dragon from Medina"), derives from its one-time high incidence in the city of Medina (in modern Saudi Arabia), and its common name, Guinea worm, is due to a similar past high incidence along the Guinea coast of West Africa. It is no longer endemic in either location. Eradication
The campaign to eradicate dracunculiasis began at the urging of the CDC in 1980. Following smallpox eradication (last case in 1977; eradication certified in 1981), dracunculiasis was considered an achievable eradication target since it was relatively uncommon and preventable with only behavioral changes. | Dracunculiasis, also called Guinea-worm disease, is a parasitic infection by the Guinea worm, Dracunculus medinensis. A person becomes infected by drinking water containing water fleas infected with guinea worm larvae. The worms penetrate the digestive tract and escape into the body. Around a year later, the adult worm migrates to an exit site – usually a lower limb – and induces an intensely painful blister on the skin. The blister eventually bursts to form an intensely painful open wound, from which the worm slowly crawls over several weeks. The wound remains painful throughout the worms emergence, disabling the infected person for the three to ten weeks it takes the worm to emerge. During this time, the open wound can become infected with bacteria, leading to death in around 1% of cases.There is no medication to treat dracunculiasis. Instead, the mainstay of treatment is the careful wrapping of the emerging worm around a small stick to encourage its exit. Each day, a few more centimeters of the worm emerge, and the stick is turned to maintain gentle tension. With too much tension, the worm can break and die in the wound, causing severe pain and swelling at the ulcer site. Dracunculiasis is a disease of extreme poverty, occurring in places with poor access to clean drinking water. Prevention efforts center on filtering drinking water to remove water fleas, as well as public education campaigns to discourage people from soaking their emerging worms in sources of drinking water. | 11
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On October 9, 2000, senior Lilly research physician Robert Baker noted that an academic advisory board to which he belonged was "quite impressed by the magnitude of weight gain on olanzapine and implications for glucose. "Lilly had threatened Egilman with criminal contempt charges regarding the documents he took and provided to reporters; in September 2007, he agreed to pay Lilly $100,000 in return for the companys agreement to drop the threat of charges.In September 2008, Judge Weinstein issued an order to make public Lillys internal documents about the drug in a different suit brought by insurance companies, pension funds, and other payors.In March 2008, Lilly settled a suit with the state of Alaska, and in October 2008, Lilly agreed to pay $62 million to 32 states and the District of Columbia to settle suits brought under state consumer protection laws.In 2009, Eli Lilly pleaded guilty to a US federal criminal misdemeanor charge of illegally marketing Zyprexa for off-label use and agreed to pay $1.4 billion. The settlement announcement stated "Eli Lilly admits that between September 1999 and March 31, 2001, the company promoted Zyprexa in elderly populations as treatment for dementia, including Alzheimer’s dementia. Eli Lilly has agreed to pay a $515 million criminal fine and to forfeit an additional $100 million in assets. "The outcomes described here, and their legal ramifications, were fueled by motions and appeals that were not resolved until 2010. | Cariprazine, sold under the brand names Vraylar and Reagila among others, is an on oral atypical antipsychotic originated by Gedeon Richter, which is used in the treatment of schizophrenia, bipolar mania, and bipolar depression. It acts primarily as a D3 and D2 receptor partial agonist, with a preference for the D3 receptor. Cariprazine is also a partial agonist at the serotonin 5-HT1A receptor and acts as an antagonist at 5-HT2B and 5-HT2A receptors, with high selectivity for the D3 receptor. Positive Phase III study results were published for schizophrenia and mania in early 2012, and for bipolar disorder I depression from a Phase II trial in 2015.Cariprazine was approved for medical use in the United States in September 2015. Medical uses
Cariprazine is used to treat schizophrenia and manic, depressive, or mixed episodes associated with bipolar I disorder. In the United States it is approved for schizophrenia in adults, acute treatment of manic or mixed episodes associated with bipolar I disorder in adults and treatment of depressive episodes associated with bipolar I disorder (bipolar depression).Cariprazine consistently improved depressive symptoms across a spectrum of patients with bipolar I depression. In Australia, UK and Europe it is currently approved only for schizophrenia. Side effects
Side effects may first appear on the first day after starting cariprazine. The most prevalent side effects for cariprazine include akathisia, and insomnia. Cariprazine does not appear to impact prolactin levels, and unlike many other antipsychotics, does not increase the QT interval on the electrocardiogram (ECG). | 0-1
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Related issues have also been studied extensively by Greg Littmann of the University of Illinois, and by Colin Allen (a professor at Indiana University) regarding the literature and research studying artificial intelligence in androids.The most commonly given answer is that we attribute consciousness to other people because we see that they resemble us in appearance and behavior; we reason that if they look like us and act like us, they must be like us in other ways, including having experiences of the sort that we do. There are, however, a variety of problems with that explanation. For one thing, it seems to violate the principle of parsimony, by postulating an invisible entity that is not necessary to explain what we observe. Some philosophers, such as Daniel Dennett in an essay titled The Unimagined Preposterousness of Zombies, argue that people who give this explanation do not really understand what they are saying. More broadly, philosophers who do not accept the possibility of zombies generally believe that consciousness is reflected in behavior (including verbal behavior), and that we attribute consciousness on the basis of behavior. A more straightforward way of saying this is that we attribute experiences to people because of what they can do, including the fact that they can tell us about their experiences. Animal consciousness
The topic of animal consciousness is beset by a number of difficulties. It poses the problem of other minds in an especially severe form, because non-human animals, lacking the ability to express human language, cannot tell humans about their experiences. | Similarly, gold is associated with perfect or divine principles, such as in the case of the golden ratio and the golden rule. Gold is further associated with the wisdom of aging and fruition. The fiftieth wedding anniversary is golden. A persons most valued or most successful latter years are sometimes considered "golden years". The height of a civilization is referred to as a golden age. Religion
In some forms of Christianity and Judaism, gold has been associated both with the sacred and evil. In the Book of Exodus, the Golden Calf is a symbol of idolatry, while in the Book of Genesis, Abraham was said to be rich in gold and silver, and Moses was instructed to cover the Mercy Seat of the Ark of the Covenant with pure gold. In Byzantine iconography the halos of Christ, Virgin Mary and the saints are often golden.In Islam, gold (along with silk) is often cited as being forbidden for men to wear. Abu Bakr al-Jazaeri, quoting a hadith, said that "[t]he wearing of silk and gold are forbidden on the males of my nation, and they are lawful to their women". This, however, has not been enforced consistently throughout history, e.g. in the Ottoman Empire. | 0-1
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Cold sensitivity or cold intolerance is unusual discomfort felt by some people when in a cool environment.There is much variation in the sensitivity to cold experienced by different people, with some putting on many layers of clothing while others in the same environment feel comfortable in one layer.Cold sensitivity may be a symptom of hypothyroidism, anemia, fibromyalgia or vasoconstriction. Vitamin B12 deficiency usually accompanies cold intolerance as well. There are other conditions that may cause a cold intolerance, including low body weight, high body temperature and low blood pressure. There may also be differences in people in the expression of uncoupling proteins, thus affecting their amount of thermogenesis. Psychology may also play a factor in perceived temperature. See also
Apparent temperature
Thermoception
Raynaud syndrome
== References == | Klippel–Feil syndrome (KFS), also known as cervical vertebral fusion syndrome, is a rare congenital condition characterized by the abnormal fusion of any two of the seven bones in the neck (cervical vertebrae). : 578 It results in a limited ability to move the neck and shortness of the neck, resulting in the appearance of a low hairline.The syndrome is difficult to diagnose, as it occurs in a group of patients affected with many different abnormalities who can only be unified by the presence of fused or segmental cervical vertebrae. KFS is not always genetic and not always known about on the date of birth. The disease was initially reported in 1884 by Maurice Klippel and André Feil from France. In 1919, in his Doctor of Philosophy thesis, André Feil suggested another classification of the syndrome, encompassing not only deformation of the cervical spine, but also deformation of the lumbar and thoracic spine. Signs and symptoms
KFS is associated with many other abnormalities of the body, hence thorough evaluation of all patients with fused cervical vertebrae at birth is required. Furthermore, it is unclear whether KFS is a unique disease, or if it is one part of a spectrum of congenital spinal deformities.KFS is usually diagnosed after birth. | 0-1
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HPA-1a is present in 98% of the population of the United States, suggesting that approximately 2% of women who are HPA-1a negative may be at risk for NAIT during pregnancy. Of course, the antigen expression of the father must also be taken into account - in most cases the father is HPA-1a/1a or 1a/1b and the mother is HPA-1b/1b with anti-HPA-1a antibodies. In women of Asian descent, HPA-4 antigens are the most frequently implicated.Studies have shown a relationship between maternal HLA type DRw52a (DRB3* 0101) and the development of anti-HPA-1a.The offending antibodies are IgG subtype and therefore capable of crossing the placenta and entering the fetal circulation.Unlike hemolytic disease of the fetus and newborn, NAIT occurs during the first pregnancy in up to 50% of cases, and the affected fetuses may develop severe thrombocytopenia (<50,000 μL−1) very early during pregnancy (as early as 20 weeks gestation, consistent with the development of platelet antigens, and the majority of the time in utero). Usually, the thrombocytopenia increases as gestation progresses. During the first pregnancy, NAIT is often not detected until birth when the newborn presents with classic symptoms of thrombocytopenia including petechiae, bruising or intracranial hemorrhage. In utero intracranial hemorrhage occurs in about 10% to 30% of affected cases (and NAIT is thought to be the underlying cause in the majority of cases of intracranial hemorrhage due to thrombocytopenia- greater than all other causes of thrombocytopenia combined). | A double inlet left ventricle (DILV) or "single ventricle", is a congenital heart defect appearing in 5 in 100,000 newborns, where both the left atrium and the right atrium feed into the left ventricle. The right ventricle is hypoplastic or does not exist. Both atria communicate with the ventricle by a single atrio-ventricular valve. There is a big shunt left-right with a quickly evolutive pulmonary hypertension. Without life-prolonging interventions, the condition is fatal, but with intervention, the newborn may survive. Even if there is no foetal sickness, the diagnosis can be made in utero by foetal echocardiography. Presentation
Infants born with DILV cannot feed normally (breathlessness) and have difficulty gaining weight. The mixed blood in systemic circulation leads to hypoxia (lack of oxygen to the body and organs), so infants develop cyanosis and breathlessness early. Diagnosis
Treatment
In the first few days, if there is no pulmonary valve stenosis, a pulmonary valve banding is necessary to prevent pulmonary hypertension and the ductus must be kept open to allow blood-flow using medication containing prostaglandin. At same time, if necessary, the atrial and ventricular septum communications must be enlarged. When possible Glenn procedure is done. Later, surgical options include the Damus–Kaye–Stansel procedure, the Fontan procedure, and the Norwood procedure. The goal of all of these is separating the pulmonary and the systemic circulation.Usually, DILV is associated with other cardiac malformations. Prognosis
Mortality is very high in the first 2 years, 85%, but after it decreases and between 2 and 15 years old the mortality is only around 9%. | 0-1
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Carrión developed the disease three weeks after the inoculation and kept a meticulous record of clinical symptoms and signs until the disease rendered him incapable of the task and he died at age 28 several weeks later—October 5, 1885. Carrión proved that Oroya fever and verruga peruana were two stages of the same disease, and not two different diseases as was thought at the time. His work did not result in a cure immediately, but his research started the process. Peru has named October 5 as "Peruvian Medicine Day" in his honor.Peruvian microbiologist Alberto Barton discovered the causative bacterium in 1905, but his results were not published until 1909. Barton originally identified them as "endoglobular" structures, bacteria living inside red blood cells. Until 1993, the genus Bartonella, within the family Bartonellaceae, contained only one species; 23 are now identified. CSD
In 1988, English et al. isolated and cultured a bacterium that was named Afipia felis in 1992 after the team at the Armed Forces Institute of Pathology that discovered it. This agent was considered the cause of cat-scratch Disease (CSD) but further studies failed to support this conclusion. Serologic studies associated CSD with Bartonella henselae, reported in 1992. In 1993, Dolan isolated Rochalimae henselae (now called Bartonella henselae) from lymph nodes of patients with CSD. Bartonella spp. are commonly treated with antibiotics including azithromycin, based on a single small randomized clinical trial. Treatment may take up to one year to eliminate the disease. CSD often resolves spontaneously without treatment. | Serology and protein-based methods
IFA (immunofluorescence antibody assay) testing for the presence of antibodies in serum is used to diagnose B. henselae infection at the acute onset of Cat Scratch Disease symptoms, followed by PCR to confirm infecting species. IFA can generally be used to confirm a diagnosis of Bartonella infection, but is limited by antibody cross-reactivity with other bacteria species which can cause a false positive, and antigen variability which can result in false negatives.Bartonella spp. often evade an immune response, thus antibodies may not be detected even concurrent with an infection, resulting in an IFA false negative rate of up to 83% in chronically infected patients when other test results (e.g. organism isolation or PCR) are positive. IFA sensitivity may range from 14 to 100%, causing discrepancies between PCR and serology test results. Positive IFA results do not distinguish between current infection and prior exposure.ELISA (enzyme-linked immunosorbent assay) is another method that has been used to detect Bartonella, but it has a low sensitivity (17-35%). Western blot for protein detection of Bartonella-associated proteins has also been reported, but this method does not show clear immunoreactive profiles. PCR
The CDC states that PCR testing from a single blood draw is not sufficiently sensitive for B. henselae testing, and can result in high false negative rates due to a small sample volume and levels below the limit of molecular detection.Bartonella spp. | 11
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Celecoxib, sold under the brand name Celebrex among others, is a COX-2 inhibitor and nonsteroidal anti-inflammatory drug (NSAID). It is used to treat the pain and inflammation in osteoarthritis, acute pain in adults, rheumatoid arthritis, ankylosing spondylitis, painful menstruation, and juvenile rheumatoid arthritis. It may also be used to decrease the risk of colorectal adenomas in people with familial adenomatous polyposis. It is taken by mouth. Benefits are typically seen within an hour.Common side effects include abdominal pain, nausea, and diarrhea. Serious side effects may include heart attacks, strokes, gastrointestinal perforation, gastrointestinal bleeding, kidney failure, and anaphylaxis. Use is not recommended in people at high risk for heart disease. The risks are similar to other NSAIDs, such as ibuprofen and naproxen. Use in the later part of pregnancy or during breastfeeding is not recommended.Celecoxib was patented in 1993 and came into medical use in 1999. It is available as a generic medication. In 2019, it was the 102nd most commonly prescribed medication in the United States, with more than 6 million prescriptions. Medical uses
Celecoxib is indicated for the treatment of osteoarthritis, rheumatoid arthritis, acute pain, musculoskeletal pain, painful menstruation, ankylosing spondylitis, juvenile rheumatoid arthritis, and to reduce the number of colon and rectal polyps in people with familial adenomatous polyposis. It may be used in children with juvenile rheumatoid arthritis who are older than two years of age and weigh more than 10 kg (22 lb).For postoperative pain, it is more or less equal to ibuprofen. | In February 2007, the American Heart Association warned that with respect to "patients with a prior history of or at high risk for cardiovascular disease... use of COX-2 inhibitors for pain relief should be limited to patients for whom there are no appropriate alternatives, and then, only in the lowest dose and for the shortest duration necessary. "In 2005, a study published in the Annals of Internal Medicine found that cardiovascular effects of COX-2 inhibitors differ, depending on the drug. Other COX-2-selective inhibitors, such as rofecoxib, have significantly higher myocardial infarction rates than celecoxib. In April 2005, after an extensive review of data, the FDA concluded it was likely "that there is a class effect for increased CV risk for all NSAIDs". In a 2006 meta-analysis of randomized control studies, the cerebrovascular events associated with COX-2 inhibitors were examined, but no significant risks were found when compared to nonselective NSAIDs or placebos. Drug interactions
Celecoxib is predominantly metabolized by cytochrome P450 2C9. Caution must be exercised with concomitant use of 2C9 inhibitors, such as fluconazole, which can greatly elevate celecoxib serum levels. If used concomitantly with lithium, celecoxib increases lithium plasma levels. If used concomitantly with warfarin, celecoxib may result in increased risk of bleeding complications. The risk of bleeding and gastric ulcers also increase further when SSRIs are used in combination with celecoxib. The drug may increase the risk of kidney failure with angiotensin-converting enzyme-inhibitors, such as lisinopril, and diuretics, such as hydrochlorothiazide. | 11
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During Mansa Musas (ruler of the Mali Empire from 1312 to 1337) hajj to Mecca in 1324, he passed through Cairo in July 1324, and was reportedly accompanied by a camel train that included thousands of people and nearly a hundred camels where he gave away so much gold that it depressed the price in Egypt for over a decade, causing high inflation. A contemporary Arab historian remarked:
Gold was at a high price in Egypt until they came in that year. The mithqal did not go below 25 dirhams and was generally above, but from that time its value fell and it cheapened in price and has remained cheap till now. The mithqal does not exceed 22 dirhams or less. This has been the state of affairs for about twelve years until this day by reason of the large amount of gold which they brought into Egypt and spent there [...]. The European exploration of the Americas was fueled in no small part by reports of the gold ornaments displayed in great profusion by Native American peoples, especially in Mesoamerica, Peru, Ecuador and Colombia. The Aztecs regarded gold as the product of the gods, calling it literally "god excrement" (teocuitlatl in Nahuatl), and after Moctezuma II was killed, most of this gold was shipped to Spain. However, for the indigenous peoples of North America gold was considered useless and they saw much greater value in other minerals which were directly related to their utility, such as obsidian, flint, and slate. | Prevalence
Although exact rates of prevalence are not available, general population data shows a 0.002% prevalence over a year-long period and higher prevalence within clinical populations. Caffeine
Caffeine is a methylxanthine, and is hydrophobic. The structure of caffeine allows the molecule to pass freely through biological membranes including the blood-brain barrier. Absorption in the gastrointestinal tract reaches near completion at about 99% after only 45 minutes. Half-life of caffeine for most adults is between 2.5 and 4.5 hours when consumption is limited to less than 10 mg/kg. However, during neonatal development, half-life for the fetus is significantly longer and decreases exponentially after birth to reach a normal rate at about 6 months. Cytochrome P-450, a hemeprotein, acts in liver microsomes to metabolize caffeine into dimethylxanthines, monomethylxanthines, dimethyl uric acids, monomethyl uric acids, trimethylallantoin, dimethylallantoin, and derivatives of uracil. Most caffeine is metabolized by 3-methyl demethylation, forming the metabolite of paraxanthine. Many metabolites, in addition to caffeine, act within the body and are partly responsible for the physiological response to caffeine. Mechanism of caffeine action
Caffeine acts in multiple ways within the brain and the rest of the body. However, due to the concentration of caffeine required, antagonism of adenosine receptors is the primary mode of action. The following mechanisms are ways in which caffeine may act within the body, but depending on necessary caffeine concentration and other factors may not be responsible for the clinical effects of the substance. | 0-1
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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. | Parasitic infections
In the body, disulfiram is rapidly metabolized to diethyldithiocarbamate (ditiocarb), which binds to metal ions such as zinc or copper to form zinc or copper diethyldithiocarbamate (zinc or copper ditiocarb). The zinc diethyldithiocarbamate (zinc-ditiocarb) metabolite of disulfiram is extremely potent against the diarrhea and liver abscess-causing parasite Entamoeba histolytica and might be active against other deadly parasites. HIV
Disulfiram has also been identified by systematic high-throughput screening as a potential HIV latency reversing agent (LRA). Reactivation of latent HIV infection in patients is part of an investigational strategy known as "shock and kill" which may be able to reduce or eliminate the HIV reservoir. Recent phase II dose-escalation studies in patients with HIV who are controlled on antiretroviral therapy have observed an increase in cell-associated unspliced HIV RNA with increasing exposure to disulfiram and its metabolites. Disulfiram is also being investigated in combination with vorinostat, another investigational latency reversing agent, to treat HIV. COVID-19
Disulfiram has been shown to inhibit the papain-like proteases of MERS-CoV and SARS-CoV. It has been examined in a small inconclusive retrospective observational study for its effects on COVID-19 symptoms and is currently in Phase 2 clinical trials. References
External links
"Disulfiram". Drug Information Portal. U.S. National Library of Medicine. Toxicity, Mushroom - Disulfiramlike Toxins at eMedicine
CDC - NIOSH Pocket Guide to Chemical Hazards | 11
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In acquired amusia, inability to perceive music correlates with an inability to perform other higher-level functions. In this case, as musical ability improves, so too do the higher cognitive functions which suggests that musical ability is closely related to these higher-level functions, such as memory and learning, mental flexibility, and semantic fluency.Amusia can also be related to aprosody, a disorder in which the persons speech is affected, becoming extremely monotonous. It has been found that both amusia and aprosody can arise from seizures occurring in the non-dominant hemisphere. They can also both arise from lesions to the brain, as can Brocas aphasia come about simultaneously with amusia from injury. There is a relation between musical abilities and the components of speech; however, it is not understood very well. Diagnosis
The diagnosis of amusia requires multiple investigative tools all described in the Montreal Protocol for Identification of Amusia. This protocol has at its center the Montreal Battery of Evaluation of Amusia (MBEA), which involves a series of tests that evaluate the use of musical characteristics known to contribute to the memory and perception of conventional music, but the protocol also allow for the ruling out of other conditions that can explain the clinical signs observed. The battery comprises six subtests which assess the ability to discriminate pitch contour, musical scales, pitch intervals, rhythm, meter, and memory. | Primary central nervous system lymphoma (PCNSL), also termed primary diffuse large B-cell lymphoma of the central nervous system (DLBCL-CNS), is a primary intracranial tumor appearing mostly in patients with severe immunodeficiency (typically patients with AIDS). It is a subtype and one of the most aggressive of the diffuse large B-cell lymphomas. PCNSLs represent around 20% of all cases of lymphomas in HIV infections. (Other types are Burkitts lymphomas and immunoblastic lymphomas). Primary CNS lymphoma is highly associated with Epstein-Barr virus (EBV) infection (> 90%) in immunodeficient patients (such as those with AIDS and those immunosuppressed), and does not have a predilection for any particular age group. Mean CD4+ count at time of diagnosis is ~50/uL. In immunocompromised patients, prognosis is usually poor. In immunocompetent patients (that is, patients who do not have AIDS or some other immunodeficiency), there is rarely an association with EBV infection or other DNA viruses. In the immunocompetent population, PCNSLs typically appear in older patients in their 50s and 60s. Importantly, the incidence of PCNSL in the immunocompetent population has been reported to have increased more than 10-fold from 2.5 cases to 30 cases per 10 million population. The cause for the increase in incidence of this disease in the immunocompetent population is unknown. Signs and symptoms
A primary CNS lymphoma usually presents with seizure, headache, cranial nerve findings, altered mental status, or other focal neurological deficits typical of a mass effect. Systemic symptoms may include fever, night sweats, or weight loss. | 0-1
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Skin pigmentation
Melanin is a pigment in the epidermis that functions to protect keratinocytes from the damage caused by UV radiation; it is found in higher concentrations in the epidermis of darker-skinned individuals, affording them protection against the development of AKs. Fair-skinned individuals have a significantly increased risk of developing AKs when compared to olive-skinned individuals (odds ratios of 14.1 and 6.5, respectively), and AKs are uncommon in dark-skinned people of African descent. Other phenotypic features seen in fair-skinned individuals that are associated with an increased propensity to develop AKs include:
Freckling
Light hair and eye color
Propensity to sunburn
Inability to tan
Other risk factors
Immunosuppression: People with a compromised immune system from medical conditions (such as AIDS) or immunosuppressive therapy (such as chronic immunosuppression after organ transplantation, or chemotherapy for cancer) are at increased risk for developing AKs. They may develop AK at an earlier age or have an increased number of AK lesions compared to immunocompetent people. Human papillomavirus (HPV): The role of HPV in the development of AK remains unclear, but evidence suggests that infection with the betapapillomavirus type of HPV may be associated with an increased likelihood of AK. Genodermatoses: Certain genetic disorders interfere with DNA repair after sun exposure, thereby putting these individuals at higher risk for the development of AKs. Examples of such genetic disorders include xeroderma pigmentosum and Bloom syndrome. Balding: AKs are commonly found on the scalps of balding men. | The Imiquimod 3.75% cream has been validated in a treatment regimen consisting of daily application to entire face and scalp for two 2-week treatment cycles, with a complete clearance rate of 36%.While the clearance rate observed with the Imiquimod 3.75% cream was lower than that observed with the 5% cream (36 and 50 percent, respectively), there are lower reported rates of adverse reactions with the 3.75% cream: 19% of individuals using Imiquimod 3.75% cream reported adverse reactions including local erythema, scabbing, and flaking at the application site, while nearly a third of individuals using the 5% cream reported the same types of reactions with Imiquimod treatment. However, it is ultimately difficult to compare the efficacy of the different strength creams directly, as current study data varies in methodology (e.g. duration and frequency of treatment, and amount of skin surface area covered). Ingenol mebutate gel
Ingenol mebutate is a newer treatment for AK used in Europe and the United States. It works in two ways, first by disrupting cell membranes and mitochondria resulting cell death, and then by inducing antibody-dependent cellular cytotoxicity to eliminate remaining tumor cells. A 3-day treatment course with the 0.015% gel is recommended for the scalp and face, while a 2-day treatment course with the 0.05% gel is recommended for the trunk and extremities. Treatment with the 0.015% gel was found to completely clear 57% of AK, while the 0.05% gel had a 34% clearance rate. Advantages of ingenol mebutate treatment include the short duration of therapy and a low recurrence rate. | 11
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The surface texture is irregular compared to homogeneous leukoplakia, and may be flat (papular), nodular or exophytic. "Verrucous leukoplakia" (or "verruciform leukoplakia") is a descriptive term used for thick, white, papillary lesions. Verrucous leukoplakias are usually heavily keratinized and are often seen in elderly people. Some verrucous leukoplakias may have an exophytic growth pattern, and some may slowly invade surrounding mucosa, when the term proliferative verrucous leukoplakia may be used. Non-homogeneous leukoplakias have a greater risk of cancerous changes than homogeneous leukoplakias. Proliferative verrucous leukoplakia
Proliferative verrucous leukoplakia (PVL) is a recognized high risk subtype of non-homogeneous leukoplakia. It is uncommon, and usually involves the buccal mucosa and the gingiva (the gums). This condition is characterized by (usually) extensive, papillary or verrucoid keratotic plaques that tends to slowly enlarge into adjacent mucosal sites. An established PVL lesion is usually thick and exophytic (prominent), but initially it may be flat. Smoking does not seem to be as strongly related as it is to leukoplakia generally, and another dissimilarity is the preponderance for women over 50. There is a very high risk of dysplasia, transformation to squamous cell carcinoma with high mortality (PVL does not transform into verrucous carcinoma, which is a lesion with a good prognosis usually; the similarity of names does not reflect the common origin, but only the resemblance of their appearance). Erythroleukoplakia
Erythroleukoplakia (also termed speckled leukoplakia, erythroleukoplasia or leukoerythroplasia) is a non-homogeneous lesion of mixed white (keratotic) and red (atrophic) color. | The degree of hyperkeratosis, epithelial thickness (acanthosis/atrophy), dysplasia and inflammatory cell infiltration in the underlying lamina propria are variable. In mucous membranes, hyperkeratosis can be defined as "an increase in the thickness of the keratin layer of the epithelium, or the presence of such a layer in a site where none would normally be expected." In leukoplakia, the hyperkeratosis varies in thickness and may be either ortho- or para-keratosis, (depending upon whether cell nuclei are lost or retained in the superficial layers respectively), or a mixture of both in different areas of the lesion.The epithelium may show hypertrophy (e.g. acanthosis) or atrophy. Red areas within leukoplakia represent atrophic or immature epithelium which has lost the ability to keratinize. The transition between the lesion and normal surrounding mucosa may be well-demarcated, or poorly defined. Melanin, a pigment naturally produced in oral mucosa, can leak from cells and give a grey color to some leukoplakia lesions.Hyperkeratosis and altered epithelial thickness may be the only histologic features of a leukoplakia lesion, but some show dysplasia. The word "dysplasia" generally means "abnormal growth", and specifically, in the context of oral red or white lesions, refers to microscopic changes ("cellular atypia") in the mucosa that indicate a risk of malignant transformation. When dysplasia is present, there is generally an inflammatory cell infiltration in the lamina propria. The following are commonly cited as being possible features of epithelial dysplasia in leukoplakia specimens:
Cellular pleomorphism, in which cells are of abnormal and different shapes. | 11
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KSHV/HHV8-negative primary effusion lymphoma
Effusion-based lymphoma, KSHV/HHV8-negative (also termed Type II PEL) has been described by some researchers. These cases closely resemble KSHV/HHV8-positive (also termed Type I PEL) but have yet to be defined by the World Health Organization (2017). Compared to Type I PEL, Type II PEL occurs more often in older individuals, is less often associated with EBV, and more often afflicts individuals who lack evidence of being immunocompromised. That is, the majority of HHV-8-negative EBL cases do not evidence a potentially PEL causative agent, such as HIV, EBV, HCV, or iatrogenic immunodeficiency, except for old age and, in 20% to 40% of cases, the presence of hepatitis C virus infection. Type II PEL also tends to involve malignant plasmablasts, anaplastic cells, and/or Reed-Sternberg-like cells that have somewhat different expression patters of protein markers (e.g. the malignant cells in Type II PEL frequently express CD20 but often do not express CD30) and gene abnormalities (e.g. the malignant cells in Type II PEL more commonly evidence rearrangements in their Myc, BCL2, and BCL6 genes) than the malignant cells in Type I PEL. The response to treatment and prognosis of Type II PEL is poor but may be somewhat better than the treatment-responsiveness and prognosis of Type I PEL. | Pathology
Characteristic feature is the identification of intimately related syncytiotrophoblasts and cytotrophoblasts without formation of definite placental type villi. Since choriocarcinomas include syncytiotrophoblasts (beta-HCG producing cells), they cause elevated blood levels of beta-human chorionic gonadotropin. Syncytiotrophoblasts are large multi-nucleated cells with eosinophilic cytoplasm. They often surround the cytotrophoblasts, reminiscent of their normal anatomical relationship in chorionic villi. Cytotrophoblasts are polyhedral, mononuclear cells with hyperchromatic nuclei and a clear or pale cytoplasm. Extensive hemorrhage is a common finding. Treatment
Since gestational choriocarcinoma (which arises from a hydatidiform mole) contains paternal DNA (and thus paternal antigens), it is exquisitely sensitive to chemotherapy. The cure rates, even for metastatic gestational choriocarcinoma, more than 90% when using chemotherapy for invasive mole and choriocarcinoma.As of 2019, treatment with either single-agent methotrexate or actinomycin-D is recommended for low-risk disease, while intense combination regimens including EMACO (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (Oncovin) are recommended for intermediate or high-risk disease.Hysterectomy (surgical removal of the uterus) can also be offered to patients >40 years of age or those for whom sterilisation is not an obstacle. It may be required for those with severe infection and uncontrolled bleeding. Choriocarcinoma arising in the testicle is rare, malignant and highly resistant to chemotherapy. The same is true of choriocarcinoma arising in the ovary. Testicular choriocarcinoma has the worst prognosis of all germ-cell cancers. References
External links
00976 at CHORUS | 0-1
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pancreatic disease or coeliac disease, in which the nutrients are left in the lumen to pull in water. Or it can be caused by osmotic laxatives (which work to alleviate constipation by drawing water into the bowels). In healthy individuals, too much magnesium or vitamin C or undigested lactose can produce osmotic diarrhea and distention of the bowel. A person who has lactose intolerance can have difficulty absorbing lactose after an extraordinarily high intake of dairy products. In persons who have fructose malabsorption, excess fructose intake can also cause diarrhea. High-fructose foods that also have a high glucose content are more absorbable and less likely to cause diarrhea. Sugar alcohols such as sorbitol (often found in sugar-free foods) are difficult for the body to absorb and, in large amounts, may lead to osmotic diarrhea. In most of these cases, osmotic diarrhea stops when the offending agent, e.g. milk or sorbitol, is stopped. Exudative
Exudative diarrhea occurs with the presence of blood and pus in the stool. This occurs with inflammatory bowel diseases, such as Crohns disease or ulcerative colitis, and other severe infections such as E. coli or other forms of food poisoning. Inflammatory
Inflammatory diarrhea occurs when there is damage to the mucosal lining or brush border, which leads to a passive loss of protein-rich fluids and a decreased ability to absorb these lost fluids. Features of all three of the other types of diarrhea can be found in this type of diarrhea. | In the case of Rotavirus, which was responsible for around 6% of diarrheal episodes and 20% of diarrheal disease deaths in the children of developing countries, use of a Rotavirus vaccine in trials in 1985 yielded a slight (2–3%) decrease in total diarrheal disease incidence, while reducing overall mortality by 6–10%. Similarly, a Cholera vaccine showed a strong reduction in morbidity and mortality, though the overall impact of vaccination was minimal as Cholera is not one of the major causative pathogens of diarrheal disease. Since this time, more effective vaccines have been developed that have the potential to save many thousands of lives in developing nations, while reducing the overall cost of treatment, and the costs to society.Rotavirus vaccine decrease the rates of diarrhea in a population. New vaccines against rotavirus, Shigella, Enterotoxigenic Escherichia coli (ETEC), and cholera are under development, as well as other causes of infectious diarrhea. Nutrition
Dietary deficiencies in developing countries can be combated by promoting better eating practices. Zinc supplementation proved successful showing a significant decrease in the incidence of diarrheal disease compared to a control group. The majority of the literature suggests that vitamin A supplementation is advantageous in reducing disease incidence. Development of a supplementation strategy should take into consideration the fact that vitamin A supplementation was less effective in reducing diarrhea incidence when compared to vitamin A and zinc supplementation, and that the latter strategy was estimated to be significantly more cost effective. | 11
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doi:10.3949/ccjm.80a.12155. PMID 23908107. S2CID 28081941. "Ovarian cyst - Treatment". National Health Service. 3 October 2018. Gerber, B.; Müller, H.; Külz, T.; Krause, A.; Reimer, T. (1 April 1997). "Simple ovarian cysts in premenopausal patients". International Journal of Gynecology & Obstetrics. 57 (1): 49–55. doi:10.1016/S0020-7292(97)02832-4. PMID 9175670. S2CID 34289061. Potter, Andrew W.; Chandrasekhar, Chitra A. (October 2008). "US and CT Evaluation of Acute Pelvic Pain of Gynecologic Origin in Nonpregnant Premenopausal Patients". RadioGraphics. 28 (6): 1645–1659. doi:10.1148/rg.286085504. PMID 18936027. Crespigny, Lachlan Ch. ; Robinson, Hugh P.; Davoren, Ruth A. M.; Fortune, Denys (September 1989). "The simple ovarian cyst: aspirate or operate?". BJOG. 96 (9): 1035–1039. doi:10.1111/j.1471-0528.1989.tb03377.x. PMID 2679871. S2CID 22501317. | This observation is supported by the fact that most patients live at high altitudes (>1000 m above sea level), and the condition improves in many patients when they move to lower altitudes. However, some patients who are affected already live at sea level.18,19,27 •Some authors are considering a food photosensitizer or a nutritional selective deficiency as a cause; however, no evidence proves this theory.27
Treatment
Currently there is no cure for actinic prurigo, and treatment focuses on relieving the dermatologic symptoms, by way of topical steroid creams or systemic immunosuppressants. Prescribed treatments include:
topical creams such as Tacrolimus and Betamethasone. systemic immunosuppressants such as Prednisone. In some cases, Thalidomide has proven to be effective in controlling the symptoms of actinic prurigo.All patients with AP are encouraged to minimize sun exposure, and to use strong sunscreen throughout the year, and even on cloudy or overcast days, as UVA light, unlike UVB light, is able to penetrate cloud cover and remains constant throughout the day. Alternative treatment methods might include UV Hardening, Meditation and/or cognitive behavioral therapy. UV-A desensitization phototherapy has also been shown to be effective in cases. History
Actinic prurigo (AP) was first described by Escalona in Mexico, in 1954. See also
Photosensitivity with HIV infection
List of human leukocyte antigen alleles associated with cutaneous conditions
Hydroa vacciniforme
References
External links
http://dermnetnz.org/reactions/actinic-prurigo.html
Actinic Prurigo at eMedicine
Torres-Alvarez, B; Baranda, L; Fuentes, C; Delgado, C; Santos-Martinez, L; Portales-Perez, D; Moncada, B; Gonzalez-Amaro, R (January 1998). "An immunohistochemical study of UV-induced skin lesions in actinic prurigo. Resistance of langerhans cells to UV light". European Journal of Dermatology. | 0-1
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The balance between these systems is of significance for a normal sexual response. By modulating serotonin and dopamine activity in certain parts of the brain, flibanserin may improve the balance between these neurotransmitter systems in the regulation of sexual response. Society and culture
Flibanserin was originally developed as an antidepressant, before being repurposed for the treatment of HSDD. Names
Former proposed but abandoned brand names of flibanserin include Ectris and Girosa, and its former developmental code name was BIMT-17. The brand name is Addyi. Approval process and advocacy
On June 18, 2010, a federal advisory panel to the US Food and Drug Administration (FDA) unanimously voted against recommending approval of flibanserin, citing an inadequate risk-benefit ratio. The Committee acknowledged the validity of hypoactive sexual desire as a diagnosis, but expressed concern with the drugs side effects and insufficient evidence for efficacy, especially the drugs failure to show a statistically significant effect on the co-primary endpoint of sexual desire. Earlier in the week, a FDA staff report also recommended non-approval of the drug. Ahead of the votes, Boehringer Ingelheim had mounted a publicity campaign to promote the controversial disorder of "hypoactive sexual desire". In 2010 the FDA issued a Complete Response Letter, stating that the New Drug Application could not be approved in its current form. The letter cited several concerns, including the failure to demonstrate a statistical effect on the co-primary endpoint of sexual desire and overly restrictive entry criteria for the two Phase 3 trials. | An editorial in JAMA noted that, "Although flibanserin is not the first product to be supported by a consumer advocacy group in turn supported by pharmaceutical manufacturers, claims of gender bias regarding the FDAs regulation have been particularly noteworthy, as have the extent of advocacy efforts ranging from social media campaigns to letters from members of Congress".The Even the Score campaign was managed by Blue Engine Message & Media, a public relations firm, and received funding from Sprout. Acquisition by Valeant Pharmaceuticals
On 20 August 2015 Valeant Pharmaceuticals and Sprout Pharmaceuticals announced that Valeant will acquire Sprout, on a debt-free basis, for approximately $1 billion in cash, plus a share of future profits based upon the achievement of certain milestones. Reception
The initial response since the 2015 introduction of flibanserin to the U.S. market was slow with 227 prescriptions written during the first three weeks. The slow response may be related to a number of factors: physicians require about 10 minutes of online training to get certified; the medication has to be taken daily and costs about US$400 per month; and questions about the drugs efficacy and need. Prescriptions for the drug continue to be few with less than 4,000 being made as of February 2016. References
Further reading
Dean L (September 2019). "Flibanserin Therapy and CYP2C19 Genotype". In Pratt VM, McLeod HL, Rubinstein WS, et al. (eds.). Medical Genetics Summaries. National Center for Biotechnology Information (NCBI). PMID 31550099. Aubert, Yves (December 2012). | 11
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This has been recognized in the settings of certain cancers (such as myeloid leukemia), lung infections, or environmental exposure to dusts or chemicals, such as nickel.Although the cause of PAP was not originally understood, a major breakthrough in the understanding of the cause of the disease came by the chance observation that mice bred for experimental study to lack a hematologic growth factor known as granulocyte-macrophage colony stimulating factor (GM-CSF) developed a pulmonary syndrome of abnormal surfactant accumulation resembling human PAP.The implications of this finding are still being explored, but significant progress was reported in February 2007. Researchers in that report discussed the presence of anti-GM-CSF autoantibodies in patients with PAP, and duplicated that syndrome with the infusion of these autoantibodies into mice.Familial or sporadic inactivating mutations in one of the two parental GATA2 genes produces an autosomal dominant disorder termed GATA2 deficiency. The GATA2 gene produces the GATA2 transcription factor which is critical for the embryonic development, maintenance, and functionality of blood-forming, lympathic-forming, and other tissue-forming cells. Individuals with a single GATA2 inactivating mutation present with a wide range of disorders including pulmonary alveolar proteinosis. GATA2 mutation-based pulmonary alveolar proteinosis is associated with normal levels of GM-CSF and commonly improves or is avoided in afflicted individuals who successfully receive a hematopoietic stem cell transplantation. Genetics
Hereditary pulmonary alveolar proteinosis is a recessive genetic condition in which individuals are born with genetic mutations that deteriorate the function of the CSF2 receptor alpha on alveolar macrophages. | Consequently, a messenger molecule known as granulocyte/macrophage-colony stimulating factor (GM-CSF) is unable to stimulate alveolar macrophages to clear surfactant, leading to difficulty with breathing. The gene for the CSF2 receptor alpha is located in the 5q31 region of chromosome 5, and the gene product can also be referred to as granulocyte macrophage colony-stimulating factor receptor. Diagnosis
The diagnosis of PAP is made using a combination of a persons symptoms, chest imaging, and microscopic evaluation of lung washing/tissue. Additional testing for serum anti-GM-CSF antibodies are helpful for confirmation.Although both the symptoms and imaging findings are stereotypical and well-described, they are non-specific and indistinguishable from many other conditions. For example, chest x-ray may show alveolar opacities, and a CT may show a crazy paving lung pattern, both of which are seen more commonly in numerous other conditions. Thus, the diagnosis primarily depends on the pathology findings.Lung washings or tissue for histopathologic analysis are most commonly obtained using bronchoalveolar lavage and/or lung biopsy. Characteristic biopsy findings show filling of the alveoli (and sometimes terminal bronchioles) with an amorphous eosinophilic material, which stains strongly positive on PAS stain and the PAS diastase stain. The surrounding alveoli and pulmonary interstitium remain relatively normal. Electron microscopy of the sample, although not typically performed due to impracticality, shows lamellated bodies representing surfactant. An alternative diagnosis with similar histomorphologic findings is Pneumocystis jirovicii pneumonia.Lung washings characteristically yield a fluid which is "milky"composition. Under the microscope, samples show 20-50 micrometer PAS-positive globules on a background of finely granular or amorphous PAS-positive material. | 11
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A vehicle (from Latin: vehiculum) is a machine that transports people or cargo. Vehicles include wagons, bicycles, motor vehicles (motorcycles, cars, trucks, buses, mobility scooters for disabled people), railed vehicles (trains, trams), watercraft (ships, boats, underwater vehicles), amphibious vehicles (screw-propelled vehicles, hovercraft), aircraft (airplanes, helicopters, aerostats) and spacecraft.Land vehicles are classified broadly by what is used to apply steering and drive forces against the ground: wheeled, tracked, railed or skied. ISO 3833-1977 is the standard, also internationally used in legislation, for road vehicles types, terms and definitions. History
The oldest boats found by archaeological excavation are logboats, with the oldest logboat found, the Pesse canoe found in a bog in the Netherlands, being carbon dated to 8040 - 7510 BC, making it 9,500–10,000 years old,
a 7,000-year-old seagoing boat made from reeds and tar has been found in Kuwait. Boats were used between 4000 -3000 BC in Sumer, ancient Egypt and in the Indian Ocean. There is evidence of camel pulled wheeled vehicles about 4000–3000 BC. The earliest evidence of a wagonway, a predecessor of the railway, found so far was the 6 to 8.5 km (4 to 5 mi) long Diolkos wagonway, which transported boats across the Isthmus of Corinth in Greece since around 600 BC. Wheeled vehicles pulled by men and animals ran in grooves in limestone, which provided the track element, preventing the wagons from leaving the intended route. In 200 CE, Ma Jun built a south-pointing chariot, a vehicle with an early form of guidance system. | Locomotion
Locomotion consists of a means that allows displacement with little opposition, a power source to provide the required kinetic energy and a means to control the motion, such as a brake and steering system. By far, most vehicles use wheels which employ the principle of rolling to enable displacement with very little rolling friction. Energy source
It is essential that a vehicle have a source of energy to drive it. Energy can be extracted from external sources, as in the cases of a sailboat, a solar-powered car, or an electric streetcar that uses overhead lines. Energy can also be stored, provided it can be converted on demand and the storing mediums energy density and power density are sufficient to meet the vehicles needs. Human power is a simple source of energy that requires nothing more than humans. Despite the fact that humans cannot exceed 500 W (0.67 hp) for meaningful amounts of time, the land speed record for human-powered vehicles (unpaced) is 133 km/h (83 mph), as of 2009 on a recumbent bicycle.The most common type of energy source is fuel. External combustion engines can use almost anything that burns as fuel, whilst internal combustion engines and rocket engines are designed to burn a specific fuel, typically gasoline, diesel or ethanol. Another common medium for storing energy is batteries, which have the advantages of being responsive, useful in a wide range of power levels, environmentally friendly, efficient, simple to install, and easy to maintain. Batteries also facilitate the use of electric motors, which have their own advantages. | 11
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Among the freshwater leeches are the Glossiphoniidae, dorso-ventrally flattened animals mostly parasitic on vertebrates such as turtles, and unique among annelids in both brooding their eggs and carrying their young on the underside of their bodies.The terrestrial Haemadipsidae are mostly native to the tropics and subtropics, while the aquatic Hirudinidae have a wider global range; both of these feed largely on mammals, including humans. A distinctive family is the Piscicolidae, marine or freshwater ectoparasites chiefly of fish, with cylindrical bodies and usually well-marked, bell-shaped, anterior suckers. Not all leeches feed on blood; the Erpobdelliformes, freshwater or amphibious, are carnivorous and equipped with a relatively large, toothless mouth to ingest insect larvae, molluscs, and other annelid worms, which are swallowed whole. In turn, leeches are prey to fish, birds, and invertebrates.The name for the subclass, Hirudinea, comes from the Latin hirudo (genitive hirudinis), a leech; the element -bdella found in many leech group names is from the Greek βδέλλα bdella, also meaning leech. The name Les hirudinées was given by Jean-Baptiste Lamarck in 1818. Leeches were traditionally divided into two infraclasses, the Acanthobdellidea (primitive leeches) and the Euhirudinea (true leeches). The Euhirudinea are divided into the proboscis-bearing Rhynchobdellida and the rest, including some jawed species, the "Arhynchobdellida", without a proboscis.The phylogenetic tree of the leeches and their annelid relatives is based on molecular analysis (2019) of DNA sequences. | It leads successively into the pharynx, a short oesophagus, a crop (in some species), a stomach and a hindgut, which ends at an anus located just above the posterior sucker. The stomach may be a simple tube, but the crop, when present, is an enlarged part of the midgut with a number of pairs of ceca that store ingested blood. The leech secretes an anticoagulant, hirudin, in its saliva which prevents the blood from clotting before ingestion. A mature medicinal leech may feed only twice a year, taking months to digest a blood meal. The bodies of predatory leeches are similar, though instead of a jaw many have a protrusible proboscis, which for most of the time they keep retracted into the mouth. Such leeches are often ambush predators that lie in wait until they can strike prey with the proboscises in a spear-like fashion. Predatory leeches feed on small invertebrates such as snails, earthworms and insect larvae. The prey is usually sucked in and swallowed whole. Some Rhynchobdellida however suck the soft tissues from their prey, making them intermediate between predators and blood-suckers. Blood-sucking leeches use their anterior suckers to connect to hosts for feeding. Once attached, they use a combination of mucus and suction to stay in place while they inject hirudin into the hosts blood. In general, blood-feeding leeches are non host-specific, and do little harm to their host, dropping off after consuming a blood meal. Some marine species however remain attached until it is time to reproduce. | 11
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Fungal keratitis is a fungal infection of the cornea, which can lead to blindness. It generally presents with a red, painful eye and blurred vision. There is also increased sensitivity to light, and excessive tears or discharge.It is caused by fungal organisms such as Fusarium, Aspergillus or Candida.Fungal keratitis has a worldwide distribution, but is more common in the tropics. Around 1 million people become blind every year due to fungal keratitis. Theodor Leber first described a case of fungal keratitis caused by Aspergillus in 1879. Signs and symptoms
The symptoms of fungal keratitis typically emerge over 5-10 days and present with a painful eye, blurred vision, and redness of eye. There is increased sensitivity to light, and excessive tears or discharge. The symptoms are markedly less as compared to a similar bacterial ulcer. Symptoms may be noted to persist after contact lenses are removed, or following antibiotic treatment.Signs: The eyelids and adnexa involved shows edema and redness, conjunctiva is chemosed. Ulcer may be present. It is a dry looking corneal ulcer with satellite lesions in the surrounding cornea. Usually associated with fungal ulcer is hypopyon, which is mostly white fluffy in appearance. Rarely, it may extend to the posterior segment to cause endophthalmitis in later stages, leading to the destruction of the eye. (Note: Fungal endophthalmitis is extremely rare)
Causes
Fungal keratitis has been reported to be caused by more than 70 different fungi, of which Fusarium, Aspergillus and Candida are responsible for 95% of cases.A. | flavus and A. fumigatus are the most common types of Aspergillus to cause fungal keratitis. F. Solani is the most common type of Fusarium and others include Curvularia and Acremonium. C. albicans, C. guilliermondii and C. parapsilosis are the main types of Candida to cause fungal keratitis. Pathophysiology
The precipitating event for fungal keratitis is trauma with a vegetable / organic matter. A thorn injury, or in agriculture workers, trauma with a wheat plant while cutting the harvest is typical. This implants the fungus directly in the cornea. The fungus grows slowly in the cornea and proliferates to involve the anterior and posterior stromal layers. The fungus can break through the descemets membrane and pass into the anterior chamber. The patient presents a few days or weeks later with fungal keratitis. Diagnosis
The diagnosis is made by an ophthalmologist/optometrist correlating typical history, symptoms and signs. Many times it may be missed and misdiagnosed as bacterial ulcer. A definitive diagnosis is established only after a positive culture report (lactophenol cotton blue, calcoflour medium), typically taking a week, from the corneal scraping. Recent advances have been made in PCR ref 3./immunologic tests which can give a much quicker result. Classification
Infectious keratitis can be bacterial, fungal, viral, or protozoal. Remarkable differences in presentation of the patient allows presumptive diagnosis by the eye care professional, helping in institution of appropriate anti-infective therapy. Prevention
Prevention of trauma with vegetable / organic matter, particularly in agricultural workers while harvesting can reduce the incidence of fungal keratitis. | 11
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For the specific effect, in general, there is no implication that a contributory cause is necessary, though it may be so. In general, a factor that is a contributory cause is not sufficient, because it is by definition accompanied by other causes, which would not count as causes if it were sufficient. For the specific effect, a factor that is on some occasions a contributory cause might on some other occasions be sufficient, but on those other occasions it would not be merely contributory.J. L. Mackie argues that usual talk of "cause" in fact refers to INUS conditions (insufficient but non-redundant parts of a condition which is itself unnecessary but sufficient for the occurrence of the effect). An example is a short circuit as a cause for a house burning down. Consider the collection of events: the short circuit, the proximity of flammable material, and the absence of firefighters. Together these are unnecessary but sufficient to the houses burning down (since many other collections of events certainly could have led to the house burning down, for example shooting the house with a flamethrower in the presence of oxygen and so forth). Within this collection, the short circuit is an insufficient (since the short circuit by itself would not have caused the fire) but non-redundant (because the fire would not have happened without it, everything else being equal) part of a condition which is itself unnecessary but sufficient for the occurrence of the effect. | Tolmetin is a nonsteroidal anti-inflammatory drug (NSAID) of the heterocyclic acetic acid derivative class. It is used primarily to reduce hormones that cause pain, swelling, tenderness, and stiffness in conditions such as osteoarthritis and rheumatoid arthritis, including juvenile rheumatoid arthritis. In the United States it is marketed as Tolectin and comes as a tablet or capsule. Clinical trials
Tolmetin is applicable in the treatment of rheumatoid arthritis, osteoarthrosis, pain, and ankylosing spondylitis. Mechanism of action
Although the mechanism of action of tolmetin is unknown, research involving humans and animals has shown that tolmetin does not achieve anti-inflammatory response by stimulation of the adrenal or pituitary gland, but it has shown tolmetin restrains prostaglandin synthetase in vitro and reduces plasma levels of prostaglandin E, possibly causing the anti-inflammatory response. When tested in rats, tolmetin prevented experimentally stimulated polyarthritis and reduced inflammation. In patients with rheumatoid arthritis or osteoarthritis tolmetin restrained disease activity as efficiently as aspirin and indometacin, although the occurrence of mild gastrointestinal adverse effects and tinnitus was lower in patients treated with tolmetin than it was with aspirin-treated patients and the occurrence of adverse effects of the central nervous system was lower with tolmetin than it was with indometacin. Side effects
Tolmetin can increase the risk of heart or circulatory conditions such as heart attacks and strokes. It should not be taken shortly before or after coronary artery bypass surgery. Tolmetin can also increase the risk of gastrointestinal conditions such as perforation or bleeding, which is fatal. | 0-1
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There is a 25% risk of having a child with the disorder, when both parents are carriers of an autosomal recessive trait. Cystinosis affects approximately 1 in 100,000 to 200,000 newborns. and there are only around 2,000 known individuals with cystinosis in the world. The incidence is higher in the province of Brittany, France, where the disorder affects 1 in 26,000 individuals. Diagnosis
Cystinosis is a rare genetic disorder that causes an accumulation of the amino acid cystine within cells, forming crystals that can build up and damage the cells. These crystals negatively affect many systems in the body, especially the kidneys and eyes.The accumulation is caused by abnormal transport of cystine from lysosomes, resulting in a massive intra-lysosomal cystine accumulation in tissues. Via an as yet unknown mechanism, lysosomal cystine appears to amplify and alter apoptosis in such a way that cells die inappropriately, leading to loss of renal epithelial cells. This results in renal Fanconi syndrome, and similar loss in other tissues can account for the short stature, retinopathy, and other features of the disease. Definitive diagnosis and treatment monitoring are most often performed through measurement of white blood cell cystine level using tandem mass spectrometry. Types
Online Mendelian Inheritance in Man (OMIM): 219800 – Infantile nephropathic
Online Mendelian Inheritance in Man (OMIM): 219900 – Adolescent nephropathic
Online Mendelian Inheritance in Man (OMIM): 219750 – Adult nonnephropathic
Treatment
Cystinosis is normally treated with cysteamine, which is available in capsules and in eye drops. | He linked ochronosis with the accumulation of alkaptans in 1902, and his views on the subject, including its mode of heritance, were summarized in a 1908 Croonian Lecture at the Royal College of Physicians. The genetics of it was also studied by William Bateson in the 1902.The defect was narrowed down to homogentisic acid oxidase deficiency in a study published in 1958. The genetic basis was elucidated in 1996, when HGD mutations were demonstrated.A 1977 study showed that an ochronotic Egyptian mummy had probably suffered from alkaptonuria. Research directions
Research collaborations by several national centres have been established to find a more definitive treatment for alkaptonuria. This has included studies on the use of nitisinone and investigations into antioxidants to inhibit ochronosis. The ideal treatment would replace HGD enzyme function without accumulating other substances. See also
List of cutaneous conditions
List of radiographic findings associated with cutaneous conditions
References
== External links == | 0-1
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In contexts of poly-substance use, blood fentanyl concentrations of approximately 7 ng/ml or greater have been associated with fatalities. Over 85% of overdoses involved at least one other drug, and there was no clear correlation showing at which level the mixtures were fatal. The dosages of fatal mixtures varied by over three magnitudes in some cases. This extremely unpredictable volatility with other drugs makes it especially difficult to avoid fatalities.Naloxone can completely or partially reverse an opioid overdose. In July 2014, the Medicines and Healthcare products Regulatory Agency (MHRA) of the UK issued a warning about the potential for life-threatening harm from accidental exposure to transdermal fentanyl patches, particularly in children, and advised that they should be folded, with the adhesive side in, before being discarded. The patches should be kept away from children, who are most at risk from fentanyl overdose. In the US, fentanyl and fentanyl analogs caused over 29,000 deaths in 2017, a large increase over the previous four years. Most of the recent increases in fentanyl deaths do not involve prescription fentanyl but are related to illicitly made fentanyl that is being mixed with or sold as heroin. Death from fentanyl overdose continues to be a public health issue of national concern in Canada since September 2015. In 2016, deaths from fentanyl overdoses in the province of British Columbia averaged two persons per day. | This risk is higher in specific groups, like those with obstructive sleep apnea.Other factors that increase the risk of respiratory depression are:
High fentanyl doses
Sleep
Older age
Simultaneous use of CNS depressants like benzodiazepines, barbiturates, alcohol, and inhaled anesthetics
Hyperventilation
Decreased CO2 levels in the serum
Respiratory acidosis
Decreased fentanyl clearance from the body
Decreased blood flow to the liver
Renal insufficiencySustained release fentanyl preparations, such as patches, may also produce unexpected delayed respiratory depression. The precise reason for sudden respiratory depression is unclear, but there are several hypotheses:
Saturation of the body fat compartment in people with rapid and profound body fat loss (people with cancer, cardiac or infection-induced cachexia can lose 80% of their body fat). Early carbon dioxide retention causing cutaneous vasodilation (releasing more fentanyl), together with acidosis, which reduces protein binding of fentanyl, releasing yet more fentanyl. Reduced sedation, losing a useful early warning sign of opioid toxicity and resulting in levels closer to respiratory-depressant levels.Another related complication of fentanyl overdoses includes the so-called wooden chest syndrome, which quickly induces complete respiratory failure by paralyzing the thoracic muscles, explained in more detail in the Muscle rigidity section below. Heart and blood vessels
Bradycardia: Fentanyl decreases the heart rate by increasing vagal nerve tone in the brainstem, which increases the parasympathetic drive. Vasodilation: It also vasodilates arterial and venous blood vessels through a central mechanism, by primarily slowing down vasomotor centers in the brainstem. To a lesser extent, it does this by directly affecting blood vessels. | 11
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Philosopher Galen Strawson writes that the death that many people wish for is an instant, painless, unexperienced annihilation. In this unlikely scenario, the person dies without realizing it and without being able to fear it. One moment the person is walking, eating, or sleeping, and the next moment, the person is dead. Strawson reasons that this type of death would not take anything away from the person, as he believes that a person cannot have a legitimate claim to ownership in the future. Society and culture
In society, the nature of death and humanitys awareness of its own mortality has for millennia been a concern of the worlds religious traditions and of philosophical inquiry. This includes belief in resurrection or an afterlife (associated with Abrahamic religions), reincarnation or rebirth (associated with Dharmic religions), or that consciousness permanently ceases to exist, known as eternal oblivion (associated with Secular humanism).Commemoration ceremonies after death may include various mourning, funeral practices and ceremonies of honouring the deceased. The physical remains of a person, commonly known as a corpse or body, are usually interred whole or cremated, though among the worlds cultures there are a variety of other methods of mortuary disposal. In the English language, blessings directed towards a dead person include rest in peace (originally the Latin requiescat in pace), or its initialism RIP. Death is the center of many traditions and organizations; customs relating to death are a feature of every culture around the world. | From the mid-18th century onwards, there was an upsurge in the publics fear of being mistakenly buried alive, and much debate about the uncertainty of the signs of death. Various suggestions were made to test for signs of life before burial, ranging from pouring vinegar and pepper into the corpses mouth to applying red hot pokers to the feet or into the rectum. Writing in 1895, the physician J.C. Ouseley claimed that as many as 2,700 people were buried prematurely each year in England and Wales, although others estimated the figure to be closer to 800.In cases of electric shock, cardiopulmonary resuscitation (CPR) for an hour or longer can allow stunned nerves to recover, allowing an apparently dead person to survive. People found unconscious under icy water may survive if their faces are kept continuously cold until they arrive at an emergency room. This "diving response", in which metabolic activity and oxygen requirements are minimal, is something humans share with cetaceans called the mammalian diving reflex.As medical technologies advance, ideas about when death occurs may have to be re-evaluated in light of the ability to restore a person to vitality after longer periods of apparent death (as happened when CPR and defibrillation showed that cessation of heartbeat is inadequate as a decisive indicator of death). The lack of electrical brain activity may not be enough to consider someone scientifically dead. | 11
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patients selected for treatment with a new regimen may be less ill than average patients with the disease and therefore have an intrinsically less aggressive (i.e. longer overall survival time) disease. Primary plasma cell leukemia
Recent case report studies suggest that treatment regimens which include a proteasome inhibitor drug, particularly bortezomib, and/or autologous stem-cell transplantation have improved pPCL survival. For example, 28 patients treated with a bortezomib-based induction regimen followed by autologous stem-cell transplantation and then a maintenance regimen of lenaldomide (an immunosuppressant related to thalidomide), bortezomib, and dexamethasone (a corticosteroid) has a progression free survival rate of 66% at 3 years and an overall survival rate of 73% at 4 years. In one study, patients receiving intensive chemotherapy plus autologous stem-cell transplantation had a median survival of 34 months while those receiving chemotherapy alone had a median survival of 11 months. Two other studies that included bortezomib in their chemotherapy regimens likewise found that the addition of autologous stem-cell transplantation improved results. Current recommendations for treating pPCL often include induction with a three drug regimen such as borezomib-lenalidomide-dexamethasone followed by autologous stem-cell transplantion and consolidation/maintenance with of combination of immunomodulator agents (e.g. thalidomide, lenalidomide, or pomalidomide) plus a proteasome inhibitor (bortezomib, ixazomib, or carfilzomib. Secondary plasma cell leukemia
As the end stage of multiple myeloma that has failed or broken through one or more therapeutic regimens, sPCL continues to be highly refractory to various treatment regimens (<50%), very short response times of these regiments, and poor overall survival rates (median survival of 2–8 to months). | Spindle cell rhabdomyosarcoma is a subtype of embryonal rhabdomyosarcoma first described by Cavazzana, Schmidt and Ninfo in 1992. This subtype has a more favorable clinical course and prognosis than usual embryonal rhabdomyosarcoma. Spindle cell rhabdomyosarcoma typically occurs in young males and most commonly occurs in paratesticular soft tissue, followed by the head and neck. == References == | 0-1
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There are several theorized causations for the onset of Schizoaffective disorder, including, genetics, general brain function, like chemistry, and structure, and stress.Only after these relevant and known causes of psychosis have been ruled out can a psychiatric differential diagnosis be made. A mental health clinician will incorporate family history, observation of a psychotic persons behavior while the person is experiencing active symptoms, to begin a psychiatric differential diagnosis. Diagnosis also includes self-reported experiences, as well as behavioral abnormalities reported by family members, friends, or significant others. Mistakes in this stage include:
Not screening for dissociative disorders. Dissociative identity disorder and psychotic symptoms in schizoaffective disorder have considerable overlap, yet a different overall treatment approach. DSM-5 criteria
The most widely used criteria for diagnosing schizoaffective disorder are from the American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders-5.The DSM-IV schizoaffective disorder definition was plagued by problems of being inconsistently (or unreliably) used on patients; when the diagnosis is made, it does not stay with most patients over time, and it has questionable diagnostic validity (that is, it does not describe a distinct disorder, nor predict any particular outcome). These problems have been slightly reduced (or "modestly improved") in the DSM-5 according to Carpenter.When psychotic symptoms are confined to an episode of mania or depression (with or without mixed features), the diagnosis is that of a “psychotic” mood disorder, namely either psychotic bipolar disorder or psychotic major depression. | Current studies employing the use of FDOPA PET scanning (FDOPA PET) as a possible method for identifying CBD have focused on analyzing the efficiency of neurons in the striatum that utilize the neurotransmitter dopamine. These studies have concluded that, in general, dopamine uptake was diminished in the caudate and the putamen. This characteristic also has the potential to be useful in distinguishing CBD from the similar PD, as individuals having been diagnosed with PD were more likely to have a lower uptake of dopamine than in individuals with CBD.Other clinical tests or procedures that monitor the presence of dopamine within the brain (β-CIT SPECT and IBZM SPECT) have shown similar findings. β-CIT serves as an indicator for presynaptic dopaminergic neurons, whereas IBZM is a tracer that shows an affinity for the postsynaptic neurons of the same type. Despite agreement with other imaging studies, these two SPECT methods suffer some scrutiny due to better accuracy in other imaging methods. However, β-CIT SPECT has proven to be helpful in distinguishing CBD from PSP and multiple system atrophy (MSA). Corticobasal syndrome
All of the disorders and dysfunctions associated with CBD can often be categorized into a class of symptoms that present with the disease of CBD. These symptoms that aid in clinical diagnosis are collectively referred to as corticobasal syndrome (CBS) or corticobasal degeneration syndrome (CBDS). Alzheimers disease, Picks disease, FTDP-17 and progressive supranuclear palsy can display a corticobasal syndrome. | 0-1
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Living in a humid region increases sweat and the accumulation of moisture, contributing to the aggravation of the skin. Similarly, poor hygiene can exacerbate friction as this brings dirt and other particles to build up, increasing the potential and severity of an inflammatory response. Infants tendency to drool onto their skin folds also puts them at greater risk for infection and intertrigo. Diagnosis
Streptococcal intertrigo is diagnosed by a medical professional after performing a detailed physical examination and taking an overnight culture of the affected areas. A second sample is tested with a rapid antigen detection test for Group A streptococcus. Upon physical examination, streptococcal intertrigo commonly presents with a marked area of redness of the skin, a distinct, foul smell, and a lack of satellite lesions. The presence of satellite lesions, or lesions smaller and further away from the main affected region, may point to a differential diagnosis of candidal intertrigo, which is a more common cause of these characteristics. Streptococcal intertrigo is frequently underdiagnosed and should be considered as a causative agent when standard therapy for candidal intertrigo fails.Other differential diagnoses which may present similarly include seborrheic dermatitis, atopic dermatitis, irritant contact dermatitis, allergic contact dermatitis, mixed bacterial intertrigo, scabies, erythrasma, and inverse psoriasis. Prevention
Given the main etiology of streptococcal intertrigo is the warm and moist skin surface, in order to prevent future infection and repeat incident of this kind, it is best to keep the affected area and other skin folds clean and dry of moisture. | Littoral cell angioma, abbreviated LCA, and formally known as littoral cell angioma of the spleen, is a benign tumour of the spleen that arises from the cells that line the red pulp. Symptoms
LCAs most often are not clinically detectable. On occasion, their first presentation may be with splenic rupture.Most patients show no symptoms and the tumours are found incidentally. Diagnosis
Littoral cell angiomas show in CT scans. They are diagnosed by pathologists by taking a sample of the tumour via Fine Needle Aspiration or Core Needle Aspiration or from a splenectomy. Histologically, they have anastoming small vascular channels and cystic spaces with papillary projections. Treatment
The treatment for a littoral cell angioma is a splenectomy. See also
Vascular tumor
References
External links
Micrograph of a LCA (webpathology.com). | 0-1
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Four other of these transcripts included a myotubularin (MTMR8), a potential human homologue of the mouse Amac1 enzyme, a transcript similar to the mouse L-threonine 3-dehydrogenase gene, and one similar to a human oncogene. The remaining seven transcripts did not resemble any currently known genes. In all, none of the twelve transcripts displayed any evidence of pathogenic involvement with KWE. As a transcriptional map of this critical area is being drawn, based on microsatellite identification, haplotype analysis and other measures; localization of the gene associated with KWE pathogenesis is an ongoing process. Diagnosis
Treatment
Epidemiology
Oudtshoorn is a town in Western Cape (formerly Cape Province), South Africa, where KWE ("Oudtshoorn skin") was first described. The disorder is quite prevalent among Afrikaners of South Africa, a population which can be defined as caucasoid native-speakers of Afrikaans, with northwestern European lineage. Among this group, KWE occurs at a rate of approximately 1/7,200.This relatively high rate of occurrence has been attributed to the founder effect, in which a small, often consanguinous population is formed out of the larger ancestral population, resulting in a loss of genetic diversity. In the context of KWE, the founder effect was confirmed by haplotype analysis, which indicates that the chromosomal origin of a possible genetic mutation responsible for the disorder is particularly common among affected Afrikaners. | This is also true in other South Africans of European descent with KWE, and the chromosome of interest in both these and Afrikaner patients strongly points to an unspecified ancestor or ancestral group that may have settled around the Oudtshoorn area.A second lineage known to exhibit KWE has been reported in Germany, although there it is less prevalent and appears to involve the chromosome from a different ancestral origin than that seen in Afrikaners. KWE has also been noted in other countries around the northwestern region of Europe, such as Denmark. See also
Integumentary system
Cape Town
Africa
List of cutaneous conditions
References
== External links == | 11
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Randomized controlled trials have shown that DBT and MBT may be the most effective, and the two share many similarities. Researchers are interested in developing shorter versions of these therapies to increase accessibility, to relieve the financial burden on patients, and to relieve the resource burden on treatment providers.Some research indicates that mindfulness meditation may bring about favorable structural changes in the brain, including changes in brain structures that are associated with BPD. Mindfulness-based interventions also appear to bring about an improvement in symptoms characteristic of BPD, and some clients who underwent mindfulness-based treatment no longer met a minimum of five of the DSM-IV-TR diagnostic criteria for BPD. Medications
A 2010 review by the Cochrane collaboration found that no medications show promise for "the core BPD symptoms of chronic feelings of emptiness, identity disturbance, and abandonment". However, the authors found that some medications may impact isolated symptoms associated with BPD or the symptoms of comorbid conditions. A 2017 review examined evidence published since the 2010 Cochrane review and found that "evidence of effectiveness of medication for BPD remains very mixed and is still highly compromised by suboptimal study design". A 2020 review found that research into pharmacological treatments had declined, with more results confirming no benefits. The review found "moderate to large, statistically significant effects for both doses of quetiapine (150 mg/day and 300 mg/day) regarding BPD severity, psychosocial impairment and aggression, and an additional effect for the higher dose regarding manic symptoms." | Epiphora may refer to:
Epiphora (medicine), an excessive tear production usually a result from an irritation of the eye
Epistrophe, also known as epiphora, the repetition of the same word or words at the end of successive phrases, clauses or sentences
Epiphora (fungus), a fungus genus in the order Dothideomycetes
Epiphora (moth), a moth genus in the family Saturniidae
Epiphora, an orchid genus nowadays considered a synonym of Polystachya | 0-1
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Novolin is the brand name of three distinct insulin-containing products manufactured by Novo Nordisk:
Novolin 70/30, an insulin preparation containing mixed NPH and regular insulin, respectively
Novolin N, an insulin preparation containing NPH insulin
Novolin R, an insulin preparation containing regular insulin
See also
Insulin (medication)
== References == | A vast amount of carbohydrate binding molecules (lectins) depend on correct glycosylation for appropriate binding; the selectins, involved in leukocyte extravasation, is a prime example. Their binding depends on a correct fucosylation of cell surface glycoproteins. Lack thereof leads to leukocytosis and increase sensitivity to infections as seen in SLC35C1-CDG(CDG-IIc); caused by a GDP-fucose (Fuc) transporter deficiency.All N-linked oligosaccharides originate from a common lipid-linked oligosaccharide (LLO) precursor, synthesized in the ER on a dolichol-phosphate (Dol-P) anchor. The mature LLO is transferred co-translationally to consensus sequence Asn residues in the nascent protein, and is further modified by trimming and re-building in the Golgi. Deficiencies in the genes involved in N-linked glycosylation constitute the molecular background to most of the CDGs. Type I defects involve the synthesis and transfer of the LLO
Type II defects impair the modification process of protein-bound oligosaccharides. Type I
Type II
The mature LLO chain is next transferred to the growing protein chain, a process catalysed by the oligosaccharyl transferase (OST) complex. Once transferred to the protein chain, the oligosaccharide is trimmed by specific glycosidases. This process is vital since the lectin chaperones calnexin and calreticulin, involved in protein quality, bind to the Glc1Man9GlcNAc-structure and assure proper folding. Lack of the first glycosidase (GCS1) causes CDG-IIb. Removal of the Glc residues and the first Man residue occurs in the ER. The glycoprotein then travels to the Golgi, where a multitude of different structures with different biological activities are formed. | 0-1
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If the bilirubin is not rapidly reduced, ABE quickly progresses to chronic bilirubin encephalopathy. Chronic bilirubin encephalopathy (CBE)
CBE is a chronic state of severe bilirubin-induced neurological lesions. Reduction of bilirubin in this state will not reverse the sequelae. Clinically, manifestations of CBE include:
movement disorders – dyskinetic CP with often spasticity. 60% have severe motor disability (unable to walk). auditory dysfunction – auditory neuropathy (ANSD)
visual/oculomotor impairments (nystagmus, strabismus, impaired upward or downward gaze, and/or cortical visual impairment). In rare cases, decreased visual acuity(blindness) can occur. dental enamel hypoplasia/dysplasia of the deciduous teeth,
gastroesophageal reflux,
impaired digestive function. slightly decreased intellectual function: Although most individuals (approximately 85%) with kernicterus fall in normal or dull-normal range. epilepsy is uncommon.These impairments are associated with lesions in the basal ganglia, auditory nuclei of the brain stem, and oculomotor nuclei of the brain stem. Cortex and white matter are subtly involved. Cerebellum may be involved. Severe cortical involvement is uncommon. Subtle bilirubin encephalopathy (SBE)
SBE is a chronic state of mild bilirubin-induced neurological dysfunction (BIND). Clinically, this may result in neurological, learning and movement disorders, isolated hearing loss and auditory dysfunction. In the past it was thought that kernicterus (KI) often cause an intellectual disability. This was assumed due to difficulty with hearing, that is typically not detected in a normal audiogram accompanied by impairments of speech, with choreoathetosis. With advances in technology, this has proven to not be the case as those living with KI have repeatedly demonstrated their intelligence using Augmentative Communication devices. | Kernicterus is a bilirubin-induced brain dysfunction. The term was coined in 1904 by Christian Georg Schmorl. Bilirubin is a naturally occurring substance in the body of humans and many other animals, but it is neurotoxic when its concentration in the blood is too high, a condition known as hyperbilirubinemia. Hyperbilirubinemia may cause bilirubin to accumulate in the grey matter of the central nervous system, potentially causing irreversible neurological damage. Depending on the level of exposure, the effects range from clinically unnoticeable to severe brain damage and even death. When hyperbilirubinemia increases past a mild level, it leads to jaundice, raising the risk of progressing to kernicterus. When this happens in adults, it is usually because of liver problems. Newborns are especially vulnerable to hyperbilirubinemia-induced neurological damage, because in the earliest days of life, the still-developing liver is heavily exercised by the breakdown of fetal hemoglobin as it is replaced with adult hemoglobin and the blood–brain barrier is not as developed. Mildly elevated serum bilirubin levels are common in newborns, and neonatal jaundice is not unusual, but bilirubin levels must be carefully monitored in case they start to climb, in which case more aggressive therapy is needed, usually via light therapy but sometimes even via exchange transfusion. Classification
Acute bilirubin encephalopathy (ABE)
ABE is an acute state of elevated bilirubin in the central nervous system. Clinically, it encompasses a wide range of symptoms. These include lethargy, decreased feeding, hypotonia or hypertonia, a high-pitched cry, spasmodic torticollis, opisthotonus, setting sun sign, fever, seizures, and even death. | 11
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The genetic variant(s) can be inherited from either the father or the mother, and can be passed along to both sons (who may be asymptomatic carriers or may have symptoms such as early baldness and/or excessive hair) and daughters, who will show signs of PCOS. The phenotype appears to manifest itself at least partially via heightened androgen levels secreted by ovarian follicle theca cells from women with the allele. The exact gene affected has not yet been identified. In rare instances, single-gene mutations can give rise to the phenotype of the syndrome. Current understanding of the pathogenesis of the syndrome suggests, however, that it is a complex multigenic disorder.Due to the scarcity of large-scale screening studies, the prevalence of endometrial abnormalities in PCOS remains unknown, though women with the condition may be at increased risk for endometrial hyperplasia and carcinoma as well as menstrual dysfunction and infertility. The severity of PCOS symptoms appears to be largely determined by factors such as obesity. PCOS has some aspects of a metabolic disorder, since its symptoms are partly reversible. Even though considered as a gynecological problem, PCOS consists of 28 clinical symptoms.Even though the name suggests that the ovaries are central to disease pathology, cysts are a symptom instead of the cause of the disease. Some symptoms of PCOS will persist even if both ovaries are removed; the disease can appear even if cysts are absent. Since its first description by Stein and Leventhal in 1935, the criteria of diagnosis, symptoms, and causative factors are subject to debate. | In a 2020 systematic review and meta-analysis of sexual dysfunction related to PCOS which included 5,366 women with PCOS from 21 studies, testosterone levels were analyzed and were found to be 2.34 nmol/L (67 ng/dL) in women with PCOS and 1.57 nmol/L (45 ng/dL) in women without PCOS. In a 1995 study of 1,741 women with PCOS, mean testosterone levels were 2.6 (1.1–4.8) nmol/L (75 (32–140) ng/dL). In a 1998 study which reviewed many studies and subjected them to meta-analysis, testosterone levels in women with PCOS were 62 to 71 ng/dL (2.2–2.5 nmol/L) and testosterone levels in women without PCOS were about 32 ng/dL (1.1 nmol/L). In a 2010 study of 596 women with PCOS which used liquid chromatography–mass spectrometry (LC–MS) to quantify testosterone, median levels of testosterone were 41 and 47 ng/dL (with 25th–75th percentiles of 34–65 ng/dL and 27–58 ng/dL and ranges of 12–184 ng/dL and 1–205 ng/dL) via two different labs. If testosterone levels are above 140 to 200 ng/dL (per different sources), other possible causes of hyperandrogenism such as congenital adrenal hyperplasia or an androgen-secreting tumor may be present and should be excluded. Associated conditions
Many individuals arent under the impression that the first warning sign is usually a change in appearance. | 11
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When people pop pimples, pus comes out, which has the dead white blood cells in it that originally came to diffuse the inflammation. Depending on the continuation of the stressors, the inflammatory pimples (also known as papules and pustules) can develop into nodules and cysts, which are more severe forms of acne that are rooted deeper within the skin. Diagnosis
Acne mechanica can be diagnosed by a dermatologist via a physical examination. In more extreme cases, a skin biopsy is performed to examine the pathology. Family and medical history are also looked at to see if the patient has a hereditary tendency to certain conditions that cause different types of acne, which may play a role in acne mechanica development. For example, if a patients parents had acne, there is a very strong probability they will also have similar issues. The issues can range from things like overproducing dead skin cells or the pores having a higher tendency to clog. Treatment
Acne mechanica has no direct cure, however, there are preventive measures that can be taken to minimize its breakouts. The most obvious solution to prevent extra rubbing or heat entrapment on the surface of the skin is to wear either loose-fitting clothes or wearing clothes made out of more breathable fabrics, especially during exercising, playing sports, or when performing physical activities such as hiking. Loose clothes will not rub as much and create the mechanical stress on the skin. | Taliglucerase alfa, sold under the brand name Elelyso among others, is a biopharmaceutical medication developed by Protalix and Pfizer. The drug, a recombinant glucocerebrosidase used to treat Gauchers disease, is the first plant-made pharmaceutical to win approval by the U.S. Food and Drug Administration (FDA). Each vial has 200 units of taliglucerase alfa. Approval history
The U.S. FDA New Drug Application (NDA) was granted approval in May 2012, for use in adults. The U.S. FDA Supplemental New Drug Application (sNDA) for pediatric use was granted approved in August 2014. In Israel, the Israeli Ministry of Health granted approval in September 2012. In Brazil, the Brazilian Health Surveillance Agency (ANVISA) granted approval in March 2013. In Canada, Health Canada issued a Notice of Compliance in May 2014, for both adults and pediatric patients.Taliglucerase alfa is made by the Israeli biotherapeutics company Protalix and sold by the American pharmaceutical company Pfizer. Society and culture
Economics
For 2016, Elelyso was ranked third for pharmaceuticals with the highest cost-per-patient, with an average cost of $483,242 per year. References
External links
"Taliglucerase alfa". Drug Information Portal. U.S. National Library of Medicine. | 0-1
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This has been suggested to be due to in situ conversion of adrenal androgens into estrone and then estradiol (via local 17β-HSD) in breast tissue (where aromatase activity may be particularly high).The symptoms of AEXS, in males, include heterosexual precocity (precocious puberty with phenotypically-inappropriate secondary sexual characteristics; i.e., a fully or mostly feminized appearance), severe prepubertal or peripubertal gynecomastia (development of breasts in males before or around puberty), high-pitched voice, sparse facial hair, hypogonadism (dysfunctional gonads), oligozoospermia (low sperm count), small testes, micropenis (an unusually small penis), advanced bone maturation, an earlier peak height velocity (an accelerated rate of growth in regards to height), and short final stature due to early epiphyseal closure. The incidence of gynecomastia appears to be 100%, with 20 of 30 male cases opting for mastectomy according to a review.In females, symptoms of AEXS include isosexual precocity (precocious puberty with phenotypically-appropriate secondary sexual characteristics), macromastia (excessively large breasts), an enlarged uterus, menstrual irregularities, and, similarly to males, accelerated bone maturation and short final height. Of seven females described in one report, three (43%) had macromastia. Pubertal breast hypertrophy in association with AEXS has been described in two young girls.Fertility, though usually affected to one degree or another—especially in males—is not always impaired significantly enough to prevent sexual reproduction, as evidenced by vertical transmission of the condition by both sexes. Cause
The root cause of AEXS is not entirely clear, but it has been elucidated that inheritable, autosomal dominant genetic mutations affecting CYP19A1, the gene which encodes aromatase, are involved in its etiology. | Borderline tuberculoid leprosy is a cutaneous condition similar to tuberculoid leprosy except the skin lesions are smaller and more numerous. : 345
See also
Leprosy
Skin lesion
References
== External links == | 0-1
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Almost always, a small area of maximal pain is covered by a larger area of altered skin sensibility with somatosensory disturbances such as hypoesthesia as well as hyperesthesia or hyperalgesia and change of cool perception. Pinching the skin between thumb and index finger is extremely painful compared to the opposite non-involved side.Confirmation of a diagnosis of ACNES is warranted using an abdominal wall infiltration with a local anesthetic agent near the painful spot. Treatment
Treatment consists of several such anesthetic injections, sometimes combined with corticosteroids. Such an approach yields persistent pain relief in two-thirds of patients. This beneficial effect on pain has been demonstrated in a prospective double blind trial. The physical volume of the injection may also break apart the adhesions or fibrosis responsible for the entrapment symptoms.Patients who do not respond to a stratagem of repetitive local trigger point injections can be offered a surgical approach. Terminal branches of an intercostal nerve are removed at the level of the anterior sheath of the rectus abdominal muscle (anterior neurectomy). Several larger series demonstrated a successful response in approximately two out of three patients, which was confirmed in another prospective double blind surgical trial: 73% of the patients who underwent a neurectomy were pain free, compared to 18% in the non-nerve resected group. Patients not responding to an anterior neurectomy, or those in whom the pain syndrome recurs after an initial pain free period (10%) may choose to undergo secondary surgery. This involves a repeated exploration combined with a posterior neurectomy. | Duct ectasia of the breast, mammary duct ectasia or plasma cell mastitis is a condition that occurs when a milk duct beneath the nipple widens, the duct walls thicken, and the duct fills with fluid. This is the most common cause of greenish discharge. Mammary duct ectasia can mimic breast cancer. It is a disorder of peri- or post-menopausal age.Duct ectasia syndrome is a synonym for nonpuerperal mastitis, but the term has also been occasionally used to describe special cases of fibrocystic diseases or mastalgia or as a wastebasket definition of benign breast disease. Correlation of duct widening with the "classical" symptoms of duct ectasia syndrome is unclear. However, duct widening was recently very strongly correlated with noncyclic breast pain.Duct diameter is naturally variable, subject to hormonal interactions. Duct ectasia syndrome in the classical meaning is associated with additional histological changes. Symptoms
Signs of duct ectasia can include nipple retraction, inversion, pain, and classic green-brown discharge. Causes
Breasts are made up of fibrous connective tissues, which are made up of cells, fibers and a gel-like substance. Pathogenesis
The duct widening is commonly believed to be a result of secretory stasis, including stagnant colostrum, which also causes periductal inflammation and fibrosis. However, because nonspecific duct widening is common it might be also coincidental finding in many processes. Smokers seem more often affected by duct ectasia syndrome although the reported results are not entirely consistent. The correlation with smoking status appears weaker than for subareolar abscess. Correlation with the actual duct widening is not known. | 0-1
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