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Exotropia	Exotropia is a form of strabismus where the eyes are deviated outward. It is the opposite of esotropia and usually involves more severe axis deviation than exophoria. People with exotropia often experience crossed diplopia. Intermittent exotropia is a fairly common condition. "Sensory exotropia" occurs in the presence of poor vision in one eye. Infantile exotropia (sometimes called "congenital exotropia") is seen during the first year of life, and is less common than "essential exotropia" which usually becomes apparent several years later. The brains ability to see three-dimensional objects depends on proper alignment of the eyes. When both eyes are properly aligned and aimed at the same target, the visual portion of the brain fuses the two forms from the two eyes into a single image. When one eye turns inward, outward, upward, or downward, two different pictures are sent to the brain. Thus, the brain can no longer fuse the two images coming from the two eyes. This causes loss of depth perception and binocular vision. The term is from Greek exo meaning "outward" and trope meaning "a turning". Signs and symptoms The earliest sign of exotropia is usually a noticeable outward deviation of the eye. This sign may at first be intermittent, occurring when a child is daydreaming, not feeling well, or tired. It may also be more noticeable when the child looks at something in the distance. Squinting or frequent rubbing of the eyes is also common with exotropia. The child probably will not mention seeing double, i.e., double vision or diplopia. However, he or she may close one eye to compensate for the problem. In children, the reason for not seeing double is that the brain may ignore the image it receives from the squinting eye. This shutting down is known as Suppression. Generally, exotropia progresses in frequency and duration. As the disorder progresses, the eyes start to turn out when looking at close objects as well as those in the distance. If left untreated, the eye may turn out continually, causing a loss of binocular vision or stereopsis. In young children with any form of strabismus, the brain may learn to ignore the misaligned eyes image and see only the image from the best-seeing eye. This is called amblyopia, or lazy eye, and results in a loss of binocular vision, impairing depth perception. In adults who develop strabismus, double vision sometimes occurs because the brain has already been trained to receive images from both eyes and cannot ignore the image from the turned eye. Additionally in adults who have had exotropia since childhood, the brain may adapt to using a "blind-spot", whereby it receives images from both eyes, but no full image from the deviating eye, thus avoiding double vision, and in fact, increasing peripheral vision on the side of the deviating eye. According to a study published in the American Journal of Ophthalmology, over 90 percent of children with intermittent exotropia become nearsighted by the time they’re 20. Causes The causes of exotropia are not fully understood. Six muscles control eye movement, four that move the eye up and down and two that move it left and right. All these muscles must be coordinated and working properly for the brain to see a single image. When one or more of these muscles does not work properly, some form of strabismus may occur. Strabismus is more common in children with disorders that affect the brain such as cerebral palsy, Down syndrome, hydrocephalus, and brain tumors. One study has found that children with exotropia are three times more likely to develop a psychiatric disorder in comparison with the general population. Treatment A comprehensive eye examination including an ocular motility (i.e., eye movement) evaluation and an evaluation of the internal ocular structures allows an eye doctor to accurately diagnose exotropia. Although glasses and/or patching therapy, exercises, or prisms may reduce or help control the outward-turning eye in some children, surgery is often required. A common form of exotropia is known as "convergence insufficiency" that responds well to orthoptic vision therapy including exercises. This disorder is characterized by an inability of the eyes to work together when used for near viewing, such as reading. Instead of the eyes focusing together on the near object, one deviates outward. Consecutive exotropia arises after an initial esotropia. Most often it results from surgical overcorrection of the initial esotropia. It can be addressed with further surgery or with vision therapy; vision therapy has shown promising results if the consecutive exotropia is intermittent, alternating, and of small magnitude. (Consecutive exotropia may however also spontaneously develop from esotropia, without surgery or botulinum toxin treatment.) Because of the risks of surgery, and because about 35% of people require at least one more surgery, many people try vision therapy first. This consists of visual exercises. Although vision therapy is generally not covered by American health insurance companies, many large insurers such as Aetna have recently begun offering full or partial coverage in response to recent studies. Strabismus surgery is sometimes recommended if the exotropia is present for more than half of each day or if the frequency is increasing over time. It is also indicated if a child has significant exotropia when reading or viewing near objects or if evidence shows that the eyes are losing their ability to work as a single unit (binocular vision). Finally, if there is a complaint of headaches, and no other cause for the headaches can be found, then these headaches could be because the child or adult is trying to control the exotropia. If none of these criteria are met, surgery may be postponed pending simple observation with or without some form of eyeglass and/or patching therapy. In very mild cases, a chance exists that the exotropia will diminish with time. The long-term success of surgical treatment for conditions such as intermittent exotropia is not well proven, and surgery can often result in a worsening of symptoms due to overcorrection. Evidence from systematic reviews of interventions show clinical benefits for patching for children ages 12 months to ten years. There was insufficient evidence related to the benefits conferred by surgical interventions.The surgical procedure for the correction of exotropia involves making a small incision in the tissue covering the eye to reach the eye muscles. The appropriate muscles are then repositioned to allow the eye to move properly. The procedure is usually done under general anaesthesia. Recovery time is rapid, and most people are able to resume normal activities within a few days. Following surgery, corrective eyeglasses may be needed, and in many cases, further surgery is required later to keep the eyes straight. When a child requires surgery, the procedure is usually performed before the child attains school age. This is easier for the child and gives the eyes a better chance to work together. As with all surgery, some risks occur. However, strabismus surgery is usually a safe and effective treatment. References External links eMedicine on congenital exotropia
Episodic ataxia	Episodic ataxia (EA) is an autosomal dominant disorder characterized by sporadic bouts of ataxia (severe discoordination) with or without myokymia (continuous muscle movement). There are seven types recognized but the majority are due to two recognized entities. Ataxia can be provoked by psychological stress or startle, or heavy exertion, including exercise. Symptoms can first appear in infancy. There are at least six loci for EA, of which 4 are known genes. Some patients with EA also have migraine or progressive cerebellar degenerative disorders, symptomatic of either familial hemiplegic migraine or spinocerebellar ataxia. Some patients respond to acetazolamide though others do not. Signs and symptoms Typically, episodic ataxia presents as bouts of ataxia induced by startle, stress, or exertion. Some patients also have continuous tremors of various motor groups, known as myokymia. Other patients have nystagmus, vertigo, tinnitus, diplopia or seizures. Cause The various symptoms of EA are caused by dysfunction of differing areas. Ataxia, the most common symptom, is due to misfiring of Purkinje cells in the cerebellum. This is either due to direct malfunction of these cells, such as in EA2, or improper regulation of these cells, such as in EA1. Seizures are likely due to altered firing of hippocampal neurons (KCNA1 null mice have seizures for this reason). Pathophysiology EA1: KCNA1 Type 1 episodic ataxia (EA1) is characterized by attacks of generalized ataxia induced by emotion or stress, with myokymia both during and between attacks. This disorder is also known as episodic ataxia with myokymia (EAM), hereditary paroxysmal ataxia with neuromyotonia and Isaacs-Mertens syndrome. Onset of EA1 occurs during early childhood to adolescence and persists throughout the patients life. Attacks last from seconds to minutes. Mutations of the gene KCNA1, which encodes the voltage-gated potassium channel KV1.1, are responsible for this subtype of episodic ataxia. KV1.1 is expressed heavily in basket cells and interneurons that form GABAergic synapses on Purkinje cells. The channels aid in the repolarization phase of action potentials, thus affecting inhibitory input into Purkinje cells and, thereby, all motor output from the cerebellum. EA1 is an example of a synaptopathy. There are currently 17 KV1.1 mutations associated with EA1, Table 1 and Figure 1. 15 of these mutations have been at least partly characterized in cell culture based electrophysiological assays wherein 14 of these 15 mutations have demonstrated drastic alterations in channel function. As described in Table 1, most of the known EA1 associated mutations result in a drastic decrease in the amount of current through KV1.1 channels. Furthermore, these channels tend to activate at more positive potentials and slower rates, demonstrated by positive shifts in their V½ values and slower τ activation time constants, respectively. Some of these mutations, moreover, produce channels that deactivate at faster rates (deactivation τ), which would also result in decreased current through these channels. While these biophysical changes in channel properties likely underlie some of the decrease in current observed in experiments, many mutations also seem to result in misfolded or otherwise mistrafficked channels, which is likely to be the major cause of dysfunction and disease pathogenesis. It is assumed, though not yet proven, that decrease in KV1.1 mediated current leads to prolonged action potentials in interneurons and basket cells. As these channels are important in the regulation of Purkinje cell activity, it is likely that this results increased and aberrant inhibitory input into Purkinje cells and, thus, disrupted Purkinje cell firing and cerebellum output. EA2: CACNA1A Type 2 episodic ataxia (EA2) is characterized by acetazolamide-responsive attacks of ataxia with or without migraine. Patients with EA2 may also present with progressive cerebellar atrophy, nystagmus, vertigo, visual disturbances and dysarthria. These symptoms last from hours to days, in contrast with EA1, which lasts from seconds to minutes. Attacks can be accompanied by increased heart rate and blood pressure, moderate to severe shaking, and stuttering. Like EA1, attacks can be precipitated by exercise, emotional stress/agitation, physical stress, or heat (overheated body temperature) but also by coffee and alcohol. EA2 is caused by mutations in CACNA1A, which encodes the P/Q-type voltage-gated calcium channel CaV2.1, and is also the gene responsible for causing spinocerebellar ataxia type-6 and familial hemiplegic migraine type-1. EA2 is also referred to as episodic ataxia with nystagmus, hereditary paroxysmal cerebellopathy, familial paroxysmal ataxia and acetazolamide-responsive hereditary paroxysmal cerebellar ataxia (AHPCA). There are currently 19 mutations associated with EA2, though only 3 have been characterized electrophysiologically, table 2 and figure 2. Of these, all result in decreased current through these channels. It is assumed that the other mutations, especially the splicing and frameshift mutations, also result in a drastic decrease in CaV2.1 currents, though this may not be the case for all mutations. CACNA1A is heavily expressed in Purkinje cells of the cerebellum where it is involved in coupling action potentials with neurotransmitter release. Thus, decrease in Ca2+ entry through CaV2.1 channels is expected to result in decreased output from Purkinje cells, even though they will fire at an appropriate rate. The tottering mouse is a widely used model to study EA2, as it developed a spontaneous homologous mutation in Cacna1a in the early 1960s. Alternatively, some CACNA1A mutations, such as those seen in familial hemiplegic migraine type-1, result in increased Ca2+ entry and, thereby, aberrant transmitter release. This can also result in excitotoxicity, as may occur in some cases of spinocerebellar ataxia type-6. EA3: 1q42 Episodic ataxia type-3 (EA3) is similar to EA1 but often also presents with tinnitus and vertigo. Patients typically present with bouts of ataxia lasting less than 30 minutes and occurring once or twice daily. During attacks, they also have vertigo, nausea, vomiting, tinnitus and diplopia. These attacks are sometimes accompanied by headaches and precipitated by stress, fatigue, movement and arousal after sleep. Attacks generally begin in early childhood and last throughout the patients lifetime. Acetazolamide administration has proved successful in some patients. As EA3 is extremely rare, there is currently no known causative gene. The locus for this disorder has been mapped to the long arm of chromosome 1 (1q42). EA4 Also known as periodic vestibulocerebellar ataxia, type-4 episodic ataxia (EA4) is an extremely rare form of episodic ataxia differentiated from other forms by onset in the third to sixth generation of life, defective smooth pursuit and gaze-evoked nystagmus. Patients also present with vertigo and ataxia. There are only two known families with EA4, both located in North Carolina. The locus for EA4 is unknown. EA5: CACNB4 There are two known families with type-5 episodic ataxia (EA5).These patients can present with an overlapping phenotype of ataxia and seizures similar to juvenile myoclonic epilepsy. In fact, juvenile myoclonic epilepsy and EA5 are allelic and produce proteins with similar dysfunction.Patients with pure EA5 present with recurrent episodes of ataxia with vertigo. Between attacks they have nystagmus and dysarthria. These patients are responsive to acetazolamide. Both juvenile myoclonic epilepsy and EA5 are a result of mutations in CACNB4, a gene that encodes the calcium channel β4 subunit. This subunit coassembles with α-subunits and produces channels that slowly inactivate after opening.EA5 patients have a cysteine to phenylalanine mutation at position 104.Thus results in channels with 30% greater current than wild-type. As this subunit is expressed in the cerebellum, it is assumed that such increased current results in neuronal hyperexcitability Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. EA6: SLC1A3 Type-6 episodic ataxia (EA6) is a rare form of episodic ataxia, identified initially in a 10-year-old boy who first presented with 30 minute bouts of decreased muscle tone during infancy. He required "balance therapy" as a young child to aid in walking and has a number of ataxic attacks, each separated by months to years. These attacks were precipitated by fever. He has cerebellar atrophy and subclinical seizures. During later attacks, he also presented with distortions of the left hemifield, ataxia, slurred speech, followed by headache. After enrolling in school, he developed bouts of rhythmic arm jerking with concomitant confusion, also lasting approximately 30 minutes. He also has presented, at various times, with migraines. This patient carries a proline to arginine substitution in the fifth transmembrane-spanning segment of the gene SLC1A3. This gene encodes the excitatory amino acid transporter 1 (EAAT1) protein, which is responsible for glutamate uptake. In cell culture assays, this mutation results in drastically decreased glutamate uptake in a dominant-negative manner. This is likely due to decreased synthesis or protein stability. As this protein is expressed heavily in the brainstem and cerebellum, it is likely that this mutation results in excitotoxicity and/or hyperexcitability leading to ataxia and seizures. Mutations in EAAT1 (GLAST) have subsequently been identified in a family with episodic ataxia. Diagnosis Treatment Depending on subtype, many patients find that acetazolamide therapy is useful in preventing attacks. In some cases, persistent attacks result in tendon shortening, for which surgery is required. References External links GeneReviews/NCBI/NIH/UW entry on Episodic Ataxia Type 1, Episodic Ataxia with Myokymia, Hereditary Cerebellar Ataxia with Neuromyotonia GeneReviews/NCBI/NIH/UW entry on Episodic ataxia type 2
Mouth ulcer	A mouth ulcer (aphtha) is an ulcer that occurs on the mucous membrane of the oral cavity. Mouth ulcers are very common, occurring in association with many diseases and by many different mechanisms, but usually there is no serious underlying cause. Rarely, a mouth ulcer that does not heal may be a sign of oral cancer. These ulcers may form individually or multiple ulcers may appear at once (i.e., a "crop" of ulcers). Once formed, an ulcer may be maintained by inflammation and/or secondary infection. The two most common causes of oral ulceration are local trauma (e.g. rubbing from a sharp edge on a broken filling or braces, biting ones lip, etc.) and aphthous stomatitis ("canker sores"), a condition characterized by recurrent formation of oral ulcers for largely unknown reasons. Mouth ulcers often cause pain and discomfort and may alter the persons choice of food while healing occurs (e.g. avoiding acidic, sugary, salty or spicy foods and beverages). Definition An ulcer (; from Latin ulcus, "ulcer, sore") is a break in the skin or mucous membrane with loss of surface tissue and the disintegration and necrosis of epithelial tissue. A mucosal ulcer is an ulcer which specifically occurs on a mucous membrane. An ulcer is a tissue defect which has penetrated the epithelial-connective tissue border, with its base at a deep level in the submucosa, or even within muscle or periosteum. An ulcer is a deeper breach of epithelium compared to an erosion or excoriation, and involves damage to both epithelium and lamina propria.An erosion is a superficial breach of the epithelium, with little damage to the underlying lamina propria. A mucosal erosion is an erosion which specifically occurs on a mucous membrane. Only the superficial epithelial cells of the epidermis or of the mucosa are lost, and the lesion can reach the depth of the basement membrane. Erosions heal without scar formation.Excoriation is a term sometimes used to describe a breach of the epithelium which is deeper than an erosion but shallower than an ulcer. This type of lesion is tangential to the rete pegs and shows punctiform (small pinhead spots) bleeding, caused by exposed capillary loops. Causes Ulcers and erosions can be the result of a spectrum of conditions including: Those causing auto-immune epithelial damage, damage because of an immune defect (e.g., HIV, leukemia) Infections (e.g. herpes viruses) Nutritional disorders (e.g., vitamin deficiencies). Chemicals such as SLS (a common ingredient in many toothpastes) have been linked to mouth ulcers, and have been recognized by public health agencies such as the NHS as a risk factor. Injuries (e.g. biting of the lip, tongue, and cheek, hard foods can scrape the oral tissues, hot foods can cause burns) Stress: When the body is stressed, the immune symptom may trigger mouth sores Pathophysiology The exact pathogenesis is dependent upon the cause. Simple mechanisms which predispose the mouth to trauma and ulceration are xerostomia (dry mouth – as saliva usually lubricates the mucous membrane and controls bacterial levels) and epithelial atrophy (thinning, e.g., after radiotherapy), making the lining more fragile and easily breached.: 7 Stomatitis is a general term meaning inflammation within the mouth, and often may be associated with ulceration.Pathologically, the mouth represents a transition between the gastrointestinal tract and the skin, meaning that many gastrointestinal and cutaneous conditions can involve the mouth. Some conditions usually associated with the whole gastrointestinal tract may present only in the mouth, e.g., orofacial granulomatosis/oral Crohns disease.Similarly, cutaneous (skin) conditions can also involve the mouth and sometimes only the mouth, sparing the skin. The different environmental conditions (saliva, thinner mucosa, trauma from teeth and food), mean that some cutaneous disorders which produce characteristic lesions on the skin produce only non specific lesions in the mouth. The vesicles and bullae of blistering mucocutaneous disorders progress quickly to ulceration in the mouth, because of moisture and trauma from food and teeth. The high bacterial load in the mouth means that ulcers may become secondarily infected. Cytotoxic drugs administered during chemotherapy target cells with fast turnovers such as malignant cells. However, the epithelia of the mouth also has a high turnover rate and makes oral ulceration (mucositis) a common side effect of chemotherapy.Erosions, which involve the epithelial layer, are red in appearance since the underlying lamina propria shows through. When the full thickness of the epithelium is penetrated (ulceration), the lesion becomes covered with a fibrinous exudate and takes on a yellow-grey color. Because an ulcer is a breach of the normal lining, when seen in cross section, the lesion is a crater. A "halo" may be present, which is a reddening of the surrounding mucosa and is caused by inflammation. There may also be edema (swelling) around the ulcer. Chronic trauma may produce an ulcer with a keratotic (white, thickened mucosa) margin. Malignant lesions may ulcerate either because the tumor infiltrates the mucosa from adjacent tissues, or because the lesion originates within the mucosa itself, and the disorganized growth leads to a break in the normal architecture of the lining tissues. Repeat episodes of mouth ulcers can be indicative of an immunodeficiency, signaling low levels of immunoglobulin in the oral mucous membranes. Chemotherapy, HIV, and mononucleosis are all causes of immunodeficiency/immunosuppression with which oral ulcers may become a common manifestation. Autoimmunity is also a cause of oral ulceration. Mucous membrane pemphigoid, an autoimmune reaction to the epithelial basement membrane, causes desquamation/ulceration of the oral mucosa. Numerous aphthous ulcers could be indicative of an inflammatory autoimmune disease called Behçets disease. This can later involve skin lesions and uveitis in the eyes. Vitamin C deficiency may lead to scurvy which impairs wound healing, which can contribute to ulcer formation. For a detailed discussion of the pathophysiology of aphthous stomatitis, see Aphthous stomatitis#Causes. Diagnostic Diagnosis of mouth ulcers usually consists of a medical history followed by an oral examination as well as examination of any other involved area. The following details may be pertinent: The duration that the lesion has been present, the location, the number of ulcers, the size, the color and whether it is hard to touch, bleeds or has a rolled edge. As a general rule, a mouth ulcer that does not heal within 2 or 3 weeks should be examined by a health care professional who is able to rule out oral cancer (e.g. a dentist, oral physician, oral surgeon, or maxillofacial surgeon). If there have been previous ulcers that have healed, then this again makes cancer unlikely. An ulcer that keeps forming on the same site and then healing may be caused by a nearby sharp surface, and ulcers that heal and then recur at different sites are likely to be RAS. Malignant ulcers are likely to be single in number, and conversely, multiple ulcers are very unlikely to be oral cancer. The size of the ulcers may be helpful in distinguishing the types of RAS, as can the location (minor RAS mainly occurs on non-keratinizing mucosa, major RAS occurs anywhere in the mouth or oropharynx). Induration, contact bleeding and rolled margins are features of a malignant ulcer. There may be nearby causative factor, e.g. a broken tooth with a sharp edge that is traumatizing the tissues. Otherwise, the person may be asked about problems elsewhere, e.g. ulceration of the genital mucous membranes, eye lesions or digestive problems, swollen glands in neck (lymphadenopathy) or a general unwell feeling.The diagnosis comes mostly from the history and examination, but the following special investigations may be involved: blood tests (vitamin deficiency, anemia, leukemia, Epstein-Barr virus, HIV infection, diabetes) microbiological swabs (infection), or urinalysis (diabetes). A biopsy (minor procedure to cut out a small sample of the ulcer to look at under a microscope) with or without immunofluorescence may be required, to rule out cancer, but also if a systemic disease is suspected. Ulcers caused by local trauma are painful to touch and sore. They usually have an irregular border with erythematous margins and the base is yellow. As healing progresses, a keratotic (thickened, white mucosa) halo may occur.: 52 Differential diagnosis Due to various factors (saliva, relative thinness of oromucosa, trauma from teeth, chewing, etc.), vesicles and bullae which form on the mucous membranes of the oral cavity tend to be fragile and quickly break down to leave ulcers. Aphthous stomatitis and local trauma are very common causes of oral ulceration; the many other possible causes are all rare in comparison. Traumatic ulceration Most mouth ulcers that are not associated with recurrent aphthous stomatitis are caused by local trauma. The mucous membrane lining of the mouth is thinner than the skin, and easily damaged by mechanical, thermal (heat/cold), chemical, or electrical means, or by irradiation. Mechanical Common causes of oral ulceration include rubbing on sharp edges of teeth, fillings, crowns, false teeth (dentures), or braces (orthodontic appliances), or accidental biting caused by a lack of awareness of painful stimuli in the mouth (e.g., following local anesthetic used during dental treatment, which the person becomes aware of as the anesthetic wears off).Eating hard foods (e.g., potato chips) can damage the lining of the mouth. Some people cause damage inside their mouths themselves, either through an absentminded habit or as a type of deliberate self-harm (factitious ulceration). Examples include biting the cheek, tongue, or lips, or rubbing a fingernail, pen, or toothpick inside the mouth. Tearing (and subsequent ulceration) of the upper labial frenum may be a sign of child abuse (non-accidental injury).Iatrogenic ulceration can also occur during dental treatment, where incidental abrasions to the soft tissues of the mouth are common. Some dentists apply a protective layer of petroleum jelly to the lips before carrying out dental work to minimize this.The lingual frenum is also vulnerable to ulceration by repeated friction during oral sexual activity ("cunnilingus tongue"). Rarely, infants can ulcerate the tongue or lower lip with the teeth, termed Riga-Fede disease. Thermal and electrical burn Thermal burns usually result from placing hot food or beverages in the mouth. This may occur in those who eat or drink before a local anesthetic has worn off. The normal painful sensation is absent and a burn may occur. Microwave ovens sometimes produce food that is cold externally and very hot internally, and this has led to a rise in the frequency of intra-oral thermal burns. Thermal food burns are usually on the palate or posterior buccal mucosa, and appear as zones of erythema and ulceration with necrotic epithelium peripherally. Electrical burns more commonly affect the oral commissure (corner of the mouth). The lesions are usually initially painless, charred and yellow with little bleeding. Swelling then develops and by the fourth day following the burn the area becomes necrotic and the epithelium sloughs off.Electrical burns in the mouth are usually caused by chewing on live electrical wiring (an act that is relatively common among young children). Saliva acts as a conducting medium and an electrical arc flows between the electrical source and the tissues, causing extreme heat and possible tissue destruction. Chemical injury Caustic chemicals may cause ulceration of the oral mucosa if they are of strong-enough concentration and in contact for a sufficient length of time. The holding of medication in the mouth instead of swallowing it occurs mostly in children, those under psychiatric care, or simply because of a lack of understanding. Holding an aspirin tablet next to a painful tooth in an attempt to relieve pulpitis (toothache) is common, and leads to epithelial necrosis. Chewable aspirin tablets should be swallowed, with the residue quickly cleared from the mouth.Other caustic medications include eugenol and chlorpromazine. Hydrogen peroxide, used to treat gum disease, is also capable of causing epithelial necrosis at concentrations of 1–3%. Silver nitrate, sometimes used for pain relief from aphthous ulceration, acts as a chemical cauterant and destroys nerve endings, but the mucosal damage is increased. Phenol is used during dental treatment as a cavity sterilizing agent and cauterizing material, and it is also present in some over-the-counter agents intended to treat aphthous ulcerations. Mucosal necrosis has been reported to occur with concentrations of 0.5%. Other materials used in endodontics are also caustic, which is part of the reason why use of a rubber dam is now recommended. Irradiation As a result of radiotherapy to the mouth, radiation-induced stomatitis may develop, which can be associated with mucosal erosions and ulceration. If the salivary glands are irradiated, there may also be xerostomia (dry mouth), making the oral mucosa more vulnerable to frictional damage as the lubricating function of saliva is lost, and mucosal atrophy (thinning), which makes a breach of the epithelium more likely. Radiation to the bones of the jaws causes damage to osteocytes and impairs the blood supply. The affected hard tissues become hypovascular (reduced number of blood vessels), hypocellular (reduced number of cells), and hypoxic (low levels of oxygen). Osteoradionecrosis is the term for when such an area of irradiated bone does not heal from this damage. This usually occurs in the mandible, and causes chronic pain and surface ulceration, sometimes resulting in non-healing bone being exposed through a soft tissue defect. Prevention of osteradionecrosis is part of the reason why all teeth of questionable prognosis are removed before the start of a course of radiotherapy. Aphthous stomatitis Aphthous stomatitis (also termed recurrent aphthous stomatitis, RAS, and commonly called "canker sores") is a very common cause of oral ulceration. 10–25% of the general population have this non-contagious condition. Three types of aphthous stomatitis exists based on their appearance, namely minor, major and herpetiform major aphthous ulceration. Minor aphthous ulceration is the most common type, presenting with 1–6 small (2-4mm diameter), round/oval ulcers with a yellow-grey color and an erythematous (red) "halo". These ulcers heal with no permanent scarring in about 7–10 days. Ulcers recur at intervals of about 1–4 months. Major aphthous ulceration is less common than the minor type, but produces more severe lesions and symptoms. Major aphthous ulceration presents with larger (>1 cm diameter) ulcers that take much longer to heal (10–40 days) and may leave scarring. The minor and major subtypes of aphthous stomatitis usually produce lesions on the non-keratinized oral mucosa (i.e. the inside of the cheeks, lips, underneath the tongue and the floor of mouth), but less commonly major aphthous ulcers may occur in other parts of the mouth on keratinized mucosal surfaces. The least common type is herpetiform ulceration, so named because the condition resembles primary herpetic gingivostomatitis. Herpetiform ulcers begin as small blisters (vesicles) which break down into 2-3mm sized ulcers. Herpetiform ulcers appear in "crops" sometimes hundreds in number, which can coalesce to form larger areas of ulceration. This subtype may cause extreme pain, heals with scarring and may recur frequently.The exact cause of aphthous stomatitis is unknown, but there may be a genetic predisposition in some people. Other possible causes include hematinic deficiency (folate, vitamin B, iron), stopping smoking, stress, menstruation, trauma, food allergies or hypersensitivity to sodium lauryl sulphate (found in many brands of toothpaste). Aphthous stomatitis has no clinically detectable signs or symptoms outside the mouth, but the recurrent ulceration can cause much discomfort to those affected. Treatment is aimed at reducing the pain and swelling and speeding healing, and may involve systemic or topical steroids, analgesics (pain killers), antiseptics, anti-inflammatories or barrier pastes to protect the raw area(s). Infection Many infections can cause oral ulceration (see table). The most common are herpes simplex virus (herpes labialis, primary herpetic gingivostomatitis), varicella zoster (chicken pox, shingles), and coxsackie A virus (hand, foot and mouth disease). Human immunodeficiency virus (HIV) creates immunodeficiencies which allow opportunistic infections or neoplasms to proliferate. Bacterial processes leading to ulceration can be caused by Mycobacterium tuberculosis (tuberculosis) and Treponema pallidum (syphilis).Opportunistic activity by combinations of otherwise normal bacterial flora, such as aerobic streptococci, Neisseria, Actinomyces, spirochetes, and Bacteroides species can prolong the ulcerative process. Fungal causes include Coccidioides immitis (valley fever), Cryptococcus neoformans (cryptococcosis), and Blastomyces dermatitidis ("North American Blastomycosis"). Entamoeba histolytica, a parasitic protozoan, is sometimes known to cause mouth ulcers through formation of cysts. Epstein-Barr virus-positive mucocutaneous ulcer is a rare form of the Epstein-Barr virus-associated lymphoproliferative diseases in which infiltrating, Epstein-Barr virus (i.e. EBV)-infected B cells cause solitary, well-circumscribed ulcers in mucous membranes and skin. Drug-induced Many drugs can cause mouth ulcers as a side effect. Common examples are alendronate (a bisphosphonate, commonly prescribed for osteoporosis), cytotoxic drugs (e.g. methotrexate, i.e. chemotherapy), non-steroidal anti-inflammatory drugs, nicorandil (may be prescribed for angina) and propylthiouracil (e.g. used for hyperthyroidism). Some recreational drugs can cause ulceration, e.g. cocaine. Malignancy Rarely, a persistent, non-healing mouth ulcer may be a cancerous lesion. Malignancies in the mouth are usually carcinomas, but lymphomas, sarcomas and others may also be possible. Either the tumor arises in the mouth, or it may grow to involve the mouth, e.g. from the maxillary sinus, salivary glands, nasal cavity or peri-oral skin. The most common type of oral cancer is squamous cell carcinoma. The main risk factors are long-term smoking and alcohol consumption (particularly when combined) and betel use. Common sites of oral cancer are the lower lip, the floor of the mouth, and the sides, underside of the tongue and mandibular alveolar ridge, but it is possible to have a tumor anywhere in the mouth. Appearances vary greatly, but a typical malignant ulcer would be a persistent, expanding lesion that is totally red (erythroplasia) or speckled red and white (erythroleukoplakia). Malignant lesions also typically feel indurated (hardened) and attached to adjacent structures, with "rolled" margins or a punched out appearance and bleeds easily on gentle manipulation. If someone has an unexplained mouth ulcer persisting for more than 3 weeks this may indicate a need for a referral from the GDP or GP to hospital to exclude oral cancer. Vesiculobullous diseases Some of the viral infections mentioned above are also classified as vesiculobullous diseases. Other example vesiculobullous diseases include pemphigus vulgaris, mucous membrane pemphigoid, bullous pemphigoid, dermatitis herpetiformis, linear IgA disease, and epidermolysis bullosa.: 1, 22 Allergy Rarely, allergic reactions of the mouth and lips may manifest as erosions; however, such reactions usually do not produce frank ulceration. An example of one common allergen is Balsam of Peru. If individuals allergic to this substance have oral exposure they may experience stomatitis and cheilitis (inflammation, rash, or painful erosion of the lips, oropharyngeal mucosa, or angles of their mouth). Balsam of Peru is used in foods and drinks for flavoring, in perfumes and toiletries for fragrance, and in medicine and pharmaceutical items for healing properties. Other causes A wide range of other diseases may cause mouth ulcers. Hematological causes include anemia, hematinic deficiencies, neutropenia, hypereosinophilic syndrome, leukemia, myelodysplastic syndromes, other white cell dyscrasias, and gammopathies. Gastrointestinal causes include celiac disease, Crohns disease (orofacial granulomatosis), and ulcerative colitis. Dermatological causes include chronic ulcerative stomatitis, erythema multiforme (Stevens-Johnson syndrome), angina bullosa haemorrhagica and lichen planus. Other examples of systemic disease capable of causing mouth ulcers include lupus erythematosus, Sweet syndrome, reactive arthritis, Behçet syndrome, granulomatosis with polyangiitis, periarteritis nodosa, giant cell arteritis, diabetes, glucagonoma, sarcoidosis and periodic fever, aphthous stomatitis, pharyngitis and adenitis.The conditions eosinophilic ulcer and necrotizing sialometaplasia may present as oral ulceration. Macroglossia, an abnormally large tongue, can be associated with ulceration if the tongue protrudes constantly from the mouth. Caliber persistent artery describes a common vascular anomaly where a main arterial branch extends into superficial submucosal tissues without a reduction of diameter. This commonly occurs in elderly people on the lip and may be associated with ulceration. Treatment Treatment is cause-related, but also symptomatic if the underlying cause is unknown or not correctable. It is also important to note that most ulcers will heal completely without any intervention. Treatment can range from: Smoothing or removing a local cause of trauma Addressing dry mouth Substituting a problem medication or SLS-free toothpaste Maintaining good oral hygiene and use of an antiseptic mouthwash or spray (e.g. chlorhexidine), which can prevent secondary infection and therefore hasten healing A topical analgesic (e.g. benzydamine mouthwash) to reduce pain Topical (gels, creams or inhalers) or systemic steroids may be used to reduce inflammation An antifungal drug may be used to prevent oral candidiasis developing in those who use prolonged steroids People with mouth ulcers may prefer to avoid hot or spicy foods, which can increase the pain Self-inflicted ulceration can be difficult to manage, and psychiatric input may be required in some people: 53 For recurrent ulcers, vitamin B12 has been shown to be effective Epidemiology Oral ulceration is a common reason for people to seek medical or dental advice.: 52 A breach of the oral mucosa probably affects most people at various times during life. For a discussion of the epidemiology of aphthous stomatitis, see the epidemiology of aphthous stomatitis. See also Sodium dodecyl sulfate References External links Learning materials related to Oral ulceration at Wikiversity Mouth ulcer at Curlie
Hospitalism	Hospitalism (or anaclitic depression in its sublethal form) was a pediatric diagnosis used in the 1930s to describe infants who wasted away while in a hospital. The symptoms could include decreased physical development and disruption of perceptual-motor skills and language. In the first half of the 20th century, hospitalism was discovered to be linked to social deprivation between an infant and its caregiver. The term was used by the psychotherapist René Spitz in 1945, but the term can be traced back as early as 1897.It appears under adjustment disorders at F43.2, in the World Health Organizations classification of diseases, ICD-10. History In 1945, the psychoanalyst René Spitz published an article in which he explained how deprivation of social interactions can lead to a condition named "hospitalism" in infants. According to Spitz, young children who are cared for in institutions can suffer from severe impairment in their development because they are not provided with sufficient maternal care. Spitz did not coin the term "hospitalism," which can be traced back to the end of the 19th century. In 1897, Floyd M. Crandall published an article in the Archive of Pediatrics in which he used the term to describe a condition in institutionalized infants characterized by loss of weight, susceptibility to various diseases, and ultimately death. According to Crandall, this high mortality rate of institutionalized children under one-year-old was suspected to be caused by a lack of hygiene, food, air, exercise and personal contact.After rapid growth in welfare centres for infants at the beginning of the 20th century, hospitalism became a more public concern. One solution that was offered was the improvement of general hygiene to avoid the spread of infections. Breastfeeding became increasingly important since it was considered to provide sufficient nutrition and to improve the infants immune systems, which helped to reduce the mortality rate. The assumption that infants had no social competence or dependence on personal interactions had developed. Nurses began to replace the mothers role for institutionalized infants, and mothers were usually not allowed to visit their children more than once a week. This was supposed to minimize the risk of infections and was considered to be a solution to hospitalism. The pediatrician Meinhard von Pfaundler criticized this approach and argued that this rational and distant care would damage the infants’ physical and emotional well-being. He claimed that children needed more external stimulation than was provided in the environment of hospitals.In the early 1930s, researchers at the Vienna Psychological Institute started to concentrate on the development of infants. The so-called Viennese Baby Tests were created by Charlotte Bühler and could be used to assess the mental, social, and physical development of children. Katherine Wolf and Hildegard Durfee used these tests to conduct studies on infants in different institutions. They concluded that the environment influenced the development of children and that this was especially important for the development of social competence. According to them, infants needed to be in contact with their mothers to receive sufficient love and care for their development. In the 1940s, the idea that infections led to hospitalism was increasingly criticized, especially since hospitalized infants were often kept alone in small cubicles, without any contact with caregivers or external stimuli, to prevent cross-infections.In 1945, the psychoanalyst René Spitz redefined the term hospitalism by arguing that the mortality rate of infants was still high, despite the isolation in cubicles, because the lack of maternal care impaired their development. Spitz conducted research for his hypothesis by comparing infants in a foundling hospital in Mexico and in a prison nursery in New York with two control groups of children growing up with their families. With the help of Katherine Wolf, he assessed the development of the infants using the Viennese Baby Tests. Spitz concluded that the decline in development and the high susceptibility to diseases he discovered in institutionalized babies were not due to a lack of environmental stimuli, since the prison nursery infants actually had access to toys, but mostly due to emotional and social deprivation. According to Spitz, a stable and intimate mother-child relationship is critical for the healthy development of the child. In his short film, Grief: A Peril in Infancy, he demonstrated the consequences of hospitalism. This idea had a strong influence on other researchers, and in 1951, the British psychoanalyst John Bowlby published a report on homeless children in the USA. This report, which was titled Maternal Care and Mental Health, was commissioned by the WHO and supported his theory of maternal deprivation. According to Bowlby, a child needs to have a loving and continuous relationship with the mother to avoid permanent developmental damage and hospitalism. Causes There are three conditions which determine the likelihood of hospitalism in a patient: How healthy the person is before the admission into the hospital How well the operation or appointment gets done How the patient is taken care of after the operation or appointment, including the number of patients in the hospital in general and the hygiene of the hospitalThe most investigated causes which have been observed are those from infants and children in hospitals or nursery homes. The main cause of hospitalism in children and infants is the separation of the child from the mother. They experience a massive desperation and distress due to the isolation from their mother. An example is children or infants in a nursery home when they are only held in cribs, depriving them of the opportunity to interact with their environment and other people. This deprivation might happen since the nurse has to take care of multiple children at once. A lot of causes, as well as assumptions of causes, still have to get scientifically proved and investigated. Symptoms Symptoms of hospitalism are numerous. Symptoms are largely observable in behaviour, but a patients psychological or physical impairments are largely driven by the cause of their condition, and as such not all patients experience the same suite of problems. Physical impairments include physical underdevelopment, reduced motor speed, and increased risk of rapid-onset muscle atrophy. Patients commonly suffer from maladaptive or disruptive eating behaviour, which results in a general decrease in stamina. This has been linked to malnutrition, extreme weight loss, and food addiction. Patients tend to have a strong predisposition to marasmus, which increases mental and physical fragility, alongside an impairment of their immune system, leading them to be at higher risk for infections and viral diseases. Infants also experience a higher mortality rate. The psychological circumstances fit this image. Especially in children that stayed in orphanages for a long time and suffer from deprivation syndrome – the sensory withdrawal before adulthood resulting in physical and psychological damages – one can observe a reduction of activities due to a lack of motivation and suppression of feelings. Sleeplessness, loss of weight and apathy are additional symptoms of depression that can also play a role. Another effect of withdrawal of sensory desires in an early age are personality disorders as for example borderline and attachment and adjustment disorders that are especially seen in behavioral abnormalities.These abnormalities can consist of stereotypes – a motor restlessness that results in showing repetitive and consistent motor processes and spoken utterances that do not have any goal or function and occur in absolutely unfitting situations. Stereotypic movement might also result in self harm. Behavioral abnormalities can also hinder social relations effectively. Affected individuals tend to become apathetic and withdrawn. Antisocial behavior might manifest as lying or stealing. Disrupted social functions related to a lack of socialization and integration can lead to further isolation. Hygiene and appearance may also be negatively impacted. Consequences and complication The consequences of hospitalism can be detrimental for the people affected and reveal themselves in different ways. It is noteworthy that the symptoms can vary across different individuals, and several factors, such as age, play a significant role.Patients are also at higher risk for various mental disorders and anti-social behaviors: anxiety disorders depression borderline-personality disorder suicidal tendencies apathy low self-esteem autoaggressive behaviour attachment anxiety adjustment and communication disorders tendencies towards aggressive behaviour lack of personal hygieneIndividuals suffering from hospitalism are also at risk for sensory perception problems: altered or delayed pain perception fear of touch hypersensitivity Other common consequences relate to cognitive disorders, such as: learning disabilities rarely memory lapses or even loss of long- or short-term memory motor disorders such as monotonous and sterotyped movements (for example, banging the head against the wall) or a severely reduced ability to reactLong-term consequences, which is causally related to traumatic experiences, can be expressed in different ways. People showing signs of hospitalism might express an extreme aversion towards showing or accepting emotional or physical affection, effectively shutting themselves off from others. A different response could be promiscuity, whereas people strive for love and affection. Prevention and solutions Prevention and solutions of hospitalism largely focuses on efforts that seek to counter-act deprivation. During their stay, skin-to-skin contact between mother and child has shown to beneficial. Also, conducting various types of play activities with children, which will meet their need for physical activity can provide an opportunity to establish an intimate emotional relationship with the mother or a substitute. Therapeutic interventions should be carried out by specially trained professionals, psychotherapists, psychologists, social workers, teachers, and a network of non-professionals for people who are physically, mentally, or emotionally handicapped. Efforts are made to place parentless children in suitable accommodations, such as children’s villages and foster care. Special attention should focus on the suitability of the environment for the child. These institutions should provide the necessary support and the right environment so that children can develop normally.For the care of elderly and sick people assisted living and community houses are used for prevention. Accessibility and affordability are to continuously be improved. High-quality accommodation is also important for the proper treatment of existing illnesses and disorders. A very unique approach is lived in the Belgium city Geel, where it is common for people with mental illnesses to live with local families. See also Failure to thrive Attachment theory Maternal deprivation Stress-related disorders Philosophy of dialogue Orphan Feral child Infant cognitive development References Encyclopedia of Childhood and Adolescence
Pseudohypoaldosteronism	Pseudohypoaldosteronism (PHA) is a condition that mimics hypoaldosteronism. However, the condition is due to a failure of response to aldosterone, and levels of aldosterone are actually elevated, due to a lack of feedback inhibition. Types Presentation PHA2 is clinically characterised by hypertension, hyperkalaemia, metabolic acidosis and normal renal function. Mechanism PHA2 is also known as familial hyperkalaemic hypertension, or Gordon syndrome. The underlying genetic defect leads to increased sodium chloride reabsorption in the distal tubule in the kidney, leading to volume expansion, hypertension and lowered renin levels. The hyperkalemia found in PHA2 is proposed to be a function of diminished sodium delivery to the cortical collecting tubule (potassium excretion is mediated by the renal outer medullary potassium channel ROMK in which sodium reabsorption plays a role). Alternatively, WNK4 mutations that result in a gain of function of the Na-Cl co-transporter may inhibit ROMK activity resulting in hyperkalemia. Unlike in PHA1 in which aldosterone resistance is present, in PHA2 the volume expansion leads to relatively low aldosterone levels. Treatment Treatment of severe forms of PHA1 requires relatively large amounts of sodium chloride. These conditions also involve hyperkalemia.In contrast, PHA2 (Gordons syndrome) requires salt restriction and use of thiazide diuretics to block sodium chloride reabsorption and normalise blood pressure and serum potassium. History This syndrome was first described by Cheek and Perry in 1958. Later pediatric endocrinologist Aaron Hanukoglu reported that there are two independent forms of PHA with different inheritance patterns: A renal form with autosomal dominant inheritance exhibiting salt loss mainly from the kidneys, and a multi-system form with autosomal recessive form exhibiting salt loss from kidney, lung, and sweat and salivary glands.The hereditary lack of responsiveness to aldosterone could be due to at least two possibilities: 1. A mutation in the mineralocorticoid receptor that binds aldosterone, or 2. A mutation in a gene that is regulated by aldosterone. Linkage analysis on patients with the severe form of PHA excluded the possibility of linkage of the disease with the mineralocorticoid receptor gene region. Later, the severe form of PHA was discovered to be due to mutations in the genes SCNN1A, SCNN1B, and SCNN1G that code for the epithelial sodium channel subunits, α, β, and γ, respectively.A stop mutation in the SCNN1A gene has been shown to be associated with female infertility. See also Hyperchloremic acidosis Pseudohyperaldosteronism References External links GeneReviews/NCBI/NIH/UW entry on Pseudohypoaldosteronism Type II
Ischial bursitis	Ischial bursitis (also known as weavers bottom) is inflammation of the synovial bursa located between gluteus maximus muscle and ischial tuberosity. Signs and symptoms Ischial bursitis causes pain down the posterior aspect of the upper thigh. There may be pain over the ischial tuberosity. Chronic ischial bursitis may cause paraesthesia. This pain may become immediately more severe when sitting down. Cause Ischial bursitis is usually caused by prolonged sitting on a hard surface. It may also be related to ischial apophysitis, which may be caused by exercise, particularly in young and athletic patients. Mechanism The ischial bursa is a synovial bursa located between gluteus maximus muscle and ischial tuberosity. When in a seated position, the ischial bursa is put under the highest amount of pressure, which is most significant against a hard surface.Friction from exercise can lead to inflammation of the ischial bursa, known as bursitis. Diagnosis Ischial bursitis is usually diagnosed clinically based on symptoms. An x-ray (using injected contrast agent) may be used to identify the formation of calluses. Treatment Ischial bursitis is usually treated conservatively. Lifestyle changes may be advised, avoiding certain exercises and sitting on hard surfaces. Analgesics, such as nonsteroidal anti-inflammatory drugs, may be used relieve pain.Ischial bursitis may be treated with medical and surgical interventions if it is persistent or particularly severe. Analgesics, anaesthetics, or triamcinolone may be injected to relive pain. Epidemiology Ischial bursitis is a fairly rare illness. When a patient presents with symptoms, other conditions such as a spinal disc herniation may be considered. History Ischial bursitis is also known as "weavers bottom" and "tailors bottom" after professions which involve prolonged sitting on a hard surface. == References ==
Caffeine-induced anxiety disorder	Caffeine-induced anxiety disorder is a subclass of the DSM-5 diagnosis of substance/medication-induced anxiety disorder.Consumption of caffeine has long been linked to anxiety. The effects of caffeine and the symptoms of anxiety both increase activity within the sympathetic nervous system. Caffeine has been linked to the aggravation and maintenance of anxiety disorders, and the initiation of panic or anxiety attacks in those who are already predisposed to such phenomena. Caffeine usage surpassing 200 mg has been shown to increase the likelihood for anxiety and panic attacks in a population. Excessive amounts of caffeine can result in symptoms from general anxiety to obsessive-compulsive and phobic symptoms. DSM-5 classification Diagnostic criteria Caffeine-induced anxiety disorder is a subclass of the DSM-5 diagnosis of substance/medication-induced anxiety disorder. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, or DSM-5, is the current authority for psychiatric diagnosis in the United States. Substance/medication-induced anxiety disorder falls under the category of anxiety disorders in the DSM-5, and not the category of substance-related and addictive disorders, even though the symptoms are due to the effects of a substance.Diagnosis according to the DSM-5 is dependent on various criteria. Patients must present symptoms of either panic attacks or anxiety. There must also be evidence that the panic or anxiety symptoms are a direct result of the use of the intoxicating substance. In caffeine-induced anxiety disorder, such symptoms would be due to the consumption of caffeine. The DSM-5 makes the distinction that the substance must be physiologically capable of leading to the anxiety and panic symptoms. This establishes the relationship between the abused chemical agent and the observed clinical effects. Caffeine has been proven to act as an antagonist on adenosine receptors, which acts as a stimulant and therefore fulfills this criteria. Symptoms must also not have a more likely clinical cause, such as another type of anxiety disorder, come before the ingestion of the intoxicating substance, or last for an extended amount of time after stopping the use of the substance. Diagnosis also requires that the panic attacks or anxiety due to the use of the intoxicating substance cause a certain amount of disturbance in the patient or lead to deficiency of varying types of daily performance. Diagnostic features In addition to the criteria above, it is important to recognize that the diagnostic criteria for substance/medication-induced anxiety disorder are not met if the symptoms of panic come before the intoxication by the substance. In caffeine-induced anxiety disorder, a diagnosis will not be made if symptoms of anxiety or panic precede the ingestion of caffeine. Also, if symptoms persist for more than one month after substance intoxication, the diagnosis cannot be made. Persistence and continuation of symptoms beyond the initial consumption of caffeine suggest an alternate diagnosis that would better explain the long-lasting symptoms. Anxiety symptoms caused by caffeine are often mistaken for serious mental disorders including bipolar disorder and schizophrenia, leaving patients medicated for the wrong issue. A caffeine-induced anxiety disorder diagnosis should be made, rather than a substance abuse or intoxication diagnosis, when symptoms of panic attacks or anxiety predominate. 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. Mobilization of intracellular calcium At very high concentrations of about 1–2 mM, caffeine lowers the excitability threshold in muscle cells, leading to prolonged contraction. The introduction of such high doses of caffeine allows calcium to enter the muscle cell through the plasma membrane and sarcoplasmic reticulum more readily. Influx of calcium through the membranes in muscle cells requires at least 250 μM of caffeine. Normally, other toxic effects of caffeine begin to occur in concentrations over 200 μM, however average consumption averages lead to concentrations less than 100 μM. This means that calcium influx and mobilization are most likely not the cause of caffeines effect on the central nervous system, and are therefore not the cause of caffeine-induced anxiety disorder. Inhibition of phosphodiesterases Methylxanthines such as caffeine inhibit the action of cyclic nucleotide phosphodiesterase, which normally acts to break down cAMP. Cyclic adenosine monophosphate, or cAMP, is a second messenger important in many cellular processes and is a critical factor in signal transduction. The inhibition of the phosphodiesterase would lead to a buildup of cAMP, increasing the activity of the second messenger throughout the cell. Though this mechanism is possible, it only occurs after levels of caffeine have reached a toxic level, and therefore it is unlikely to explain the mechanism of caffeine in the brain. Antagonism of adenosine receptors There are four well-known adenosine receptors found in the body, A1, A2A, A2B, and A3. The endogenous agonist for these receptors is adenosine, which is a purine nucleoside that is important for processes such as energy transfer in the form of adenosine triphosphate (ATP) and adenosine monophosphate (AMP) and signal transduction in the form of cyclic adenosine monophosphate (cAMP). A2B and A3 receptors require concentrations of caffeine that do not occur at normal physiological levels or with normal levels of caffeine consumption in order to be antagonized, and will therefore not be considered as a possible mechanism for caffeine-induced anxiety.Caffeine acts as an antagonist of adenosine A1 and A2A receptors. Adenosine is a normal neuromodulator that activates adenosine g-protein coupled receptors. The actions of A1 and A2A receptors oppose each other but are both inhibited by caffeine due to its function as an antagonist.A2A receptors are coupled to Gs proteins which activate adenylate cyclase and some voltage gated Ca2+ channels. A2A receptors are located in dopamine rich brain regions. A2A receptor mRNA was found in the same neurons as the dopamine receptor D2 within the dorsal striatum, nucleus accumbens and tuberculum olfactorium. A2A receptors are not found in neurons that express the dopamine receptor D1 receptors and Substance P. Within the striatum, part of the basal ganglia, activation of A2A receptors by adenosine increases GABA release, an inhibitory neurotransmitter. When caffeine binds to the receptor, less inhibitory neurotransmitter is released, supporting caffeines role as a central nervous system stimulant.A1 receptors are paired with the G-proteins of Gi-1, Gi-2, Gi-3, Go1, and Go2. The g-proteins of A1 receptors continue to inhibit adenylate cyclase, some voltage gated Ca2+ channels, and activate some K+ channels, and phospholipase C and D. A1 receptors are primarily located in the hippocampus, cerebral and cerebellar cortex, and particular thalamic nuclei. Adenosine acts on A1 receptors to decrease opening of N-type Ca2+ channels in some hippocampal neurons, and therefore decrease the rate of firing since Ca2+ is necessary for neurotransmitter release. Caffeines antagonistic action on the A1 receptor thus decreases the action of adenosine, allowing increased Ca2+ entry through N-type channels and higher rates of neurotransmitter release. Other actions of caffeine Though antagonism of adenosine receptors is the primary mechanism of caffeine, Introduction of the methylxanthine into the body also increases the rate of release and recycling of some monoamine neurotransmitters such as noradrenaline and dopamine. Caffeine also has an excitatory effect on mesocortical cholinergic neurons by acting as an antagonist on adenosine receptors that normally inhibit the neuron. Genetics and variability of caffeine consumption While many factors contribute to individual differences in a persons response to caffeine, such as environmental and demographic factors (i.e. age, drug use, circadian factors, etc.), genetics play an important role in individual variability. This inconsistency in responses to caffeine can take place either at the metabolic or at the drug-receptor level. The effects of genetic factors can occur either directly by changing acute or chronic reactions to the drug or indirectly by altering other psychological or physiological processes.Some of these processes include wakefulness, stimulation, and mood and cognition enhancement. Low doses can result in psychological effects of "mild euphoria, alertness, and enhanced cognitive performance"; higher doses produce physiological side effects of nausea, anxiety, trembling, and jitteriness. There are individuals who are prone to caffeines anxiogenic effects whilst others are susceptible to its caffeine-induced sleep disturbances and insomnia. Studies with twins have shown that genetics influence individual differences in response to caffeine. Homozygous twins have been found to react in more consistent ways to the caffeine than heterozygous twins. Behavioral effects Caffeines widespread appeal is due primarily to its mild psychostimulant properties, which increase alertness and cognitive arousal and diminish fatigue. Caffeine also produces a wide range of other symptoms, including upregulation of the cardiovascular system, increased global cognitive processing, and improved physical functioning. Cardiovascular effects can range from increased heart rate and reactivity to severe cardiac arrhythmia. The cognitive effects of caffeine include increased performance in memory, attention, and text reading. The physical effects of caffeine include lowered sensations of pain, less perceived effort, and increased muscle strength and endurance. However, at doses above ~400 mg, both cognitive and physical performance begins to worsen and symptoms of anxiety increase. One study that explored ad lib caffeine consumption in 159 college students found that high consumers reported lower academic performance. The same study also concluded that moderate and high consumers combined reported significantly higher trait anxiety and depression scores when compared with abstainers. These anxiety symptoms include persisting insomnia, nervousness, and mood fluctuations.When undergoing stress, the body activates a system-wide response mechanism known as the HPA axis. This stress signal begins at the level of the hypothalamus in the brain and undergoes subsequent amplifications throughout the body. This system elevates levels of stress hormones in the blood, which results in the body shutting down secondary bodily processes and increasing alertness to better prepare for response to the perceived threat. Studies show that activation of this pathway is correlated with anxiety-like behaviors, including panic, post-traumatic stress, and generalized anxiety disorders, as well as depression. Rodent studies show that caffeine consumption in adolescence results in dysregulation of HPA axis function as well as central nervous system response, which impairs the bodys response to stressful stimuli.In cases of prolonged consumption of excess amounts of caffeine, studies show that individuals exhibit a reduced response to HPA axis activation by the hormone ACTH and a generalized increase in basal levels of stress hormone corticosterone. Researchers concluded that the sensitivity of adrenal glands to ACTH is diminished by caffeine consumption. People diagnosed with panic disorder show less HPA activity following stressful stimuli than their healthy control counterparts. Susceptible populations Caffeine has varying effects on anxiety across given populations. The populations most susceptible to caffeine-induced anxiety disorder include those already diagnosed with an anxiety disorder and adolescents. Adolescents, particularly, are at increased risk for developing anxiety disorders and anxiety-related symptoms. While few human studies have been done to investigate this connection, many rodent studies show a correlation between caffeine consumption in adolescence and increased anxiety. These studies showed that in adolescent rodents exposed to caffeine, functioning of serotonin systems was affected, leading to increased anxiety; anxiety-related behaviors were higher than in adult rats exposed to the same amount of caffeine; and reward seeking behaviors as well as mood fluctuations were increased as the rodents matured. Long-term health effects When consumed in moderation, caffeine can have many beneficial effects. However, over the course of several years, chronic caffeine consumption can produce various long-term health deficits in individuals. Among these, rodent studies have suggested caffeine intake may permanently alter the brains excitability. As previously stated, long-term effects are most often seen in adolescents who regularly consume excess amounts of caffeine. This can affect their neuroendocrine functions and increase the risk of anxiety-disorder development. Treatment For individuals being treated with benzodiazepines such as alprazolam (Xanax) for anxiety disorders, even small amounts of caffeine may have negative effects on treatment. Caffeine is able to negate the effects of benzodiazepines which can lead to heightened levels of anxiety and even panic attacks. Studies have linked caffeine intake to increased rates of cytotoxicity and cell death by necrosis associated with benzodiazepine use. However, this phenomenon (thought to be mediated via TSPO) is also present with benzodiazepine use alone. The clinical significance of caffeine-benzodiazepine induced cytotoxicity in humans is unclear and has not been shown to be harmful. Although benzodiazepines are effective at managing acute caffeine-induced anxiety symptoms, avoiding caffeine is generally recommended rather than increasing benzodiazepine intake. Treatments for caffeine-induced anxiety disorder tend to focus on abstinence from or a reduction of caffeine intake and behavioral therapy. Some doctors may recommend a continuance of caffeine consumption but with the provision that the patient actively takes note of physiological changes that happen after caffeine intake. The goal of this approach is to help patients better understand the effects of caffeine on the body and to distinguish threatening symptoms from normal reactions. == References ==
Pathological demand avoidance	Pathological demand avoidance (PDA) is a profile of autism spectrum disorder and a proposed sub-type. Characteristics ascribed to the condition include greater refusal to do what is asked of the person, even to activities the person would normally like, due to extreme levels of anxiety and lack of autonomy. Although PDA has its own traits that are separate from autism, they generally meet the diagnostic criteria by having significant impairments in social interaction and communication and presenting restricted and repetitive behaviors. Some notable differences in PDA compared to classic autism spectrum disorders are that individuals appear to be more sociable, have far better social skills and social understanding, tend to be more interested in people than objects, are more comfortable with pretend play, and tend to be more imaginative. It is not recognized by either the DSM-5 or the ICD-10 and is unlikely to be separated out now that the umbrella diagnosis of ASD has been adopted. In 2011, it was suggested that these symptoms could represent the condition oppositional defiant disorder (ODD). Elizabeth ONions and others argue that unlike ASD, “children with PDA are said to use socially manipulative avoidance strategies”; and unlike ODD, they “resort to extreme, embarrassing or age-inappropriate behaviour”.The term was proposed in 1980 by the UK child psychologist Elizabeth Ann Newson. Recognition Pathological demand avoidance is not recognized by the DSM-5 or ICD-10, the two main classification systems for mental disorders. To be recognized, a sufficient amount of consensus and clinical history needs to be present, and as a newly proposed condition, PDA had not met the standard of evidence required at the time of recent revisions. However, DSM-5 also moved from sub-type classification to the use of ‘Autistic Spectrum Disorder’, which allows for the behavioural traits of different profiles to be described. In 2011, the National Institute for Health and Care Excellence commented on the fact that PDA has been proposed as part of the autism spectrum but did not include further discussion within the guideline. NICE guidance also expects an ‘ASD’ diagnosis be accompanied by a diagnostic assessment, providing a profile of key strengths and difficulties. Demand Avoidance is listed as a ‘sign or symptom of ASD’ (Appendix 3).Christopher Gillberg wrote a commentary article in 2014 that reviewed recent research and stated, “Experienced clinicians throughout child psychiatry, child neurology and paediatrics testify to its existence and the very major problems encountered when it comes to intervention and treatment.” Proposed diagnostic criteria As of 2014 there are no recognized diagnostic criteria. Criteria proposed by Newson include: Passive early history in the first year, avoiding ordinary demands and missing milestones Continuing to avoid demands, panic attacks if demands are escalated Surface sociability, but apparent lack of sense of social identity Lability of mood and impulsivity Comfortable in role play and pretending Language delay, seemingly the result of passivity, often caught up quickly Obsessive behavior Neurological signs (awkwardness, similar to autism spectrum disorders)The underlying cause of this avoidance is said to be a high level of anxiety, usually from expectations of demands being placed on children, which can lead to a feeling of not being in control of a situation. Children with PDA feel threatened when they are not in control of their environment and their actions, which triggers the fight, flight or freeze response. History Newson first began to look at PDA as a specific syndrome in the 1980s when certain children referred to the Child Development Clinic at the University of Nottingham appeared to display and share many of the same characteristics. These children had often been referred because they seemed to show many autistic traits, but were not typical in their presentation like those with classical autism or Aspergers syndrome. They had often been labelled as atypical autism or Persistent Development Disorder-Not Otherwise Specified (PDD-NOS). Both of these terms were felt by parents to be unhelpful. When Newson was made professor of developmental psychology at the University of Nottingham in 1994, she dedicated her inaugural lecture to talking about pathological demand avoidance syndrome.In 1997, the PDA Society was established in the UK by parents of children with a PDA profile of autism. It became a registered charity in January 2016.In July 2003, Newson published in Archives of Disease in Childhood for PDA to be recognized as a separate syndrome within the pervasive developmental disorders.In 2020, an Incorporated Association was established in Australia. Pathological Demand Avoidance Australia Inc. became a registered charity early 2021. Bibliography Fidler, Ruth; Christie, Phil (2019). Collaborative Approaches to Learning for Pupils with PDA: Strategies for Education Professionals. Jessica Kingsley Publishers. ISBN 9781784502614. == References ==
Malakoplakia	Malakoplakia (from Greek Malako "soft" + Plako "plaque") is a rare inflammatory condition which makes its presence known as a papule, plaque or ulceration that usually affects the genitourinary tract.: 274 However, it may also be associated with other bodily organs. It was initially described in the early 20th century as soft yellowish plaques found on the mucosa of the urinary bladder. Microscopically it is characterized by the presence of foamy histiocytes (called von Hansemann cells) with basophilic inclusions called Michaelis–Gutmann bodies. It usually involves gram-negative bacteria. Causes Malakoplakia is thought to result from the insufficient killing of bacteria by macrophages. Therefore, the partially digested bacteria accumulate in macrophages and leads to a deposition of iron and calcium. The impairment of bactericidal activity manifests itself as the formation of an ulcer, plaque or papule. Malakoplakia is associated with patients with a history of immunosuppression due to lymphoma, diabetes mellitus, kidney transplantation, or because of long-term therapy with systemic corticosteroids. Diagnosis As malakoplakia is a condition associated with chronic cystitis, it usually presents itself as a cystitis condition. The following investigations may help in making the diagnosis of malakoplakia: Urinalysis which indicates presence of bacteria and white blood cells. Urine culture Cystoscopic evaluation confirms presence of ulcer or papule. Biopsy to rule out other causes. The presence of large multinucleated malakoplakia giant cells with concretions called as Michaelis Gutman bodies on microscopy. Treatment Treatments for malakoplakia include catheterizing the affected person with full aseptic precautions. Additionally, irrigating the bladder with distilled water three times daily with 3 way Foleys catheter and urinary antiseptics like pyridium may be used to help relieve urinary symptoms. Antibiotics such as trimethoprim-sulfamethoxazole or ciprofloxacin may be used. History Leonor Michaelis and Carl Gutmann first described malakoplakia in 1902 after analyzing a patients tumor at the request of David Paul von Hansemann. See also List of inclusion bodies that aid in diagnosis of cutaneous conditions References == External links ==
Bartons fracture	A Bartons fracture is a type of wrist injury where there is a broken bone associated with a dislocated bone in the wrist, typically occurring after falling on top of a bent wrist. It is an intra-articular fracture of the distal radius with dislocation of the radiocarpal joint.There exist two types of Bartons fracture – dorsal and palmar, the latter being more common. The Bartons fracture is caused by a fall on an extended and pronated wrist increasing carpal compression force on the dorsal rim. Intra-articular component distinguishes this fracture from a Smiths or a Colles fracture. Treatment of this fracture is usually done by open reduction and internal fixation with a plate and screws, but occasionally the fracture can be treated conservatively. Eponym It is named after John Rhea Barton (1794–1871), an American surgeon who first described this in 1838. Additional images References External links 01217 at CHORUS
Megaduodenum	Megaduodenum is a congenital or acquired dilation and elongation of the duodenum with hypertrophy of all layers that presents as a feeling of gastric fullness, abdominal pain, belching, heartburn, and nausea with vomiting sometimes of food eaten 24 hours prior.Megaduodenum does not let the muscles of the duodenum function properly, the movement of waste material in the intestines gets impaired, which in turn affects digestion and nutrition.This condition is a rare entity in adults, because it may be either primary idiopathic or secondary. The secondary causes include Chagas disease, systematic sclerosis, duodenal stenosis, and visceral myopathy. Signs and Symptoms The signs of duodenum can vary amongst patients. A high rate of chromosomal damage found in blood lymphocytes can indicate the presence of megaduodenum.Symptoms include: Dilated Duodenum Abdominal distention Nausea Vomiting and diarrhea Severe digestive pseudo-obstruction Recurrent urinary retention Vacuolar degeneration and fibrosis of the longitudinal layer of gastrointestinal muscle.It is possible that this disease can be misdiagnosed and mimic other intestinal disorders, or later increase the chances of becoming a tumor. Causes Although environmental factors can play a role in the development of Megaduodenum, genetic factors are responsible for creating tumors. Therefore, many complications of chromosomal damage in the blood lymphocytes can be possible causes. However, the main causes are: Annular pancreas Adhesions Systemic sclerosis Superior mesenteric artery syndrome Aneurysm. Duodenal atresiaMegaduodenum due to its duodenal ganglionitis is an unusual condition, Megaduodenums similarity to megacolon and megaesophagus diseases can better explain the most plausible causes of it. In addition, some theories state that megaduodenum can be associated with the following causes: post-vagotomy, vitamin deficiency, and collagen diseases. Mechanism/Pathophysiology Megaduodenum can be passed down through families, it occurs when a patient inherits one copy of a muted megaduodenum gene from one parent. When the gene gets interrupted in the cells, it causes tumors. Acute pancreatitis, adhesions, aneurysm all clinically lead to Megaduodenum. Diagnosis Diagnostic tests and procedures can vary for different types of intestinal disorders. These can include colonoscopy, upper GI endoscopy, capsule endoscopy, endoscopic ultrasound. Since patients with megaduodenum often have atypical symptoms such as hematemesis, steatorrhea, and acute pancreatitis. Therefore, physical and histological examination helps demonstrate the grade of distention and the nutritional status of the patient. Many of the physical examinations include: blood pressure, bowel sounds, blood tests, and thyroid function. In addition, a histological examination such as upper endoscopy, an X-ray of the abdomen, and biopsies can also be performed to diagnose megaduodenum efficiently. Prevention/Treatment The treatment mainly depends on the underlying conditions and the degree of distention of the duodenum. It can be symptomatic and based on diet and control of bacterial overgrowth. To relieve the obstructive symptoms, latero-lateral duodenojejunostomy, gastrojejunostomy, duodenal-jejunal bypass (DJB), enteral and parenteral nutrition may be helpful. Therefore, early diagnosis and treatment may improve patients outcome and reduce morbidity. Prognosis As long as Megaduodenum is treated promptly, the chances of making full recovery is possible. Posturing maneuvers during meals may be helpful in some patients, also to relive any compression of the duodenum the patient may lie down in right decubitus position. If the conservative treatments fail, surgery may be performed. Some of the surgeries may include duodenojejunostomy, laparoscopic duodenojejunostomy, or laparoscopic surgery.The timeline for recovery is 7 weeks. Epidemiology No statistical information has been identified. Megaduodenum is an uncommon disease, and because of its extreme rarity of the condition only few cases has been reported in the literatures. Current Research Since Megaduodenum is a rare disease, treatments and decisions are made based on the patients initial conditions and their responses to the provided treatments or surgeries.There are currently several ongoing clinical trials for megaduodenum. One study involves research of idiopathic megaduodenum in children which is a rare condition. The purpose of this study is to present the management of idiopathic megaduodenum in children. References Further reading Basilisco, G (1997). "Hereditary megaduodenum". The American Journal of Gastroenterology. 92 (1): 150–3. PMID 8995957. Law, David H.; Ten Eyck, Edward A. (1962). "Familial megaduodenum and megacystis". The American Journal of Medicine. 33 (6): 911. doi:10.1016/0002-9343(62)90222-X. Sturtevant, Mills (1939). "Megaduodenum and Duodenal Obstruction: Criteria for Diagnosis". Radiology. 33 (2): 185–8. doi:10.1148/33.2.185. Raia, Arrigo; Acquaroni, Danilo; Netto, Alipio Correa (1961). "Pathogenesis and treatment of acquired megaduodenum". The American Journal of Digestive Diseases. 6 (8): 757–71. doi:10.1007/BF02231059. PMID 13739156. S2CID 7354820. Gillespie, H. W. (1939). "Megaduodenum and Gastromegaly". British Journal of Radiology. 12 (136): 221–4. doi:10.1259/0007-1285-12-136-221. == External links ==
Werner syndrome	Werner syndrome (WS) or Werners syndrome, also known as "adult progeria", is a rare, autosomal recessive disorder which is characterized by the appearance of premature aging.Werner syndrome is named after the German scientist Otto Werner. He identified the syndrome in four siblings observed with premature aging, which he explored as the subject of his dissertation of 1904.It has a global incidence rate of less than 1 in 100,000 live births (although incidence in Japan and Sardinia is higher, affecting 1 in 20,000–40,000 and 1 in 50,000, respectively). 1,300 cases had been reported as of 2006. Affected individuals typically grow and develop normally until puberty; the mean age of diagnosis is twenty-four, often realized when the adolescent growth spurt is not observed. The youngest person diagnosed was six years old. The median and mean ages of death are 47–48 and 54 years, respectively. The main causes of death are cardiovascular disease and cancer. Presentation Werner syndrome patients exhibit growth retardation, short stature, premature graying of hair, alopecia (hair loss), wrinkling, prematurely aged faces with beaked noses, skin atrophy (wasting away) with scleroderma-like lesions, lipodystrophy (loss of fat tissues), abnormal fat deposition leading to thin legs and arms, and severe ulcerations around the Achilles tendon and malleoli (around ankles). Other symptoms include change in voice (weak, hoarse, high-pitched), atrophy of gonads leading to reduced fertility, bilateral cataracts (clouding of lens), premature arteriosclerosis (thickening and loss of elasticity of arteries), calcinosis (calcium deposits in blood vessels), atherosclerosis (blockage of blood vessels), type 2 diabetes, osteoporosis (loss of bone mass), telangiectasia, and malignancies. The prevalence of rare cancers, such as meningiomas, are increased in individuals with Werner syndrome. Gene expression Gene transcription changes found in WS cells are strikingly similar to those observed in normal aging. At the level of gene expression, WRN protein deficiency causes changes in the pattern of gene expression that markedly resemble those of normal old age. DNA methylation The blood of WS patients exhibits accelerated DNA methylation changes that are similar to those observed in normal aging according to a molecular biomarker of aging known as epigenetic clock. Diagnosis and clinical symptoms The mutation in the WRN gene that causes Werner syndrome is autosomal and recessive, meaning that sufferers must inherit a copy of the gene from each parent. Patients display rapid premature aging beginning in young adulthood, usually in their early twenties. Diagnosis is based on six cardinal symptoms: premature graying of the hair or hair loss, presence of bilateral cataracts, atrophied or tight skin, soft tissue calcification, sharp facial features, and an abnormal, high-pitched voice. Patients are generally short-statured due to absence of the adolescent growth spurt. Patients also display decreased fertility. The most common symptom of the six is premature graying and loss of hair. This is also generally the earliest observed symptom, with hair loss occurring first on the scalp and the eyebrows.Werner syndrome patients often have skin that appears shiny and tight, and may also be thin or hardened. This is due to atrophy of the subcutaneous tissue and dermal fibrosis. Over time, the characteristic facial features may be more apparent due to these skin conditions. Other associated skin conditions include ulcers, which are very difficult to treat in Werner syndrome patients, and are caused in part by decreased potential of skin cells for replication.WS cataracts are distinctly different from those of normal aging. They are associated with problems in the lens posterior cortex and subcapsular regions. These cataracts are generally treatable with cataract surgery, which should restore normal vision.Symptoms become apparent in the late teens and early twenties and continue to progress. Most patients live to about fifty years of age. The most common causes of death for people are associated diseases and complications, especially atherosclerosis and cancer. Associated diseases Werner syndrome patients are at increased risk for several other diseases, many associated with aging. Atherosclerosis, the thickening of artery walls due to cholesterol buildup, is one common complication. While normal atherosclerosis generally involves the major arteries, smaller arterioles are more likely to be affected. It is possible nervous system disorders are associated. Brain atrophy is present in 40% of patients. Osteoporosis, the loss of bone mineral density common in post-menopausal women, is another common symptom. In contrast with the normal population, the rate of osteoporosis is especially high for male patients. Diabetes mellitus is another common accompaniment. Skin ulcers occur in about 75% of patients – and can be difficult to treat. If skin ulcers become badly infected or develop gangrene, they often require amputation. Unlike most other related diseases and complications, these ulcers are not associated with normal aging.Patients are also at an increased risk of cancer, especially malignant melanoma. Soft-tissue sarcomas are the most common cancer types. Other types of skin cancer, other epithelial cancers such as thyroid and liver cancers, MDS (myelodysplastic syndrome), and MFH (malignant fibrous histiocytoma) are also prevalent among. Mutations in the WRN gene, especially single-nucleotide polymorphisms (SNPs), are associated with many of the cancers and other associated diseases. WRN SNPs correlate with cancers such as sarcomas and non-Hodgkin lymphomas, as well as diabetes and cardiovascular problems including atherosclerosis. Causes Approximately 90% of individuals presenting Werner syndrome have any of a range of mutations in the gene, WRN, the only gene currently attributed to cause Werner syndrome. WRN, which lies on chromosome 8 in humans, encodes the WRNp protein, a 1432 amino acid protein with a central domain resembling members of the RecQ helicases. RecQ helicases are a special type of helicase that function at unique times during DNA repair of doubled stranded breaks, which are a form of DNA damage that results in a break of both strands of DNA. Thus, RecQ helicases are important for maintaining DNA stability, and loss of function of these helicases has important implications in the development of Werner syndrome. In addition to the central domain, there are three exonuclease domains at the N-terminus and a Helicase and Ribonuclease D C-terminal (HRDC) domain at the C-terminus.When functioning normally, the WRN gene and its associated protein (WRNp) are important for maintaining genome stability. WRNp is active in unwinding DNA, a step necessary in DNA repair and DNA replication. Specifically, it has an important role in responding to replication malfunctions, particularly double-stranded breaks, and stalled replication machinery. WRNp may reactivate replication by preventing unwanted recombination processes from occurring or by promoting recombination, depending on the type of DNA damage. In addition, WRNp physically interacts with or binds to several other proteins that are involved in processing DNA. For example, when WRNp binds to RPA, its helicase activity is stimulated. WRNp also physically interacts with p53, a tumor suppressor gene that stops the formation of tumors and the progression of cancers, which inhibits the exonuclease activity of the WRNp. Since WRNps function depends on DNA, it is only functional when localized to the nucleus.Surprisingly, complete loss of WRN helicase activity does not cause clinical Werner syndrome. DNA repair processes The finding that WRN protein interacts with DNA-PKcs and the Ku protein complex, combined with evidence that WRN deficient cells produce extensive deletions at sites of joining of non-homologous DNA ends, suggests a role for WRN protein in the DNA repair process of non-homologous end joining (NHEJ). WRN protein also physically interacts with the major NHEJ factor X4L4 (XRCC4-DNA ligase 4 complex). X4L4 stimulates WRN exonuclease activity that likely facilitates DNA end processing prior to final ligation by X4L4.WRN protein appears to play a role in resolving recombination intermediate structures during homologous recombinational repair (HRR) of DNA double-strand breaks.WRN protein participates in a complex with RAD51, RAD54, RAD54B and ATR proteins in carrying out the recombination step during inter-strand DNA cross-link repair.Evidence was presented that WRN protein plays a direct role in the repair of methylation induced DNA damage. This process likely involves the helicase and exonuclease activities of WRN protein that operate together with DNA polymerase beta in long patch base excision repair. Effects on cell structure and function Mutations which cause Werner syndrome all occur at the regions of the gene which encode for protein, and not at non-coding regions. There are 35 different known mutations of WRN, which correspond to stop codons, insertions, or deletions that result in a frameshift mutation. These mutations can have a range of effects. They may decrease the stability of the transcribed messenger RNA (mRNA), which increases the rate at which they are degraded. With less mRNA, less is available to be translated into the WRNp protein. Mutations may also lead to the truncation (shortening) of the WRNp protein, leading to the loss of its nuclear localization signal sequence, thus it is no longer transported into the nucleus where it interacts with the DNA. This leads to a reduction in DNA repair. Furthermore, mutated proteins are more likely to be degraded than normal WRNp. Apart from causing defects in DNA repair, its aberrant association with p53 down-regulates the function of p53, leading to a reduction in p53-dependent apoptosis and increasing the survival of these dysfunctional cells. Cells of affected individuals also have reduced lifespan in culture, have more chromosome breaks and translocations and have extensive deletions.Patients with Werner syndrome lose the RecQ helicase activity in the WRN protein because of the loss of its C-terminus region, but the mechanism by which this happens is unclear. The loss of the helicase activity can have far-reaching consequences in terms of cell stability and mutation. One instance of these consequences involves telomeres. It is thought that the WRN helicase activity is important not only for DNA repair and recombination, but also for maintaining telomere length and stability. Thus, WRN helicase is important for preventing catastrophic telomere loss during DNA replication. In a normal cell, the telomeres (the ends of chromosomes) undergo repeated shortening during the cell cycle, which can prevent the cell from dividing and multiplying. This event can be counteracted by telomerase, an enzyme that extends the ends of the chromosomes by copying the telomeres and synthesizing an identical, but new end that can be added to the existing chromosome. However, patients with Werner syndrome often exhibit accelerated telomere shortening, indicating that there may be a connection between the loss of the WRN helicase activity and telomere and cell instability. While evidence shows that telomere dysfunction is consistent with the premature aging in WS, it has yet to be determined if it is the actual cause of the genomic instability observed in cells and the high rate of cancer in WS patients.Without the WRN protein, the interwoven pathways of DNA repair and telomere maintenance fail to suppress cancer and the aging symptoms seen in patients with WS. Events such as rapid telomere shortening cause Werner syndrome cells to exhibit low responses to overall cellular stress. In addition to telomere dysfunction, over-expression of oncogenes and oxidation can induce this type of response. High stress causes a synergistic effect, where WS cells become even more sensitive to agents that increase cell stress and agents that damage DNA. As a result, WS cells show a drastic reduction in replicative lifespan and enter into a stage of aging prematurely. The accumulation of these damaged cells due to telomere shortening over many years may be indicative of why Werner syndrome symptoms only appear after an individual is about twenty years old. Protection of DNA against oxidative damage WRN protein was found to have a specific role in preventing or repairing DNA damages resulting from chronic oxidative stress, particularly in slowly replicating cells. This finding suggested that WRN may be important in dealing with oxidative DNA damage that underlies normal aging (see DNA damage theory of aging). Diagnosis Treatment A cure for Werner syndrome has not yet been discovered. It is often treated by managing the associated diseases and relieving symptoms to improve quality of life. The skin ulcers that accompany WS can be treated in several ways, depending on the severity. Topical treatments can be used for minor ulcers, but are not effective in preventing new ulcers from occurring. In the most severe cases, surgery may be required to implant a skin graft or amputate a limb if necessary. Diseases commonly associated with Werner syndrome such as diabetes and cancer are treated in generally the same ways as they would be for a non-Werner syndrome individual. A change in diet and exercise can help prevent and control arteriosclerosis, and regular cancer screenings can allow for early detection of cancer.There is evidence that suggests that the cytokine-suppressive anti-inflammatory drug SB203580 may be a possible therapeutic option for patients with Werners syndrome. This drug targets the p38 signaling pathway, which may become activated as a result of genomic instability and stalled replication forks that are characteristic mutations in WS. This activation of p38 may play a role in the onset of premature cell aging, skin aging, cataracts, and graying of the hair. The p38 pathway has also been implicated in the inflammatory response that causes atherosclerosis, diabetes, and osteoporosis, all of which are associated with Werners syndrome. This drug has shown to revert the aged characteristics of young WS cells to those seen in normal, young cells and improve the lifespan of WS cells in vitro. SB203580 is in the clinical trial stages, and the same results have not yet been seen in vivo.In 2010, vitamin C supplementation was found to reverse the premature aging and several tissue dysfunctions in a genetically modified mouse model of the disease. Vitamin C supplementation also appeared to normalize several age-related molecular markers such as the increased levels of the transcription factor NF-κB. In addition, it decreases activity of genes activated in human Werner syndrome and increases gene activity involved in tissue repair. Supplementation of vitamin C is suspected to be beneficial in the treatment of human Werner syndrome, although there was no evidence of anti-aging activity in nonmutant mice. In general, treatments are available for only the symptoms or complications and not for the disease itself. History Otto Werner was the first to observe Werner syndrome in 1904 as a part of his dissertation research. As a German ophthalmologist, Werner described several progeria-like features and juvenile cataracts in many of his patients. He noticed these symptoms particularly in a family with four sequential children who all showed the characteristics of the syndrome at around the same age. He assumed the cause to be genetic, though most of his evidence was clinical. Between 1934 and 1941, two internists from New York, Oppenheimer and Kugel, coined the term "Werner Syndrome," igniting a wave of interest and research on the disease. During that time, Agatson and Gartner suggested a possible link between Werners syndrome and cancer. However, it was not until 1966 that there was a general consensus on the autosomal recessive mode of inheritance for the syndrome. By 1981, geneticists had located the WRN gene on chromosome 8, leading to its cloning in 1996. This cloning of the WRN was significant because it revealed the predicted WRN protein was made from a family of DNA helicases. Prior to 1996, Werner syndrome was thought to be a model for accelerated aging. Since the discovery of the gene, it has become clear that the premature aging displayed in Werner syndrome is not the same, on a cellular level, as normal aging. The role of WRN in DNA repair and its exonuclease and helicase activities have been the subject of many studies in recent years.Since the initial discovery in 1904, several other cases of Werner syndrome have been recorded. Many of these cases have occurred in Japan, where a founder effect has caused a higher incidence rate than in other populations. The incidence rate of Werner syndrome in Japan is approximately 1 case per 100 thousand people (1:100,000), a large contrast with the rate of incidence for the rest of the world, which is between 1:1,000,000 and 1:10,000,000. A founder effect is also apparent in Sardinia, where there have been 18 recorded cases of Werner syndrome. Society and culture On the episode "Stargazer in a Puddle" from the television series Bones, the victim has Werner syndrome. The team discovers in the course of the investigation that her mother killed her because she was dying of another disease, and worried that her daughter would have nobody to look after her afterwards, with the tragic twist that the mother began to recover from her disease after her daughters death.Werner syndrome is featured in the 1989 film The Fly II, starring Eric Stoltz, in which his character is born as a 2 year old baby. He never sleeps and grows 5 times his normal age due to his biological father having half fly genes from the first 1986 film The Fly.Werner syndrome is also featured in the 1996 film Jack, starring Robin Williams, in which his character ages four times faster than normal.In an early cutscene from the game Metal Gear Solid 4, Otacon cites "classic Werner syndrome" as the most likely cause of Solid Snakes premature aging, though he goes on to say that testing had been inconclusive. It is however later said that Solid Snakes body, created as a genetically engineered clone, had been designed to break down quickly.In season 3 episode 9, "The Ballad of Kevin and Tess", of the TV series The 4400, Kevin is said to have Werner syndrome to hide his real condition from the public.In The Invisible Man season 1 episode 6, "Impetus", the new character Gloria has an experimentally altered type of Werner syndrome that causes it to become contagious.The central character in Gail Tsukiyamas novel DREAMING WATER (2002) has Werners syndrome.In season 1 episode 8 "Cold Comfort" from TV series Dark Angel, a character has a "form of progeria, similar to Werner syndrome", due to genetic manipulation. With an appropriate treatment, her condition seems to be stabilized.In Resident Evil: The Final Chapter (2016), the deadly "T-Virus", which causes the viral pandemic in the Resident Evil film series, is revealed to be the cure for "adult progeria". James Marcus originally develops the virus to cure his young daughter Alicia Marcus.Ratsasan (2018), a Tamil movie (as well as its Telugu remake Rakshasudu), features a young man born with Werners and is a victim of childhood bullying due to his appearance and has bad experience proposing to a girl, who turns into serial killer and hunts down and kills school girls. See also References External links This article incorporates public domain text from The U.S. National Library of Medicine Werner Syndrome from GeneReviews, contains extensive information on the disorder
Haemophilia C	Haemophilia C (also known as plasma thromboplastin antecedent (PTA) deficiency or Rosenthal syndrome) is a mild form of haemophilia affecting both sexes, due to factor XI deficiency. It predominantly occurs in Ashkenazi Jews. It is the fourth most common coagulation disorder after von Willebrands disease and haemophilia A and B. In the United States, it is thought to affect 1 in 100,000 of the adult population, making it 10% as common as haemophilia A. Signs and symptoms In terms of the signs/symptoms of haemophilia C, unlike individuals with Haemophilia A and B, people affected by it are not ones to bleed spontaneously. In these cases, haemorrhages tend to happen after a major surgery or injury. However, people affected with haemophilia C might experience symptoms closely related to those of other forms of haemophilia such as the following: Cause Haemophilia C is caused by a deficiency of coagulation factor XI and is distinguished from haemophilia A and B by the fact it does not lead to bleeding into the joints. Furthermore, it has autosomal recessive inheritance, since the gene for factor XI is located on chromosome 4 (near the prekallikrein gene); and it is not completely recessive, individuals who are heterozygous also show increased bleeding.Many mutations exist, and the bleeding risk is not always influenced by the severity of the deficiency. Haemophilia C is occasionally observed in individuals with systemic lupus erythematosus, because of inhibitors to the FXI protein. Diagnosis The diagnosis of haemophilia C (factor XI deficiency) is centered on prolonged activated partial thromboplastin time (aPTT).One will find that the factor XI has decreased in the individuals body. In terms of differential diagnosis one must consider: haemophilia A, haemophilia B, lupus anticoagulant and heparin contamination. The prolongation of the activated partial thromboplastin time should completely correct with a 1:1 mixing study with normal plasma if haemophilia C is present; in contrast, if a lupus anticoagulant is present as the cause of a prolonged aPTT, the aPTT will not correct with a 1:1 mixing study. Treatment In terms of haemophilia C medication tranexamic acid is often used for both treatment after an incident of bleeding and as a preventive measure to avoid excessive bleeding during oral surgery.Treatment is usually not necessary, except in relation to operations, leading to many of those having the condition not being aware of it. In these cases, fresh frozen plasma or recombinant factor XI may be used, but only if necessary.Those affected may often develop nosebleeds, while females can experience unusual menstrual bleeding which can be avoided by taking birth control such as: IUDs and oral or injected contraceptives to increase coagulation ability by adjusting hormones to levels similar to pregnancy. See also References Further reading Zucker, M.; Zivelin, A.; Landau, M.; Salomon, O.; Kenet, G.; Bauduer, F.; Samama, M.; Conard, J.; Denninger, M.-H.; Hani, A.-S.; Berruyer, M.; Feinstein, D.; Seligsohn, U. (1 October 2007). "Characterization of seven novel mutations causing factor XI deficiency". Haematologica. 92 (10): 1375–1380. doi:10.3324/haematol.11526. ISSN 0390-6078. PMID 18024374. Orkin, Stuart H.; Nathan, David G. (2008). Nathan and Oskis Hematology of Infancy and Childhood. Elsevier Health Sciences. ISBN 978-1416034308. Retrieved 12 July 2016. Goldman, Lee; Schafer, Andrew I. (2016). Goldman-Cecil Medicine Elsevieron VitalSource. Elsevier Health Sciences. ISBN 9780323322850. Retrieved 12 July 2016. == External links ==
Imperforate anus	An imperforate anus or anorectal malformations (ARMs) are birth defects in which the rectum is malformed. ARMs are a spectrum of different congenital anomalies which vary from fairly minor lesions to complex anomalies. The cause of ARMs is unknown; the genetic basis of these anomalies is very complex because of their anatomical variability. In 8% of patients, genetic factors are clearly associated with ARMs. Anorectal malformation in Currarino syndrome represents the only association for which the gene HLXB9 has been identified. Types There are other forms of anorectal malformations though imperforate anus is most common. Other variants include anterior ectopic anus. This form is more commonly seen in females and presents with constipation. Presentation There are several forms of imperforate anus and anorectal malformations. The new classification is in relation of the type of associated fistula.The classical Wingspread classification was in low and high anomalies: A low lesion, in which the colon remains close to the skin. In this case, there may be a stenosis (narrowing) of the anus, or the anus may be missing altogether, with the rectum ending in a blind pouch. A high lesion, in which the colon is higher up in the pelvis and there is a fistula connecting the rectum and the bladder, urethra or the vagina. A persistent cloaca (from the term cloaca, an analogous orifice in birds, reptiles and amphibians), in which the rectum, vagina and urinary tract are joined into a single channel.Imperforate anus is usually present along with other birth defects—spinal problems, heart problems, tracheoesophageal fistula, esophageal atresia, renal anomalies and limb anomalies are among the possibilities, collectively being called the VACTERL association. Associated anomalies Imperforate anus is associated with an increased incidence of some other specific anomalies as well, together being called the VACTERL association.Other entities associated with an imperforate anus are trisomies 18 and 21, the cat-eye syndrome (partial trisomy or tetrasomy of a maternally derived chromosome 22), Baller–Gerold syndrome, Currarino syndrome, caudal regression syndrome, FG syndrome, Johanson–Blizzard syndrome, McKusick–Kaufman syndrome, Pallister–Hall syndrome, short rib–polydactyly syndrome type 1, Townes–Brocks syndrome, 13q deletion syndrome, urorectal septum malformation sequence and the OEIS complex (omphalocele, exstrophy of the cloaca, imperforate anus, spinal defects). Diagnosis When an infant is born with an anorectal malformation, it is usually detected quickly as it is a very obvious defect. Doctors will then determine the type of birth defect the child was born with and whether or not there are any associated malformations. It is important to determine the presence of any associated defects during the newborn period in order to treat them early and avoid further sequelae. There are two main categories of anorectal malformations: those that require a protective colostomy and those that do not. The decision to open a colostomy is usually taken within the first 24 hours of birth.Sonography can be used to determine the type of imperforate anus. Treatment Imperforate anus usually requires immediate surgery to open a passage for feces unless a fistula can be relied on until corrective surgery takes place. Depending on the severity of the imperforate, it is treated either with a perineal anoplasty or with a colostomy. While many surgical techniques to definitively repair anorectal malformations have been described, the posterior sagittal approach (PSARP) has become the most popular. It involves dissection of the perineum without entry into the abdomen and 90% of defects in boys can be repaired this way. Prognosis With a high lesion, many children have problems controlling bowel function and most also become constipated. With a low lesion, children generally have good bowel control, but they may still become constipated. For children who have a poor outcome for continence and constipation from the initial surgery, further surgery to better establish the angle between the anus and the rectum may improve continence and, for those with a large rectum, surgery to remove that dilated segment may significantly improve the bowel control for the patient. An antegrade enema mechanism can be established by joining the appendix to the skin (Malone stoma); however, establishing more normal anatomy is the priority. Epidemiology Imperforate anus has an estimated incidence of 1 in 5000 births. It affects boys and girls with similar frequency. However, imperforate anus will present as the low version 90% of the time in females and 50% of the time in males. Imperforate anus is an occasional complication of sacrococcygeal teratoma. Society and culture Ribbon The ribbon to represent anorectal malformations/imperforate anus abnormalities is turquoise, which encapsulates hope, strength and a positive attitude. Zebra stripes were added to show the uniqueness and represent just how no two zebra markings are the same, nor are people living with ARM/IA. Awareness day The international awareness day for anorectal abnormalities is 1 May. The day aims to raise awareness about an abnormality many have not heard of by creating a human connection for an abnormality that often leaves people feeling alone. The day 1 May was chosen to represent the incidence of such malformations, which occur in roughly 1 in 5,000 babies. History Seventh-century Byzantine physician Paulus Aegineta described a surgical treatment for imperforate anus for the first time. tenth-century Persian physician Haly Abbas was the first to highlight preserving the sphincter muscles throughout the surgery and the prevention of strictures with a stent. He has reported the use of wine for wound care in this surgery. Some reports of children surviving this surgery are available from the early medieval Islamic era. References External links Medline Plus Medical Encyclopedia: Imperforate anus
Phlyctenular keratoconjunctivitis	Phlyctenular keratoconjunctivitis is an inflammatory syndrome caused by a delayed (aka type-IV) hypersensitivity reaction to one or more antigens. The triggering antigen is usually a bacterial protein (particularly from Staphylococcus aureus), but may also be a virus, fungus (particularly Candida albicans), or nematode. Symptoms Irritation Discomfort or pain Foreign-body sensation Tearing Blepharospasm Photophobia Mucopurulent discharge (rarely) In cases where the cornea is affected, pain and photophobia are more likely, and corneal scarring can occur (potentially impairing vision). Presentation The syndrome is marked by the appearance of characteristic lesions, known as phlyctenules, on the cornea and/or conjunctiva. These usually manifest as small (1 - 3 or 1 - 4 mm) raised nodules, pinkish-white or yellow in color, which may ulcerate (or, more rarely, necrose) and are often surrounded by dilated blood vessels. Corneal lesions are usually triangular in shape, with the base at the limbus and the apex pointing towards the center of the cornea. Diagnosis Clinical findings of Corneal lesion or corneal ulceration. Treatment The symptoms of phlyctenular keratoconjunctivitis are primarily treated with application of an appropriate corticosteroid eye drop, such as prednisolone acetate (Pred Forte) or loteprednol (Lotemax). Loteprednol is increasingly preferred due to its lower risk of elevating intraocular pressure. The corticosteroid suppresses the immune response, reducing inflammation and improving most symptoms.The causative agent (i.e. the source of the antigen that triggered the hypersensitive immune response) should also be identified. Staphylococcus aureus is usually the primary suspect, along with Mycobacterium tuberculosis in areas where TB is endemic, followed by Chlamydia trachomatis. Active bacterial infections may be treated with a topical antibiotic or a combination antibiotic-steroid eye drop, such as tobramycin/dexamethasone (Tobradex). An oral tetracycline antibiotic (such as doxycycline) may be used in systemic or particularly severe/intractable infections. Erythromycin may be an effective alternative, especially in pediatric cases where the side effects of tetracyclines are unacceptable.Artificial tears can reduce dryness and discomfort from corneal lesions. Photophobic discomfort can be mitigated with dark sunglasses. See also Blepharitis Allergic conjunctivitis Conjunctivitis Keratitis Keratoconjunctivitis Corneal abrasion == References ==
Chilblain lupus erythematosus	Chilblain lupus erythematosus is a chronic, unremitting form of lupus erythematosus with the fingertips, rims of ears, calves, and heels affected, especially in women. See also Lupus erythematosus List of cutaneous conditions References == External links ==
Multicentric carpotarsal osteolysis syndrome	Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare autosomal dominant condition. This condition is also known as idiopathic multicentric osteolysis with nephropathy. It is characterised by carpal-tarsal destruction and kidney failure. Signs and symptoms The presentation is of gradual loss of the small bones in the carpus and tarsus. This may lead to joint subluxation and instability. The kidney failure, when present, usually presents as the presence of protein in the urine. In some cases, there may also be craniofacial abnormalities including Triangular facies Micrognathia Maxillary hypoplasia ExophthalmosHistology of renal biopsies show glomerulosclerosis and severe tubulointerstitial fibrosis. Intellectual disability may occur. Genetics This condition is caused by mutations in the transcription factor MafB, or V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB), gene. This gene encodes a basic leucine zipper (bZIP) transcription factor. The gene is located on the long arm of chromosome 20 (20q11.2-q13.1). Pathogenesis How this mutation causes the clinical picture is not currently clear. Diagnosis The diagnosis may be suspected on the basis of the constellation of clinical features. It is made by sequencing the MAFB gene. Classification This condition has been classified into five types. Type 1: hereditary multicentric osteolysis with dominant transmission Type 2: hereditary multicentric osteolysis with recessive transmission Type 3: nonhereditary multicentric osteolysis with nephropathy Type 4: Gorham–Stout syndrome Differential diagnosis The condition should be differentially diagnosed from juvenile rheumatoid arthritis and other genetic skeletal dysplasias as Multicentric Osteolysis, Nodulosis, and Arthropathy. Treatment Optimal treatment for this condition is unclear. Bisphosphonates and denosumab may be of use for the bone lesions. Cyclosporine A may be of use for treating the nephropathy. Steroids and other immunosuppressant drugs do not seem to be of help. History This condition was first described by Shurtleff et al. in 1964. == References ==
Myeloid sarcoma	A myeloid sarcoma (chloroma, granulocytic sarcoma,: 744 extramedullary myeloid tumor) is a solid tumor composed of immature white blood cells called myeloblasts. A chloroma is an extramedullary manifestation of acute myeloid leukemia; in other words, it is a solid collection of leukemic cells occurring outside of the bone marrow. Types In acute leukemia Chloromas are rare; exact estimates of their prevalence are lacking, but they are uncommonly seen even by physicians specializing in the treatment of leukemia. Chloromas may be somewhat more common in patients with the following disease features: French–American–British (FAB) classification class M2 WHO Classification (2016 revision) is a separate entity under the "Acute myeloid leukemia (AML) and related neoplasms" those with specific cytogenetic abnormalities (e.g. t(8;21) or inv(16)) those whose myeloblasts express T-cell surface markers, CD13, or CD14 those with high peripheral white blood cell countsHowever, even in patients with the above risk factors, chloroma remains an uncommon complication of acute myeloid leukemia. Rarely, a chloroma can develop as the sole manifestation of relapse after apparently successful treatment of acute myeloid leukemia. In keeping with the general behavior of chloromas, such an event must be regarded as an early herald of a systemic relapse, rather than as a localized process. In one review of 24 patients who developed isolated chloromas after treatment for acute myeloid leukemia, the mean interval until bone marrow relapse was 7 months (range, 1 to 19 months). In myeloproliferative or myelodysplastic syndromes Chloromas may occur in patients with a diagnosis of myelodysplastic syndrome (MDS) or myeloproliferative syndromes (MPS) (e.g. chronic myelogenous leukemia (CML), polycythemia vera, essential thrombocytosis, or myelofibrosis). The detection of a chloroma is considered de facto evidence these premalignant conditions have transformed into an acute leukemia requiring appropriate treatment. For example, presence of a chloroma is sufficient to indicate chronic myelogenous leukemia has entered its blast crisis phase. In Eosinophilic leukemia At least one case of FIP1L1-PDGFRA fusion gene-induced eosinophilic leukemia presenting with myeloid sarcoma and eosinophilia has been reported. This form of myeloid sarcoma is distinguished by its highly successful treatment with imatinib (the recommended treatment for FIP1L1-PDGRGA fusion gene-induced eosinophilic leukemia) rather than more aggressive and toxic therapy. Primary chloroma Very rarely, chloroma can occur without a known pre-existing or concomitant diagnosis of acute leukemia, acute promyelocytic leukemia or MDS/MPS; this is known as primary chloroma. Diagnosis is particularly challenging in this situation (see below). In almost all reported cases of primary chloroma, acute leukemia has developed shortly afterward (median time to development of acute leukemia 7 months, range 1–25 months). Therefore, primary chloroma could be considered an initial manifestation of acute leukemia, rather than a localized process, and could be treated as such. Where disease development or markers indicate progresses to acute promyleocytic leukemia (AML3) treatment should be tailored to this form of disease. Location and symptoms Chloromas may occur in virtually any organ or tissue. The most common areas of involvement are the skin (also known as leukemia cutis) and the gums. Skin involvement typically appears as violaceous, raised, nontender plaques or nodules, which on biopsy are found to be infiltrated with myeloblasts Note that leukemia cutis differs from Sweets syndrome, in which the skin is infiltrated by mature neutrophils in a paraneoplastic process. Gum involvement (gingival hypertrophy) leads to swollen, sometimes painful gums which bleed easily with tooth brushing and other minor trauma. Other tissues which can be involved include lymph nodes, the small intestine, the mediastinum, the lung, epidural sites, the uterus, the ovaries, and the orbit of the eye. Symptoms of chloroma at these sites are related to their anatomic location; chloromas may also be asymptomatic and be discovered incidentally in the course of evaluation of a person with acute myeloid leukemia. Central nervous system involvement, as described above, most often takes the form of meningeal leukemia, or invasion of the subarachnoid space by leukemic cells. This condition is usually considered separately from chloroma, as it requires different treatment modalities. True chloromas (i.e. solid leukemic tumors) of the central nervous system are exceedingly rare, but have been described. Diagnosis Definitive diagnosis of a chloroma usually requires a biopsy of the lesion in question. Historically, even with a tissue biopsy, pathologic misdiagnosis was an important problem, particularly in patients without a clear pre-existing diagnosis of acute myeloid leukemia to guide the pathologist. In one published series on chloroma, the authors stated that 47% of the patients were initially misdiagnosed, most often as having a malignant lymphoma.However, with advances in diagnostic techniques, the diagnosis of chloromas can be made more reliable. Traweek et al. described the use of a commercially available panel of monoclonal antibodies, against myeloperoxidase, CD68, CD43, and CD20, to accurately diagnose chloroma via immunohistochemistry and differentiate it from lymphoma. Nowadays, immunohistochemical staining using monoclonal antibodies against CD33 and CD117 would be the mainstay of diagnosis. The increasingly refined use of flow cytometry has also facilitated more accurate diagnosis of these lesions. Prognostic significance Evidence is conflicting on the prognostic significance of chloromas in patients with acute myeloid leukemia. In general, they are felt to augur a poorer prognosis, with a poorer response to treatment and worse survival; however, others have reported chloromas associate, as a biologic marker, with other poor prognostic factors, and therefore do not have independent prognostic significance. In case of primary isolated choloroma, prognosis is better Treatment As described above, chloromas should always be considered manifestations of systemic disease, rather than isolated local phenomena, and treated as such. In the patient with newly diagnosed leukemia and an associated chloroma, systemic chemotherapy against the leukemia is typically used as the first-line treatment, unless an indication for local treatment of the chloroma (e.g. compromise of the spinal cord) emerges. Chloromas are typically quite sensitive to standard antileukemic chemotherapy. Allogeneic hematopoietic stem cell transplantation should be considered in fit patients with suitable available donor, as long term remissions have been reported.If the chloroma is persistent after completion of induction chemotherapy, local treatment, such as surgery or radiation therapy, may be considered, although neither has an effect on survival.Patients presenting with a primary chloroma typically receive systemic chemotherapy, as development of acute leukemia is nearly universal in the short term after detection of the chloroma. Patients treated for acute leukemia who relapse with an isolated chloroma are typically treated with systemic therapy for relapsed leukemia. However, as with any relapsed leukemia, outcomes are unfortunately poor. Patients with "preleukemic" conditions, such as myelodysplastic syndromes or myeloproliferative syndromes, who develop a chloroma are often treated as if they have transformed to acute leukemia. History The condition now known as chloroma was first described by the British physician A. Burns in 1811, although the term chloroma did not appear until 1853. This name is derived from the Greek word chloros (green), as these tumors often have a green tint due to the presence of myeloperoxidase. The link between chloroma and acute leukemia was first recognized in 1902 by Dock and Warthin. However, because up to 30% of these tumors can be white, gray, or brown rather than green, the more correct term granulocytic sarcoma was proposed by Rappaport in 1967 and has since become virtually synonymous with the term chloroma. Currently, any extramedullary manifestation of acute myeloid leukemia can be termed a granulocytic sarcoma or chloroma. Specific terms which overlap with granulocytic sarcoma include: Leukemia cutis, describing infiltration of the dermis (skin) by leukemic cells, which is also referred to as cutaneous granulocytic sarcoma. Meningeal leukemia, or invasion of the subarachnoid space by leukemic cells, is usually considered distinct from chloroma, although very rarely occurring solid central nervous system tumors composed of leukemic cells can be termed chloromas.In recent years, the term "myeloid sarcoma" has been favored. See also Acute myeloid leukemia References == External links ==
Hand eczema	Hand eczema presents on the palms and soles, and may sometimes be difficult or impossible to differentiate from atopic dermatitis, allergic contact dermatitis, and psoriasis, which also commonly involve the hands.: 78 Even a biopsy of all these conditions may not result in a definitive diagnosis, as all three conditions may demonstrate spongiosis and crusting on the hands.: 78 Non-communicable inflammation of the skin of the hands is referred to as hand eczema. Hand eczema is widely prevalent and, as it is a very visible condition associated with severe itching or pain, has serious consequences for the affected person including a high psychological impact. Different disease patterns can be identified according to the course of the illness, appearance of symptoms, degree of severity, or catalysts. Prognosis is hard to predict for individual cases of chronic hand eczema and usually differs from patient to patient. Successful treatment depends on determining the causes of the condition, obtaining an accurate diagnosis, sustainable hand protection procedures and an early, extensive, and where appropriate internal treatment. Signs and symptoms Normally, skin inflammation connected with hand eczema is accompanied by blister formation and pronounced itching, but solid calluses and painful tearing may also occur. The quality of life of the affected person is seriously diminished, especially in the case of chronic forms of the illness, and psychological impact is often very high. This impact is enhanced by the high visibility of the illness on the hands, which may lead to feelings of shame and fear of rejection. Causes There are a number of different causes of skin inflammation of the hands, the interplay of which is also significant: environmental factors such as excessive water; contact with allergens or irritants; and genetic disposition. A single catalyst is seldom responsible for the development of hand eczema in patients. Differences according to catalysts Three main factors play an essential role in the development of chronic hand eczema: excessive contact with water and irritants (cumulative-toxic stress), contact with allergens, and atopic diathesis, which has a genetic component. Individual hand eczema types are identified and named according to the main catalysts involved, i.e. cumulative-toxic, contact-allergenic, or atopic hand eczema. Activities that are stressful for the skin or involve repeated, excessive contact with water or skin-irritating substances at work or home can cause damage to the skins protective abilities and increase the chances of inflammation. This also applies to prolonged wearing of protective rubber gloves and similar materials, since sweating occurs within these gloves. Disturbance of the skins protective barrier also facilitates penetration by allergenic substances and promotes the development of contact dermatitis. Contact allergies play a very important role in the development of hand eczema. If the hand is subjected to repeated contact with a substance that leads to an allergy, the skin reacts with signs of inflammation. Numerous people affected by hand eczema also experience skin inflammation on their feet. Often, a contact allergy to an ingredient in shoe leather treatment may be the catalyst. Contact allergies in certain types of employment are especially problematic, particularly if the work involves the handling of allergenic materials, e.g. masonry work or hairdressing. People allergic to Balsam of Peru may experience a flare-up of hand eczema if they use or consume products that use it as an ingredient.Severe and chronic eczema qualifies as one of the most frequent occupational illnesses. Patients should therefore be referred to an occupational-dermatological specialist as soon as possible. Patients with a history of neurodermitis, hay fever, or allergic asthma often develop hand eczema. These sicknesses reflect the individuals particular susceptibility or genetic predisposition to react over-sensitively to various environmental influences. This is described as atopy or atopy diathesis. Atopic diathesis is frequently accompanied by genetically conditioned problems with the skins protective barriers, which causes a weakening of the skins resistance against irritating substances and moisture, as well as easier penetration by allergens, which may lead to the development of contact allergies. Differences according to prevailing signs of skin illness (morphology) The clinical appearance of various subtypes of hand eczema differs. The term dyshidrotic hand eczema is used to describe formations that mainly exhibit pronounced, itching blister formations, while callus and tear formations typically indicate hyperkeratotic fissured hand eczema. Differences according to degree of severity and course Independent of the triggering cause or the prevailing signs of skin illness, the selection and planning of treatment options is important, since different types of illness also differ in terms of their degree of severity and the course of the illness. While light hand eczema heals relatively quickly following dermatological therapy and patient participation, more pronounced hand eczema may persist over several weeks. Severe hand eczema is characterised by consistent or recurring, extended inflammation of the skin that severely affects the patient. Hand eczema is described as chronic if it lasts at least 3 months in spite of dermatological treatment, or if it recurs at least twice within a period of 12 months (relapsed) . Severe and chronic patterns of hand eczema are often resilient to treatment, making the condition extremely stressful for those affected. Diagnosis During diagnosis it is important to determine the type of hand eczema and plan specific treatment accordingly. An additional diagnosis of allergies will indicate whether contact allergies or atopy diathesis are the cause of the hand eczema. Discussion concerning frequency of contact with water, irritants, and allergens in private and professional environments will also help evaluate individual stresses on the patients skin. The hands may also exhibit various other skin illnesses and potential fungal infection or psoriasis must be ruled out. Usually, taking the patients personal history into account will help provide an accurate diagnosis. Patch testing has been found to be helpful in the diagnosis of hand eczema. Treatment Hand eczema is a complex condition, and treatment should only be administered by a dermatologist with specialist knowledge. Treatment may be very costly. Treatment should follow certain basic principles, and chronic and severe cases of hand eczema in particular require complex treatment concepts. Besides skin care, hand protection, and external (topical) applications with preparations containing effective ingredients or light therapy, an internal (systemic) therapy may be considered. Avoidance of catalysts, basic procedures, and skin protection Of primary importance is the strict removal and avoidance of catalysts for the development of chronic hand eczema, such as skin-irritating damage, excessive contact with water, or proven allergenic substances. Treatment of every type of hand eczema and degree of severity must include sustainable replenishment of the natural oils and moisture contained in the skin with creams and salves free of fragrances and preservatives; this is an essential basic step. In addition, protection procedures developed especially for the individuals skin stresses must be applied, e.g. use of cotton or hypoallergenic plastic gloves. Depending on the individuals own needs, these procedures should continue after the hand eczema heals, since they will also have a preventive effect. External treatment External treatment should be oriented primarily according to the prevailing signs of illness. In the case of blister forming, drying treatments such as hand baths containing synthetic tannins or oily-moist preparations may hinder itching. If callus development exhibiting tear formation is present, the focus should be on softening the skin with preparations containing urea or salicylic acid. In order to reduce inflammation, creams and salves containing cortisone are often very effective. Topical corticosteroids are a standard treatment for hand eczema, but their efficacy in comparison to UV phototherapy is not clear. Severe and chronic cases seldom respond sufficiently and require long periods of treatment which can increase the risk of side effects occurring. In individual cases, and especially in the case of atopic hand eczema, the dermatologist may prefer to use cortisone-free, anti-inflammatory creams or salves, which include calcineurin inhibitors tacrolimus or pimecrolimus. A 55 patient trial found topical bexarotene 1% gel monotherapy to be effective and well-tolerated (79% response rate for ≥50% clinical improvement; 39% response rate for ≥90% improvement). Phototherapy Phototherapy can be effective in the treatment of chronic hand eczema. However, not all dermatologists or dermatology clinics offer this form of therapy, and it involves extended periods of treatment for the patient. A period of four to six weeks should involve 3–4 radiation sessions. The most frequently applied form of light therapy is PUVA therapy. This first treats the hands with a cream that contains an ingredient that causes the skin to become light-sensitive, the hands are then irradiated with ultraviolet A light (UV-A). After two days of treatment, a pause of one day must occur. Due to possible risks such as premature skin aging or chronic light damage caused to the skin, phototherapy cannot be considered for the long term. Systemic treatment Besides skin care, skin protection, and an external treatment, severe and chronic cases of hand eczema often also require systemic treatment. Various preparations are available for this. For acute, severe episodes exhibiting blister formation, internal cortisone preparations, sometimes in combination with certain antibiotics, may be helpful in the short term. The active agent ciclosporin, which is approved for treatment of severely pronounced neurodermitis, may also be used for severe, atopic hand eczema. Other substances that suppress the immune system have also shown effectiveness in some cases. However, these substances are not approved for hand eczema. In the last couple of years an internal medicine has been approved for the first time for the treatment of chronic hand eczema. This involves a derivative of vitamin A, called alitretinoin, which is also naturally present in the human body. Alitretinoin can be used to treat all forms of severe chronic hand eczema which have not reacted to external cortisone preparations. The effectiveness of this form of treatment has been tested extensively in clinical study programs and proven prior to its approval. The trial results showed that two thirds of patients did not have a recurrence 6 months after application of the medication, and that re-treatment is effective if hand eczema reoccurs. The duration of alitretinoin treatment is 3 to 6 months. During treatment and one month prior to beginning and one month after completion, women of childbearing-age must use contraceptives and also test for pregnancy each month since, as with all derivatives of vitamin A, the substance involved is teratogenic. Side effects mainly include temporary headaches during the initial days of treatment, as well as a possible increase in blood fat and cholesterol values. Regular laboratory tests of blood values are recommended to monitor this. Epidemiology Hand eczema is a common condition: study data indicates a one-year prevalence of up to 10% in the general population. It is estimated that only 50–70% of people affected consult a doctor. The frequency of severe, chronic and recurrent forms of hand eczema is estimated at 5–7%. Approximately 2–4% of hand eczema patients also report that external (topical) therapy is insufficient.Several factors adversely affect the long-term prognosis, including the development of the condition prior to the 20th birthday, the severity of initial manifestations, and eczema during childhood. Women, especially those under 30, are more frequently affected than men. References == External links ==
Hyperestrogenism	Hyperestrogenism, hyperestrogenic state, or estrogen excess, is a medical condition characterized by an excessive amount of estrogenic activity in the body. Signs and symptoms Signs of hyperestrogenism may include heightened levels of one or more of the estrogen sex hormones (usually estradiol and/or estrone), lowered levels of follicle-stimulating hormone and/or luteinizing hormone (due to suppression of the hypothalamic–pituitary–gonadal axis by estrogen), and lowered levels of androgens such as testosterone (generally only relevant to males). Symptoms of the condition in women may consist of menstrual irregularities, amenorrhea, abnormal vaginal bleeding, and enlargement of the uterus and breasts. It may also present as isosexual precocity in children and as hypogonadism, gynecomastia, feminization, impotence, and loss of libido in males. If left untreated, hyperestrogenism may increase the risk of estrogen-sensitive cancers such as breast cancer later in life. Causes Hyperestrogenism can be caused by ovarian tumors, genetic conditions such as aromatase excess syndrome (also known as familial hyperestrogenism), or overconsumption of exogenous sources of estrogen, including medications used in hormone replacement therapy and hormonal contraception. Liver cirrhosis is another cause, though through lowered metabolism of estrogen, not oversecretion or overconsumption like the aforementioned. Its necessary to know there exist two kinds of hyperestrogenism: Absolute (more concentration than usual of estrogen) and relative (a normal concentration of estrogen, higher with respect to progesterone). An example of absolute hyperestrogenism could be: persistent follicles that later undergo atresia without ovulating; and the example of relative hyperestrogenism: luteal insufficiency. Diagnosis Treatments Treatment may consist of surgery in the case of tumors, lower doses of estrogen in the case of exogenously-mediated estrogen excess, and estrogen-suppressing medications like gonadotropin-releasing hormone analogues and progestogens. In addition, androgens may be supplemented in the case of males. See also Aromatase deficiency Aromatase excess syndrome Estrogen insensitivity syndrome High-dose estrogen Hyperandrogenism Hypergonadism Hypergonadotropic hypergonadism Hypoandrogenism Hypoestrogenism Hypogonadism == References ==
Postcholecystectomy syndrome	Postcholecystectomy syndrome (PCS) describes the presence of abdominal symptoms after a cholecystectomy (gallbladder removal). Symptoms occur in about 5 to 40 percent of patients who undergo cholecystectomy, and can be transient, persistent or lifelong. The chronic condition is diagnosed in approximately 10% of postcholecystectomy cases. The pain associated with postcholecystectomy syndrome is usually ascribed to either sphincter of Oddi dysfunction or to post-surgical adhesions. A recent 2008 study shows that postcholecystectomy syndrome can be caused by biliary microlithiasis. Approximately 50% of cases are due to biliary causes such as remaining stone, biliary injury, dysmotility and choledococyst. The remaining 50% are due to non-biliary causes. This is because upper abdominal pain and gallstones are both common but are not always related. Non-biliary causes of PCS may be caused by a functional gastrointestinal disorder, such as functional dyspepsia.Chronic diarrhea in postcholecystectomy syndrome is a type of bile acid diarrhea (type 3). This can be treated with a bile acid sequestrant like cholestyramine, colestipol or colesevelam, which may be better tolerated. Presentation Symptoms of postcholecystectomy syndrome may include: Dyspepsia, nausea and vomiting. Flatulence, bloating and diarrhea. Persistent pain in the upper right abdomen. Diagnostics Ultrasound of the abdominal cavity. General and biochemical blood. Intravenous cholangiography. Esophagogastroduodenoscopy for examination of the stomach, duodenum and the area major duodenal papilla. Retrograde cholangiopancreatography. Analysis of biliary sludge obtained through endoscopic retrograde cholangiopancreatography (ERCP) SeHCAT or other test for bile acid diarrhea Treatment Some individuals may benefit from diet modification, such as a reduced fat diet, following cholecystectomy. The liver produces bile and the gallbladder acts as reservoir. From the gallbladder, bile enters the intestine in individual portions. In the absence of a gallbladder, bile enters the intestine constantly, but in small quantities. Thus, it may be insufficient for the digestion of fatty foods. Postcholecystectomy syndrome treatment depends on the identified violations that led to it. Typically, the patient is recommended a dietary restriction table with fatty foods, enzyme preparations, antispasmodics, and sometimes cholagogue.If the pain is caused by biliary microlithiasis, oral ursodeoxycholic acid can alleviate the condition.A trial of bile acid sequestrant therapy is recommended for bile acid diarrhea.Functional dyspepsia is subdivided into Epigastric Distress Syndrome (EPS) and Post-Prandial Distress Syndrome (PDS). Treatment for EPS and PDS can both include proton pump inhibitors and dopamine antagonists. Tricyclic antidepressants have also been proven effective for nausea, vomiting, early satiety, impaired motility and other related symptoms.When investigation reveals no abnormalities within the abdominal cavity, the attending physician may consider Anterior cutaneous nerve entrapment syndrome (ACNES) as a possible cause. ACNES may present with pseudovisceral symptoms, including nausea, bloating, diarrhea and early satiety. References == External links ==
Biphenotypic acute leukaemia	Biphenotypic acute leukaemia (BAL) is an uncommon type of leukemia which arises in multipotent progenitor cells which have the ability to differentiate into both myeloid and lymphoid lineages. It is a subtype of "leukemia of ambiguous lineage".The direct reasons leading to BAL are still not clear. BAL can be de novo or secondary to previous cytotoxic therapy. Many factors, such viruses, hereditary factors, and radiation, might have a relationship with BAL. BAL is hard to treat. Usually the chemotherapy is chosen according to the morphology of the blast (ALL or AML). A blood-forming stem-cell transplantation is highly recommended. About 5% of acute leukaemia cases are BAL. BAL can occur in all ages of people but occurs more in adults than in children. Signs and symptoms BAL has similar symptoms to other types of leukemia, but they are usually more serious. Symptoms caused by bone marrow damage Bruising, spotting: the reason is lack of platelets. it is very common in BAL patients, most of patients die due to the A low level of red blood cells in the bloodstream: Because the decline of hematopoietic function, need blood transfusion therapy Persistent fever, infection prolonged healing: Diffuse hemorrhage: which is dangerous and might lead to death. Symptoms caused by blood cancer cells infiltration into tissues: Swollen lymph nodes Joint pain Swelling of the gums Enlargement of the liver and spleen Headache and vomiting: blood cancer infiltration into the wear performance of the central nervous system. Skin lumps: Because look was slightly green, also known as the "Green tumor." Pericardial or pleural effusion Causes The cause that directly leads to BAL is unclear. Exposure to radiation, chemical exposure, virus and genetics are the primary reasons proposed by researchers. Mechanisms The mechanism of BAL is related to several mutations. The most common abnormalities are t(9;22) and MLL gene rearrangement at 11q23. T(9;22) affect the ABL gene at 9q34 and BCR at 22q11. The hybrid gene product ABL/BCR is an oncogene which could lead several types of leukemia including BAL. ABL/BCR could active several molecular pathways: RAS signaling could be activated by BCR/ABL by GRB2 adaptor which interact with Y177 of BCR. Through AKT/PKB, PI3-K pathway could also be activated. STAT5, 1, and 6 has been reported that is a major molecular signaling event activated by BCR/ABL. Some focal adhesion complex (PAXILLIN, FAK0 could be activated by BCR/ABL with adaptor molecule CRK-L. BCR/ABL could inactivate negative regulatory molecules PTP1B and Abi-1. Their inactivation is related with progression into blast crisis. BCR/ABL pathway could also active PI64K/Akt/STAT5 pathway which has anti-apoptotic activity. BCR/ABL induce cell adhesive and migratory abnormalities because the mutation will lead an abnormal response to chemokine SDF-1 MLL gene encode Histone-lysine N-methyltransferase (HRX), which is a histone methyltransferase. It is a positive regulator for gene transcription. It has been shown that associates with Host cell factor C1, CREB binding protein, WDR5, CTBP, MEN1, etc. The rearrangement of MLL are related with different kinds of aggressive acute leukemias. Most of biphenotypic leukemia in children is due to the rearrangement of MLL Besides them, other gene abnormalities has been reported. Such as t(8;21), t(15;17), del(6q), del(12p), t(x;12) and t(14;19). In BAL patients, it is prone to bruising, spotting, which is due to megakaryocytes that could produce platelets decrease, resulting in a lack of platelets. Anemia: reduction metrocytes that could produce red blood cells, resulting in a lack of red blood cells. Patients are prone to asthma and dizziness in walking or exercise. Persistent fever, infection prolonged healing: Most of the white blood cells are leukemia cells, no normal function, leading to decreased immunity, susceptible to infection. Diagnosis Following observation of the symptoms, the patients need to get complete blood counts and a bone marrow examination. If the patient has leukemia, the morphology and immunophenotype check is needed to make sure the type of leukemia. The morphology of the blast in BAL is not certain. The cells could display both myeloid lineage and lymphoid or undifferentiated morphology. Therefore, the diagnosis cannot based on the morphology result. The immunophenotype check is the most important basis of the diagnosis of BAL. Before 2008, the diagnosis of BAL was based on a score system proposed by the European Group for the Immunological Classification of Leukemias (EGIL) which could differentiate from other kinds of acute leukemia. The table shows this method. If the score of only one lineage is higher than 2, the acute leukemia could be acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). According to the original EGIL scoring system BAL is defined when scores are over two points for both myeloid and T- or B- lymphoid lineages. In 2008, WHO established a new and strict criteria standard for diagnosis of BAL. The presence of specific T-lymphoid antigens, cytoplasmic CD3 (cCD3), MPO and CD 19 became the most important standard for recognizing the lineage. Other B-lineage markers (CD22, CD79a, CD 10) and monocytic markers are also needed. Table 2 shows the method. Compared with the EGIL scoring system, the current 2008 WHO criteria applied less but more specific markers to define the lineage of the blasts, and incorporated the intensity of markers expression into the diagnostic algorithm. The diagnosis of BAL is so difficult that sometimes is misdiagnosed with AML or ALL because the morphology thus the therapy would not have a good effect. Treatment BAL is difficult to treat, most patients receive treatment based on the morphology of blasts and get AML or ALL induction chemotherapy. The induction drug for AML such as cytarabine and anthracycline, drug for ALL such as prednisolone, dexamethasone, vincristine, asparaginase or daunorubicin is common for BAL remission induction therapy. Recently, researches showed that using both myeloid and lymphoid induction therapy may be better for prognosis.Chemotherapy has strong side effects such as typhlitis, gastrointestinal distress, anemia, fatigue, hair loss, nausea and vomiting, etc. Thus, the different dose and times of chemotherapy for different individuals is important. If the patients enter fully remission, the consolidation with stem cell transplantation is highly recommended. Prognosis The prognosis for BAL patients is not good which is worse than ALL and AML. Medical Blood Institute reported cases of CR rate was 31.6%, with a median remission are less than 6 months The median survival time is only 7.5 months. The life quality is also low because the immune function of patient is damaged seriously. They have to stay in hospital and need 24h care. In another study, the results showed that young age, normal karyotype and ALL induction therapy will have a better prognosis than Ph+, adult patients. The study shows median survival of children is 139 months versus 11 months of adults, 139 months for normal karyotype patients versus 8 months for ph+ patients. Recent research Research on the mechanisms of BAL does not show a great progress in terms of the causes, molecular processes and therapy. Some new translocate case of BAL has been reported, such as t(15,17) and t(12,13). For t(15;17), the blasts with morphology of acute lymphoblastic leukemia co-expressed in B-lymphoid and myeloid lineages, and the cytogenetic study showed that the 4q21 abnormalities and t(15;17). However, promyelocytic-retinoid acid receptor rearrangement was not found by fluorescence in situ hybridization on interphase nuclei. Researchers also found some new chemotherapy method for specific cases. For example, The chemotherapy for ALL and gemtuzuab ozogamicin without all-trans-retinoic acid remain complete remission of the BAL patients with t(15,17) for more than 3.7 years. The detection of BCR-ABL1 chimeric gene neutrophils was also found a good method for diagnosis some cases of BAL. References == External links ==
Fungal infection	Fungal infection, also known as mycosis, is disease caused by fungi. Different types are traditionally divided according to the part of the body affected; superficial, subcutaneous, and systemic. Superficial fungal infections include common tinea of the skin, such as tinea of the body, groin, hands, feet and beard, and yeast infections such as pityriasis versicolor. Subcutaneous types include eumycetoma and chromoblastomycosis, which generally affect tissues in and beneath the skin. Systemic fungal infections are more serious and include cryptococcosis, histoplasmosis, pneumocystis pneumonia, aspergillosis and mucormycosis. Signs and symptoms range widely. There is usually a rash with superficial infection. Fungal infection within the skin or under the skin may present with a lump and skin changes. Pneumonia-like symptoms or meningitis may occur with a deeper or systemic infection.Fungi are everywhere, but only some cause disease. Fungal infection occurs after spores are either breathed in, come into contact with skin or enter the body through the skin such as via a cut, wound or injection. It is more likely to occur in people with a weak immune system. This includes people with illnesses such as HIV/AIDS, and people taking medicines such as steroids or cancer treatments. Fungi that cause infections in people include yeasts, molds and fungi that are able to exist as both a mold and yeast. The yeast Candida albicans can live in people without producing symptoms, and is able to cause both superficial mild candidiasis in healthy people, such as oral thrush or vaginal yeast infection, and severe systemic candidiasis in those who cannot fight infection themselves.Diagnosis is generally based on signs and symptoms, microscopy, culture, sometimes requiring a biopsy and the aid of medical imaging. Some superficial fungal infections of the skin can appear similar to other skin conditions such as eczema and lichen planus. Treatment is generally performed using antifungal medicines, usually in the form of a cream or by mouth or injection, depending on the specific infection and its extent. Some require surgically cutting out infected tissue.Fungal infections have a world-wide distribution and are common, affecting more than one billion people every year. An estimated 1.7 million deaths from fungal disease were reported in 2020. Several, including sporotrichosis, chromoblastomycosis and mycetoma are neglected.A wide range of fungal infections occur in other animals, and some can be transmitted from animals to people. Classification Mycoses are traditionally divided into superficial, subcutaneous, or systemic, where infection is deep, more widespread and involving internal body organs. They can affect the nails, vagina, skin and mouth. Some types such as blastomycosis, cryptococcus, coccidioidomycosis and histoplasmosis, affect people who live or visit certain parts of the world. Others such as aspergillosis, pneumocystis pneumonia, candidiasis, mucormycosis and talaromycosis, tend to affect people who are unable to fight infection themselves. Mycoses might not always conform strictly to the three divisions of superficial, subcutaneous and systemic. Some superficial fungal infections can cause systemic infections in people who are immunocompromised. Some subcutaneous fungal infections can invade into deeper structures, resulting in systemic disease. Candida albicans can live in people without producing symptoms, and is able to cause both mild candidiasis in healthy people and severe invasive candidiasis in those who cannot fight infection themselves. ICD-11 codes ICD-11 codes include: Superficial mycoses Superficial mycoses include candidiasis in healthy people, common tinea of the skin, such as tinea of the body, groin, hands, feet and beard, and malassezia infections such as pityriasis versicolor. Subcutaneous Subcutaneous fungal infections include sporotrichosis, chromoblastomycosis, and eumycetoma. Systemic Systemic fungal infections include histoplasmosis, cryptococcosis, coccidioidomycosis, blastomycosis, mucormycosis, aspergillosis, pneumocystis pneumonia and systemic candidiasis.Systemic mycoses due to primary pathogens originate normally in the lungs and may spread to other organ systems. Organisms that cause systemic mycoses are inherently virulent.. Systemic mycoses due to opportunistic pathogens are infections of people with immune deficiencies who would otherwise not be infected. Examples of immunocompromised conditions include AIDS, alteration of normal flora by antibiotics, immunosuppressive therapy, and metastatic cancer. Examples of opportunistic mycoses include Candidiasis, Cryptococcosis and Aspergillosis. Signs and symptoms Most common mild mycoses often present with a rash. Infections within the skin or under the skin may present with a lump and skin changes. Less common deeper fungal infections may present with pneumonia like symptoms or meningitis. Causes Mycoses are caused by certain fungi; yeasts, molds and some fungi that can exist as both a mold and yeast. They are everywhere and infection occurs after spores are either breathed in, come into contact with skin or enter the body through the skin such as via a cut, wound or injection. Candida albicans is the most common cause of fungal infection in people, particularly as oral or vaginal thrush, often following taking antibiotics. Risk factors Fungal infections are more likely in people with weak immune systems. This includes people with illnesses such as HIV/AIDS, and people taking medicines such as steroids or cancer treatments. People with diabetes also tend to develop fungal infections. Very young and very old people, also, are groups at risk.Individuals being treated with antibiotics are at higher risk of fungal infections.Children whose immune systems are not functioning properly (such as children with cancer) are at risk of invasive fungal infections. COVID-19 During the COVID-19 pandemic some fungal infections have been associated with COVID-19. Fungal infections can mimic COVID-19, occur at the same time as COVID-19 and more serious fungal infections can complicate COVID-19. A fungal infection may occur after antibiotics for a bacterial infection which has occurred following COVID-19. The most common serious fungal infections in people with COVID-19 include aspergillosis and invasive candidiasis. COVID-19–associated mucormycosis is generally less common, but in 2021 was noted to be significantly more prevalent in India. Mechanism Fungal infections occur after spores are either breathed in, come into contact with skin or enter the body through a wound. Diagnosis Diagnosis is generally by signs and symptoms, microscopy, biopsy, culture and sometimes with the aid of medical imaging. Differential diagnosis Some tinea and candidiasis infections of the skin can appear similar to eczema and lichen planus. Pityriasis versicolor can look like seborrheic dermatitis, pityriasis rosea, pityriasis alba and vitiligo.Some fungal infections such as coccidioidomycosis, histoplasmosis, and blastomycosis can present with fever, cough, and shortness of breath, thereby resembling COVID-19. Prevention Keeping the skin clean and dry, as well as maintaining good hygiene, will help larger topical mycoses. Because some fungal infections are contagious, it is important to wash hands after touching other people or animals. Sports clothing should also be washed after use. Treatment Treatment depends on the type of fungal infection, and usually requires topical or systemic antifungal medicines. Pneumocystosis does not respond to anti-fungals is treated with co-trimoxazole. Sometimes, infected tissue needs to be surgically cut away. Epidemiology Worldwide, every year fungal infections affect more than one billion people. An estimated 1.6 million deaths from fungal disease were reported in 2017. The figure has been rising, with an estimated 1.7 million deaths from fungal disease reported in 2020. Fungal infections also constitute a significant cause of illness and mortality in children.According to the Global Action Fund for Fungal Infections, every year there are over 10 million cases of fungal asthma, around 3 million cases of long-term aspergillosis of lungs, 1 million cases of blindness due to fungal keratitis, more than 200,000 cases of meningitis due to cryptococcus, 700,000 cases of invasive candidiasis, 500,000 cases of pneumocystosis of lungs, 250,000 cases of invasive aspergillosis, and 100,000 cases of histoplasmosis. History In 500BC, an apparent account of ulcers in the mouth by Hippocrates may have been thrush. The Hungarian microscopist based in Paris David Gruby first reported that human disease could be caused by fungi in the early 1840s. SARS 2003 During the 2003 SARS outbreak, fungal infections were reported in 14.8–33% of people affected by SARS, and it was the cause of death in 25–73.7% of people with SARS. Other animals A wide range of fungal infections occur in other animals, and some can be transmitted from animals to people, such as Microsporum canis from cats. See also Fungal infection in plants § Fungi Actinomycosis References == External links ==
Skin manifestations of sarcoidosis	Sarcoidosis, an inflammatory disease, involves the skin in about 25% of patients. The most common lesions are erythema nodosum, plaques, maculopapular eruptions, subcutaneous nodules, and lupus pernio. Treatment is not required, since the lesions usually resolve spontaneously in two to four weeks. Although it may be disfiguring, cutaneous sarcoidosis rarely causes major problems. Classification Morphology Ulcerative sarcoidosis is a cutaneous condition affecting roughly 5% of people with sarcoidosis.: 710 Annular sarcoidosis is a cutaneous condition characterized by papular skin lesions arranged in annular patterns, usually with a red-brown hue.: 709 Pattern Morpheaform sarcoidosis is a very rare cutaneous condition characterized by specific cutaneous skin lesions of sarcoidosis accompanied by substantial fibrosis, simulating morphea.: 711 Erythrodermic sarcoidosis is a cutaneous condition and very rare form of sarcoidosis.: 710 Hypopigmented sarcoidosis is a cutaneous condition characterized by areas of hypopigmented skin. It is usually diagnosed in darkly pigmented races and may be the earliest sign of sarcoidosis.: 709 Papular sarcoid is a cutaneous condition characterized by papules, which are the most common morphology of cutaneous sarcoidosis.: 708 Ichthyosiform sarcoidosis is a cutaneous condition resembling ichthyosis vulgaris or acquired ichthyosis, with fine scaling usually on the distal extremities, by caused by sarcoidosis.: 710 Location Subcutaneous sarcoidosis (also known as "Darier–Roussy disease" and "Darier-Roussy sarcoid") is a cutaneous condition characterized by numerous 0.5- to 0.3-cm deep-seated nodules on the trunk and extremities.: 710 Scar sarcoid (also known as "Sarcoidosis in scars") is a cutaneous condition characterized by infiltration and elevation of tattoos and old flat scars due to sarcoidosis.: 710 Mucosal sarcoidosis is a cutaneous condition characterized by pinhead-sized papules that may be grouped and fused together to form a flat plaque.: 711 Erythrodermic sarcoidosis is a cutaneous condition and very rare form of sarcoidosis.: 710 References == External links ==
Laurence–Moon syndrome	Laurence–Moon syndrome (LMS) is a rare autosomal recessive genetic disorder associated with retinitis pigmentosa, spastic paraplegia, and mental disabilities. Signs and symptoms Intellectual disability, hexadactyly, central diabetes insipidus, blindness (usually by 30 years due to central retinal degeneration). Genetics LMS is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder. Diagnosis The syndrome was originally thought to have five cardinal features (and recently a sixth was added), on the basis of which a diagnostic criterion was developed: 4 primary features or 3 primary features and 2 secondary features must be present. The primary features are: 1. Polydactyly 2. Rod-cone dystrophy 3. Learning disabilities 4. Obesity 5. Hypogonadism in males 6. Renal abnormalities While the secondary features are stated to be as: 1. Speech disorder and/or developmental delay 2. Ophthalmic abnormalities other than rod-cone dystrophy (strabismus, cataract, astigmatism etc.) 3. Brachydactyly or Syndactyly 4. Polyuria and/or polydipsia (nephrogenic diabetes insipidus) 5. Ataxia, poor coordination, imbalance 6. Mild spasticity (especially lower limbs) 7. Diabetes mellitus 8. Dental crowding, hypodontia, small roots, high arched palate 9. Congenital heart disease 10. Hepatic fibrosis Treatment There is no cure to LNMS. However, symptomatic treatment is often provided. The patients with LNMS often experience ataxia, spasticity and contractures, restricting their movements and daily activities. Therefore, multi-disciplinary approach is required including physical therapies, psychiatric and ophthalmologic consultations, nutrition and well-balanced diet. Physical therapy aims at improving the strength and ability using assisting tools such as ankle-foot orthitic braces, weight-bearing walkers and regular exercise. Eponym and nomenclature It is named after the physicians John Zachariah Laurence and Robert Charles Moon who provided the first formal description of the condition in a paper published in 1866. In the past, LMS has also been referred to as Laurence–Moon–Bardet–Biedl or Laurence–Moon–Biedl–Bardet syndrome, but Bardet–Biedl syndrome (BBS) is now usually recognized as a separate entity.Recent advances in genetic typing of the phenotypically-wide variation in patients clinically diagnosed with either Bardet-Biedl Syndrome (BBS) or Laurence-Moon Syndrome (LMS) have questioned whether LMS and BBS are genetically distinct. For example, a 1999 epidemiological study of BBS and LMS reported that "BBS proteins interact and are necessary for the development of many organs." "Two patients [in the study] were diagnosed clinically as LMS but both had mutations in a BBS gene. The features in this population do not support the notion that BBS and LMS are distinct." A more recent 2005 paper also suggests that the two conditions are not distinct. References == External links ==
Fuchs dystrophy	Fuchs dystrophy, also referred to as Fuchs endothelial corneal dystrophy (FECD) and Fuchs endothelial dystrophy (FED), is a slowly progressing corneal dystrophy that usually affects both eyes and is slightly more common in women than in men. Although early signs of Fuchs dystrophy are sometimes seen in people in their 30s and 40s, the disease rarely affects vision until people reach their 50s and 60s. Signs and symptoms As a progressive, chronic condition, signs and symptoms of Fuchs dystrophy gradually progress over decades of life, starting in middle age. Early symptoms include blurry vision upon wakening which improves during the morning, as fluid retained in the cornea is unable to evaporate through the surface of the eye when the lids are closed overnight. As the disease worsens, the interval of blurry morning vision extends from minutes to hours.In moderate stages of the disease, an increase in guttae and swelling in the cornea can contribute to changes in vision and decreased sharpness throughout the day. Contrast sensitivity may be affected. The change in the refractive index of the cornea may result in subtle refractive shifts, which affected individuals may experience as a small change in their eyeglass prescription. In the late stages of the disease, the cornea is unable to maintain its fluid content and blisters, known as bullae, form on the surface of the cornea. These cause foreign body sensations and can be painful. The cornea may not heal from such epithelial defects, until corneal transplantation is able to restore the endothelial pump function. Cause FECD is a degenerative disease of the corneal endothelium with accumulation of focal outgrowths called guttae (drops) and thickening of Descemets membrane, leading to corneal edema and loss of vision. The corneal endothelial cell layer and its basement membrane (Descemets membrane) act as a barrier to hydration of the corneal stroma by aqueous humor and are "pump" cells of the cornea that function to maintain hydration of the cornea at a specific level that maintains corneal stromal clarity through precise spatial arrangement of collagen fibers. In FED, Descemets membrane is grossly thickened with accumulation of abnormal wide-spaced collagen and numerous guttae. Corneal endothelial cells in end-stage FED are reduced in number and appear attenuated, causing progressive stromal edema (swelling). Progressive endothelial cell loss causes relative influx of aqueous humor into the cornea, leading to swelling (corneal stromal edema), which results in blurred vision. Eventually, the epithelium also becomes edematous, resulting in more severe visual impairment. Focal blisters of epithelial edema ("bullae") may be particularly painful when they burst.The inheritance of FECD is complex and polymorphic such that although inheritance is autosomal dominant there are genetic and environmental modifiers that determine the degree to which members of the same family express the disease. There is reasonable evidence of associations between transcription factor 4 (TCF4) genetic polymorphisms and risk of Fuchs endothelial dystrophy (FED). Endothelial cell loss may be aggravated or accelerated by intraocular trauma or surgery. A common scenario involves prolonged corneal swelling or edema following cataract surgery or other types of ocular surgery. Hence, patients with a history of Fuchs dystrophy may be at a greater risk of corneal edema after ocular surgery as they have fewer functioning endothelial cells.FECD is classified into 4 stages, from early signs of guttae formation to end-stage subepithelial scarring. Diagnosis is made by biomicroscopic examination in the clinic. Other modalities, such as corneal thickness measurement (pachymetry), in-vivo confocal biomicroscopy, and specular microscopy can be used in conjunction.The exact pathogenesis is unknown but factors include endothelial cell apoptosis, sex hormones, inflammation, and aqueous humor flow and composition. Mutations in collagen VIII, a major component of Descemets membrane secreted by endothelial cells, have been linked to the early-onset FECD.As a genetically heterogeneous disease, the phenotype, or clinical experience of patients with Fuchs dystrophy may reflect the combination of genetic contributors to the disease. Some genetic lesions correlate with more severe disease and earlier onset. Therefore, some individuals may experience symptoms of the disease at a much earlier age, while others may not experience symptoms until late in life.Genes include: Diagnosis The diagnosis of Fuchs dystrophy is often made with slit lamp biomicroscopy. With direct illumination, the clinician can visualize guttae, the characteristic pathological changes in disease.Scheimpflug imaging, anterior segment optical coherence tomography, confocal microscopy, and specular microscopy are additional imaging techniques that can identify the presence of guttae and quantify the thickness of the cornea. While corneal thickness can be a valuable indicator of how the cornea is changing over time, it is affected by multiple factors and is not adequate itself as a screening tool to diagnose Fuchs dystrophy. Treatment Non-surgical treatments of FECD may be used to treat symptoms of early disease. Medical management includes topical hypertonic saline, the use of a hairdryer to dehydrate the precorneal tear film, and therapeutic soft contact lenses. Hypertonic saline draws water out of the cornea through osmosis. When using a hairdryer, the patient is instructed to hold it at an arms length or directed across the face in a cold setting, to dry out the epithelial blisters. This can be done two or three times a day. Scleral lenses can improve vision when it is affected by irregularities on the surface of the cornea, but may stress the corneal endothelium. Corneal transplantation is the definitive treatment for FECD. The most common types of surgery for FECD are Descemets stripping automated endothelial keratoplasty (DSAEK) and Descemets membrane endothelial keratoplasty (DMEK), which account for over half of corneal transplants in the United States. Injection of cultured endothelial cells is under investigation and in a series of 11 patients in Japan with bullous keratopathy, was able to clear corneal edema. Epidemiology Few studies have examined the prevalence of FECD on a large scale. First assessed in a clinical setting, Fuchs himself estimated the occurrence of dystrophia epithelialis corneae to be one in every 2000 patients; a rate that is likely reflective of those who progress to advanced disease. Cross-sectional studies suggest a relatively higher prevalence of disease in European countries relative to other areas of the world. Fuchs dystrophy rarely affects individuals under 50 years of age. History The condition was first described by Austrian ophthalmologist Ernst Fuchs (1851–1930), after whom it is named. In 1910, Fuchs first reported 13 cases of central corneal clouding, loss of corneal sensation and the formation of epithelial bullae, or blisters, which he labeled dystrophia epithelialis corneae. It was characterized by late onset, slow progression, decreased visual acuity in the morning, lack of inflammation, diffuse corneal opacity, intense centrally, and roughened epithelium with vesicle-like features.A shift to the understanding of FECD as primarily a disease of the corneal endothelium resulted after a number of observations in the 1920s. Crystal-like features of the endothelium were noted by Kraupa in 1920, who suggested that the epithelial changes were dependent on the endothelium. Using a slit lamp, Vogt described the excrescences associated with FCD as drop-like in appearance in 1921. In 1924, Graves then provided an extremely detailed explanation of the endothelial elevations visible with slit lamp biomicroscopy. A patient with unilateral epithelial dystrophy and bilateral endothelial changes was described by the Friedenwalds in 1925; subsequent involvement of the second eye led them to emphasize that endothelial changes preceded epithelial changes. As only a subset of patients with endothelial changes proceeded to epithelial involvement, Graves stated on 19 October 1925 to the New York Academy of Medicine that "Fuchs epithelial dystrophy may be a very late sequel to severer cases of the deeper affection". See also Fuchs heterochromic iridocyclitis (a disease of the iris) Ocular straylight References External links Facts About the Cornea and Corneal Disease - The National Eye Institute (United States) Fuchs dystrophy at Curlie
Inappropriate sinus tachycardia	Inappropriate sinus tachycardia (IST) is a rare type of cardiac arrhythmia within the category of supraventricular tachycardia (SVT). IST may be caused by the sinus node itself having an abnormal structure or function, or it may be part of a problem called dysautonomia, a disturbance and/or failure of the autonomic nervous system. Research into the mechanism and etiology (cause) of inappropriate sinus tachycardia is ongoing. IST is viewed by most to be a benign condition in the long-term. Symptoms of IST, however, may be distracting and warrant treatment. The heart is a strong muscle and typically can sustain the higher-than-normal heart rhythm, though monitoring the condition is generally recommended. The mechanism and primary etiology of inappropriate sinus tachycardia has not been fully elucidated. An autoimmune mechanism has been suggested, as several studies have detected autoantibodies that activate beta adrenoreceptors in some patients. The mechanism of the arrhythmia primarily involves the sinus node and peri-nodal tissue and does not require the AV node for maintenance. Treatments in the form of pharmacological therapy or catheter ablation are available, but the condition is currently difficult to treat successfully. Symptoms Symptoms reported by patients vary in frequency and severity. They may include: Frequent or sustained palpitations Dyspnea (shortness of breath) and palpitations on exertion Pre-syncope (feeling as if about to faint) Fatigue Dizziness Exercise intolerance Occasional paresthesia and cramping Symptoms associated with autonomic nervous system disturbance, including gastrointestinal disturbance Diagnosis No formal diagnostic criteria exist. A diagnosis of inappropriate sinus tachycardia is primarily one of exclusion, and the following may be observed: Exclusion of all other causes of sinus tachycardia Common forms of supraventricular tachycardia (SVT) must be excluded Normal P wave morphology A resting sinus tachycardia is usually (but not always) present Nocturnal dip in heart rate Inappropriate heart rate response on exertion Mean heart rate in 24hrs >95 bpm Symptoms are documented to be due to tachycardia Hypotension is occasionally observed Syncope (fainting) is occasionally reported Treatment IST has been treated both pharmacologically and invasively, with varying degrees of success. IST, in and of itself, is not indicative of higher rates of mortality, and non-treatment is an option chosen by many if they have minimal symptoms.Some types of medication tried by cardiologists and other physicians include: beta blockers, selective sinus node If channel inhibitors (such as ivabradine), calcium channel blockers, and antiarrhythmic agents. Some SSRI drugs are also occasionally tried, as are treatments more commonly used to treat postural orthostatic tachycardia syndrome, such as fludrocortisone.Invasive treatments include forms of catheter ablation such as sinus node modification (selective ablation of the sinus node), complete sinus node ablation (with associated implantation of a permanent artificial pacemaker), and AV node ablation in very resistant cases (creation of iatrogenic complete heart block, necessitating implantation of a permanent artificial pacemaker). However, invasive treatments can also make the symptoms worse. See also Supraventricular tachycardia Sinus tachycardia Postural orthostatic tachycardia syndrome Dysautonomia References Further reading Yusuf, Shamil; Camm, A. John (2005). "Deciphering the sinus tachycardias". Clinical Cardiology. 28 (6): 267–76. doi:10.1002/clc.4960280603. PMC 6654702. PMID 16028460. Still, A; Raatikainen, P; et al. (2005). "Prevalence, characteristics and natural course of inappropriate sinus tachycardia". Europace. 7 (2): 104–12. doi:10.1016/j.eupc.2004.12.007. PMID 15763524. Leon, Hernando; Guzman, Juan Camilo; et al. (2005). "Impaired Baroreflex Gain in Patients with Inappropriate Sinus Tachycardia". Journal of Cardiovascular Electrophysiology. 16 (1): 64–8. doi:10.1046/j.1540-8167.2005.04441.x. PMID 15673390. Sanchez-Quintana, D; Cabrera, JA; et al. (2005). "Sinus node revisited in the era of electroanatomical mapping and catheter ablation". Heart. 91 (2): 189–94. doi:10.1136/hrt.2003.031542. PMC 1768731. PMID 15657230. Cruz Filho, Fernando E. S.; Maia, Ivan G.; et al. (1998). "Modificação do nódulo sinusal via cateter por energia de radiofreqüência em paciente com taquicardia sinusal inapropriada. Avaliação dos resultados imediatos e tardios" [Sinus node modification by catheter using radiofrequency current in a patient with inappropriate sinus tachycardia. Evaluation of early and late results]. Arquivos Brasileiros de Cardiologia (in Portuguese). 70 (3): 173–6. doi:10.1590/S0066-782X1998000300006. PMID 9674178. Lee, SH; Cheng, JJ; et al. (1997). "Radiofrequency catheter modification of sinus node for inappropriate sinus tachycardia: A case report". Zhonghua Yi Xue Za Zhi. 60 (2): 117–23. PMID 9360339.
Systemic scleroderma	Systemic scleroderma, or systemic sclerosis, is an autoimmune rheumatic disease characterised by excessive production and accumulation of collagen, called fibrosis, in the skin and internal organs and by injuries to small arteries. There are two major subgroups of systemic sclerosis based on the extent of skin involvement: limited and diffuse. The limited form affects areas below, but not above, the elbows and knees with or without involvement of the face. The diffuse form also affects the skin above the elbows and knees and can also spread to the torso. Visceral organs, including the kidneys, heart, lungs, and gastrointestinal tract can also be affected by the fibrotic process. Prognosis is determined by the form of the disease and the extent of visceral involvement. Patients with limited systemic sclerosis have a better prognosis than those with the diffuse form. Death is most often caused by lung, heart, and kidney involvement. The risk of cancer is increased slightly.Survival rates have greatly increased with effective treatment for kidney failure. Therapies include immunosuppressive drugs, and in some cases, glucocorticoids. Signs and symptoms Calcinosis, Raynauds phenomenon, Esophageal dysfunction, Sclerodactyly, and Telangiectasia (CREST syndrome) are associated with limited scleroderma. Other symptoms include: Skin symptoms In the skin, systemic sclerosis causes hardening and scarring. The skin may appear tight, reddish, or scaly. Blood vessels may also be more visible. Where large areas are affected, fat and muscle wastage may weaken limbs and affect appearance. Patients report severe and recurrent itching of large skin areas. The severity of these symptoms varies greatly among patients: Some having scleroderma of only a limited area of the skin (such as the fingers) and little involvement of the underlying tissue, while others have progressive skin involvement. Digital ulcers—open wounds especially on fingertips and less commonly the knuckles—are not uncommon. Other organs Diffuse scleroderma can cause musculoskeletal, pulmonary, gastrointestinal, renal, and other complications. Patients with greater cutaneous involvement are more likely to have involvement of the internal tissues and organs. Most patients (over 80%) have vascular symptoms and Raynauds phenomenon, which leads to attacks of discoloration of the hands and feet in response to cold. Raynauds normally affects the fingers and toes. Systemic scleroderma and Raynauds can cause painful ulcers on the fingers or toes, which are known as digital ulcers. Calcinosis (deposition of calcium in lumps under the skin) is also common in systemic scleroderma, and is often seen near the elbows, knees, or other joints. MusculoskeletalThe first joint symptoms that patients with scleroderma have are typically nonspecific joint pains, which can lead to arthritis, or cause discomfort in tendons or muscles. Joint mobility, especially of the small joints of the hand, may be restricted by calcinosis or skin thickening. Patients may develop muscle weakness, or myopathy, either from the disease or its treatments. LungsSome impairment in lung function is almost universally seen in patients with diffuse scleroderma on pulmonary function testing, but it does not necessarily cause symptoms, such as shortness of breath. Some patients can develop pulmonary hypertension, or elevation in the pressures of the pulmonary arteries. This can be progressive, and can lead to right-sided heart failure. The earliest manifestation of this may be a decreased diffusion capacity on pulmonary function testing. Other pulmonary complications in more advanced disease include aspiration pneumonia, pulmonary hemorrhage and pneumothorax. Digestive tract Diffuse scleroderma can affect any part of the gastrointestinal tract. The most common manifestation in the esophagus is reflux esophagitis, which may be complicated by esophageal strictures or benign narrowing of the esophagus. This is best initially treated with proton pump inhibitors for acid suppression, but may require bougie dilatation in the case of stricture.Scleroderma can decrease motility anywhere in the gastrointestinal tract. The most common source of decreased motility is the esophagus and the lower esophageal sphincter, leading to dysphagia and chest pain. As scleroderma progresses, esophageal involvement from abnormalities in decreased motility may worsen due to progressive fibrosis (scarring). If this is left untreated, acid from the stomach can back up into the esophagus, causing esophagitis and gastroesophageal reflux disease. Further scarring from acid damage to the lower esophagus many times leads to the development of fibrotic narrowing, also known as strictures, which can be treated by dilatation, and Barretts esophagus.In patients with neuromuscular disorders, particularly progressive systemic sclerosis and visceral myopathy, the duodenum is frequently involved. Dilatation may occur, which is often more pronounced in the second, third, and fourth parts. The dilated duodenum may be slow to empty, and the grossly dilated, atonic organ may produce a sump effect.The small intestine can also become involved, leading to bacterial overgrowth and malabsorption of bile salts, fats, carbohydrates, proteins, and vitamins. The colon can be involved, and can cause pseudo-obstruction or ischemic colitis.Rarer complications include pneumatosis cystoides intestinalis, or gas pockets in the bowel wall, wide-mouthed diverticula in the colon and esophagus, and liver fibrosis. Patients with severe gastrointestinal involvement can become profoundly malnourished.Scleroderma may also be associated with gastric antral vascular ectasia, also known as "watermelon stomach". This is a condition in which atypical blood vessels proliferate, usually in a radially symmetric pattern around the pylorus of the stomach. It can be a cause of upper gastrointestinal bleeding or iron-deficiency anemia in patients with scleroderma. Kidneys Kidney involvement, in scleroderma, is considered a poor prognostic factor and frequently a cause of death.The most important clinical complication of scleroderma involving the kidney is scleroderma renal crisis (SRC), the symptoms of which are malignant hypertension (high blood pressure with evidence of acute organ damage), hyperreninemia (high renin levels), azotemia (kidney failure with accumulation of waste products in the blood), and microangiopathic hemolytic anemia (destruction of red blood cells). Apart from the high blood pressure, hematuria (blood in the urine) and proteinuria (protein loss in the urine) may be indicative of SRC.In the past, SRC was almost uniformly fatal. While outcomes have improved significantly with the use of ACE inhibitors, the prognosis is often guarded, as a significant number of patients are refractory to treatment and develop kidney failure. About 7–9% of all diffuse cutaneous scleroderma patients develop renal crisis at some point in the course of their disease. Patients who have rapid skin involvement have the highest risk of renal complications. It is most common in diffuse cutaneous scleroderma, and is often associated with antibodies against RNA polymerase (in 59% of cases). Many proceed to dialysis, although this can be stopped within three years in about a third of cases. Higher age and (paradoxically) a lower blood pressure at presentation make dialysis more likely to be needed.Treatments for SRC include ACE inhibitors. Prophylactic use of ACE inhibitors is currently not recommended, as recent data suggest a poorer prognosis in patient treated with these drugs prior to the development of renal crisis. Transplanted kidneys are known to be affected by scleroderma, and patients with early-onset renal disease (within one year of the scleroderma diagnosis) are thought to have the highest risk for recurrence. Causes No clear cause for scleroderma and systemic sclerosis has been identified. Genetic predisposition appears to be limited, as genetic concordance is small; still, a familial predisposition for autoimmune disease is often seen. Polymorphisms in COL1A2 and TGF-β1 may influence severity and development of the disease. Evidence implicating cytomegalovirus (CMV) as the original epitope of the immune reaction is limited, as is parvovirus B19. Organic solvents and other chemical agents have been linked with scleroderma.One of the suspected mechanisms behind the autoimmune phenomenon is the existence of microchimerism, i.e. fetal cells circulating in maternal blood, triggering an immune reaction to what is perceived as foreign material.A distinct form of scleroderma and systemic sclerosis may develop in patients with chronic kidney failure. This form, nephrogenic fibrosing dermopathy or nephrogenic systemic fibrosis, has been linked to exposure to gadolinium-containing radiocontrast.Bleomycin (a chemotherapeutic agent) and possibly taxane chemotherapy may cause scleroderma, and occupational exposure to solvents has been linked to an increased risk of systemic sclerosis. Pathophysiology Overproduction of collagen is thought to result from an autoimmune dysfunction, in which the immune system starts to attack the kinetochore of the chromosomes. This would lead to genetic malfunction of nearby genes. T cells accumulate in the skin; these are thought to secrete cytokines and other proteins that stimulate collagen deposition. Stimulation of the fibroblast, in particular, seems to be crucial to the disease process, and studies have converged on the potential factors that produce this effect. A significant player in the process is transforming growth factor (TGFβ). This protein appears to be overproduced, and the fibroblast (possibly in response to other stimuli) also overexpresses the receptor for this mediator. An intracellular pathway (consisting of SMAD2/SMAD3, SMAD4, and the inhibitor SMAD7) is responsible for the secondary messenger system that induces transcription of the proteins and enzymes responsible for collagen deposition. Sp1 is a transcription factor most closely studied in this context. Apart from TGFβ, connective tissue growth factor (CTGF) has a possible role. Indeed, a common CTGF gene polymorphism is present at an increased level in systemic sclerosis.Damage to endothelium is an early abnormality in the development of scleroderma, and this, too, seems to be due to collagen accumulation by fibroblasts, although direct alterations by cytokines, platelet adhesion, and a type II hypersensitivity reaction similarly have been implicated. Increased endothelin and decreased vasodilation have been documented.Jimenez and Derk describe three theories about the development of scleroderma: The abnormalities are primarily due to a physical agent, and all other changes are secondary or reactive to this direct insult. The initial event is fetomaternal cell transfer causing microchimerism, with a second summative cause (e.g. environmental) leading to the actual development of the disease. Physical causes lead to phenotypic alterations in susceptible cells (e.g. due to genetic makeup), which then effectuate DNA changes that alter the cells behavior. Diagnosis In 1980, the American College of Rheumatology agreed on diagnostic criteria for scleroderma.Diagnosis is by clinical suspicion, presence of autoantibodies (specifically anticentromere and anti-scl70/antitopoisomerase antibodies), and occasionally by biopsy. Of the antibodies, 90% have a detectable antinuclear antibody. Anticentromere antibody is more common in the limited form (80–90%) than in the diffuse form (10%), and anti-scl70 is more common in the diffuse form (30–40%) and in African-American patients (who are more susceptible to the systemic form).Other conditions may mimic systemic sclerosis by causing hardening of the skin. Diagnostic hints that another disorder is responsible include the absence of Raynauds phenomenon, a lack of abnormalities in the skin on the hands, a lack of internal organ involvement, and a normal antinuclear antibodies test result. Treatment No cure for scleroderma is known, though treatments exist for some of the symptoms, including drugs that soften the skin and reduce inflammation. Some patients may benefit from exposure to heat. Holistic care of patients comprising patient education tailored to patients education level is useful in view of the complex nature of the disease symptoms and progress. Topical/symptomatic Topical treatment for the skin changes of scleroderma do not alter the disease course, but may improve pain and ulceration. A range of nonsteroidal anti-inflammatory drugs, such as naproxen, can be used to ease painful symptoms. The benefit from steroids such as prednisone is limited. Episodes of Raynauds phenomenon sometimes respond to nifedipine or other calcium channel blockers; severe digital ulceration may respond to prostacyclin analogue iloprost, and the dual endothelin-receptor antagonist bosentan may be beneficial for Raynauds phenomenon. Skin tightness may be treated systemically with methotrexate and ciclosporin. and the skin thickness can be treated with penicillamine. Kidney disease Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis that may be the initial manifestation of the disease. Renal vascular injury (due in part to collagen deposition) leads to renal ischemia, which results in activation of the renin-angiotensin-aldosterone system (RAAS). This raises blood pressure and further damages the renal vasculature, causing a vicious cycle of worsening hypertension and renal dysfunction (e.g., elevated creatinine, edema). Hypertensive emergency with end-organ dysfunction (e.g., encephalopathy, retinal hemorrhage) is common. Thrombocytopenia and microangiopathic hemolytic anemia can be seen. Urinalysis is usually normal but may show mild proteinuria, as in this patient; casts are unexpected.The mainstay of therapy for SRC includes ACE inhibitors, which reduce RAAS activity and improve renal function and blood pressure. Short-acting ACE inhibitors (typically captopril) are used because they can be rapidly uptitrated. An elevated serum creatinine level is not a contraindication for ACE inhibitors in this population, and slight elevations in creatinine are common during drug initiation. Scleroderma renal crisis, the occurrence of acute kidney injury, and malignant hypertension (very high blood pressure with evidence of organ damage) in people with scleroderma are effectively treated with drugs from the class of the ACE inhibitors. The benefit of ACE inhibitors extends even to those who have to commence dialysis to treat their kidney disease, and may give sufficient benefit to allow the discontinuation of renal replacement therapy. Lung disease Active alveolitis is often treated with pulses of cyclophosphamide, often together with a small dose of steroids. The benefit of this intervention is modest.Pulmonary hypertension may be treated with epoprostenol, treprostinil, bosentan, and possibly aerolized iloprost. Nintedanib was approved for use in the United States Food and Drug Administration on September 6, 2019, to slow the rate of decline in pulmonary function in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). Other Some evidence indicates that plasmapheresis (therapeutic plasma exchange) can be used to treat the systemic form of scleroderma. In Italy, it is a government-approved treatment option. This is done by replacing blood plasma with a fluid consisting of albumin, and is thought to keep the disease at bay by reducing the circulation of scleroderma autoantibodies. Epidemiology Systemic scleroderma is a rare disease, with an annual incidence that varies in different populations. Estimates of incidence (new cases per million people) range from 3.7 to 43 in the United Kingdom and Europe, 7.2 in Japan, 10.9 in Taiwan, 12.0 to 22.8 in Australia, 13.9 to 21.0 in the United States, and 21.2 in Buenos Aires. The interval of peak onset starts at age 30 and ends at age 50.Globally, estimates of prevalence vary from 31.0 to 658.6 affected people per million. Systemic sclerosis has a female:male ratio of 3:1 (8:1 in mid- to late childbearing years). Incidence is twice as high among African Americans. Full-blooded Choctaw Native Americans in Oklahoma have the highest prevalence in the world (469 per 100,000).The disease has some hereditary association. It may also be caused by an immune reaction to a virus (molecular mimicry) or by toxins. Society and culture Support groups The Juvenile Scleroderma Network is an organization dedicated to providing emotional support and educational information to parents and their children living with juvenile scleroderma, supporting pediatric research to identify the cause of and the cure for juvenile scleroderma, and enhancing public awareness.In the US, the Scleroderma Foundation is dedicated to raise awareness of the disease and assist those who are affected.The Scleroderma Research Foundation sponsors research into the condition. Comedian and television presenter Bob Saget, a board member of the SRF, directed the 1996 ABC TV movie For Hope, starring Dana Delany, which depicts a young woman fatally affected by scleroderma; the film was based on the experiences of Sagets sister Gay.Scleroderma and Raynauds UK is a British charity formed by the merger of two smaller organisations in 2016 to provide support for people with scleroderma and fund research into the condition. Prognosis A 2018 study placed 10-year survival rates at 88%, without differentiation based on subtype. Diffuse systemic sclerosis, internal organ complications, and older age at diagnosis are associated with worse prognoses. Research Given the difficulty in treating scleroderma, treatments with a smaller evidence base are often tried to control the disease. These include antithymocyte globulin and mycophenolate mofetil; some reports have shown improvements in the skin symptoms, as well as delaying the progress of systemic disease, but neither has been subjected to large clinical trials.Autologous hematopoietic stem cell transplantation (HSCT) is based on the assumption that autoimmune diseases such as systemic sclerosis occur when the white blood cells of the immune system attack the body. In this treatment, stem cells from the patients blood are extracted and stored to preserve them. The patients white blood cells are destroyed with cyclophosphamide and rabbit antibodies against the white blood cells. Then, the stored blood is returned to the patients bloodstream to reconstitute a healthy blood and immune system that will not attack the body. The results of a phase-III trial, the Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, with 156 patients, were published in 2014. HSCT itself has a high treatment mortality, so in the first year, the survival of patients in the treatment group was lower than the placebo group, but at the end of 10 years, the survival in the treatment group was significantly higher. The authors concluded that HSCT could be effective, if limited to patients who were healthy enough to survive HSCT itself. Therefore, HSCT should be given early in the progression of the disease, before it does damage. Patients with heart disease, and patients who smoked cigarettes, were less likely to survive. Another trial, the Stem Cell Transplant vs. Cyclophosphamide (SCOT) trial, is ongoing. References == External links ==
Hair follicle nevus	Hair follicle nevus is a cutaneous condition that presents as a small papule from which fine hairs protrude evenly from the surface. See also Skin lesion List of cutaneous conditions == References ==
Intrauterine growth restriction	Intrauterine growth restriction (IUGR), or fetal growth restriction, refers to poor growth of a fetus while in the womb during pregnancy. IUGR is defined by clinical features of malnutrition and evidence of reduced growth regardless of an infants birth weight percentile. The causes of IUGR are broad and may involve maternal, fetal, or placental complications.At least 60% of the 4 million neonatal deaths that occur worldwide every year are associated with low birth weight (LBW), caused by intrauterine growth restriction (IUGR), preterm delivery, and genetic abnormalities, demonstrating that under-nutrition is already a leading health problem at birth. Intrauterine growth restriction can result in a baby being small for gestational age (SGA), which is most commonly defined as a weight below the 10th percentile for the gestational age. At the end of pregnancy, it can result in a low birth weight. Types There are two major categories of IUGR: pseudo IUGR and true IUGRWith pseudo IUGR, the fetus has a birth weight below the tenth percentile for the corresponding gestational age but has a normal ponderal index, subcutaneous fat deposition, and body proportion. Pseudo IUGR occurs due to uneventful intrauterine course and can be rectified by proper postnatal care and nutrition. Such babies are also called small for gestational age.True IUGR occurs due to pathological conditions which may be either fetal or maternal in origin. In addition to low body weight they have abnormal ponderal index, body disproportion, and low subcutaneous fat deposition. There are two types-symmetrical and asymmetrical. Some conditions are associated with both symmetrical and asymmetrical growth restriction. Asymmetrical Asymmetrical IUGR accounts for 70-80% of all IUGR cases. In asymmetrical IUGR, there is decreased oxygen or nutrient supply to the fetus during the third trimester of pregnancy due to placental insufficiency. This type of IUGR is sometimes called "head sparing" because brain growth is typically less affected, resulting in a relatively normal head circumference in these children. Because of decreased oxygen supply to the fetus, blood is diverted to the vital organs, such as the brain and heart. As a result, blood flow to other organs - including liver, muscle, and fat - is decreased. This causes abdominal circumference in these children to be decreased.A lack of subcutaneous fat leads to a thin and small body out of proportion with the liver. Normally at birth the brain of the fetus is 3 times the weight of its liver. In IUGR, it becomes 5-6 times. In these cases, the embryo/fetus has grown normally for the first two trimesters but encounters difficulties in the third, sometimes secondary to complications such as pre-eclampsia. Other symptoms than the disproportion include dry, peeling skin and an overly-thin umbilical cord. The baby is at increased risk of hypoxia and hypoglycemia. This type of IUGR is most commonly caused by extrinsic factors that affect the fetus at later gestational ages. Specific causes include: Chronic high blood pressure Severe malnutrition Genetic mutations, Ehlers–Danlos syndrome Symmetrical Symmetrical IUGR is commonly known as global growth restriction, and indicates that the fetus has developed slowly throughout the duration of the pregnancy and was thus affected from a very early stage. The head circumference of such a newborn is in proportion to the rest of the body. Since most neurons are developed by the 18th week of gestation, the fetus with symmetrical IUGR is more likely to have permanent neurological sequelae. Common causes include: Early intrauterine infections, such as cytomegalovirus, rubella or toxoplasmosis Chromosomal abnormalities Anemia Maternal substance use (prenatal alcohol use can result in Fetal alcohol syndrome) Causes IUGR is caused by a variety of factors; these can be fetal, maternal, placental or genetic factors. Maternal Pre-pregnancy weight and nutritional status Poor weight gain during pregnancy Malnutrition Anemia Substance use: smoking, alcohol, drugs including marijuana or cocaine Medication: warfarin, steroids, anticonvulsants Inter-pregnancy interval of less than 6 months Assisted reproductive technologies Pre-gestational diabetes Gestational diabetes Pulmonary disease Cardiovascular disease Kidney disease Hypertension Celiac disease increases the risk of intrauterine growth restriction by an odds ratio of approximately 2.48 Subclinical hypothyroidism Blood clotting disorder/disease (e.g., Factor V Leiden) Uteroplacental Preeclampsia Multiple gestation Uterine malformations Placental insufficiency Fetal Chromosomal abnormalities Vertically transmitted infections: TORCH, Malaria, congenital HIV infection, Syphilis Erythroblastosis fetalis Congenital abnormalities Genetic Placental genes Maternal genes: Endothelin-1 over-expression, Leptin under-expression Fetal genes Pathophysiology If the cause of IUGR is extrinsic to the fetus (parental or uteroplacental), transfer of oxygen and nutrients to the fetus is decreased. This causes a reduction in the fetus’ stores of glycogen and lipids. This often leads to hypoglycemia at birth. Polycythemia can occur secondary to increased erythropoietin production caused by the chronic hypoxemia. Hypothermia, thrombocytopenia, leukopenia, hypocalcemia, and bleeding in the lungs are often results of IUGR.Infants with IUGR are at increased risk of perinatal asphyxia due to chronic hypoxia, usually associated with placental insufficiency, placental abruption, or a umbilical cord accident. This chronic hypoxia also places IUGR infants at elevated risk of persistent pulmonary hypertension of the newborn, which can impair an infants blood oxygenation and transition to postnatal circulation.If the cause of IUGR is intrinsic to the fetus, growth is restricted due to genetic factors or as a sequela of infection. IUGR is associated with a wide range of short- and long-term neurodevelopmental disorders. Cardiovascular In IUGR, there is an increase in vascular resistance in the placental circulation, causing an increase in cardiac afterload. There is also increased vasoconstriction of the arteries in the periphery, which occurs in response to chronic hypoxia in order to preserve adequate blood flow to the fetus vital organs. This prolonged vasoconstriction leads to remodeling and stiffening of the arteries, which also contributes to the increase in cardiac afterload. Therefore, the fetal heart must work harder to contract during each heartbeat, which leads to an increase in wall stress and cardiac hypertrophy. These changes in the fetal heart lead to increased long-term risk of hypertension, atherosclerosis, cardiovascular disease, and stroke. Pulmonary Normal lung development is interrupted in fetuses with IUGR, which increases their risk for respiratory compromise and impaired lung function later in life. Preterm infants with IUGR are more likely to have bronchopulmonary dysplasia (BPD), a chronic lung disease that is thought to be associated with prolonged use of mechanical ventilation. Neurological IUGR is associated with long-term motor deficits and cognitive impairment. In order to adapt to the chronic hypoxia associated with placental insufficiency, blood flow is redirected to the brain to try to preserve brain growth and development as much as possible. Even though this is thought to be protective, fetuses with IUGR who have undergone this brain-sparing adaptation have worse neurological outcomes compared with those who have not undergone this adaptation.Magnetic resonance imaging (MRI) can detect changes in volume and structural development of infants with IUGR compared with those whose growth is appropriate for gestational age (AGA). But MRI is not easily accessible for all patients.White matter effects – In postpartum studies of infants, it was shown that there was a decrease of the fractal dimension of the white matter in IUGR infants at one year corrected age. This was compared to at term and preterm infants at one year adjusted corrected age.Grey matter effects – Grey matter was also shown to be decreased in infants with IUGR at one year corrected age.Children with IUGR are often found to exhibit brain reorganization including neural circuitry. Reorganization has been linked to learning and memory differences between children born at term and those born with IUGR.Studies have shown that children born with IUGR had lower IQ. They also exhibit other deficits that point to frontal lobe dysfunction.IUGR infants with brain-sparing show accelerated maturation of the hippocampus which is responsible for memory. This accelerated maturation can often lead to uncharacteristic development that may compromise other networks and lead to memory and learning deficiencies. Management Mothers whose fetus is diagnosed with intrauterine growth restriction can be managed with several monitoring and delivery methods. It is currently recommended that any fetus that has growth restriction and additional structural abnormalities should be evaluated with genetic testing. In addition to evaluating the fetal growth velocity, the fetus should primarily be monitored by ultrasonography every 3–4 weeks. An additional monitoring technique is an Doppler velocimetry. Doppler velocimetry is useful in monitoring blood flow through the uterine and umbilical arteries, and may indicate signs of uteroplacental insufficiency. This method may also detect blood vessels, specifically the ductus venosus and middle cerebral arteries, which are not developing properly or may not adapt well after birth. Monitoring via Doppler velocimetry has been shown to decrease the risk of morbidity and mortality before and after parturition among IUGR patients. Standard fetal surveillance via nonstress tests and/or biophysical profile scoring is also recommended. Bed rest has not been found to improve outcomes and is not typically recommended. There is currently a lack of evidence supporting any dietary or supplemental changes that may prevent the development of IUGR.The optimal timing of delivery for a fetus with IUGR is unknown. However, the timing of delivery is currently based on the cause of IUGR and parameters collected from the umbilical artery doppler. Some of these include: pulsatility index, resistance index, and end-diastolic velocities, which are measurements of the fetal circulation. Fetuses with an anticipated delivery before 34 weeks gestation are recommended to receive corticosteroids to facilitate fetal maturation. Anticipated births before 32 weeks should receive magnesium sulfate to protect development of the fetal brain. Outcomes Postnatal complications After correcting for several factors such as low gestational parental weight, it is estimated that only around 3% of pregnancies are affected by true IUGR. 20% of stillborn infants exhibit IUGR. Perinatal mortality rates are 4-8 times higher for infants with IUGR, and morbidity is present in 50% of surviving infants. Common causes of mortality in fetuses/infants with IUGR include: severe placental insufficiency and chronic hypoxia, congenital malformations, congenital infections, placental abruption, cord accidents, cord prolapse, placental infarcts, and severe perinatal depression.IUGR is more common in preterm infants than in full term (37–40 weeks gestation) infants, and its frequency decreases with increasing gestational age. Relative to premature infants who do not exhibit IUGR, premature infants with IUGR are more likely to have adverse neonatal outcomes, including respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis. This association with prematurity suggests utility of screening for IUGR as a potential risk factor for preterm labor.Feeding intolerance, hypothermia, hypoglycemia, and hyperglycemia are all common in infants in the postnatal period, indicating the need to closely manage these patients temperature and nutrition. Furthermore, rapid metabolic and physiologic changes in the first few days after birth can yield susceptibility to hypocalcemia, polycythemia, immunologic compromise, and renal dysfunction. Long-term consequences According to the theory of thrifty phenotype, intrauterine growth restriction triggers epigenetic responses in the fetus that are otherwise activated in times of chronic food shortage. If the offspring actually develops in an environment where food is readily accessible, it may be more prone to metabolic disorders, such as obesity and type II diabetes.Infants with IUGR may continue to show signs of abnormal growth throughout childhood. Infants with asymmetric IUGR (head-sparing) typically have more robust catch-up postnatal growth, as compared with infants with symmetric IUGR, who may remain small throughout life. The majority of catch-up growth occurs in the first 6 months of life, but can continue throughout the first two years. Approximately 10% of infants who are small for gestational age due to IUGR will still have short stature in late childhood.Infants with IUGR are also at elevated risk for neurodevelopmental abnormalities, including motor delay and cognitive impairments. Low IQ in adulthood may occur in up to one third of infants born small for gestational age due to IUGR. Infants who fail to display adequate catch-up growth in the first few years of life may exhibit worse outcomes.Catch-up growth can alter fat distribution in children diagnosed with IUGR as infants and increase risk of metabolic syndrome. Infants with IUGR may be susceptible to long-term dysfunction of several endocrine processes, including growth hormone signaling, the hypothalamic-pituitary-adrenal axis, and puberty. Renal dysfunction, disrupted lung development, and impaired bone metabolism are also associated with IUGR. Animals In sheep, intrauterine growth restriction can be caused by heat stress in early to mid pregnancy. The effect is attributed to reduced placental development causing reduced fetal growth. Hormonal effects appear implicated in the reduced placental development. Although early reduction of placental development is not accompanied by concurrent reduction of fetal growth; it tends to limit fetal growth later in gestation. Normally, ovine placental mass increases until about day 70 of gestation, but high demand on the placenta for fetal growth occurs later. (For example, research results suggest that a normal average singleton Suffolk x Targhee sheep fetus has a mass of about 0.15 kg at day 70, and growth rates of about 31 g/day at day 80, 129 g/day at day 120 and 199 g/day at day 140 of gestation, reaching a mass of about 6.21 kg at day 140, a few days before parturition.) In adolescent ewes (i.e. ewe hoggets), overfeeding during pregnancy can also cause intrauterine growth restriction, by altering nutrient partitioning between dam and conceptus. Fetal growth restriction in adolescent ewes overnourished during early to mid pregnancy is not avoided by switching to lower nutrient intake after day 90 of gestation; whereas such switching at day 50 does result in greater placental growth and enhanced pregnancy outcome. Practical implications include the importance of estimating a threshold for "overnutrition" in management of pregnant ewe hoggets. In a study of Romney and Coopworth ewe hoggets bred to Perendale rams, feeding to approximate a conceptus-free live mass gain of 0.15 kg/day (i.e. in addition to conceptus mass), commencing 13 days after the midpoint of a synchronized breeding period, yielded no reduction in lamb birth mass, where compared with feeding treatments yielding conceptus-free live mass gains of about 0 and 0.075 kg/day. In both of the above models of IUGR in sheep, the absolute magnitude of uterine blood flow is reduced. Evidence of substantial reduction of placental glucose transport capacity has been observed in pregnant ewes that had been heat-stressed during placental development. See also Runt Interspecific pregnancy can cause this in animals References == External links ==
Iridocorneal endothelial syndrome	Iridocorneal endothelial (ICE) syndromes are a spectrum of diseases characterized by slowly progressive abnormalities of the corneal endothelium and features including corneal edema, iris distortion, and secondary angle-closure glaucoma. ICE syndromes are predominantly unilateral and nonhereditary. The condition occurs in predominantly middle-aged women. Signs and symptoms Many cases are asymptomatic, however patients many have decreased vision, glare, monocular diplopia or polyopia, and noticeable iris changes. On exam patients have normal to decreased visual acuity, and a "beaten metal appearance" of the corneal endothelium, corneal edema, increased intraocular pressure, peripheral anterior synechiae, and iris changes. Mechanism The exact mechanism is unknown, however there appears to be a component of abnormal corneal endothelium that proliferates onto the iris forming a membrane that then obstructs the trabecular meshwork, leading to iris distortion. Nodule formation can also occur when the abnormal corneal endothelium causes contractions around the iris stroma. Herpesvirus DNA has been identified in some patients following keratoplasty, suggesting the possibility that herpes simplex virus may induce the abnormal endotheliazation in the anterior chamber angle and on the surface of the iris. Variations The Chandler variant of ICE is characterized by pathology on the inner surface of the cornea leading to abnormal endothelial pump function. Other features include possible mild iris changes, corneal edema, and normal to slight elevations in intraocular pressure.Cogan-Reese variant is characterized by multiple pigmented iris nodules. This variant is most commonly unilateral and seen in middle-aged females. Diagnosis Treatment Penetrating karatoplasty and endothelial keratoplasty can be used as treatments for severe cases of ICE. Because glaucoma and elevated intraocular pressure are often present in ICE patients, long term follow up may be needed to ensure adequate intraocular pressures are maintained. Prognosis The disease is chronic and often progresses slowly. Prognosis is generally poor when associated with glaucoma. References External links Facts About the Cornea and Corneal Disease The National Eye Institute (NEI).
Pityriasis	Pityriasis commonly refers to flaking (or scaling) of the skin. The word comes from the Greek πίτυρον "bran". Classification Types include: Pityriasis alba Pityriasis lichenoides chronica Pityriasis lichenoides et varioliformis acuta Pityriasis rosea Pityriasis circinata Pityriasis rubra pilaris Pityriasis versicolor Dandruff, historically called Pityriasis capitis Pityriasis amiantacea See also Desquamation List of cutaneous conditions References == External links ==
Tic disorder	Tic disorders are defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM) based on type (motor or phonic) and duration of tics (sudden, rapid, nonrhythmic movements). Tic disorders are defined similarly by the World Health Organization (ICD-10 codes). Classification DSM-5 The fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), published in May 2013, classifies Tourette syndrome and tic disorders as motor disorders listed in the neurodevelopmental disorder category.Tic disorders, in ascending order of severity, are: 307.20 Other specified tic disorder (specify reason) 307.20 Unspecified tic disorder 307.21 Provisional tic disorder 307.22 Persistent (chronic) motor or vocal tic disorder (specify motor or vocal) 307.23 Tourettes disorderDevelopmental coordination disorder and stereotypic movement disorder are also classified as motor disorders. ICD-10 ICD10 diagnosis codes are: F95.0 Transient tic disorder F95.1 Chronic motor or vocal tic disorder F95.2 Combined vocal and multiple motor tic disorder [Gilles de la Tourette] F95.8 Other tic disorders F95.9 Tic disorder, unspecified Diagnosis Tics should be distinguished from other causes of tourettism, stereotypies, chorea, dyskinesias, myoclonus and obsessive-compulsive disorder. Treatment Education, and a "watch and wait" strategy, are the only treatment needed for many, and the majority of individuals with tics do not seek treatment. When needed, management of tic disorders is similar to management of Tourette syndrome. Epidemiology Tic disorders are more commonly diagnosed in males than females.At least one in five children experience some form of tic disorder, most frequently between the ages of seven and twelve. Tourette syndrome is the more severe expression of a spectrum of tic disorders, which are thought to be due to the same genetic vulnerability. Nevertheless, most cases of Tourette syndrome are not severe. Although a significant amount of investigative work indicates genetic linkage of the various tic disorders, further study is needed to confirm the relationship. History DSM-IV-TR In the fourth revision of the DSM (DSM-IV-TR), tic disorders were classified as follows: Transient tic disorder consisted of multiple motor and/or phonic tics with duration of at least 4 weeks, but less than 12 months. Chronic tic disorder was either single or multiple motor or phonic tics, but not both, which were present for more than a year. Tourette syndrome was diagnosed when both motor and phonic tics were present for more than a year. Tic disorder NOS was diagnosed when tics were present, but did not meet the criteria for any specific tic disorder. From DSM-IV-TR to DSM-5 DSM-5 was published in 2013, updating DSM-IV-TR, which was published in 2000. The following changes were made: The word stereotyped was removed from tic definition: stereotypies and stereotypic movement disorder are frequently misdiagnosed as tics or Tourette syndrome. The definition of tic was made consistent for all tic disorders, and the word stereotyped was removed to help distinguish between stereotypies (common in autism spectrum disorders) and tic disorders. Provisional tic disorder approximately replaced transient tic disorder: because initially presenting tics may eventually be diagnosed as chronic tic disorder or Tourettes, transient suggested it could only be defined in retrospect (though that perception did not follow the DSM-IV-TR definition). The term provisional "satisfies experts with a more systematic epidemiological approach to disorders", but should not imply that treatment might not be called for. Differentiation of chronic motor or vocal tic disorder: DSM-5 added a specifier to distinguish between vocal and motor tics that are chronic. This distinction was added because higher rates of comorbid diagnoses are present with vocal tics relative to motor tics. Now includes as Tourettes Disorder patients with tics who experienced a 3-month or longer remission since the first tic, as long as the first tic was at least a year ago. Stimulant use as a cause removed: there is no evidence that the use of stimulants causes tic disorders. New categories, Other specified and Unspecified: for tic disorders that result in significant impairment to the individual yet do not meet the full criteria for other tic disorders. The new categories account for tics with onset in adulthood, or tics triggered by other medical conditions or illicit drug use. References External links The Tourette Syndrome Classification Study Group. "Definitions and classification of tic disorders". Arch Neurol. 1993 Oct;50(10):1013-6. PMID 8215958. Retrieved on 2005-03-22 Walkup JT, Ferrão Y, Leckman JF, Stein DJ, Singer H. Tic disorders: some key issues for DSM-V (PDF). Depress Anxiety. 2010 Jun;27(6):600–10. PMID 20533370 doi:10.1002/da.20711
Superior canal dehiscence syndrome	Superior semicircular canal dehiscence syndrome is a set of hearing and balance symptoms, related to a rare medical condition of the inner ear, known as superior canal dehiscence. The symptoms are caused by a thinning or complete absence of the part of the temporal bone overlying the superior semicircular canal of the vestibular system. There is evidence that this rare defect, or susceptibility, is congenital. There are also numerous cases of symptoms arising after physical trauma to the head. It was first described in 1998 by Lloyd B. Minor of Johns Hopkins University in Baltimore. Symptoms Superior canal dehiscence (SCD) can affect both hearing and balance to different extents in different people.Symptoms of SCDS include: Autophony – persons own speech or other self-generated noises (e.g. heartbeat, eye movements, creaking joints, chewing) are heard unusually loudly in the affected ear Dizziness/ vertigo/ chronic disequilibrium caused by the dysfunction of the superior semicircular canal Tullio phenomenon – sound-induced vertigo, disequilibrium or dizziness, nystagmus and oscillopsia Pulse-synchronous oscillopsia Hyperacusis – the over-sensitivity to sound Low-frequency conductive hearing loss A feeling of fullness in the affected ear Pulsatile tinnitus Brain fog Fatigue Headache/migraine Tinnitus – high pitched ringing in the ear Symptoms in detail SCDS-related autophony differs greatly in quality and range from the more common form which results from an open, or patulous Eustachian tube through which sufferers of this disorder hear the sound of their own voice and breathing. In contrast, patients with SCDS-related autophony report hearing their own voice as a disturbingly loud and distorted "kazoo-like" sound deep inside the head as if relayed through "a cracked loudspeaker." Additionally they may hear the creaking and cracking of joints, the sound of their footsteps when walking or running, their heartbeat and the sound of chewing and other digestive noises. Some sufferers of this condition experience such a high level of conductive hyperacusis that a tuning fork placed on the ankle will be heard in the affected ear. The bizarre phenomenon of being able to hear the sound of the eyeballs moving in their sockets (e.g. when reading in a quiet room) "like sandpaper on wood" is one of the more distinctive features of this condition and is almost exclusively associated with SCDS. Tullio phenomenon, another of the more identifiable symptoms leading to a positive SCD diagnosis is sound-induced loss of balance. Patients showing this symptom may experience a loss of equilibrium, a feeling of motion sickness or even actual nausea, triggered by normal everyday sounds. Although this is often associated with loud noises, volume is not necessarily a factor. Patients describe a wide range of sounds that affect balance: the rattle of a plastic bag; a cashier tossing coins into the register; a telephone ringing; a knock at the door; music; the sound of children playing and even the patients own voice are typical examples of sounds that can cause a loss of balance when this condition is present, although there are countless others. The presence of Tullio may also mean that involuntary eye movements (nystagmus), sometimes rotational, are set off by sound, giving the sufferer the impression that the world is tipping, clockwise or anticlockwise, depending on the site of the dehiscence. Some patients report this tilt as being as much as 15°. For such persons, a visit to the concert hall or to a noisy playground may seem like being at the epicenter of an earthquake. A change of pressure within the middle ear (for example when flying or nose-blowing) may equally set off a bout of disequilibrium or nystagmus. Low-frequency conductive hearing loss is present in many patients with SCDS and is explained by the dehiscence acting as a "third window." Vibrations entering the ear canal and middle ear are then abnormally diverted through the superior semicircular canal and up into the intracranial space where they become absorbed instead of being registered as sound in the hearing center, the cochlea. Due to the difference in resistance between the normal round window and the pathological dehiscence window this hearing loss is more serious in the lower frequencies and may initially be mistaken for otosclerosis. In some patients there is true enhancement of low frequency hearing via bone conducted sound. A clinical sign of this phenomenon is the ability of the patient to hear (not feel) a tuning fork placed upon the ankle bone. Pulsatile tinnitus is yet another of the typical symptoms of SCDS and is caused by the gap in the dehiscent bone allowing the normal pulse-related pressure changes within the cranial cavity to enter the inner ear abnormally. These pressure change thus affect the sound of the tinnitus which will be perceived as containing a pulse-synchronized "wave" or "blip" which patients describe as a "swooshing" sound or as being like the chirrup of a cricket or grasshopper. Brain fog and fatigue are both common SCDS symptoms and are caused by the brain having to spend an unusual amount of its energy on the simple act of keeping the body in a state of equilibrium when it is constantly receiving confusing signals from the dysfunctional semicircular canal. Headache and migraine are also often mentioned by patients showing other symptoms of SCDS due to the body overcompensating for poor hearing in the affected ear by tensing up nearby parts of the face, head, and neck and using them as almost a secondary eardrum. Causes According to current research, in approximately 2.5% of the general population the bones of the head develop to only 60–70% of their normal thickness in the months following birth. This genetic predisposition may explain why the section of temporal bone separating the superior semicircular canal from the cranial cavity, normally 0.8 mm thick, shows a thickness of only 0.5 mm, making it more fragile and susceptible to damage through physical head trauma or from slow erosion. An explanation for this erosion of the bone has not yet been found. Diagnosis The presence of dehiscence can be detected by a high definition (0.6 mm or less) coronal CT scan of the temporal bone, currently the most reliable way to distinguish between superior canal dehiscence syndrome (SCDS) and other conditions of the inner ear involving similar symptoms such as Ménières disease, perilymphatic fistula and cochlea-facial nerve dehiscence. Other diagnostic tools include the vestibular evoked myogenic potential or VEMP test, videonystagmography (VNG), electrocochleography (ECOG) and the rotational chair test. An accurate diagnosis is of great significance as unnecessary exploratory middle ear surgery may thus be avoided. Several of the symptoms typical to SCDS (e.g. vertigo and Tullio) may also be present singly or as part of Ménières disease, sometimes causing the one illness to be confused with the other. There are reported cases of patients being affected by both Ménières disease and SCDS concurrently.As SCDS is a very rare and still a relatively unknown condition, obtaining an accurate diagnosis of this distressing (and even disabling) disease may take some time as many health care professionals are not yet aware of its existence and frequently dismiss symptoms as being mental health-related. Treatment Once diagnosed, the gap in the temporal bone can be repaired by surgical resurfacing of the affected bone or plugging of the superior semicircular canal. These techniques are performed by accessing the site of the dehiscence either via a middle fossa craniotomy or via a canal drilled through the transmastoid bone behind the affected ear. Bone cement has been the material most often used, in spite of its tendency to slippage and resorption, and a consequent high failure rate; recently, soft tissue grafts have been substituted. Eponym Occasionally this disorder has been referred to as Minors syndrome, after its discoverer, Lloyd B. Minor. However, that eponym has also been given to an unrelated condition, the paralysis and anaesthesia following a spinal injury, which is named after the Russian neurologist, Lazar Salomowitch Minor (1855–1942). In the latter case this term is now nearly obsolete. References External links Ward, Bryan K.; Carey, John P.; Minor, Lloyd B. (28 April 2017). "Superior Canal Dehiscence Syndrome: Lessons from the First 20 Years". Frontiers in Neurology. 8: 177. doi:10.3389/fneur.2017.00177. PMC 5408023. PMID 28503164.
Poliosis	Poliosis (also called poliosis circumscripta), is the decrease or absence of melanin (or colour) in head hair, eyebrows, eyelashes or any other hairy area. It is popularly known as white forelock when it affects hair directly above the forehead. This condition can cause single or, less commonly, multiple white patches on the hair. Some mistake these white patches for simple birth marks. In poliosis there is decreased or absent melanin in the hair bulbs of affected hair follicles; the melanocytes of the skin are usually not affected. Associated medical conditions Poliosis occurs in several genetic syndromes such as piebaldism, Waardenburg syndrome, neurofibromatosis type I, and tuberous sclerosis. It can also occur in conditions such as vitiligo, Vogt–Koyanagi–Harada disease, alopecia areata, sarcoidosis, and in association with neoplasms and some medications. Popular culture It is sometimes called a Mallen streak, after a fictional family with hereditary poliosis. The Mallen family featured in a sequence of novels by Catherine Cookson, of which The Mallen Streak was the first. She later adapted them into a TV series called The Mallens.Sports presenter Dickie Davies, runner Sam Brown, punk singer Dave Vanian, and fashion expert Stacy London are also known for their Mallen streaks.During his tenure as the host of Talk Soup, host John Henson repeatedly referred to his own poliosis as a "skunk spot".In DC Comics one of Batmans Robins, Jason Todd, is sometimes portrayed with a white forelock.In Marvel Comics, the X-Men member Rogue has a prominent Mallen streak which is a consistent visual trademark of the character. In her earliest appearances, the character was drawn with a closed-cropped hairdo which had two small white streaks originating above her temples and reaching back over her ears to the back of her head. Over time, she came to be drawn with a larger section of white hair at her forelock, although its size varies greatly from artist to artist. This visual aspect of Rogues appearance has been consistently portrayed in every adaptation of the character, however, in the 2000 X-Men live action film, Rogue is shown to initially have all brown hair, developing the permanent white streak after being forced to absorb a significant amount of power from Magneto.The characters Percy Jackson and Annabeth Chase each develop a white streak in their hair from the strain of holding up the sky in The Titans Curse, the third novel in the book series Percy Jackson and the Olympians.Cruella De Vil is thought of to have this condition with her half black / half white hair.The main character Jio Fleed of the Satan 666 manga series seems to have the condition.During his Christmas special, Jeff Dunham was doing a bit with Achmed the Dead Terrorist and mistakenly combined scoliosis with polio, making poliosis.A Mallen streak is a minor plot point in the 2021 film Dont Breathe 2.In the popular web series Dream SMP, the character Wilbur Soot - played by the content creator of the same name - develops a prominent Mallen streak from the stress of being magically revived. Ironically, the characters son Fundy is often portrayed with the same natural poliosis as his actor.In the web series Sanders Sides, the character Remus Sanders (the embodiment of Dark Creativity) has a white forelock. References == External links ==
Major aortopulmonary collateral artery	Major aortopulmonary collateral arteries (or MAPCAs) are arteries that develop to supply blood to the lungs when native pulmonary circulation is underdeveloped. Instead of coming from the pulmonary trunk, supply develops from the aorta and other systemic arteries. Pathogenesis and anatomy Major aortopulmonary collateral arteries (MAPCAs) develop early in embryonic life but regress as the normal pulmonary arteries (vessels that will supply deoxygenated blood to the lungs) develop. In certain heart conditions the pulmonary arteries do not develop. The collaterals continue to grow, and can become the main supply of blood to the lungs. Though it is usually associated with congenital heart diseases with decreased pulmonary blood flow like tetralogy of Fallot or pulmonary atresia it may be seen sometimes in isolation i.e. not associated with any congenital heart disease in that case it is termed as isolated aortopulmonary collateral artery. In these cases it may be one of the cause of congestive cardiac failure in neonates.Pulmonary arteries come from the right side of the heart, and usually carry deoxygenated blood from the body. These collateral arteries carry blood which has already been oxygenated by the lungs, so are of little use in helping the body to get oxygen. Associated conditions Pulmonary atresia with ventricular septal defect (or Tetralogy of Fallot with pulmonary atresia) will result in the development of systemic collaterals. Implications of a systemic collateral supply Major aortopulmonary collateral arteries come from the systemic circulation, because of this they will often have higher pressure than normal found in the lungs, leading to pulmonary hypertension. These vessels are not programmed to exist beyond early fetal life, and eventually became narrowed. Treatment The aim of treatment of the MAPCAs is to group them together and convert their supply to deoxygenated blood from the right side of the heart. External links Interactive videogame graphic showing repair of tetralogy of Fallot with pulmonary atresia - from Lucile Packard Childrens Hospital Stanford & Lighthaus Inc. Management of Tetralogy of Fallot with pulmonary atresia - contains angiographic images of MAPCAs. == References ==
Autosomal recessive axonal neuropathy with neuromyotonia	Autosomal recessive axonal neuropathy with neuromyotonia, also known as Gamstorp-Wohlfart syndrome, is a rare hereditary disorder which is characterized by progressive poly-neuropathy, neuromyotonia, myokymia, pseudo-myotonia, hand-foot contractures, and abnormal neuro-myotonic/myokimic activity visible on needle EMG. According to OMIM, around 52 cases have been reported in medical literature However; new cases (mostly from Europe and North America) have been reported since 2014. Description People with this disorder usually show the following symptoms: axonal neuropathy, atrophy (wasting/degeneration) of the muscles in the hands, feet and legs, chronic muscular weakness which is very apparent when exercise is being done, abnormal gait, high chance of accidental falls, and joint contractures, neuromyotonia, and myokymia. In some people, the axonal neuropathy ends up reducing their sensitivity to cold and hot temperatures and touch in the distal parts of the arms and legs. Some of the symptoms worsen temporarily when a person with this disorder is exposed to cold temperatures. Causes This disorder is caused by a homozygous mutation in the HINT1 gene, in chromosome 5 (c.334 C > A, p.H112 N). Etimology This condition was discovered in 1991 by Hahn et al., when they described two Chinese-Canadian siblings of the opposite sex. The male had difficulties releasing his grip, childhood-onset neuromyotonia and muscle stiffness, progressive motor neuropathy, finger cramping while and after writing, involuntary twitches of the finger, thigh and forearm muscles, foot drop-associated gait problems, hand weakness, hyporeflexia, and tongue percussion, his younger sister wasnt as affected as his brother, she only shared some of his symptoms, these include; upper and lower distal muscle weakness. Both siblings were revealed to have a chronic motor neuropathy, peripheral nerve fiber hyperexcitability, and multiple denervations. Muscle biopsies performed in the brother detected chronic partial denervation.Through the siblings reported by Hahn et al. and 50 new patients from 33 families across the world, it was found that this disorder is caused by HINT1 mutations. == References ==
Arachnodactyly	Arachnodactyly ("spider fingers") is a medical condition that is characterized by fingers and toes that are abnormally long and slender, in comparison to the palm of the hand and arch of the foot. In some cases, the thumbs of an individual with the condition are pulled inwards towards the palm. This condition is present at birth. Causes This feature can occur on its own with no underlying health problems, or it can be associated with certain medical conditions, including Marfan syndrome, Ehlers–Danlos syndromes, Loeys–Dietz syndrome, and homocystinuria. It is also seen in congenital contractural arachnodactyly, which is caused by mutation in the gene encoding fibrillin-2 on chromosome 5q23. Notable cases It remains unconfirmed whether composer Sergei Rachmaninoffs abnormally large reach on a piano was a result of arachnodactyly due to Marfan syndrome, as the pianist exhibited no other signs of the disease.It is also uncertain if blues guitarist and vocalist Robert Johnsons long fingers were attributed to the disease also due to Marfan syndrome. See also Marfanoid References == External links ==
Secondary sclerosing cholangitis	Secondary sclerosing cholangitis (SSC) is a chronic cholestatic liver disease. SSC is a sclerosing cholangitis with a known cause. Alternatively, if no cause can be identified, then primary sclerosing cholangitis is diagnosed. SSC is an aggressive and rare disease with complex and multiple causes. It is characterized by inflammation, fibrosis, destruction of the biliary tree and biliary cirrhosis. It can be treated with minor interventions such as continued antibiotic use and monitoring, or in more serious cases, laparoscopic surgery intervention, and possibly a liver transplant. Cause SSC is thought to develop as a consequence of known injuries or pathological processes of the biliary tree, such as biliary obstruction, surgical trauma to the bile duct, or ischemic injury to the biliary tree. Secondary causes of SSC include intraductal stone disease, surgical or blunt abdominal trauma, intra-arterial chemotherapy, and recurrent pancreatitis. It has been clearly demonstrated that sclerosing cholangitis can develop after an episode of severe bacterial cholangitis. Also it was suggested that it can result from insult to the biliary tree by obstructive cholangitis secondary to choledocholithiasis, surgical damage, trauma, vascular insults, parasites, or congenital fibrocystic disorders. Additional causes of secondary SC are toxic, due to chemical agents or drugs. Diagnosis SSC is clinically related to primary sclerosing cholangitis (PSC), but originates from a known pathological process. Diagnosis of PSC requires the exclusion of all secondary causes of sclerosing cholangitis; else, if a known aetiology can be uncovered, SSC is diagnosed. Its clinical and cholangiographic features may mimic PSC, yet its natural history may be more favorable if recognition is prompt and appropriate therapy is introduced. Sclerosing cholangitis in critically ill patients, however, is associated with rapid disease progression and poor outcome. Serologic testing, radiological imaging and histological analysis can help diagnose SSC. Treatment First lines of treatment can include mass spectrum antibiotics or drainage of the bile duct that is infected followed by close monitoring. Endoscopic surgery is favored over open procedures to reduce infection and quicker recovery times. If these fail a liver transplant may be necessary. References == External links ==
Dermatophytosis	Dermatophytosis, also known as ringworm, is a fungal infection of the skin. Typically it results in a red, itchy, scaly, circular rash. Hair loss may occur in the area affected. Symptoms begin four to fourteen days after exposure. Multiple areas can be affected at a given time.About 40 types of fungus can cause ringworm. They are typically of the Trichophyton, Microsporum, or Epidermophyton type. Risk factors include using public showers, contact sports such as wrestling, excessive sweating, contact with animals, obesity, and poor immune function. Ringworm can spread from other animals or between people. Diagnosis is often based on the appearance and symptoms. It may be confirmed by either culturing or looking at a skin scraping under a microscope.Prevention is by keeping the skin dry, not walking barefoot in public, and not sharing personal items. Treatment is typically with antifungal creams such as clotrimazole or miconazole. If the scalp is involved, antifungals by mouth such as fluconazole may be needed.Globally, up to 20% of the population may be infected by ringworm at any given time. Infections of the groin are more common in males, while infections of the scalp and body occur equally in both sexes. Infections of the scalp are most common in children while infections of the groin are most common in the elderly. Descriptions of ringworm date back to ancient history. Signs and symptoms Infections on the body may give rise to typical enlarging raised red rings of ringworm. Infection on the skin of the feet may cause athletes foot and in the groin, jock itch. Involvement of the nails is termed onychomycosis, and they may thicken, discolour, and finally crumble and fall off. They are common in most adult people, with up to 20% of the population having one of these infections at any given moment.Animals including dogs and cats can also be affected by ringworm, and the disease can be transmitted between animals and humans, making it a zoonotic disease. Specific signs can be: red, scaly, itchy or raised patches patches may be redder on outside edges or resemble a ring patches that begin to ooze or develop a blister bald patches may develop when the scalp is affected nails may thicken, discolour or begin to crack Causes Fungi thrive in moist, warm areas, such as locker rooms, tanning beds, swimming pools, and skin folds; accordingly, those that cause dermatophytosis may be spread by using exercise machines that have not been disinfected after use, or by sharing towels, clothing, footwear, or hairbrushes. Diagnosis Dermatophyte infections can be readily diagnosed based on the history, physical examination, and potassium hydroxide (KOH) microscopy. Classification A number of different species of fungus are involved in dermatophytosis. Dermatophytes of the genera Trichophyton and Microsporum are the most common causative agents. These fungi attack various parts of the body and lead to the conditions listed below. The Latin names are for the conditions (disease patterns), not the agents that cause them. The disease patterns below identify the type of fungus that causes them only in the cases listed: Dermatophytosis Tinea pedis (athletes foot): fungal infection of the feet Tinea unguium: fungal infection of the fingernails and toenails, and the nail bed Tinea corporis: fungal infection of the arms, legs, and trunk Tinea cruris (jock itch): fungal infection of the groin area Tinea manuum: fungal infection of the hands and palm area Tinea capitis: fungal infection of the scalp and hair Tinea faciei (face fungus): fungal infection of the face Tinea barbae: fungal infestation of facial hair Other superficial mycoses (not classic ringworm, since not caused by dermatophytes) Tinea versicolor: caused by Malassezia furfur Tinea nigra: caused by Hortaea werneckii Prevention Advice often given includes: Avoid sharing clothing, sports equipment, towels, or sheets. Wash clothes in hot water with fungicidal soap after suspected exposure to ringworm. Avoid walking barefoot; instead wear appropriate protective shoes in locker rooms and sandals at the beach. Avoid touching pets with bald spots, as they are often carriers of the fungus. Vaccination As of 2016, no approved human vaccine exist against Dermatophytosis. For horses, dogs and cats there is available an approved inactivated vaccine called Insol Dermatophyton (Boehringer Ingelheim) which provides time-limited protection against several trichophyton and microsporum fungal strains. With cattle, systemic vaccination has achieved effective control of ringworm. Since 1979 a Russian live vaccine (LFT 130) and later on a Czechoslovakian live vaccine against bovine ringworm has been used. In Scandinavian countries vaccination programmes against ringworm are used as a preventive measure to improve the hide quality. In Russia, fur-bearing animals (silver fox, foxes, polar foxes) and rabbits have also been treated with vaccines. Treatment Antifungal treatments include topical agents such as miconazole, terbinafine, clotrimazole, ketoconazole, or tolnaftate applied twice daily until symptoms resolve — usually within one or two weeks. Topical treatments should then be continued for a further 7 days after resolution of visible symptoms to prevent recurrence. The total duration of treatment is therefore generally two weeks, but may be as long as three.In more severe cases or scalp ringworm, systemic treatment with oral medications may be given.To prevent spreading the infection, lesions should not be touched, and good hygiene maintained with washing of hands and the body.Misdiagnosis and treatment of ringworm with a topical steroid, a standard treatment of the superficially similar pityriasis rosea, can result in tinea incognito, a condition where ringworm fungus grows without typical features, such as a distinctive raised border. History Dermatophytosis has been prevalent since before 1906, at which time ringworm was treated with compounds of mercury or sometimes sulfur or iodine. Hairy areas of skin were considered too difficult to treat, so the scalp was treated with X-rays and followed up with antifungal medication. Another treatment from around the same time was application of Araroba powder. Terminology The most common term for the infection, "ringworm", is a misnomer, since the condition is caused by fungi of several different species and not by parasitic worms. Other animals Ringworm caused by Trichophyton verrucosum is a frequent clinical condition in cattle. Young animals are more frequently affected. The lesions are located on the head, neck, tail, and perineum. The typical lesion is a round, whitish crust. Multiple lesions may coalesce in "map-like" appearance. Clinical dermatophytosis is also diagnosed in sheep, dogs, cats, and horses. Causative agents, besides Trichophyton verrucosum, are T. mentagrophytes, T. equinum, Microsporum gypseum, M. canis, and M. nanum.Dermatophytosis may also be present in the holotype of the Cretaceous eutriconodont mammal Spinolestes, suggesting a Mesozoic origin for this disease. Diagnosis Ringworm in pets may often be asymptomatic, resulting in a carrier condition which infects other pets. In some cases, the disease only appears when the animal develops an immunodeficiency condition. Circular bare patches on the skin suggest the diagnosis, but no lesion is truly specific to the fungus. Similar patches may result from allergies, sarcoptic mange, and other conditions. Three species of fungi cause 95% of dermatophytosis in pets: these are Microsporum canis, Microsporum gypseum, and Trichophyton mentagrophytes. Veterinarians have several tests to identify ringworm infection and identify the fungal species that cause it: Woods test: This is an ultraviolet light with a magnifying lens. Only 50% of M. canis will show up as an apple-green fluorescence on hair shafts, under the UV light. The other fungi do not show. The fluorescent material is not the fungus itself (which does not fluoresce), but rather an excretory product of the fungus which sticks to hairs. Infected skin does not fluoresce. Microscopic test: The veterinarian takes hairs from around the infected area and places them in a staining solution to view under the microscope. Fungal spores may be viewed directly on hair shafts. This technique identifies a fungal infection in about 40%–70% of the infections, but cannot identify the species of dermatophyte. Culture test: This is the most effective, but also the most time-consuming, way to determine if ringworm is on a pet. In this test, the veterinarian collects hairs from the pet, or else collects fungal spores from the pets hair with a toothbrush, or other instrument, and inoculates fungal media for culture. These cultures can be brushed with transparent tape and then read by the veterinarian using a microscope, or can be sent to a pathological lab. The three common types of fungi which commonly cause pet ringworm can be identified by their characteristic spores. These are different-appearing macroconidia in the two common species of Microspora, and typical microconidia in Trichophyton infections.Identifying the species of fungi involved in pet infections can be helpful in controlling the source of infection. M. canis, despite its name, occurs more commonly in domestic cats, and 98% of cat infections are with this organism. It can also infect dogs and humans, however. T. mentagrophytes has a major reservoir in rodents, but can also infect pet rabbits, dogs, and horses. M. gypseum is a soil organism and is often contracted from gardens and other such places. Besides humans, it may infect rodents, dogs, cats, horses, cattle, and swine. Treatment Pet animals Treatment requires both systemic oral treatment with most of the same drugs used in humans—terbinafine, fluconazole, or itraconazole—as well as a topical "dip" therapy.Because of the usually longer hair shafts in pets compared to those of humans, the area of infection and possibly all of the longer hair of the pet must be clipped to decrease the load of fungal spores clinging to the pets hair shafts. However, close shaving is usually not done because nicking the skin facilitates further skin infection. Twice-weekly bathing of the pet with diluted lime sulfur dip solution is effective in eradicating fungal spores. This must continue for 3 to 8 weeks.Washing of household hard surfaces with 1:10 household sodium hypochlorite bleach solution is effective in killing spores, but it is too irritating to be used directly on hair and skin. Pet hair must be rigorously removed from all household surfaces, and then the vacuum cleaner bag, and perhaps even the vacuum cleaner itself, discarded when this has been done repeatedly. Removal of all hair is important, since spores may survive 12 months or even as long as two years on hair clinging to surfaces. Cattle In bovines, an infestation is difficult to cure, as systemic treatment is uneconomical. Local treatment with iodine compounds is time-consuming, as it needs scraping of crusty lesions. Moreover, it must be carefully conducted using gloves, lest the worker become infested. Epidemiology Worldwide, superficial fungal infections caused by dermatophytes are estimated to infect around 20-25% of the population and it is thought that dermatophytes infect 10-15% of the population during their lifetime. The highest incidence of superficial mycoses result from dermatophytoses which are most prevalent in tropical regions. Onychomycosis, a common infection caused by dermatophytes, is found with varying prevalence rates in many countries. Tinea pedis + onychomycosis, Tinea corporis, Tinea capitis are the most common dermatophytosis found in humans across the world. Tinea capitis has a greater prevalence in children. The increasing prevalence of dermatophytes resulting in Tinea capitis has been causing epidemics throughout Europe and America. In pets, cats are the most affected by dermatophytosis. Pets are susceptible to dermatophytoses caused by Microsporum canis, Microsporum gypseum, and Trichophyton. For dermatophytosis in animals, risk factors depend on age, species, breed, underlying conditions, stress, grooming, and injuries.Numerous studies have found Tinea capitis to be the most prevalent dermatophyte to infect children across the continent of Africa. Dermatophytosis has been found to be most prevalent in children ages 4 to 11, infecting more males than females. Low socioeconomic status was found to be a risk factor for Tinea capitis. Throughout Africa, dermatophytoses are common in hot- humid climates and with areas of overpopulation.Chronicity is a common outcome for dermatophytosis in India. The prevalence of dermatophytosis in India is between 36.6 and 78.4% depending on the area, clinical subtype, and dermatophyte isolate. Individuals ages 21–40 years are most commonly affected.A 2002 study looking at 445 samples of dermatophytes in patients in Goiânia, Brazil found the most prevalent type to be Trichophyton rubrum (49.4%), followed by Trichophyton mentagrophytes (30.8%), and Microsporum canis (12.6%).A 2013 study looking at 5,175 samples of Tinea in patients in Tehran, Iran found the most prevalent type to be Tinea pedis (43.4%), followed by Tinea unguium. (21.3%), and Tinea cruris (20.7%). See also Mycobiota References Further reading Weitzman I, Summerbell RC (1995). "The dermatophytes". Clinical Microbiology Reviews. 8 (2): 240–259. doi:10.1128/cmr.8.2.240. PMC 172857. PMID 7621400. External links Tinea photo library at Dermnet
9q34.3 deletion syndrome	9q34 deletion syndrome is a rare genetic disorder. Terminal deletions of chromosome 9q34 have been associated with childhood hypotonia, a distinctive facial appearance and developmental disability. The facial features typically described include arched eyebrows, small head circumference, midface hypoplasia, prominent jaw and a pouting lower lip. Individuals with this disease may often have speech impediments, such as speech delays. Other characteristics of this disease include: epilepsy, congenital and urogenital defects, microcephaly, corpulence, and psychiatric disorders. From analysis of chromosomal breakpoints, as well as gene sequencing in suggestive cases, Kleefstra and colleagues identified EHMT1 as the causative gene. This gene is responsible for producing the protein histone methyltransferase which functions to alter histones. Ultimately, histone methyltransferases are important in deactivating certain genes, needed for proper growth and development. Moreover, a frameshift, missense, or nonsense error in the coding sequence of EHMT1 can result in this condition in an individual. Signs and symptoms Physical symptoms Heart defects Characteristics of autism Genital defects (in males) Childhood hypotonia Respiratory infections Motor delay Renal defects Severe delay or total lack of speech Happy disposition Dysmorphic facial featuresBehavioural symptoms Passiveness Sociability Aggression Biting or hitting Moodiness Disliking routine changes Genetics Despite the associated effects of Kleefstra, there is insubstantial information regarding to the lethality of Kleefstras. Most of the documented cases are de novo with the exception of one case due to hereditary factors; however, some cases may be a result of chromosomal translocations. In the exception case, the mother transferred the EHMT1 point mutation on to her child as she was a carrier of this gene defect. According to Mitter, et al. (2012), the mothers phenotype of the NM_024757.4:c.2712+1G>A mutation displayed mosaicism at certain tissues. This mutation resulted in the disregard of exon 18 on the EHMT1 gene, as opposed to removing it through the spliceosomes. In another transcript, however, an intron was placed between exon 18 and 19 of the EHMT1 gene. The combination of the intron insertion and the mosaicism in the mother was transferred to the child, resulting in the pathogenesis of the disease.In the past, research showed that the austerity of the disease was directly proportional to the number of EHMT1 deletions prevalent in an individual. The greater the deletions, the greater the severity of the condition. However, in recent studies, 9q34 deletion syndrome occurs when the EHMT1 gene is non-functioning, as opposed to strictly deletion. Diagnosis Tests are either conducted at birth, or later in early childhood via: fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA), array comparative genomic hybridization (aCGH), and EHMT1 sequencing.FISH is a screening test that uses multicolour probes or comparative genomic hybridization to find any chromosome irregularities in a genome. It can be used for gene mapping, detecting aneuploidy, locating tumours etc. The multicolour probes attach to a certain DNA fragment. MLPA is a test that finds and records DNA copy change numbers through the use of PCR. MLPA can be used to detect tumours in the glial cells of the brain, as well as chromosomal abnormalities. Array-based comparative genomic hybridization (aCGH) tracks chromosome deletions and or amplifications using fluorescent dyes on genomic sequences of DNA samples. The DNA samples (which are 25-80 base pairs in length) are then placed on slides to be observed under microscope. Lastly, EHMT1 sequencing is a process in which a single-strand of DNA from the EHMT1 gene is removed, and DNA polymerase is added in order to synthesize complementary strands. In turn, this allows scientists to map out a persons DNA sequence allowing for a diagnosis to be made. Treatment Individual manifestations are treated by a multidisciplinary team. Epidemiology Kleefstra syndrome affects males and females equally and approximately 75% of all documented cases are caused by Eu-HMTase1 disruptions while only 25% are caused by 9q34.3 deletions. There are no statistics on the effect the disease has on life expectancy due to the lack of information available. History Kleefstra syndrome is a new condition that has only been known about for a few years and there have been fewer than 200 cases, reported. Due to the lack of cases worldwide, the history behind the origination is unclear. Research A study published by the American Journal of Human Genetics performed an EHMT1 mutation analysis on 23 patients that showed symptoms of 9q34 deletion syndrome. The patients all varied in age. With respect to all the analyses, however, the clinical data focused on five patients, the majority being children. The first patient developed epilepsy early on in childhood, and had speech problems past age 8. He had hypoplasia and had prominent facial features, such as lips and mouth. The second patient had no trace of mitral regurgitation (MR) in her family history, but had slight hypotonia. Patient three was the oldest at 36 who began to walk at age 3. She later gained weight at eleven and developed epilepsy in her late twenties. The fourth patient had problems associated with eating as a young child and was diagnosed with slowed development. Patient five had behavioural issues and struggled with MR in addition to being overweight. The geneticists discovered three new mutations within the EHMT1 gene. The first was an interstitial deletion, while the second and third were a nonsense and frameshift. Their findings supported the notion that a disruption in the EHMT1 gene contributes to the pathogenesis of Kleefstra syndrome.In another study published by the Journal of Medical Genetics, DNA from forty patients were extracted and subjected to MLPA, FISH or EHMT1 sequencing. The forty patients were divided into two groups: 1 group of 16 patients with the 9q34 deletion, and 1 group of 24 with typical FISH/MPLA results. The geneticists examined how a missense mutation would affect the function of the DNA by looking at DNA models. After, they screened each persons DNA using one of three tests, the results for the first group showed six patients had the same deletion of the same size (700 kb). In the second group, after EHMT1 sequencing was performed, six intragenic mutations were discovered. The scientists investigating this experiment conclude these mutations may be infective agents for the disease. Lastly, the patients behavioural, physical, and psychiatric symptoms are included on the data chart. References External links The Genetics Home Reference website
Nonpuerperal mastitis	The term nonpuerperal mastitis describes inflammatory lesions of the breast (mastitis) that occur unrelated to pregnancy and breastfeeding. It is sometimes equated with duct ectasia, but other forms can be described. Types Duct ectasia—periductal mastitis complex Duct ectasia in the literal sense (literally: duct widening) is a very common and thus rather unspecific finding, increasing with age. However, in the way in which the term is mostly used, duct ectasia is an inflammatory condition of the larger-order lactiferous ducts. It is considered likely that the condition is associated with aseptic (chemical) inflammation related to the rupture of ducts or cysts. It is controversial whether duct dilation occurs first and leads to secretory stasis and subsequent periductal inflammation or whether inflammation occurs first and leads to an inflammatory weakening of the duct walls and then stasis. When the inflammation is complicated by necrosis and secondary bacterial infection, breast abscesses may form. Subareolar abscess, also called Zuskas disease (only nonpuerperal case), is a frequently aseptic inflammation and has been associated with squamous metaplasia of the lactiferous ducts. The duct ectasia—periductal mastitis complex affects two groups of women: young women (in their late teens and early 20s) and perimenopausal women. Women in the younger group mostly have inverted nipples due to squamous metaplasia that lines the ducts more extensively compared to other women and produces keratin plugs which in turn lead to duct obstruction and then duct dilation, secretory stasis, inflammation, infection and abscess. This is not typically the case for women in the older group; in this group, there is likely a multifactorial etiology involving the balance in estrogen, progesterone and prolactin.Treatment of mastitis and/or abscess in nonlactating women is largely the same as that of lactational mastitis, generally involving antibiotics treatment, possibly surgical intervention by means of fine-needle aspiration and/or incision and drainage and/or interventions on the lactiferous ducts (for details, see also the articles on treatment of mastitis, of breast abscess and of subareolar abscess). Additionally, an investigation for possible malignancy is needed, normally by means of mammography, and a pathological investigation such as a biopsy may be necessary to exclude malignant mastitis. Although no causal relation with breast cancer has been established, there appears to be an increased statistical risk of breast cancer, warranting a long-term surveillance of patients diagnosed with non-puerperal mastitis.Nonpuerperal breast abscesses have a higher rate of recurrence compared to puerperal breast abscesses. There is a high statistical correlation of nonpuerperal breast abscess with diabetes mellitus (DM). On this basis, it has recently been suggested that diabetes screening should be performed on patients with such abscesses. Granulomatous mastitis Characteristic for granulomatous mastitis are multinucleated giant cells and epithelioid histiocytes around lobules. Often minor ductal and periductal inflammation is present. The lesion is in some cases very difficult to distinguish from breast cancer. Comedo mastitis Comedo mastitis is a very rare form similar to granulomatous mastitis but with tissue necrosis. Because it is so rare it may be sometimes confused with comedo carcinoma of the breast although the conditions appear to be completely unrelated. == References ==
Juvenile hemochromatosis	Juvenile hemochromatosis, also known as hemochromatosis type 2, is a rare form of hereditary hemochromatosis, which emerges in young individuals, typically between 15 and 30 years of age, but occasionally later. It is characterized by an inability to control how much iron is absorbed by the body, in turn leading to iron overload, where excess iron accumulates in many areas of the body and causes damage to the places it accumulates.It is a genetic disorder that can be caused by mutations in either the HJV (also called HFE2) or HAMP genes, and is inherited in an autosomal recessive fashion. Depending on which of these genes is affected, the disease can be further subdivided into types 2A and 2B. Signs and Symptoms The most common symptoms of juvenile hemochromatosis are as follows: Weakness Lethargy Hyperpigmentation (darkening of the skin) Arthropathy (joint disease) Diabetes Heart disease (dilated cardiomyopathy). Complications of heart disease are the main cause of death in those with untreated hemochromatosis. Hypogonadism (reduced activity of the genitals), which may result in decreased libido and infertility Amenorrhea in females Erectile dysfunction in males Loss of appetite Increased risk of infection by certain bacteria including V. vulnificus.Other common complications include: Congenital hepatic fibrosisLess common symptoms and complications include: Osteoporosis Hepatomegaly (liver enlargement) Liver cirrhosis Cardiac arrhythmias Hypothyroidism Adrenocortical insufficiency Genetics Juvenile hemochromatosis can be caused by inheriting two mutated copies (alleles), one from each parent, of the genes for the proteins hemojuvelin (HFE2/HJV) or hepcidin (HAMP), and the disease can be subdivided into hemochromatosis types 2A and 2B according to which gene/protein is affected. Type 2A is caused by inheriting two mutated alleles, one from each parent, for the HJV (aka HFE2) gene, which encodes the protein hemojuvelin. Hemojuvelin is responsible for the maintaining correct levels of the protein hepcidin, which regulates iron absorption in the blood. Without functional hemojuvelin, hepcidin levels are reduced, and the amount of iron absorbed into the blood during digestion is unable to be halted. Type 2B is caused by inheriting two mutated alleles, one from each parent, for the HAMP gene, which encodes the protein hepcidin. Hepcidin is responsible for regulating absorption of iron from the small intestine to the blood during the digestion of food, such to prevent blood iron levels from becoming too high. A lack of functional hepcidin prevents the body from stopping iron absorption when it has already reached adequate levels.Type 2A is the most common form, accounting for roughly 9 out of every 10 cases of the disease. Diagnosis An individual may be suspected to have this condition based on their medical history, physical exam findings, and blood tests, and confirmation of the diagnosis can be made with further testing, often with use of gene panels. Differential Diagnosis Juvenile hemochromatosis shares signs and symptoms with many other conditions including: Other types of hereditary hemochromatosis Atransferrinemia Aceruloplasminemia African iron overload Neonatal hemochromatosis Transfusional iron overload and other forms of secondary hemochromatosis Porphyria cutanea tarda Blood Testing The presence of hemochromatosis may be discovered incidentally on blood testing, or a diagnosis suspected based on symptoms may be supported or ruled out by blood testing. Elevated serum ferritin, an indicator of blood iron levels, and transferrin saturation, which is involved with absorption of iron from the gut, are very common. Transferrin saturation may approach or reach 100%, where a normal value would lie between 16% and 45%. If transferrin saturation is normal, juvenile hemochromatosis can be ruled out. Serum ferritin may only be slightly elevated as the disease progresses, however may quickly reach in excess of 1000ng/mL. Genetic Testing In patients suspected to have juvenile hemochromatosis, the diagnosis can be confirmed through genetic testing for specific genes: A single gene study may be considered in those that demonstrate iron overload at a very young age, and specifically looks for mutations in either the HJV (HFE2) or HAMP genes. As HJV is more commonly associated with the disease, this may be checked first, and if no alterations are found, HAMP may be tested next. A multi-gene study may be considered to more effectively search for genetic causes of the patients symptoms, and can include HJV, HAMP, and other genes associated with similar conditions like HFE. Imaging MRI may be utilized in order to assess the extent to which iron has been deposited in certain tissues and organs, however does not have significant weight in the diagnosis of the condition. Biopsy Liver biopsy, or removal of a small piece of liver tissue for analysis, can be done to assess the extent of iron overload in the liver, however is considered not to have a significant weight in the diagnosis of the condition. Treatment Treatment for juvenile hemochromatosis is similar to that for other forms of hemochromatosis and iron overload, and focuses on reducing the amount of iron in the body in order to prevent complications of iron overload. However, if the disease is not discovered early enough, or if progress is not well controlled, further treatments may be aimed at the symptoms of organ damage which may develop. Phlebotomy Phlebotomy, the removal of blood from the body, is the main treatment for juvenile hemochromatosis. One unit of blood, the amount typically given during blood donation, is typically removed per session, and it is generally recommended that this be done once weekly until acceptable levels of iron are in the blood, which may take years. After these levels are reached, phlebotomy will be continued, but less often than once weekly, perhaps every few months. Chelation Therapy In the event that phlebotomy is not an appropriate option or is not enough on its own to reduce iron levels, chelation medications, those that bind and remove certain metals from the blood, may be utilized. Examples of chelators specifically for iron include deferoxamine and deferasirox. Dietary Modification It is recommended that those with juvenile hemochromatosis refrain from eating iron supplements, vitamin C supplements, and uncooked/undercooked seafood and shellfish, and reduce or eliminate consumption of alcoholic beverages and red meat. Additional Treatments If the disease is advanced enough, further treatments can be aimed at the complications of the disease, depending on which are present: Diabetes may be treated with oral medications and/or insulin as indicated. Heart failure may require followup with cardiology specialist, as well as medical treatment with certain medications including ACE inhibitors and diuretics. Hypogonadism may require treatment with hormone replacement therapy, which has also been shown to reduce the likelihood of developing osteoporosis later on. Liver cirrhosis may require beta blockers, a kind of antihypertensive medication. Joint pain, called arthralgias, can be treated with NSAIDs, a type of pain medication available over-the-counter. Epidemiology The incidence of juvenile hemochromatosis in the general population remains unknown at this time, however it is very rare. It more commonly occurs in those of European descent, becoming apparent during the first to third decades of life, and affects males and females at similar rates. References External links GeneReview/NIH/UW entry on Juvenile Hereditary Hemochromatosis
Cherry angioma	Cherry angioma, also called cherry hemangioma, is a small bright red dome-shaped bump on the skin. It ranges between 0.5 – 6 mm in diameter and usually several are present, typically on the chest and arms, and increasing in number with age. If scratched, they may bleed.They are a harmless benign tumour, containing an abnormal proliferation of blood vessels, and have no relationship to cancer. They are the most common kind of angioma, and increase with age, occurring in nearly all adults over 30 years. Campbell de Morgan is the nineteenth-century British surgeon who first described them. Signs and symptoms Cherry angiomas are made up of clusters of capillaries at the surface of the skin, forming a small round dome ("papule"), which may be flat topped. They range in colour from bright red to purple. When they first develop, they may be only a tenth of a millimeter in diameter and almost flat, appearing as small red dots. However, they then usually grow to about one or two millimeters across, and sometimes to a centimeter or more in diameter. As they grow larger, they tend to expand in thickness, and may take on the raised and rounded shape of a dome. Multiple adjoining angiomas form a polypoid angioma. Because the blood vessels comprising an angioma are so close to the skins surface, cherry angiomas may bleed profusely if they are injured.One study found that the majority of capillaries in cherry hemangiomas are fenestrated and stain for carbonic anhydrase activity. Cause Cherry angiomas appear spontaneously in many people in middle age but can also, less commonly, occur in young people. They can also occur in an aggressive eruptive manner in any age. The underlying cause for the development of cherry angiomas is not understood. Cherry angioma may occur through two different mechanisms: angiogenesis (the formation of new blood vessels from pre-existing vessels), and vasculogenesis (the formation of totally new vessels, which usually occurs during embryonic and fetal development).One study published in 2010 found that a regulatory nucleic acid suppresses protein growth factors that cause vascular growth. This regulatory nucleic acid was lower in tissue samples of hemangiomas, and the growth factors were elevated, which suggests that the elevated growth factors may cause hemangiomas. The study found that the level of microRNA 424 is significantly reduced in senile hemangiomas compared to normal skin resulting in increased protein expression of MEK1 and cyclin E1. By inhibiting mir-424 in normal endothelial cells they could observe the same increased protein expression of MEK1 and cyclin E1 which, important for the development of senile hemangioma, induced cell proliferation of the endothelial cells. They also found that targeting MEK1 and cyclin E1 with small interfering RNA decreased the number of endothelial cells. A study published in 2019 identified that somatic mutations in GNAQ and GNA11 genes are present in many cherry angiomas. These specific missense mutations found in hemangiomas are also associated with port-wine stains and uveal melanoma. Chemicals and compounds that have been seen to cause cherry angiomas are mustard gas, 2-butoxyethanol, bromides, and cyclosporine.A significant increase in the density of mast cells has been seen in cherry hemangiomas compared with normal skin. Diagnosis The diagnosis is based on the clinical appearance of the lesions. Examination with a dermatoscope shows characteristic red, purple, or blue-black lagoons. The differential diagnosis includes nodular basal cell carcinoma, amelanotic melanoma, and angiokeratoma. Treatment These lesions generally do not require treatment. If they are cosmetically unappealing or are subject to bleeding angiomas may be removed by electrocautery, a process of destroying the tissue by use of a small probe with an electric current running through it. Removal may cause scarring. More recently pulsed dye laser or intense pulsed light (IPL) treatment has also been used.Future treatment based on a locally acting inhibitor of MEK1 and Cyclin E1 could possibly be an option. A natural MEK1 inhibitor is myricetin. Prognosis In most patients, the number and size of cherry angiomas increases with advancing age. They are harmless, having no relation to cancer at all. Eruptive cherry hemangiomatosis, has been rarely reported as a heralding sign of multicentric Castleman disease (MCD), multiple myeloma and other lymphoproliferative diseases. Epidemiology Cherry angiomas occur in all races, ethnic backgrounds, and sexes. References External links eMedicine with picture showing small red dots Pereira, José Marcos (2004). "Hemangioma rubi no couro cabeludo". Anais Brasileiros de Dermatologia. 79: 83–89. doi:10.1590/S0365-05962004000100010.
Ectromelia	Ectromelia is a congenital condition where long bones are missing or underdeveloped. Examples include: Amelia Hemimelia Phocomelia Sirenomelia References == External links ==
Triplegia	Triplegia is a medical condition characterized by the paralysis of three limbs. While there is no typical pattern of involvement, it is usually associated with paralysis of both legs and one arm—but can also involve both arms and one leg. Triplegia can sometimes be considered a combination of hemiplegia (paralysis of arm and leg of one side of the body) overlaying diplegia (paralysis of both legs), or as quadriplegia (paralysis of four limbs) with less involvement in one extremity.The condition is commonly associated with cerebral palsy, although conditions such as strokes can also lead to it. Triplegia has also been found to be due to an increase in intracranial pressure associated with hydrocephalus resulting from traumatic brain injury.A similar condition is triparesis, in which a person has paresis in three limbs, meaning that the limbs are very weak, but not completely paralyzed. In a case reported only due to its rarity, triplegia was reported following a surgical removal of the tonsils. An eight-year-old boy was sent to Willard Parker Hospital on August 12, 1929, and had been diagnosed with poliomyelitis. After an unrelated, and routine, tonsillectomy there was complete flaccid paralysis and loss of feeling in both the legs, right arm, and muscles in the trunk. == References ==
Hypolipoproteinemia	Hypolipoproteinemia, hypolipidemia, or hypolipidaemia (British English) is a form of dyslipidemia that is defined by abnormally lowered levels of any or all lipids and/or lipoproteins in the blood. It occurs through genetic disease (namely, hypoalphalipoproteinemia and hypobetalipoproteinemia), malnutrition, malabsorption, wasting disease, cancer, hyperthyroidism, and liver disease. Causes Causes of hypolipidemia include: Hypobetalipoproteinemia (low levels of LDL cholesterol or apolipoprotein B) Malnutrition Malabsorption Wasting disease Certain cancers Hyperthyroidism (an overactive thyroid) Liver disease Diagnosis It can be diagnosed via blood study that identifies fat particles. The patient must fast overnight to prevent interference from fat in the blood due to food intake. The criteria for this (without the involvement of cholesterol-lowering drugs) are total cholesterol levels below 120 mg/dL and LDL cholesterol levels under 50 mg/dL. Critical illness In the setting of critical illness, low cholesterol levels are predictive of clinical deterioration, and are correlated with altered cytokine levels.In humans with genetic loss-of-function variants in one copy of the ANGPTL3 gene, the serum LDL-C levels are reduced. In those with loss-of-function variants in both copies of ANGPTL3, low LDL-C, low HDL-C, and low triglycerides are seen ("familial combined hypolipidemia").Hooft disease is a rare condition evidenced by low blood lipid level, red rash and mental and physical retardation. Treatment Vitamin E supplements have shown to help children with the deficiency. See also Hypercholesterolemia Primary hyperlipoproteinemia ANGPTL3 References == External links ==
Cervicocranial syndrome	Cervicocranial syndrome or (Craniocervical Junction Syndrome: CCJ syndrome) is a neurological illness. It is a combination of symptoms that are caused by an abnormality in the neck. The bones of the neck that are affected are cervical vertebrae (C1 - C7). This syndrome can be identified by confirming cervical bone shifts, collapsed cervical bones or misalignment of the cervical bone leading to improper functioning of cervical spinal nerves.[1] Cervicocranial syndrome is either congenital or acquired (as a result of injury or disease). Some examples of diseases that could result in cervicocranial syndrome are Chiari disease, Klippel-Feil malformation osteoarthritis, and trauma. Treatment options include neck braces, pain medication and surgery. The quality of life for individuals suffering from CCJ syndrome can improve through surgery. Signs and Symptoms Cervicocranial syndrome has a wide range of symptoms. These symptoms often include: Vertigo Chronic Headache aka Cephalea Tinnitus Facial Pain Ear Pain Dysphagia Carotidynia Neck Pain (ex: during movement such extension and flexion) Syncope Sinus congestion Neck Crepitus Sound Loss of vision Involuntary eye-movement Severe Fatigue Chest Pain Brain Fog Cause The cause of cervicocranial syndrome is either due to a defect (genetic mutation or development of diseases later in life) or an injury pertaining to the neck: cervical area, that damages the spinal nerves traveling through the cervical region resulting in ventral subluxation. Examples of cases that can result in cervicocranial syndrome are: car accidents, trauma, osteoarthritis, tumor, degenerative pathology and other numerous causes of vertebral instability. There is no single cause that can mainly cause cervicocranial syndrome. Genetic The genes GDF6, GDF3, MEOX1 used as examples, encode for making proteins that help with development. For example GDF6 gene plays an important role in bone development and joint formation. The mutation in these genes can result in Klippel-Feil syndrome. As a result of having congenital Klippel-Feil syndrome, the spinal anatomy of the individual will present abnormal fusion of any two of the seven cervical bones in the neck. This is considered to be an anomaly of cervical bones. It affects the functioning of cervical spinal nerves (C1 - C8) because of compression on the spinal cord. Spinal stenosis also adds damage to the spinal cord resulting in symptoms that are caused by cervicocranial syndrome. Trauma Traumatic injuries are caused when external forces damage the cervical spine, giving rise to various symptoms. In a motor vehicle accident, the vehicle jerks the neck forward and backward resulting in cervical spine damage. This is called whiplash. The neurological and biological symptoms resulting from neck trauma emerge as a culmination of clinically isolated or combined symptoms caused by cervicocranial syndrome. Pathophysiology The body is innervated by spinal nerves that branch off from the spinal cord. This innervation enables the brain to receive sensory inputs and send motor outputs. There are 8 cervical spinal nerves of the peripheral nervous system. Cervical spinal nerves C1, C2 and C3 help control the movements of the head and neck. Cervical spinal nerve C4 helps control upward shoulder movements. Cervical spinal nerve C3, C4 and C5 help power the diaphragm and aid in breathing. Cervical spinal nerve C6 helps in wrist extension and some functioning of biceps. Cervical spinal nerve C7 controls triceps and wrist extension. Cervical spinal nerve C8 helps control the hand. The cervicocranial syndrome occurs when symptoms arise due to cervical vertebrae damage (misalignment, collapse, shift or disease, such as tumor) resulting in the improper functioning of the cervical spinal nerves. Examples of Cervicocranial Syndrome Pathophysiology Chordoma The craniocervical junction region comprises C1 (Atlas), C2 (Axis) and the lower part of the skull: occipital bone. In case of tumor: chordoma, in the craniocervical junction region, this leads to pressure on the cervical spinal nerves, which results in their improper functioning of the cervical spinal nerves. Hence, leading to symptoms of cervicocranial syndrome. To decompress the pressure on the nerves, the tumor is removed and the foramen through which the spinal nerve roots travel through is enlarged to allow the nerves to pass through so that symptoms of cervicocranial syndrome can be reduced and the nerves are sending signals. Atlanto-Occipital Assimilation When the occipital bone and the atlas (C1) are fused together in a condition called atlanto-occipital assimilation, it causes improper functioning of the cervical spinal nerves due to the vascular compression. Surgical procedure can decompress the nerves and reduce symptoms. Trauma Traumatic injuries are caused when external forces damage the cervical spine, giving rise to various symptoms. In a car accident, the vehicle jerks the neck forward and backward resulting in cervical spine damage resulting in a whiplash. As a result, the cervical spine become misaligned and produces direct spinal cord irritation creating tighter muscles on one side of the body Neck braces can help temporarily. Surgery is required if needed. Non-surgical treatment, to realign spinal misalignment, is corrected by a chiropractor. Diagnosis Once there is an onset of the symptoms in the patient, the patients are screened through cervical-spinal imaging techniques: X-ray, CT, MRI. [2] The scanning technique points out any cervical vertebrae defects and misalignments. (Image 1. and 2.) When cervicocranial syndrome is caused as a result of a genetic disease, then family history and genetic testing aid in making an accurate diagnosis of cervicocranial syndrome. Prevention/Treatment The treatment options vary since there are numerous causes of cervicocranial syndrome. General treatments include: Pressure release via realignment of the vertebrae Pain medication: acetominophen, aspirin, or ibuprofen Manipulation of neck by Chiropractor : For example, vertigo symptoms can be relieved Neck braces to avoid movement of neck and provide stability Physical therapy Injection: Combination (anesthetic and cortisone) drug to help alleviate the pain Surgery to restore function and form of the spine Cervical spinal cord stimulation (cSCS) When cervicocranical syndrome is caused by a mutation in genes and it runs in the family due to other co-morbidities, genetic counseling helps patients cover risks, prevention and expectations of caring and passing genes to a newborn. Prognosis The prognosis of an individual living with cervicocranial syndrome varies because of the multiple causes such as co-morbidities and varied trauma. Instability of the cervical spine can cause endangerment of patients and their neurological integrity. Correction and decompression cervical spinal surgeries significantly increase quality of life and reduce symptoms. Post-surgery, 93 to 100 percent patients report reduced cervicocranical syndrome symptoms such as neck pain. Epidemiology Cervicocranial syndrome significantly affects the aging world population and is associated with significant morbidity. It affects men and women equally when occurring due to atlanto-occipital assimilation. Increased incidences among low-socioeconomic groups and among groups that do not have access to healthcare show subsequently higher rates of morbidity and mortality. Research Directions Cervicocranial syndrome can be caused with or as a result of numerous neurological problems so not one single disease can be pinpointed. Further research can explore the common neurological problems causing cervicocranial syndrome and look at various treatments including therapeutic ones. For example, a study, "The influence of cranio-cervical rehabilitation in patients with myofascial temporomandibular pain disorders," explored the therapeutic options of physical therapy and concluded that 88% from a total of 98 patients (79 female and 19 male), felt reduced pain. On the contrary another study, "The efficacy of manual therapy and therapeutic exercise in patients with chronic neck pain: A narrative review" conducted in 2018, concluded that there is a lack of evidence that support therapeutic exercise to reduce neck pain via manipulation. References == External links ==
Idiopathic pure sudomotor failure	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. Epidemiology The overwhelming majority of reported AIGA patients are Japanese, but whether AIGA is truly rare in whites or has been simply underreported by Western physicians remains unclear.AIGA is most prevalent among young men. In a 64 case review of the literature 58 reported cases were males and 6 female, with a mean age of onset at 28 ± 11 years. Cholinergic urticaria or sharp pain over the entire body induced by elevated body temperature was reported in 32 cases (50%). Of 28 cases tested, 12 (43%) displayed elevated serum IgE levels. Skin biopsy was performed in 53 cases, with normal findings in 20 cases (38%), and cellular infiltrates in sweat glands or ducts in 23 cases (43%). See also Hypohidrosis References == External links ==
Glomeruloid hemangioma	Glomeruloid hemangioma is a distinctive vascular tumor first described in 1990 when found to be associated with POEMS syndrome and Castleman disease.: 595 See also List of cutaneous conditions == References ==
Ludwigs angina	Ludwigs angina (lat.: Angina ludovici) is a type of severe cellulitis involving the floor of the mouth and is often caused by bacterial sources. Early in the infection, floor of the mouth raises due to swelling, leading to difficulty swallowing saliva. As a result, patients may present with difficulty speaking and drooling. As the condition worsens, the airway may be compromised and hardening of the spaces on both sides of the tongue may develop. Overall, this condition has a rapid onset over a few hours. The majority of cases follow a dental infection. Other causes include a parapharyngeal abscess, mandibular fracture, cut or piercing inside the mouth, or submandibular salivary stones. The infection spreads through the connective tissue of the floor of the mouth and is normally caused by infectious and invasive organisms such as Streptococcus, Staphylococcus, and Bacteroides.Prevention is by appropriate dental care including management of dental infections. Initial treatment is generally with broad-spectrum antibiotics and corticosteroids. In more advanced cases endotracheal intubation or tracheostomy may be required.With the advent of antibiotics in 1940s, improved oral and dental hygiene, and more aggressive surgical approaches for treatment, the risk of death due to Ludwigs angina has significantly reduced. It is named after a German physician, Wilhelm Frederick von Ludwig, who first described this condition in 1836. Signs and symptoms Ludwigs angina is a form of severe, widespread cellulitis of the floor of the mouth, usually with bilateral involvement. Infection is usually primarily within the submandibular space, and the sublingual and submental spaces can also be involved. It presents with an acute onset and spreads very rapidly, therefor early diagnosis and immediate treatment planning is vital and lifesaving. The external signs may include bilateral lower facial swelling around the jaw and upper neck. Signs inside the mouth may include elevation of the floor of mouth due to sublingual space involvement and posterior displacement of the tongue, creating the potential for a compromised airway. Additional symptoms may include painful neck swelling, drooling, tooth pain, dysphagia, shortness of breath, fever, and general malaise. Stridor, trismus, and cyanosis may also be seen when an impending airway crisis is nearing. Causes The most prevalent cause of Ludwigs angina is dental related, accounting for approximately 75% to 90% of cases. Infections of the lower second and third molars are usually implicated due to their roots extending below the mylohyoid muscle. Periapical abscesses of these teeth also result in lingual cortical penetration, leading to submandibular infection.Other causes such as oral ulcerations, infections secondary to oral malignancy, mandible fractures, sialolithiasis-related submandibular gland infections, and penetrating injuries of the mouth floor have also been documented as potential causes of Ludwigs angina. Patients with systemic illness, such as diabetes mellitus, malnutrition, compromised immune system, and organ transplantation are also commonly predisposed to Ludwigs angina. A review reporting the incidence of illnesses associated with Ludwig angina found that 18% of cases involved diabetes mellitus, 9% involved acquired immune deficiency syndrome, and another 5% were human immunodeficiency virus (HIV) positive. Diagnosis Infections originating in the roots of teeth can be identified with a dental X-ray. A CT scan of the neck with contrast material is used to identify deep neck space infections. If there is suspicion of the infection of the chest cavity, a chest scan is sometimes done.Angioneurotic oedema, lingual carcinoma and sublingual hematoma formation following anticoagulation should be ruled out as possible diagnoses. Microbiology There are a few methods that can be used for determining the microbiology of Ludwigs angina. Traditionally, a culture sample is collected although it has some limitations, primarily being the time-consuming and sometimes unreliable results if the culture is not processed correctly. Ludwigs angina is most often found to be polymicrobial and anaerobic. Some of the commonly found microbes are Viridans Streptococci, Staphylococci, Peptostreptococci, Prevotella, Porphyromonas and Fusobacterium. Treatment For each patient, the treatment plan should be consider the patients stage of infection, airway control, and comorbidities. Other things to consider include physician experience, available resources, and personnel are critical factors in formulation of a treatment plan. There are four principles that guide the treatment of Ludwigs Angina: Sufficient airway management, early and aggressive antibiotic therapy, incision and drainage for any who fail medical management or form localized abscesses, and adequate nutrition and hydration support. Airway management Airway management has been found to be the most important factor in treating patients with Ludwigs Angina, i.e. it is the “primary therapeutic concern”. Airway compromise is known to be the leading cause of death from Ludwigs Angina. The basic method to achieve this is to allow the patient to sit in an upright position with supplemental oxygen provided by masks or nasal prongs. Patients airway can rapidly deteriorate and therefor close observation and preparation for more invasive methods such as endotracheal intubation or tracheostomy if needed is vital. If the oxygen saturation levels are adequate and antimicrobials have been given, simple airway observation can be done. This is a suitable method to adopt in the management of children, as a retrospective study described that only 10% of children required airway control. However, a tracheostomy was performed on 52% of those affected with Ludwigs Angina over 15 years old. If more invasive or surgical airway control is necessary, there are multiple things to considerFlexible nasotracheal intubation require skills and experience. If nasotracheal intubation is not possible, cricothyrotomy and tracheostomy under local anaesthetic can be done. This procedure is carried out on patients with advanced stage of Ludwigs Angina. Endotracheal intubation has been found to be in association with high failure rate with acute deterioration in respiratory status. Elective tracheostomy is described as a safer and more logical method of airway management in patients with fully developed Ludwigs Angina. Fibre-optic nasoendoscopy can also be used, especially for patients with floor of mouth swellings. Antibiotics Antibiotic therapy is empirical, it is given until culture and sensitivity results are obtained. The empirical therapy should be effective against both aerobic and anaerobic bacteria species commonly involved in Ludwigs Angina. Only when culture and sensitivity results return should therapy be tailored to the specific requirements of the patient.Empirical coverage should consist of either a penicillin with a B-lactamase inhibitor such as amoxicillin/ticarcillin with clavulanic acid or a Beta-lactamase resistant antibiotic such as cefoxitin, cefuroxime, imipenem or meropenem. This should be given in combination with a drug effective against anaerobes such as clindamycin or metronidazole. Parenteral antibiotics are suggested until the patient is no longer febrile for at least 48 hours. Oral therapy can then commence to last for 2 weeks, with amoxicillin with clavulanic acid, clindamycin, ciprofloxacin, trimethoprim-sulfamethoxazole, or metronidazole. Incision and drainage Surgical incision and drainage are the main methods in managing severe and complicated deep neck infections that fail to respond to medical management within 48 hours. It is indicated in cases of:Airway compromise Septicaemia Deteriorating condition Descending infection Diabetes mellitus Palpable or radiographic evidence of abscess formation Bilateral submandibular incisions should be carried out in addition to a midline submental incision. Access to the supramylohyoid spaces can be gained by blunt dissection through the mylohyoid muscle from below. Penrose drains are recommended in both supramylohyoid and inframylohyoid spaces bilaterally. In addition, through and through drains from the submandibular space to the submental space on both sides should be placed as well. The incision and drainage process is completed with the debridement of necrotic tissue and thorough irrigation. It is necessary to mark drains in order to identify their location. They should be sutured with loops as well so it will be possible to advance them without re-anaesthetizing the patient while drains are re-sutured to the skin. An absorbent dressing is then applied. A bandnet dressing retainer can be constructed so as to prevent the use of tape. Other things to consider Nutritional support Adequate nutrition and hydration support is essential in any patient following surgery, particularly young children. In this case, pain and swelling in the neck region would usually cause difficulties in eating or swallowing, hence reducing patients food and fluid intake. Patients must therefore be well-nourished and hydrated to promote wound healing and to fight off infection. Post-operative care Extubation, which is the removal of endotracheal tube to liberate the patient from mechanical ventilation, should only be done when the patients airway is proved to be patent, allowing adequate breathing. This is indicated by a decrease in swelling and patients capability of breathing adequately around an uncuffed endotracheal tube with the lumen blocked.During the hospital stay, patients condition will be closely monitored by: carrying out cultures and sensitivity tests to decide if any changes need to be made to patients antibiotic course observing for signs of further infection or sepsis including fevers, hypotension, and tachycardia monitoring patients white blood cell count - a decrease implies effective and sufficient drainage repeating CT scans to prove patients restored health status or if infection extends, the anatomical areas that are affected. Etymology The term “angina”, is derived from the Latin word “angere”, which means “choke”; and the Greek word “ankhone”, which means “strangle”. Placing it into context, Ludwigs angina refers to the feeling of strangling and choking, secondary to obstruction of the airway, which is the most serious potential complication of this condition. See also Anticor References == External links ==
Omphalitis of newborn	Omphalitis of newborn is the medical term for inflammation of the umbilical cord stump in the neonatal newborn period, most commonly attributed to a bacterial infection. Typically immediately after an infant is born, the umbilical cord is cut with a small remnant (often referred to as the stump) left behind. Normally the stump separates from the skin within 3–45 days after birth. A small amount of pus-like material is commonly seen at the base of the stump and can be controlled by keeping the stump open to air to dry. Certain bacteria can grow and infect the stump during this process and as a result significant redness and swelling may develop, and in some cases the infection can then spread through the umbilical vessels to the rest of the body. While currently an uncommon anatomical location for infection in the newborn in the United States, it has caused significant morbidity and mortality both historically and in areas where health care is less readily available. In general, when this type of infection is suspected or diagnosed, antibiotic treatment is given, and in cases of serious complications surgical management may be appropriate. Signs and symptoms Clinically, neonates with omphalitis present within the first two weeks of life with signs and symptoms of a skin infection (cellulitis) around the umbilical stump (redness, warmth, swelling, pain), pus from the umbilical stump, fever, fast heart rate (tachycardia), low blood pressure (hypotension), somnolence, poor feeding, and yellow skin (jaundice). Omphalitis can quickly progress to sepsis and presents a potentially life-threatening infection. In fact, even in cases of omphalitis without evidence of more serious infection such as necrotizing fasciitis, mortality is high (in the 10% range). Causes Omphalitis is most commonly caused by bacteria. The culprits usually are Staphylococcus aureus, Streptococcus, and Escherichia coli. The infection is typically caused by a combination of these organisms and is a mixed Gram-positive and Gram-negative infection. Anaerobic bacteria can also be involved. Diagnosis In a normal umbilical stump, you first see the umbilicus lose its characteristic bluish-white, moist appearance and become dry and black After several days to weeks, the stump should fall off and leave a pink fleshy wound which continues to heal as it becomes a normal umbilicus.For an infected umbilical stump, diagnosis is usually made by the clinical appearance of the umbilical cord stump and the findings on history and physical examination. There may be some confusion, however, if a well-appearing neonate simply has some redness around the umbilical stump. In fact, a mild degree is common, as is some bleeding at the stump site with detachment of the umbilical cord. The picture may be clouded even further if caustic agents have been used to clean the stump or if silver nitrate has been used to cauterize granulomata of the umbilical stump. Prevention During the 1950s there were outbreaks of omphalitis that then led to anti-bacterial treatment of the umbilical cord stump as the new standard of care. It was later determined that in developed countries keeping the cord dry is sufficient, (known as "dry cord care") as recommended by the American Academy of Pediatrics. The umbilical cord dries more quickly and separates more readily when exposed to air However, each hospital/birthing center has its own recommendations for care of the umbilical cord after delivery. Some recommend not using any medicinal washes on the cord. Other popular recommendations include triple dye, betadine, bacitracin, or silver sulfadiazine. With regards to the medicinal treatments, there is little data to support any one treatment (or lack thereof) over another. However one recent review of many studies supported the use of chlorhexidine treatment as a way to reduce risk of death by 23% and risk of omphalitis by anywhere between 27 and 56% in community settings in underdeveloped countries. This study also found that this treatment increased the time that it would take for the umbilical stump to separate or fall off by 1.7 days. Lastly this large review also supported the notion that in hospital settings no medicinal type of cord care treatment was better at reducing infections compared to dry cord care. Treatment Treatment consists of antibiotic therapy aimed at the typical bacterial pathogens in addition to supportive care for any complications which might result from the infection itself such as hypotension or respiratory failure. A typical regimen will include intravenous antibiotics such as from the penicillin-group which is active against Staphylococcus aureus and an aminoglycoside for activity against Gram-negative bacteria. For particularly invasive infections, antibiotics to cover anaerobic bacteria may be added (such as metronidazole). Treatment is typically for two weeks and often necessitates insertion of a central venous catheter or peripherally inserted central catheter. Epidemiology The current incidence in the United States is somewhere around 0.5% per year; overall, the incidence rate for developed world falls between 0.2 and 0.7%. In developing countries, the incidence of omphalitis varies from 2 to 7 for 100 live births. There does not appear to be any racial or ethnic predilection. Like many bacterial infections, omphalitis is more common in those patients who have a weakened or deficient immune system or who are hospitalized and subject to invasive procedures. Therefore, infants who are premature, sick with other infections such as blood infection (sepsis) or pneumonia, or who have immune deficiencies are at greater risk. Infants with normal immune systems are at risk if they have had a prolonged birth, birth complicated by infection of the placenta (chorioamnionitis), or have had umbilical catheters. References == External links ==
Tuberculosis	Tuberculosis (TB) is an infectious disease usually caused by Mycobacterium tuberculosis (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in which case it is known as latent tuberculosis. Around 10% of latent infections progress to active disease which, if left untreated, kill about half of those affected. Typical symptoms of active TB are chronic cough with blood-containing mucus, fever, night sweats, and weight loss. It was historically referred to as consumption due to the weight loss associated with the disease. Infection of other organs can cause a wide range of symptoms.Tuberculosis is spread from one person to the next through the air when people who have active TB in their lungs cough, spit, speak, or sneeze. People with Latent TB do not spread the disease. Active infection occurs more often in people with HIV/AIDS and in those who smoke. Diagnosis of active TB is based on chest X-rays, as well as microscopic examination and culture of body fluids. Diagnosis of Latent TB relies on the tuberculin skin test (TST) or blood tests.Prevention of TB involves screening those at high risk, early detection and treatment of cases, and vaccination with the bacillus Calmette-Guérin (BCG) vaccine. Those at high risk include household, workplace, and social contacts of people with active TB. Treatment requires the use of multiple antibiotics over a long period of time. Antibiotic resistance is a growing problem with increasing rates of multiple drug-resistant tuberculosis (MDR-TB).In 2018, one quarter of the worlds population was thought to have a latent infection of TB. New infections occur in about 1% of the population each year. In 2020, an estimated 10 million people developed active TB, resulting in 1.5 million deaths, making it the second leading cause of death from an infectious disease after COVID-19. As of 2018, most TB cases occurred in the regions of South-East Asia (44%), Africa (24%), and the Western Pacific (18%), with more than 50% of cases being diagnosed in seven countries: India (27%), China (9%), Indonesia (8%), the Philippines (6%), Pakistan (6%), Nigeria (4%), and Bangladesh (4%). By 2021 the number of new cases each year was decreasing by around 2% annually. About 80% of people in many Asian and African countries test positive while 5–10% of people in the United States population test positive via the tuberculin test. Tuberculosis has been present in humans since ancient times. Signs and symptoms Tuberculosis may infect any part of the body, but most commonly occurs in the lungs (known as pulmonary tuberculosis). Extrapulmonary TB occurs when tuberculosis develops outside of the lungs, although extrapulmonary TB may coexist with pulmonary TB.General signs and symptoms include fever, chills, night sweats, loss of appetite, weight loss, and fatigue. Significant nail clubbing may also occur. Pulmonary If a tuberculosis infection does become active, it most commonly involves the lungs (in about 90% of cases). Symptoms may include chest pain and a prolonged cough producing sputum. About 25% of people may not have any symptoms (i.e. they remain asymptomatic). Occasionally, people may cough up blood in small amounts, and in very rare cases, the infection may erode into the pulmonary artery or a Rasmussens aneurysm, resulting in massive bleeding. Tuberculosis may become a chronic illness and cause extensive scarring in the upper lobes of the lungs. The upper lung lobes are more frequently affected by tuberculosis than the lower ones. The reason for this difference is not clear. It may be due to either better air flow, or poor lymph drainage within the upper lungs. Extrapulmonary In 15–20% of active cases, the infection spreads outside the lungs, causing other kinds of TB. These are collectively denoted as extrapulmonary tuberculosis. Extrapulmonary TB occurs more commonly in people with a weakened immune system and young children. In those with HIV, this occurs in more than 50% of cases. Notable extrapulmonary infection sites include the pleura (in tuberculous pleurisy), the central nervous system (in tuberculous meningitis), the lymphatic system (in scrofula of the neck), the genitourinary system (in urogenital tuberculosis), and the bones and joints (in Pott disease of the spine), among others. A potentially more serious, widespread form of TB is called "disseminated tuberculosis", it is also known as miliary tuberculosis. Miliary TB currently makes up about 10% of extrapulmonary cases. Causes Mycobacteria The main cause of TB is Mycobacterium tuberculosis (MTB), a small, aerobic, nonmotile bacillus. The high lipid content of this pathogen accounts for many of its unique clinical characteristics. It divides every 16 to 20 hours, which is an extremely slow rate compared with other bacteria, which usually divide in less than an hour. Mycobacteria have an outer membrane lipid bilayer. If a Gram stain is performed, MTB either stains very weakly "Gram-positive" or does not retain dye as a result of the high lipid and mycolic acid content of its cell wall. MTB can withstand weak disinfectants and survive in a dry state for weeks. In nature, the bacterium can grow only within the cells of a host organism, but M. tuberculosis can be cultured in the laboratory.Using histological stains on expectorated samples from phlegm (also called sputum), scientists can identify MTB under a microscope. Since MTB retains certain stains even after being treated with acidic solution, it is classified as an acid-fast bacillus. The most common acid-fast staining techniques are the Ziehl–Neelsen stain and the Kinyoun stain, which dye acid-fast bacilli a bright red that stands out against a blue background. Auramine-rhodamine staining and fluorescence microscopy are also used. The M. tuberculosis complex (MTBC) includes four other TB-causing mycobacteria: M. bovis, M. africanum, M. canetti, and M. microti. M. africanum is not widespread, but it is a significant cause of tuberculosis in parts of Africa. M. bovis was once a common cause of tuberculosis, but the introduction of pasteurized milk has almost eliminated this as a public health problem in developed countries. M. canetti is rare and seems to be limited to the Horn of Africa, although a few cases have been seen in African emigrants. M. microti is also rare and is seen almost only in immunodeficient people, although its prevalence may be significantly underestimated. Other known pathogenic mycobacteria include M. leprae, M. avium, and M. kansasii. The latter two species are classified as "nontuberculous mycobacteria" (NTM) or atypical mycobacteria. NTM cause neither TB nor leprosy, but they do cause lung diseases that resemble TB. Transmission When people with active pulmonary TB cough, sneeze, speak, sing, or spit, they expel infectious aerosol droplets 0.5 to 5.0 µm in diameter. A single sneeze can release up to 40,000 droplets. Each one of these droplets may transmit the disease, since the infectious dose of tuberculosis is very small (the inhalation of fewer than 10 bacteria may cause an infection). Risk of transmission People with prolonged, frequent, or close contact with people with TB are at particularly high risk of becoming infected, with an estimated 22% infection rate. A person with active but untreated tuberculosis may infect 10–15 (or more) other people per year. Transmission should occur from only people with active TB – those with latent infection are not thought to be contagious. The probability of transmission from one person to another depends upon several factors, including the number of infectious droplets expelled by the carrier, the effectiveness of ventilation, the duration of exposure, the virulence of the M. tuberculosis strain, the level of immunity in the uninfected person, and others. The cascade of person-to-person spread can be circumvented by segregating those with active ("overt") TB and putting them on anti-TB drug regimens. After about two weeks of effective treatment, subjects with nonresistant active infections generally do not remain contagious to others. If someone does become infected, it typically takes three to four weeks before the newly infected person becomes infectious enough to transmit the disease to others. Risk factors A number of factors make individuals more susceptible to TB infection and/or disease. Active disease risk The most important risk factor globally for developing active TB is concurrent HIV infection; 13% of those with TB are also infected with HIV. This is a particular problem in sub-Saharan Africa, where HIV infection rates are high. Of those without HIV infection who are infected with tuberculosis, about 5–10% develop active disease during their lifetimes; in contrast, 30% of those co-infected with HIV develop the active disease.Use of certain medications, such as corticosteroids and infliximab (an anti-αTNF monoclonal antibody), is another important risk factor, especially in the developed world.Other risk factors include: alcoholism, diabetes mellitus (3-fold increased risk), silicosis (30-fold increased risk), tobacco smoking (2-fold increased risk), indoor air pollution, malnutrition, young age, recently acquired TB infection, recreational drug use, severe kidney disease, low body weight, organ transplant, head and neck cancer, and genetic susceptibility (the overall importance of genetic risk factors remains undefined). Infection susceptibility Tobacco smoking increases the risk of infections (in addition to increasing the risk of active disease and death). Additional factors increasing infection susceptibility include young age. Pathogenesis About 90% of those infected with M. tuberculosis have asymptomatic, latent TB infections (sometimes called LTBI), with only a 10% lifetime chance that the latent infection will progress to overt, active tuberculous disease. In those with HIV, the risk of developing active TB increases to nearly 10% a year. If effective treatment is not given, the death rate for active TB cases is up to 66%. TB infection begins when the mycobacteria reach the alveolar air sacs of the lungs, where they invade and replicate within endosomes of alveolar macrophages. Macrophages identify the bacterium as foreign and attempt to eliminate it by phagocytosis. During this process, the bacterium is enveloped by the macrophage and stored temporarily in a membrane-bound vesicle called a phagosome. The phagosome then combines with a lysosome to create a phagolysosome. In the phagolysosome, the cell attempts to use reactive oxygen species and acid to kill the bacterium. However, M. tuberculosis has a thick, waxy mycolic acid capsule that protects it from these toxic substances. M. tuberculosis is able to reproduce inside the macrophage and will eventually kill the immune cell. The primary site of infection in the lungs, known as the Ghon focus, is generally located in either the upper part of the lower lobe, or the lower part of the upper lobe. Tuberculosis of the lungs may also occur via infection from the blood stream. This is known as a Simon focus and is typically found in the top of the lung. This hematogenous transmission can also spread infection to more distant sites, such as peripheral lymph nodes, the kidneys, the brain, and the bones. All parts of the body can be affected by the disease, though for unknown reasons it rarely affects the heart, skeletal muscles, pancreas, or thyroid.Tuberculosis is classified as one of the granulomatous inflammatory diseases. Macrophages, epithelioid cells, T lymphocytes, B lymphocytes, and fibroblasts aggregate to form granulomas, with lymphocytes surrounding the infected macrophages. When other macrophages attack the infected macrophage, they fuse together to form a giant multinucleated cell in the alveolar lumen. The granuloma may prevent dissemination of the mycobacteria and provide a local environment for interaction of cells of the immune system. However, more recent evidence suggests that the bacteria use the granulomas to avoid destruction by the hosts immune system. Macrophages and dendritic cells in the granulomas are unable to present antigen to lymphocytes; thus the immune response is suppressed. Bacteria inside the granuloma can become dormant, resulting in latent infection. Another feature of the granulomas is the development of abnormal cell death (necrosis) in the center of tubercles. To the naked eye, this has the texture of soft, white cheese and is termed caseous necrosis.If TB bacteria gain entry to the blood stream from an area of damaged tissue, they can spread throughout the body and set up many foci of infection, all appearing as tiny, white tubercles in the tissues. This severe form of TB disease, most common in young children and those with HIV, is called miliary tuberculosis. People with this disseminated TB have a high fatality rate even with treatment (about 30%).In many people, the infection waxes and wanes. Tissue destruction and necrosis are often balanced by healing and fibrosis. Affected tissue is replaced by scarring and cavities filled with caseous necrotic material. During active disease, some of these cavities are joined to the air passages (bronchi) and this material can be coughed up. It contains living bacteria and thus can spread the infection. Treatment with appropriate antibiotics kills bacteria and allows healing to take place. Upon cure, affected areas are eventually replaced by scar tissue. Diagnosis Active tuberculosis Diagnosing active tuberculosis based only on signs and symptoms is difficult, as is diagnosing the disease in those who have a weakened immune system. A diagnosis of TB should, however, be considered in those with signs of lung disease or constitutional symptoms lasting longer than two weeks. A chest X-ray and multiple sputum cultures for acid-fast bacilli are typically part of the initial evaluation. Interferon-γ release assays and tuberculin skin tests are of little use in most of the developing world. Interferon gamma release assays (IGRA) have similar limitations in those with HIV.A definitive diagnosis of TB is made by identifying M. tuberculosis in a clinical sample (e.g., sputum, pus, or a tissue biopsy). However, the difficult culture process for this slow-growing organism can take two to six weeks for blood or sputum culture. Thus, treatment is often begun before cultures are confirmed.Nucleic acid amplification tests and adenosine deaminase testing may allow rapid diagnosis of TB. Blood tests to detect antibodies are not specific or sensitive, so they are not recommended. Latent tuberculosis The Mantoux tuberculin skin test is often used to screen people at high risk for TB. Those who have been previously immunized with the Bacille Calmette-Guerin vaccine may have a false-positive test result. The test may be falsely negative in those with sarcoidosis, Hodgkins lymphoma, malnutrition, and most notably, active tuberculosis. Interferon gamma release assays, on a blood sample, are recommended in those who are positive to the Mantoux test. These are not affected by immunization or most environmental mycobacteria, so they generate fewer false-positive results. However, they are affected by M. szulgai, M. marinum, and M. kansasii. IGRAs may increase sensitivity when used in addition to the skin test, but may be less sensitive than the skin test when used alone.The US Preventive Services Task Force (USPSTF) has recommended screening people who are at high risk for latent tuberculosis with either tuberculin skin tests or interferon-gamma release assays. While some have recommend testing health care workers, evidence of benefit for this is poor as of 2019. The Centers for Disease Control and Prevention (CDC) stopped recommending yearly testing of health care workers without known exposure in 2019. Prevention Tuberculosis prevention and control efforts rely primarily on the vaccination of infants and the detection and appropriate treatment of active cases. The World Health Organization (WHO) has achieved some success with improved treatment regimens, and a small decrease in case numbers. Some countries have legislation to involuntarily detain or examine those suspected to have tuberculosis, or involuntarily treat them if infected. Vaccines The only available vaccine as of 2021 is bacillus Calmette-Guérin (BCG). In children it decreases the risk of getting the infection by 20% and the risk of infection turning into active disease by nearly 60%.It is the most widely used vaccine worldwide, with more than 90% of all children being vaccinated. The immunity it induces decreases after about ten years. As tuberculosis is uncommon in most of Canada, Western Europe, and the United States, BCG is administered to only those people at high risk. Part of the reasoning against the use of the vaccine is that it makes the tuberculin skin test falsely positive, reducing the tests usefulness as a screening tool. Several vaccines are being developed.Intradermal MVA85A vaccine in addition to BCG injection is not effective in preventing tuberculosis. Public health Public health campaigns which have focused on overcrowding, public spitting and regular sanitation (including hand washing) during the 1800s helped to either interrupt or slow spread which when combined with contact tracing, isolation and treatment helped to dramatically curb the transmission of both tuberculosis and other airborne diseases which led to the elimination of tuberculosis as a major public health issue in most developed economies. Other risk factors which worsened TB spread such as malnutrition were also ameliorated, but since the emergence of HIV a new population of immunocompromised individuals was available for TB to infect. The World Health Organization (WHO) declared TB a "global health emergency" in 1993, and in 2006, the Stop TB Partnership developed a Global Plan to Stop Tuberculosis that aimed to save 14 million lives between its launch and 2015. A number of targets they set were not achieved by 2015, mostly due to the increase in HIV-associated tuberculosis and the emergence of multiple drug-resistant tuberculosis. A tuberculosis classification system developed by the American Thoracic Society is used primarily in public health programs. In 2015, it launched the End TB Strategy to reduce deaths by 95% and incidence by 90% before 2035. The goal of tuberculosis elimination is hampered by the lack of rapid testing, of short and effective treatment courses, and of completely effective vaccines.The benefits and risks of giving anti-tubercular drugs in those exposed to MDR-TB is unclear. Making HAART therapy available to HIV-positive individuals significantly reduces the risk of progression to an active TB infection by up to 90% and can mitigate the spread through this population. Treatment Treatment of TB uses antibiotics to kill the bacteria. Effective TB treatment is difficult, due to the unusual structure and chemical composition of the mycobacterial cell wall, which hinders the entry of drugs and makes many antibiotics ineffective.Active TB is best treated with combinations of several antibiotics to reduce the risk of the bacteria developing antibiotic resistance. The routine use of rifabutin instead of rifampicin in HIV-positive people with tuberculosis is of unclear benefit as of 2007. Latent TB Latent TB is treated with either isoniazid or rifampin alone, or a combination of isoniazid with either rifampicin or rifapentine.The treatment takes three to nine months depending on the medications used. People with latent infections are treated to prevent them from progressing to active TB disease later in life.Education or counselling may improve the latent tuberculosis treatment completion rates. New onset The recommended treatment of new-onset pulmonary tuberculosis, as of 2010, is six months of a combination of antibiotics containing rifampicin, isoniazid, pyrazinamide, and ethambutol for the first two months, and only rifampicin and isoniazid for the last four months. Where resistance to isoniazid is high, ethambutol may be added for the last four months as an alternative. Treatment with anti-TB drugs for at least 6 months results in higher success rates when compared with treatment less than 6 months, even though the difference is small. Shorter treatment regimen may be recommended for those with compliance issues. There is also no evidence to support shorter anti-tuberculosis treatment regimens when compared to a 6-month treatment regimen. However recently, results from an international, randomized, controlled clinical trial indicate that a four-month daily treatment regimen containing high-dose, or "optimized," rifapentine with moxifloxacin (2PHZM/2PHM) is as safe and effective as the existing standard six-month daily regimen at curing drug-susceptible tuberculosis (TB) disease. Recurrent disease If tuberculosis recurs, testing to determine which antibiotics it is sensitive to is important before determining treatment. If multiple drug-resistant TB (MDR-TB) is detected, treatment with at least four effective antibiotics for 18 to 24 months is recommended. Medication administration Directly observed therapy, i.e., having a health care provider watch the person take their medications, is recommended by the World Health Organization (WHO) in an effort to reduce the number of people not appropriately taking antibiotics. The evidence to support this practice over people simply taking their medications independently is of poor quality. There is no strong evidence indicating that directly observed therapy improves the number of people who were cured or the number of people who complete their medicine. Moderate quality evidence suggests that there is also no difference if people are observed at home versus at a clinic, or by a family member versus a health care worker. Methods to remind people of the importance of treatment and appointments may result in a small but important improvement. There is also not enough evidence to support intermittent rifampicin-containing therapy given two to three times a week has equal effectiveness as daily dose regimen on improving cure rates and reducing relapsing rates. There is also not enough evidence on effectiveness of giving intermittent twice or thrice weekly short course regimen compared to daily dosing regimen in treating children with tuberculosis. Medication resistance Primary resistance occurs when a person becomes infected with a resistant strain of TB. A person with fully susceptible MTB may develop secondary (acquired) resistance during therapy because of inadequate treatment, not taking the prescribed regimen appropriately (lack of compliance), or using low-quality medication. Drug-resistant TB is a serious public health issue in many developing countries, as its treatment is longer and requires more expensive drugs. MDR-TB is defined as resistance to the two most effective first-line TB drugs: rifampicin and isoniazid. Extensively drug-resistant TB is also resistant to three or more of the six classes of second-line drugs. Totally drug-resistant TB is resistant to all currently used drugs. It was first observed in 2003 in Italy, but not widely reported until 2012, and has also been found in Iran and India. There is some efficacy for linezolid to treat those with XDR-TB but side effects and discontinuation of medications were common. Bedaquiline is tentatively supported for use in multiple drug-resistant TB.XDR-TB is a term sometimes used to define extensively resistant TB, and constitutes one in ten cases of MDR-TB. Cases of XDR TB have been identified in more than 90% of countries.For those with known rifampicin or MDR-TB, molecular tests such as the Genotype® MTBDRsl Assay (performed on culture isolates or smear positive specimens) may be useful to detect second-line anti-tubercular drug resistance. Prognosis Progression from TB infection to overt TB disease occurs when the bacilli overcome the immune system defenses and begin to multiply. In primary TB disease (some 1–5% of cases), this occurs soon after the initial infection. However, in the majority of cases, a latent infection occurs with no obvious symptoms. These dormant bacilli produce active tuberculosis in 5–10% of these latent cases, often many years after infection.The risk of reactivation increases with immunosuppression, such as that caused by infection with HIV. In people coinfected with M. tuberculosis and HIV, the risk of reactivation increases to 10% per year. Studies using DNA fingerprinting of M. tuberculosis strains have shown reinfection contributes more substantially to recurrent TB than previously thought, with estimates that it might account for more than 50% of reactivated cases in areas where TB is common. The chance of death from a case of tuberculosis is about 4% as of 2008, down from 8% in 1995.In people with smear-positive pulmonary TB (without HIV co-infection), after 5 years without treatment, 50-60% die while 20-25% achieve spontaneous resolution (cure). TB is almost always fatal in those with untreated HIV co-infection and death rates are increased even with antiretroviral treatment of HIV. Epidemiology Roughly one-quarter of the worlds population has been infected with M. tuberculosis, with new infections occurring in about 1% of the population each year. However, most infections with M. tuberculosis do not cause disease, and 90–95% of infections remain asymptomatic. In 2012, an estimated 8.6 million chronic cases were active. In 2010, 8.8 million new cases of tuberculosis were diagnosed, and 1.20–1.45 million deaths occurred (most of these occurring in developing countries). Of these, about 0.35 million occur in those also infected with HIV. In 2018, tuberculosis was the leading cause of death worldwide from a single infectious agent. The total number of tuberculosis cases has been decreasing since 2005, while new cases have decreased since 2002.Tuberculosis incidence is seasonal, with peaks occurring every spring and summer. The reasons for this are unclear, but may be related to vitamin D deficiency during the winter. There are also studies linking tuberculosis to different weather conditions like low temperature, low humidity and low rainfall. It has been suggested that tuberculosis incidence rates may be connected to climate change. At-risk groups Tuberculosis is closely linked to both overcrowding and malnutrition, making it one of the principal diseases of poverty. Those at high risk thus include: people who inject illicit drugs, inhabitants and employees of locales where vulnerable people gather (e.g., prisons and homeless shelters), medically underprivileged and resource-poor communities, high-risk ethnic minorities, children in close contact with high-risk category patients, and health-care providers serving these patients.The rate of tuberculosis varies with age. In Africa, it primarily affects adolescents and young adults. However, in countries where incidence rates have declined dramatically (such as the United States), tuberculosis is mainly a disease of the elderly and immunocompromised (risk factors are listed above). Worldwide, 22 "high-burden" states or countries together experience 80% of cases as well as 83% of deaths.In Canada and Australia, tuberculosis is many times more common among the aboriginal peoples, especially in remote areas. Factors contributing to this include higher prevalence of predisposing health conditions and behaviours, and overcrowding and poverty. In some Canadian aboriginal groups, genetic susceptibility may play a role.Socioeconomic status (SES) strongly affects TB risk. People of low SES are both more likely to contract TB and to be more severely affected by the disease. Those with low SES are more likely to be affected by risk factors for developing TB (e.g. malnutrition, indoor air pollution, HIV co-infection, etc.), and are additionally more likely to be exposed to crowded and poorly ventilated spaces. Inadequate healthcare also means that people with active disease who facilitate spread are not diagnosed and treated promptly; sick people thus remain in the infectious state and (continue to) spread the infection. Geographical epidemiology The distribution of tuberculosis is not uniform across the globe; about 80% of the population in many African, Caribbean, South Asian, and eastern European countries test positive in tuberculin tests, while only 5–10% of the U.S. population test positive. Hopes of totally controlling the disease have been dramatically dampened because of many factors, including the difficulty of developing an effective vaccine, the expensive and time-consuming diagnostic process, the necessity of many months of treatment, the increase in HIV-associated tuberculosis, and the emergence of drug-resistant cases in the 1980s
Tuberculosis	.In developed countries, tuberculosis is less common and is found mainly in urban areas. In Europe, deaths from TB fell from 500 out of 100,000 in 1850 to 50 out of 100,000 by 1950. Improvements in public health were reducing tuberculosis even before the arrival of antibiotics, although the disease remained a significant threat to public health, such that when the Medical Research Council was formed in Britain in 1913 its initial focus was tuberculosis research.In 2010, rates per 100,000 people in different areas of the world were: globally 178, Africa 332, the Americas 36, Eastern Mediterranean 173, Europe 63, Southeast Asia 278, and Western Pacific 139. Russia Russia has achieved particularly dramatic progress with a decline in its TB mortality rate—from 61.9 per 100,000 in 1965 to 2.7 per 100,000 in 1993; however, mortality rate increased to 24 per 100,000 in 2005 and then recoiled to 11 per 100,000 by 2015. China China has achieved particularly dramatic progress, with about an 80% reduction in its TB mortality rate between 1990 and 2010. The number of new cases has declined by 17% between 2004 and 2014. Africa In 2007, the country with the highest estimated incidence rate of TB was Eswatini, with 1,200 cases per 100,000 people. In 2017, the country with the highest estimated incidence rate as a % of the population was Lesotho, with 665 cases per 100,000 people. India As of 2017, India had the largest total incidence, with an estimated 2,740,000 cases. According to the World Health Organization (WHO), in 2000–2015, Indias estimated mortality rate dropped from 55 to 36 per 100,000 population per year with estimated 480 thousand people died of TB in 2015. In India a major proportion of tuberculosis patients are being treated by private partners and private hospitals. Evidence indicates that the tuberculosis national survey does not represent the number of cases that are diagnosed and recorded by private clinics and hospitals in India. North America In the United States Native Americans have a fivefold greater mortality from TB, and racial and ethnic minorities accounted for 84% of all reported TB cases.In the United States, the overall tuberculosis case rate was 3 per 100,000 persons in 2017. In Canada, tuberculosis is still endemic in some rural areas. Western Europe In 2017, in the United Kingdom, the national average was 9 per 100,000 and the highest incidence rates in Western Europe were 20 per 100,000 in Portugal. History Tuberculosis has existed since antiquity. The oldest unambiguously detected M. tuberculosis gives evidence of the disease in the remains of bison in Wyoming dated to around 17,000 years ago. However, whether tuberculosis originated in bovines, then transferred to humans, or whether both bovine and human tuberculosis diverged from a common ancestor, remains unclear. A comparison of the genes of M. tuberculosis complex (MTBC) in humans to MTBC in animals suggests humans did not acquire MTBC from animals during animal domestication, as researchers previously believed. Both strains of the tuberculosis bacteria share a common ancestor, which could have infected humans even before the Neolithic Revolution. Skeletal remains show some prehistoric humans (4000 BC) had TB, and researchers have found tubercular decay in the spines of Egyptian mummies dating from 3000 to 2400 BC. Genetic studies suggest the presence of TB in the Americas from about AD 100.Before the Industrial Revolution, folklore often associated tuberculosis with vampires. When one member of a family died from the disease, the other infected members would lose their health slowly. People believed this was caused by the original person with TB draining the life from the other family members.Although Richard Morton established the pulmonary form associated with tubercles as a pathology in 1689, due to the variety of its symptoms, TB was not identified as a single disease until the 1820s. Benjamin Marten conjectured in 1720 that consumptions were caused by microbes which were spread by people living in close proximity to each other. In 1819 René Laennec claimed that tubercles were the cause of pulmonary tuberculosis. J. L. Schönlein first published the name "tuberculosis" (German: Tuberkulose) in 1832. Between 1838 and 1845, John Croghan, the owner of Mammoth Cave in Kentucky from 1839 onwards, brought a number of people with tuberculosis into the cave in the hope of curing the disease with the constant temperature and purity of the cave air; each died within a year. Hermann Brehmer opened the first TB sanatorium in 1859 in Görbersdorf (now Sokołowsko) in Silesia. In 1865 Jean Antoine Villemin demonstrated that tuberculosis could be transmitted, via inoculation, from humans to animals and among animals. (Villemins findings were confirmed in 1867 and 1868 by John Burdon-Sanderson.) Robert Koch identified and described the bacillus causing tuberculosis, M. tuberculosis, on 24 March 1882. He received the Nobel Prize in Physiology or Medicine in 1905 for this discovery. Koch did not believe the cattle and human tuberculosis diseases were similar, which delayed the recognition of infected milk as a source of infection. During the first half of the 1900s the risk of transmission from this source was dramatically reduced after the application of the pasteurization process. Koch announced a glycerine extract of the tubercle bacilli as a "remedy" for tuberculosis in 1890, calling it "tuberculin". Although it was not effective, it was later successfully adapted as a screening test for the presence of pre-symptomatic tuberculosis. World Tuberculosis Day is marked on 24 March each year, the anniversary of Kochs original scientific announcement. Albert Calmette and Camille Guérin achieved the first genuine success in immunization against tuberculosis in 1906, using attenuated bovine-strain tuberculosis. It was called bacille Calmette–Guérin (BCG). The BCG vaccine was first used on humans in 1921 in France, but achieved widespread acceptance in the US, Great Britain, and Germany only after World War II.Tuberculosis caused widespread public concern in the 19th and early 20th centuries as the disease became common among the urban poor. In 1815 one in four deaths in England was due to "consumption". By 1918, TB still caused one in six deaths in France. After TB was determined to be contagious, in the 1880s, it was put on a notifiable-disease list in Britain; campaigns started to stop people from spitting in public places, and the infected poor were "encouraged" to enter sanatoria that resembled prisons (the sanatoria for the middle and upper classes offered excellent care and constant medical attention). Whatever the benefits of the "fresh air" and labor in the sanatoria, even under the best conditions, 50% of those who entered died within five years (c. 1916). When the Medical Research Council formed in Britain in 1913, it initially focused on tuberculosis research.In Europe, rates of tuberculosis began to rise in the early 1600s to a peak level in the 1800s, when it caused nearly 25% of all deaths. In the 18th and 19th century, tuberculosis had become epidemic in Europe, showing a seasonal pattern. By the 1950s mortality in Europe had decreased about 90%. Improvements in sanitation, vaccination, and other public-health measures began significantly reducing rates of tuberculosis even before the arrival of streptomycin and other antibiotics, although the disease remained a significant threat. In 1946 the development of the antibiotic streptomycin made effective treatment and cure of TB a reality. Prior to the introduction of this medication, the only treatment was surgical intervention, including the "pneumothorax technique", which involved collapsing an infected lung to "rest" it and to allow tuberculous lesions to heal.Because of the emergence of multidrug-resistant tuberculosis (MDR-TB), surgery has been re-introduced for certain cases of TB infections. It involves the removal of infected chest cavities ("bullae") in the lungs to reduce the number of bacteria and to increase exposure of the remaining bacteria to antibiotics in the bloodstream. Hopes of eliminating TB ended with the rise of drug-resistant strains in the 1980s. The subsequent resurgence of tuberculosis resulted in the declaration of a global health emergency by the World Health Organization (WHO) in 1993. Society and culture Names Tuberculosis has been known by many names from the technical to the familiar. Phthisis (Φθισις) is a Greek word for consumption, an old term for pulmonary tuberculosis; around 460 BCE, Hippocrates described phthisis as a disease of dry seasons. The abbreviation TB is short for tubercle bacillus. Consumption was the most common nineteenth century English word for the disease. The Latin root con meaning completely is linked to sumere meaning to take up from under. In The Life and Death of Mr Badman by John Bunyan, the author calls consumption "the captain of all these men of death." "Great white plague" has also been used. Art and literature Tuberculosis was for centuries associated with poetic and artistic qualities among those infected, and was also known as "the romantic disease". Major artistic figures such as the poets John Keats, Percy Bysshe Shelley, and Edgar Allan Poe, the composer Frédéric Chopin, the playwright Anton Chekhov, the novelists Franz Kafka, Katherine Mansfield, Charlotte Brontë, Fyodor Dostoevsky, Thomas Mann, W. Somerset Maugham, George Orwell, and Robert Louis Stevenson, and the artists Alice Neel, Jean-Antoine Watteau, Elizabeth Siddal, Marie Bashkirtseff, Edvard Munch, Aubrey Beardsley and Amedeo Modigliani either had the disease or were surrounded by people who did. A widespread belief was that tuberculosis assisted artistic talent. Physical mechanisms proposed for this effect included the slight fever and toxaemia that it caused, allegedly helping them to see life more clearly and to act decisively.Tuberculosis formed an often-reused theme in literature, as in Thomas Manns The Magic Mountain, set in a sanatorium; in music, as in Van Morrisons song "T.B. Sheets"; in opera, as in Puccinis La bohème and Verdis La Traviata; in art, as in Monets painting of his first wife Camille on her deathbed; and in film, such as the 1945 The Bells of St. Marys starring Ingrid Bergman as a nun with tuberculosis. Public health efforts In 2014 the WHO adopted the "End TB" strategy which aims to reduce TB incidence by 80% and TB deaths by 90% by 2030. The strategy contains a milestone to reduce TB incidence by 20% and TB deaths by 35% by 2020. However, by 2020 only a 9% reduction in incidence per population was achieved globally, with the European region achieving 19% and the African region achieving 16% reductions. Similarly, the number of deaths only fell by 14%, missing the 2020 milestone of a 35% reduction, with some regions making better progress (31% reduction in Europe and 19% in Africa). Correspondingly, also treatment, prevention and funding milestones were missed in 2020, for example only 6.3 million people were started on TB prevention short of the target of 30 million.The World Health Organization (WHO), the Bill and Melinda Gates Foundation, and the U.S. government are subsidizing a fast-acting diagnostic tuberculosis test for use in low- and middle-income countries as of 2012. In addition to being fast-acting, the test can determine if there is resistance to the antibiotic rifampicin which may indicate multi-drug resistant tuberculosis and is accurate in those who are also infected with HIV. Many resource-poor places as of 2011 have access to only sputum microscopy.India had the highest total number of TB cases worldwide in 2010, in part due to poor disease management within the private and public health care sector. Programs such as the Revised National Tuberculosis Control Program are working to reduce TB levels among people receiving public health care.A 2014 EIU-healthcare report finds there is a need to address apathy and urges for increased funding. The report cites among others Lucica Ditui "[TB] is like an orphan. It has been neglected even in countries with a high burden and often forgotten by donors and those investing in health interventions."Slow progress has led to frustration, expressed by the executive director of the Global Fund to Fight AIDS, Tuberculosis and Malaria – Mark Dybul: "we have the tools to end TB as a pandemic and public health threat on the planet, but we are not doing it." Several international organizations are pushing for more transparency in treatment, and more countries are implementing mandatory reporting of cases to the government as of 2014, although adherence is often variable. Commercial treatment providers may at times overprescribe second-line drugs as well as supplementary treatment, promoting demands for further regulations. The government of Brazil provides universal TB care, which reduces this problem. Conversely, falling rates of TB infection may not relate to the number of programs directed at reducing infection rates but may be tied to an increased level of education, income, and health of the population. Costs of the disease, as calculated by the World Bank in 2009 may exceed US$150 billion per year in "high burden" countries. Lack of progress eradicating the disease may also be due to lack of patient follow-up – as among the 250 million rural migrants in China.There is insufficient data to show that active contact tracing helps to improve case detection rates for tuberculosis. Interventions such as house-to-house visits, educational leaflets, mass media strategies, educational sessions may increase tuberculosis detection rates in short-term. There is no study that compares new methods of contact tracing such as social network analysis with existing contact tracing methods. Stigma Slow progress in preventing the disease may in part be due to stigma associated with TB. Stigma may be due to the fear of transmission from affected individuals. This stigma may additionally arise due to links between TB and poverty, and in Africa, AIDS. Such stigmatization may be both real and perceived; for example, in Ghana, individuals with TB are banned from attending public gatherings.Stigma towards TB may result in delays in seeking treatment, lower treatment compliance, and family members keeping cause of death secret – allowing the disease to spread further. In contrast, in Russia stigma was associated with increased treatment compliance. TB stigma also affects socially marginalized individuals to a greater degree and varies between regions.One way to decrease stigma may be through the promotion of "TB clubs", where those infected may share experiences and offer support, or through counseling. Some studies have shown TB education programs to be effective in decreasing stigma, and may thus be effective in increasing treatment adherence. Despite this, studies on the relationship between reduced stigma and mortality are lacking as of 2010, and similar efforts to decrease stigma surrounding AIDS have been minimally effective. Some have claimed the stigma to be worse than the disease, and healthcare providers may unintentionally reinforce stigma, as those with TB are often perceived as difficult or otherwise undesirable. A greater understanding of the social and cultural dimensions of tuberculosis may also help with stigma reduction. Research The BCG vaccine has limitations, and research to develop new TB vaccines is ongoing. A number of potential candidates are currently in phase I and II clinical trials. Two main approaches are used to attempt to improve the efficacy of available vaccines. One approach involves adding a subunit vaccine to BCG, while the other strategy is attempting to create new and better live vaccines. MVA85A, an example of a subunit vaccine, is in trials in South Africa as of 2006, is based on a genetically modified vaccinia virus. Vaccines are hoped to play a significant role in treatment of both latent and active disease.To encourage further discovery, researchers and policymakers are promoting new economic models of vaccine development as of 2006, including prizes, tax incentives, and advance market commitments. A number of groups, including the Stop TB Partnership, the South African Tuberculosis Vaccine Initiative, and the Aeras Global TB Vaccine Foundation, are involved with research. Among these, the Aeras Global TB Vaccine Foundation received a gift of more than $280 million (US) from the Bill and Melinda Gates Foundation to develop and license an improved vaccine against tuberculosis for use in high burden countries.A number of medications are being studied as of 2012 for multidrug-resistant tuberculosis, including bedaquiline and delamanid. Bedaquiline received U.S. Food and Drug Administration (FDA) approval in late 2012. The safety and effectiveness of these new agents are uncertain as of 2012, because they are based on the results of relatively small studies. However, existing data suggest that patients taking bedaquiline in addition to standard TB therapy are five times more likely to die than those without the new drug, which has resulted in medical journal articles raising health policy questions about why the FDA approved the drug and whether financial ties to the company making bedaquiline influenced physicians support for its use.Steroids add-on therapy has not shown any benefits for active pulmonary tuberculosis infection. Other animals Mycobacteria infect many different animals, including birds, fish, rodents, and reptiles. The subspecies Mycobacterium tuberculosis, though, is rarely present in wild animals. An effort to eradicate bovine tuberculosis caused by Mycobacterium bovis from the cattle and deer herds of New Zealand has been relatively successful. Efforts in Great Britain have been less successful.As of 2015, tuberculosis appears to be widespread among captive elephants in the US. It is believed that the animals originally acquired the disease from humans, a process called reverse zoonosis. Because the disease can spread through the air to infect both humans and other animals, it is a public health concern affecting circuses and zoos. References External links Tuberculosis at Curlie "Tuberculosis (TB)". Centers for Disease Control and Prevention (CDC). 24 October 2018. "Tuberculosis (TB)". London: Health Protection Agency. Archived from the original on 5 July 2007. WHO global 2016 TB report (infographic) WHO tuberculosis country profiles "Tuberculosis Among African Americans", 1990-11-01, In Black America; KUT Radio, American Archive of Public Broadcasting (WGBH and the Library of Congress) Working Group on New TB drugs, tracking clinical trials and drug candidates
Large granular lymphocytic leukemia	Large granular lymphocytic (LGL) leukemia is a chronic lymphoproliferative disorder that exhibits an unexplained, chronic (> 6 months) elevation in large granular lymphocytes (LGLs) in the peripheral blood.It is divided in two main categories: T-cell LGL leukemia (T-LGLL) and natural-killer (NK)-cell LGL leukemia (NK-LGLL). As the name suggests, T-cell large granular lymphocyte leukemia is characterized by involvement of cytotoxic-T cells).In a study based in the US, the average age of diagnosis was 66.5 years whereas in a French study the median age at diagnosis was 59 years (with an age range of 12–87 years old). In the French study, only 26% of patients were younger than 50 years which suggests that this disorder is associated with older age at diagnosis. Due to lack of presenting symptoms, the disorder is likely to be underdiagnosed in the general population. Signs and symptoms This disease is known for an indolent clinical course and incidental discovery. The most common physical finding is moderate splenomegaly. B symptoms are seen in a third of cases, and recurrent infections due to anaemia and/or neutropenia are seen in almost half of cases.Rheumatoid arthritis is commonly observed in people with T-LGLL, leading to a clinical presentation similar to Feltys syndrome. Signs and symptoms of anemia are commonly found, due to the association between T-LGLL and erythroid hypoplasia. Sites of involvement The leukemic cells of T-LGLL can be found in peripheral blood, bone marrow, spleen, and liver. Nodal involvement is rare. Cause The postulated cells of origin of T-LGLL leukemia are transformed CD8+ T-cell with clonal rearrangements of β chain T-cell receptor genes for the majority of cases and a CD8- T-cell with clonal rearrangements of γ chain T-cell receptor genes for a minority of cases. Diagnosis Laboratory findings The requisite lymphocytosis of this disease is typically 2-20x109/L.Immunoglobulin derangements including hypergammaglobulinemia, autoantibodies, and circulating immune complexes are commonly seen. Peripheral blood The neoplastic lymphocytes seen in this disease are large in size with azurophilic granules that contains proteins involved in cell lysis such as perforin and granzyme B. Flow cytometry is also commonly used. Bone marrow Bone marrow involvement in this disease is often present, but to a variable extent. Bone marrow biopsy is commonly used for diagnosis. The lymphocytic infiltrate is usually interstitial, but a nodular pattern rarely occurs. Immunophenotype The neoplastic cells of this disease display a mature T-cell immunophenotype, with the majority of cases showing a CD4-/CD8+ T-cell subset immunophenotype versus other permutations of those markers. Variable expression of CD11b, CD56, and CD57 are observed. Immunohistochemistry for perforin, TIA-1, and granzyme B are usually positive. Genetic findings Clonal rearrangements of the T-cell receptor (TCR) genes are a necessary condition for the diagnosis of this disease. The gene for the β chain of the TCR is found to be rearranged more often than the γ chain. of the TCR.Current evidence suggests that patients with STAT3 mutations are more likely to respond to methotrexate therapy. Treatment First line treatment is immunosuppressive therapy. A weekly dosage of Methotrexate (with or without daily Prednisone) may induce partial or complete response in some patients while others may require Cyclosporine or Cyclophosphamide.Alemtuzumab has been investigated for use in treatment of refractory T-cell large granular lymphocytic leukemia.Experimental data suggests that treatment with calcitrol (the active form of vitamin D) may be useful in treating T-cell LGL due to its ability to decrease pro-inflammatory cytokines. Prognosis The 5 year survival has been noted as 89% in at least one study from France of 201 patients with T-LGL leukemia. Epidemiology T-LGLL is a rare form of leukemia, comprising 2-3% of all cases of chronic lymphoproliferative disorders. History LGLL was discovered in 1985 by Thomas P. Loughran Jr. while working at Fred Hutchinson Cancer Research Center. Specimens from patients with LGLL are banked at the University of Virginia for research purposes, the only bank for such purposes. References == External links ==
Dermatofibroma	A dermatofibroma, or benign fibrous histiocytomas, is a benign nodule in the skin, typically on the legs, elbows and chest of an adult. It is usually painless.Its size usually ranges from 0.2cm to 2cm, and have been reported to be larger. It typically results from mild trauma such as an insect bite. Risk factors for developing multiple dermatofibromas include lupus, HIV, blood cancer and some medicines that weaken immunity.It is usually diagnosed by its appearance, but a biopsy may be required. Other bumps such as granular cell tumor, melanoma, clear cell acanthoma and dermatofibrosis lenticularis disseminata may look similar. Reassurance is generally given and usually no treatment is needed. It can remain unchanged for years, but can resolve spontaneously. Signs and symptoms Dermatofibromas are hard solitary slow-growing papules (rounded bumps) that may appear in a variety of colours, usually brownish to tan; they are often elevated or pedunculated. A dermatofibroma is associated with the dimple sign; by applying lateral pressure, there is a central depression of the dermatofibroma. Although typical dermatofibromas cause little or no discomfort, itching and tenderness can occur. Dermatofibromas can be found anywhere on the body, but most often they are found on the legs and arms. They occur most often in women; the male to female ratio is about 1:4. The age group in which they most commonly occur is 20 to 45 years. Some physicians and researchers believe dermatofibromas form as a reaction to previous injuries such as insect bites or thorn pricks. They are composed of disordered collagen laid down by fibroblasts. Dermatofibromas are classed as benign skin lesions, meaning they are completely harmless, though they may be confused with a variety of subcutaneous tumours. Deep penetrating dermatofibromas may be difficult to distinguish, even histologically, from rare malignant fibrohistocytic tumours like dermatofibrosarcoma protuberans.Dermatofibromas typically have a positive buttonhole sign, or central dimpling in the center. Diagnosis Immunohistochemical staining See also Acrochordon, also called skin tags Dermatology List of cutaneous conditions Seborrheic keratosis References == External links ==
Color blindness	Color blindness (color vision deficiency) is the decreased ability to see color or differences in color. It can impair tasks such as selecting ripe fruit, choosing clothing, and reading traffic lights. Color blindness may make some academic activities more difficult. However, issues are generally minor, and the colorblind automatically develop adaptations and coping mechanisms. People with total color blindness (achromatopsia) may also be uncomfortable in bright environments and have decreased visual acuity. The most common cause of color blindness is an inherited problem or variation in the functionality of one or more of the three classes of cone cells in the retina, which mediate color vision. Males are more likely to be color blind than females, because the genes responsible for the most common forms of color blindness are on the X chromosome. Non-color-blind females can carry genes for color blindness and pass them on to their children. Color blindness can also result from physical or chemical damage to the eye, the optic nerve, or parts of the brain. Screening for color blindness is typically done with the Ishihara color test.There is no cure for color blindness. Diagnosis may allow an individual, or their parents/teachers to actively accommodate the condition. Special lenses such as EnChroma glasses or X-chrom contact lenses may help people with red–green color blindness at some color tasks, but they do not grant the wearer "normal color vision". Mobile apps can help people identify colors.Red–green color blindness is the most common form, followed by blue–yellow color blindness and total color blindness. Red–green color blindness affects up to 1 in 12 males (8%) and 1 in 200 females (0.5%). The ability to see color also decreases in old age. In certain countries, color blindness may make people ineligible for certain jobs, such as those of aircraft pilots, train drivers, crane operators, and people in the armed forces. The effect of color blindness on artistic ability is controversial, but a number of famous artists are believed to have been color blind. Signs and symptoms Color blindness describes both a symptom of reduced color perception, as well as several conditions where colorblindness is the primary – or only – symptom. This section will focus only on color blindness as a symptom. A colorblind subject will have decreased (or no) color discrimination along the red-green axis, blue-yellow axis, or both, though the vast majority of the colorblind are only affected on their red-green axis. The first indication of colorblindness generally consists of a person using the wrong color for an object, such as when painting, or calling a color by the wrong name. The colors that are confused are very consistent among people with the same type of color blindness. Confusion colors Confusion colors are pairs or groups of colors that will often be mistaken by the colorblind. Confusion colors for red-green color blindness include: Cyan and Grey Rose-Pink and Grey Blue and Purple Yellow and Neon Green Red, Green, Orange, BrownConfusion colors for blue-yellow color blindness include: Yellow and Grey Blue and Green Dark Blue/Violet and Black Violet and Yellow-Green Red and Rose-PinkThese colors of confusion are defined quantitatively by straight confusion lines plotted in CIEXYZ, usually plotted on the corresponding chromaticity diagram. The lines all intersect at a copunctal point, which varies with the type of color blindness. Chromaticities along a confusion line will appear metameric to dichromats of that type. Anomalous trichromats of that type will see the Chromaticities as metameric if they are close enough, depending on the strength of their CVD. For two colors on a confusion line to be metameric, the Chromaticities first have to be made isoluminant, i.e. to have the same Lightness. Note also that colors that may be isoluminant to the standard observer (typical trichromat) may not be isoluminant to a dichromat. Color tasks Cole describes four color tasks, all of which are impeded to some degree by color blindness: Comparative – When multiple colors must be compared, such as with mixing paint Connotative – When colors are given an implicit meaning, such as red = stop Denotative – When identifying colors, for example by name, such as “where is the yellow ball?” Aesthetic – When colors look nice – or convey an emotional response – but don’t carry explicit meaningColor blindness causes difficulty in all four kinds of color tasks. The following sections will describe specific color tasks that the colorblind typically have difficulty with. Food Colorblindness causes difficulty with the connotative color tasks associated with selecting or preparing food, for example: Selecting food for ripeness can be difficult. The green-yellow transition of bananas is particularly hard to identify. Detecting bruises, mold or rot on some foods Determining when meat is done by color Distinguishing some varietals, such as a Braeburn from a Granny Smith apple Distinguishing colors associated with artificial flavors (e.g. jelly beans, sports drinks) Skin color Changes in skin color due to bruising, sunburn, rashes or even blushing are easily missed by those with red-green colorblindness. These discolorations are often linked to the blood oxygen saturation, which affects skin reflectance. Traffic lights The colors of traffic lights can be difficult for the red-green colorblind. This includes distinguishing: red/amber lights from sodium street lamps; green lights (closer to cyan) from normal white lights. Red from amber lights, especially when there are no positional clues available (see image).The main coping mechanism to overcome these challenges is to memorize the position of lights. The order of the common triplet traffic light is standardized as red-amber-green from top to bottom or left to right. Cases that deviate from this standard are rare. One such case is a traffic light in Tipperary Hill in Syracuse, New York, which is upside-down (green-amber-red top to bottom) due to the sentiments of its Irish American community. However, it has been criticized due to the potential hazard it poses for color-blind drivers. Signal lights Navigation lights in marine and aviation settings employ red and green lights to signal the relative position of other ships or aircraft. Railway signal lights also rely heavily on red-green-yellow colors. In both cases, these color combinations can be difficult for the red-green colorblind. Lantern Tests are a common means of simulating these light sources to determine not necessarily whether someone is colorblind, but whether they can functionally distinguish these specific signal colors. Those who cannot pass this test are generally completely restricted from working on aircraft, ships or rail. Fashion Color analysis is the analysis of color in its use in fashion, to determine personal color combinations that are most aesthetic. Colors to combine can include clothing, accessories, makeup, hair color, skin color, eye color, etc. Color analysis involves many aesthetic and comparative color task that can be difficult for the color blind. Most colorblind individuals conservatively avoid brightly colored clothes to avoid combining colors that may be viewed as unaesthetic by people with normal color vision. Advantages People with deuteranomaly are better at distinguishing shades of khaki, which may be advantageous when looking for predators, food, or camouflaged objects hidden among foliage. Dichromats tend to learn to use texture and shape clues and so may be able to penetrate camouflage that has been designed to deceive individuals with normal color vision.In the presence of chromatic noise, the colorblind are more capable of seeing a luminous signal, as long as the chromatic noise appears metameric to them. This is the effect behind most "reverse" Pseudoisochromatic plates (e.g. "hidden digit" Ishihara plates) that are discernible to the colorblind, but unreadable to color normals. Classification Much terminology has existed and does exist for the classification of color blindness, but the typical classification for color blindness follows the von Kries classifications, which uses severity and affected cone for naming. Based on severity Based on clinical appearance, color blindness may be described as total or partial. Total color blindness (monochromacy) is much less common than partial color blindness. Partial colorblindness includes dichromacy and anomalous trichromacy, but is often clinically defined as mild, moderate or strong. Monochromacy Monochromacy is often called total color blindness since there is no ability to see color. Although the term may refer to acquired disorders such as cerebral achromatopsia, it typically refers to congenital color vision disorders, namely rod monochromacy and blue cone monochromacy).In cerebral achromatopsia, a person cannot perceive colors even though the eyes are capable of distinguishing them. Some sources do not consider these to be true color blindness, because the failure is of perception, not of vision. They are forms of visual agnosia.Monochromacy is the condition of possessing only a single channel for conveying information about color. Monochromats are unable to distinguish any colors and perceive only variations in brightness. Congenital monochromacy occurs in two primary forms: Rod monochromacy, frequently called complete achromatopsia, where the retina contains no cone cells, so that in addition to the absence of color discrimination, vision in lights of normal intensity is difficult. Cone monochromacy is the condition of having only a single class of cone. A cone monochromat can have good pattern vision at normal daylight levels, but will not be able to distinguish hues. Cone monochromacy is divided into classes defined by the single remaining cone class. However, red and green cone monochromats have not been definitively described in the literature. Blue cone monochromacy is caused by lack of functionality of L (red) and M (green) cones, and is therefore mediated by the same genes as red–green color blindness (on the X chromosome). Peak spectral sensitivities are in the blue region of the visible spectrum (near 440 nm). People with this condition generally show nystagmus ("jiggling eyes"), photophobia (light sensitivity), reduced visual acuity, and myopia (nearsightedness). Visual acuity usually falls to the 20/50 to 20/400 range. Dichromacy Dichromats can match any color they see with some mixture of just two primary colors (in contrast to those with normal sight (trichromats) who can distinguish three primary colors). Dichromats usually know they have a color vision problem, and it can affect their daily lives. Dichromacy in humans includes protanopia, deuteranopia, and tritanopia. Out of the male population, 2% have severe difficulties distinguishing between red, orange, yellow, and green. (Orange and yellow are different combinations of red and green light.) Colors in this range, which appear very different to a normal viewer, appear to a dichromat to be the same or a similar color. The terms protanopia, deuteranopia, and tritanopia come from Greek, and respectively mean "inability to see (anopia) with the first (prot-), second (deuter-), or third (trit-) [cone]". Anomalous trichromacy Anomalous trichromacy is the mildest type of color deficiency, but the severity ranges from almost dichromacy (strong) to almost normal trichromacy (mild). In fact, many mild anomalous trichromats have very little difficulty carrying out tasks that require normal color vision and some may not even be aware that they have a color vision deficiency. The types of anomalous trichromacy include protanomaly, deuteranomaly and tritanomaly. It is approximately three times more common than dichromacy. Anomalous trichromats exhibit trichromacy, but the color matches they make differ from normal trichromats. In order to match a given spectral yellow light, protanomalous observers need more red light in a red/green mixture than a normal observer, and deuteranomalous observers need more green. This difference can be measured by an instrument called an Anomaloscope, where red and green lights are mixed by a subject to match a yellow light. Based on affected cone There are two major types of color blindness: difficulty distinguishing between red and green, and difficulty distinguishing between blue and yellow. These definitions are based on the phenotype of the partial colorblindness. Clinically, it is more common to use a genotypical definition, which describes which cone/opsin is affected. Red–green color blindness Red-green color blindness includes protan and deutan CVD. Protan CVD is related to the L-cone and includes protanomaly (anomalous trichromacy) and protanopia (dichromacy). Deutan CVD is related to the M-cone and includes deuteranomaly (anomalous trichromacy) and deuteranopia (dichromacy). The phenotype (visual experience) of deutans and protans is quite similar. Common colors of confusion include red/brown/green/yellow as well as blue/purple. Both forms are almost always congenital (genetic) and sex-linked: affecting males much more often than females. This form of colorblindness is sometimes referred to as daltonism after John Dalton, who had red-green dichromacy. In some languages, daltonism is still used to describe red-green color blindness. Protan (2% of males): Lacking, or possessing anomalous L-opsins for long-wavelength sensitive cone cells. Protans have a neutral point at a cyan-like wavelength around 492 nm (see spectral color for comparison)—that is, they cannot discriminate light of this wavelength from white. For a protanope, the brightness of red, is much reduced compared to normal. This dimming can be so pronounced that reds may be confused with black or dark gray, and red traffic lights may appear to be extinguished. They may learn to distinguish reds from yellows primarily on the basis of their apparent brightness or lightness, not on any perceptible hue difference. Violet, lavender, and purple are indistinguishable from various shades of blue. A very few people have been found who have one normal eye and one protanopic eye. These unilateral dichromats report that with only their protanopic eye open, they see wavelengths shorter than neutral point as blue and those longer than it as yellow. Deutan (6% of males): Lacking, or possessing anomalous M-opsins for medium-wavelength sensitive cone cells. Their neutral point is at a slightly longer wavelength, 498 nm, a more greenish hue of cyan. Deutans have the same hue discrimination problems as protans, but without the dimming of long wavelengths. Deuteranopic unilateral dichromats report that with only their deuteranopic eye open, they see wavelengths shorter than neutral point as blue and longer than it as yellow. Blue–yellow color blindness Blue-yellow color blindness includes tritan CVD. Tritan CVD is related to the S-cone and includes tritanomaly (anomalous trichromacy) and tritanopia (dichromacy). Blue-yellow color blindness is much less common than red-green color blindness, and more often has acquired causes than genetic. Tritans have difficulty discerning between bluish and greenish hues. Tritans have a neutral point at 571 nm (yellowish). Tritan (<0.01% of individuals): Lacking, or possessing anomalous S-opsins or short-wavelength sensitive cone cells. Tritans see short-wavelength colors (blue, indigo and spectral violet) as greenish and drastically dimmed, some of these colors even as black. Yellow and orange are indistinguishable from white and pink respectively, and purple colors are perceived as various shades of red. Unlike protans and deutans, the mutation for this color blindness is carried on chromosome 7. Therefore, it is not sex-linked (equally prevalent in both males and females). The OMIM gene code for this mutation is 304000 "Colorblindness, Partial Tritanomaly". Tetartan is the "fourth type" of colorblindness, and a type of blue-yellow color blindness. However, its existence is hypothetical and given the molecular basis of human color vision, it is unlikely this type could exist. Summary of cone complements The below table shows the cone complements for different types of human color vision, including those considered color blindness, normal color vision and superior color vision. The cone complement contains the types of cones (or their opsins) expressed by an individual. Causes Color vision deficiencies can be classified as inherited or acquired. Inherited: inherited or congenital/genetic color vision deficiencies are most commonly caused by mutations of the genes encoding opsin proteins. However, several other genes can also lead to less common and/or more severe forms of color blindness. Acquired: color blindness that is not present at birth, may be caused by chronic illness, accidents, medication, chemical exposure or simply normal ageing processes. Genetics Color blindness is typically an inherited genetic disorder. The most common forms of colorblindness are associated with the Photopsin genes, but the mapping of the human genome has shown there are many causative mutations that dont directly affect the opsins. Mutations capable of causing color blindness originate from at least 19 different chromosomes and 56 different genes (as shown online at the Online Mendelian Inheritance in Man [OMIM]). Genetics of red–green color blindness By far the most common form of colorblindness is congenital red–green colorblindness (Daltonism), which includes protanopia/protanomaly and deuteranopia/deuteranomaly. These conditions are mediated by the OPN1LW and OPN1MW genes, respectively, both on the X chromosome. Protanopia and Deuteranopia (Dichromacy) could be caused by either a missing gene, or a mutation that renders the protein fully non-functional. Protanomaly and Deuteranomaly are caused by a mutation of the genes that causes the spectral sensitivity of the associated opsin proteins to shift towards the other. That is, either the spectral sensitivity of the L cone shifts towards the M cone (blue shift), or that of the M cone shifts towards the L cone (red shift). These are then called anomalous cones and denoted by an asterisk (L* or M). Since the mutated OPN1LW and OPN1MW genes are on the X chromosome, they are sex-linked, and therefore affected males and females disproportionately. Because the colorblind alleles are recessive, colorblindness follows X-linked recessive inheritance. Males have only one X chromosome (XY), and females have two (XX); Because the male only has one allele of each gene, if it is mutated, the male will be colorblind. Because a female has two alleles of each gene (one on each chromosome), if only one allele is mutated, the dominant normal alleles will "override" the mutated, recessive allele and the female will have normal color vision. However, if the female has two mutated alleles, she will still be colorblind. This is why there is a disproportionate prevalence of colorblindness, with ~8% of males exhibiting colorblindness and ~0.5% of females (0.08² = 0.0064 = 0.64%). The following table shows the possible allele/chromosome combinations and how their interactions will manifest in an individual. The exact phenotype of some of the combinations depend on whether the mutation yields an anomalous or non-functioning opsin. Blue cone monochromacy also follows these inheritance patterns, since it essentially a superposition of protanopia and deuteranopia. Y male-only chromosome, no affect on colorblindness. X X chromosome. M (as subscript), normal M opsin. L (as subscript), normal L opsin. M (as subscript), mutated M opsin. L* (as subscript), mutated L opsin.The following table shows the pattern of inheritance for congenital red–green colorblindness (protan/deutan) given affected, unaffected or carrier parents. When daughter 1 and daughter 2 (or son 1 and son 2) differ, this indicates a 50% chance of each outcome. Some conclusions from the table include: A male cannot inherit colorblindness from his father. A colorblind female must have a colorblind father. A female must inherit colorblindness alleles from both parents to be colorblind. Colorblind females can only produce colorblind males. Because carrier females often have a colorblind father, colorblind males often will have a colorblind maternal grandfather (or great grandfather). In this way, colorblindness is often said to skip a generation.Note: these conclusions do not apply to other forms of colorblindness (e.g. tritanopia). Genetics of blue–yellow color blindness Blue-yellow color blindness is a rarer form of colorblindness including tritanopia/tritanomaly. These conditions are mediated by the OPN1SW gene on Chromosome 7. Other genetic causes Several inherited diseases are known to cause color blindness: achromatopsia(also called rod monochromatism, stationary cone dystrophy or cone dysfunction syndrome) cone dystrophy cone-rod dystrophy Lebers congenital amaurosis retinitis pigmentosa(initially affects rods but can later progress to cones and therefore color blindness).They can be congenital (from birth) or can commence in childhood or adulthood. They can be stationary, that is, remain the same throughout a persons lifetime, or progressive. As progressive phenotypes involve deterioration of the retina and other parts of the eye, many of the above forms of color blindness can progress to legal blindness, i.e. an acuity of 6/60 (20/200) or worse, and often leave a person with complete blindness. Non-genetic causes Physical trauma can cause color blindness, either neurologically – brain trauma which produces swelling of the brain in the occipital lobe – or retinally, either acute (e.g. from laser exposure) or chronic (e.g. from ultraviolet light exposure). Color blindness may also present itself as a symptom of degenerative diseases of the eye, such as cataract and age-related macular degeneration, and as part of the retinal damage caused by diabetes. Vitamin A deficiency may also cause color blindness.Color blindness may be a side effect of prescription drug use. For example, red–green color blindness can be caused by ethambutol, a drug used in the treatment of tuberculosis. Blue-yellow color blindness can be caused by sildenafil, an active component of Viagra. Hydroxychloroquine can also lead to hydroxychloroquine retinopathy, which includes various color defects. Exposure to chemicals such as styrene or organic solvents can also lead to color vision defects. Mechanism Color blindness is any deviation of color vision from normal trichromatic color vision (often as defined by the standard observer) that produces a reduced gamut. Mechanisms for color blindness are related to the functionality of cone cells, and often to the expression of photopsins, the photopigments that catch photons and thereby convert light into chemical signals. When an individual does not satisfy the requirements for trichromatic vision, they will express dichromacy or monochromacy and be colorblind. The main requirement for trichromacy is three cone cell classes that are each sensitive to different wavelengths of light and therefore have different spectral sensitivities. Dichromats only express two cone classes and cone monochromats express one. For each cone missing, one of the opponent channels (red-green and blue-yellow) that are responsible for color discrimination are disabled. This is the mechanism for protanopia, deuteranopia, blue cone monochromacy and tritanopia. Even when there is trichromatic color vision and all three opponent channels are active, the size of an individuals color gamut is determined by the dynamic range of the opponent channels, which can be affected by several factors. One of these factors is the peak wavelengths of the spectral sensitivities of the three cones, namely the spectral distance between two cones contributing to an opponent channel. When this distance is smaller, the dynamic range is smaller and the color gamut is smaller, leading to a color vision deficiency. This is the mechanism for congenital protanomaly and deuteranomaly, though not of tritanomaly. The opponent channels can also be affected by the prevalence of certain cones in the retinal mosaic. The cones are not equally prevalent and not evenly distributed in the retina. When the number of one of these cone types is significantly reduced, this can also lead to or contribute to a color vision deficiency. This is one of the causes of tritanomaly. Simple colored filters can also create mild color vision deficiencies. John Daltons original hypothesis for his deuteranopia was actually that the vitreous humor of his eye was discolored: I was led to conjecture that one of the humours of my eye must be a transparent, but coloured, medium, so constituted as to absorb red and green rays principally... I suppose it must be the vitreous humor. An autopsy of his eye after his death in 1844 showed this to be definitively untrue, though other filters are possible. Actual physiological examples usually affect the blue-yellow opponent channel and are named Cyanopsia and Xanthopsia, and are most typically an effect of yellowing or removal of the lens. Tetrachromacy in carriers of CVD Females that are heterozygous for anomalous trichromacy (i.e. carriers) may be tetrachromats. These females have two alleles for either the OPN1MW or OPN1LW gene, and therefore express both the normal and anomalous opsins. Because one X chromosome is inactivated at random in each photoreceptor cell during a females development, those normal and anomalous opsins will be segregated into their own cone cells, and because these cells have different spectral sensitivity, they can functionally operate as different opsins. This theoretical female would therefore have cones with peak sensitivities at 420nm (S cone), 530nm (M cone), 560nm (L cone) and the fourth (anomalous) cone between 530nm and 560nm (either M* or L* cone).If a female is heterozygous for both protanomaly and deuteranomaly, she could be pentachromatic. The degree to which women who are carriers of either protanomaly or deuteranomaly are demonstrably tetrachromatic and require a mixture of four spectral lights to match an arbitrary light is very variable. Jameson et al. have shown that with appropriate and sufficiently sensitive equipment it can be demonstrated that any female carrier of red–green color blindness (i.e. heterozygous protanomaly, or heterozygous deuteranomaly) is a tetrachromat to a greater or lesser extent. Since the incidence of anomalous trichromacy in males is ~6%, which should equal the incidence of anomalous M opsin or L opsin alleles, it follows that the prevalence of unaffected female carriers of colorblindness (and therefore of potential tetrachromats) is 11.3% (i.e. 94% × 6% × 2), based on the Hardy–Weinberg principle. One such woman has been widely reported to be a true or functional tetrachromat, as she can discriminate colors most other people cant. Diagnosis There are several color perception tests, or color vision standards that are capable of diagnosing or screening for color blindness. The Ishihara color test, which consists of a series of pictures of colored spots, is the test most often used to detect red–green color deficiencies and most often recognized by the public. However, this can be attributed more to its ease of application, and less to do with its precision. In fact, there are several types of common color perception tests. Most clinical tests are designed to be fast, simple, and effective at identifying broad categories of color blindness. In academic studies of color blindness, on the other hand, there is more interest in developing flexible tests to collect precise datasets, identify copunctal points, and measure just noticeable differences. Pseudoisochromatic plates A pseudoisochromatic plate (from Greek pseudo, meaning "false", iso, meaning "same" and chromo, meaning "color") is the type of test exemplified by the Ishihara test, where a figure (usually one or more numerals) is embedded in the plate as
Color blindness	a number of spots surrounded by spots of a slightly different color. The figure can be seen with normal color vision, but not with a particular color defect. The figure and background colors must be carefully chosen to appear isochromatic to a color deficient individual, but not an individual with normal color vision. Pseudoisochromatic Plates are used as screening tools because they are cheap, fast and simple, but they do not provide precise diagnosis of CVD, and are often followed with another test if a user fails the Ishihara test.The basic Ishihara test may not be useful in diagnosing young, preliterate children, who cant read the numerals, but larger editions contain plates that showcase a simple path to be traced with a finger, rather than numerals.One of the most common alternative color vision tests based on pseudoisochromatic plates is the HRR color test (developed by Hardy, Rand, and Rittler), which solves many of the criticisms of the Ishihara test. For example, it detects blue-yellow color blindness, is less susceptible to memorization and uses shapes, so it is accessible to the illiterate and young children. Lantern Instead of the Ishihara test, the US Navy and US Army also allow testing with the a lantern, such as the Farnsworth Lantern Test. Lanterns project small colored lights to a subject, who is required to identify the color of the lights. The colors are those of typical signal lights, i.e. red, green and yellow, which also happen to be colors of confusion of red-green CVD. Lanterns do not diagnose colorblind, but they are occupational screening tests to ensure an applicant has sufficient color discrimination to be able to perform a job. This test allows 30% of color deficient individuals, generally with mild CVD, to pass. Arrangement tests Arrangement tests can be used as screening or diagnostic tools. The Farnsworth–Munsell 100 hue test is sensitive enough that it not only can detect color blindness, but also evaluate the color vision of color normals, ranking them as low, average or superior. The Farnsworth D-15 is simpler and is used for screening for CVD. In either case, the subject is asked to arrange a set of colored caps or chips to form a gradual transition of color between two anchor caps. Anomaloscope An instrument called an anomaloscope can also be used for diagnosis. These instruments are very expensive and require expertise to administer, so are generally only used in academic settings. However, they are very precise, being able to diagnose the type and severity of color blindness with high confidence. An anomaloscope designed to detect red-green color blindnesses is based on the Rayleigh match, which compares a mixture of red and green light in variable proportions to a fixed spectral yellow of variable luminosity. The subject must change the two variables until the colors appear to match. The values of the variables at match (and the deviation from the variables of a color normal subject) are used to diagnose the type and severity of colorblindness. For example, deutans will put too much green in the mixture and protans will put too much red in the mixture. Genetic testing Most tests evaluate the phenotype of the subject, i.e. the functionality of their color vision, but the genotype can also be directly evaluated. This is especially useful for progressive forms that do not have a strongly deviant phenotype at a young age. However, it can also be used to sequence the L and M opsins on the X Chromosome. The most common anomalous alleles of these two genes are known and have even been related to exact spectral sensitivities and peak wavelengths. A subjects anomalous alleles can therefore be classified through genetic testing. Management Despite much recent improvement in Gene therapy for color blindness, there is currently no FDA approved treatment for any form of CVD, and otherwise no cure for CVD currently exists. Management of the condition by using lenses to alleviate symptoms or smartphone apps to aid with daily tasks is possible. Lenses There are several kinds of lenses that an individual can wear that can increase their accuracy in some color related tasks. However, none of these will "fix" color blindness or grant the wearer normal color vision. There are three kinds of lenses: A red-tint contact lens worn over the non-dominant eye, will leverage binocular disparity to improve discrimination of some colors. However, it can make other colors more difficult to distinguish. A 1981 review of various studies to evaluate the effect of the X-chrom (one brand) contact lens concluded that, while the lens may allow the wearer to achieve a better score on certain color vision tests, it did not correct color vision in the natural environment. A case history using the X-Chrom lens for a rod monochromat is reported and an X-Chrom manual is online. Tinted glasses (e.g. Pilestone/Colorlite glasses) apply a tint (e.g. magenta) to incoming light that can distort colors in a way that makes some color tasks easier to complete. These glasses can circumvent many colorblind tests, though this is typically not allowed. Glasses with a notch filter (e.g. EnChroma glasses) filter a narrow band of light that excites both the L and M cones (yellow-green wavelengths). When combined with an additional stopband in the short wavelength (blue) region, these lenses may constitute a neutral-density filter (have no color tint). They improve on the other lens types by causing less distortion of colors and will essentially increase the saturation of some colors. They will only work on trichromats (anomalous or normal), and unlike the other types, do not have a significant effect on Dichromats. The glasses do not significantly increase ones ability on colorblind tests. Apps Many mobile and computer applications have been developed to aid color blind individuals in completing color tasks: Some applications can identify a color - by name or RGB code - of a color on screen or the color of an object by using the devices camera. Some applications will make images easier to interpret by the colorblind by enhancing color contrast in natural images and/or information graphics. These methods are generally called daltonization algorithms. Some applications can simulate color blindness by applying a filter to an image or screen that reduces the gamut of an image to that of a specific type of color blindness. While they dont directly help colorblind people, they allow those with normal color vision to understand how people with color blindness see the world. Their use can help improve inclusive design by allowing designers to simulate their own images to ensure they are accessible to the colorblind. Epidemiology Color blindness affects a large number of individuals, with protans and deutans being the most common types. In individuals with Northern European ancestry, as many as 8 percent of men and 0.4 percent of women experience congenital color deficiency. Interestingly, even Daltons very first paper already arrived upon this 8% number: ...it is remarkable that, out of 25 pupils I once had, to whom I explained this subject, 2 were found to agree with me... However, despite his accuracy, the number varies among groups. Isolated communities with a restricted gene pool sometimes produce high proportions of color blindness, including the less usual types. Examples include rural Finland, Hungary, and some of the Scottish islands. In the United States, about 7 percent of the male population—or about 10.5 million men—and 0.4 percent of the female population either cannot distinguish red from green, or see red and green differently from how others do (Howard Hughes Medical Institute, 2006). More than 95 percent of all variations in human color vision involve the red and green receptors in male eyes. It is very rare for males or females to be "blind" to the blue end of the spectrum. History During the 17th and 18th century, several philosophers hypothesized that not all individuals perceived colors in the same way: ...there is no reason to suppose a perfect resemblance in the disposition of the Optic Nerve in all Men, since there is an infinite variety in every thing in Nature, and chiefly in those that are Material, tis therefore very probable that all Men see not the same Colours in the same Objects. In the power of conceiving colors, too, there are striking differences among individuals: and, indeed, I am inclined to suspect, that, in the greater number of instances, the supposed defects of sight in this respect ought to be ascribed rather to a defect in the power of conception. The phenomenon only came to be scientifically studied in 1794, when English chemist John Dalton gave the first account of colour blindness in a paper to the Manchester Literary and Philosophical Society, which was published in 1798 as Extraordinary Facts relating to the Vision of Colours: With Observations. Genetic analysis of Daltons preserved eyeball confirmed him as having deuteranopia in 1995, some 150 years after his death.Influenced by Dalton, German writer J. W. von Goethe studied color vision abnormalities in 1798 by asking two young subjects to match pairs of colors.In 1875, the Lagerlunda train crash in Sweden brought color blindness to the forefront. Following the crash, Professor Alarik Frithiof Holmgren, a physiologist, investigated and concluded that the color blindness of the engineer (who had died) had caused the crash. Professor Holmgren then created the first test for color vision using multicolored skeins of wool to detect color blindness and thereby exclude the colorblind from jobs in the transportation industry requiring color vision to interpret safety signals. However, there is a claim that there is no firm evidence that color deficiency did cause the collision, or that it might have not been the sole cause.In 1920, Frederick William Edridge-Green devised an alternative theory of color vision and color blindness based on Newtons classification of 7 fundamental colors (ROYGBIV). Edridge-Green classified color vision based on how many distinct colors a subject could see in the spectrum. Normal subjects were termed hexachromic as they could not discern Indigo. Subjects with superior color vision, who could discern indigo, where heptachromic. The colorblind were therefore dichromic (equivalent to dichromacy) or tri-, tetra- or pentachromic (anomalous trichromacy). Society and culture Design implications Color codes are useful tools for designers to convey information. The interpretation of this information requires users to perform a variety of Color Tasks, usually comparative but also sometimes connotative or denotative. However, these tasks are often problematic for the colorblind when design of the color code has not followed best practices for accessibility. For example, one of the most ubiquitous connotative color codes is the "red means bad and green means good" or similar systems, based on the classic signal light colors. However, this color coding will almost always be undifferentiable to either (Deutans or Protans) and therefore should be avoided or supplemented with a parallel connotative system (symbols, smileys, etc.). Good practices to ensure design is accessible to the colorblind, include: When possible (e.g. in simple video games or apps), allowing the user to choose their own colors is the most inclusive design practice. Using other signals that are parallel to the color coding, such as patterns, shapes, size or order. This not only helps color blind people, but also aids understanding by normally sighted people by providing them with multiple reinforcing cues. Using brightness contrast (different shades) in addition to color contrast (different hues) To achieve good contrast, conventional wisdom suggests converting a (digital) design to grayscale to ensure there is sufficient brightness contrast between colors. However, this does not account for the different perceptions of brightness to different varieties of colorblindness, especially Protans, Tritans and Monochromats. Viewing the design through a CVD Simulator to ensure the information carried by color is still sufficiently conveyed. At a minimum, the design should be visible for Deutans, the most common kind of colorblindness. Maximizing the area of colors (e.g. increase size, thickness or boldness of colored element) makes the color easier to identify. Color contrast improves as the angle the color subtends on the retina increases. This applies to all types of color vision. Maximizing brightness (value) and saturation (chroma) of the colors to maximize color contrast. Converting connotative tasks to comparative tasks by including a legend, even when the meaning is considered obvious (e.g. red means danger). Avoiding denotative color tasks (color naming) when possible. Some denotative tasks can be converted to comparative tasks by depicting the actual color whenever the color name is mentioned; for example, colored typography in "purple", or "purple (█)". For denotative tasks (color naming), using the most common shades of colors. For example, green and yellow are colors of confusion in red-green CVD, but it is very common to mix forest green (█) with bright yellow (█). Mistakes by the colorblind increase drastically when uncommon shades are used, e.g. neon green (█) with dark yellow (█). For denotative tasks, using colors that are classically associated with a color name. For example, dont use burgundy (█) to represent "red". Unordered Information A common task for designers is to select a subset of colors (qualitative colormap) that are as mutually differentiable as possible (salient). For example, player pieces in a board game should be as different as possible. Classic advice suggests using Brewer palettes, but several of these are not actually colorblind-accessible. A recent, free, powerful tool that checks color contrast of a group of colors is Adobes Color Blind Safe Tool. Unfortunately, the colors with the greatest contrast to the red-green colorblind tend to be colors of confusion to the blue-yellow colorblind, and vice versa. However, since red-green is much more prevalent than blue-yellow CVD, design should generally prioritize those users (Deutans, then Protans). Ordered Information A common task for data visualization is to represent a color scale, or sequential colormap, often in the form of a heat map or choropleth. Several scales are designed with special consideration for the colorblind and are widespread in academia, including Cividis, Viridis and Parula (Matlab). These comprise a light-to-dark scale superimposed on a yellow-to-blue scale, making them monotonic and perceptually uniform to all forms of color vision. Occupations Color blindness may make it difficult or impossible for a person to engage in certain occupations. Persons with color blindness may be legally or practically barred from occupations in which color perception is an essential part of the job (e.g., mixing paint colors), or in which color perception is important for safety (e.g., operating vehicles in response to color-coded signals). This occupational safety principle originates from the aftermath of the 1875 Lagerlunda train crash, which Alarik Frithiof Holmgren blamed on the color blindness of the engineer and created the first occupational screening test against the colorblind. ...I consider that to [Holmgren] above all others do we owe the present and future control of color-blindness on land and sea, by which life and property are safer, and the risks of travelling less. Color vision is important for occupations using telephone or computer networking cabling, as the individual wires inside the cables are color-coded using green, orange, brown, blue and white colors. Electronic wiring, transformers, resistors, and capacitors are color-coded as well, using black, brown, red, orange, yellow, green, blue, violet, gray, white, silver, gold. Driving Red-green colorblindness can make it difficult to drive, primarily due to the inability to differentiate red-amber-green traffic lights. Protans are further disadvantaged due to the darkened perception of reds, which can make it more difficult to quickly recognize brake lights. In response, some countries have refused to grant drivers licenses to individuals with color blindness: In April 2003, Romania removed color blindness from its list of disqualifying conditions for learner drivers licenses. It is now qualified as a condition that could potentially compromise driver safety, therefore a driver may have to be evaluated by an authorized ophthalmologist to determine if they can drive safely. As of May 2008, there is an ongoing campaign to remove the legal restrictions that prohibit colorblind citizens from getting drivers licenses. In June 2020, India relaxed its ban on drivers licenses for the colorblind to now only apply to those with strong CVD. While previously restricted, those who test as mild or moderate can now pass the medical requirements. Australia instituted a tiered ban on the colorblind from obtaining commercial drivers licenses in 1994. This included a ban for all protans, and a stipulation that deutans must pass the Farnsworth Lantern. The stipulation on deutans was revoked in 1997 citing a lack of available test facilities, and the ban on protans was revoked in 2003. All colorblind individuals are banned from obtaining a drivers license in China and since 2016 in Russia (2012 for dichromats). There are several features available that help the colorblind compensate for their color vision deficiency: British Rail signals use more easily identifiable colors: the red is blood red, the amber is yellow and the green is a bluish color. The relative position of traffic lights is fixed internationally as red, amber, green from top to bottom. Horizontal lights will differ depending on the country, but right hand traffic typically follows a "red light always on the left" pattern. Most British road traffic lights are mounted vertically on a black rectangle with a white border (forming a "sighting board") so drivers can more easily look for the position of the light. In the eastern provinces of Canada traffic lights are sometimes differentiated by shape in addition to color: square for red, diamond for yellow, and circle for green (see included image of horizontal traffic light from Nova Scotia). Piloting aircraft Although many aspects of aviation depend on color coding, only a few of them are critical enough to be interfered with by some milder types of color blindness. Some examples include color-gun signaling of aircraft that have lost radio communication, color-coded glide-path indications on runways, and the like. Some jurisdictions restrict the issuance of pilot credentials to persons with color blindness for this reason. Restrictions may be partial, allowing color-blind persons to obtain certification but with restrictions, or total, in which case color-blind persons are not permitted to obtain piloting credentials at all.In the United States, the Federal Aviation Administration requires that pilots be tested for normal color vision as part of their medical clearance in order to obtain the required medical certificate, a prerequisite to obtaining a pilots certification. If testing reveals color blindness, the applicant may be issued a license with restrictions, such as no night flying and no flying by color signals—such a restriction effectively prevents a pilot from holding certain flying occupations, such as that of an airline pilot, although commercial pilot certification is still possible, and there are a few flying occupations that do not require night flight and thus are still available to those with restrictions due to color blindness (e.g., agricultural aviation). The government allows several types of tests, including medical standard tests (e.g., the Ishihara, Dvorine, and others) and specialized tests oriented specifically to the needs of aviation. If an applicant fails the standard tests, they will receive a restriction on their medical certificate that states: "Not valid for night flying or by color signal control". They may apply to the FAA to take a specialized test, administered by the FAA. Typically, this test is the "color vision light gun test". For this test an FAA inspector will meet the pilot at an airport with an operating control tower. The color signal light gun will be shone at the pilot from the tower, and they must identify the color. If they pass they may be issued a waiver, which states that the color vision test is no longer required during medical examinations. They will then receive a new medical certificate with the restriction removed. This was once a Statement of Demonstrated Ability (SODA), but the SODA was dropped, and converted to a simple waiver (letter) early in the 2000s.Research published in 2009 carried out by the City University of Londons Applied Vision Research Centre, sponsored by the UKs Civil Aviation Authority and the U.S. Federal Aviation Administration, has established a more accurate assessment of color deficiencies in pilot applicants red/green and yellow–blue color range which could lead to a 35% reduction in the number of prospective pilots who fail to meet the minimum medical threshold. Art Inability to distinguish color does not necessarily preclude the ability to become a celebrated artist. The 20th century expressionist painter Clifton Pugh, three-time winner of Australias Archibald Prize, on biographical, gene inheritance and other grounds has been identified as a protanope. 19th century French artist Charles Méryon became successful by concentrating on etching rather than painting after he was diagnosed as having a red–green deficiency. Jin Kims red–green color blindness did not stop him from becoming first an animator and later a character designer with Walt Disney Animation Studios. Rights of the color blind Brazil A Brazilian court ruled that people with color blindness are protected by the Inter-American Convention on the Elimination of All Forms of Discrimination against Person with Disabilities.At trial, it was decided that the carriers of color blindness have a right of access to wider knowledge, or the full enjoyment of their human condition. United States In the United States, under federal anti-discrimination laws such as the Americans with Disabilities Act, color vision deficiencies have not been found to constitute a disability that triggers protection from workplace discrimination. Research Some tentative evidence finds that color blind people are better at penetrating certain color camouflages. Such findings may give an evolutionary reason for the high rate of red–green color blindness. There is also a study suggesting that people with some types of color blindness can distinguish colors that people with normal color vision are not able to distinguish. In World War II, color blind observers were used to penetrate camouflage.In September 2009, the journal Nature reported that researchers at the University of Washington and University of Florida were able to give trichromatic vision to squirrel monkeys, which normally have only dichromatic vision, using gene therapy.In 2003, a cybernetic device called eyeborg was developed to allow the wearer to hear sounds representing different colors. Achromatopsic artist Neil Harbisson was the first to use such a device in early 2004; the eyeborg allowed him to start painting in color by memorizing the sound corresponding to each color. In 2012, at a TED Conference, Harbisson explained how he could now perceive colors outside the ability of human vision. See also List of people with color blindness Motion blindness Red–green color space Tetrachromacy City university test Color anomia - Ability to see colors, but inability to name colors. Color agnosia - Ability to see colors, but inability to recognize colors. References Further reading External links Color blindness at Curlie "A Glossary of Color Science."
Cat eye syndrome	Cat eye syndrome (CES) or Schmid–Fraccaro syndrome is a rare condition caused by an abnormal extra chromosome, i.e. a small supernumerary marker chromosome. This chromosome consists of the entire short arm and a small section of the long arm of chromosome 22. In consequence, individuals with the cat eye syndrome have three (trisomic) or four (tetrasomic) copies of the genetic material contained in the abnormal chromosome instead of the normal two copies. The prognosis for patients with CES varies depending on the severity of the condition and their associated signs and symptoms, especially when heart or kidney abnormalities are seen. Signs and symptoms Unilateral or bilateral iris coloboma (absence of tissue from the colored part of the eyes) Preauricular pits/tags (small depressions/growths of skin on the outer ears) Anal atresia (abnormal obstruction of the anus) Downward-slanting palpebral fissures (openings between the upper and lower eyelids) Cleft palate Kidney problems (missing, extra, or underdeveloped kidneys) Short stature Scoliosis/skeletal problems Cardiac defects (such as TAPVR) Micrognathia (smaller jaw) Hernias Biliary atresia Rarer malformations can affect almost any organ Intellectual disability – many are intellectually normal; about 30% of CES patients have moderately impaired mental development, although severe intellectual disability is rare.The term "cat eye" syndrome was coined because of the particular appearance of the vertical colobomas in the eyes of some patients, but over half of the CES patients in the literature do not present with this trait. Genetics The small supernumerary marker chromosome (sSMC) in CES usually arises spontaneously. It may be hereditary and parents may be mosaic for the marker chromosome, but show no phenotypic symptoms of the syndrome. This sSMC may be small, large, or ring-shaped, and typically includes 2 Mb, i.e. 2 million DNA base pairs, termed the CES critical region, located on its q arm(s) between its band 11 and terminus (area notated as 22pter→q11)(also see small supernumerary marker chromosomes in cat eye syndrome). This area contains the CECR1, SLC25A18, and ATP6V1E1 genes which are strong candidate genes for causing or promoting at least some of the birth defects in CES. Diagnosis History The abnormalities common to CES were first cataloged in 1899, and described in association with a small marker chromosome in 1965. Early reports of CES discuss the possibility of chromosome 13 involvement. Now, CES is considered to be present with the chromosome 22 trisomy findings. See also Trisomy 22 References == External links ==
Ligneous conjunctivitis	Ligneous conjunctivitis is a rare form of chronic conjunctivitis characterized by recurrent, fibrin-rich pseudomembranous lesions of wood-like consistency that develop mainly on the underside of the eyelid (tarsal conjunctiva). It is generally a systemic disease which may involve the periodontal tissue, the upper and lower respiratory tract, kidneys, middle ear, and female genitalia. It can be sight-threatening, and death can occasionally occur from pulmonary involvement.It has been speculated hola ligneous conjunctivitis may be a manifestation of IgG4-related disease (IgG4-RD) involving the conjunctiva. Pathogenesis Histopathological findings from affected humans indicate that wound healing is impaired due to a deficiency in plasmin-mediated extracellular fibrinolysis. Episodes may be triggered by minor trauma, eye surgery, or by systemic events such as infections or antifibrinolytic therapy. Histology shows amorphous subepithelial deposits of eosinophilic material consisting predominantly of fibrin. Diagnosis Treatment Ligneous conjunctivitis may be managed by topical treatments of plasminogen, topical and subconjunctival fresh frozen plasma, and fibrinolytic therapy. References == External links ==
Worth syndrome	Worth syndrome, also known as benign form of Worth hyperostosis corticalis generalisata with torus platinus, autosomal dominant osteosclerosis, autosomal dominant endosteal hyperostosis or Worth disease, is a rare autosomal dominant congenital disorder that is caused by a mutation in the LRP5 gene. It is characterized by increased bone density and benign bony structures on the palate. Causes Worth syndrome is caused by a mutation in the LRP5 gene, located on human chromosome 11q13.4. The disorder is inherited in an autosomal dominant fashion. This indicates that the defective gene responsible for a disorder is located on an autosome (chromosome 11 is an autosome), and only one copy of the defective gene is sufficient to cause the disorder, when inherited from a parent who has the disorder. Diagnosis Treatment History The condition was first reported by H. M. Worth in 1966. In 1977, two doctors, R.J. Gorlin and L. Glass, distinguished the syndrome from van Buchem disease. In 1987 a group of Spanish doctors pointed out that the condition may not be benign, and may sometimes cause nerve damage. References == External links ==
Pelvic kidney	A pelvic kidney, also known as an ectopic kidney, is a normal kidney located in the pelvis, instead of the abdomen. This occurs when a kidney does not ascend from its original location in the pelvis to its final location during prenatal development. They usually present no symptoms, but can increase risk of certain illnesses and healthcare problems. Signs and symptoms Often, a person with a pelvic kidney will go through their whole life not even knowing they have a pelvic kidney. Complications Typically, the kidney functions normally despite being in the wrong location. However, it can develop complications. A pelvic kidney can make it more difficult to diagnose kidney infections and kidney cancer. The renal artery and the renal vein may be stretched if they remain attached to the normal locations on the abdominal aorta and the inferior vena cava, which can lead to illness. Causes In the development of the human embryo, the metanephric kidneys fail to ascend and usually remain at the brim of the pelvis. This clinical scenario may present no signs or symptoms and the kidneys may function normally. It is associated at times with Mullerian dysgenesis. Diagnosis A pelvic kidney is discovered on newborn kidney ultrasound screening. It may also be detected if complications arise later in life for this or a completely different reason, and during investigations. Epidemiology Between 1 in 2,200 and 1 in 3,000 people may have a pelvic kidney. History A pelvic kidney is also known as an ectopic kidney. == References ==
Gunshot wound	A gunshot wound (GSW) is a penetrating injury caused by a projectile (e.g. a bullet) from a gun (typically firearm or air gun). Damages may include bleeding, bone fractures, organ damage, wound infection, loss of the ability to move part of the body and, in more severe cases, death. Damage depends on the part of the body hit, the path the bullet follows through the body, and the type and speed of the bullet. Long-term complications can include lead poisoning and post-traumatic stress disorder (PTSD).Factors that determine rates of gun violence vary by country. These factors may include the illegal drug trade, easy access to firearms, substance misuse including alcohol, mental health problems, firearm laws, social attitudes, economic differences and occupations such as being a police officer. Where guns are more common, altercations more often end in death.Before management begins it should be verified the area is safe. This is followed by stopping major bleeding, then assessing and supporting the airway, breathing, and circulation. Firearm laws, particularly background checks and permit to purchase, decrease the risk of death from firearms. Safer firearm storage may decrease the risk of firearm-related deaths in children.In 2015, about a million gunshot wounds occurred from interpersonal violence. In 2016, firearms resulted in 251,000 deaths globally, up from 209,000 in 1990. Of these deaths 161,000 (64%) were the result of assault, 67,500 (27%) were the result of suicide, and 23,000 (9%) were accidents. In the United States, guns resulted in about 40,000 deaths in 2017. Firearm-related deaths are most common in males between the ages of 20 to 24 years. Economic costs due to gunshot wounds have been estimated at US$140 billion a year in the United States. Signs and symptoms Trauma from a gunshot wound varies widely based on the bullet, velocity, mass, entry point, trajectory, affected anatomy, and exit point. Gunshot wounds can be particularly devastating compared to other penetrating injuries because the trajectory and fragmentation of bullets can be unpredictable after entry. Moreover, gunshot wounds typically involve a large degree of nearby tissue disruption and destruction caused by the physical effects of the projectile correlated with the bullet velocity classification.The immediate damaging effect of a gunshot wound is typically severe bleeding with the potential for hypovolemic shock, a condition characterized by inadequate delivery of oxygen to vital organs. In the case of traumatic hypovolemic shock, this failure of adequate oxygen delivery is due to blood loss, as blood is the means of delivering oxygen to the bodys constituent parts. Devastating effects can result when a bullet strikes a vital organ such as the heart, lungs or liver, or damages a component of the central nervous system such as the spinal cord or brain.Common causes of death following gunshot injury include bleeding, low oxygen caused by pneumothorax, catastrophic injury to the heart and major blood vessels, and damage to the brain or central nervous system. Non-fatal gunshot wounds frequently have mild to severe long-lasting effects, typically some form of major disfigurement such as amputation because of a severe bone fracture and may cause permanent disability. A sudden blood gush may take effect immediately from a gunshot wound if a bullet directly damages larger blood vessels, especially arteries. Pathophysiology The degree of tissue disruption caused by a projectile is related to the cavitation the projectile creates as it passes through tissue. A bullet with sufficient energy will have a cavitation effect in addition to the penetrating track injury. As the bullet passes through the tissue, initially crushing then lacerating, the space left forms a cavity; this is called the permanent cavity. Higher-velocity bullets create a pressure wave that forces the tissues away, creating not only a permanent cavity the size of the caliber of the bullet but a temporary cavity or secondary cavity, which is often many times larger than the bullet itself. The temporary cavity is the radial stretching of tissue around the bullets wound track, which momentarily leaves an empty space caused by high pressures surrounding the projectile that accelerate material away from its path. The extent of cavitation, in turn, is related to the following characteristics of the projectile: Kinetic energy: KE = 1/2mv2 (where m is mass and v is velocity). This helps to explain why wounds produced by projectiles of higher mass and/or higher velocity produce greater tissue disruption than projectiles of lower mass and velocity. The velocity of the bullet is a more important determinant of tissue injury. Although both mass and velocity contribute to the overall energy of the projectile, the energy is proportional to the mass while proportional to the square of its velocity. As a result, for constant velocity, if the mass is doubled, the energy is doubled; however, if the velocity of the bullet is doubled, the energy increases four times. The initial velocity of a bullet is largely dependent on the firearm. The US military commonly uses 5.56-mm bullets, which have a relatively low mass as compared with other bullets; however, the speed of these bullets is relatively fast. As a result, they produce a larger amount of kinetic energy, which is transmitted to the tissues of the target. The size of the temporary cavity is approximately proportional to the kinetic energy of the bullet and depends on the resistance of the tissue to stress. Muzzle energy, which is based on muzzle velocity, is often used for ease of comparison. Yaw: Handgun bullets will generally travel in a relatively straight line or make one turn if a bone is hit. Upon travel through deeper tissue, high-energy rounds may become unstable as they decelerate, and may tumble (pitch and yaw) as the energy of the projectile is absorbed, causing stretching and tearing of the surrounding tissue. Fragmentation: Most commonly, bullets do not fragment, and secondary damage from fragments of shattered bone is a more common complication than bullet fragments. Diagnosis Classification Gunshot wounds are classified according to the speed of the projectile using the Gustilo open fracture classification: Low-velocity: Less than 1,100 ft/s (340 m/s)Low velocity wounds are typical of small caliber handguns and display wound patterns like Gustilo Anderson Type 1 or 2 wounds Medium-velocity: Between 1,200 ft/s (340 m/s) and 2,000 ft/s (610 m/s)These are more typical of shotgun blasts or higher caliber handguns like magnums. The risk of infection from these types of wounds can vary depending on the type and pattern of bullets fired as well as the distance from the firearm. High-velocity: Between 2,000 ft/s (610 m/s) and 3,500 ft/s (1,100 m/s)Usually caused by powerful assault or hunting rifles and usually display wound pattern similar to Gustilo Anderson Type 3 wounds. The risk of infection is especially high due to the large area of injury and destroyed tissue.Bullets from handguns are sometimes less than 1,000 ft/s (300 m/s) but with modern pistol loads, they usually are slightly above 1,000 ft/s (300 m/s), while bullets from most modern rifles exceed 2,500 ft/s (760 m/s). One recently developed class of firearm projectiles is the hyper-velocity bullet, such cartridges are usually either wildcats made for achieving such high speed or purpose-built factory ammunition with the same goal in mind. Examples of hyper velocity cartridges include the .220 Swift, .17 Remington and .17 Mach IV cartridges. The US military commonly uses 5.56mm bullets, which have a relatively low mass as compared with other bullets (40-62 grains); however, the speed of these bullets is relatively fast (Approximately 2,800 ft/s (850 m/s), placing them in the high velocity category). As a result, they produce a larger amount of kinetic energy, which is transmitted to the tissues of the target. However, one must remember that high kinetic energy does not necessarily equate to high stopping power, as incapacitation usually results from remote wounding effects such as bleeding, rather than raw energy transfer. High energy does indeed result in more tissue disruption, which plays a role in incapacitation, but other factors such as wound size and shot placement play as big of, if not a bigger role in stopping power and thus, effectiveness. Muzzle velocity does not consider the effect of aerodynamic drag on the flight of the bullet for the sake of ease of comparison. Prevention Medical organizations in the United States recommend a criminal background check being held before a person buys a gun and that a person who has convictions for crimes of violence should not be permitted to buy a gun. Safe storage of firearms is recommended, as well as better mental health care and removal of guns from those at risk of suicide. In an effort to prevent mass shootings greater regulations on guns that can rapidly fire many bullets is recommended. Management Initial assessment for a gunshot wound is approached in the same way as other acute trauma using the advanced trauma life support (ATLS) protocol. These include: A) Airway - Assess and protect airway and potentially the cervical spine B) Breathing - Maintain adequate ventilation and oxygenation C) Circulation - Assess for and control bleeding to maintain organ perfusion including focused assessment with sonography for trauma (FAST) D) Disability - Perform basic neurological exam including Glasgow Coma Scale (GCS) E) Exposure - Expose entire body and search for any missed injuries, entry points, and exit points while maintaining body temperatureDepending on the extent of injury, management can range from urgent surgical intervention to observation. As such, any history from the scene such as gun type, shots fired, shot direction and distance, blood loss on scene, and pre-hospital vitals signs can be very helpful in directing management. Unstable people with signs of bleeding that cannot be controlled during the initial evaluation require immediate surgical exploration in the operating room. Otherwise, management protocols are generally dictated by anatomic entry point and anticipated trajectory. Neck A gunshot wound to the neck can be particularly dangerous because of the high number of vital anatomical structures contained within a small space. The neck contains the larynx, trachea, pharynx, esophagus, vasculature (carotid, subclavian, and vertebral arteries; jugular, brachiocephalic, and vertebral veins; thyroid vessels), and nervous system anatomy (spinal cord, cranial nerves, peripheral nerves, sympathetic chain, brachial plexus). Gunshots to the neck can thus cause severe bleeding, airway compromise, and nervous system injury.Initial assessment of a gunshot wound to the neck involves non-probing inspection of whether the injury is a penetrating neck injury (PNI), classified by violation of the platysma muscle. If the platysma is intact, the wound is considered superficial and only requires local wound care. If the injury is a PNI, surgery should be consulted immediately while the case is being managed. Of note, wounds should not be explored on the field or in the emergency department given the risk of exacerbating the wound. Due to the advances in diagnostic imaging, management of PNI has been shifting from a "zone-based" approach, which uses anatomical site of injury to guide decisions, to a "no-zone" approach which uses a symptom-based algorithm. The no-zone approach uses a hard signs and imaging system to guide next steps. Hard signs include airway compromise, unresponsive shock, diminished pulses, uncontrolled bleeding, expanding hematoma, bruits/thrill, air bubbling from wound or extensive subcutaneous air, stridor/hoarseness, neurological deficits. If any hard signs are present, immediate surgical exploration and repair is pursued alongside airway and bleeding control. If there are no hard signs, the person receives a multi-detector CT angiography for better diagnosis. A directed angiography or endoscopy may be warranted in a high-risk trajectory for the gunshot. A positive finding on CT leads to operative exploration. If negative, the person may be observed with local wound care. Chest Important anatomy in the chest includes the chest wall, ribs, spine, spinal cord, intercostal neurovascular bundles, lungs, bronchi, heart, aorta, major vessels, esophagus, thoracic duct, and diaphragm. Gunshots to the chest can thus cause severe bleeding (hemothorax), respiratory compromise (pneumothorax, hemothorax, pulmonary contusion, tracheobronchial injury), cardiac injury (pericardial tamponade), esophageal injury, and nervous system injury.Initial workup as outlined in the Workup section is particularly important with gunshot wounds to the chest because of the high risk for direct injury to the lungs, heart, and major vessels. Important notes for the initial workup specific for chest injuries are as follows. In people with pericardial tamponade or tension pneumothorax, the chest should be evacuated or decompressed if possible prior to attempting tracheal intubation because the positive pressure ventilation can cause hypotention or cardiovascular collapse. Those with signs of a tension pneumothorax (asymmetric breathing, unstable blood flow, respiratory distress) should immediately receive a chest tube (> French 36) or needle decompression if chest tube placement is delayed. FAST exam should include extended views into the chest to evaluate for hemopericardium, pneumothorax, hemothorax, and peritoneal fluid.Those with cardiac tamponade, uncontrolled bleeding, or a persistent air leak from a chest tube all require surgery. Cardiac tamponade can be identified on FAST exam. Blood loss warranting surgery is 1–1.5 L of immediate chest tube drainage or ongoing bleeding of 200-300 mL/hr. Persistent air leak is suggestive of tracheobronchial injury which will not heal without surgical intervention. Depending on the severity of the persons condition and if cardiac arrest is recent or imminent, the person may require surgical intervention in the emergency department, otherwise known as an emergency department thoracotomy (EDT).However, not all gunshot to the chest require surgery. Asymptomatic people with a normal chest X-ray can be observed with a repeat exam and imaging after 6 hours to ensure no delayed development of pneumothorax or hemothorax. If a person only has a pneumothorax or hemothorax, a chest tube is usually sufficient for management unless there is large volume bleeding or persistent air leak as noted above. Additional imaging after initial chest X-ray and ultrasound can be useful in guiding next steps for stable people. Common imaging modalities include chest CT, formal echocardiography, angiography, esophagoscopy, esophagography, and bronchoscopy depending on the signs and symptoms. Abdomen Important anatomy in the abdomen includes the stomach, small bowel, colon, liver, spleen, pancreas, kidneys, spine, diaphragm, descending aorta, and other abdominal vessels and nerves. Gunshots to the abdomen can thus cause severe bleeding, release of bowel contents, peritonitis, organ rupture, respiratory compromise, and neurological deficits. The most important initial evaluation of a gunshot wound to the abdomen is whether there is uncontrolled bleeding, inflammation of the peritoneum, or spillage of bowel contents. If any of these are present, the person should be transferred immediately to the operating room for laparotomy. If it is difficult to evaluate for those indications because the person is unresponsive or incomprehensible, it is up to the surgeons discretion whether to pursue laparotomy, exploratory laparoscopy, or alternative investigative tools. Although all people with abdominal gunshot wounds were taken to the operating room in the past, practice has shifted in recent years with the advances in imaging to non-operative approaches in more stable people. If the persons vital signs are stable without indication for immediate surgery, imaging is done to determine the extent of injury. Ultrasound (FAST) and help identify intra-abdominal bleeding and X-rays can help determine bullet trajectory and fragmentation. However, the best and preferred mode of imaging is high-resolution multi-detector CT (MDCT) with IV, oral, and sometimes rectal contrast. Severity of injury found on imaging will determine whether the surgeon takes an operative or close observational approach. Diagnostic peritoneal lavage (DPL) has become largely obsolete with the advances in MDCT, with use limited to centers without access to CT to guide requirement for urgent transfer for operation. Extremities The four main components of extremities are bones, vessels, nerves, and soft tissues. Gunshot wounds can thus cause severe bleeding, fractures, nerve deficits, and soft tissue damage. The Mangled Extremity Severity Score (MESS) is used to classify the severity of injury and evaluates for severity of skeletal and/or soft tissue injury, limb ischemia, shock, and age. Depending on the extent of injury, management can range from superficial wound care to limb amputation. Vital sign stability and vascular assessment are the most important determinants of management in extremity injuries. As with other traumatic cases, those with uncontrolled bleeding require immediate surgical intervention. If surgical intervention is not readily available and direct pressure is insufficient to control bleeding, tourniquets or direct clamping of visible vessels may be used temporarily to slow active bleeding. People with hard signs of vascular injury also require immediate surgical intervention. Hard signs include active bleeding, expanding or pulsatile hematoma, bruit/thrill, absent distal pulses and signs of extremity ischemia.For stable people without hard signs of vascular injury, an injured extremity index (IEI) should be calculated by comparing the blood pressure in the injured limb compared to an uninjured limb in order to further evaluate for potential vascular injury. If the IEI or clinical signs are suggestive of vascular injury, the person may undergo surgery or receive further imaging including CT angiography or conventional arteriography. In addition to vascular management, people must be evaluated for bone, soft tissue, and nerve injury. Plain films can be used for fractures alongside CTs for soft tissue assessment. Fractures must be debrided and stabilized, nerves repaired when possible, and soft tissue debrided and covered. This process can often require multiple procedures over time depending on the severity of injury. Epidemiology In 2015, about a million gunshot wounds occurred from interpersonal violence. Firearms, globally in 2016, resulted in 251,000 deaths up from 209,000 in 1990. Of these deaths 161,000 (64%) were the result of assault, 67,500 (27%) were the result of suicide, and 23,000 were accidents. Firearm related deaths are most common in males between the ages of 20 to 24 years.The countries with the greatest number of deaths from firearms are Brazil, United States, Mexico, Colombia, Venezuela, Guatemala and South Africa which make up just over half the total. In the United States in 2015 about half of the 44,000 people who died by suicide did so with a gun.As of 2016, the countries with the highest rates of gun violence per capita were El Salvador, Venezuela, and Guatemala with 40.3, 34.8, and 26.8 violent gun deaths per 100,000 people respectively. The countries with the lowest rates of were Singapore, Japan, and South Korea with 0.03, 0.04, and 0.05 violent gun deaths per 100,000 people respectively. Canada In 2016, about 893 people died due to gunshot wounds in Canada (2.1 per 100,000). About 80% were suicides, 12% were assaults, and 4% percent were an accident. United States In 2017, there were 39,773 deaths in the United States as a result gunshot wounds. Of these 60% were suicides, 37% were homicides, 1.4% were by law enforcement, 1.2% were accidents, and 0.9% were from an unknown cause. This is up from 37,200 deaths in 2016 due to a gunshot wound (10.6 per 100,000). With respect to those that pertain to interpersonal violence, it had the 31st highest rate in the world with 3.85 deaths per 100,000 people in 2016. The majority of all homicides and suicides are firearm-related, and the majority of firearm-related deaths are the result of murder and suicide. When sorted by GDP, however, the United States has a much higher violent gun death rate compared to other developed countries, with over 10 times the number of firearms assault deaths than the next four highest GDP countries combined. Gunshot violence is the third most costly cause of injury and the fourth most expensive form of hospitalization in the United States. History Until the 1880s, the standard practice for treating a gunshot wound called for physicians to insert their unsterilized fingers into the wound to probe and locate the path of the bullet. Standard surgical theory such as opening abdominal cavities to repair gunshot wounds, germ theory, and Joseph Listers technique for antiseptic surgery using diluted carbolic acid, had not yet been accepted as standard practice. For example, sixteen doctors attended to President James A. Garfield after he was shot in 1881, and most probed the wound with their fingers or dirty instruments. Historians agree that massive infection was a significant factor in Garfields death.At almost the same time, in Tombstone, Arizona Territory, on 13 July 1881, George E. Goodfellow performed the first laparotomy to treat an abdominal gunshot wound.: M-9 Goodfellow pioneered the use of sterile techniques in treating gunshot wounds, washing the persons wound and his hands with lye soap or whisky, and his patient, unlike the President, recovered. He became Americas leading authority on gunshot wounds and is credited as the United States first civilian trauma surgeon.Mid-nineteenth-century handguns such as the Colt revolvers used during the American Civil War had muzzle velocities of just 230–260 m/s and their powder and ball predecessors had velocities of 167 m/s or less. Unlike todays high-velocity bullets, nineteenth-century balls produced almost little or no cavitation and, being slower moving, they were liable to lodge in unusual locations at odds with their trajectory.Wilhelm Röntgens discovery of X-rays in 1895 led to the use of radiographs to locate bullets in wounded soldiers.Survival rates for gunshot wounds improved among US military personnel during the Korean and Vietnam Wars, due in part to helicopter evacuation, along with improvements in resuscitation and battlefield medicine. Similar improvements were seen in US trauma practices during the Iraq War. Some military trauma care practices are disseminated by citizen soldiers who return to civilian practice. One such practice is to transfer major trauma cases to an operating theater as soon as possible, to stop internal bleeding. Within the United States, the survival rate for gunshot wounds has increased, leading to apparent declines in the gun death rate in states that have stable rates of gunshot hospitalizations. Research Research into gunshot wounds in the USA is hampered by lack of funding. Federal-funded research into firearm injury, epidemiology, violence, and prevention is minimal. See also Blast injury, an injury that may present similar dangers to a gunshot wound. Bullet hit squib, the simulated equivalent of a gunshot wound used in the film industry to portray a gunshot wound. Stab wound, an equivalent penetrating injury caused by a bladed weapon or any other sharp objects. References External links Virtual Autopsy – CT scans of fatal gunshot wounds Patient.info
Radiation burn	A radiation burn is a damage to the skin or other biological tissue and organs as an effect of radiation. The radiation types of greatest concern are thermal radiation, radio frequency energy, ultraviolet light and ionizing radiation. The most common type of radiation burn is a sunburn caused by UV radiation. High exposure to X-rays during diagnostic medical imaging or radiotherapy can also result in radiation burns. As the ionizing radiation interacts with cells within the body—damaging them—the body responds to this damage, typically resulting in erythema—that is, redness around the damaged area. Radiation burns are often discussed in the same context as radiation-induced cancer due to the ability of ionizing radiation to interact with and damage DNA, occasionally inducing a cell to become cancerous. Cavity magnetrons can be improperly used to create surface and internal burning. Depending on the photon energy, gamma radiation can cause deep gamma burns, with 60Co internal burns common. Beta burns tend to be shallow as beta particles are not able to penetrate deeply into a body; these burns can be similar to sunburn. Alpha particles can cause internal alpha burns if inhaled, with external damage (if any) being limited to minor erythema. Radiation burns can also occur with high power radio transmitters at any frequency where the body absorbs radio frequency energy and converts it to heat. The U.S. Federal Communications Commission (FCC) considers 50 watts to be the lowest power above which radio stations must evaluate emission safety. Frequencies considered especially dangerous occur where the human body can become resonant, at 35 MHz, 70 MHz, 80-100 MHz, 400 MHz, and 1 GHz. Exposure to microwaves of too high intensity can cause microwave burns. Types Radiation dermatitis (also known as radiodermatitis) is a skin disease associated with prolonged exposure to ionizing radiation.: 131–2 Radiation dermatitis occurs to some degree in most patients receiving radiation therapy, with or without chemotherapy.There are three specific types of radiodermatitis: acute radiodermatitis, chronic radiodermatitis, and eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy.: 39–40 Radiation therapy can also cause radiation cancer.: 40 With interventional fluoroscopy, because of the high skin doses that can be generated in the course of the intervention, some procedures have resulted in early (less than two months after exposure) and/or late (two months or more after exposure) skin reactions, including necrosis in some cases.: 773 Radiation dermatitis, in the form of intense erythema and vesiculation of the skin, may be observed in radiation ports.: 131 As many as 95% of patients treated with radiation therapy for cancer will experience a skin reaction. Some reactions are immediate, while others may be later (e.g., months after treatment). Acute Acute radiodermatitis occurs when an "erythema dose" of ionizing radiation is given to the skin, after which visible erythema appears up to 24 hours after.: 39 Radiation dermatitis generally manifests within a few weeks after the start of radiotherapy.: 143 Acute radiodermatitis, while presenting as red patches, may sometimes also present with desquamation or blistering. Erythema may occur at a dose of 2 Gy radiation or greater. Chronic Chronic radiodermatitis occurs with chronic exposure to "sub-erythema" doses of ionizing radiation over a prolonged period, producing varying degrees of damage to the skin and its underlying parts after a variable latent period of several months to several decades.: 40 In the distant past this type of radiation reaction occurred most frequently in radiologists and radiographers who were constantly exposed to ionizing radiation, especially before the use of X-ray filters.: 40 Chronic radiodermatitis, squamous and basal cell carcinomas may develop months to years after radiation exposure.: 130 Chronic radiodermatitis presents as atrophic indurated plaques, often whitish or yellowish, with telangiectasia, sometimes with hyperkeratosis.: 130 Other Eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy is a skin condition that occurs most often in women receiving cobalt radiotherapy for internal cancer.: 39–40 Radiation-induced erythema multiforme may occur when phenytoin is given prophylactically to neurosurgical patients who are receiving whole-brain therapy and systemic steroids.: 130 Delayed effects Radiation acne is a cutaneous condition characterized by comedo-like papules occurring at sites of previous exposure to therapeutic ionizing radiation, skin lesions that begin to appear as the acute phase of radiation dermatitis begins to resolve.: 501 Radiation recall reactions occur months to years after radiation treatment, a reaction that follows recent administration of a chemotherapeutic agent and occurs with the prior radiation port, characterized by features of radiation dermatitis. Restated, radiation recall dermatitis is an inflammatory skin reaction that occurs in a previously irradiated body part following drug administration. There does not appear to be a minimum dose, nor an established radiotherapy dose relationship. Alpha burns "Alpha burns" are caused by alpha particles, which can cause extensive tissue damage if inhaled. Due to the keratin in the epidermal layer of the skin, external alpha burns are limited to only mild reddening of the outermost layer of skin. Beta burns "Beta burns"—caused by beta particles—are shallow surface burns, usually of skin and less often of lungs or gastrointestinal tract, caused by beta particles, typically from hot particles or dissolved radionuclides that came to direct contact with or close proximity to the body. They can appear similar to sunburn. Unlike gamma rays, beta emissions are stopped much more effectively by materials and therefore deposit all their energy in only a shallow layer of tissue, causing more intense but more localized damage. On cellular level, the changes in skin are similar to radiodermatitis. High doses of radiation can cause rapid browning of skin, known as "nuclear tan".The dose is influenced by relatively low penetration of beta emissions through materials. The cornified keratine layer of epidermis has enough stopping power to absorb beta radiation with energies lower than 70 keV. Further protection is provided by clothing, especially shoes. The dose is further reduced by limited retention of radioactive particles on skin; a 1 millimeter particle is typically released in 2 hours, while a 50 micrometer particle usually does not adhere for more than 7 hours. Beta emissions are also severely attenuated by air; their range generally does not exceed 6 feet (1.8 m) and intensity rapidly diminishes with distance.The eye lens seems to be the most sensitive organ to beta radiation, even in doses far below maximum permissible dose. Safety goggles are recommended to attenuate strong beta.Beta burns can occur also to plants. An example of such damage is the Red Forest, a victim of the Chernobyl accident. Careful washing of exposed body surface, removing the radioactive particles, may provide significant dose reduction. Exchanging or at least brushing off clothes also provides a degree of protection. If the exposure to beta radiation is intense, the beta burns may first manifest in 24–48 hours by itching and/or burning sensation that last for one or two days, sometimes accompanied by hyperaemia. After 1–3 weeks burn symptoms appear; erythema, increased skin pigmentation (dark colored patches and raised areas), followed by epilation and skin lesions. Erythema occurs after 5–15 Gy, dry desquamation after 17 Gy, and bullous epidermitis after 72 Gy. Chronic radiation keratosis may develop after higher doses. Primary erythema lasting more than 72 hours is an indication of injury severe enough to cause chronic radiation dermatitis. Edema of dermal papillae, if present within 48 hours since the exposition, is followed by transepidermal necrosis. After higher doses, the malpighian layer cells die within 24 hours; lower doses may take 10–14 days to show dead cells. Inhalation of beta radioactive isotopes may cause beta burns of lungs and nasopharyngeal region, ingestion may lead to burns of gastrointestinal tract; the latter being a risk especially for grazing animals. In first degree beta burns the damage is largely limited to epidermis. Dry or wet desquamation occurs; dry scabs are formed, then heal rapidly, leaving a depigmented area surrounded with irregular area of increased pigmentation. The skin pigmentation returns to normal within several weeks. Second degree beta burns lead to formation of blisters. Third and fourth degree beta burns result in deeper, wet ulcerated lesions, which heal with routine medical care after covering themselves with dry scab. In case of heavy tissue damage, ulcerated necrotic dermatitis may occur. Pigmentation may return to normal within several months after wound healing.Lost hair begins regrowing in nine weeks and is completely restored in about half a year.The acute dose-dependent effects of beta radiation on skin are as follows: According to other source: As shown, the dose thresholds for symptoms vary by source and even individually. In practice, determining the exact dose tends to be difficult. Similar effects apply to animals, with fur acting as additional factor for both increased particle retention and partial skin shielding. Unshorn thickly wooled sheep are well protected; while the epilation threshold for sheared sheep is between 23 and 47 Gy (2500–5000 rep) and the threshold for normally wooled face is 47–93 Gy (5000–10000 rep), for thickly wooled (33 mm hair length) sheep it is 93–140 Gy (10000–15000 rep). To produce skin lesions comparable with contagious pustular dermatitis, the estimated dose is between 465 and 1395 Gy. Energy vs penetration depth The effects depend on both the intensity and the energy of the radiation. Low-energy beta (sulfur-35, 170 keV) produces shallow ulcers with little damage to dermis, while cobalt-60 (310 keV), caesium-137 (550 keV), phosphorus-32 (1.71 MeV), strontium-90 (650 keV) and its daughter product yttrium-90 (2.3 MeV) damage deeper levels of the dermis and can result in chronic radiation dermatitis. Very high energies from electron beams from particle accelerators, reaching tens of megaelectronvolts, can be deeply penetrating. Conversely, megavolt-scale beams can deposit their energy deeper with less damage to the dermis; modern radiotherapy electron beam accelerators take advantage of this. At yet higher energies, above 16 MeV, the effect does not show significantly anymore, limiting the usefulness of higher energies for radiotherapy. As a convention, surface is defined as the topmost 0.5 mm of skin. High-energy beta emissions should be shielded with plastic instead of lead, as high-Z elements generate deeply penetrating gamma bremsstrahlung. The electron energies from beta decay are not discrete but form a continuous spectrum with a cutoff at maximum energy. The rest of the energy of each decay is carried off by an antineutrino which does not significantly interact and therefore does not contribute to the dose. Most energies of beta emissions are at about a third of the maximum energy. Beta emissions have much lower energies than what is achievable from particle accelerators, no more than few megaelectronvolts. The energy-depth-dose profile is a curve starting with a surface dose, ascending to the maximum dose in a certain depth dm (usually normalized as 100% dose), then descends slowly through depths of 90% dose (d90) and 80% dose (d80), then falls off linearly and relatively sharply though depth of 50% dose (d50). The extrapolation of this linear part of the curve to zero defines the maximum electron range, Rp. In practice, there is a long tail of weaker but deep dose, called "bremsstrahlung tail", attributable to bremsstrahlung. The penetration depth depends also on beam shape, narrower beam tend to have less penetration. In water, broad electron beams, as is the case in homogeneous surface contamination of skin, have d80 about E/3 cm and Rp about E/2 cm, where E is the beta particle energy in MeV.The penetration depth of lower-energy beta in water (and soft tissues) is about 2 mm/MeV. For a 2.3 MeV beta the maximum depth in water is 11 mm, for 1.1 MeV it is 4.6 mm. The depth where maximum of the energy is deposited is significantly lower.The energy and penetration depth of several isotopes is as follows: For a wide beam, the depth-energy relation for dose ranges is as follows, for energies in megaelectronvolts and depths in millimeters. The dependence of surface dose and penetration depth on beam energy is clearly visible. Causes Radiation burns are caused by exposure to high levels of radiation. Levels high enough to cause burn are generally lethal if received as a whole-body dose, whereas they may be treatable if received as a shallow or local dose. Medical imaging Fluoroscopy may cause burns if performed repeatedly or for too long.Similarly, X-ray computed tomography and traditional projectional radiography have the potential to cause radiation burns if the exposure factors and exposure time are not appropriately controlled by the operator. A study of radiation-induced skin injuries has been performed by the Food and Drug Administration (FDA) based on results from 1994, followed by an advisory to minimize further fluoroscopy-induced injuries. The problem of radiation injuries due to fluoroscopy has been further investigated in review articles in 2000, 2001, 2009 and 2010. Radioactive fallout Beta burns are frequently the result of exposure to radioactive fallout after nuclear explosions or nuclear accidents. Shortly after the explosion, the fission products have very high beta activity, with about two beta emissions per each gamma photon. After the Trinity test, the fallout caused localized burns on the backs of cattle in the area downwind. The fallout had the appearance of small flaky dust particles. The cattle showed temporary burns, bleeding, and loss of hair. Dogs were also affected; in addition to localized burns on their backs, they also had burned paws, likely from the particles lodged between their toes as hoofed animals did not show problems with feet. About 350–600 cattle were affected by superficial burns and localized temporary loss of dorsal hair; the army later bought 75 most affected cows as the discolored regrown hair lowered their market value. The cows were shipped to Los Alamos and Oak Ridge, where they were observed. They healed, now sporting large patches of white fur; some looked as if they had been scalded.The fallout produced by the Castle Bravo test was unexpectedly strong. A white snow-like dust, nicknamed by the scientists "Bikini snow" and consisting of contaminated crushed calcined coral, fell for about 12 hours upon the Rongelap Atoll, depositing a layer of up to 2 cm. Residents developed beta burns, mostly on the backs of their necks and on their feet, and were resettled after three days. After 24–48 hours their skin was itching and burning; in a day or two the sensations subsided, to be followed after 2–3 weeks by epilation and ulcers. Darker-colored patches and raised areas appeared on their skin, blistering was uncommon. Ulcers formed dry scabs and healed. Deeper lesions, painful, weeping and ulcerated, formed on more contaminated residents; the majority healed with simple treatment. In general, the beta burns healed with some cutaneous scarring and depigmentation. Individuals who bathed and washed the fallout particles from their skin did not develop skin lesions. The fishing ship Daigo Fukuryu Maru was affected by the fallout as well; the crew suffered skin doses between 1.7 and 6.0 Gy, with beta burns manifesting as severe skin lesions, erythema, erosions, sometimes necrosis, and skin atrophy. Twenty-three U.S. radar servicemen of the 28-member weather station on Rongerik were affected, experiencing discrete 1–4 mm skin lesions which healed quickly, and ridging of fingernails several months later. Sixteen crew members of the aircraft carrier USS Bairoko received beta burns, and there was an increased cancer rate.During the Zebra test of the Operation Sandstone in 1948, three men had beta burns on their hands when removing sample collection filters from drones flying through the mushroom cloud; their estimated skin surface dose was 28 to 149 Gy, and their disfigured hands required skin grafts. A fourth man showed weaker burns after the earlier Yoke test.The Upshot–Knothole Harry test at the Frenchman Flat site released a large amount of fallout. A significant number of sheep died after grazing on contaminated areas. The AEC however had a policy to compensate farmers only for animals showing external beta burns, so many claims were denied. Other tests on the Nevada Test Site also caused fallout and corresponding beta burns to sheep, horses and cattle. During the Operation Upshot–Knothole, sheep as far as 50 miles (80 km) from the test site developed beta burns to their backs and nostrils.During underground nuclear testing in Nevada, several workers developed burns and skin ulcers, in part attributed to exposure to tritium. Nuclear accidents Beta burns were a serious medical issue for some victims of the Chernobyl disaster; from 115 patients treated in Moscow, 30% had burns covering 10–50% of body surface, 11% were affected on 50–100% of skin; the massive exposure was often caused by clothes drenched with radioactive water. Some firefighters developed beta burns of lungs and nasopharyngeal region after inhalation of massive amounts of radioactive smoke. Out of 28 deaths, 16 had skin injuries listed among the causes. The beta activity was extremely high, with beta/gamma ratio reaching 10–30 and beta energy high enough to damage basal layer of the skin, resulting in large area portals for infections, exacerbated by damage to bone marrow and weakened immune system. Some patients received skin dose of 400–500 Gy. The infections caused more than half of the acute deaths. Several died of fourth degree beta burns between 9–28 days after dose of 6–16 Gy. Seven died after dose of 4–6 Gy and third degree beta burns in 4–6 weeks. One died later from second degree beta burns and dose 1-4 Gy. The survivors have atrophied skin which is spider veined and with underlying fibrosis.The burns may manifest at different times at different body areas. The Chernobyl liquidators burns first appeared on wrists, face, neck and feet, followed by chest and back, then by knees, hips and buttocks.Industrial radiography sources are a common source of beta burns in workers. Radiation therapy sources can cause beta burns during exposure of the patients. The sources can be also lost and mishandled, as in the Goiânia accident, during which several people had external beta burns and more serious gamma burns, and several died. Numerous accidents also occur during radiotherapy due to equipment failures, operator errors, or wrong dosage. Electron beam sources and particle accelerators can be also sources of beta burns. The burns may be fairly deep and require skin grafts, tissue resection or even amputation of fingers or limbs. Treatment Radiation burns should be covered by a clean, dry dressing as soon as possible to prevent infection. Wet dressings are not recommended. The presence of combined injury (exposure to radiation plus trauma or radiation burn) increases the likelihood of generalized sepsis. This requires administration of systemic antimicrobial therapy. See also Effective radiated power Radiation poisoning Radiation protection Therac-25 References External links ARRL: RF Exposure Safety FCC: Radio Frequency Safety FAQ
Pinguecula	A pinguecula is a common type of conjunctival stromal degeneration in the eye. It appears as an elevated yellow-white plaque in the bulbar conjunctiva near the limbus. Calcification may also seen occasionally. Etiology The exact etiology is unknown, but it may be associated with aging and excessive exposure to UV light. Signs and symptoms It is seen as a yellow-white deposit on the conjunctiva adjacent to the limbus (the junction between the cornea and sclera). (It is to be distinguished clinically from a pterygium, which is a wedge shaped area of fibrosis that may grow onto the cornea.) A pinguecula usually does not cause any symptoms. It is most common in tropical climates and there is a direct correlation with UV exposure. Histologically, there is degeneration of the collagen fibers of the conjunctival stroma with thinning of the overlying epithelium and occasionally calcification. Actinic exposure of the thin conjunctival tissue is thought to cause fibroblasts to produce more elastin fibers, which are more twisted than normal elastin fibers and may lead to the degradation of the collagen fibers. Alternatively, it has been postulated that the sub-epithelial collagen fibers undergo degradation and assume the qualities of elastic tissue while fragmenting and twisting in a different configuration from their normal state.It is thought that the high reflectivity of the solid white scleral tissue underlying the conjunctival tissue may result in additional UV exposure to the back side of the tissue. The side of the nose also reflects sunlight on to the conjunctiva. As a result, pingueculae tend to occur more often on the nasal side of the eye. While most pingueculae are found in people over the age of 40, they are not uncommon in 20- and 30-year-old adults who spend significant time in the sun. The surface of the conjunctival tissue overlying a pinguecula interferes with the normal spreading of the tear film. The tear ferning test reveals abnormalities of the mucous component of the tear film, making it useful as a predictor of a persons tolerance of hydrophilic soft contact lenses. Contact lens intolerance can also result from the elevation of the peripheral edge of the contact lens if it overlies a pinguecula. The plural form of pinguecula is pingueculae. Pinguecula is derived from the Latin word "pinguis" for fat or grease. Associated conditions A pinguecula is one of the differential diagnoses for a limbal nodule. It may have an increased prevalence in Gauchers disease. Diagnosis Diagnosis of pinguecula is usually done by an eye care professional during routine eye examination using slit lamp. Conjunctival biopsy may be advised if malignancy is suspected. Treatment Pingueculae may enlarge slowly over time, but are a benign condition, usually requiring no treatment. Artificial tears may help to relieve discomfort, if it occurs. If cosmesis is a concern, or if there is discomfort in contact lens use, surgical excision may be done. Occasionally, a pinguecula may become inflamed, a condition called pingueculitis. The cause of pingueculitis is unknown and there are no known infectious agents associated with it. If an inflamed pinguecula is causing discomfort or cosmetic concerns, it may be treated with short course of topical steroid. Laser photocoagulation may also be used to remove pinguecula. See also Peripheral light focusing Pterygium (conjunctiva) References == External links ==
Coats disease	Coats disease is a rare congenital, nonhereditary eye disorder, causing full or partial blindness, characterized by abnormal development of blood vessels behind the retina. Coats disease can also fall under glaucoma. It can have a similar presentation to that of retinoblastoma. Signs and symptoms The most common sign at presentation is leukocoria (abnormal white reflection of the retina). Symptoms typically begin as blurred vision, usually pronounced when one eye is closed (due to the unilateral nature of the disease). Often the unaffected eye will compensate for the loss of vision in the other eye; however, this results in some loss of depth perception and parallax. Deterioration of sight may begin in either the central or peripheral vision. Deterioration is likely to begin in the upper part of the vision field as this corresponds with the bottom of the eye where blood usually pools. Flashes of light, known as photopsia, and floaters are common symptoms. Persistent color patterns may also be perceived in the affected eye. Initially, these may be mistaken for psychological hallucinations, but are actually the result of both retinal detachment and foreign fluids mechanically interacting with the photoreceptors located on the retina. One early warning sign of Coats disease is yellow-eye in flash photography. Just as the red-eye effect is caused by a reflection off blood vessels in the back of a normal eye, an eye affected by Coats will glow yellow in photographs as light reflects off cholesterol deposits. Children with yellow-eye in photographs are typically advised to immediately seek evaluation from an optometrist or ophthalmologist, who will assess and diagnose the condition and refer to a vitreo-retinal specialist. Coats disease itself is painless. Pain may occur if fluid is unable to drain from the eye properly, causing the internal pressure to swell, resulting in painful glaucoma. Presentation Coats usually affects only one eye (unilateral) and occurs predominantly in young males 1/100,000, with the onset of symptoms generally appearing in the first decade of life. Peak age of onset is between 6–8 years of age, but onset can range from 5 months to 71 years.Coats disease results in a gradual loss of vision. Blood leaks from the abnormal vessels into the back of the eye, leaving behind cholesterol deposits and damaging the retina. Coats disease normally progresses slowly. At advanced stages, retinal detachment is likely to occur. Glaucoma, atrophy, and cataracts can also develop secondary to Coats disease. In some cases, removal of the eye may be necessary (enucleation). Coats disease is a rare extramuscular manifestation of facioscapulohumeral muscular dystrophy (FSHD). A single study reported it in 1 percent of FSHD patients, most often those with FSHD type 1 (FSHD1) with large D4Z4 deletions. Pathogenesis Coats disease is thought to result from breakdown of the blood-retinal barrier in the endothelial cells, resulting in leakage of blood products containing cholesterol crystals and lipid-laden macrophages into the retina and subretinal space. Over time, the accumulation of this proteinaceous exudate thickens the retina, leading to massive, exudative retinal detachment. Diagnosis On funduscopic eye examination, the retinal vessels in early Coats disease appear tortuous and dilated, mainly confined to the peripheral and temporal portions of retina. In moderate to severe Coats disease, massive retinal detachment and hemorrhage from the abnormal vessels may be seen. Imaging findings Imaging studies such as ultrasonography (US), Computerized Tomography (CT) and Magnetic Resonance Imaging (MRI) can aid diagnosis. On ultrasound, Coats disease appears as a hyperechoic mass in the posterior vitreous without posterior acoustic shadowing; vitreous and subretinal hemorrhage may often be observed.On CT, the globe appears hyperdense compared to normal vitreous due to the proteinaceous exudate, which may obliterate the vitreous space in advanced disease. The anterior margin of the subretinal exudate enhances with contrast. Since the retina is fixed posteriorly at the optic disc, this enhancement has a V-shaped configuration.On MRI, the subretinal exudate shows high signal intensity on both T1- and T2-weighted images. The exudate may appear heterogeneous if hemorrhage or fibrosis is present. The subretinal space does not enhance with gadolinium contrast. Mild to moderate linear enhancement may be seen between the exudate and the remaining vitreous. The exudate shows a large peak at 1–1.6 ppm on proton MR spectroscopy. Pathologic findings Grossly, retinal detachment and yellowish subretinal exudate containing cholesterol crystals are commonly seen. Microscopically, the wall of retinal vessels may be thickened in some cases, while in other cases the wall may be thinned with irregular dilatation of the lumen. The subretinal exudate consists of cholesterol crystals, macrophages laden with cholesterol and pigment, erythrocytes, and hemosiderin. A granulomatous reaction, induced by the exudate, may be seen with the retina. Portions of the retina may develop gliosis as a response to injury. Treatment In the early stages, there are a few treatment options. Laser surgery or cryotherapy (freezing) can be used to destroy the abnormal blood vessels, thus halting progression of the disease. However, if the leaking blood vessels are clustered around the optic nerve, this treatment is not recommended as accidental damage to the nerve itself can result in permanent blindness. Although Coats disease tends to progress to visual loss, it may stop progressing on its own, either temporarily or permanently. Cases have been documented in which the condition even reverses itself. However, once total retinal detachment occurs, sight loss is permanent in most cases. Removal of the eye (enucleation) is an option if pain or further complications arise. History Coats disease is named after George Coats. References External links GeneReviews/NIH/NCBI/UW entry on NDP-Related Retinopathies http://www.orpha.net/data/patho/GB/uk-Coats.pdf
Adrenal crisis	Adrenal crisis is a potentially life-threatening medical condition requiring immediate emergency treatment. It is a constellation of symptoms (caused by insufficient levels of the hormone cortisol) that indicate severe adrenal insufficiency. This may be the result of either previously undiagnosed or untreated Addisons disease, a disease process suddenly affecting adrenal function (such as bleeding from the adrenal glands in Waterhouse–Friderichsen syndrome), suddenly stopping intake of glucocorticoids or an intercurrent problem (e.g. infection, trauma, in fact any form of physical or mental stress) in someone known to have Addisons disease, congenital adrenal hyperplasia (CAH), or other form of primary adrenal insufficiency. Signs and symptoms Characteristic symptoms are: Sudden penetrating pain in the legs, lower back or abdomen Confusion, psychosis, slurred speech Severe lethargy Convulsions Fever Hyperkalemia (elevated potassium level in the blood) Hypercalcemia (elevated calcium level in the blood): the cause of hypercalcemia is a combination of increased calcium input into the extracellular space and reduced calcium removal by the kidney, this last caused by decreased glomerular filtration and increased tubular calcium reabsorption. Both renal factors are secondary to volume depletion and, in fact, improve rapidly during rehydration with saline infusion. Hypoglycemia (reduced level of blood glucose) Hyponatremia (low sodium level in the blood) Hypotension (low blood pressure) Hypothyroidism (low T4 level) Severe vomiting and diarrhea, resulting in dehydration Syncope (transient loss of consciousness) and/or orthostatic hypotension (drop in blood pressure on standing, leading to loss of balance) Causes Adrenal crisis is caused by a deficiency of cortisol resulting from Addisons disease, congenital adrenal hyperplasia (CAH), corticosteroid biosynthetic enzyme defects or pituitary disorders (such as Sheehans syndrome, pituitary adenoma, hypopituitarism (inactive or underactive pituitary) causing failure to activate the adrenal glands. May also be a side effect of Zytiga (Abiraterone) for prostate cancer. Diagnosis Various investigations aid the diagnosis: ACTH (cosyntropin) stimulation test Cortisol level (to assess the level of glucocorticoids) Fasting blood sugar Serum potassium (to assess the level of mineralocorticoids) Serum sodium Prevention Adrenal crisis is triggered by physiological stress (such as trauma) or severe psychological stress. Activities that have an elevated risk of trauma are best avoided. Treatment must be given within two hours of trauma and consequently it is advisable to carry injectable hydrocortisone in remote areas. Treatment Acute adrenal insufficiency is a medical emergency and needs to be treated with injectable hydrocortisone and fluid support. 1L of 0.9% saline over 30-60 min with 100 mg of i.v. Bolus hydrocortisone. Continuous infusion of saline within 24hours with 100 mg I.m. hydrocortisone 6-hourly. Glucose To be shifted to oral medication based on the patients state. Hydrocortisone 20 mg 8-hourly reduced to 20–30 mg in divided doses over few days. Fludrocortisone is given later. Epidemiology Hahner et al. investigated the frequency, causes and risk factors for adrenal crisis in patients with chronic adrenal insufficiency. See also Stress dose References External links Acute adrenal crisis on PubmedHealth Adrenal Crisis on Patient.info
Amusia	Amusia is a musical disorder that appears mainly as a defect in processing pitch but also encompasses musical memory and recognition. Two main classifications of amusia exist: acquired amusia, which occurs as a result of brain damage, and congenital amusia, which results from a music-processing anomaly present since birth. Studies have shown that congenital amusia is a deficit in fine-grained pitch discrimination and that 4% of the population has this disorder. Acquired amusia may take several forms. Patients with brain damage may experience the loss of ability to produce musical sounds while sparing speech, much like aphasics lose speech selectively but can sometimes still sing. Other forms of amusia may affect specific sub-processes of music processing. Current research has demonstrated dissociations between rhythm melody and emotional processing of music. Amusia may include impairment of any combination of these skill sets. Signs and symptoms Symptoms of amusia are generally categorized as receptive, clinical, or mixed. Symptoms of receptive amusia, sometimes referred to as "musical deafness" or "tone deafness", include the inability to recognize familiar melodies, the loss of ability to read musical notation, and the inability to detect wrong or out-of tune notes. Clinical, or expressive, symptoms include the loss of ability to sing, write musical notation, and/or play an instrument. A mixed disorder is a combination of expressive and receptive impairment.Clinical symptoms of acquired amusia are much more variable than those of congenital amusia and are determined by the location and nature of the lesion. Brain injuries may affect motor or expressive functioning, including the ability to sing, whistle, or hum a tune (oral-expressive amusia), the ability to play an instrument (instrumental amusia or musical apraxia), and the ability to write music (musical agraphia). Additionally, brain damage to the receptive dimension affects the faculty to discriminate tunes (receptive or sensorial amusia), the ability to read music (musical alessia), and the ability to identify songs that were familiar prior to the brain damage (amnesic amusia).Research suggests that patients with amusia also have difficulty when it comes to spatial processing. Amusics performed more quickly than normal individuals on a combined task of both spatial and musical processing tasks, which is most likely due to their deficit. Normal individuals experience interference due to their intact processing of both musical and spatial tasks, while amusics do not. Pitch processing normally depends on the cognitive mechanisms that are usually used to process spatial representations.Those with congenital amusia show impaired performance on discrimination, identification and imitation of sentences with intonational differences in pitch direction in their final word. This suggests that amusia can in subtle ways impair language processing. Social and emotional Amusic individuals have a remarkable sparing of emotional responses to music in the context of severe and lifelong deficits in processing music. Some individuals with amusia describe music as unpleasant. Others simply refer to it as noise and find it annoying. This can have social implications because amusics often try to avoid music, which in many social situations is not an option.In China and other countries where tonal languages are spoken, amusia may have a more pronounced social and emotional impact: difficulty in speaking and understanding the language. However, context clues are often strong enough to determine the correct meaning, similarly to how homophones can be understood. Related diseases Amusia has been classified as a learning disability that affects musical abilities. Research suggests that in congenital amusia, younger subjects can be taught tone differentiation techniques. This finding leads researchers to believe that amusia is related to dyslexia and other similar disorders. Research has been shown that amusia may be related to an increase in size of the cerebral cortex, which may be a result of a malformation in cortical development. Conditions such as dyslexia and epilepsy are due to a malformation in cortical development and also lead to an increase in cortical thickness, which leads researchers to believe that congenital amusia may be caused by the identical phenomenon in a different area of the brain.Amusia is also similar to aphasia in that they affect similar areas of the brain near the temporal lobe. Most cases of those with amusia do not show any symptoms of aphasia. However, a number of cases have shown that those who have aphasia can exhibit symptoms of amusia, especially in acquired aphasia. The two are not mutually exclusive and having one does not imply possession of the other. 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. An individual is considered amusic if they perform two standard deviations below the mean obtained by musically competent controls.This musical pitch disorder represents a phenotype that serves to identify the associated neuro-genetic factors. Both MRI-based brain structural analyses and electroencephalography (EEG) are common methods employed to uncover brain anomalies associated with amusia (See Neuroanatomy). Additionally, voxel-based morphometry (VBM) is used to detect anatomical differences between the MRIs of amusic brains and musically intact brains, specifically with respect increased and/or decreased amounts of white and grey matter. Classifications There are two general classifications of amusia: congenital amusia and acquired amusia. Congenital amusia Congenital amusia, commonly known as tone deafness, refers to a musical disability that cannot be explained by prior brain lesion, hearing loss, cognitive defects, or lack of environmental stimulation, and it affects about 4% of the population. Individuals with congenital amusia seem to lack the musical predispositions with which most people are born. They are unable to recognize or hum familiar tunes even if they have normal audiometry and above-average intellectual and memory skills. Also, they do not show sensitivity to dissonant chords in a melodic context, which, as discussed earlier, is one of the musical predispositions exhibited by infants. The hallmark of congenital amusia is a deficit in fine-grained pitch discrimination, and this deficit is most apparent when congenital amusics are asked to pick out a wrong note in a given melody. If the distance between two successive pitches is small, congenital amusics are not able to detect a pitch change. As a result of this defect in pitch perception, a lifelong musical impairment may emerge due to a failure to internalize musical scales. A lack of fine-grained pitch discrimination makes it extremely difficult for amusics to enjoy and appreciate music, which consists largely of small pitch changes.Tone-deaf people seem to be disabled only when it comes to music as they can fully interpret the prosody or intonation of human speech. Tone deafness has a strong negative correlation with belonging to societies with tonal languages. This could be evidence that the ability to reproduce and distinguish between notes may be a learned skill; conversely, it may suggest that the genetic predisposition towards accurate pitch discrimination may influence the linguistic development of a population towards tonality. A correlation between allele frequencies and linguistic typological features has been recently discovered, supporting the latter hypothesis.Tone deafness is also associated with other musical-specific impairments such as the inability to keep time with music (beat deafness, or the lack of rhythm), or the inability to remember or recognize a song. These disabilities can appear separately, but some research shows that they are more likely to appear in tone-deaf people. Experienced musicians, such as W. A. Mathieu, have addressed tone deafness in adults as correctable with training. Acquired amusia Acquired amusia is a musical disability that shares the same characteristics as congenital amusia, but rather than being inherited, it is the result of brain damage. It is also more common than congenital amusia. While it has been suggested that music is processed by music-specific neural networks in the brain, this view has been broadened to show that music processing also encompasses generic cognitive functions, such as memory, attention, and executive processes. A study was published in 2009 which investigated the neural and cognitive mechanisms that underlie acquired amusia and contribute to its recovery. The study was performed on 53 stroke patients with a left or right hemisphere middle cerebral artery (MCA) infarction one week, three months, and six months after the stroke occurred. Amusic subjects were identified one week following their stroke, and over the course of the study, amusics and non-amusics were compared in both brain lesion location and their performances on neuropsychological tests.Results showed that there was no significant difference in the distribution of left and right hemisphere lesions between amusic and non-amusic groups, but that the amusic group had a significantly higher number of lesions to the frontal lobe and auditory cortex. Temporal lobe lesions were also observed in patients with amusia. Amusia is a common occurrence following an ischemic MCA stroke, as evidenced by the 60% of patients who were found to be amusic at the one-week post-stroke stage. While significant recovery takes place over time, amusia can persist for long periods of time. Test results suggest that acquired amusia and its recovery in the post-stroke stage are associated with a variety of cognitive functions, particularly attention, executive functioning and working memory. Neuroanatomy Neurologically intact individuals appear to be born musical. Even before they are able to talk, infants show remarkable musical abilities that are similar to those of adults in that they are sensitive to musical scales and a regular tempo. Also, infants are able to differentiate between consonant and dissonant intervals. These perceptual skills indicate that music-specific predispositions exist.Prolonged exposure to music develops and refines these skills. Extensive musical training does not seem to be necessary in the processing of chords and keys. The development of musical competence most likely depends on the encoding of pitch along musical scales and maintaining a regular pulse, both of which are key components in the structure of music and aid in perception, memory, and performance. Also, the encoding of pitch and temporal regularity are both likely to be specialized for music processing. Pitch perception is absolutely crucial to processing music. The use of scales and the organization of scale tones around a central tone (called the tonic) assign particular importance to notes in the scale and cause non-scale notes to sound out of place. This enables the listener to ascertain when a wrong note is played. However, in individuals with amusia, this ability is either compromised or lost entirely.Music-specific neural networks exist in the brain for a variety of music-related tasks. It has been shown that Brocas area is involved in the processing of musical syntax. Furthermore, brain damage can disrupt an individuals ability to tell the difference between tonal and atonal music and detect the presence of wrong notes, but can preserve the individuals ability to assess the distance between pitches and the direction of the pitch. The opposite scenario can also occur, in which the individual loses pitch discrimination capabilities, but can sense and appreciate the tonal context of the work. Distinct neural networks also exist for music memories, singing, and music recognition. Neural networks for music recognition are particularly intriguing. A patient can undergo brain damage that renders them unable to recognize familiar melodies that are presented without words. However, the patient maintains the ability to recognize spoken lyrics or words, familiar voices, and environmental sounds. The reverse case is also possible, in which the patient cannot recognize spoken words, but can still recognize familiar melodies. These situations overturn previous claims that speech recognition and music recognition share a single processing system. Instead, it is clear that there are at least two distinct processing modules: one for speech and one for music.Many research studies of individuals with amusia show that a number of cortical regions appear to be involved in processing music. Some report that the primary auditory cortex, secondary auditory cortex, and limbic system are responsible for this faculty, while more recent studies suggest that lesions in other cortical areas, abnormalities in cortical thickness, and deficiency in neural connectivity and brain plasticity may contribute to amusia. While various causes of amusia exist, some general findings that provide insight to the brain mechanisms involved in music processing are discussed below. Pitch relations Studies suggest that the analysis of pitch is primarily controlled by the right temporal region of the brain. The right secondary auditory cortex processes pitch change and manipulation of fine tunes; specifically, this region distinguishes the multiple pitches that characterize melodic tunes as contour (pitch direction) and interval (frequency ratio between successive notes) information. The right superior temporal gyrus recruits and evaluates contour information, while both right and left temporal regions recruit and evaluate interval information. In addition, the right anterolateral part of Heschls gyrus (primary auditory cortex) is also concerned with processing pitch information. Temporal relations The brain analyzes the temporal (rhythmic) components of music in two ways: (1) it segments the ongoing sequences of music into temporal events based on duration, and (2) it groups those temporal events to understand the underlying beat to music. Studies on rhythmic discrimination reveal that the right temporal auditory cortex is responsible for temporal segmenting, and the left temporal auditory cortex is responsible for temporal grouping. Other studies suggest the participation of motor cortical areas in rhythm perception and production. Therefore, a lack of involvement and networking between bilateral temporal cortices and neural motor centers may contribute to both congenital and acquired amusia. Memory Memory is required in order to process and integrate both melodic and rhythmic aspects of music. Studies suggest that there is a rich interconnection between the right temporal gyrus and frontal cortical areas for working memory in music appreciation. This connection between the temporal and frontal regions of the brain is extremely important since these regions play critical roles in music processing. Changes in the temporal areas of the amusic brain are most likely associated with deficits in pitch perception and other musical characteristics, while changes in the frontal areas are potentially related to deficits in cognitive processing aspects, such as memory, that are needed for musical discrimination tasks. Memory is also concerned with the recognition and internal representation of tunes, which help to identify familiar songs and confer the ability to sing tunes in ones head. The activation of the superior temporal region and left inferior temporal and frontal areas is responsible for the recognition of familiar songs, and the right auditory cortex (a perceptual mechanism) is involved in the internal representation of tunes. These findings suggest that any abnormalities and/or injuries to these regions of the brain could facilitate amusia. Other regions of the brain possibly linked to amusia Lesions in (or the absence of) associations between the right temporal lobe and inferior frontal lobe. In nine of ten tone-deaf people, the superior arcuate fasciculus in the right hemisphere could not be detected, suggesting a disconnection between the posterior superior temporal gyrus and the posterior inferior frontal gyrus. Researchers suggested the posterior superior temporal gyrus was the origin of the disorder. Cortical thickness and reduced white matter – in a recent study, voxel-based morphometry, an imaging technique used to explore structural differences in the brain, revealed a decrease in white matter concentration in the right inferior frontal gyrus of amusic individuals as compared to controls. Lack of extensive exposure to music could be a contributing factor to this white matter reduction. For example, amusic individuals may be less inclined to listen to music than others, which could ultimately cause reduced myelination of connections to the frontal areas of the brain. Involvement of the parahippocampal gyrus (responsible for the emotional reaction to music) Treatment Currently, no forms of treatment have proven effective in treating amusia. One study has shown tone differentiation techniques to have some success; however, future research on treatment of this disorder will be necessary to verify this technique as an appropriate treatment. History In 1825, F. Gall mentioned a "musical organ" in a specific region of the human brain that could be spared or disrupted after a traumatic event resulting in brain damage. In 1865, Jean-Baptiste Bouillaud described the first series of cases that involved the loss of music abilities that were due to brain injury. In 1878, Grant Allen was the first to describe in the medical literature what would later be termed congenital amusia, calling it "note-deafness". Later, during the late nineteenth century, several influential neurologists studied language in an attempt to construct a theory of cognition. While not studied as thoroughly as language, music and visual processing were also studied. In 1888–1890, August Knoblauch produced a cognitive model for music processing and termed it amusia. This model for music processing was the earliest produced.While the possibility that certain individuals may be born with musical deficits is not a new notion, the first documented case of congenital amusia was published only in 2002. The study was conducted with a female volunteer, referred to as Monica, who declared herself to be musically impaired in response to an advertisement in the newspaper. Monica had no psychiatric or neurological history, nor did she have any hearing loss. MRI scans showed no abnormalities. Monica also scored above average on a standard intelligence test, and her working memory was evaluated and found to be normal. However, Monica had a lifelong inability to recognize or perceive music, which had persisted even after involvement with music through church choir and band during her childhood and teenage years. Monica said that she does not enjoy listening to music because, to her, it sounded like noise and evoked a stressful response. In order to determine if Monicas disorder was amusia, she was subjected to the MBEA series of tests. One of the tests dealt with Monicas difficulties in discriminating pitch variations in sequential notes. In this test, a pair of melodies was played, and Monica was asked if the second melody in the pair contained a wrong note. Monicas score on this test was well below the average score generated by the control group. Further tests showed that Monica struggled with recognizing highly familiar melodies, but that she had no problems in recognizing the voices of well-known speakers. Thus, it was concluded that Monicas deficit seemed limited to music. A later study showed that not only do amusics experience difficulty in discriminating variations in pitch, but they also exhibit deficits in perceiving patterns in pitch.This finding led to another test that was designed to assess the presence of a deficiency in pitch perception. In this test, Monica heard a sequence of five piano tones of constant pitch followed by a comparison sequence of five piano tones in which the fourth tone could be the same pitch as the other notes in the sequence or a completely different pitch altogether. Monica was asked to respond "yes" if she detected a pitch change on the fourth tone or respond "no" if she could not detect a pitch change. Results showed that Monica could barely detect a pitch change as large as two semitones (whole tone), or half steps. While this pitch-processing deficit is extremely severe, it does not seem to include speech intonation. This is because pitch variations in speech are very coarse compared with those used in music. In conclusion, Monicas learning disability arose from a basic problem in pitch discrimination, which is viewed as the origin of congenital amusia. Research Over the past decade, much has been discovered about amusia. However, there remains a great deal more to learn. While a method of treatment for people with amusia has not been defined, tone differentiation techniques have been used on amusic patients with some success. It was found with this research that children reacted positively to these tone differentiation techniques, while adults found the training annoying. However, further research in this direction would aid in determining if this would be a viable treatment option for people with amusia. Additional research can also serve to indicate which processing component in the brain is essential for normal music development. Also, it would be extremely beneficial to investigate musical learning in relation to amusia since this could provide valuable insights into other forms of learning disabilities such as dysphasia and dyslexia. Notable cases In fiction Horatio Hornblower Grace from Home on the Range James Fraser from Outlander by Diana Gabaldon Rodrigo from Mozart in the Jungle See also Absolute pitch, the human ability to name a musical note when played or sung (less common than relative pitch) Auditory agnosia Cognitive neuroscience of music Color blindness Musical aptitude Music-specific disorders Relative pitch, the human ability to accurately distinguish pitch intervals (more common than absolute pitch) Synesthesia Tonal memory References Further reading Kazez D (1985). "The myth of tone deafness". Music Educators Journal. 71 (8): 46–47. doi:10.2307/3396499. JSTOR 3396499. S2CID 144988256. Kleist, Karl (1962). Sensory aphasia and amusia; the myeloarchitectonic basis. Oxford: Pergamon Press. OCLC 1649635. External links MedicineNet: Amusia NIH: Distorted Tunes Test The Listening Book: Tone-Deaf Choir audio description by W. A. Mathieu
Polyhydramnios	Polyhydramnios is a medical condition describing an excess of amniotic fluid in the amniotic sac. It is seen in about 1% of pregnancies. It is typically diagnosed when the amniotic fluid index (AFI) is greater than 24 cm. There are two clinical varieties of polyhydramnios: chronic polyhydramnios where excess amniotic fluid accumulates gradually, and acute polyhydramnios where excess amniotic fluid collects rapidly. The opposite to polyhydramnios is oligohydramnios, not enough amniotic fluid. Presentation Associated conditions Fetuses with polyhydramnios are at risk for a number of other problems including cord prolapse, placental abruption, premature birth and perinatal death. At delivery the baby should be checked for congenital abnormalities. Causes In most cases, the exact cause cannot be identified. A single case may have one or more causes, including intrauterine infection (TORCH), rh-isoimmunisation, or chorioangioma of the placenta. In a multiple gestation pregnancy, the cause of polyhydramnios usually is twin-to-twin transfusion syndrome. Maternal causes include cardiac problems, kidney problems, and maternal diabetes mellitus, which causes fetal hyperglycemia and resulting polyuria (fetal urine is a major source of amniotic fluid). A recent study distinguishes between mild and severe polyhydramnios and showed that Apgar score of less than 7, perinatal death and structural malformations only occurred in women with severe polyhydramnios. In another study, all patients with polyhydramnios, that had a sonographically normal fetus, showed no chromosomal anomalies.(M/C for polyhydramnio is fetal anomalies Williams Obstetrics, 24th Edition – Cunningham, Leveno, Bloom et al. Table 11–2) but these anomalies include: gastrointestinal abnormalities such as esophageal atresia and duodenal atresia (causing inability to swallow amniotic fluid), anencephaly, facial cleft, neck masses, tracheoesophageal fistula, and diaphragmatic hernias. An annular pancreas causing obstruction may also be the cause. Bochdaleks hernia, in which the pleuro-peritoneal membranes (especially the left) will fail to develop and seal the pericardio-peritoneal canals. This results in the stomach protrusion up into the thoracic cavity, and the fetus is unable to swallow sufficient amounts of amniotic fluid. fetal renal disorders that result in increased urine production during pregnancy, such as in antenatal Bartter syndrome. Molecular diagnosis is available for these conditions. neurological abnormalities such as anencephaly, which impair the swallowing reflex. Anencephaly is failure of closure of the rostral neuropore (rostral neural tube defect). If the rostral neuropore fails to close there will be no neural mechanism for swallowing. chromosomal abnormalities such as Down syndrome and Edwards syndrome, which is itself often associated with gastrointestinal abnormalities. Skeletal dysplasia, or dwarfism. There is a possibility of the chest cavity not being large enough to house all of the babys organs causing the trachea and esophagus to be restricted, not allowing the baby to swallow the appropriate amount of amniotic fluid. sacrococcygeal teratoma Diagnosis There are several pathologic conditions that can predispose a pregnancy to polyhydramnios. These include a maternal history of diabetes mellitus, Rh incompatibility between the fetus and mother, intrauterine infection, and multiple pregnancies. During the pregnancy, certain clinical signs may suggest polyhydramnios. In the mother, the physician may observe increased abdominal size out of proportion for her weight gain and gestation age, uterine size that outpaces gestational age, shiny skin with stria (seen mostly in severe polyhydramnios), dyspnea, and chest heaviness. When examining the fetus, faint fetal heart sounds are also an important clinical sign of this condition. Treatment Mild asymptomatic polyhydramnios is managed expectantly. A woman with symptomatic polyhydramnios may need hospital admission. Antacids may be prescribed to relieve heartburn and nausea. No data support dietary restriction of salt and fluid. In some cases, amnioreduction, also known as therapeutic amniocentesis, has been used in response to polyhydramnios. See also Amniotic fluid index References External links 00329 at CHORUS
Paraneoplastic pemphigus	Paraneoplastic pemphigus (PNP) is an autoimmune disorder stemming from an underlying tumor. It is hypothesized that antigens associated with the tumor trigger an immune response resulting in blistering of the skin and mucous membranes. While patients with malignant and benign tumors are both at risk, malignancy is associated with high mortality rates (near 90%). Current treatment focuses on general wound healing and administering corticosteroids, which has not demonstrated a high success rate. Recent research developments aim to treat the underlying tumor in order to alleviate the symptoms of PNP. Signs and symptoms While the presence of lesions is the denominator among patients with PNP, the characteristics of the lesions differ. The five clinical presentations of lesions associated with PNP include: "Pemphigus-like": Flaccid blister (discrete), crusts over the raw exuding skin lesions "Pemphigoid-like": Tense blister(s) on brick red erythema "Erythema multiforme-like": Severe polymorphic skin and/or mucous membrane lesions "Graft-vs.-host disease-like": Widespread lichenoid eruption with severe mucous membrane involvement "Lichen planus-like": Small red flat-topped scaly papulesIt is most common that mucous membrane lesions of the oral cavity are presented first. They can involve the oropharynx, nasopharynx, tongue, and vermilion (red portion) of the lips. They are also known to develop in the conjunctiva of the eye, anogenital (perineum) region, and esophagus. Cutaneous lesions tend to follow the onset of mucosal lesions. The blisters often erupt in waves, usually affecting the upper trunk, head, neck, and proximal extremities. Pemphigoid-like lesions are seen more often on the extremities. Lichenoid lesions are more common among children, presenting on the trunk and limbs, ranging from small red scaly papules to extensive violet to brown papules extending to the face and neck. Within the spectrum of lichenoid presentations are wounds that have features of erythema multiforme and graft-vs.-host disease. Scaly lesions on the palms of the hand and soles of the feet have been noted to coincide with the lichenoid lesions. Lesions of varying morphology may present simultaneously and transform from one type to another as the disease progresses. Mechanism Underlying cause PNP is ultimately caused by the presence of a tumor. There is a strong association between the development of PNP and malignancy of the tumor. However, it is not uncommon for the tumor to be benign, as in the case of afflictions such as thymoma and Castlemans disease. Only one patient without a tumor has met the diagnostic criteria for PNP. However, they rapidly reached their demise and it is suggested they may have had an undiagnosed tumor. Mechanism behind display of major symptoms The underlying tumor causes circulating and tissue-bound antibodies to direct themselves against antigens in the plakin family, which are involved in the intracellular attachment structures in various levels of the skin/respiratory tract/membranes (keeping skin tissue together throughout the body). The number of target antigens varies on a case by case basis. The variability is likely what accounts for the different presentations of PNP. Through immunoprecipitation, target antigens have been found to include desmoglein-3, desmoglein-1, envoplakin, periplakin, desmoplakin 1, desmoplakin 2, and bullous pemphigoid antigen I.The precise mechanism for how tumors are able to induce autoantibodies toward the plakin proteins is unknown. Suggested theories include tumor production of plakin proteins which initiate an autoimmune response against them, and cross-reactivity of tumor antigens and epidermal antigens.Once the molecules that hold the various levels of the membranes together are attacked, they are unable to function properly, and the tissue breaks apart. This is manifested as the associated blistering and lesions of PNP. Diagnosis In order to diagnose paraneoplastic pemphigus, several tests may be performed. Initially, samples are obtained via skin biopsy for routine microscopy and direct immunofluorescence (DIF) testing. The skin sample needs to be obtained from an unaffected area adjacent to a lesion. Testing in more detail follows depending on the results from the DIF. Prompt diagnosis of PNP is crucial due to the high mortality rate of the disease. Camisa and Helm revised the original criteria from Anhalt et al. into major and minor signs indicating PNP:Major: Polymorphic mucocutaneous eruption Concurrent internal tumor Serum antibodies with a specific immunoprecipitation patternMinor: Histologic evidence of acantholysis (loss of intercellular connections leading to breaking apart of the skin; lesion) Direct immunofluorescence showing intercellular and basement membrane staining Indirect immunofluorescence staining with rat bladder epithelium Microscopy Microscopy of the skin sample obtained from the biopsy is used to detect the presence of cleavage within the dermis, epidermal acantholysis (breaking apart of the skin), dyskeratotic keratinocytes and vacuolar changes in the layers of the skin, interfacial dermatitis, and epidermal exocytosis. Presentation of these characteristics suggests PNP. Direct immunofluorescence testing The presence of Immunoglobulin G, A, or M in the epidermis is normal. Detection in other locations such as intercellular and areas below the epidermis (subepidermal), as well as along the dermoepidermal junction (area that joins the epidermis and dermis), suggests paraneoplastic pemphigus. Follow-up tests for confirmation Indirect immunofluorescence (IDIF) Patients with high concentration of antibodies show intercellular, intraepidermal antibodies as well as along the dermoepidermal junction. Patients with low concentration of antibodies only present with them inside the cells (intercellular).If the results are negative, perform the additional assays regardless. Cases have been confirmed that reported with initial negative DIF and IDIF tests. Assays Immunoprecipitation, immunoblotting and enzyme-link immunosorbent assay (ELISA) Poot et al. 2013 determined that immunoprecipitation for antibodies against envoplakin and periplakin or alpha2-macroglobulin-like–1 is the most sensitive test. However, alpha2-macroglobulin-like-1 can also be detected in patients with toxic epidermal necrosis. Similar diseases with overlapping symptoms Bullous Pemphigoid, Cicatricial Pemphigoid, Drug Eruptions. Epidermolysis Bullosa, Epidermolysis Bullosa Acquisita, Erythema Multiforme, Lichen Planus, pemphigus vulgaris, Stevens–Johnson syndrome and toxic epidermal necrolysis.PNP is most commonly mistaken for pemphigus vulgaris, due to the extreme similarities of the lesions that develop. However, the difference lies in the specificity of the autoreactive antibodies in each case. Treatment Wound healing Initial treatment involves addressing any existing infections that may have occurred due to the broken state of the skin. Existing wounds are treated with warm compresses, non-adherent (non-stick) dressing, and topical antibiotic ointment. Immunosuppressive agents are administered in attempt to decrease blistering; this is not often effective. The first medication given aiming to heal the wounds are high dose corticosteroids. This is followed by steroid sparing agents which may reduce steroid intake and therefore lessen the side effects. Skin lesions are more likely to respond to this line of treatment than mucosal lesions. However, a high level of caution is advised in patients with a confirmed malignancy, where immunosuppression is vital and dictates treatment options. If the initial therapy fails to control the symptoms of PNP, and the condition of the patient deteriorates, a more aggressive approach may be necessary. Medication Prednisone Prednisone is an immunosuppressive agent which affects all of the organ systems. Effects on the cellular level include cell activation, replication, differentiation, and mobility. The overall goal is to decrease blistering (inhibition of immediate and delayed hypersensitivity) through decreasing the production of autoantibodies. In order to suppress the production of antibodies, higher doses must be administered. Lesser doses can be prescribed in order to achieve suppression of monocyte function. Azathioprine Azathioprine is a steroid-sparing agent used in combination with Prednisone. It functions by inhibiting RNA and DNA synthesis. Ciclosporin Ciclosporin is an immunosuppressive agent most often used in organ transplantation that has demonstrated to be effective with skin disorders. It functions by lessening production of autoantibodies and therefore diminishing the development of blisters and erosions. The mechanism of action is by inhibiting the production of T lymphocytes and lymphokines. Cyclophosphamide Cyclophosphamide is an immunomodulator used in combination with systemic steroids to remove bone marrow. This is followed by transplanting peripheral blood stem cells. Prognosis Quality of life/ Life expectancy If the lesions are mild, the patient will be subject to a good deal of pain. If the lesions are severe, the overall quality of life is devastating. The impaired skin barrier function commonly leads to localized infection, which sepsis and death may follow. The pain from the oral and pharyngeal ulcers interfere with eating, which can compromise nutritional health.The general prognosis for PNP is poor. It is more hopeful if the tumor is benign, but in the case of malignant tumors, the mortality rate is roughly 90%. The two most commonly associated types of tumors are non-Hodgkin lymphoma and chronic lymphocytic lymphoma; nearly all of these patients die within two years of diagnosis. This is attributed to the effects of the tumor combined with the negative side effects of the medication administered to treat PNP.Roughly 1/3 of the deaths from PNP stem from pulmonary insufficiency which is brought about by the action of PNP on the respiratory mucosa. It manifests as dyspnea and progresses to bronchiolitis obliterans (non-reversible obstructive lung disease) via an unknown mechanism. Risk Factors As PNP is ultimately caused by the presence of a tumor, it is not contagious. There is no known way to predict who will become afflicted with it. Patients with cancer are therefore a group at risk. Although PNP has been known to affect all age groups, it is more likely to afflict middle-aged to older patients. Recent research The Development of ELISA testing for specific diagnosis of PNP was released in 2009. The research focuses on the specific determination of autoantibodies involved in the mechanism of PNP. Specifically, antibodies against envoplakin and periplakin were being investigated. Further use of ELISA testing on these antibodies confirmed the presence of anti-envoplakin and anti-periplakin autoantibodies in patients with PNP.Further research in 2013 outlined the various types of assays that could be used to determine which antibodies were involved in PNP. Demonstration of certain antibodies in the serum was named as the basis for diagnosis of PNP. This piece labeled PNP as a "multiorgan disease characterized by antibodies against plakins, desmogleins and the α2-macroglobulin-like-1 (A2ML1) protein, in association with an underlying neoplasm".A study concluded in 2009, summarized in 2010, surrounded the surgical removal of the associated tumor as a means to treat PNP. While 7/22 of the subjects perished due to resulting infection from the bodys inability to heal itself after surgery, the other 15 cases survived. This study outlined the importance of early detection and prompt treatment as of utmost important in the treatment of PNP.In 2011, a case study of a woman with ulcers on the back of her leg reported as being diagnosed with PNP. The underlying tumors are almost exclusively of B-cell lineage. However, T-cells and CD56+ Natural Killer cells have also been postulated to be associated effectors of paraneoplastic pemphigus. This case demonstrated the rare association between Natural Killer cell lymphoma and PNP, suggesting that Natural Killer cells could be involved in the pathogenesis of PNP. The article warned clinicians to be alert to the possibility that paraneoplastic pemphigus in lymphomas not of B-cell lineage. This added to the already complex, not fully understood pathogenesis of PNP.A study in 2013 outlined the effectiveness of plasma exchange in PNP patients with benign tumors.The University of Toronto has been working to develop a form of treatment that improves the patients overall quality of life while remaining economically achievable. They believe they have achieved this through fixed-dose rituximab. It has proven to be effective among auto-immune diseases, but the correct administration process for treating PNP is yet to be defined. The results of the study demonstrated varying levels of remission. References Notes == External links ==
Sandhoff disease	Sandhoff disease is a lysosomal genetic, lipid storage disorder caused by the inherited deficiency to create functional beta-hexosaminidases A and B. These catabolic enzymes are needed to degrade the neuronal membrane components, ganglioside GM2, its derivative GA2, the glycolipid globoside in visceral tissues, and some oligosaccharides. Accumulation of these metabolites leads to a progressive destruction of the central nervous system and eventually to death. The rare autosomal recessive neurodegenerative disorder is clinically almost indistinguishable from Tay–Sachs disease, another genetic disorder that disrupts beta-hexosaminidases A and S. There are three subsets of Sandhoff disease based on when first symptoms appear: classic infantile, juvenile and adult late onset. Symptoms and signs Sandhoff disease symptoms are clinically indeterminable from Tay–Sachs disease. The classic infantile form of the disease has the most severe symptoms and is incredibly hard to diagnose at this early age. The first signs of symptoms begin before 6 months of age and the parents’ notice when the child begins regressing in their development. If the children had the ability to sit up by themselves or crawl they will lose this ability. This is caused by a slow deterioration of the muscles in the child’s body from the buildup of GM2 gangliosides. Since the body is unable to create the enzymes it needs within the central nervous system, it is unable to attach to these gangliosides to break them apart and make them non-toxic. With this buildup there are several symptoms that begin to appear such as muscle/motor weakness, sharp reaction to loud noises, blindness, deafness, inability to react to stimulants, respiratory problems and infections, mental retardation, seizures, cherry red spots in the retina, enlarged liver and spleen (hepatosplenomegaly), pneumonia, or bronchopneumonia.The other two forms of Sandhoff disease have similar symptoms but to a lesser extent. Adult and juvenile forms of Sandhoff disease are more rare than the infantile form. In these cases victims suffer cognitive impairment (retardation) and a loss of muscle coordination that impairs and eventually destroys their ability to walk; the characteristic red spots in the retina also develop. The adult form of the disease, however, is sometimes milder, and may only lead to muscle weakness that impairs walking or the ability to get out of bed. Causes Two parents carrying a mutated gene and passing it on to their offspring cause the disease. Even with both parents carrying the disease in their genome, there is only a 25% chance that they will have a child containing the genetic coding for the disease (see figure right).Each form of the disease is caused by the differences in the various mutations of the genome, in particular the codons on the 14 exons in the HEX B gene located within chromosome 5 (see figure bottom), leading to the differences in severities of the symptoms. The difference in the codons has the consequence of inhibiting two enzymes located in the lysosomes of the neurons of the central nervous system. Lysosomes contain various enzymes to break down byproducts and toxins to ensure they do not accumulate enough to interfere with the function of the central nervous system.Using restriction enzymes, it was discovered that a mutation on chromosome 5 particularly within the C1214T allele caused the adult onset form of Sandhoff Disease. For the patient showing symptoms of the infantile or juvenile form they have a mutation on exon I207V from their father, and a 16 base pair deletion from their mother which can be located on as many as five exons, exons 1–5. Mutations and polymorphism Articles regarding Sandhoff disease frequencies among distinct groups of people contain discrepancies from one another. More than 25 mutations have been reported other than novel mutations.One article says that Sandhoff disease is found commonly in individuals with a non-Jewish descent.Others say that it is more commonly in: the Creole population of northern Argentina the indigenous Métis in Saskatchewan Christian Maronite communities from CyprusDiscovery of several mutations in Ashkenazi Jews may reflect ascertainment bias rather than a high population frequency, because Ashkenazi Jews were the targeted population in a mass screening program for Tay-Sachs disease. Several rare SD mutations were discovered as researchers resolved cases of enzyme deficiency among suspected TSD carriers, but no cases of the disease itself have been reported.However, since it is an autosomal recessive disease, it is likely found in any ethnic group passing from generation to generation through carriers without being expressed in their offspring. Even though the family may not have a history of Sandhoff disease, it is possible for two individuals to have a child with the disease. Since Sandhoff disease was only discovered in 1968, there are years the disease has gone undetected because of misdiagnoses. Pathophysiology Biallelic pathogenic variants in the HEXB gene cause Sandhoff disease. The gene provides instructions for making a protein crucial to the enzymes beta-hexosaminidase A and beta-hexosaminidase B, which function in nerve cells to break down fatty substances, complex sugars, and molecules that are linked to sugars. In particular, beta-hexosaminidase A breaks down a fatty compound called GM2 ganglioside. Mutations in the HEXB gene disrupt the activity of these enzymes, preventing the breakdown of GM2 ganglioside and other molecules.As a result, progressive damage caused by the resulting buildup of GM2 ganglioside leads to the destruction of nerve cells, causing the signs and symptoms associated with Sandhoff disease. Diagnosis Sandhoff disease can be detected through the following procedures (before it is apparent through physical examination): a biopsy removing a sample of tissue from the liver, genetic testing, molecular analysis of cells and tissues (to determine the presence of a genetic metabolic disorder), enzyme assay, and occasionally a urinalysis to determine if the above-noted compounds are abnormally stored within the body. For a child to suffer from this disease, both parents must be carriers, and both must transmit the mutation to the child. Thus, even in the case where both parents have the mutation, there is only a 25 percent chance their child will inherit the condition. Frequently, parents are given the opportunity to have a DNA screening if they are at high risk, to determine their carrier status before they have children. However, it is also highly recommended to undergo testing even for those parents who do not have a family history of Sandhoff disease. Over 95% of the families that have children with Sandhoff disease had no known prior family history of the condition, as the mutation in the HEXB gene does not cause clinical symptoms when only one copy is present, and often passed undetected from one generation to the next Naturally, if an individual carries the mutation, he or she has a risk of transmitting it to the unborn child. Genetic counseling is recommended for those who have the mutation.It is possible for parents who are about to have a child or had a child with Sandhoff Disease can have a PGD or PEGD. PEGD is pre-embryonic genetic diagnosis for the parents that would not benefit from a pre-implantation genetic diagnosis because of their religion or negative attitude for the discarding of embryos. PEGD sequences the genome of the embryo to be produced by two parents if they were to conceive a child. If the family has a history of Sandhoff disease it is recommended they have their genome sequenced to ensure they are not carriers or to sequence the genome of their child. Types There are three types of Sandhoff disease: classic infantile, juvenile, and adult late onset. Each form is classified by the severity of the symptoms as well as the age at which the patient shows these symptoms. Classic infantile form of the disease is classified by the development of symptoms anywhere from 2 months to 9 months of age. It is the most common and most severe of all of the forms and will lead to death before the patient reaches the age of three. Infants with this disorder typically appear normal until the age of 3 to 6 months, when development slows and muscles used for movement weaken. Affected infants lose motor skills such as turning over, sitting, and crawling. As the disease progresses, infants develop seizures, vision and hearing loss, dementia, and paralysis. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. Some infants with Sandhoff disease may have enlarged organs (organomegaly) or bone abnormalities. Children with the severe form of this disorder usually live only into early childhood. The juvenile form of the disease shows symptoms starting at age 3 ranging to age 10 and, although the child usually dies by the time they are 15, it is possible for them to live longer if they are under constant care. Symptoms include autism, ataxia, motor skills regression, spacticity, and learning disorders. Adult onset form of the disease is classified by its occurrence in older individuals and has an effect on the motor function of these individuals. It is not yet known if Sandhoff disease will cause these individuals to have a decrease in their life span.Juvenile and adult onset forms of Sandhoff disease are very rare. Signs and symptoms can begin in childhood, adolescence, or adulthood and are usually milder than those seen with the infantile form of Sandhoff disease. As in the infantile form, mental abilities and coordination are affected. Characteristic features include muscle weakness, loss of muscle coordination (ataxia) and other problems with movement, speech problems, and mental illness. These signs and symptoms vary widely among people with late-onset forms of Sandhoff disease. Treatment Currently Sandhoff disease does not have any standard treatment and does not have a cure. However, a person suffering from the disease needs proper nutrition, hydration, and maintenance of clear airways. To reduce some symptoms that may occur with Sandhoff disease, the patient may take anticonvulsants to manage seizures or medications to treat respiratory infections, and consume a precise diet consisting of puree foods due to difficulties swallowing. Infants with the disease usually die by the age of 3 due to respiratory infections. The patient must be under constant surveillance because they can suffer from aspiration or lack the ability to change from the passageway to their lungs versus their stomach and their spit travels to the lungs causing bronchopneumonia. The patient also lacks the ability to cough and therefore must undergo a treatment to shake up their body to remove the mucus from the lining of their lungs. Medication is also given to patients to lessen their symptoms including seizures.Currently the government is testing several treatments including N-butyl-deoxynojirimycin in mice, as well as stem cell treatment in humans and other medical treatments recruiting test patients. A Sandhoff disease study showing proof of principle for gene therapy in a human model system using CRISPR and virus gene correction gives the chance for clinical trials to cure the disease. The ultra-rare occurrence is a main hurdle to overcome for clinical trials. History Sandhoff disease is one of several forms of what was formerly known as amaurotic idiocy. This inherited disease is characterized by the accumulation of lipid-containing cells in the viscera and in the nervous system, mental retardation, and impaired vision or blindness. The chemical and enzymatic analysis of various patients with amaurotic idiocy by Konrad Sandhoff (1939- ), a German biochemist, led to the identification of several biochemically distinct diseases: The first biochemical description of GM1-gangliosidosis in 1963, Sandhoff disease in 1968, Tay-Sachs-Disease, the AB-variant of GM2-Gangliosidosis and the B1-variant of GM2-gangliosidosis.The molecular defect in Sandhoff disease was discovered when Konrad Sandhoff studied the biochemistry of sphingolipids and gangliosides in the laboratory of Prof. Horst Jatzkewitz (1912–2002), a German biochemist (Max- Planck-Institute for Psychiatry, Munich). In October 1966, he obtained deep-frozen autopsy material from an infantile case with amaurotic idiocy. The glycolipid analysis soon demonstrated differences from all the cases studied before. Besides the neuronal storage of GM2, the storage of GA2 was much more pronounced, and different from all cases of Tay-Sachs disease studied so far, globoside accumulated in the visceral organs and, most importantly, hexosaminidase activity was almost completely absent. The disease causing catabolic enzyme deficiency of hexosaminidases was demonstrated with four different substrates (p–nitrophenyl-β-D-N-acetylglucosaminide, p-nitrophenyl-β-D-N-acetylgalactosaminide, glycolipid [3H]GA2 and [3H]globoside) in four different organs and published in 1968. See also GM2-gangliosidosis, AB variant globoside References This article incorporates some public domain text from The U.S. National Library of Medicine External links Sandhoff at NINDS
Amalgam tattoo	Amalgam tattoo is a grey, blue or black area of discoloration on the mucous membranes of the mouth, typically on the gums of the lower jaw. It is a healthcare caused lesion, due to entry of dental amalgam into the soft tissues. It is common, painless, and benign, but it can be mistaken for melanoma. Signs and symptoms Amalgam tattoo usually occurs on the mandibular gingiva, often in an area in which an apicoectomy ("root-end filling") with amalgam was carried out.: 138 After the gingiva, the alveolar mucosa and the buccal mucosa are the next most common sites, although any mucosal site in the mouth is possible. It is painless, and appears as a blue-black or grey discolored macule on the surface of the mucosa.: 138 : 330 : 183 The borders of the tattoo are variable, and may be well defined, irregular or diffuse. Causes Amalgam tattoo is caused by implantation of amalgam into the tissues.: 183 It may occur in several ways: During placement of an amalgam filling,: 183 e.g. if abrasions on the mucosa are present which allow entry of amalgam dust Shortly after placement of an amalgam filling, e.g. amalgam particles can contaminate dental floss and lead to linear amalgam tattoos in between the teeth, especially if flossing is carried out immediately after placement of an amalgam filling with a mesial or distal aspect Polishing of an amalgam filling The pressure from high speed turbine dental drills can be enough to force amalgam particles into soft tissue, as may occur when an old amalgam filling is being removed When a tooth with an amalgam filling is extracted,: 183 e.g. broken bits of amalgam filling falling into an extraction socket unnoticed When an amalgam filling is placed in the same appointment as a tooth extracted, as may occur in "quadrant dentistry" Apicectomies are common causes of amalgam tattoo, since the amalgam is being placed inside the alveolus and the soft tissues are replaced on topOver time, the amalgam particles embedded in the soft tissues corrode.: 183 Macrophages take up the exogenous particles, and the silver in amalgam leads to staining of collagen fibers.: 183 A similar appearance can be caused by implantation of graphite (e.g. from pencil leads), and is sometimes termed a graphite tattoo, although this is less common than tattooing with amalgam.: 138 Diagnosis The diagnosis is clinical.: 138 Amalgam tattoo can be distinguished from other causes of localized oral pigmentation because it does not change significantly in size or color,: 138 although it may appear to slowly enlarge for several months after the initial implantation of the metal particles.: 183 Some amalgam tattoos appear radio-opaque on radiographs (i.e. they show up on x-rays),: 138 although in many cases, amalgam tattoos have no radiographic features since the responsible particle(s) of amalgam are very small even though clinically the area of discolored mucosa is much larger.If necessary, the diagnosis can be confirmed histologically by excisional biopsy, which excludes nevi and melanomas.: 138 If a biopsy is taken, the histopathologic appearance is: Pigmented fragments of metal within connective tissue Staining of reticulin fibers with silver salts A scattered arrangement of large, dark, solid fragments or a fine, black or dark brown granules Large particles may be surrounded by chronically inflamed fibrous tissue Smaller particles surrounded by more significant inflammation, which may be granulomatous or a mixture of lymphocytes and plasma cells Prevention Theoretically, routine use of a dental dam during dental procedures which involve amalgam should reduce the risk of amalgam tattoo. Treatment No treatment is required since the lesion is entirely benign. Some suggest that amalgam tattoos are best surgically excised so as to ensure the lesion does not represent a melanoma.: 138 Others say that excision should only be carried out if there is any doubt over the diagnosis, and that amalgam tattoos are managed by simple reassurance about the nature of the lesion.: 330 For example, if radio-opaque particles are demonstrated on the x-ray, biopsy is unnecessary. Epidemiology Amalgam tattoo is found in up to 1% of people in the general population. It is the most common cause of solitary or focal pigmentation of the oral mucosa. Notes References == External links ==
Shell shock	Shell shock is a term coined in World War I by the British psychologist Charles Samuel Myers to describe the type of post-traumatic stress disorder (PTSD) many soldiers were afflicted with during the war (before PTSD was termed). It is a reaction to the intensity of the bombardment and fighting that produced a helplessness appearing variously as panic and being scared, flight, or an inability to reason, sleep, walk or talk.During the war, the concept of shell shock was ill-defined. Cases of "shell shock" could be interpreted as either a physical or psychological injury, or as a lack of moral fibre. The term shell shock is still used by the United States’ Department of Veterans Affairs to describe certain parts of PTSD, but mostly it has entered into memory, and it is often identified as the signature injury of the war. In World War II and thereafter, diagnosis of "shell shock" was replaced by that of combat stress reaction, a similar but not identical response to the trauma of warfare and bombardment. Origin During the early stages of World War I in 1914, soldiers from the British Expeditionary Force began to report medical symptoms after combat, including tinnitus, amnesia, headaches, dizziness, tremors, and hypersensitivity to noise. While these symptoms resembled those that would be expected after a physical wound to the brain, many of those reporting sick showed no signs of head wounds. By December 1914 as many as 10% of British officers and 4% of enlisted men were experiencing "nervous and mental shock".The term "shell shock" was coined during the Battle of Loos to reflect an assumed link between the symptoms and the effects of explosions from artillery shells. The term was first published in 1915 in an article in The Lancet by Charles Myers. Some 60–80% of shell shock cases displayed acute neurasthenia, while 10% displayed what would now be termed symptoms of conversion disorder, including mutism and fugue.The number of shell shock cases grew during 1915 and 1916 but it remained poorly understood medically and psychologically. Some physicians held the view that it was a result of hidden physical damage to the brain, with the shock waves from bursting shells creating a cerebral lesion that caused the symptoms and could potentially prove fatal. Another explanation was that shell shock resulted from poisoning by the carbon monoxide formed by explosions.At the same time, an alternative view developed describing shell shock as an emotional, rather than a physical, injury. Evidence for this point of view was provided by the fact that an increasing proportion of men with shell shock symptoms had not been exposed to artillery fire. Since the symptoms appeared in men who had no proximity to an exploding shell, the physical explanation was clearly unsatisfactory.In spite of this evidence, the British Army continued to try to differentiate those whose symptoms followed explosive exposure from others. In 1915 the British Army in France was instructed that: Shell-shock and shell concussion cases should have the letter W prefixed to the report of the casualty, if it was due to the enemy; in that case the patient would be entitled to rank as wounded and to wear on his arm a wound stripe. If, however, the mans breakdown did not follow a shell explosion, it was not thought to be due to the enemy, and he was to [be] labelled Shell-shock or S (for sickness) and was not entitled to a wound stripe or a pension. However, it often proved difficult to identify which cases were which, as the information on whether a casualty had been close to a shell explosion or not was rarely provided. Management Acute At first, shell-shock casualties were rapidly evacuated from the front line – in part because of fear of their unpredictable behaviour. As the size of the British Expeditionary Force increased, and manpower became in shorter supply, the number of shell shock cases became a growing problem for the military authorities. At the Battle of the Somme in 1916, as many as 40% of casualties were shell-shocked, resulting in concern about an epidemic of psychiatric casualties, which could not be afforded in either military or financial terms.Among the consequences of this were an increasing official preference for the psychological interpretation of shell shock, and a deliberate attempt to avoid the medicalisation of shell shock. If men were uninjured it was easier to return them to the front to continue fighting. Another consequence was an increasing amount of time and effort devoted to understanding and treating shell shock symptoms. Soldiers who returned with shell shock generally could not remember much because their brain would shut out all the traumatic memories. By the Battle of Passchendaele in 1917, the British Army had developed methods to reduce shell shock. A man who began to show shell-shock symptoms was best given a few days rest by his local medical officer. Col. Rogers, Regimental Medical Officer, 4th Battalion Black Watch wrote: You must send your commotional cases down the line. But when you get these emotional cases, unless they are very bad, if you have a hold of the men and they know you and you know them (and there is a good deal more in the man knowing you than in you knowing the man) … you are able to explain to him that there is really nothing wrong with him, give him a rest at the aid post if necessary and a day or two’s sleep, go up with him to the front line, and, when there, see him often, sit down beside him and talk to him about the war and look through his periscope and let the man see you are taking an interest in him. If symptoms persisted after a few weeks at a local Casualty Clearing Station, which would normally be close enough to the front line to hear artillery fire, a casualty might be evacuated to one of four dedicated psychiatric centres which had been set up further behind the lines, and were labelled as "NYDN – Not Yet Diagnosed Nervous" pending further investigation by medical specialists. Although the Battle of Passchendaele generally became a byword for horror, the number of cases of shell shock were relatively few. 5,346 shell shock cases reached the Casualty Clearing Station, or roughly 1% of the British forces engaged. 3,963 (or just under 75%) of these men returned to active service without being referred to a hospital for specialist treatment. The number of shell shock cases reduced throughout the battle, and the epidemic of illness was ended.During 1917, "shell shock" was entirely banned as a diagnosis in the British Army, and mentions of it were censored, even in medical journals. Chronic treatment The treatment of chronic shell shock varied widely according to the details of the symptoms, the views of the doctors involved, and other factors including the rank and class of the patient. There were so many officers and men with shell shock that 19 British military hospitals were wholly devoted to the treatment of cases. Ten years after the war, 65,000 veterans of the war were still receiving treatment for it in Britain. In France it was possible to visit aged shell shock victims in hospital in 1960. Physical causes 2015 research by Johns Hopkins University has found that the brain tissue of combat veterans who have been exposed to improvised explosive devices (IEDs) exhibit a pattern of injury in the areas responsible for decision making, memory and reasoning. This evidence has led the researchers to conclude that shell shock may not only be a psychological disorder, since the symptoms exhibited by affected individuals from the First World War are very similar to these injuries. Immense pressure changes are involved in shell shock. Even mild changes in air pressure from weather have been linked to changes in behavior.There is also evidence to suggest that the type of warfare faced by soldiers would affect the probability of shell shock symptoms developing. First-hand reports from medical doctors at the time note that rates of such conditions decreased once the war was mobilized again during the 1918 German offensive, following the 1916–1917 period where the highest rates of shell shock can be found. This could suggest that it was trench warfare, and the experience of siege warfare specifically, that led to the development of these symptoms. Cowardice Some men with shell shock were put on trial, and even executed, for military crimes including desertion and cowardice. While it was recognised that the stresses of war could cause men to break down, a lasting episode was likely to be seen as symptomatic of an underlying lack of character. For instance, in his testimony to the post-war Royal Commission examining shell shock, Lord Gort said that shell shock was a weakness and was not found in "good" units. The continued pressure to avoid medical recognition of shell shock meant that it was not, in itself, considered an admissible defence. Although some doctors or medics did take procedure to try to cure soldiers shell shock, it was first done in a brutal way. Doctors would provide electric shock to soldiers in hopes that it would shock them back to their normal, heroic, pre-war self. After almost a year of giving one of his patients electric shocks, putting cigarettes on his tongue, hot plates at the back of his throat, etc., a British clinician, Lewis Yealland, said to his patient, "You will not leave this room until you are talking as well as you ever did... You must behave as the hero I expected you to be."Executions of soldiers in the British Army were not commonplace. While there were 240,000 Courts Martial and 3080 death sentences handed down, in only 346 cases was the sentence carried out. 266 British soldiers were executed for "Desertion", 18 for "Cowardice", 7 for "Quitting a post without authority", 5 for "Disobedience to a lawful command" and 2 for "Casting away arms". On 7 November 2006, the government of the United Kingdom gave them all a posthumous conditional pardon. Committee of Enquiry report The British government produced a Report of the War Office Committee of Enquiry into "Shell-Shock" which was published in 1922. Recommendations from this included: In forward areas No soldier should be allowed to think that loss of nervous or mental control provides an honourable avenue of escape from the battlefield, and every endeavour should be made to prevent slight cases leaving the battalion or divisional area, where treatment should be confined to provision of rest and comfort for those who need it and to heartening them for return to the front line. In neurological centres When cases are sufficiently severe to necessitate more scientific and elaborate treatment they should be sent to special Neurological Centres as near the front as possible, to be under the care of an expert in nervous disorders. No such case should, however, be so labelled on evacuation as to fix the idea of nervous breakdown in the patient’s mind. In base hospitals When evacuation to the base hospital is necessary, cases should be treated in a separate hospital or separate sections of a hospital, and not with the ordinary sick and wounded patients. Only in exceptional circumstances should cases be sent to the United Kingdom, as, for instance, men likely to be unfit for further service of any kind with the forces in the field. This policy should be widely known throughout the Force. Forms of treatment The establishment of an atmosphere of cure is the basis of all successful treatment, the personality of the physician is, therefore, of the greatest importance. While recognising that each individual case of war neurosis must be treated on its merits, the Committee are of opinion that good results will be obtained in the majority by the simplest forms of psycho-therapy, i.e., explanation, persuasion and suggestion, aided by such physical methods as baths, electricity and massage. Rest of mind and body is essential in all cases.The committee are of opinion that the production of hypnoidal state and deep hypnotic sleep, while beneficial as a means of conveying suggestions or eliciting forgotten experiences are useful in selected cases, but in the majority they are unnecessary and may even aggravate the symptoms for a time. They do not recommend psycho-analysis in the Freudian sense.In the state of convalescence, re-education and suitable occupation of an interesting nature are of great importance. If the patient is unfit for further military service, it is considered that every endeavour should be made to obtain for him suitable employment on his return to active life. Return to the fighting line Soldiers should not be returned to the fighting line under the following conditions:(1) If the symptoms of neurosis are of such a character that the soldier cannot be treated overseas with a view to subsequent useful employment. (2) If the breakdown is of such severity as to necessitate a long period of rest and treatment in the United Kingdom. (3) If the disability is anxiety neurosis of a severe type. (4) If the disability is a mental breakdown or psychosis requiring treatment in a mental hospital. It is, however, considered that many of such cases could, after recovery, be usefully employed in some form of auxiliary military duty. Part of the concern was that many British veterans were receiving pensions and had long-term disabilities. By 1939, some 120,000 British ex-servicemen had received final awards for primary psychiatric disability or were still drawing pensions – about 15% of all pensioned disabilities – and another 44,000 or so … were getting pensions for ‘soldier’s heart’ or Effort Syndrome. There is, though, much that statistics do not show, because in terms of psychiatric effects, pensioners were just the tip of a huge iceberg. War correspondent Philip Gibbs wrote: Something was wrong. They put on civilian clothes again and looked to their mothers and wives very much like the young men who had gone to business in the peaceful days before August 1914. But they had not come back the same men. Something had altered in them. They were subject to sudden moods, and queer tempers, fits of profound depression alternating with a restless desire for pleasure. Many were easily moved to passion where they lost control of themselves, many were bitter in their speech, violent in opinion, frightening. One British writer between the wars wrote: There should be no excuse given for the establishment of a belief that a functional nervous disability constitutes a right to compensation. This is hard saying. It may seem cruel that those whose sufferings are real, whose illness has been brought on by enemy action and very likely in the course of patriotic service, should be treated with such apparent callousness. But there can be no doubt that in an overwhelming proportion of cases, these patients succumb to ‘shock’ because they get something out of it. To give them this reward is not ultimately a benefit to them because it encourages the weaker tendencies in their character. The nation cannot call on its citizens for courage and sacrifice and, at the same time, state by implication that an unconscious cowardice or an unconscious dishonesty will be rewarded. Development of psychiatry At the beginning of World War II, the term "shell shock" was banned by the British Army, though the phrase "postconcussional syndrome" was used to describe similar traumatic responses. Society and culture Shell shock has had a profound impact in British culture and the popular memory of World War I. At the time, war writers like the poets Siegfried Sassoon and Wilfred Owen dealt with shell shock in their work. Sassoon and Owen spent time at Craiglockhart War Hospital, which treated shell shock casualties. Author Pat Barker explored the causes and effects of shell shock in her Regeneration Trilogy, basing many of her characters on real historical figures and drawing on the writings of the first world war poets and the army doctor W. H. R. Rivers. Modern cases of shell shock Although the term "shell shocked" is typically used in discussion of WWI to describe early forms of PTSD, its high-impact explosives-related nature provides modern applications as well. During their deployment in Iraq and Afghanistan, approximately 380,000 U.S. troops, about 19% of those deployed, were estimated to have sustained brain injuries from explosive weapons and devices. This prompted the U.S. Defense Advanced Research Projects Agency (DARPA) to open up a $10 million study of the blast effects on the human brain. The study revealed that, while the brain remains initially intact immediately after low level blast effects, the chronic inflammation afterwards is what ultimately leads to many cases of shell shock and PTSD. See also Combat stress reaction References Sources Coulthart, Ross. The Lost Diggers, Sydney: HarperCollins Publishers, 2012. ISBN 978-0732294618 Jones, E, Fear, N and Wessely, S. "Shell Shock and Mild Traumatic Brain Injury: A Historical Review". Am J Psychiatry 2007; 164:1641–1645 Hochschild, Adam. To End all Wars – a story of loyalty and rebellion, 1914–1918 Mariner Books, Houghton, Mifflin Harcourt, Boston & New York, 2011. ISBN 978-0547750316 Horrocks, J. (2018). The limits of endurance: Shell shock and dissent in World War one. The Journal of New Zealand Studies, (NS27). https://doi.org/10.26686/jnzs.v0ins27.5175 Leese, Peter. Shell Shock. Traumatic Neurosis and the British Soldiers of the First World War, Palgrave Macmillan, 2014. ISBN 978-1137453372. MacLeod, A. D. (2004). "Shell shock, Gordon Holmes and the Great War". Journal of the Royal Society of Medicine. 97 (2): 86–89. doi:10.1177/014107680409700215. PMC 1079301. PMID 14749410. Myers, C.S. "A contribution to the study of shell shock". Lancet, 1, 1915, pp. 316–320 Shephard, Ben. A War of Nerves: Soldiers and Psychiatrists, 1914–1994. London, Jonathan Cape, 2000. Wessely, S. "The Life and Death of Private Harry Farr" Journal of the Royal Society of Medicine, Vol 99, September 2006 External links Shell Shock during World War I, by Professor Joanna Bourke - BBC An Address on the Repression of War Experience, by W.H. Rivers, 4 December 1917 Our Present Needs a Past: A Historical Look at Shell Shock Tedx Talk by Annessa Stagner on YouTube
Bakers itch	Bakers itch is a cutaneous reaction caused by bites of Acarus siro, the flour mite. See also List of mites associated with cutaneous reactions List of cutaneous conditions == References ==
List of autoimmune diseases	This list of autoimmune diseases is categorized by organ and tissue type to help locate diseases that may be similar. Autoimmune diseases qualifiers Overview of the qualifiers for the list. Autoimmune diseases Major organs Glands Digestive system Tissue Autoimmune comorbidities This list includes conditions that are not diseases but signs common to autoimmune disease. Some, such as chronic fatigue syndrome, are controversial. These conditions are included here because they are frequently listed as autoimmune diseases but should not be included in the list above until there is more consistent evidence. Non-autoimmune At this time, there is not sufficient evidence—direct, indirect, or circumstantial—to indicate that these diseases are caused by autoimmunity. These conditions are included here because: The disease was listed in the prior version of this table The disease is included in several widely used lists of autoimmune disease and is shown here to ensure that a person visiting this page does not conclude that the disease was not considered. Before moving a condition from here to the list of autoimmune diseases, references should be provided in the Wikipedia page for the condition that point to evidence, direct or indirect, that it is an autoimmune disease. See also Autoimmune Autonomic Ganglionopathy (AAG) == References ==
Acute monocytic leukemia	Acute monocytic leukemia (AMoL, or AML-M5) is a type of acute myeloid leukemia. In AML-M5 >80% of the leukemic cells are of monocytic lineage. This cancer is characterized by a dominance of monocytes in the bone marrow. There is an overproduction of monocytes that the body does not need in the periphery. These overproduced monocytes interfere with normal immune cell production which causes many health complications for the infected individual. Causes The pathology of AML involves abnormal proliferation and differentiation of a population of myeloid stem cells. Genetic mutations are identified in the majority of cases. A common genetic mutation identified in these cases are characterized as chromosomal translocations where information from one chromosome is exchanged to a non-homologous chromosome creating an unusual rearrangement of chromosomes. This translocation is often abbreviated as t(#of one chromosome involved, #of other chromosome involved). M5 is associated with characteristic chromosomal abnormalities, often involving chromosome 11, such as t(9;11), affecting the MLL (KMTA2) locus at 11q23; however MLL translocations are also found in other leukemia subtypes. The t(8;16) translocation in AMoL is associated with hemophagocytosis. These translocations yield the formation of chimeric proteins (RUNX1-RUNX1T1 and PML-RARA, respectively) which disrupt normal myeloid precursor development. Secondary leukaemia, which may include AML-M5, has been associated with exposure to epipodophyllotoxins, such as etoposide.Many cases of AML-M5 are seen to have enhanced phosphorylation of the STAT3 protein due to increased induction of cytokines thus increasing cell proliferation and survival. Finally, genetic mutations involved in epigenetic regulation are associated with this leukemia, as they have downstream effects on cell differentiation and proliferation. Excessive cytokine release could be a byproduct of skewed epigenetic regulation. Diagnosis In order to fulfill World Health Organization (WHO) criteria for AML-5, a patient must have greater than 20% blasts in the bone marrow, and of these, greater than 80% must be of the monocytic lineage. A further subclassification (M5a versus M5b) is made depending on whether the monocytic cells are predominantly monoblasts (>80%) (acute monoblastic leukemia) or a mixture of monoblasts and promonocytes (<80% blasts). Monoblasts can be distinguished by having a roughly circular nucleus, delicate lacy chromatin, and abundant, often basophilic cytoplasm. These cells may also have pseudopods. By contrast, promonocytes have a more convoluted nucleus, and their cytoplasm may contain metachromatic granules. Monoblasts are typically MPO-negative and promonocytes are MPO variable. Both monoblasts and promonocytes stain positive for non-specific esterase (NSE), however NSE may often be negative. Immunophenotypically, M5-AML variably express myeloid (CD13, CD33) and monocytic (CD11b, CD11c) markers. Cells may aberrantly express B-cell marker CD20 and the NK marker CD56. Monoblasts may be positive for CD34. Treatment AML-M5 is treated with intensive chemotherapy (such as anthracyclines) or with bone marrow transplantation. Tyrosine kinase receptor inhibitors are a prominent treatment developed to combat the over activation of cell proliferation proteins induced by AML-5. Inhibiting the STAT3 protein is another useful form of treatment. References External links Image at hmds.org.uk
Primitive neuroectodermal tumor	Primitive neuroectodermal tumor is a malignant (cancerous) neural crest tumor. It is a rare tumor, usually occurring in children and young adults under 25 years of age. The overall 5 year survival rate is about 53%.It gets its name because the majority of the cells in the tumor are derived from neuroectoderm, but have not developed and differentiated in the way a normal neuron would, and so the cells appear "primitive".PNET belongs to the Ewing family of tumors. Genetics Using gene transfer of SV40 large T-antigen in neuronal precursor cells of rats, a brain tumor model was established. The PNETs were histologically indistinguishable from the human counterparts and have been used to identify new genes involved in human brain tumor carcinogenesis. The model was used to confirm p53 as one of the genes involved in human medulloblastomas, but since only about 10% of the human tumors showed mutations in that gene, the model can be used to identify the other binding partners of SV40 Large T- antigen, other than p53. Diagnosis Classification It is classified into two types, based on location in the body: peripheral PNET and CNS PNET. Peripheral PNET The peripheral PNET (pPNET) is now thought to be virtually identical to Ewing sarcoma: "Current evidence indicates that both Ewings sarcoma and PNET have a similar neural phenotype and, because they share an identical chromosome translocation, they should be viewed as the same tumor, differing only in their degree of neural differentiation. Tumors that demonstrate neural differentiation by light microscopy, immunohistochemistry, or electron microscopy have been traditionally labeled PNETs, and those that are undifferentiated by these analyses have been diagnosed as Ewings sarcoma." PNET of the CNS PNET of the CNS generally refer to supratentorial PNETs. In the past medulloblastomas were considered PNETs; however, they are genetically, transcriptionally and clinically distinct. As such, "infratentorial" PNETs are now referred to as medulloblastoma. Pineoblastomas are embryonal tumours originating in the pineal gland and are likely distinct from supratentorial PNETs. Treatment The approach to management of a CNS PNET is first to obtain detailed imaging through MRI, as well as additional scans of the patients body (X-ray, CT, PET, even bone marrow biopsies) to look for metastasis or other associated malignancies. The tumor will then need to be biopsied to confirm the diagnosis. After the diagnosis of a CNS PNET is confirmed, management includes neoadjuvant chemotherapy and radiation (to reduce tumor size burden), complete surgical resection with confirmed negative margins, and/or additional adjuvant post-surgical chemotherapy. CNS PNET is aggressive and must be managed as so. Palliative care services should also become involved in the patients care team when the diagnosis is made. See also Medulloblastoma Ependymoma Ewing family of tumors == References ==
Cocaine intoxication	Cocaine intoxication refers to the subjective, desired and adverse effects of cocaine on the mind and behavior of users. Both self-induced and involuntary cocaine intoxication have medical and legal implications (even in absence of relevant adverse effects). Adverse effects can develop over time due to repeated use and so become chronic conditions. However, even a one-time intake of the substance can result in severe acute intoxication. Recurrent cocaine use and dependence to the drug inevitably leads to the reduction of the desired effects perceived by the users, while the occurrence of adverse effects of intoxication increase. The last can sometimes be completely reversed without bearing consequences but they can also potentially kill the users (e.g., in cases of untreated or non-manageable overdoses). Signs and symptoms Cocaine increases alertness, feelings of well-being, euphoria, energy, sociability, and sexuality. The former are some of the desired effects of cocaine intoxication. Not having the normal use of mental faculties by reason of the introduction of cocaine is defined drug intoxication by the laws in America, Europe, and most of the rest of the World, and it is a serious crime in specific contexts (e.g., in drug-impaired driving).Mild adverse effects include anxiety, increased temperature, paranoia, restlessness, and teeth grinding. With prolonged use, the drug can cause chronic complications like insomnia, weight loss, anorexia, persistent tachycardia, heart failure, kidney failure, hallucinations, and paranoid delusions.Depression with suicidal ideation may develop in heavy users. Finally, a loss of vesicular monoamine transporters, neurofilament proteins, and other morphological changes appear to indicate a long-term damage to dopamine neurons. Chronic intranasal usage can degrade the cartilage separating the nostrils (the nasal septum), which can eventually lead to its complete disappearance.Studies have shown that cocaine usage during pregnancy triggers premature labor and may lead to abruptio placentae.In cases of severe acute intoxication, potentially lethal adverse effects include prolonged episodes of arrhythmia (i.e., a group of abnormal heart rhythms that also include tachycardia), heavy hypoglycemia, tremors, convulsions, hyperthermia (i.e., markedly increased core temperature), untreated uremia, myocardial infarction, stroke, and sudden cardiac arrest. Overdose Cocaine can be snorted, swallowed, injected, or smoked. Most deaths due to cocaine are accidental but may also be the result of body packing or stuffing with rupture in the gastrointestinal tract. Use of cocaine causes abnormally fast heart rhythms and a marked elevation of blood pressure (hypertension), which can be life-threatening. This can lead to death from acute myocardial infarction, acute respiratory failure (i.e., hypoxemia, with or without hypercapnia), stroke, cerebral hemorrhage, and sudden cardiac arrest. Cocaine overdose may result in hyperthermia as stimulation and increased muscular activity cause greater heat production. Heat loss is also inhibited by the cocaine-induced vasoconstriction. Cocaine and/or associated hyperthermia may cause muscle cell destruction (rhabdomyolysis) and myoglobinuria resulting in kidney failure. Individuals with cocaine overdose should be transported immediately to the nearest emergency department, preferably by ambulance in case cardiac arrest occurs en route. According to the National Institute on Drug Abuse, approximately 14,600 deaths occurred in the US in 2017 due to an overdose where cocaine was somehow involved in any capacity, defined or undefined. Because of the increase in heart rate, cocaine users can be prone to elevated body temperatures, tremors, chest pains, and subject to nausea and vomiting. Some psychological symptoms due to an overdose include paranoia, delirium, anxiety as well as panicked feelings. Some signs of an overdose of cocaine are difficulty breathing, loss of urine control, bluish color of the skin, loss of awareness or surroundings, and high blood pressure. Although not as common, death can be caused from an over intoxication of cocaine. Most severe overdoses occur when users combine cocaine with other substances like alcohol or heroin, which increase the effects and heighten the chances of having a dangerous overdose. Treating an overdose can be done by bringing back blood flow to the heart, and restoring the body with oxygen rich blood, especially for the brain to reduce the risk of stroke. Cocaine overdoses have fluctuated over the years. From 2006 to 2010 there has been a decline in the number of reported cases. Though, from 2010 to 2015 there has been an increase in the reported cases involving over cocaine Intoxication. Males appear to have a much higher chance of overdosing than females. The ratio of male to female cocaine overdoses is 3:1. Withdrawal Cocaine withdrawal is not as severe as the withdrawal from other substances. For example, substances like alcohol and benzodiazepines can involve severe physical withdrawal symptoms while cocaine results in mostly psychological symptoms. Physiological changes caused by cocaine withdrawal include vivid and unpleasant dreams, insomnia, hypersomnia, anger, increased appetite, weight gain, psychomotor retardation, agitation, depression, and anxiety. According to a study done by Gawin and Kleber in 1986, there are three phases in the withdrawal process. They observed the behavior of 30 cocaine-dependent individuals. Phase one, the crash, is characterized by acute dysphoria, irritability and anxiety, increased desire for sleep, exhaustion, increased appetite, decreased craving to use. Phase two, withdrawal, is characterized by increasing craving to use, poor concentration, some irritability and some lethargy, which persisted for up to 10 weeks. Lastly, phase three is characterized by the intermittent craving to use in the context of external cues. Cocaine and its metabolites are eliminated from the body by 3 days. There are not any FDA-approved medications that specifically help treat cocaine withdrawal, however, there are some useful medications that could possibly help individuals overcome their addiction. One example is propranolol. Propranolol is a beta blocker that has been approved to treat hypertension, angina, anxiety, and other related psychological problems. Buprenorphine and naltrexone are two substances that act as an effective treatment in the earlier stages of withdrawal. Pathophysiology Cocaine pharmacodynamics involve multiple complex mechanisms. Although it has a short half-life (~ 1 hour), cocaine metabolites, which rise in concentrations several hours after cocaine ingestion, persist in circulation for up to 24 hours, and may cause delayed or recurrent coronary vasoconstriction. This drug binds and blocks monoamine (dopamine, epinephrine, norepinephrine, and serotonin) re-uptake transporters with equal affinity. Monoamines accumulate in the synaptic cleft resulting in enhanced and prolonged sympathetic effects. Cocaines acute effect in the central nervous system is to raise the amount of dopamine and serotonin in the nucleus accumbens (the pleasure center in the brain). When this effect ceases due to metabolism of cocaine, depletion of associated neurotransmitters, and receptor down-regulation (tachyphylaxis), the cocaine user may experience dysphoria, or a "crash" after the initial high. The principal actions of cocaine on the cardiovascular system are from alpha- and beta-1-adrenoceptor stimulation resulting in increased heart rate, systemic arterial pressure, and myocardial contractility, which are major determinants of myocardial oxygen demand. Cocaine and its metabolites may cause arterial vasoconstriction hours after use. Epicardial coronary arteries are especially vulnerable to these effects, leading to decreased myocardial oxygen supply. Cocaine-induced platelet activation and thrombus formation is another deleterious effect, caused by alpha-adrenergic- and adenosine diphosphate-mediated increase in platelet aggregation. Plasminogen activator inhibitor is also increased following cocaine use, thereby promoting thrombosis. Cocaine acts like a class I antiarrhythmic agent by blocking sodium and potassium channels, in a similar way of local anesthetics such as lidocaine, and interferes with action potential propagation. This Vaughn-Williams class IC effect increases the risk of conduction disturbance and tachyarrhythmias. Adding to its complex toxicity, cocaine targets muscarinic acetylcholine, N-methyl-D-aspartate (NMDA), sigma, and kappa-opioid receptors. Management There is no specific antidote for cocaine. Emergency treatment of cocaine-associated high body temperature consists of giving a benzodiazepine and physical cooling. Immediate administration of aspirin is required for patients reporting cocaine-associated chest pain. Cooling is best accomplished with tepid water misting and cooling with a fan. Antipyretics (e.g., paracetamol) have no effect in lowering high temperature because cocaine is an muscarinic receptor agonist. The chest pain, high blood pressure, and increased heart rate caused by cocaine may be also treated with benzodiazepines. Multiple and escalating dose of benzodiazepines may be necessary to achieve effect, which increases risk of over-sedation and respiratory depression. A review of cocaine cardiovascular toxicity found benzodiazepines may not always reliably lower heart rate and blood pressure. Lidocaine and intravenous lipid emulsion have been successfully used for serious ventricular tachyarrhythmias in several case reports. People who are agitated are best treated with benzodiazepines, though antipsychotics such as haloperidol and olanzapine may also be useful. The alpha-2 agonist dexmedetomidine may also be useful for agitation, but effects on heart rate and blood pressure are variable based on several studies and case reports. Vasodilators Nitric-oxide mediated vasodilators, such as nitroglycerin and nitroprusside, are effective at lowering blood pressure and reversing coronary arterial vasoconstriction, but not heart rate. Nitroglycerin is useful for cocaine-induced chest pain, but the possibility of reflex tachycardia must be considered. Alpha blockers Alpha-blockers such as phentolamine have been recommended and may be used to treat cocaine-induced hypertension and coronary arterial vasoconstriction, but these agents do not reduce heart rate. Furthermore, phentolamine is rarely used, not readily available in many emergency departments, and many present-day clinicians are unfamiliar with its use. Beta blockers Although the use of beta blockers is still controversial, notwithstanding decades of practice, despite research papers and systematic reviews on this subject (more details are in the next section), the intravenous racemic mixture of labetalol, a non-selective β blocker and selective α1 blocker is recommended for treating concomitant hypertension and tachycardia. Furthermore, the use of labetolol is approved by a AHA/ACC guideline for people who have used cocaine and methamphetamine with unstable angina/non-STEMI.A relative contraindication to the use of beta-blockers is still evident in some guidelines for the treatment of cocaine toxicity despite limited evidence. The phenomenon of "unopposed alpha-stimulation," in which blood pressure increases or coronary artery vasoconstriction worsens after blockade of beta-2 vasodilation in people using cocaine, is controversial. This rarely-encountered and unpredictable adverse effect has resulted in some clinicians advocating for an absolute contraindication of all beta-blockers, including specific, non-specific, and mixed. Many clinicians have disregarded this dogma and administer beta-blockers for cocaine-related chest pain and acute coronary syndrome, especially when there is demand ischemia from uncontrolled tachycardia. Of the 1,744 people in the aforementioned systematic review, only 7 adverse events were from putative cases of "unopposed alpha-stimulation" due to propranolol (n=3), esmolol (n=3), and metoprolol (n=1). Some detractors of beta-blockers for cocaine-induced chest pain have cited minimal acute mortality and the short half-life of the medication, making it unnecessary to aggressively treat any associated tachycardia and hypertension. However, the long-term effect of cocaine use and development of heart failure, with early mortality, high morbidity, and tremendous demand on hospital utilization should be taken under consideration. Calcium channel blockers Calcium channel blockers may also be used to treat hypertension and coronary arterial vasoconstriction, but fail to lower tachycardia based on all cocaine-related studies. Non-dihydropyridine calcium channels blockers such as diltiazem and verapamil are preferable, as dihydropyridine agents such as nifedipine have much higher risk of reflex tachycardia (however, clinicians can prevent reflex tachycardia by administering beta-blockers some minutes before using the latter class of CCBs). See also Cocaine Anonymous Cocaine dependence Crack cocaine § Crack lung List of deaths from drug overdose and intoxication References == External links ==
Hypercapnia	Hypercapnia (from the Greek hyper = "above" or "too much" and kapnos = "smoke"), also known as hypercarbia and CO2 retention, is a condition of abnormally elevated carbon dioxide (CO2) levels in the blood. Carbon dioxide is a gaseous product of the bodys metabolism and is normally expelled through the lungs. Carbon dioxide may accumulate in any condition that causes hypoventilation, a reduction of alveolar ventilation (the clearance of air from the small sacs of the lung where gas exchange takes place) as well as resulting from inhalation of CO2. Inability of the lungs to clear carbon dioxide, or inhalation of elevated levels of CO2, leads to respiratory acidosis. Eventually the body compensates for the raised acidity by retaining alkali in the kidneys, a process known as "metabolic compensation". Acute hypercapnia is called acute hypercapnic respiratory failure (AHRF) and is a medical emergency as it generally occurs in the context of acute illness. Chronic hypercapnia, where metabolic compensation is usually present, may cause symptoms but is not generally an emergency. Depending on the scenario both forms of hypercapnia may be treated with medication, with mask-based non-invasive ventilation or with mechanical ventilation. Hypercapnia is a hazard of underwater diving associated with breath-hold diving, scuba diving, particularly on rebreathers, and deep diving where it is associated with increased breathing gas density due to the high ambient pressure. Signs and symptoms Hypercapnia may happen in the context of an underlying health condition, and symptoms may relate to this condition or directly to the hypercapnia. Specific symptoms attributable to early hypercapnia are dyspnea (breathlessness), headache, confusion and lethargy. Clinical signs include flushed skin, full pulse (bounding pulse), rapid breathing, premature heart beats, muscle twitches, and hand flaps (asterixis). The risk of dangerous irregularities of the heart beat is increased. Hypercapnia also occurs when the breathing gas is contaminated with carbon dioxide, or respiratory gas exchange cannot keep up with the metabolic production of carbon dioxide, which can occur when gas density limits ventilation at high ambient pressures.In severe hypercapnia (generally P a C O 2 {\displaystyle {P_{a_{CO_{2}}}}} greater than 10 kPa or 75 mmHg), symptomatology progresses to disorientation, panic, hyperventilation, convulsions, unconsciousness, and eventually death. Causes Carbon dioxide is a normal metabolic product but it accumulates in the body if it is produced faster than it is cleared. During strenuous exercise the production rate of carbon dioxide can increase more than tenfold over the production rate during rest. Carbon dioxide is dissolved in the blood and elimination is by gas exchange in the lungs during breathing. Hypercapnia is generally caused by hypoventilation, lung disease, or diminished consciousness. It may also be caused by exposure to environments containing abnormally high concentrations of carbon dioxide, such as from volcanic or geothermal activity, or by rebreathing exhaled carbon dioxide. In this situation the hypercapnia can also be accompanied by respiratory acidosis.Acute hypercapnic respiratory failure may occur in acute illness caused by chronic obstructive pulmonary disease (COPD), chest wall deformity, some forms of neuromuscular disease (such as myasthenia gravis, and obesity hypoventilation syndrome. AHRF may also develop in any form of respiratory failure where the breathing muscles become exhausted, such as severe pneumonia and acute severe asthma. It can also be a consequence of profound suppression of consciousness such as opioid overdose. During diving Normal respiration in divers results in alveolar hypoventilation resulting in inadequate CO2 elimination or hypercapnia. Lanphiers work at the US Navy Experimental Diving Unit answered the question, "Why dont divers breathe enough?": Higher inspired oxygen ( P i O 2 {\displaystyle {P_{i_{O_{2}}}}} ) at 4 atm (400 kPa) accounted for not more than 25% of the elevation in end tidal CO2 (ETCO2) above values found at the same work rate when breathing air just below the surface. Increased work of breathing accounted for most of the elevation of P a C O 2 {\displaystyle {P_{a_{CO_{2}}}}} (alveolar gas equation) in exposures above 1 atm (100 kPa), as indicated by the results when helium was substituted for nitrogen at 4 atm (400 kPa). Inadequate ventilatory response to exertion was indicated by the fact that, despite resting values in the normal range, P e t C O 2 {\displaystyle {P_{et_{CO_{2}}}}} rose markedly with exertion even when the divers breathed air at a depth of only a few feet.A variety of reasons exists for carbon dioxide not being expelled completely when the diver exhales: The diver is exhaling into a vessel that does not allow all the CO2 to escape to the environment, such as a long snorkel, full-face diving mask, or diving helmet, and the diver then reinhales from that vessel, causing increased dead space. The carbon dioxide scrubber in the divers rebreather is failing to remove sufficient carbon dioxide from the loop (higher inspired CO2), or the breathing gas is contaminated with CO2. The diver is overexercising, producing excess carbon dioxide due to elevated metabolic activity and respiratory gas exchange cannot keep up with the metabolic production of carbon dioxide. Gas density limits ventilation at high ambient pressures. The density of the breathing gas is higher at depth, so the effort required to fully inhale and exhale increases, making breathing more difficult and less efficient (high work of breathing). Higher gas density also causes gas mixing within the lung to be less efficient, thus increasing the effective dead space. The diver is deliberately hypoventilating, known as "skip breathing". Skip breathing Skip breathing is a controversial technique to conserve breathing gas when using open-circuit scuba, which consists of briefly holding ones breath between inhalation and exhalation (i.e., "skipping" a breath). It can lead to CO2 not being exhaled efficiently. The risk of burst lung (pulmonary barotrauma of ascent) is increased if the breath is held while ascending. It is particularly counterproductive with a rebreather, where the act of breathing pumps the gas around the "loop", pushing carbon dioxide through the scrubber and mixing freshly injected oxygen.In closed-circuit rebreather diving, exhaled carbon dioxide must be removed from the breathing system, usually by a scrubber containing a solid chemical compound with a high affinity for CO2, such as soda lime. If not removed from the system, it may be reinhaled, causing an increase in the inhaled concentration.Under hyperbaric conditions, hypercapnia contributes to nitrogen narcosis and oxygen toxicity by causing cerebral vasodilation which increases the dosage of oxygen to the brain. Mechanism Hypercapnia normally triggers a reflex which increases breathing and access to oxygen (O2), such as arousal and turning the head during sleep. A failure of this reflex can be fatal, for example as a contributory factor in sudden infant death syndrome.Hypercapnia can induce increased cardiac output, an elevation in arterial blood pressure (higher levels of carbon dioxide stimulate aortic and carotid chemoreceptors with afferents -CN IX and X- to medulla oblongata with following chrono- and ino-tropic effects), and a propensity toward cardiac arrhythmias. Hypercapnia may increase pulmonary capillary resistance. Physiological effects A high arterial partial pressure of carbon dioxide ( P a C O 2 {\displaystyle {P_{a_{CO_{2}}}}} ) causes changes in brain activity that adversely affect both fine muscular control and reasoning. EEG changes denoting minor narcotic effects can be detected for expired gas end tidal partial pressure of carbon dioxide ( P E T C O 2 {\displaystyle {P_{ET_{CO_{2}}}}} ) increase from 40 torrs (0.053 atm) to approximately 50 torrs (0.066 atm). The diver does not necessarily notice these effects.Higher levels of P a C O 2 {\displaystyle {P_{a_{CO_{2}}}}} have a stronger narcotic effect: Confusion and irrational behaviour may occur around 72 torrs (0.095 atm), and loss of consciousness around 90 torrs (0.12 atm). High P a C O 2 {\displaystyle {P_{a_{CO_{2}}}}} triggers the fight or flight response, affects hormone levels and can cause anxiety, irritability and inappropriate or panic responses, which can be beyond the control of the subject, sometimes with little or no warning. Vasodilation is another effect, notably in the skin, where feelings of unpleasant heat are reported, and in the brain, where blood flow can increase by 50% at a P E T C O 2 {\displaystyle {P_{ET_{CO_{2}}}}} of 50 torrs (0.066 atm), Intracranial pressure may rise, with a throbbing headache. If associated with a high P a C O 2 {\displaystyle {P_{a_{CO_{2}}}}} the high delivery of oxygen to the brain may increase the risk of CNS oxygen toxicity at partial pressures usually considered acceptable.In many people a high P a C O 2 {\displaystyle {P_{a_{CO_{2}}}}} causes a feeling of shortness of breath, but the lack of this symptom is no guarantee that the other effects are not occurring. A significant percentage of rebreather deaths have been associated with CO2 retention. The effects of high P a C O 2 {\displaystyle {P_{a_{CO_{2}}}}} can take several minutes to hours to resolve once the cause has been removed. Diagnosis Blood gas tests may be performed, typically by radial artery puncture, in the setting of acute breathing problems or other acute medical illness. Hypercapnia is generally defined as an arterial blood carbon dioxide level over 45 mmHg (6 kPa). Since carbon dioxide is in equilibrium with carbonic acid in the blood, hypercapnia drives serum pH down, resulting in respiratory acidosis. Clinically, the effect of hypercapnia on pH is estimated using the ratio of the arterial pressure of carbon dioxide to the concentration of bicarbonate ion, P a C O 2 / H C O 3 − {\displaystyle {P_{a_{CO_{2}/HCO_{3}^{-}}}}} . Tolerance CO2 toxicity in animal models Tests performed on mongrel dogs showed the physiological effect of carbon dioxide on the body of the animal: after inhalation of a 50% CO2 and 50% air mixture, respiratory movement increased for about 2 minutes, and then, it decreased for 30 to 90 minutes. Hill and Flack showed that CO2 concentrations up to 35% have an exciting effect upon both circulation and respiration, but those beyond 35% are depressant upon them. The blood pressure (BP) decreased transiently during the increased respiratory movement and then rose again and maintained the original level for a while. The heart rate slowed slightly just after the gas mixture inhalation. It is believed that the initial BP depression with the decreased heart rate is due to the direct depressant effect of CO2 upon the heart and that the return of blood pressure to its original level was due to the rapid rise of P a C O 2 {\displaystyle {P_{a_{CO_{2}}}}} . After 30–90 min, the respiratory center was depressed, and hypotension occurred gradually or suddenly from reduced cardiac output, leading to an apnea and eventually to circulatory arrest. At higher concentrations of CO2, unconsciousness occurred almost instantaneously and respiratory movement ceased in 1 minute. After a few minutes of apnea, circulatory arrest was seen. These findings imply that the cause of death in breathing high concentrations of CO2 is not the hypoxia but the intoxication of carbon dioxide. Treatment The treatment for acute hypercapnic respiratory failure depends on the underlying cause, but may include medications and mechanical respiratory support. In those without contraindications, non-invasive ventilation (NIV) is often used in preference to invasive mechanical ventilation. In the past, the drug doxapram (a respiratory stimulant), was used for hypercapnia in acute exacerbation of chronic obstructive pulmonary disease but there is little evidence to support its use compared to NIV, and it does not feature in recent professional guidelines.Very severe respiratory failure, in which hypercapnia may also be present, is often treated with extracorporeal membrane oxygenation (ECMO), in which oxygen is added to and carbon dioxide removed directly from the blood.A relatively novel modality is extracorporeal carbon dioxide removal (ECCO2R). This technique removes CO2 from the bloodstream and may reduce the time mechanical ventilation is required for those with AHRF; it requires smaller volumes of blood flow compared to ECMO. Terminology Hypercapnia is the opposite of hypocapnia, the state of having abnormally reduced levels of carbon dioxide in the blood. See also Hypocapnia – State of reduced carbon dioxide in the blood, decreased level of carbon dioxide Inert gas asphyxiation Lake Nyos – Crater lake in the Northwest Region of Cameroon Ocean acidification – Climate change-induced decline of pH levels in the ocean Permissive hypercapnia Waterboarding – Torture method simulating drowning References == External links ==
Caroli disease	Caroli disease (communicating cavernous ectasia, or congenital cystic dilatation of the intrahepatic biliary tree) is a rare inherited disorder characterized by cystic dilatation (or ectasia) of the bile ducts within the liver. There are two patterns of Caroli disease: focal or simple Caroli disease consists of abnormally widened bile ducts affecting an isolated portion of liver. The second form is more diffuse, and when associated with portal hypertension and congenital hepatic fibrosis, is often referred to as "Caroli syndrome". The underlying differences between the two types are not well understood. Caroli disease is also associated with liver failure and polycystic kidney disease. The disease affects about one in 1,000,000 people, with more reported cases of Caroli syndrome than of Caroli disease.Caroli disease is distinct from other diseases that cause ductal dilatation caused by obstruction, in that it is not one of the many choledochal cyst derivatives. Signs and symptoms The first symptoms typically include fever, intermittent abdominal pain, and an enlarged liver. Occasionally, yellow discoloration of the skin occurs. Caroli disease usually occurs in the presence of other diseases, such as autosomal recessive polycystic kidney disease, cholangitis, gallstones, biliary abscess, sepsis, liver cirrhosis, kidney failure, and cholangiocarcinoma (7% affected). People with Caroli disease are 100 times more at risk for cholangiocarcinoma than the general population. After recognizing symptoms of related diseases, Caroli disease can be diagnosed.Morbidity is common and is caused by complications of cholangitis, sepsis, choledocholithiasis, and cholangiocarcinoma. These morbid conditions often prompt the diagnosis. Portal hypertension may be present, resulting in other conditions including enlarged spleen, hematemesis, and melena. These problems can severely affect the patients quality of life. In a 10-year period between 1995 and 2005, only 10 patients were surgically treated for Caroli disease, with an average patient age of 45.8 years.After reviewing 46 cases of Caroli disease before 1990, 21.7% of the cases were the result of an intrahepatic cyst or nonobstructive biliary tree dilation, 34.7% were linked with congenital hepatic fibrosis, 13% were isolated choledochal cystic dilation, and the remaining 24.6% had a combination of all three. Causes The cause appears to be genetic; the simple form is an autosomal dominant trait, while the complex form is an autosomal recessive trait. Females are more prone to Caroli disease than males. Family history may include kidney and liver disease due to the link between Caroli disease and ARPKD. PKHD1, the gene linked to ARPKD, has been found mutated in patients with Caroli syndrome. PKHD1 is expressed primarily in the kidneys with lower levels in the liver, pancreas, and lungs, a pattern consistent with phenotype of the disease, which primarily affects the liver and kidneys. The genetic basis for the difference between Caroli disease and Caroli syndrome has not been defined. Diagnosis Modern imaging techniques allow the diagnosis to be made more easily and without invasive imaging of the biliary tree. Commonly, the disease is limited to the left lobe of the liver. Images taken by CT scan, X-ray, or MRI show enlarged intrahepatic (in the liver) bile ducts due to ectasia. Using an ultrasound, tubular dilation of the bile ducts can be seen. On a CT scan, Caroli disease can be observed by noting the many fluid-filled, tubular structures extending to the liver. A high-contrast CT must be used to distinguish the difference between stones and widened ducts. Bowel gas and digestive habits make it difficult to obtain a clear sonogram, so a CT scan is a good substitution. When the intrahepatic bile duct wall has protrusions, it is clearly seen as central dots or a linear streak. Caroli disease is commonly diagnosed after this “central dot sign” is detected on a CT scan or ultrasound. However, cholangiography is the best, and final, approach to show the enlarged bile ducts as a result of Caroli disease. Treatment The treatment depends on clinical features and the location of the biliary abnormality. When the disease is localized to one hepatic lobe, hepatectomy relieves symptoms and appears to remove the risk of malignancy. Good evidence suggests that malignancy complicates Caroli disease in roughly 7% of cases.Antibiotics are used to treat the inflammation of the bile duct, and ursodeoxycholic acid is used for hepatolithiasis. Ursodiol is given to treat cholelithiasis. In diffuse cases of Caroli disease, treatment options include conservative or endoscopic therapy, internal biliary bypass procedures, and liver transplantation in carefully selected cases. Surgical resection has been used successfully in patients with monolobar disease. An orthotopic liver transplant is another option, used only when antibiotics have no effect, in combination with recurring cholangitis. With a liver transplant, cholangiocarcinoma is usually avoided in the long run.Family studies are necessary to determine if Caroli disease is due to inheritable causes. Regular follow-ups, including ultrasounds and liver biopsies, are performed. Prognosis Mortality is indirect and caused by complications. After cholangitis occurs, patients typically die within 5–10 years. Epidemiology Caroli disease is typically found in Asia, and diagnosed in persons under the age of 22. Cases have also been found in infants and adults. As medical imaging technology improves, diagnostic age decreases. History Jacques Caroli, a gastroenterologist, first described a rare congenital condition in 1958 in Paris, France. He described it as "nonobstructive saccular or fusiform multifocal segmental dilatation of the intrahepatic bile ducts"; basically, he observed cavernous ectasia in the biliary tree causing a chronic, often life-threatening hepatobiliary disease. Caroli, born in France in 1902, learned and practiced medicine in Angers. After World War II, he was chief of service for 30 years at Saint-Antoine in Paris. Before dying in 1979, he was honored with the rank of commander in the Legion of Honour in 1976. References == External links ==
Metabolic syndrome	Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Metabolic syndrome is associated with the risk of developing cardiovascular disease and type 2 diabetes. In the U.S., about 25% of the adult population has metabolic syndrome, a proportion increasing with age, particularly among racial and ethnic minorities.Insulin resistance, metabolic syndrome, and prediabetes are closely related to one another and have overlapping aspects. The syndrome is thought to be caused by an underlying disorder of energy utilization and storage. The cause of the syndrome is an area of ongoing medical research. Signs and symptoms The key sign of metabolic syndrome is central obesity, also known as visceral, male-pattern or apple-shaped adiposity. It is characterized by adipose tissue accumulation predominantly around the waist and trunk. Other signs of metabolic syndrome include high blood pressure, decreased fasting serum HDL cholesterol, elevated fasting serum triglyceride level, impaired fasting glucose, insulin resistance, or prediabetes. Associated conditions include hyperuricemia; fatty liver (especially in concurrent obesity) progressing to nonalcoholic fatty liver disease; polycystic ovarian syndrome in women and erectile dysfunction in men; and acanthosis nigricans. Complication Metabolic syndrome can lead to several serious and chronic complications, including type-2 diabetes, cardiovascular diseases, stroke, kidney disease and nonalcoholic fatty liver disease. Causes The mechanisms of the complex pathways of metabolic syndrome are under investigation. The pathophysiology is very complex and has been only partially elucidated. Most people affected by the condition are older, obese, sedentary, and have a degree of insulin resistance. Stress can also be a contributing factor. The most important risk factors are diet (particularly sugar-sweetened beverage consumption), genetics, aging, sedentary behavior or low physical activity, disrupted chronobiology/sleep, mood disorders/psychotropic medication use, and excessive alcohol use. The pathogenic role played in the syndrome by the excessive expansion of adipose tissue occurring under sustained overeating, and its resulting lipotoxicity was reviewed by Vidal-Puig.There is debate regarding whether obesity or insulin resistance is the cause of the metabolic syndrome or if they are consequences of a more far-reaching metabolic derangement. Markers of systemic inflammation, including C-reactive protein, are often increased, as are fibrinogen, interleukin 6, tumor necrosis factor-alpha (TNF-α), and others. Some have pointed to a variety of causes, including increased uric acid levels caused by dietary fructose.Research shows that Western diet habits are a factor in development of metabolic syndrome, with high consumption of food that is not biochemically suited to humans. Weight gain is associated with metabolic syndrome. Rather than total adiposity, the core clinical component of the syndrome is visceral and/or ectopic fat (i.e., fat in organs not designed for fat storage) whereas the principal metabolic abnormality is insulin resistance. The continuous provision of energy via dietary carbohydrate, lipid, and protein fuels, unmatched by physical activity/energy demand, creates a backlog of the products of mitochondrial oxidation, a process associated with progressive mitochondrial dysfunction and insulin resistance. Stress Recent research indicates prolonged chronic stress can contribute to metabolic syndrome by disrupting the hormonal balance of the hypothalamic-pituitary-adrenal axis (HPA-axis). A dysfunctional HPA-axis causes high cortisol levels to circulate, which results in raising glucose and insulin levels, which in turn cause insulin-mediated effects on adipose tissue, ultimately promoting visceral adiposity, insulin resistance, dyslipidemia and hypertension, with direct effects on the bone, causing "low turnover" osteoporosis. HPA-axis dysfunction may explain the reported risk indication of abdominal obesity to cardiovascular disease (CVD), type 2 diabetes and stroke. Psychosocial stress is also linked to heart disease. Obesity Central obesity is a key feature of the syndrome, being both a sign and a cause, in that the increasing adiposity often reflected in high waist circumference may both result from and contribute to insulin resistance. However, despite the importance of obesity, affected people who are of normal weight may also be insulin-resistant and have the syndrome. Sedentary lifestyle Physical inactivity is a predictor of CVD events and related mortality. Many components of metabolic syndrome are associated with a sedentary lifestyle, including increased adipose tissue (predominantly central); reduced HDL cholesterol; and a trend toward increased triglycerides, blood pressure, and glucose in the genetically susceptible. Compared with individuals who watched television or videos or used their computers for less than one hour daily, those who carried out these behaviors for greater than four hours daily have a twofold increased risk of metabolic syndrome. Aging Metabolic syndrome affects 60% of the U.S. population older than age 50. With respect to that demographic, the percentage of women having the syndrome is higher than that of men. The age dependency of the syndromes prevalence is seen in most populations around the world. Diabetes mellitus type 2 The metabolic syndrome quintuples the risk of type 2 diabetes mellitus. Type 2 diabetes is considered a complication of metabolic syndrome. In people with impaired glucose tolerance or impaired fasting glucose, presence of metabolic syndrome doubles the risk of developing type 2 diabetes. It is likely that prediabetes and metabolic syndrome denote the same disorder, defining it by the different sets of biological markers.The presence of metabolic syndrome is associated with a higher prevalence of CVD than found in people with type 2 diabetes or impaired glucose tolerance without the syndrome. Hypoadiponectinemia has been shown to increase insulin resistance and is considered to be a risk factor for developing metabolic syndrome. Coronary heart disease The approximate prevalence of the metabolic syndrome in people with coronary artery disease (CAD) is 50%, with a prevalence of 37% in people with premature coronary artery disease (age 45), particularly in women. With appropriate cardiac rehabilitation and changes in lifestyle (e.g., nutrition, physical activity, weight reduction, and, in some cases, drugs), the prevalence of the syndrome can be reduced. Lipodystrophy Lipodystrophic disorders in general are associated with metabolic syndrome. Both genetic (e.g., Berardinelli-Seip congenital lipodystrophy, Dunnigan familial partial lipodystrophy) and acquired (e.g., HIV-related lipodystrophy in people treated with highly active antiretroviral therapy) forms of lipodystrophy may give rise to severe insulin resistance and many of metabolic syndromes components. Rheumatic diseases There is research that associates comorbidity with rheumatic diseases. Both psoriasis and psoriatic arthritis have been found to be associated with metabolic syndrome. Chronic obstructive pulmonary disease Metabolic syndrome is seen to be a comorbidity in up to 50 percent of those with chronic obstructive pulmonary disease (COPD). It may pre-exist or may be a consequence of the lung pathology of COPD. Pathophysiology It is common for there to be a development of visceral fat, after which the adipocytes (fat cells) of the visceral fat increase plasma levels of TNF-α and alter levels of other substances (e.g., adiponectin, resistin, and PAI-1). TNF-α has been shown to cause the production of inflammatory cytokines and also possibly trigger cell signaling by interaction with a TNF-α receptor that may lead to insulin resistance. An experiment with rats fed a diet with 33% sucrose has been proposed as a model for the development of metabolic syndrome. The sucrose first elevated blood levels of triglycerides, which induced visceral fat and ultimately resulted in insulin resistance. The progression from visceral fat to increased TNF-α to insulin resistance has some parallels to human development of metabolic syndrome. The increase in adipose tissue also increases the number of immune cells, which play a role in inflammation. Chronic inflammation contributes to an increased risk of hypertension, atherosclerosis and diabetes.The involvement of the endocannabinoid system in the development of metabolic syndrome is indisputable. Endocannabinoid overproduction may induce reward system dysfunction and cause executive dysfunctions (e.g., impaired delay discounting), in turn perpetuating unhealthy behaviors. The brain is crucial in development of metabolic syndrome, modulating peripheral carbohydrate and lipid metabolism.Metabolic syndrome can be induced by overfeeding with sucrose or fructose, particularly concomitantly with high-fat diet. The resulting oversupply of omega-6 fatty acids, particularly arachidonic acid (AA), is an important factor in the pathogenesis of metabolic syndrome. Arachidonic acid (with its precursor – linoleic acid) serves as a substrate to the production of inflammatory mediators known as eicosanoids, whereas the arachidonic acid-containing compound diacylglycerol (DAG) is a precursor to the endocannabinoid 2-arachidonoylglycerol (2-AG) while fatty acid amide hydrolase (FAAH) mediates the metabolism of anandamide into arachidonic acid. Anandamide can also be produced from N-acylphosphatidylethanolamine via several pathways. Anandamide and 2-AG can also be hydrolized into arachidonic acid, potentially leading to increased eicosanoid synthesis. Diagnosis A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity published a guideline to harmonize the definition of the metabolic syndrome. This definition recognizes that the risk associated with a particular waist measurement will differ in different populations. Whether it is better at this time to set the level at which risk starts to increase or at which there is already substantially increased risk will be up to local decision-making groups. However, for international comparisons and to facilitate the etiology, it is critical that a commonly agreed-upon set of criteria be used worldwide, with agreed-upon cut points for different ethnic groups and sexes. There are many people in the world of mixed ethnicity, and in those cases, pragmatic decisions will have to be made. Therefore, an international criterion of overweight may be more appropriate than ethnic specific criteria of abdominal obesity for an anthropometric component of this syndrome which results from an excess lipid storage in adipose tissue, skeletal muscle and liver.The previous definitions of the metabolic syndrome by the International Diabetes Federation (IDF) and the revised National Cholesterol Education Program (NCEP) are very similar, and they identify individuals with a given set of symptoms as having metabolic syndrome. There are two differences, however: the IDF definition states that if body mass index (BMI) is greater than 30 kg/m2, central obesity can be assumed, and waist circumference does not need to be measured. However, this potentially excludes any subject without increased waist circumference if BMI is less than 30. Conversely, the NCEP definition indicates that metabolic syndrome can be diagnosed based on other criteria. Also, the IDF uses geography-specific cut points for waist circumference, while NCEP uses only one set of cut points for waist circumference regardless of geography. IDF The International Diabetes Federation consensus worldwide definition of metabolic syndrome (2006) is: Central obesity (defined as waist circumference# with ethnicity-specific values) AND any two of the following: Raised triglycerides: > 150 mg/dL (1.7 mmol/L), or specific treatment for this lipid abnormality Reduced HDL cholesterol: < 40 mg/dL (1.03 mmol/L) in males, < 50 mg/dL (1.29 mmol/L) in females, or specific treatment for this lipid abnormality Raised blood pressure (BP): systolic BP > 130 or diastolic BP >85 mm Hg, or treatment of previously diagnosed hypertension Raised fasting plasma glucose (FPG): >100 mg/dL (5.6 mmol/L), or previously diagnosed type 2 diabetesIf FPG is >5.6 mmol/L or 100 mg/dL, an oral glucose tolerance test is strongly recommended, but is not necessary to define presence of the syndrome. # If BMI is >30 kg/m2, central obesity can be assumed and waist circumference does not need to be measured WHO The World Health Organization (1999) requires the presence of any one of diabetes mellitus, impaired glucose tolerance, impaired fasting glucose or insulin resistance, AND two of the following: Blood pressure ≥ 140/90 mmHg Dyslipidemia: triglycerides (TG) ≥ 1.695 mmol/L and HDL cholesterol ≤ 0.9 mmol/L (male), ≤ 1.0 mmol/L (female) Central obesity: waist:hip ratio > 0.90 (male); > 0.85 (female), or BMI > 30 kg/m2 Microalbuminuria: urinary albumin excretion ratio ≥ 20 µg/min or albumin:creatinine ratio ≥ 30 mg/g EGIR The European Group for the Study of Insulin Resistance (1999) requires insulin resistance defined as the top 25% of the fasting insulin values among nondiabetic individuals AND two or more of the following: Central obesity: waist circumference ≥ 94 cm or 37 inches (male), ≥ 80 cm or 31.5 inches (female) Dyslipidemia: TG ≥ 2.0 mmol/L and/or HDL-C < 1.0 mmol/L or treated for dyslipidemia Blood pressure ≥ 140/90 mmHg or antihypertensive medication Fasting plasma glucose ≥ 6.1 mmol/L NCEP The U.S. National Cholesterol Education Program Adult Treatment Panel III (2001) requires at least three of the following: Central obesity: waist circumference ≥ 102 cm or 40 inches (male), ≥ 88 cm or 35 inches(female) Dyslipidemia: TG ≥ 1.7 mmol/L (150 mg/dl) Dyslipidemia: HDL-C < 40 mg/dL (male), < 50 mg/dL (female) Blood pressure ≥ 130/85 mmHg (or treated for hypertension) Fasting plasma glucose ≥ 6.1 mmol/L (110 mg/dl) American Heart Association There is confusion as to whether, in 2004, the American Heart Association and National Heart, Lung, and Blood Institute intended to create another set of guidelines or simply update the National Cholesterol Education Program definition. Central obesity: waist circumference ≥ 102 cm or 40 inches (male), ≥ 88 cm or 35 inches(female) Dyslipidemia: TG ≥ 1.7 mmol/L (150 mg/dL) Dyslipidemia: HDL-C < 40 mg/dL (male), < 50 mg/dL (female) Blood pressure ≥ 130/85 mmHg (or treated for hypertension) Fasting plasma glucose ≥ 5.6 mmol/L (100 mg/dL), or use of medication for hyperglycemia Other High-sensitivity C-reactive protein has been developed and used as a marker to predict coronary vascular diseases in metabolic syndrome, and it was recently used as a predictor for nonalcoholic fatty liver disease (steatohepatitis) in correlation with serum markers that indicated lipid and glucose metabolism. Fatty liver disease and steatohepatitis can be considered manifestations of metabolic syndrome, indicative of abnormal energy storage as fat in ectopic distribution. Reproductive disorders (such as polycystic ovary syndrome in women of reproductive age), and erectile dysfunction or decreased total testosterone (low testosterone-binding globulin) in men can be attributed to metabolic syndrome. Prevention Various strategies have been proposed to prevent the development of metabolic syndrome. These include increased physical activity (such as walking 30 minutes every day), and a healthy, reduced calorie diet. Many studies support the value of a healthy lifestyle as above. However, one study stated these potentially beneficial measures are effective in only a minority of people, primarily because of a lack of compliance with lifestyle and diet changes. The International Obesity Taskforce states that interventions on a sociopolitical level are required to reduce development of the metabolic syndrome in populations.The Caerphilly Heart Disease Study followed 2,375 male subjects over 20 years and suggested the daily intake of an Imperial pint (~568 mL) of milk or equivalent dairy products more than halved the risk of metabolic syndrome. Some subsequent studies support the authors findings, while others dispute them. A systematic review of four randomized controlled trials said that, in the short term, a paleolithic nutritional pattern improved three of five measurable components of the metabolic syndrome in participants with at least one of the components. Management Medications Generally, the individual disorders that compose the metabolic syndrome are treated separately. Diuretics and ACE inhibitors may be used to treat hypertension. Various cholesterol medications may be useful if LDL cholesterol, triglycerides, and/or HDL cholesterol is abnormal. Diet Dietary carbohydrate restriction reduces blood glucose levels, contributes to weight loss, and reduces the use of several medications that may be prescribed for metabolic syndrome. Epidemiology Approximately 20–25 percent of the worlds adult population has the cluster of risk factors that is metabolic syndrome. In 2000, approximately 32% of U.S. adults had metabolic syndrome. In more recent years that figure has climbed to 34%.In young children, there is no consensus on how to measure metabolic syndrome since age-specific cut points and reference values that would indicate "high risk" have not been well established. A continuous cardiometabolic risk summary score is often used for children instead of a dichotomous measure of metabolic syndrome. History In 1921, Joslin first reported the association of diabetes with hypertension and hyperuricemia. In 1923, Kylin reported additional studies on the above triad. In 1947, Vague observed that upper body obesity appeared to predispose to diabetes, atherosclerosis, gout and calculi. In the late 1950s, the term metabolic syndrome was first used In 1967, Avogadro, Crepaldi and coworkers described six moderately obese people with diabetes, hypercholesterolemia, and marked hypertriglyceridemia, all of which improved when the affected people were put on a hypocaloric, low-carbohydrate diet. In 1977, Haller used the term "metabolic syndrome" for associations of obesity, diabetes mellitus, hyperlipoproteinemia, hyperuricemia, and hepatic steatosis when describing the additive effects of risk factors on atherosclerosis. The same year, Singer used the term for associations of obesity, gout, diabetes mellitus, and hypertension with hyperlipoproteinemia. In 1977 and 1978, Gerald B. Phillips developed the concept that risk factors for myocardial infarction concur to form a "constellation of abnormalities" (i.e., glucose intolerance, hyperinsulinemia, hypercholesterolemia, hypertriglyceridemia, and hypertension) associated not only with heart disease, but also with aging, obesity and other clinical states. He suggested there must be an underlying linking factor, the identification of which could lead to the prevention of cardiovascular disease; he hypothesized that this factor was sex hormones. In 1988, in his Banting lecture, Gerald M. Reaven proposed insulin resistance as the underlying factor and named the constellation of abnormalities syndrome X. Reaven did not include abdominal obesity, which has also been hypothesized as the underlying factor, as part of the condition. See also Metabolic disorder Portal-visceral hypothesis References == External links ==
Anomic aphasia	Anomic aphasia (also known as dysnomia, nominal aphasia, and amnesic aphasia) is a mild, fluent type of aphasia where individuals have word retrieval failures and cannot express the words they want to say (particularly nouns and verbs). Anomia is a deficit of expressive language. Anomia is a symptom of all forms of aphasia, but patients whose primary deficit is word retrieval are diagnosed with anomic aphasia. Individuals with aphasia who display anomia can often describe an object in detail and maybe even use hand gestures to demonstrate how the object is used, but cannot find the appropriate word to name the object. Patients with anomic aphasia have relatively preserved speech fluency, repetition, comprehension, and grammatical speech. Types Word selection anomia is caused by damage to the posterior inferior temporal area. This type of anomia occurs when the patient knows how to use an object and can correctly select the target object from a group of objects, and yet cannot name the object. Some patients with word selection anomia may exhibit selective impairment in naming particular types of objects, such as animals or colors. In the subtype known as color anomia, the patient can distinguish between colors but cannot identify them by name or name the color of an object. The patients can separate colors into categories, but they cannot name them. Semantic anomia is caused by damage to the angular gyrus. This is a disorder in which the meaning of words becomes lost. In patients with semantic anomia, a naming deficit is accompanied by a recognition deficit. Thus, unlike patients with word selection anomia, patients with semantic anomia are unable to select the correct object from a group of objects, even when provided with the name of the target object. Disconnection anomia results from the severing of connections between sensory and language cortices. Patients with disconnection anomia may exhibit modality-specific anomia, where the anomia is limited to a specific sensory modality, such as hearing. For example, a patient who is perfectly capable of naming a target object when it is presented via certain sensory modalities like audition or touch, may be unable to name the same object when the object is presented visually. Thus, in such a case, the patients anomia arises as a consequence of a disconnect between their visual cortex and language cortices.Patients with disconnection anomia may also exhibit callosal anomia, in which damage to the corpus callosum prevents sensory information from being transmitted between the two hemispheres of the brain. Therefore, when sensory information is unable to reach the hemisphere that is language-dominant (typically the left hemisphere in most individuals), the result is anomia. For instance, if patients with this type of disconnection anomia hold an object in their left hand, this somatosensory information about the object would be sent to the right hemisphere of the brain, but then would be unable to reach the left hemisphere due to callosal damage. Thus, this somatosensory information would fail to be transmitted to language areas in the left hemisphere, in turn resulting in the inability to name the object in the left hand. In this example, the patient would have no problem with naming, if the test object were to be held in the right hand. This type of anomia may also arise as a consequence of a disconnect between sensory and language cortices. Articulatory initiation anomia results from damage to the frontal area. Characteristics of this anomia are non-fluent output, word-finding pauses, deficient word lists. Patients perform better at confrontation naming tasks, the selection of a label for a corresponding picture, than word list tasks. Patients are aided in word selection by prompting, unlike those with word selection anomia. Phonemic substitution anomia results from damage to the inferior parietal area. Patients maintain fluent output but exhibit literal and neologistic paraphasia. Literal paraphasia is the incorrect substitution of phonemes, and neologistic paraphasia is the use of non-real words in the place of real words. Patients naming ability is contaminated by paraphasia. Modality-specific anomia is caused by damage to the sensory cortex, pathways to the dominant angular gyrus, or both. In these patients, word-finding is worst in one sensory modality, for example visual or tactile. Causes Anomic aphasia occurring by itself may be caused by damage to almost anywhere in the left hemisphere and in some cases can be seen in instances of right hemisphere damage. Anomia can be genetic or caused by damage to various parts of the parietal lobe or the temporal lobe of the brain due to traumatic injury, stroke, or a brain tumor. While anomic aphasia is primarily caused by structural lesions, they may also originate in Alzheimers disease (anomia may be the earliest language deficit in posterior cortical atrophy variant of Alzheimers) or other neurodegenerative diseases.Although the main causes are not specifically known, many researchers have found factors contributing to anomic aphasia. People with damage to the left hemisphere of the brain are more likely to have anomic aphasia. Brocas area, the speech production center in the brain, was linked to being the source for speech execution problems, with the use of functional magnetic resonance imaging (fMRI), now commonly used to study anomic patients. Other experts believe that damage to Wernickes area, which is the speech comprehension area of the brain, is connected to anomia because the patients cannot comprehend the words that they are hearing.Although many experts have believed that damage to Brocas area or Wernickes area are the main causes of anomia, current studies have shown that damage in the left parietal lobe is the cause of anomic aphasia. One study was conducted using a word repetition test as well as fMRI in order to see the highest level of activity as well as where the lesions are in the brain tissue. Fridrikkson, et al. saw that damage to neither Brocas area nor Wernickes area were the sole sources of anomia in the subjects. Therefore, the original anomia model, which theorized that damage occurred on the surface of the brain in the grey matter was debunked, and it was found that the damage was in the white matter deeper in the brain, on the left hemisphere. More specifically, the damage was in a part of the nerve tract called the arcuate fasciculus, for which the mechanism of action is unknown, though it is known to connect the posterior (back) of the brain to the anterior (front) and vice versa.While anomic aphasia is associated with lesions throughout the left hemisphere, severe and isolated anomia has been considered a sign of deep temporal lobe or lateral temporo-occipital damage. Damage to these areas is seen in patients showing infarction limited to regions supplied by the dominant posterior cerebral artery (PCA) and is referred to as posterior cerebral artery syndrome. Diagnosis The best way to see if anomic aphasia has developed is by using verbal and imaging tests. The combination seems to be most effective, since either test done alone may give false positives or false negatives. For example, the verbal test is used to see if a speech disorder presents, and whether the problem is in speech production or comprehension. Patients with Alzheimers disease have speech problems linked to dementia or progressive aphasias, which can include anomia. The imaging test, mostly done using MRI scans, is ideal for lesion mapping or viewing deterioration in the brain. However, imaging cannot diagnose anomia on its own because the lesions may not be located deep enough to damage the white matter or the arcuate fasciculus. However, anomic aphasia is very difficult to associate with a specific lesion location in the brain. Therefore, the combination of speech tests and imaging tests has the highest sensitivity and specificity.Picture-naming tests, such as the Philadelphia Naming Test (PNT), are also utilized in diagnosing aphasias. Analysis of picture-naming is compared with reading, picture categorizing, and word categorizing. There is a considerable similarity among aphasia syndromes in terms of picture-naming behavior, however anomic aphasiacs produced the fewest phonemic errors and the most multiword circumlocutions. These results suggest minimal word-production difficulty in anomic aphasia relative to other aphasia syndromes.Anomic aphasia has been diagnosed in some studies using the Aachen Aphasia Test (AAT), which tests language functioning after brain injury. This test aims to: identify the presence of aphasia; provide a profile of the speakers language functioning according to different language modalities (speaking, listening, reading, writing) and different levels of linguistic description (phonology, morphology, semantics, and syntax); give a measure of severity of any breakdown. This test was administered to patients participating in a study in 2012, and researchers found that on the naming subtest of the AAT patients showed relevant naming difficulties and tended to substitute the words they could not produce with circumlocutions.The Western Aphasia Battery is another test that is conducted with the goal of classifying aphasia subtypes and rating the severity of the aphasiac impairment. The test is composed of four language and three performance domains. Syndrome classification is determined by the pattern of performance on the four language subtests, which assess spontaneous speech, comprehension, repetition, and naming.Doing a hearing test first is important, in case the patient cannot clearly hear the words or sentences needed in the speech repetition test. In the speech tests, the person is asked to repeat a sentence with common words; if the person cannot identify the word, but he or she can describe it, then the person is highly likely to have anomic aphasia. However, to be completely sure, the test is given while a test subject is in an fMRI scanner, and the exact location of the lesions and areas activated by speech are pinpointed. Few simpler or cheaper options are available, so lesion mapping and speech repetition tests are the main ways of diagnosing anomic aphasia. Definition Anomic aphasia (anomia) is a type of aphasia characterized by problems recalling words, names, and numbers. Speech is fluent and receptive language is not impaired in someone with anomic aphasia. Subjects often use circumlocutions (speaking in a roundabout way) to avoid a name they cannot recall or to express a certain word they cannot remember. Sometimes, the subject can recall the name when given clues. Additionally, patients are able to speak with correct grammar; the main problem is finding the appropriate word to identify an object or person.Sometimes, subjects may know what to do with an object, but still not be able to give a name to the object. For example, if a subject is shown an orange and asked what it is called, the subject may be well aware that the object can be peeled and eaten, and may even be able to demonstrate this by actions or even verbal responses; however, they cannot recall that the object is called an "orange". Sometimes, when a person with this condition is multilingual, they might confuse the language they are speaking in trying to find the right word (inadvertent code-switching). Management No method is available to completely cure anomic aphasia. However, treatments can help improve word-finding skills. Although a person with anomia may find recalling many types of words to be difficult, such as common nouns, proper nouns, verbs, etc., many studies have shown that treatment for object words, or nouns, has shown promise in rehabilitation research. The treatment includes visual aids, such as pictures, and the patient is asked to identify the object or activity. However, if that is not possible, then the patient is shown the same picture surrounded by words associated with the object or activity. Throughout the process, positive encouragement is provided. The treatment shows an increase in word finding during treatment; however, word identifying decreased two weeks after the rehabilitation period. Therefore, it shows that rehabilitation effort needs to be continuous for word-finding abilities to improve from the baseline. The studies show that verbs are harder to recall or repeat, even with rehabilitation.Other methods in treating anomic aphasia include circumlocution-induced naming therapy (CIN), wherein the patient uses circumlocution to assist with his or her naming rather than just being told to name the item pictured after given some sort of cue. Results suggest that the patient does better in properly naming objects when undergoing this therapy because CIN strengthens the weakened link between semantics and phonology for patients with anomia, since they often know what an object is used for, but cannot verbally name it.Anomia is often challenging for the families and friends of those affected by it. One way to overcome this is computer-based treatment models, effective especially when used with clinical therapy. Leemann et al. provided anomic patients with computerized-assisted therapy (CAT) sessions, along with traditional therapy sessions using treatment lists of words. Some of the patients received a drug known to help relieve symptoms of anomia (levodopa), while others received a placebo. The researchers found that the drug had no significant effects on improvement with the treatment lists, but almost all of the patients improved after the CAT sessions. They concluded that this form of computerized treatment is effective in increasing naming abilities in anomic patients.Additionally, one study researched the effects of using "excitatory (anodal) transcranial direct current stimulation" over the right temporoparietal cortex, a brain area that seems to correlate to language. The electrical stimulation seemed to enhance language training outcome in patients with chronic aphasia.Contextual repetition priming treatment is a technique which involves repeated repetition of names of pictures that are related semantically, phonologically, or are unrelated. Patients with impaired access to lexical-semantic representations show no long-term improvement in naming, but patients with good access to semantics show long-term benefits.Development of self-cueing strategies can also facilitate word retrieval. Patients identify core words that can be retrieved without struggle, and establish a relationship between cue words and words that begin with the same sound but cannot be retrieved. Patients then learn to use the cue word to facilitate word retrieval for the target object. Epidemiology Many different populations can and do have anomia. For instance, deaf patients who have had a stroke can demonstrate semantic and phonological errors, much like hearing anomic patients. Researchers have called this subtype sign anomia.Multilingual patients typically experience anomia to a greater degree in just one of their fluent languages. However, evidence conflicts as to which language – first or second – is impacted more.Research on children with anomia has indicated that children who undergo treatment are, for the most part, able to gain back normal language abilities, aided by brain plasticity. However, longitudinal research on children with anomic aphasia due to head injury shows that even several years after the injury, some signs of deficient word retrieval are still observed. These remaining symptoms can sometimes cause academic difficulties later on. Patients This disorder may be extremely frustrating for people with and without the disorder. Although the persons with anomic aphasia may know the specific word, they may not be able to recall it and this can be very difficult for everyone in the conversation. Positive reinforcements are helpful.Although not many literary cases mention anomic aphasia, many nonfiction books have been written about living with aphasia. One of them is The Man Who Lost His Language by Sheila Hale. It is the story of Hales husband, John Hale, a scholar who had had a stroke and lost speech formation abilities. In her book, Hale also explains the symptoms and mechanics behind aphasia and speech formation. She adds the emotional components of dealing with a person with aphasia and how to be patient with the speech and communication. See also Conduction aphasia Expressive aphasia Lists of language disorders Primary progressive aphasia Receptive aphasia Tip of the tongue References == External links ==
Otomycosis	Otomycosis is a fungal ear infection, a superficial mycotic infection of the outer ear canal. It is more common in tropical countries. The infection may be either subacute or acute and is characterized by malodorous discharge, inflammation, pruritus, scaling, and severe discomfort. The mycosis results in inflammation, superficial epithelial exfoliation, masses of debris containing hyphae, suppuration, and pain. Diagnosis Otoscopy (exam of the ear) is best done with a binocular microscope that provides adequate lighting, depth perception, and the ability to instrument the ear to comfortably remove the fungus. Findings range from scattered saprophytic fungal colonies of various colors, causing no symptoms, to densely packed fungal debris, often intermixed with cerumen (wax), filling the entire canal and involving the tympanic membrane (eardrum). The fungus can cling to the skin and tympanic membrane, presumably because of invading hyphae, and can require significant time to accomplish complete removal. Cause Most fungal ear infections are caused by Aspergillus niger, Aspergillus fumigatus, Penicillium and Candida albicans.Otomycosis commonly results from overuse of antibacterial ear drops, which should never be used for more than 7 days. In such cases the fungus is an opportunist that results from antibacterial suppression of the normal bacterial flora, combined with the steroid the drops also contain. Signs and Symptoms Otomycosis does not usually cause as much canal skin edema as does acute bacterial external otitis. While a severe pressure type of pain is a prominent feature of advanced cases, the ear is usually much less tender, if at all, to traction or tragal pressure. Appearance of the fungus is variable, most commonly gray, white, or black, often intermixed with cerumen and clinging to the canal skin. Gray concretions may be present. It can require significant time to remove, best done with suction and microscopic ear instruments, by an ENT specialist. Treatment Treatment of otomycosis typically includes microscopic suction to remove fungal mass, topical antibiotics to be discontinued, and treatment with antifungal eardrops for three weeks. References == External links ==
Navicular syndrome	Navicular syndrome, often called navicular disease, is a syndrome of lameness problems in horses. It most commonly describes an inflammation or degeneration of the navicular bone and its surrounding tissues, usually on the front feet. It can lead to significant and even disabling lameness. Description of the navicular area Knowledge of equine forelimb anatomy is especially useful for understanding navicular syndrome. The navicular bone lies behind the coffin bone and under the small pastern bone. The deep digital flexor (DDF) tendon runs down the back of the cannon and soft tissue in that area and under the navicular bone before attaching to the back of the coffin bone. The DDF tendon flexes the coffin joint, and the navicular bone acts as a fulcrum that the DDF tendon runs over.The navicular bone is supported by several ligaments above, below, and on the side. One of these ligaments is the impar ligament, which attaches the navicular bone to the coffin bone (distal phalanx). Cartilage lies between the navicular bone and the coffin joint, as well as between the navicular bone and the DDF tendon. The navicular bursa - a small sac that protects the DDF and navicular bone from abrasion as the tendon slides over the area - lies between the navicular bone and the DDF tendon. Causes and contributing factors There is no single known cause of navicular syndrome, although there are many theories, and several primary factors. The first factor is compression of the navicular bone under the DDF tendon and the back of the small pastern bone. Repeated compression in this area can cause cartilage degeneration, with the cartilage flattening and gradually becoming less springy and shock-absorbing. It may also begin to erode. Cartilage degeneration is common in navicular horses, usually along the flexor surface. This finding, and the associated biochemical changes, have led some researchers to conclude that there are elements in navicular disease common to osteoarthritis, and to suggest similar therapeutic regimes.Cartilage erosion may progress to the point that the bone underneath will become exposed. With the cartilage no longer present to protect it, the navicular bursa and DDF tendon may become damaged by the constant rubbing against the navicular bone. Navicular bursitis (inflammation of the navicular bursa) may occur, even if cartilage damage is not severe. This is probably due to the friction between the navicular bone and the DDF tendon from compression. Constant compression can also increase the bone density directly under the cartilage surfaces, especially on the flexor side. This tends to make the bone more brittle, and thus more likely to break. Another main factor is the tension placed on the ligaments that support the navicular bone. Some experts believe that the degenerative process begins with excess tension placed on these ligaments, causing strain and inflammation. Inflammation from strain of the impar ligament can decrease blood flow to and from the navicular bone, as the major blood vessels supplying the bone run up and down this area. If the ligament continues to be strained, it can thicken and permanently reduce blood flow to the navicular bone. Because veins are more easily compressed than arteries, blood flow to the bone would be less obstructed than blood flow from the bone. This would cause a buildup of pressure within the navicular bone. The navicular bone, in response to both the increased pressure and overall decreased blood supply, would absorb mineral from its center. Excess tension can also cause exostoses where the ligaments attach to the navicular bone, giving the bone a "canoe" shape. If tension is extreme, the ligaments may actually tear. Recent research has found correlations between "toe-first landing" of the hooves and navicular problems, due to excessive strain put on the deep digital flexor tendon, as a consequence of misalignment of the lower joints. Toe-first landing, usually seen as a consequence of navicular disease, may actually be a cause or at least a contributing factor to the onset of tendon inflammation and bone modifications. Toe-first landing is often caused by frog and heel overtrimming, long toes, and/or poor shoeing. Contributing factors Conformation Certain conformational defects may contribute to navicular syndrome, especially defects that promote concussion. These include upright pasterns, small feet, narrow and upright feet, significant downhill build (commonly seen in American Quarter Horses), and long toes with low heels (commonly seen in Thoroughbreds). The long toe, low heel conformation places constant stress on the navicular bone, even as the horse is standing. Upright feet increase concussion, especially in the heel region of the hoof where the navicular bone is located. Excess concussion cannot be absorbed as well by the structures designed to do so (the frog, heels, and digital cushion), so more impact is transmitted to the structures within the foot. Poor hoof shape is usually inherited, although poor shoeing and trimming can contribute to these shapes. With the long toe, low heel conformation can come contracted heels (narrowing of the heel) which further compresses the navicular bone along with sheared heels adding more stress to the tendons and navicular bones. Shoeing Poor trimming, shoe selection, or inappropriate shoe attachment are well-known causes of lameness, and navicular disease is fairly common in the modern-day domesticated horse. However, it is also seen in wild horse populations. Those who advocate "barefoot trimming" of domestic horses propose that in nature, a horses hoof is designed to expand and contract as the horse moves. This expanding and contracting acts as an auxiliary blood pump, and aids the circulation of blood to the lower extremities. When an inflexible metal shoe is improperly attached to the hoof, the hoof can no longer work as designed, and blood flow is inhibited. However, evidence of navicular degeneration has been established in the fossil record of early horses. Mary Thompson, a vertebrate paleontologist at Idaho Museum of Natural History, has found evidence in many species of early horses and concludes, "The results of this study strongly suggest that man’s intervention (whether by increased usage or improper breeding practices) may not be the sole cause of the syndrome", although she cautions that her results are preliminary. Work Working on steep hills, galloping, and jumping all contribute to navicular syndrome, as they place greater stress on the DDF tendons, and may cause overextension of the pastern and coffin joints. Regular exercise on hard or irregular ground increases concussion on the hoof, thus increasing the risk of navicular syndrome. It is possible that standing can also increase the chance of navicular disease (such as a horse that spends most of the day in a stall with little turnout, as with some racehorses and show horses). Blood flow to the hoof decreases when the horse is not in motion. The horse is also constantly applying pressure to the navicular bones (which is intermittent as the horse moves). Body weight Horses with a high weight-to-foot-size ratio may have an increased chance of exhibiting symptoms of navicular syndrome, since the relative load on the foot increases. This might explain why the syndrome is seen more frequently in Thoroughbreds, American Quarter Horses, and Warmbloods as opposed to ponies and Arabians. Signs Heel pain is very common in horses with navicular syndrome. Lameness may begin as mild and intermittent, and progress to severe. This may be due to strain and inflammation of the ligaments supporting the navicular bone, reduced blood flow and increased pressure within the hoof, damage to the navicular bursa or DDF tendon, or from cartilage erosion. Affected horses display a "tiptoe" gait - trying to walk on the toes due to heel pain. They may stumble frequently. The lameness may switch from one leg to another, and may not be consistent. Lameness usually occurs in both front feet, although one foot may be more sore than the other. Lameness is usually mild (1–2 on a scale of 5). It can be made worse when the horse is worked on a hard surface or on a circle. After several months of pain, the feet may begin to change shape, especially the foot that has been experiencing the most pain, which tends to become more upright and narrow. Treatment and prognosis No single treatment works for all cases, probably because there is no single cause for all cases. The degenerative changes are usually quite advanced by the time the horse is consistently lame, and these changes are believed to be non-reversible. At this time, it is best to manage the condition and focus on alleviating pain and slowing the degeneration. Trimming Putting the foot into proper neurological and biomechanical balance is crucial. Often navicular horses have long toes and underrun heels with very little inner wall depth or strength. Exposing the horse to proper stimulus to improve hoof form and structure is also vital. Hoof care The issue of hoof care is a subject of great debate. Corrective shoeing can be beneficial to horses suffering from navicular disease, although sometimes the effects are only temporary. Others believe that removing the shoes altogether is the best way to manage this disease, as it allows increased circulation to the hoof. People on both sides agree that proper hoof shape and angle are an important long-term management plan for a horse with navicular disease. As with laminitis, different horses may respond in different ways to a given technique, so the farrier, owner, and veterinarian should work as a team to formulate a plan and to adapt if the initial plan is not effective. People who choose to treat navicular disease through shoeing may use a shoe designed to lift and support the heels. This can sometimes be accomplished with a flat shoe and trimming alone. Wedge pads or wedged shoes are often used, but can amplify heel-related problems if present. Another strategy is to use a bar type shoe. Often, an egg-bar shoe, or straight bar shoe. Some horses benefit from shoes that change the breakover of their foot (like a rolled toe). With or without shoes, the hoof must be trimmed in such a way as to restore the balance and angle that may have been lost. Horses with long toe-low heel conformation need careful trimming to counter this. Horses with upright feet may need their heels lowered and a shoe that will allow their heels to spread. Early intervention is key; in one study, shoeing was successful in 97% of horses treated within ten months of the onset of signs, while only 54% of horses lame for over a year responded.Advocates of barefoot trimming cite recent studies which show that removing the shoes can help alleviate the symptoms of navicular disease, and in some cases, reverse some of the damage done to the hoof. Because navicular disease can be caused, or at least exacerbated by shoeing, removing the cause is the first step in this strategy toward the management of pain in the animal. Successive carefully applied trims help to restore the natural angle and shape of the hoof, while walking helps to stimulate circulation to the hoof. It is not uncommon to find horses whose navicular disease is completely manageable through corrective barefoot trimming. However, this may require a transition period lasting from weeks to years where the horse may remain lame, or may never become sound.If there is significant degeneration in the bone, a flexor cortex cyst, adhesions to the deep digital flexor tendon, or avulsion fractures, relief is typically incomplete no matter what foot care technique is used. Exercise Horses with navicular syndrome need a less intense work schedule. Their fitness can be maintained through slow long-distance work or swimming, as opposed to being worked at high speeds, up steep hills, or on hard surfaces, irregular terrain, or deep footing. Reducing the frequency of jumping is also important. Some veterinarians and hoof care practitioners recommend exercising the horse on varied terrain to stimulate and strengthen the caudal hoof structures. Medication Vasodilators improve the blood flow into the vessels of the hoof. Examples include isoxsuprine (currently unavailable in the UK) and pentoxifylline. Anticoagulants can also improve blood flow. The use of warfarin has been proposed, but the extensive monitoring required makes it unsuitable in most cases. Anti-inflammatory drugs are used to treat the pain, and can help the lameness resolve sometimes if shoeing and training changes are made. Include Nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and other joint medications. The use of intramuscular glycosaminoglycans has been shown to decrease pain in horses with navicular disease, but this effect wanes after discontinuation of therapy. Oral glycosaminoglycans may have a similar effect.Bisphosphonates can be useful in cases where bone remodeling is causing pain.Gallium nitrate (GaN) has been hypothesized as a possible treatment for navicular disease, but its benefits have not been confirmed by formal clinical studies. One pilot study examined horses given gallium nitrate in their feed rations. While it was absorbed slowly, it did stay in the animals system, providing a baseline dosage for future studies. Surgery Palmar digital neurectomy (or "nerving" or "denerving") is not without adverse side effects and should therefore be used as a last resort. In this procedure, the palmar digital nerves are severed, so the horse loses sensation in the back of the foot. This procedure should only be performed if it will eliminate the lameness associated with navicular syndrome, and only after all other options have been explored. The procedure is usually performed on both front feet. Complications can include infection of the wound, continuation of the lameness (if the nerves regrow or if small branches of the nerves are not removed), neuromas, and rupture of the deep digital flexor tendon. After the neurectomy, if the horse becomes injured in the area the injury may go undetected for a long period of time, which risks the animals health. Due to this, the feet should be cleaned and inspected regularly. Neurectomy tends to lower the market value of a horse, and may even make the horse ineligible for competition. Neurectomy is controversial. The most common misconception about "nerving" a horse is that it will permanently solve the lameness/pain issue. In fact, though the time periods vary based on the individual horse and surgical method utilized, these nerves often regenerate and return sensation to the afflicted region within two to three years. In navicular suspensory desmotomy, the ligaments supporting the navicular bone are severed. This makes the navicular bone more mobile, and thus reduces the tension of the other ligaments. It is successful about half of the time. Prognosis The prognosis for a horse with navicular syndrome is guarded. Many times the horse does not return to its former level of competition. Others are retired. Eventually all horses with the syndrome will need to lessen the strenuousness of their work, but with proper management, a horse with navicular syndrome can remain useful for some time. References Sources King, Christine & Mansmann, Richard Equine Lameness. Equine Research (1997). (p. 610-626). PT Colahan, IG Mayhew, AM Merrit & JN Moore Manual of Equine Medicine and Surgery Copyright Mosby Inc (1999). (p. 402-407). RJ Rose & DR Hodgson Manual of Equine Practice Copyright WB Saunders (2000). (p. 126-128). See also Horse evolution
Glomerulonephritis	Glomerulonephritis (GN) is a term used to refer to several kidney diseases (usually affecting both kidneys). Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the name, but not all diseases necessarily have an inflammatory component. As it is not strictly a single disease, its presentation depends on the specific disease entity: it may present with isolated hematuria and/or proteinuria (blood or protein in the urine); or as a nephrotic syndrome, a nephritic syndrome, acute kidney injury, or chronic kidney disease. They are categorized into several different pathological patterns, which are broadly grouped into non-proliferative or proliferative types. Diagnosing the pattern of GN is important because the outcome and treatment differ in different types. Primary causes are intrinsic to the kidney. Secondary causes are associated with certain infections (bacterial, viral or parasitic pathogens), drugs, systemic disorders (SLE, vasculitis), or diabetes. Signs and symptoms Glomerulonephritis refers to an inflammation of the glomerulus, which is the unit involved in filtration in the kidney. This inflammation typically results in one or both of the nephrotic or nephritic syndromes.: 500 Nephrotic syndrome The nephrotic syndrome is characterised by the finding of edema in a person with increased protein in the urine and decreased protein in the blood, with increased fat in the blood. Inflammation that affects the cells surrounding the glomerulus, podocytes, increases the permeability to proteins, resulting in an increase in excreted proteins. When the amount of proteins excreted in the urine exceeds the livers ability to compensate, fewer proteins are detected in the blood – in particular albumin, which makes up the majority of circulating proteins. With decreased proteins in the blood, there is a decrease in the oncotic pressure of the blood. This results in edema, as the oncotic pressure in tissue remains the same. Although decreased intravascular oncotic (i.e. osmotic) pressure partially explains the patients edema, more recent studies have shown that extensive sodium retention in the distal nephron (collecting duct) is the predominant cause of water retention and edema in the nephrotic syndrome. This is worsened by the secretion of the hormone aldosterone by the adrenal gland, which is secreted in response to the decrease in circulating blood and causes sodium and water retention. Hyperlipidemia is thought to be a result of the increased activity of the liver.: 549 Nephritic syndrome The nephritic syndrome is characterised by blood in the urine (especially Red blood cell casts with dysmorphic red blood cells) and a decrease in the amount of urine in the presence of hypertension. In this syndrome, inflammatory damage to cells lining the glomerulus are thought to result in destruction of the epithelial barrier, leading to blood being found in the urine. At the same time, reactive changes, e.g. proliferation of mesangial cells, may result in a decrease in kidney blood flow, resulting in a decrease in the production of urine. The renin–angiotensin system may be subsequently activated, because of the decrease in perfusion of juxtaglomerular apparatus, which may result in hypertension.: 554 Nonproliferative This is characterised by forms of glomerulonephritis in which the number of cells is not changed. These forms usually result in the nephrotic syndrome. Causes include: Minimal change disease Minimal change disease is characterised as a cause of nephrotic syndrome without visible changes in the glomerulus on microscopy. Minimal change disease typically presents with edema, an increase in proteins passed from urine and decrease in blood protein levels, and an increase in circulating lipids (i.e., nephrotic syndrome) and is the most common cause of the nephrotic syndrome in children. Although no changes may be visible by light microscopy, changes on electron microscopy within the glomeruli may show a fusion of the foot processes of the podocytes (cells lining the basement membrane of the capillaries of glomerulus). It is typically managed with corticosteroids and does not progress to chronic kidney disease.: 500 : 550 Focal segmental glomerulosclerosis Focal segmental glomerulosclerosis is characterised by a sclerosis of segments of some glomeruli. It is likely to present as a nephrotic syndrome. This form of glomerulonephritis may be associated with conditions such as HIV and heroin abuse, or inherited as Alport syndrome. The cause of about 20–30% of focal-segmental glomerulosclerosis is unknown. On microscopy, affected glomeruli may show an increase in hyalin, a pink and homogenous material, fat cells, an increase in the mesangial matrix and collagen. Treatment may involve corticosteroids, but up to half of people with focal segmental glomerulonephritis continue to have progressive deterioration of kidney function, ending in kidney failure.: 550–551 Membranous glomerulonephritis Membranous glomerulonephritis may cause either nephrotic or a nephritic picture. About two-thirds are associated with auto-antibodies to phospholipase A2 receptor, but other associations include cancers of the lung and bowel, infections such as hepatitis B and malaria, drugs including penicillamine, and connective tissue diseases such as systemic lupus erythematosus. Individuals with cerebral shunts are at risk of developing shunt nephritis, which frequently produces MGN.Microscopically, MGN is characterized by a thickened glomerular basement membrane without a hyperproliferation of the glomerular cells. Immunofluorescence demonstrates diffuse granular uptake of IgG. The basement membrane may completely surround the granular deposits, forming a "spike and dome" pattern. Tubules also display the symptoms of a typical Type III hypersensitivity reaction, which causes the endothelial cells to proliferate, which can be seen under a light microscope with a PAS stain.Prognosis follows the rule of thirds: one-third remain with MGN indefinitely, one-third remit, and one-third progress to end-stage kidney failure. As the glomerulonephritis progresses, the tubules of the kidney become infected, leading to atrophy and hyalinisation. The kidney appears to shrink. Treatment with corticosteroids is attempted if the disease progresses. In extremely rare cases, the disease has been known to run in families, usually passed down through the females. This condition, similarly, is called Familial Membranous Glomerulonephritis. There have only been about nine documented cases in the world. Thin basement membrane disease Thin basement membrane disease is an autosomal dominant inherited disease characterized by thin glomerular basement membranes on electron microscopy. It is a benign condition that causes persistent microscopic hematuria. This also may cause proteinuria which is usually mild and overall prognosis is excellent. Fibronectin glomerulopathy Fibronectin glomerulopathy is a rare form of glomerulopathy characterised by enlarged glomeruli with deposits in the mesangium and subendothelial space. The deposits have been shown to be fibronectin. This condition is inherited in an autosomal dominant fashion. About 40% of cases are due to mutations in the fibronectin (FN1) gene located on chromosome 2 (2q34). Proliferative Proliferative glomerulonephritis is characterised by an increased number of cells in the glomerulus. These forms usually present with a triad of blood in the urine, decreased urine production, and hypertension, the nephritic syndrome. These forms usually progress to end-stage kidney failure (ESKF) over weeks to years (depending on type). IgA nephropathy IgA nephropathy, also known as Bergers disease, is the most common type of glomerulonephritis, and generally presents with isolated visible or occult hematuria, occasionally combined with low grade proteinuria, and rarely causes a nephritic syndrome characterised by proteinuria, and visible blood in the urine. IgA nephropathy is classically described as a self-resolving form in young adults several days after a respiratory infection. It is characterised by deposits of IgA in the space between glomerular capillaries.: 501 : 554–555 Henoch–Schönlein purpura refers to a form of IgA nephropathy, typically affecting children, characterised by a rash of small bruises affecting the buttocks and lower legs, with abdominal pain.: 501 Post-infectious Post-infectious glomerulonephritis can occur after essentially any infection, but classically occurs after infection with the bacteria Streptococcus pyogenes. It typically occurs 1–4 weeks after a pharyngeal infection with this bacterium, and is likely to present with malaise, a slight fever, nausea and a mild nephritic syndrome of moderately increased blood pressure, gross haematuria, and smoky-brown urine. Circulating immune complexes that deposit in the glomeruli may lead to an inflammatory reaction. : 554–555 Diagnosis may be made on clinical findings or through antistreptolysin O antibodies found in the blood. A biopsy is seldom done, and the disease is likely to self-resolve in children in 1–4 weeks, with a poorer prognosis if adults are affected or if the affected children are obese. : 501 Membranoproliferative Membranoproliferative GN (MPGN), also known as mesangiocapillary glomerulonephritis,: 502 is characterised by an increase in the number of cells in the glomerulus, and alterations in the glomerular basement membrane. These forms present with the nephritic syndrome, hypocomplementemia, and have a poor prognosis. Three subtypes have been proposed:: 552–553 Type 1 MPGN is caused by immune complex deposition in the mesangium and subendothelial space, typically secondary to systemic lupus erythematosus, hepatitis B and C, or other chronic or recurring infections. Circulating immune complexes may activate the complement system, leading to inflammation and an influx of inflammatory cells.: 552–553 Type 2 MPGN, also known as Dense Deposit Disease, is characterised by an excessive activation of the complement system. The C3 Nephritic Factor autoantibody stabilizes C3-convertase, which may lead to an excessive activation of complement.: 553 Type 2 MPGN is a subgroup of C3 glomerulopathy, a newly proposed diagnosis which also encompasses C3 Glomerulonephritis (C3GN). Type 3 MPGN, which is caused by immune complex deposition in the subepithelial space. Rapidly progressive glomerulonephritis Rapidly progressive glomerulonephritis, also known as crescentic GN, is characterised by a rapid, progressive deterioration in kidney function. People with rapidly progressive glomerulonephritis may present with a nephritic syndrome. In management, steroid therapy is sometimes used, although the prognosis remains poor. Three main subtypes are recognised:: 557–558 Type 1 is Goodpasture syndrome, an autoimmune disease also affecting the lung. In Goodpasture syndrome, IgG antibodies directed against the glomerular basement membrane trigger an inflammatory reaction, causing a nephritic syndrome and the coughing up of blood.: 557 High dose immunosuppression is required (intravenous methylprednisolone) and cyclophosphamide, plus plasmapheresis. Immunohistochemistry staining of tissue specimens shows linear IgG deposits. Type 2 is characterised by immune-complex-mediated damage, and may be associated with systemic lupus erythematosus, post-infective glomerulonephritis, IgA nephropathy, and IgA vasculitis.: 558 Type 3 rapidly progressive glomerulonephritis, also called pauciimmune type, is associated with causes of vascular inflammation including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis. No immune deposits can be seen on staining, however blood tests may be positive for the ANCA antibody.: 558–559 Histopathologically, the majority of glomeruli present "crescents". Formation of crescents is initiated by passage of fibrin into the Bowman space as a result of increased permeability of glomerular basement membrane. Fibrin stimulates the proliferation of endothelial cells of Bowman capsule, and an influx of monocytes. Rapid growing and fibrosis of crescents compresses the capillary loops and decreases the Bowman space, which leads to kidney failure within weeks or months. Diagnosis Some forms of glomerulonephritis are diagnosed clinically, based on findings on history and examination. Other tests may include: Urine examination Blood tests investigating the cause, including FBC, inflammatory markers, and special tests (including ASLO, ANCA, Anti-GBM, Complement levels, Anti-nuclear antibodies) Biopsy of the kidney Renal ultrasonography is useful for prognostic purposes in finding signs of chronic kidney disease, which however may be caused by many other diseases than glomerulonephritis. Treatment Antibiotic therapy to prevent streptococcal infection (prophylaxis). Steroids to suppress inflammation. Provide high calories & low protein, sodium & potassium diet. Monitor for sign of kidney failure, heart failure, and hypertensive encephalopathy. See also Nephritic syndrome Nephritis Lupus nephritis Rapidly progressive glomerulonephritis References == External links ==
Thrombophlebitis	Thrombophlebitis is a phlebitis (inflammation of a vein) related to a thrombus (blood clot). When it occurs repeatedly in different locations, it is known as thrombophlebitis migrans (migratory thrombophlebitis). Signs and symptoms The following symptoms or signs are often associated with thrombophlebitis, although thrombophlebitis is not restricted to the veins of the legs. Pain (area affected) Skin redness/inflammation Edema Veins hard and cord-like Tenderness Complications In terms of complications, one of the most serious occurs when the superficial blood clot is associated with a deep vein thrombosis; this can then dislodge, traveling through the heart and occluding the dense capillary network of the lungs This is a pulmonary embolism which can be life-threatening. Causes Thrombophlebitis causes include disorders related to increased tendency for blood clotting and reduced speed of blood in the veins such as prolonged immobility; prolonged traveling (sitting) may promote a blood clot leading to thrombophlebitis but this occurs relatively less. High estrogen states such as pregnancy, estrogen replacement therapy, or oral contraceptives are associated with an increased risk of thrombophlebitis.Specific disorders associated with thrombophlebitis include superficial thrombophlebitis which affects veins near the skin surface, deep vein thrombosis which affects deeper veins, and pulmonary embolism.Those with familial clotting disorders such as protein S deficiency, protein C deficiency, or factor V Leiden are also at increased risk of thrombophlebitis. Thrombophlebitis can be found in people with vasculitis including Behçets disease. Thrombophlebitis migrans can be a sign of malignancy – Trousseau sign of malignancy. Diagnosis The diagnosis for thrombophlebitis is primarily based on the appearance of the affected area. Frequent checks of the pulse, blood pressure, and temperature may be required. If the cause is not readily identifiable, tests may be performed to determine the cause, including the following: Doppler ultrasound Extremity arteriography Blood coagulation studies (Blood clotting tests) Prevention Prevention consists of walking, drinking fluids and if currently hospitalized, changing of IV lines. Walking is especially suggested after a long period seated, particularly when one travels. Treatment In terms of treatment for this condition the individual may be advised to do the following: raise the affected area to decrease swelling, and relieve pressure off of the affected area so it will encounter less pain. In certain circumstances drainage of the clot might be an option. In general, treatment may include the following: Epidemiology Thrombophlebitis occurs almost equally between women and men, though males do have a slightly higher possibility. The average age of developing thrombophlebitis, based on analyzed incidents, is 54 for men and 58 for women. See also Mondors disease Phlebothrombosis References Further reading Sadick, Neil S.; Khilnani, Neil; Morrison, Nick (2012). Practical Approach to the Management and Treatment of Venous Disorders. Springer Science & Business Media. ISBN 9781447128915. Retrieved 23 October 2016. Mulholland, Michael W.; Lillemoe, Keith D.; Doherty, Gerard M.; Maier, Ronald V.; Simeone, Diane M.; Upchurch, Gilbert R. (2012). Greenfields Surgery: Scientific Principles & Practice. Lippincott Williams & Wilkins. ISBN 9781451152920. Retrieved 23 October 2016. == External links ==
Dysmenorrhea	Dysmenorrhea, also known as painful periods or menstrual cramps, is pain during menstruation. Its usual onset occurs around the time that menstruation begins. Symptoms typically last less than three days. The pain is usually in the pelvis or lower abdomen. Other symptoms may include back pain, diarrhea or nausea.Dysmenorrhea can occur without an underlying problem. Underlying issues that can cause dysmenorrhea include uterine fibroids, adenomyosis, and most commonly, endometriosis. It is more common among those with heavy periods, irregular periods, those whose periods started before twelve years of age and those who have a low body weight. A pelvic exam and ultrasound in individuals who are sexually active may be useful for diagnosis. Conditions that should be ruled out include ectopic pregnancy, pelvic inflammatory disease, interstitial cystitis and chronic pelvic pain.Dysmenorrhea occurs less often in those who exercise regularly and those who have children early in life. Treatment may include the use of a heating pad. Medications that may help include NSAIDs such as ibuprofen, hormonal birth control and the IUD with progestogen. Taking vitamin B1 or magnesium may help. Evidence for yoga, acupuncture and massage is insufficient. Surgery may be useful if certain underlying problems are present.Estimates of the percentage of women of reproductive age affected vary from 20% to 90%. It is the most common menstrual disorder. Typically, it starts within a year of the first menstrual period. When there is no underlying cause, often the pain improves with age or following having a child. Signs and symptoms The main symptom of dysmenorrhea is pain concentrated in the lower abdomen or pelvis. It is also commonly felt in the right or left side of the abdomen. It may radiate to the thighs and lower back.Symptoms often co-occurring with menstrual pain include nausea and vomiting, diarrhea, headache, dizziness, disorientation, fainting and fatigue. Symptoms of dysmenorrhea often begin immediately after ovulation and can last until the end of menstruation. This is because dysmenorrhea is often associated with changes in hormonal levels in the body that occur with ovulation. In particular, prostaglandins induce abdominal contractions that can cause pain and gastrointestinal symptoms. The use of certain types of birth control pills can prevent the symptoms of dysmenorrhea because they stop ovulation from occurring. Dysmenorrhea is associated with increased pain sensitivity and heavy menstrual bleeding.For many women, primary dysmenorrhea gradually subsides in late second generation. Pregnancy has also been demonstrated to lessen the severity of dysmenorrhea, when menstruation resumes. However, dysmenorrhea can continue until menopause. 5–15% of women with dysmenorrhea experience symptoms severe enough to interfere with daily activities. Causes Dysmenorrhea can be classified as either primary or secondary based on the absence or presence of an underlying cause. Primary dysmenorrhea occurs without an associated underlying condition, while secondary dysmenorrhea has a specific underlying cause, typically a condition that affects the uterus or other reproductive organs.Painful menstrual cramps that result from an excess of prostaglandin release are referred to as primary dysmenorrhea. Primary dysmenorrhea usually begins within a year or two of menarche, typically with the onset of ovulatory cycles. Perimenstrual pain is often included as a component of premenstrual syndrome (PMS). Secondary dysmenorrhea is the diagnosis given when menstruation pain is a secondary cause to another disorder. Conditions causing secondary dysmenorrhea include endometriosis, uterine fibroids, uterine adenomyosis, and polycystic ovary syndrome. Rarely, congenital malformations, intrauterine devices, certain cancers, and pelvic infections cause secondary dysmenorrhea. If the pain occurs between menstrual periods, lasts longer than the first few days of the period, or is not adequately relieved by the use of non-steroidal anti-inflammatory drugs (NSAIDs) or hormonal contraceptives, this could be a sign for secondary causes of dysmenorrhea.When laparoscopy is used for diagnosis, the most common cause of dysmenorrhea is endometriosis, in approximately 70% of adolescents.Other causes of secondary dysmenorrhea include leiomyoma, adenomyosis, ovarian cysts, pelvic congestion, and cavitated and accessory uterine mass. Risk factors Genetic factors, stress and depression are risk factors for dysmenorrhea. Risk factors for primary dysmenorrhea include: early age at menarche, long or heavy menstrual periods, smoking, and a family history of dysmenorrhea.Dysmenorrhea is a highly polygenic and heritable condition. There is strong evidence of familial predisposition and genetic factors increasing susceptibility to dysmenorrhea. There have been multiple polymorphisms and genetic variants in both metabolic genes and genes responsible for immunity which have been associated with the disorder.Three distinct possible phenotypes have been identified for dysmenorrhea which include "multiple severe symptoms", "mild localized pain", and "severe localized pain". While there are likely differences in genotypes underlying each phenotype, the specific correlating genotypes have not yet been identified. These phenotypes are prevalent at different levels in different population demographics, suggesting different allelic frequencies across populations (in terms of race, ethnicity, and nationality).Polymorphisms in the ESR1 gene have been commonly associated with severe dysmenorrhea. Variant genotypes in the metabolic genes such as CYP2D6 and GSTM1 have been similarly been correlated with an increased risk of severe menstrual pain, but not with moderate or occasional phentoypes.The occurrence and frequency of secondary dysmenorrhea (SD) has been associated with different alleles and genotypes of those with underlying pathologies, which can affect the pelvic region or other areas of the body. Individuals with disorders may have genetic mutations related to their diagnoses which produce dysmenorrhea as a symptom of their primary diagnosis. It has been found that those with fibromyalgia who have the ESR1 gene variation Xbal and possess the Xbal AA genotype are more susceptible to experiencing mild to severe menstrual pain resulting from their primary pathology. Commonly, genetic mutations which are a hallmark of or associated with specific disorders can produce dysmenorrhea as a symptom which accompanies the primary disorder. In contrast with secondary dysmenorrhea, primary dysmenorrhea (PD) has no underlying pathology. Genetic mutation and variations have therefore been thought to underlie this disorder and contribute to the pathogenesis of PD. There are multiple single-nucleotide polymorphisms (SNP) associated with PD. Two of the most well studied include an SNP in the promoter of MIF and an SNP in the tumor necrosis factor (TNF-α) gene. When a cytosine 173 base pairs upstream of macrophage migration inhibitory factor (MIF) promoter was replaced by a guanine there was an associated increase in the likelihood of the individual experiencing PD. While a CC/GG genotype led to an increase in likelihood of the individual experiencing severe menstrual pain, a CC/GC genotype led to a more significant likelihood of the disorder impacting the individual overall and increasing the likelihood of any of the three phenotypes. A second associated SNP was located 308 base pairs upstream from the start codon of the TNF-α gene, in which guanine was substituted for adenine. A GG genotype at the loci is associated with the disorder and has been proposed as a possible genetic marker to predict PD.There has also been an association with mutations in the MEFV gene and dysmenorrhea, which are considered to be causative. The phenotypes associated with these mutations in the MEFV genes have been better studied; individuals who are heterozygous for these mutations are more likely to be affected by PD which presents as a severe pain phenotype.Genes related to immunity have been identified as playing a significant role in PD as well. IL1A was found to be the gene most associated with primary dysmenorrhea in terms of its phenotypic impact. This gene encodes a protein essential for the regulation of immunity and inflammation.15 While the mechanism of how it influences PD has yet to be discovered, it is assumed that possible mutations in IL1A or genes which interact with it impact the regulation of inflammation during menstruation. These mutations may therefore affect pain responses during menstruation which lead to the differing phenotypes associated with dysmenorrhea. Two additionally well studied SNPs which are suspected to contribute to PD were found in ZM1Z1 (the mutant allele called rs76518691) and NGF (the mutant allele called rs7523831). Both ZMIZ1 and NGF are associated with autoimmune responses and diseases, as well as pain response. The implication of these genes impacting Dysmenorrhea is significant as it suggests mutations which affect the immune system (specifically the inflammatory response) and pain response may also be a cause of primary dysmenorrhea. Mechanism The underlying mechanism of primary dysmenorrhea is the contractions of the muscles of the uterus which induce a local ischemia.During an individuals menstrual cycle, the endometrium thickens in preparation for potential pregnancy. After ovulation, if the ovum is not fertilized and there is no pregnancy, the built-up uterine tissue is not needed and thus shed. Prostaglandins and leukotrienes are released during menstruation, due to the build up of omega-6 fatty acids. Release of prostaglandins and other inflammatory mediators in the uterus cause the uterus to contract and can result in systemic symptoms such as nausea, vomiting, bloating and headaches or migraines. Prostaglandins are thought to be a major factor in primary dysmenorrhea. When the uterine muscles contract, they constrict the blood supply to the tissue of the endometrium, which, in turn, breaks down and dies. These uterine contractions continue as they squeeze the old, dead endometrial tissue through the cervix and out of the body through the vagina. These contractions, and the resulting temporary oxygen deprivation to nearby tissues, are thought to be responsible for the pain or cramps experienced during menstruation. Compared with non-dysmnenorrhic individuals, those with primary dysmenorrhea have increased activity of the uterine muscle with increased contractility and increased frequency of contractions. Diagnosis The diagnosis of dysmenorrhea is usually made simply on a medical history of menstrual pain that interferes with daily activities. However, there is no universally accepted standard technique for quantifying the severity of menstrual pains. There are various quantification models, called menstrual symptometrics, that can be used to estimate the severity of menstrual pains as well as correlate them with pain in other parts of the body, menstrual bleeding and degree of interference with daily activities. Further work-up Once a diagnosis of dysmenorrhea is made, further workup is required to search for any secondary underlying cause of it, in order to be able to treat it specifically and to avoid the aggravation of a perhaps serious underlying cause. Further work-up includes a specific medical history of symptoms and menstrual cycles and a pelvic examination. Based on results from these, additional exams and tests may be motivated, such as: Gynecologic ultrasonography Laparoscopy Management Treatments that target the mechanism of pain include non-steroidal anti-inflammatory drugs (NSAIDs) and hormonal contraceptives. NSAIDs inhibit prostaglandin production. With long-term treatment, hormonal birth control reduces the amount of uterine fluid/tissue expelled from the uterus. Thus resulting in shorter, less painful menstruation. These drugs are typically more effective than treatments that do not target the source of the pain (e.g. acetaminophen). Regular physical activity may limit the severity of uterine cramps. NSAIDs Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen are effective in relieving the pain of primary dysmenorrhea. They can have side effects of nausea, dyspepsia, peptic ulcer, and diarrhea. Hormonal birth control Use of hormonal birth control may improve symptoms of primary dysmenorrhea. A 2009 systematic review found limited evidence that the low or medium doses of estrogen contained in the birth control pill reduces pain associated with dysmenorrhea. In addition, no differences between different birth control pill preparations were found.Norplant and Depo-provera are also effective, since these methods often induce amenorrhea. The intrauterine system (Mirena IUD) may be useful in reducing symptoms. Other A review indicated the effectiveness of transdermal nitroglycerin. Reviews indicated magnesium supplementation seemed to be effective. A review indicated the usefulness of using calcium channel blockers. Heat is effective compared to NSAIDs and is a preferred option by many patients, as it is easy to access and has no known side effects.Tamoxifen has been used effectively to reduce uterine contractility and pain in dysmenorrhea patients.There is some evidence that exercises performed 3 times a week for about 45 to 60 minutes, without particular intensity, reduces menstrual pain. Alternative medicine There is insufficient evidence to recommend the use of many herbal or dietary supplements for treating dysmenorrhea, including melatonin, vitamin E, fennel, dill, chamomile, cinnamon, damask rose, rhubarb, guava, and uzara. Further research is recommended to follow up on weak evidence of benefit for: fenugreek, ginger, valerian, zataria, zinc sulphate, fish oil, and vitamin B1. A 2016 review found that evidence of safety is insufficient for most dietary supplements. There is some evidence for the use of fenugreek.One review found thiamine and vitamin E to be likely effective. It found the effects of fish oil and vitamin B12 to be unknown. Reviews found tentative evidence that ginger powder may be effective for primary dysmenorrhea. Reviews have found promising evidence for Chinese herbal medicine for primary dysmenorrhea, but that the evidence was limited by its poor methodological quality.A 2016 Cochrane review of acupuncture for dysmenorrhea concluded that it is unknown if acupuncture or acupressure is effective. There were also concerns of bias in study design and in publication, insufficient reporting (few looked at adverse effects), and that they were inconsistent. There are conflicting reports in the literature, including one review which found that acupressure, topical heat, and behavioral interventions are likely effective. It found the effect of acupuncture and magnets to be unknown.A 2007 systematic review found some scientific evidence that behavioral interventions may be effective, but that the results should be viewed with caution due to poor quality of the data.Spinal manipulation does not appear to be helpful. Although claims have been made for chiropractic care, under the theory that treating subluxations in the spine may decrease symptoms, a 2006 systematic review found that overall no evidence suggests that spinal manipulation is effective for treatment of primary and secondary dysmenorrhea.Valerian, Humulus lupulus and Passiflora incarnata may be safe and effective in the treatment of dysmenorrhea. TENS A 2011 review stated that high-frequency transcutaneous electrical nerve stimulation may reduce pain compared with sham TENS, but seems to be less effective than ibuprofen. Surgery One treatment of last resort is presacral neurectomy. Epidemiology Dysmenorrhea is one of the most common gynecological conditions, regardless of age or race. It is one of the most frequently identified etiology of pelvic pain in menstruating adults. The prevalence of dysmenorrhea can vary between 16% and 91% of surveyed individuals, with severe pain observed in 2% to 29% of menstruating individuals. Reports of dysmenorrhea are greatest among individuals in their late teens and 20s, with reports usually declining with age. The prevalence in adolescent females has been reported to be 67.2% by one study and 90% by another. It has been stated that there is no significant difference in prevalence or incidence between races, although one study of Hispanic adolescent females indicated an elevated prevalence and impact in this group. Another study indicated that dysmenorrhea was present in 36.4% of participants, and was significantly associated with lower age and lower parity. Childbearing is said to relieve dysmenorrhea, but this does not always occur. One study indicated that in nulliparous individuals with primary dysmenorrhea, the severity of menstrual pain decreased significantly after age 40.A survey in Norway showed that 14 percent of females between the ages of 20 to 35 experience symptoms so severe that they stay home from school or work. Among adolescent girls, dysmenorrhea is the leading cause of recurrent short-term school absence. References External links Dysmenorrhea at Curlie
Miliary tuberculosis	Miliary tuberculosis is a form of tuberculosis that is characterized by a wide dissemination into the human body and by the tiny size of the lesions (1–5 mm). Its name comes from a distinctive pattern seen on a chest radiograph of many tiny spots distributed throughout the lung fields with the appearance similar to millet seeds—thus the term "miliary" tuberculosis. Miliary TB may infect any number of organs, including the lungs, liver, and spleen. Miliary tuberculosis is present in about 2% of all reported cases of tuberculosis and accounts for up to 20% of all extra-pulmonary tuberculosis cases. Signs and symptoms Patients with miliary tuberculosis often experience non-specific signs, such as coughing and enlarged lymph nodes. Miliary tuberculosis can also present with enlarged liver (40% of cases), enlarged spleen (15%), inflammation of the pancreas (<5%), and multiple organ dysfunction with adrenal insufficiency (adrenal glands do not produce enough steroid hormones to regulate organ function). Stool may also be diarrheal in nature and appearance.Other symptoms include fever, hypercalcemia, choroidal tubercles, and cutaneous lesions. Firstly, many patients can experience a fever lasting several weeks with daily spikes in morning temperatures.Secondly, hypercalcemia prevails in 16 to 51% of tuberculosis cases. It is thought that hypercalcemia occurs as a response to increased macrophage activity in the body. Such that, 1,25 dihydroxycholecalciferol (also referred to as calcitriol) improves the ability of macrophages to kill bacteria; however, higher levels of calcitriol lead to higher calcium levels, and thus hypercalcemia in some cases. Thus, hypercalcemia proves to be an important symptom of miliary tuberculosis.Thirdly, chorodial tubercules, pale lesions on the optic nerve, typically indicate miliary tuberculosis in children. These lesions may occur in one eye or both; the number of lesions varies between patients. Chorodial tubercules may serve as important symptoms of miliary tuberculosis, since their presence can often confirm suspected diagnosis.Lastly, between 10 and 30% of adults, and 20–40% of children with miliary tuberculosis have tuberculosis meningitis. This relationship results from mycobacteria from miliary tuberculosis spreading to the brain and the subarachnoid space; as a result, leading to tuberculosis meningitis.The risk factors for contracting miliary tuberculosis are being in direct contact with a person who has it, living in unsanitary conditions, and poor nutrition. In the U.S., risk factors for contracting the disease include homelessness and HIV/AIDS. Cause Miliary tuberculosis is a form of tuberculosis that is the result of Mycobacterium tuberculosis travelling to extrapulmonary organs, such as the liver, spleen and kidneys. Although it is well understood that the bacteria spread from the pulmonary system to the lymphatic system and eventually the blood stream, the mechanism by which this occurs is not well understood.One proposed mechanism is that tuberculous infection in the lungs results in erosion of the epithelial layer of alveolar cells and the spread of infection into a pulmonary vein. Once the bacteria reach the left side of the heart and enter the systemic circulation, they may multiply and infect extrapulmonary organs. Once infected, the cell-mediated immune response is activated. The infected sites become surrounded by macrophages, which form granuloma, giving the typical appearance of miliary tuberculosis.Alternatively, the bacteria may attack the cells lining the alveoli and enter the lymph node(s). The bacteria then drain into a systemic vein and eventually reach the right side of the heart. From the right side of the heart, the bacteria may seed—or re-seed as the case may be—the lungs, causing the eponymous "miliary" appearance. Diagnosis Testing for miliary tuberculosis is conducted in a similar manner as for other forms of tuberculosis, although a number of tests must be conducted on a patient to confirm diagnosis. Tests include chest x-ray, sputum culture, bronchoscopy, open lung biopsy, head CT/MRI, blood cultures, fundoscopy, and electrocardiography. The tuberculosis (TB) blood test, also called an Interferon Gamma Release Assay or IGRA, is a way to diagnose latent TB. A variety of neurological complications have been noted in miliary tuberculosis patients—tuberculous meningitis and cerebral tuberculomas being the most frequent. However, a majority of patients improve following antituberculous treatment. Rarely lymphangitic spread of lung cancer could mimic miliary pattern of tuberculosis on regular chest X-ray. The tuberculin skin test, commonly used for detection of other forms of tuberculosis, is not useful in the detection of miliary tuberculosis. The tuberculin skin test fails due to the high numbers of false negatives. These false negatives may occur because of higher rates of tuberculin anergy compared to other forms of tuberculosis.A case of miliary tuberculosis in an 82-year-old woman: Treatment The standard treatment recommended by the WHO is with isoniazid and rifampicin for six months, as well as ethambutol and pyrazinamide for the first two months. If there is evidence of meningitis, then treatment is extended to twelve months. The U.S. guidelines recommend nine months treatment. "Common medication side effects a patient may have such as inflammation of the liver if a patient is taking pyrazinamide, rifampin, and isoniazid. A patient may also have drug resistance to medication, relapse, respiratory failure, and acute respiratory distress syndrome." Prognosis If left untreated, miliary tuberculosis is almost always fatal. Although most cases of miliary tuberculosis are treatable, the mortality rate among children with miliary tuberculosis remains 15 to 20% and for adults 25 to 30%. One of the main causes for these high mortality rates includes late detection of disease caused by non-specific symptoms. Non-specific symptoms include: coughing, weight loss, or organ dysfunction. These symptoms may be implicated in numerous disorders, thus delaying diagnosis. Misdiagnosis with tuberculosis meningitis is also a common occurrence when patients are tested for tuberculosis, since the two forms of tuberculosis have high rates of co-occurrence. History John Jacob Manget described a form of disseminated tuberculosis in 1700 and expressed its resemblance to numerous millet seeds in size and appearance and coined the term from Latin word miliarius, meaning related to millet seed. See also Lupus vulgaris Metastatic tuberculous abscess or ulceration Thomas Wolfe List of cutaneous conditions References Further reading Sharma, SK; Mohan, A; Sharma, A (2012). "Challenges in the diagnosis & treatment of miliary tuberculosis" (PDF). The Indian Journal of Medical Research. 135 (5): 703–30. PMC 3401706. PMID 22771605. Reichman, Lee B., M.D., M.P.H. & Tanne, Janice H. (2002). "Timebomb: The Global Epidemic of Multi-Drug-Resistant Tuberculosis. Mcgraw-Hill. ISBN 0-07-135924-9 Albino, Juan A.; Reichman, Lee B. (1 January 1998). "The Treatment of Tuberculosis". Respiration. 65 (4): 237–255. doi:10.1159/000029271. PMID 9730789. S2CID 7216163. Rieder, Hans L (November–December 1998). "How to Combat Tuberculosis in the Year 2000?". Respiration. 65 (6): 423–431. doi:10.1159/000029309. PMID 9817956. S2CID 46865618. External links Media related to Miliary tuberculosis at Wikimedia Commons
Gray matter heterotopia	Gray matter heterotopias are neurological disorders caused by clumps of gray matter (nodules of neurons) located in the wrong part of the brain. A grey matter heterotopia is characterized as a type of focal cortical dysplasia. The neurons in heterotopia appear to be normal, except for their mislocation; nuclear studies have shown glucose metabolism equal to that of normally positioned gray matter. The condition causes a variety of symptoms, but usually includes some degree of epilepsy or recurring seizures, and often affects the brains ability to function on higher levels. Symptoms range from nonexistent to profound; the condition is occasionally discovered as an incidentaloma when brain imaging performed for an unrelated problem and has no apparent ill effect on the patient. At the other extreme, heterotopia can result in severe seizure disorder, loss of motor skills, and mental retardation. Fatalities are practically unknown, other than the death of unborn male fetuses with a specific genetic defect. Preliminary Material: Neurological Development of the Human Fetus The development of the brain in the human fetus is extraordinarily complex and is still not fully understood. Neural matter originates in the outer, ectodermic layer of the gastrula; thus, it originates from the cell layer primarily responsible for skin, hair, nails, etc., rather than from the layers that develop into other internal organs. The nervous system originates as a tiny, simple open tube called the neural tube; the front of this tube develops into the brain (and retinas of the eye), while the spinal cord develops from the very back end. Neurons begin to form early, but most of them become structural rather than active nerve cells. The brain generally forms from the inside-out, especially in the case of the neocortex. The difficulties arising from this are readily apparent, as each successive layer of cells must travel through the previous layer to reach its destination. Therefore, nervous tissue develops ladders made of radial glial cells that neurons climb, through the previous layers, to reach their proper destination. Some destinations, such as the cerebral cortex, even have "placeholder" neurons that travel up the ladder to form a structure; when the final neurons germinate, they find a correct placeholder and then the placeholder cell dies. Heterotopia The complexity of neural development makes it fraught with opportunities for error. Grey matter heterotopia is such an example. It is believed that gray matter heterotopia are caused by arrested migration of neurons to the cerebral cortex; that is, when neurons that are supposed to form part of the cerebral cortex. fail to climb to the end of their ladder correctly and are permanently situated in the wrong location. Gray matter heterotopia are common malformations of cortical development classed as neuronal migration disorders. Heterotopias are classed in two groups: nodular and diffuse. Nodular types are subependymal and subcortical; diffuse types are termed band heterotopias. Affected patients are generally divided into three groups, depending on the location of the formation: subependymal, subcortical, and band heterotopia. In addition, especially with heterotopia that are genetically linked, there are gender differences. Men seem to develop more severe symptoms than women with similar formations. In general, band heterotopia, also known as double cortex syndrome, are seen exclusively in women; men with a mutation of the related gene (called XLIS or DCX) usually die in utero or have a much more severe brain anomaly. Symptoms in affected women vary from normal to severe developmental delay or intellectual disability; the severity of the syndrome is related to the thickness of the band of arrested neurons. Nearly all affected patients that come to medical attention have epilepsy, with partial complex and atypical absence epilepsy being the most common syndromes. Some of the more severely affected patients develop drop attacks. Periventricular or subependymal Periventricular means beside the ventricle, while subependymal (also spelled subepydymal) means beneath the ependyma; because the ependyma is the thin epithelial sheet lining the ventricles of the brain, these two terms are used to define heterotopia occurring directly next to a ventricle. This is by far the most common location for heterotopia. Patients with isolated subependymal heterotopia usually present with a seizure disorder in the second decade of life. Subependymal heterotopia present in a wide array of variations. They can be a small single node or a large number of nodes, can exist on either or both sides of the brain at any point along the higher ventricle margins, can be small or large, single or multiple, and can form a small node or a large wavy or curved mass. Symptomatic women with subependymal heterotopia typically present with partial epilepsy during the second decade of life; development and neurologic examinations up to that point are typically normal. Symptoms in men with subependymal heterotopia vary, depending on whether their disease is linked to their X-chromosome. Men with the X-linked form more commonly have associated anomalies, which can be neurological or more widespread, and they usually suffer from developmental problems. Otherwise (i.e., in non-X-linked cases) the symptomology is similar in both sexes. Focal subcortical Subcortical heterotopia form as distinct nodes in the white matter, "focal" indicating specific area. In general, patients present fixed neurologic deficits and develop partial epilepsy between the ages of 6 and 10. The more extensive the subcortical heterotopia, the greater the deficit; bilateral heterotopia are almost invariably associated with severe developmental delay or intellectual disability. The cortex itself often has an absence of gray matter and may be unusually thin or lack deep sulci. Subependymal heterotopia are frequently accompanied by other structural abnormalities, including an overall decrease in cortical mass. Patients with focal subcortical heterotopia have a variable motor and intellectual disturbance depending on the size and site of the heterotopion. Band form Like focal subcortical heterotopia, "band" heterotopia form in the white matter beneath the cortex, but the gray matter is more diffuse and is symmetric between the hemispheres. On imaging, band heterotopia appears as bands of gray matter situated between the lateral ventricle and cerebral cortex and separated from both by a layer of normal appearing white matter. Band heterotopia may be complete, surrounded by simple white matter, or partial. The frontal lobes seem to be more frequently involved when it is partial. Patients with band heterotopia may present at any age with variable developmental delay and seizure disorder, which vary widely in severity. Subcortical band heterotopia, also known as "double cortex" syndrome, refers to a band of subcortical heterotopia neurons, located midway between the ventricles and the cerebral cortex. The disorder is seen primarily in females and typically causes varying degrees of intellectual disability and almost all of them have epilepsy. Approximately two thirds of patients with epilepsy ultimately develop intractable seizures. MRI of the brain in subcortical band heterotopia demonstrates two parallel layers of gray matter: a thin outer ribbon and a thick inner band, separated by a very thin layer of white matter between them. The severity of epilepsy and developmental delay is directly correlated with the degree of migration arrest, as indicated by the thickness of the subcortical band heterotopia. Subcortical band heterotopia is caused by mutations in the microtubule-associated DCX gene. The DCX protein is thought to direct neuronal migration by regulating the organization and stability of microtubules, necessary for neuronal motility. The malformation is seen only in females, as the gene is found on the X-chromosome. Since there are two X chromosomes in females, after X-inactivation, only some neurons lose doublecortin function. These neurons with the mutant DCX gene fail to migrate into the cortex and thus form the underlying heterotopic band, while neurons which express the normal gene successfully migrate out to the cortical plate. Males with DCX mutations develop classical lissencephaly. Diagnosis Detection of heterotopia generally occurs when a patient receives brain imaging—usually an MRI or CT scan—to diagnose seizures that are resistant to medication. Correct diagnosis requires a high degree of radiological skill, due to the heterotopias resemblance to other masses in the brain. Treatment When seizures are present in any forms of cortical dysplasia, they are resistant to medication. Frontal lobe resection provides significant relief from seizures to a minority of patients with periventricular lesions. Prognosis In general, gray matter heterotopia is fixed in both its occurrence and symptoms; that is, once symptoms occur, it does not tend to progress. Varying results from surgical resection of the affected area have been reported. Although such surgery cannot reverse developmental disabilities, it may provide full or partial relief from seizures. Heterotopia are most commonly isolated anomalies, but may be part of a number of syndromes, including chromosomal abnormalities and fetal exposure to toxins (including alcohol). Footnotes Further reading GeneReviews/NCBI/NIH/UW entry on X-Linked Periventricular Heterotopia Ferland, Russell J.; Batiz, Luis Federico; Neal, Jason; Lian, Gewei; Bundock, Elizabeth; Lu, Jie; Hsiao, Yi-Chun; Diamond, Rachel; Mei, Davide; Banham, Alison H.; Brown, Philip J.; Vanderburg, Charles R.; Joseph, Jeffrey; Hecht, Jonathan L.; Folkerth, Rebecca; Guerrini, Renzo; Walsh, Christopher A.; Rodriguez, Esteban M.; Sheen, Volney L. (2009). "Disruption of neural progenitors along the ventricular and subventricular zones in periventricular heterotopia". Human Molecular Genetics. 18 (3): 497–516. doi:10.1093/hmg/ddn377. PMC 2722192. PMID 18996916.
Susacs syndrome	Susacs syndrome (retinocochleocerebral vasculopathy) is a very rare form of microangiopathy characterized by encephalopathy, branch retinal artery occlusions and hearing loss. The cause is unknown but it is theorized that antibodies are produced against endothelial cells in tiny arteries which leads to damage and the symptoms related to the illness. Despite this being an extremely rare disease, there are 4 registries collecting data on the illness; two are the United States, one in Germany, and one in Portugal. Presentation Susacs syndrome is named for Dr. John Susac (1940–2012), of Winter Haven, Florida, who first described it in 1979. Susacs syndrome is a very rare disease, of unknown cause, and many persons who experience it do not display the bizarre symptoms named here. Their speech can be affected, such as the case of a female of late teens who suffered speech issues and hearing problems, and many experience unrelenting and intense headaches and migraines, some form of hearing loss, and impaired vision. The problem usually corrects itself, but this can take up to five years. In some cases, subjects can become confused. The syndrome usually affects women around the age of 18 years, with female to male ratio of cases of 2:1. William F. Hoyt was the first to call the syndrome "Susac syndrome" and later Robert Daroff asked Dr. Susac to write an editorial in Neurology about the disorder and to use the eponym of Susac syndrome in the title, forever linking this disease with him. Pathogenesis In the March 1979 report in Neurology, Drs. Susac, Hardman and Selhorst reported two patients with the triad of encephalopathy, hearing loss and microangiopathy of the retina. The first patient underwent brain biopsy, which revealed sclerosis of the media and adventitia of small pial and cortical vessels, suggestive of a healed angiitis. Both patients underwent fluorescein retinal angiography that demonstrated multifocal retinal artery occlusions without evidence of embolic disease. Though the exact pathogenesis of this disorder is unknown, the retinal and brain biopsy findings suggest a small vessel vasculopathy leading to arteriolar occlusion and microinfarction of cerebral, retinal and cochlear tissue. Demyelination is not a typical feature of Susacs syndrome. Muscle biopsies from such patients are usually normal, but some have also shown nonspecific signs of inflammation such as dense hyaline material surrounding endomysial capillaries. This suggests a possible systemic component of this disease, despite the predominance of central nervous system features. The latest thinking is that an antibody directed against endothelial cells is the pathogenic mechanism in this disease which causes the microscopic strokes in the brain, retina, and inner ear. Diagnosis Patients typically present with low frequency hearing loss detectable via an audiogram. Headaches are frequently present in addition to roaring tinnitus and often some degree of paranoia. Partial vision loss is often present and caused by branch retinal artery occlusions. The presence of refractile or non-refractile yellow Gass plaques in the retinal arterioles is near pathognomonic for the disease. Fluorescein angiography may demonstrate leakage in areas remote from the retinal infarctions. Radiographic appearance In a recent analysis (Susac et al., 2003), MRI images from 27 patients fulfilling the diagnostic criteria of Susacs syndrome were reviewed. Multifocal supratentorial lesions were present in all patients. Most lesions were small (3 to 7 mm), though some were larger than 7 mm. All 27 patients had corpus callosum lesions. These all had a punched-out appearance on follow up MRI. Though most commonly involving white matter, many patients also had lesions in deep grey matter structures, as well as leptomeningeal enhancement. Multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM) can mimic the MRI changes seen in patients with Susacs syndrome. However, the callosal lesions in Susacs syndrome are centrally located. In comparison, patients with MS and ADEM typically have lesions involving the undersurface of the corpus callosum. Deep gray matter involvement commonly occurs in ADEM but is very rare in MS. Leptomeningeal involvement is not typical of either MS or ADEM. What this means is that if 10 lesions are found in the brain of an MS patient, a lesion may be found in the corpus callosum. If you have 10 lesions in a Susac patient, more than half will be in the corpus callosum. A concern about this illness is that it mimics multiple sclerosis when looking at the vision loss and brain lesions. If close attention is not paid to the retina of a patient with vision loss and brain lesions, their symptoms may be mistaken for MS instead of Susacs syndrome. This may account for the low prevalence of the illness. There is also a pathological similarity between the endotheliopathy in Susacs syndrome with that seen in juvenile dermatomyositis. Treatment Early and aggressive treatment is important to prevent irreversible neurological damage, hearing loss, or vision loss. Medications used include immunosuppressive agents and corticosteroids such a prednisone, or intravenous immunoglobulins (IVIG). Other drugs that have been used are mycophenolate mofetil (Cellcept), azathioprine (Imuran), cyclophosphamide, rituximab, and anti-TNF therapies.Hearing aids or cochlear implants may be necessary in the event of hearing loss. References Egan RA, Nguyen TH, Gass JDM, Rizzo JF, Tivnan J, Susac JO. Retinal Artery Wall Plaques in Susac Syndrome. American Journal of Ophthalmology 135: 483-6; 2003 Susac JO, Murtagh FR, Egan RA, Berger JR, Fox RJ, Galetta S, Costello F, Lee AG, Bakshi R, Lincoff N, Clark J, Daroff R. MRI Findings in Susac Syndrome. Neurology 61: 1783-1787; 2003 Egan RA, Hills WL, Susac JO. Gass Plaques and Fluorescein Leakage in Susac Syndrome. Journal of Neurological Sciences 299(1-2): 97-100; 2010 Susac JO, Rennebohm RM, Egan RA, Daroff RB. Susac’s Syndrome – Update. Journal of Neurological Sciences 299(1-2): 86-91; 2010 Susac JO. Susac Syndrome: the triad of microangiopathy of the brain and retina with hearing loss in young women. Neurology 44(4): 591-3; 1994 Dörr J, Krautwald S, Wildemann B, Jarius S, Ringelstein M, Duning T, Aktas O, Ringelstein EB, Paul F, Kleffner I. Characteristics of Susac Syndrome: a review of all reported cases. Nat Rev Neurol 9(6): 307-16; 2013 Groh S, One of three hundred - My Life with Susac Syndrome. ISBN 9783752679120 == External links ==
Syndactyly	Syndactyly is a condition wherein two or more digits are fused together. It occurs normally in some mammals, such as the siamang and diprotodontia, but is an unusual condition in humans. The term is from Greek σύν, syn together and δάκτυλος, daktulos finger. Classification Syndactyly can be simple or complex. In simple syndactyly, adjacent fingers or toes are joined by soft tissue. In complex syndactyly, the bones of adjacent digits are fused. The kangaroo exhibits complex syndactyly.Syndactyly can be complete or incomplete. In complete syndactyly, the skin is joined all the way to the tip of the involved digits. In incomplete syndactyly, the skin is only joined part of the distance to the tip of the involved digits.Complex syndactyly occurs as part of a syndrome (such as Apert syndrome) and typically involves more digits than simple syndactyly. Fenestrated syndactyly, also known as acrosyndactyly or terminal syndactyly, means the skin is joined for most of the digit but in a proximal area there are gaps in the syndactyly with normal skin. This type of syndactyly is found in amniotic band syndrome. Simple syndactyly can be full or partial, and is present at birth (congenital). In early human fetal development, webbing (syndactyly) of the toes and fingers is normal. At about 6 weeks of gestation, apoptosis takes place due to a protein named sonic hedgehog, also known as SHH, which dissolves the tissue between the fingers and toes, and the webbing disappears. In some fetuses, this process does not occur completely between all fingers or toes and some residual webbing remains. Genetics Five types of syndactyly have been identified in humans. The corresponding loci associated with these types and their common phenotypical expression are as follows: type I: 2q34-q36; webbing occurs between middle and ring fingers and/or second and third toes. type II: 2q31; also involves long and ring fingers, but has a sixth finger merged in between. type III: 6q21-q23; small finger is merged into the ring finger. type IV: 7q36; involves all fingers and/or toes. type V: 2q31-q32; similar to type I, but the metacarpals and metatarsals may also be fused. Management Syndactyly of the border digits (thumb/index finger or ring/small fingers) is treated at early age to prevent the larger digit from curving towards the smaller digit with growth. Typically, syndactyly of these digits is treated at six months of age. The treatment of syndactyly of the other digits is elective and is more commonly performed when the digits have grown, at 18–24 months of age. Techniques Because the circumference of the conjoined fingers is smaller than the circumference of the two separated fingers, there is not enough skin to cover both digits once they are separated at the time of surgery. Therefore, the surgeon must bring new skin into the area at the time of surgery. This is most commonly done with a skin graft (from groin or anterior elbow). Skin can also be used from the back of the hand by mobilizing it (called a "graftless" syndactyly correction), which requires planning over a period of months prior to surgery. Complications The most common problem with syndactyly correction is creeping of the skin towards the fingertip over time. This is likely due to tension at the site of the repair between the digits. Additional surgery may be required to correct this. One critique of using skin grafts is that the grafts darken in the years after surgery and become more noticeable. Also, if the skin grafts are harvested from the groin area, the skin may grow hair. Finally, the fingers may deviate after surgery. This is most commonly seen in complex syndactyly (when there has been a bone joining of the fingers). History The earliest appreciation of syndactyly as a birth anomaly or burn-trauma can be traced back to the Andalusian Muslim surgeon Al-Zahrawi (d. 1013 CE), known in the West as Abulcasis. The French barber surgeon Ambroise Paré also described syndactyly in the sixteenth century. See also Dactyly, the arrangement of fingers and toes in different kinds of animals Webbed toes, the common name for syndactyly affecting the feet References External links Media related to Syndactyly at Wikimedia Commons
PES	Pes (Latin for "foot") or the acronym PES may refer to: Pes Pes (unit), a Roman unit of length measurement roughly corresponding with a foot Pes or podatus, a Neume § Neumes representing two notes Pes (rural locality), several rural localities in Russia Pes (river), a river in northwestern Russia Pes (anatomy), zoological term for the distal portion of the hind limb of tetrapod animals Talipes equinovarus (pes equinovarus), clubfoot Talipes cavus (pes cavus), clawfoot Talipes planus (pes planus), flat feet Talipes valgus (pes valgus), valgus deformity of the foot Talipes varus (pes varus), varus deformity of the foot Pes anserinus (leg) Pes anserine bursitis, inflammatory of the inner knee at the bursa of the pes anserinus Parotid plexus, pes anserinus of the facial nerve PES Education PES University, formerly P.E.S. Institute of Technology, a university in Bangalore, India Providence Elementary School, an elementary school in Chesterfield County, Virginia Computing Pro Evolution Soccer, a multi-platform video game series developed by Konami Packetized elementary stream, part of the MPEG communication protocol Peripheral Event System, an implementation of autonomous peripheral operations in microcontrollers PSTN Emulation System for IP Multimedia Subsystem (IMS) Organizations Postal Express Service, United States military mail during World War I Power Engineering Society, now the Power & Energy Society of the Institute of Electrical and Electronics Engineers Premier Election Solutions, formerly Diebold Election Systems Party of European Socialists, a centre-left pan-European political party Social Encounter Party, a Mexican former political party Solidarity Encounter Party, a Mexican former political party Science Pallasite Eagle Station, a pallasite meteorite grouplet Photoemission spectroscopy, a measurement of a substances binding energy using the photoelectric effect Poly(ethylene succinate), a type of polyester Polyester, an artificially produced organic chemical that is spun and woven to make fabric Polyethersulfone, a thermoplastic polymer Potential energy surface, in physics and chemistry Programmed electrical stimulation, a type of electrophysiologic study Pseudoexfoliation syndrome, an eye problem Other PES (director) (born 1973), film director and animator born Adam Pesapane Passenger Environment Survey, quality-control system for transit systems Payment for ecosystem services, incentives offered to farmers or landowners Pensarn railway station, Gwynedd, Wales, by National Rail station code Price elasticity of supply, a measure used in economics PULHHEEMS, a system of grading physical and mental fitness used by Britains armed forces See also Pez (disambiguation)
Waardenburg syndrome	Waardenburg syndrome is a group of rare genetic conditions characterised by at least some degree of congenital hearing loss and pigmentation deficiencies, which can include bright blue eyes (or one blue eye and one brown eye), a white forelock or patches of light skin. These basic features constitute type 2 of the condition; in type 1, there is also a wider gap between the inner corners of the eyes called telecanthus, or dystopia canthorum. In type 3, which is rare, the arms and hands are also malformed, with permanent finger contractures or fused fingers, while in type 4, the person also has Hirschsprungs disease. There also exist at least two types (2E and PCWH) that can result in central nervous system (CNS) symptoms such as developmental delay and muscle tone abnormalities.The syndrome is caused by mutations in any of several genes that affect the division and migration of neural crest cells during embryonic development (though some of the genes involved also affect the neural tube). Neural crest cells are stem cells left over after the closing of the neural tube that go on to form diverse non-CNS cells in different parts of the body, including melanocytes, various bones and cartilage of the face and inner ear and the peripheral nerves of the intestines. Type 1 is caused by a mutation in the PAX3 gene, while the gene that most often causes type 2 when mutated is MITF. Type 3 is a more severe presentation of type 1 and is caused by a mutation in the same gene, while type 4 is most often caused by a mutation in SOX10. Mutations in other genes can also cause the different types, and some of these have been given their own lettered subtypes. Most types are autosomal dominant. The estimated prevalence of Waardenburg syndrome is 1 in 42,000. Types 1 and 2 are the most common, comprising approximately half and a third of cases, respectively, while type 4 comprises a fifth and type 3 less than 2% of cases. An estimated 2–5% of congenitally deaf people have Waardenburg syndrome. Descriptions of the syndrome date back to at least the first half of the 20th century, however it is named after Dutch ophthalmologist and geneticist Petrus Johannes Waardenburg, who described it in 1951. Its subtypes were progressively discovered in the following decades and had genes attributed to them mostly in the 1990s and 2000s. Signs and symptoms Waardenburg syndrome has multiple different types with some variations in symptoms, and symptoms can vary among those with the same type. The two features consistent across all types of Waardenburg syndrome are some degree of congenital sensorineural hearing loss and some degree of pigmentation deficiencies, most consistently in the eyes. Type 1 Type 1 is characterised by congenital sensorineural hearing loss, pigmentary deficiencies of the hair such as a white lock of hair (poliosis) in the front-centre of the head or premature greying, pigmentary deficiencies of the eyes such as different-coloured eyes (complete heterochromia iridum), multiple colours in an eye (sectoral heterochromia iridum) or brilliant blue eyes, patches of skin depigmentation, and a wider gap between the inner corners of the eyes called telecanthus or dystopia canthorum. Other facial features associated with type 1 can include a high nasal bridge, a flat nose tip, a unibrow (synophrys), smaller edges of the nostrils (alae) or a smooth philtrum. Type 2 The difference that defines type 2 from type 1 is that patients do not have the wider gap between the inner corners of the eyes (telecanthus/dystopia canthorum). Sensorineural hearing loss tends to be more common and more severe in this type. By far the most common gene to cause this type when mutated is MITF (classified as type 2A). If two individuals with a mutation in this gene have a child carrying both mutations (homozygous), for which there is 25% chance, additional symptoms are present in the child, such as a hole in the iris (coloboma), small eyes (microphthalmia), hardened bones (osteopetrosis), macrocephaly, albinism and deafness.There have been two known patients identified with mutations in both copies of SNAI2 (classified as type 2D); these individuals presented with Waardenburg syndrome type 2 but did not have hair pigmentation deficiencies.When Waardenburg syndrome type 2 is caused by a mutation in SOX10 (classified as type 2E), it can on some occasions present with multiple neurological symptoms. These can include developmental delay, early childhood nystagmus, increased muscle tone, white matter anomalies or hypomyelination in the brain, autistic-like behaviour and the underdevelopment or complete absence of many inner-ear structures such as the vestibular system or cochlea. Lack of a sense of smell (anosmia) due to a missing olfactory bulb in the brain may also be present. Type 3 Also known as Klein–Waardenburg syndrome, or Waardenburg–Klein syndrome, type 3 has the same symptoms as type 1 (and is caused by mutations in the same gene) but has additional symptoms that affect the arms and hands. These can include joint contractures of the fingers (camptodactyly), due to underdeveloped muscles, as well as fused digits (syndactyly) or winged scapulae. Microcephaly and developmental delay are also possible. Type 4 Also known as Shah–Waardenburg syndrome, or Waardenburg–Shah syndrome, type 4 has most of the same features as type 2 (i.e. no telecanthus, or apparent wider eye gap), but with the addition of Hirschsprungs disease, which is a congenital lack of nerves in the intestines leading to bowel dysfunction. Additionally, hearing loss is not as common as in type 2. Rarely, cleft lip has been reported in this form of Waardenburg syndrome.Type 4 can also be caused by a mutation in SOX10 (the same gene as in type 2E), in which it is known as type 4C; hearing loss is very common and severe in this type. PCWH A mutation in SOX10, the gene involved in type 2E and type 4C, can sometimes result in the symptoms of both types (neurological symptoms, as sometimes seen in type 2E, and Hirschsprungs disease, as seen in type 4). When this happens, it is called peripheral demyelinating neuropathy–central dysmyelinating leukodystrophy–Waardenburg syndrome–Hirschsprung disease (PCWH). Cause Waardenburg syndrome is caused by mutations in any of several genes that affect the operation of neural crest cells in embryonic development. Most types of Waardenburg syndrome are caused by autosomal dominant mutations. The few that are autosomal recessive are rare. In most cases, an affected person has inherited it from one parent with one of the dominant forms of the condition. A small percentage of cases result from spontaneous new mutations in the gene, where no family history of the condition exists.The neural crest is a group of temporary migratory cells that are left over after the neural tube has closed (neurulation), around the fourth week of embryonic development. They are responsible for differentiating into a diverse group of cells that reach different areas of the body. The neural tube and neural crest are derived from the ectoderm; the neural tube goes on to form the brain and spinal cord, while the neural crest cells eventually go on to form various bones and cartilage of the skull and face by migrating through the pharyngeal arches. They also differentiate into the stria vascularis of the cochlea, the nerves and glia of the intestines (myenteric plexus), Schwann cells, which myelinate the peripheral nervous system to allow sufficient conductivity, odontoblasts, which produce dentin deep in the teeth, some neuroendocrine cells, connective tissue around the salivary, lacrimal, pituitary, thymus and thyroid glands, connective tissue of the eye, such as the stroma of the iris and cornea and the trabecular meshwork, and melanocytes, including those in the stroma of the iris that give rise to brown eye colour through melanin. Neural crest cells also have a role in muscle formation, including the wall muscle of certain cardiac arteries. Causes of subtypes Type 1 is caused by an autosomal dominant mutation in the gene PAX3. PAX3, or paired box 3, is a transcription factor that has a role in maintaining an open window of time for certain neural crest cells (such as those of the head and eyes) to divide and migrate before their terminal differentiation (i.e. to maintain them in the stem-cell state). Mutations in this gene therefore prematurely arrest their division and migration, resulting in a minor lack of development of certain face cartilage and bones, as well as underdeveloped inner-ear structures and a lack of melanocytes in the iris stroma. Some evidence shows that PAX3 also regulates cells from before the neural crest forms, i.e. the neural tube, since mice with loss-of-function mutations in one of the copies of PAX3 have neural tube defects such as spina bifida or exencephaly. Type 2 is caused by a mutation in any of a range of genes, the most common being MITF, when it is classed as type 2A. Type 2A is caused by an autosomal dominant mutation in the gene MITF. MITF, or microphthalmia-associated transcription factor, has a more specialised role in the neural crest and is more strictly involved after the neural crest forms (PAX3 and SOX10 have been found to activate MITF). It is known to allow melanocytes, osteoclasts, mast cells and retinal pigment epithelial cells to divide and migrate. The involvement in osteoclasts explains why mutations in both copies of MITF can lead to bone hardening (osteopetrosis), as the osteoclasts are responsible for breaking down bone. MITF also activates transcription of tyrosinase, the enzyme that performs the first step in the creation of melanin (oxidising tyrosine). A mutation in a copy of MITF can also lead to Tietz syndrome, which is distinguished from Waardenburg syndrome by uniform albinism instead of patchy depigmentation. Type 2B is caused by an autosomal dominant mutation in an unknown gene on chromosome 1 in the locus range of 1p21–1p13.3. The gene has been provisionally termed WS2B. Type 2C is caused by an autosomal dominant mutation in an unknown gene on chromosome 8 in the locus of 8p23. The gene has been provisionally termed WS2C. Type 2D is caused by an autosomal recessive mutation in both copies of the gene SNAI2. The study that discovered this association found that SNAI2 is activated by MITF as part of neural crest development, and this explained why mutations in MITF cause Waardenburg syndrome, as it results in a lack of activation of SNAI2. Mutations in a single copy of SNAI2 have also been found to cause patches of hair depigmentation (piebaldism) without any other symptoms. Type 2E is caused by an autosomal dominant mutation in the gene SOX10. Rarely, a mutation in a gene other than those currently known may be responsible for a Waardenburg syndrome with features of type 2. This is usually initially classified as simply type 2 but may be given its own subtype once a gene or locus is identified and established. Type 3 is caused by a mutation in the gene PAX3, the same gene as in type 1. It can be inherited in an autosomal dominant or autosomal recessive manner; it is possible for two parents with Waardenburg syndrome type 1 to have a child carrying both mutated copies of the PAX3 gene (25% chance) and present with Waardenburg syndrome type 3. A missense mutation has been documented to have this effect. However, it is also possible for Waardenburg syndrome type 3 to present spontaneously with just one mutated copy of PAX3. A deletion of the paired domain region of the gene has been documented to have this effect. However, no major correlation has been found between type of mutation and disease severity. Severity tends to be dictated by mutations in other genes (epistasis), as evidenced by distinct familial patterns in severity not tied to Waardenburg mutation type. Mutations in both copies of PAX3 have sometimes led to death before or shortly after birth, and mice with loss-of-function mutations in both copies of the gene do not survive. Type 4 is caused by a mutation in any of a range of genes, the most common being SOX10, when it is classed as type 4C. Type 4A is caused by an autosomal dominant or autosomal-recessive mutation in the gene EDNRB. Type 4B is caused by an autosomal dominant or autosomal-recessive mutation in the gene EDN3. Type 4C is caused by an autosomal dominant or autosomal-recessive mutation in the gene SOX10, the same gene as in type 2E.A study was done on a rare case of a double heterozygous child with each parent having only single mutations in MITF or PAX3. The effect of double heterozygous mutations in the genes MITF and PAX3 in WS1 and WS2 can increase the pigment-affected symptoms. It leads to the conclusion that the double mutation of MITF is associated with the extremity of Waardenburg syndrome and may affect the phenotypes or symptoms of the syndrome. Classification table Treatment There is currently no treatment or cure for Waardenburg syndrome. The symptom most likely to be of practical importance is deafness, and this is treated as any other irreversible deafness would be. In marked cases, there may be cosmetic issues. Other abnormalities (neurological, structural, Hirschsprungs disease) associated with the syndrome are treated symptomatically. Epidemiology The prevalence of all types of Waardenburg syndrome is estimated at around 1 in 42,000. Types 1 and 2 are by far the most common, with type 1 appearing to be slightly more common. In a 2015 review looking at 417 patients, type 1 was found to be the most common type, encompassing around half of all cases (47%), while type 2 was the second-most common type, encompassing around a third (33%). The vast majority (around 85%) of type 2 cases are type 2A. The prevalence of type 2B is unknown, as it was only reported in one 1996 study. Type 2C has so far only been found in one Italian family, and type 2D had only been found in 2 unrelated patients as of 2018. The number of known cases of type 2E that involved neurological abnormalities was reported to be 23 as of 2017, while the number of the rest is unknown. Type 3 is rarer than types 1, 2 and 4, comprising less than 2% of cases. Type 4 appears to encompass around a fifth of cases (19%). Of its subtypes, type 4C is by far the most common (about 71% of type 4), followed by type 4A (19%) and type 4B (10%).It is estimated that Waardenburg syndrome is present in 2–5% of congenitally deaf people. Congenital deafness comprises around half of deafness as a whole. About 1 in 30 students in schools for the deaf have Waardenburg syndrome. The variable presentation of the syndrome makes it difficult to arrive at precise figures for its prevalence. History Early descriptions In 1916, Dutch ophthalmologist Jan van der Hoeve (1878–1952) described a pair of twin girls with deafness and a particular type of blepharophimosis, believed to be the dystopia canthorum found in Waardenburg syndrome types 1 and 3. Blepharophimosis describes eyelids which are underdeveloped such that they permanently cover part of the eyes. In 1926, German physician Irmgard Mende described a family of four generations in which five children had symptoms of depigmentation of hair, skin and eyes, deafness and a "mongoloid" appearance. (Waardenburg later attributed this description to the dystopia canthorum.) This later led to the synonym Mende syndrome being recorded in some databases.In 1929, Dutch physician K. T. A. Halbertsma described a familial pattern to dystopia canthorum, and in 1930, Italian physician Vincenzo Gualdi (1891–1976) also confirmed a hereditary pattern to dystopia canthorum. This later led to the synonym Van der Hoeve–Halbertsma–Waardenburg–Gualdi syndrome being recorded in some databases.In 1947, Swiss ophthamologist David Klein (1908–1993) first reported a patient with bilateral deafness, pigmentation deficiencies, characteristic facial features and malformation of the arms. Although this was the first full description of a patient with Waardenburg syndrome type 3, contemporary clinicians did not consider the syndrome he described to be the same as that described by Waardenburg four years later, in part due to how severe the arm malformations were in his patient.The syndrome was first fully formalised and described by Dutch ophthalmologist and geneticist Petrus Johannes Waardenburg (1886–1979) in 1951. The condition he described is now categorised as Waardenburg syndrome type 1. Descriptions of subtypes Type 2 was first established in 1971 when a study noticed that some Waardenburg syndrome patients did not have dystopia canthorum. A 1977 study confirmed a familial pattern to this other presentation. Two 1994 studies first confirmed a link between this type of Waardenburg syndrome and mutations in the MITF gene (now classed as type 2A), located on chromosome 3 at locus 3p14.1–p12.3.Type 2B was first established in 1994 when the same study which found mutations in MITF in patients with Waardenburg syndrome type 2 also found that some patients did not have any mutations in this region. A second 1994 study found a link to chromosome 1 in the locus 1p21–p13.3. This became known as type 2B of the condition (with the gene designated WS2B), however it has not been documented since, and the gene responsible remains unknown.Type 2C was established in 2001 when a study of an Italian family with Waardenburg syndrome type 2 features found that they were due to an unknown gene on chromosome 8 at locus 8q23 that had been broken by a chromosomal translocation. The study established a provisional name for the gene, WS2C. However, mutations in this region in Waardenburg syndrome patients have not been found since.Type 2D was established in 2002 when a study looking to find mutations in the human version of the SNAI2 gene, known to cause depigmentation in mice, found deletions of both copies of this gene in two unrelated individuals with Waardenburg syndrome type 2. Mutations in both copies of this gene have not been found in those with Waardenburg syndrome type 2 since.Type 2E was first established in 1996 when a study identified a girl with symptoms of Waardenburg syndrome type 2 but with additional underdevelopment of the front of the eye, leading to blindness. In 1999, it was found that she had a mutation in her SOX10 gene, and later studies confirmed the association between mutations in this gene and this phenotype, as well as neurological symptoms such as developmental delay.Type 3 was first given its name by Goodman et al. in 1981, in collaboration with Klein, in which they established the association with arm abnormalities first reported by Klein in 1947. Mutations in PAX3 were first linked to this phenotype in 1992.The comorbidity with Hirschsprungs disease, which would later constitute type 4, was first noticed in various studies in the 1970s. Indian paediatrician Krishnakumar Shah and his associates first outlined the syndrome as a possible variant of Waardenburg syndrome in 1981. The variant was first attributed to a mutation in EDNRB in 1994 (now classed as type 4A). Type 4B was established in 1996 when mutations in EDN3 were found to lead to this type of Waardenburg syndrome, and type 4C was first established in 1998 when mutations in SOX10 were also found to lead to this type. Society and culture Popular culture The 2001 novel Shock by Robin Cook mentions a character with the disorder. Enzo MacLeod, protagonist of Peter Mays 2006–2017 book series The Enzo Files, has Waardenburg syndrome. His eyes are different colors, and he has a white streak in his hair. In the 2011 season 6 episode of Bones "The Signs in the Silence", the team must solve a case in which the suspected killer has Waardenburg syndrome. The 2013 book Reconstructing Amelia by Kimberly McCreight features several characters with Waardenburg symptoms. The 2014 book Closer Than You Think by Karen Rose features three characters, siblings, with Waardenburg syndrome. The 2017 book Murder at the Mayan Temple by M.J. Mandrake features several characters with Waardenburg syndrome. The 2019 novel The Whisper Network by Chandler Baker uses the syndrome as a plot point. Notable people Canadian YouTube vlogger Stef Sanjati has Waardenburg syndrome type 1. Other animals Waardenburg syndrome type 2A (with a mutation in MITF) has been found in dogs, Fleckvieh cattle, minks, mice and a golden hamster. Degeneration of the cochlea and saccule, as seen in Waardenburg syndrome, has also been found in deaf white cats, Dalmatians and other dog breeds, white minks and mice.Domesticated cats with blue eyes and white coats are often completely deaf. Deafness is far more common in white cats than in those with other coat colors. According to the ASPCA Complete Guide to Cats, "17 to 20 percent of white cats with non-blue eyes are deaf; 40 percent of "odd-eyed" white cats with one blue eye are deaf; and 65 to 85 percent of blue-eyed white cats are deaf." Although few studies have been done to link this to genes known to be involved in human Waardenburg syndrome, a genetic disruption to neural crest development would lead to this presentation in cats as well. One of the genes that leads to deafness and a white coat in cats when mutated, KIT, has been found to increase MITF expression.Lethal white syndrome is a syndrome in horses caused by mutations in both copies of EDNRB. It leads to death from intestinal pseudo-obstruction due to Hirschsprungs disease. A mutation in a single copy of EDNRB, however, as in Waardenburg syndrome type 4A, produces the patchy white overo coat with deafness.Ferrets with Waardenburg syndrome have a small white stripe along the top or back of the head and sometimes down the back of the neck (known as a "blaze" coat pattern), or a solid-white head from nose to shoulders (known as a "panda" coat pattern). Affected ferrets often have a very slightly flatter skull and wider-set eyes than healthy ferrets. As healthy ferrets have poor hearing, deafness may only be detected by lack of reaction to loud noises. As this is an inherited disorder, affected animals should not be used for breeding. A study of the correlation between coat variations and deafness in European ferrets found, "All (n=27) panda, American panda, and blaze ferrets were deaf." See also Chédiak–Higashi syndrome, a similar syndrome including immunodeficiency and peripheral neuropathy Tietz syndrome, a condition similar to Waardenburg syndrome type 2 involving uniform albinism (caused by mutations in MITF) Vogt–Koyanagi–Harada disease, an autoimmune disease causing uveitis, patchy depigmentation and inner ear symptoms References External links GeneReviews/NCBI/NIH/UW entry on Waardenburg Syndrome Type I OMIM Genetic disorder catalog — Waardenburg syndrome
Vasculitis	Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily caused by leukocyte migration and resultant damage. Although both occur in vasculitis, inflammation of veins (phlebitis) or arteries (arteritis) on their own are separate entities. Signs and symptoms Possible signs and symptoms include: General symptoms: Fever, unintentional weight loss Skin: Palpable purpura, livedo reticularis Muscles and joints: Muscle pain or inflammation, joint pain or joint swelling Nervous system: Mononeuritis multiplex, headache, stroke, tinnitus, reduced visual acuity, acute visual loss Heart and arteries: Heart attack, high blood pressure, gangrene Respiratory tract: Nosebleeds, bloody cough, lung infiltrates GI tract: Abdominal pain, bloody stool, perforations (hole in the GI tract) Kidneys: Inflammation of the kidneys filtration units (glomeruli) Cause Classification Vasculitis can be classified by the cause, the location, the type of vessel or the size of vessel. Underlying cause. For example, the cause of syphilitic aortitis is infectious (aortitis simply refers to inflammation of the aorta, which is an artery.) However, the causes of many forms of vasculitis are poorly understood. There is usually an immune component, but the trigger is often not identified. In these cases, the antibody found is sometimes used in classification, as in ANCA-associated vasculitides. Clinical studies with immunosuppressive drugs targeting specific cytokines and cells can also be used to understand the heterogeneous immunopathogenic mechanisms of vasculitis and support a mechanistic immunological classification. Location of the affected vessels. For example, ICD-10 classifies "vasculitis limited to skin" with skin conditions (under "L"), and "necrotizing vasculopathies" (corresponding to systemic vasculitis) with musculoskeletal system and connective tissue conditions (under "M"). Arteritis/phlebitis on their own are classified with circulatory conditions (under "I"). Type or size of the blood vessels that they predominantly affect. Apart from the arteritis/phlebitis distinction mentioned above, vasculitis is often classified by the caliber of the vessel affected. However, there can be some variation in the size of the vessels affected.A small number have been shown to have a genetic basis. These include adenosine deaminase 2 deficiency and haploinsufficiency of A20. According to the size of the vessel affected, vasculitis can be classified into: Large vessel: Takayasus arteritis, Temporal arteritis Medium vessel: Buergers disease, Kawasaki disease, Polyarteritis nodosa Small vessel: Behçets syndrome, Eosinophilic granulomatosis with polyangiitis, Cutaneous vasculitis, granulomatosis with polyangiitis, Henoch–Schönlein purpura, and microscopic polyangiitis. Condition of some disorders have vasculitis as their main feature. The major types are given in the table below:Takayasus arteritis, polyarteritis nodosa and giant cell arteritis mainly involve arteries and are thus sometimes classed specifically under arteritis. There are also many conditions that have vasculitis as an accompanying or atypical feature, including: Rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and dermatomyositis Cancer, such as lymphomas Infections, such as hepatitis C Primary Immunodeficiencies, such as DADA2, GATA2, and RAG deficiency Exposure to chemicals and drugs, such as amphetamines, cocaine, and anthrax vaccines which contain the Anthrax Protective Antigen as the primary ingredient. Sympathomimetics such as phenylpropanolamine, methylphenidate, and others are also implicated.In pediatric patients varicella inflammation may be followed by vasculitis of intracranial vessels. This condition is called post varicella angiopathy and this may be responsible for arterial ischaemic strokes in children.Several of these vasculitides are associated with antineutrophil cytoplasmic antibodies. These are: Granulomatosis with polyangiitis Eosinophilic granulomatosis with polyangiitis Microscopic polyangiitis Diagnosis Laboratory tests of blood or body fluids are performed for patients with active vasculitis. Their results will generally show signs of inflammation in the body, such as increased erythrocyte sedimentation rate (ESR), elevated C-reactive protein (CRP), anemia, increased white blood cell count and eosinophilia. Other possible findings are elevated antineutrophil cytoplasmic antibody (ANCA) levels and hematuria. Other organ functional tests may be abnormal. Specific abnormalities depend on the degree of various organs involvement. A brain SPECT can show decreased blood flow to the brain and brain damage. The definite diagnosis of vasculitis is established after a biopsy of involved organ or tissue, such as skin, sinuses, lung, nerve, brain, and kidney. The biopsy elucidates the pattern of blood vessel inflammation.Some types of vasculitis display leukocytoclasis, which is vascular damage caused by nuclear debris from infiltrating neutrophils. It typically presents as palpable purpura. Conditions with leucocytoclasis mainly include hypersensitivity vasculitis (also called leukocytoclastic vasculitis) and cutaneous small-vessel vasculitis (also called cutaneous leukocytoclastic angiitis).An alternative to biopsy can be an angiogram (x-ray test of the blood vessels). It can demonstrate characteristic patterns of inflammation in affected blood vessels. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT)has become a widely used imaging tool in patients with suspected Large Vessel Vasculitis, due to the enhanced glucose metabolism of inflamed vessel walls. The combined evaluation of the intensity and the extension of FDG vessel uptake at diagnosis can predict the clinical course of the disease, separating patients with favourable or complicated progress. Acute onset of vasculitis-like symptoms in small children or babies may instead be the life-threatening purpura fulminans, usually associated with severe infection.In this table: ANA = antinuclear antibodies, CRP = C-reactive protein, ESR = erythrocyte sedimentation rate, dsDNA = double-stranded DNA, ENA = extractable nuclear antigens, RNP = ribonucleoproteins; VDRL = Venereal Disease Research Laboratory Treatment Treatments are generally directed toward stopping the inflammation and suppressing the immune system. Typically, corticosteroids such as prednisone are used. Additionally, other immune suppression medications, such as cyclophosphamide and others, are considered. In case of an infection, antimicrobial agents including cephalexin may be prescribed. Affected organs (such as the heart or lungs) may require specific medical treatment intended to improve their function during the active phase of the disease. References == External links ==
Polydactyly	Polydactyly or polydactylism (from Greek πολύς (polys) many, and δάκτυλος (daktylos) finger), also known as hyperdactyly, is an anomaly in humans and animals resulting in supernumerary fingers and/or toes. Polydactyly is the opposite of oligodactyly (fewer fingers or toes). Signs and symptoms In humans/animals this condition can present itself on one or both hands. The extra digit is usually a small piece of soft tissue that can be removed. Occasionally it contains bone without joints; rarely it may be a complete functioning digit. The extra digit is most common on the ulnar (little finger) side of the hand, less common on the radial (thumb) side, and very rarely within the middle three digits. These are respectively known as postaxial (little finger), preaxial (thumb), and central (ring, middle, index fingers) polydactyly. The extra digit is most commonly an abnormal fork in an existing digit, or it may rarely originate at the wrist as a normal digit does.The incidence of congenital deformities in newborns is approximately 2%, and 10% of these deformities involve the upper extremity. Congenital anomalies of the limb can be classified in seven categories, proposed by Frantz and O’Rahilly and modified by Swanson, based on the embryonic failure causing the clinical presentation. These categories are failure of formation of parts, failure of differentiation, duplication, overgrowth, undergrowth, congenital constriction band syndrome, and generalized skeletal abnormalities. Polydactyly belongs to the category of duplication. Because there is an association between polydactyly and several syndromes, children with a congenital upper extremity deformity should be examined by a geneticist for other congenital anomalies. This should also be done if a syndrome is suspected, or if more than two or three generations of the family are affected. Research has shown that the majority of congenital anomalies occur during the 4-week embryologic period of rapid limb development. Polydactyly has been associated with 39 genetic mutations. More specific loci and genetic mechanisms responsible for disorders of duplications will be defined with time, as molecular research continues. Polydactyly can be divided into three major types, which are discussed below. Ulnar or postaxial polydactyly This is the most common situation, in which the extra digit is on the ulnar side of the hand, thus the side of the little finger. This can also be called postaxial polydactyly. It can manifest itself very subtly, for instance only as a nubbin on the ulnar side of the little finger, or very distinctly, as a fully developed finger. Most commonly, the extra finger is rudimentary, consisting of an end phalanx with a nail, and connected to the hand with a small skin pedicle. Mostly one neurovascular bundle can be identified, with no tendons present in the extra digit. In case of a fully developed extra finger, the duplication usually presents itself at the level of the metacarpophalangeal joint. A triplication of the little finger is very rare. Ulnar polydactyly occurs ten times more often in African populations. The incidence in Caucasians is reported as 1 in 1,339 live births, compared with 1 in 143 live births in Africans and African Americans. Ulnar polydactyly is also often part of a syndrome. In patients with African ancestry ulnar polydactyly mostly occurs isolated, whereas the presentation in Caucasians is often associated with a syndrome, though in a retrospective review, only 4 of 37 cases of ulnar polydactyly in Caucasians were syndromic. Radial or preaxial polydactyly This is a less common situation, in which the affectation is on the side of the hand towards the thumb. Radial polydactyly refers to the presence of an extra digit (or extra digits) on the radial side of the hand. It is most frequent in Indian populations and it is the second most common congenital hand disorder. The incidence of radial polydactyly is reported as 1 in every 3,000 live births. The clinical features of radial polydactyly will depend upon the extent of duplication. Radial polydactyly varies from a barely visible radial skin tag to complete duplication. Thumb polydactyly varies from barely visible broadening of the distal phalanx to full duplication of the thumb including the first metacarpal. Radial polydactyly is frequently associated with several syndromes. Central polydactyly This is a very rare situation, in which the extra digit is on the ring, middle or index finger. Of these fingers, the index finger is most often affected, whereas the ring finger is rarely affected. This type of polydactyly can be associated with syndactyly, cleft hand and several syndromes. Polysyndactyly presents various degrees of syndactyly affecting fingers three and four. Causes Polydactyly is associated with different mutations, either mutations in a gene itself or in a cis-regulatory element responsible for the expression of a specific gene. Mutations in Hoxa- or Hoxd clusters are reported leading to polydactyly. Interactions of Hoxd13 and GLI3 induce synpolydactyly, a combination of extra and consolidated digits. Other signal transduction pathways in this context are the Wnt signaling pathway or Notch.In the specific case of preaxial polydactyly (Hemingway mutant), a cis-acting mutation approximately 1Mb upstream of SHH gene has been implicated. Normally SHH is expressed in an organiser region, called the zone of polarizing activity (ZPA) on the posterior limb side. From there it diffuses anteriorly, laterally to the growth direction of the limb. In the mutant, smaller ectopic expression in a new organiser region is seen on the anterior side of the limb. This ectopic expression causes cell proliferation delivering the raw material for one or more new digits.In addition to the study of genetic causes of polydactyly, limb patterning models are used to simulate the congenital disorder at the limb, being able to explain the development paths of polydactyly.Polydactyly can occur by itself, or more commonly, as one feature of a syndrome of congenital anomalies. When it occurs by itself, it is associated with autosomal dominant mutations in single genes, i.e. it is not a multifactorial trait. But mutation in a variety of genes can give rise to polydactyly. Typically the mutated gene is involved in developmental patterning, and a syndrome of congenital anomalies results, of which polydactyly is one feature or two.Polydactyly has been linked to the prenatal environment, however, with a recent study showing a relationship to maternal pollution exposure in China.Types include: 97 genetic syndromes have been associated with different kinds of polydactyly. Ulnar polydactyly Ulnar polydactyly is often bilateral and associated with syndactyly and polydactyly of the feet. This can be a simple or complex polydactyly. Ulnar polydactyly occurs as an isolated congenital condition, but can also be part of a syndrome. The syndromes which occur with ulnar polydactyly are: Trisomy 13, Greig cephalopolysyndactyly syndrome, Meckel syndrome, Ellis–van Creveld syndrome, McKusick–Kaufman syndrome, Down syndrome, Bardet–Biedl syndrome, Smith–Lemli–Opitz syndrome Radial polydactyly Type VII of radial polydactyly is associated with several syndromes: Holt–Oram syndrome, Fanconi anemia (aplastic anemia by the age of 6), Townes–Brocks syndrome, and Greig cephalopolysyndactyly (also known to occur with ulnar polydactyly). Central polydactyly The syndromes associated with central polydactyly are: Bardet–Biedl syndrome, Meckel syndrome, Pallister–Hall syndrome, Legius syndrome, Holt–Oram syndrome. Also, central polydactyly can be associated with syndactyly and cleft hand. Other syndromes including polydactyly include acrocallosal syndrome, basal cell nevus syndrome, Biemond syndrome, ectrodactyly-ectodermal dysplasias-cleft lip/palate syndrome, mirror hand deformity, Mohr syndrome, oral-facial-digital syndrome, Rubinstein-Taybi syndrome, short rib polydactyly, and VATER association. It can also occur with a triphalangeal thumb. Diagnosis Classification is performed by using x-ray imaging to see the bone structures. Ulnar polydactyly The classification of ulnar polydactyly exists of either two or three types. The two-stage classification, according to Temtamy and McKusick, involves type A and B. In type A there is an extra little finger at the metacarpophalangeal joint, or more proximal including the carpometacarpal joint. The little finger can be hypoplastic or fully developed. Type B varies from a nubbin to an extra, non-functional little finger part on a pedicle. According to the three-type classification, type I includes nubbins or floating little fingers, type II includes duplications at the MCPJ, and type III includes duplications of the entire ray. Radial polydactyly The Wassel classification is the most widely used classification of radial polydactyly, based upon the most proximal level of skeletal duplication. The most common type is Wassel 4 (about 50% of such duplications) followed by Wassel 2 (20%) and Wassel 6 (12%). Central polydactyly The classification of central polydactyly is based on the extent of duplication and involves the following three types: Type I is a central duplication, not attached to the adjacent finger by osseous or ligamentous attachments; it frequently does not include bones, joints, cartilage, or tendons. Type IIA is a nonsyndactylous duplication of a digit or part of a digit with normal components, and articulates with a broad or bifid metacarpal or phalanx. Type IIB is a syndactylous duplication of a digit or part of a digit with normal components, and articulates with a broad or bifid metacarpal or phalanx. Type III is a complete digital duplication, which has a well-formed duplicated metacarpal. Treatment Ulnar polydactyly Ulnar polydactyly usually does not interfere with hand function, but for social reasons it can be treated operatively. Type A ulnar polydactyly The treatment of Type A ulnar polydactyly is complex as its goal is to remove the accessory digit while maintaining a stable, functional small finger. When the duplicated proximal phalanx articulates with a common, broad metacarpal head, the ulnar collateral ligament must be considered. In those cases with a common articulation or with a sixth metacarpal the muscle executing the abduction of the little finger (abductor digiti minimi) must be preserved. In patients with a common metacarpal articulation an elliptical incision at the base of the post-axial digit is made. This incision may be extended proximally in order to adequately expose the abductor digiti minimi. The ulnar collateral ligament and the insertions of the abductor digiti minimi are then elevated with a periosteal sleeve. The duplicated extensor and flexor tendons to the ulnar digit are transected and after that the digit is amputated at its articulation with the metacarpal. If the articular surface is wide the metacarpal may be shaved. At last the collateral ligament and abductor digiti minimi are reinserted at the base of the preserved proximal phalanx and a wire is then placed across the reconstructed joint. In patients with a duplicated metacarpal, the accessory digit is amputated in a standard ray fashion with transfer of the abductor digiti minimi to the retained small finger. Type B ulnar polydactyly In this situation there is an absence of osseous and ligamentous structures. The surgical technique is analogous to radial polydactyly, in which the level of duplication and anatomical components should guide operative treatment. The pedicled ulnar extra digit can be removed by suture ligation to devise the skin bridge of the newborn child. This might be easier than an excision of the extra digit when the child is 6 to 12 months old. Ligation occludes the vascular supply to the duplicated digit, resulting in dry gangrene and subsequent autoamputation. This must be done with consideration of the presence of a neurovascular bundle, even in very small skin bridges. When the ligation is done inappropriately it can give a residual nubbin. Also, a neuroma can develop in the area of the scar. An excision can prevent the development of a residual nubbin and the sensitivity due to a neuroma. For infants with ulnar type B polydactyly the recommended treatment is ligation in the neonatal nursery. Studies have shown that excision of the extra digit in the neonatal nursery is a safe and simple procedure with a good clinical and cosmetic outcome. Radial polydactyly Because neither of the two thumb components is normal, a decision should be taken on combining which elements to create the best possible composite digit. Instead of amputating the most hypoplastic thumb, preservation of skin, nail, collateral ligaments and tendons is needed to augment the residual thumb. Surgery is recommended in the first year of life, generally between 9 and 15 months of age. Surgical options depend on type of polydactyly. Bilhaut-Cloquet procedure This type of procedure is recommended for Wassel types 1 and 2 (in which both thumbs are severely hypoplastic) by some congenital hand surgeons. The technique contains a composite wedge resection of the central bone and soft-tissue. This will be achieved with approach of the lateral tissue of each thumb. The goal is to achieve a normal thumb, what concerns the size, which is possible. If the width of the nail bed is greater than 70% of the contralateral thumb, it may be split. Ablation with collateral ligament reconstruction This type of procedure is used for all Wassel types of polydactyly and is the most commonly used technique. It is recommended in all cases of thumb duplication with a hypoplastic, less-functional thumb. Otherwise, one could consider the Bilhaut-Cloquet. The ulnar thumb is preferably preserved as it is the more developed one in most cases.By detaching the radial collateral ligament from distal to proximal, a periosteal sleeve can be preserved. In this way, the radial collateral band of the radial digit, will function as the absent radial collateral ligament of the preserved ulnar thumb. Elevation of the APB and FPB is performed in Wassel type 4 duplication; this can be accomplished via the periosteum or separately. As the tendons insert proximally, the elevation is performed proximally too to potentially rebalance the ulnar thumb. After the radial thumb is amputated, the ulnar elements are centralized and fixed with a Kirschner wire. In most cases, a longitudinal and sagittal osteotomy is needed to centralize the bony parts of the ulnar thumb. While the soft-tissue of the radial thumb was preserved, it is now attached to the radial side of the ulnar thumb together with the periosteal sleeve. The APB and FPB of the ablated radial thumb are attached to the distal phalanx for more stability. If necessary, the extensor pollicis longus and the flexor pollicis longus are reattached to centralize their course.In Wassel type 5 and 6 the opponens pollicis muscle must be transferred to the ulnar metacarpal. Soft tissue with collateral ligament reconstruction is used to avoid any angular deformity in the preserved thumb. Tendon centralization is also often used for correction. Still, cases with osseous deformities may happen. To provide alignment, osteotomies are necessary to be done. This operation may need bone grafting, which is obtained from the amputated thumb. On top plasty procedure This type is indicated when one thumb is larger proximally and the other thumb has a larger distal component. (The procedure is initially described as a way to lengthen amputated digits.) The goal is to create a functional thumb by combining less-hypoplastic components. On top plasty procedure is rarely employed in the treatment of congenital thumb duplication. It might be necessary for Wassel types 4, 5, 6.At the level of the mid-proximal phalanx or mid-metacarpal, the distal component is transferred to the proximal component. The tendons of the distal component are preserved as the rest of the distal component is amputated. The neurovascular bundle which supplies the distal component is reserved and transferred proximally. Central polydactyly Early osteotomy and ligament reconstructions should be done to prevent deformities, such as angular growth deformities.The surgical treatment of central polydactyly is highly variable. After the surgery the hand must be functional and stable, but also aesthetically pleasing. This requires intraoperative creativity and flexibility. The surgeon must also consider whether retention of a fully functional supranumerary digit is preferable to surgical intervention. In contrast, a functional, four-fingered hand achieved via ray amputation may be preferable to a five-fingered hand with a deformed or stiff reconstructed finger.Cases of polysyndactyly are approached through a standard opposing zig-zag incision. The incision is favored toward the accessory digit, preserving extra skin for subsequent closure. Depending on the level and extent of duplication, the flexor and extensor tendons may require centralization or rebalancing. Also, the collateral ligaments must be preserved or reconstructed. Wide articular surfaces should be narrowed and phalangeal wedge osteotomies may be required to provide an axial alignment. Attention must also be given to reconstruct the intermetacarpal ligament. Furthermore, one should take in mind the provision for adequate web-space soft tissue. Prognosis Ulnar polydactyly Type A ulnar polydactyly There are no substantive outcome studies regarding the function of these hands following surgical intervention. This is mainly caused by the fact that there is a generally normal function of these patients’ hands following ablation with collateral ligament reconstruction. In a study on 27 patients undergoing surgical excision for Type A ulnar polydactyly, only one complication was noted in the form of an infection However, no investigators have objectively reviewed functional range of motion or articular stability. Type B ulnar polydactyly In a study on 21 patients with Type B ulnar polydactyly treated with suture ligation it was found that the duplicated digit was typically amputated at an average of 10 days and no complications of infection or bleeding were reported. In a large study on 105 patients treated with suture ligation an overall complication rate of 23.5% was reported, citing a residual tender or unacceptable bump in 16%, infection in 6%, and bleeding in 1% of patients. In general, suture ligation is safe and effective when applied to appropriate cases of Type B polydactyly in which no substantial ligamentous or osseous structures are present within the pedicle. Parents should be educated as to the progression of necrosis, and that revision of residual tissue or scar may be necessary when the child is six months of age or older. Radial polydactyly Bilhaut procedure Advantages: By combining two hypoplastic thumbs a sufficient thumb size is acquired. Furthermore, the IP and MCP joints are very stable as the collateral ligaments are not violated during reconstruction. Disadvantages: Violation during reconstruction can lead to growth arrest or asymmetric growth. Nail deformity could also occur after reconstruction. Although the joints are stable, restriction of flexion may be possible. The average IP flexion in a reconstructed thumb is 55 degrees less than the contralateral thumb. MCP flexion averaged 55 degrees in reconstructed thumbs, compared to 75 degrees in the contralateral thumb. Ablation with collateral ligament reconstruction Advantages: The reconstructed joints tend to remain flexible. Also, it preserves the nail bed and physis, this increases the prevention of nail deformities over time. Disadvantages: Although surgeons try to obtain a stable thumb of appropriate size, instability of the IP and MCP joint may occur, as well as a size mismatch. Thumbs are defined as unacceptable if IP joint deviation exceeds 15 degrees, MCP joint deviation exceeds 30 degrees, and thumb size is inappropriate based on the examiners assessment. Also, thumb size one-third greater or less than the contralateral thumb is defined as unacceptable. On-top plasty procedure No surgical outcomes studies exist for evaluating the function of the thumbs after an on-top plasty reconstruction. Central polydactyly Few clinical outcome studies exist regarding the treatment of central polydactyly. Tada and colleagues note that satisfactory surgical correction of central polydactyly is difficult to achieve and that outcomes are generally poor. In Tadas study, 12 patients were reviewed. All patients required secondary surgical procedures to address flexion contractures and angular deviation at the IP joint level. However, several primary factors contribute to the complexity of central polydactyly reconstruction. Hypoplastic joints and soft tissues that predispose the reconstructed finger to joint contracture, and angular deformities as well as complex tendon anomalies, are often difficult to address. Therefore, treatment is wholly dependent on the anatomic components present, the degree of syndactyly, and the function of the duplicated finger. Epidemiology The condition has an estimated occurrence of 0.3–3.6 per 1000 live births. Postaxial hand polydactyly is most frequent in the United States in Black males. Preaxial polydactyly occurs in 0.08 to 1.4 in 1,000 live births. In the United States, it is more common in White people and also relatively frequent in Native American and Asian people. A 1994 study by Finley et al. combined data from Jefferson County, Alabama, United States, and Uppsala County, Sweden. This study found incidence of all types of polydactyly at rates of 2.3 per 1000 live births of White males, 0.6 per 1000 live births of White females, 13.5 per 1000 live births of Black males, and 11.1 per 1000 live births of Black females. Society and culture People with polydactyly Antonio Alfonseca, retired MLB professional baseball pitcher known as "El Pulpo" – Spanish for "the Octopus" with regard to his extra digit on each extremity. Endre Ady, Hungarian poet born with six fingers, but one was removed as a child. The poet later interpreted it as a sign of his selection (according to the ancient Hungarian belief, the táltos are born with more bones, such as six fingers). Brites de Almeida, a legendary Portuguese woman who killed seven hiding Castilian soldiers in her oven after the Battle of Aljubarrota, had six fingers on each hand. The actress Gemma Arterton was born with six fingers on each hand, the additional fingers being removed after birth. Anne Boleyn, former Queen of England, was rumoured to have six fingers on one hand. However, considering that this rumour first emerged in the 1580s from a Catholic dissenter, it is generally deemed false. Robert Chambers, purported author of Vestiges of the Natural History of Creation, and his brother William had six digits on each limb. Lucille Clifton, an African-American poet and civil rights advocate. Zerah Colburn, American prodigious math calculating savant. Calvin Choy, a Hong Konger singer and actor nicknamed "Sir One One" (Sir11) as he has six digits on his right hand. Several members of a Da Silva family in São Paulo, Brazil, have two thumbs on each hand. Vicente Fox, former President of Mexico, has six toes on each foot. Danny Garcia, boxing champion, has six toes on his right foot. Yoandri Hernández Garrido, nicknamed "Veinticuatro" ("twenty four" in Spanish), has six fully formed fingers on both hands and six perfect toes on each foot. Hampton Hawes, jazz pianist, was born with six fingers on each hand (the extra fingers were surgically removed shortly after birth). Henry II the Pious, High Duke of Poland 1238–1241, had six toes on his left foot. A boy named Hong Hong born in Pingjiang County, Hunan province, China, has 31 fingers and toes. Kamani Hubbard, a boy in California was born in 2009 with a rare case of polydactyly, with 12 fingers and 12 toes, all fully functional. Johann Jacob Freiherr von Moscon (1621–1661), Lower Styrian baron, is depicted with six fingers at his left hand on a portrait from Brežice, Slovenia. Jiang Qing, Mao Zedongs fourth wife, reportedly had six toes on her right foot. Hrithik Roshan, a Bollywood actor born with a supernumerary thumb on his right hand. Nayanthara, an Indian actress who is a polydactyl, with a rudimentary finger on her left hand. Akshat Saxena from Uttar Pradesh, India is the world record holder for highest number of digits. He was born in 2010 with seven digits on each hand and 10 digits on each foot, for a total of 34 digits. Garfield Sobers, West Indian cricketer, had an extra finger on each hand which he removed himself during childhood "with the aid of catgut and a sharp knife". Theodore Roosevelt "Hound Dog" Taylor, American Chicago-based blues guitarist, was born with polydactyly on both hands, although around age 41, he removed the extra finger on his right hand. Varalakshmi V, a girl from Bangalore with eight fingers on each hand and about four to five extra toes on each foot. Volcacius Sedigitus, a Roman poet of the 1st century, probably received his epithet, signifying "Sixfinger", because he was born with six fingers on each hand, according to Pliny, Zhu Yunming, a Chinese calligrapher, had six fingers on his right hand. Reggy B, a drag queen and contestant on the second season of Drag Race Holland, revealed on the show that she was born with an extra thumb on her left hand, three extra toes on one foot, and two extra toes on her other foot. Her extra fingers and toes were surgically removed at a young age. Ish Madon (איש מדון), a biblical Philistean figure who fought against King Davids army. The Bible mentions he was a relative to Goliath. Fictional people In The Silence of the Lambs, Hannibal Lecter is described as having mid-ray duplication polydactyly (a duplicated middle finger) on his left hand, which he later removes in Hannibal as part of his cosmetic surgery to disguise himself. In the cartoon series Gravity Falls, Stanford
Polydactyly	Pines ("Grunkle Ford") has six fingers on both of his hands, a trait which also identifies him in the shows mythology. Tyrone Rugen, a Count in The Princess Bride, is described many times as the "six-fingered man." Void, an antagonist of the manga series Berserk, has six fingers on each hand. Billy, a character from Adventure Time had six fingers on each hand. Other animals Polydactyly occurs in numerous types of animals. The condition is sporadically seen in livestock, where it affects cattle, sheep, pigs, and occasionally horses. Conversely, it is a common trait in several heritage chicken breeds. Chickens normally have 4 toes on each foot. The chicken breeds known for being polydactyl are the Dorking, Faverolle, Houdan, Lincolnshire Buff, Meusienne, Sultan, and non-bearded Silkie Bantams. The breed standard of these varieties of chickens calls for five toes on each foot, although sometimes more than five toes will occur. The extra digit in these breeds presents as an extra "thumb" that does not touch the ground. Mixed-breed chickens may also have extra digits if the aforementioned breeds are part of their genetic makeup.Polydactyly also occurs in dogs, cats, and small mammals such as guinea pigs and mice. Cats normally have five digits on the front paws and four on the rear. Polydactyl cats have more, and this is a moderately common condition, especially in certain cat populations. Dogs, like other canids, normally have four claws on their rear paws; a fifth is often called a dewclaw and is especially found in certain dog breeds, including the Norwegian Lundehund and Great Pyrenees. A number of mutations of the LMBR1 gene, in dogs, humans, and mice, can cause polydactyly. A 2014 report indicated that mice could also exhibit polydactyly arising from mutation in the VPS25 gene. In cattle, it appears to be polygenic with a dominant gene at one locus and a homozygous recessive at another.Polydactyly was believed to be common in early tetrapods, the extinct amphibians that represented the earliest landliving vertebrates. Their number of toes fluctuated until the early Carboniferous period when they finally began developing a uniform number of toes. Amniotes settled on five toes per limb, while amphibians developed four toes on each front limb and five toes on each back limb. (For more information, see Polydactyly in early tetrapods). Polydactyly also occurs in modern extant reptiles and amphibians. Polydactyly was a non-pathological, reacquired condition in extinct marine reptiles such as ichthyosaurs and hupehsuchians, some of which containing upwards of ten digits within their flippers. References == External links ==
Right ventricular hypertrophy	Right ventricular (RVH) is a condition defined by an abnormal enlargement of the cardiac muscle surrounding the right ventricle. The right ventricle is one of the four chambers of the heart. It is located towards the lower-end of the heart and it receives blood from the right atrium and pumps blood into the lungs. Since RVH is an enlargement of muscle it arises when the muscle is required to work harder. Therefore, the main causes of RVH are pathologies of systems related to the right ventricle such as the pulmonary artery, the tricuspid valve or the airways. RVH can be benign and have little impact on day-to-day life or it can lead to conditions such as heart failure, which has a poor prognosis. Signs and symptoms Symptoms Although presentations vary, individuals with right ventricular hypertrophy can experience symptoms that are associated with pulmonary hypertension, heart failure and/or a reduced cardiac output. These include: Difficulty breathing on exertion Chest pain (angina) on exertion Fainting (syncope) on exertion General fatigue/lethargy Dizziness Feeling of fullness in the upper abdominal area Discomfort or pain in the right upper abdomen Reduced appetite Swelling (oedema) of the legs, ankles or feet Racing heart beat (palpitations)People may rarely present with the symptoms of Ortners syndrome, which include cough, haemoptysis and hoarseness. Signs On physical examination, the most prominent features are due to the development of right-sided heart failure. These can include a raised jugular venous pressure, ascites, left parasternal heave and a tender, enlarged liver on palpation. On inspection, patients may be chronically ill, cyanotic, cachectic and occasionally jaundiced.On auscultation, an accentuated second pulmonary sound (S2), a third heart sound termed a ‘right ventricular gallop’, as well as a systolic murmur over the tricuspid area accentuated by inspiration may be present. On occasion, the systolic murmur can be transmitted and auscultated over the liver. Less typically, diastolic murmur may also be heard as a result of pulmonary insufficiency. Causes RVH usually occurs due to chronic lung disease or structural defects in the heart. One of the most common causes of RVH is pulmonary hypertension (PH), defined as increased blood pressure in the vessels supplying blood to the lungs. PH leads to increased pulmonary artery pressure. The right ventricle tries to compensate for this increased pressure by changing its shape and size. Hypertrophy of individual myocytes results in an increase in right ventricular wall thickness. The worldwide incidence of PH is 4 per million people. RVH occurs in approximately 30% of these cases.PH is broadly split into five categories by the World Health Organization, based on the underlying cause. The incidence of RVH varies between the groups. Common causes of PH include chronic obstructive pulmonary disease (COPD), pulmonary embolism, and other restrictive lung diseases. RVH often occurs as a result of these disorders. RVH is seen in 76% of patients with advanced COPD and 50% of patients with restrictive lung disease.RVH also occurs in response to structural defects in the heart. One common cause is tricuspid insufficiency. This is a disorder where the tricuspid valve fails to close properly, allowing backward flow of blood. Other structural defects which lead to RVH include tetralogy of Fallot, ventricular septal defects, pulmonary valve stenosis, and atrial septal defects. RVH is also associated with abdominal obesity, elevated fasting blood glucose, high systolic blood pressure, and fractional shortening of the left ventricular mid-wall.Other risk factors for RVH include smoking, sleep apnea, and strenuous activity. These increase the risk of heart and lung disease and hence RVH. Pathophysiology Right ventricular hypertrophy can be both a physiological and pathophysiological process. It becomes pathophysiological (damaging) when there is excessive hypertrophy. The pathophysiological process mainly occurs through aberrant signalling of the neuroendocrine hormones; angiotensin II, endothelin-1 and the catecholamines (e.g. noradrenaline). Angiotensin-II and endothelin-1 Angiotensin-II and endothelin-1 are hormones that bind to the angiotensin (AT) and endothelin (ET) receptors. These are G-protein coupled receptors that act via internal signalling pathways. Through several intermediates, these pathways directly or indirectly increase reactive oxygen species (ROS) production causing accumulation in myocardial cells. This can subsequently induce necrotic cell death, fibrosis, and mitochondrial dysfunction.This has been demonstrated in animal studies. Protein Kinase C (PKC) is an intermediate molecule in the signalling pathway and mice lacking PKC shown resistance to heart failure compared to mice overexpressing PKC which shown heart dysfunction.Targeting the renin–angiotensin (RAAS) system (using angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers) are a well-recognized clinical approach for reversing maladaptive cardiac hypertrophy independently of blood pressure. Catecholamines Catecholamines levels increase due to increased sympathetic nervous system activity. Catecholamines can act on the alpha-adrenergic receptors and beta-adrenergic receptors which are G-protein coupled receptors. This binding initiates the same intracellular signalling pathways as angiotensin and endothelin. There is also activation of cAMP and an increase in intracellular Ca2+ which leads to contractile dysfunction and fibrosis. Others Hormones are not the only cause of RVH. Hypertrophy can also be caused by mechanical forces, mTOR pathways, nitric oxide and immune cells. Immune cells can cause hypertrophy by inducing inflammation. Diagnosis The two main diagnostic tests used to confirm right ventricular hypertrophy are electrocardiography and echocardiography. Electrocardiography The use of electrocardiogram (ECG) to measure cardiac chamber hypertrophy is well established but since the left ventricular activity is dominant on the ECG a large degree of RVH is often required for any detectable changes. Nonetheless, the ECG is used to assist with the diagnosis of RVH. A post mortem study on 51 adult male patients concluded that anatomical RVH may be diagnosed using one or more of the following ECG criteria: Right axis deviation of more than (or equal to) 110° (see hexaxial reference figure) R-wave dominant over S-wave in V1 or V2 S-wave dominant over R-wave in V6However, the American Heart Association recommended the use of additional diagnostic tests to diagnose RVH because no single criteria or set of criteria were considered sufficiently reliable. Echocardiography Echocardiography can be used to directly visualise right ventricular wall thickness. The preferred technique is the trans-oesophageal approach giving a view of 4 chambers. The normal thickness of a right ventricular free wall ranges from 2-5 millimetres, with a value above 5 mm considered to be hypertrophic. Treatment It is important to understand that right ventricular hypertrophy in itself is not the main issue, but what right ventricular hypertrophy represents is. Right ventricular hypertrophy is the intermediate stage between increased right ventricular pressure (in the early stages) and right ventricle failure (in the later stages). As such, management of right ventricular hypertrophy is about either preventing the development of right ventricular hypertrophy in the first place, or preventing the progression towards right ventricle failure. Right ventricular hypertrophy in itself has no (pharmacological) treatment. Treating the cause Since the main causes of right ventricular hypertrophy is tricuspid regurgitation or pulmonary hypertension (discussed above), management involves treatment of these conditions. Tricuspid regurgitation is typically treated conservatively by aiming to treat the underlying cause and following up the patient regularly. Surgery is considered in more serious situations where the patient is severely symptomatic. Surgical options include either: replacement of the valve or repair of the valve (termed annuloplasty). When it comes to replacement, there is a choice between a bioprosthetic valve or a mechanical valve, depending upon the specific patient characteristics. Mechanical valve has greater durability, but requires anti-coagulation to reduce the risk of thrombosis. Treatment of pulmonary hypertension will depend on the specific cause of the pulmonary hypertension. On top of this, the following may also be considered: diuretic, oxygen and anti-coagulant therapy. Managing the complications After a prolonged period, the right ventricle fails to adapt sufficiently to pump against increased right ventricle pressure, which is termed right ventricular failure. This right ventricular failure is the main complication of right ventricular hypertrophy. The mechanisms underlying the progression from hypertrophy to failure is not well understood, and the best management approach involves reducing/minimising the risk factors of progression. Lifestyle changes can often help to reduce the risk of this progression. Lifestyle changes include: eating less salty food as salt consumption leads to greater fluid retention by the body; smoking cessation; avoiding excessive alcohol consumption as alcohol reduces the force of heart contractions. Once right ventricular hypertrophy progresses to right ventricular failure, the treatment becomes that of heart failure. Briefly, this includes the use of: Diuretics 3 ACEi Beta Blockers Aldosterone Antongists Cardiac glycosides Vasodilators References External links 02004 at CHORUS
Galactosemia	Galactosemia (British galactosaemia, from Greek γαλακτόζη + αίμα, meaning galactose + blood, accumulation of galactose in blood) is a rare genetic metabolic disorder that affects an individuals ability to metabolize the sugar galactose properly. Galactosemia follows an autosomal recessive mode of inheritance that confers a deficiency in an enzyme responsible for adequate galactose degradation. Friedrich Goppert (1870–1927), a German physician, first described the disease in 1917, with its cause as a defect in galactose metabolism being identified by a group led by Herman Kalckar in 1956. Galactosemia was the second disorder found to be detectable through newborn screening methods by Robert Guthrie.Its incidence is about 1 per 60,000 births for people of European ancestry. In other populations the incidence rate differs. Galactosaemia is about one hundred times more common (1:480 births) in the Irish Traveller population. Symptoms Adults Infants Infants may appear asymptomatic at birth, however, upon ingestion of galactose a few days later (via breast and/or formula feeding), children start to experience life-threatening symptoms, which include: poor feeding, and weight gain vomiting and diarrhea hepatocellular damage lethargy, and hypotoniaProgression of this acute neonatal toxicity syndrome may include the development of sepsis, cataracts, and even pseudotumor cerebri (which may cause a bulging of fontanelle). Cause Lactose in food (such as dairy products) is broken down by the enzyme lactase into glucose and galactose. In individuals with galactosemia, the enzymes needed for further metabolism of galactose (Galactokinase and galactose-1-phosphate uridyltransferase) are severely diminished or missing entirely, leading to toxic levels of galactose or galactose 1-phosphate (depending on which enzyme is missing) in various tissues as in the case of classic galactosemia, resulting in hepatomegaly (an enlarged liver), cirrhosis, kidney failure, cataracts, vomiting, seizure, low blood sugar (hypoglycemia), lethargy, brain damage, and ovarian failure. Without treatment, mortality in infants with galactosemia is about 75%.Galactosemia is inherited in an autosomal recessive manner, meaning a child must inherit one defective gene from each parent to show the disease. Heterozygotes are carriers, because they inherit one normal gene and one defective gene. Carriers show no symptoms of galactosemia. Accumulation of galactose Reduction to galactitol In galactosemic patients, the accumulation of galactose becomes the substrate for enzymes that catalyze the polyol pathway of carbohydrate metabolism. The first reaction of this pathway is the reduction of aldoses, types of sugars including galactose, to sugar alcohols. Recent data suggests that aldose reductase is the enzyme responsible for the primary stage of this pathway. Therefore, aldose reductase reduces galactose to its sugar alcohol form, galactitol. Galactitol, however, is not a suitable substrate for the next enzyme in the polyol pathway, polyol dehydrogenase. Thus, galactitol accumulates in body tissues and is excreted in the urine of galactosemic patients. Accumulation of galactitol has been attributed to many of the negative effects of galactosemia, and high concentrations of galactitol have been found in people with classic galactosemia (GALT deficiency or Galactose-1-phosphate uridylyltransferase deficiency), galactokinase deficiency, and epimerase deficiency with glucose. Oxidation to galactonate Accumulated galactose can also undergo an alternative reaction: Oxidation to galactonate. The mechanism of galactonate formation is still unclear. However, recent studies suggest that galactose dehydrogenase is responsible for converting galactose to galactonolactone, which then spontaneously or enzymatically converts to galactonate. Once formed, galactonate may enter the pentose phosphate pathway. Thus, Oxidation to galactonate serves as an alternate pathway for metabolizing galactose. This oxidative pathway renders accumulated galactonate less harmful than accumulated galactitol. Diagnosis In many states throughout the world, infants routinely undergo newborn screening (NBS) for galactosemia. This allows a diagnosis to be made while the person is still an infant. Infants affected by galactosemia typically present with symptoms of lethargy, vomiting, diarrhea, failure to thrive, and jaundice. None of these symptoms are specific to galactosemia, often leading to diagnostic delays. If the family of the baby has a history of galactosemia, doctors can test prior to birth by taking a sample of fluid from around the fetus (amniocentesis) or from the placenta (chorionic villus sampling or CVS). Galactosemia is normally first detected through newborn screening which if available, is able to diagnose the majority of affected infants. A galactosemia test is a blood test (from the heel of the infant) or urine test that checks for three enzymes that are needed to change galactose sugar that is found in milk and milk products into glucose, a sugar that the human body uses for energy. A person with galactosemia doesnt have one of these enzymes. This causes high levels of galactose in the blood or urine.Affected children can have serious, irreversible effects or even die within days from birth. It is important that newborns be screened for metabolic disorders without delay. Galactosemia can even be detected through NBS before any ingestion of galactose-containing formula or breast milk. Detection of the disorder through NBS does not depend on protein or lactose ingestion, and, therefore, it should be identified on the first specimen unless the infant has been transfused. A specimen should be taken prior to transfusion. The enzyme is prone to damage if analysis of the sample is delayed or exposed to high temperatures. The routine NBS is accurate for detection of galactosemia. Two screening tests are used to screen infants affected with galactosemia—the Beutlers test and the Hill test. The Beutlers test screens for galactosemia by detecting the level of enzyme of the infant. Therefore, the ingestion of formula or breast milk does not affect the outcome of this part of the NBS, and the NBS is accurate for detecting galactosemia prior to any ingestion of galactose. Duarte galactosemia is a milder form of classical galactosemia and usually has no long term side effects. Types Galactose is converted into glucose by the action of three enzymes, known as the Leloir pathway. There are diseases associated with deficiencies of each of these three enzymes: Treatment The only treatment for classic galactosemia is eliminating lactose and galactose from the diet (e.g. exclusion of dairy products containing lactose).Lactose restricted diet is efficient in resolving acute complications, however, it is not sufficient to prevent long-term complications affecting the brain and female gonads. Some individuals may experience long-term complications such as speech difficulties, learning disabilities, neurological impairment (e.g. tremors, etc.), and ovarian failure.Symptoms that have not been associated with Duarte galactosemia, and many individuals with Duarte galactosemia do not need to restrict their diet at all. However, research corroborates a previously overlooked theory that Duarte galactosemia may lead to language developmental issues in children with no clinical symptoms. Infants with classic galactosemia cannot be breast-fed due to lactose in human breast milk which consists of both galactose and glucose and are usually fed a soy-based formula.Galactosemia is sometimes confused with lactose intolerance, but galactosemia is a more serious condition. Lactose intolerant individuals have an acquired or inherited shortage of the enzyme lactase, and experience abdominal pains after ingesting dairy products, but no long-term effects. In contrast, a galactosemic individual who consumes galactose can cause permanent damage to their bodies.Long term complication of galactosemia includes: Speech deficits Ataxia Dysmetria Diminished bone density Premature ovarian failure Cataract See also Galactosemic cataract Other Inborn errors of carbohydrate metabolism References == External links ==
Receptive aphasia	Wernickes aphasia, also known as receptive aphasia, sensory aphasia or posterior aphasia, is a type of aphasia in which individuals have difficulty understanding written and spoken language. Patients with Wernickes aphasia demonstrate fluent speech, which is characterized by typical speech rate, intact syntactic abilities and effortless speech output. Writing often reflects speech in that it tends to lack content or meaning. In most cases, motor deficits (i.e. hemiparesis) do not occur in individuals with Wernickes aphasia. Therefore, they may produce a large amount of speech without much meaning. Individuals with Wernickes aphasia are typically unaware of their errors in speech and do not realize their speech may lack meaning. They typically remain unaware of even their most profound language deficits. Like many acquired language disorders, Wernickes aphasia can be experienced in many different ways and to many different degrees. Patients diagnosed with Wernickes aphasia can show severe language comprehension deficits; however, this is dependent on the severity and extent of the lesion. Severity levels may range from being unable to understand even the simplest spoken and/or written information to missing minor details of a conversation. Many diagnosed with Wernickes aphasia have difficulty with repetition in words and sentences and/or working memory.Wernickes aphasia was named after German physician Carl Wernicke, who is credited with discovering the area of the brain responsible for language comprehension (Wernickes area). Signs and symptoms The following are common symptoms seen in patients with Wernickes aphasia: Impaired comprehension: deficits in understanding (receptive) written and spoken language. This is because Wernickes area is responsible for assigning meaning to the language that is heard, so if it is damaged, the brain cannot comprehend the information that is being received. Poor word retrieval: ability to retrieve target words is impaired. This is also referred to as anomia. Fluent speech: individuals with Wernickes aphasia do not have difficulty with producing connected speech that flows. Although the connection of the words may be appropriate, the words they are using may not belong together or make sense (see Production of jargon below). Production of jargon: speech that lacks content, consists of typical intonation, and is structurally intact. Jargon can consist of a string of neologisms, as well as a combination of real words that do not make sense together in context. The jargon may include word salads. Awareness: Individuals with Wernickes aphasia are often not aware of their incorrect productions, which would further explain why they do not correct themselves when they produce jargon, paraphasias, or neologisms. Paraphasias:Phonemic (literal) paraphasias: involves the substitution, addition, or rearrangement of sounds so that an error can be defined as sounding like the target word. Often, half of the word is still intact which allows for easy comparison to the appropriate, original word. E.g. "bap" for "map" Semantic (verbal) paraphasias: saying a word that is related to the target word in meaning or category; frequently observed in Wernickes aphasia. E.g. "jet" for "airplane" or "knife" for "fork" Neologisms: nonwords that have no relation to the target word.E.g. "dorflur" for "shoe" Circumlocution: talking around the target word.E.g. "uhhh its white... its flat... you write on it..." (when referencing paper) Press of speech: run-on speech.If a clinician asks, "what do you do at a supermarket?" And the individual responds with "Well, the supermarket is a place. It is a place with a lot of food. My favorite food is Italian food. At a supermarket, I buy different kinds of food. There are carts and baskets. Supermarkets have lots of customers, and workers..." Lack of hemiparesis: typically, no motor deficits are seen with a localized lesion in Wernickes area. Reduced retention span: reduced ability to retain information for extended periods of time. Impairments in reading and writing: impairments can be seen in both reading and writing with differing severity levels.How to differentiate from other types of aphasia Expressive aphasia (non-fluent Brocas aphasia): individuals have great difficulty forming complete sentences with generally only basic content words (leaving out words like "is" and "the"). Global aphasia: individuals have extreme difficulties with both expressive (producing language) and receptive (understanding language). Anomic aphasia: the biggest hallmark is ones poor word-finding abilities; ones speech is fluent and appropriate, but full of circumlocutions (evident in both writing and speech). Conduction aphasia: individuals can comprehend what is being said and are fluent in spontaneous speech, but they cannot repeat what is being said to them. Causes The most common cause of Wernickes aphasia is stroke. Strokes may occur when blood flow to the brain is completely interrupted or severely reduced. This has a direct effect on the amount of oxygen and nutrients being able to supply the brain, which causes brain cells to die within minutes."The middle cerebral arteries supply blood to the cortical areas involved in speech, language and swallowing. The left middle cerebral artery provides Brocas area, Wernickes area, Heschls gyrus, and the angular gyrus with blood". Therefore, in patients with Wernickes aphasia, there is typically an occlusion to the left middle cerebral artery.As a result of the occlusion in the left middle cerebral artery, Wernickes aphasia is most commonly caused by a lesion in the posterior superior temporal gyrus (Wernickes area). This area is posterior to the primary auditory cortex (PAC) which is responsible for decoding individual speech sounds. Wernickes primary responsibility is to assign meaning to these speech sounds. The extent of the lesion will determine the severity of the patients deficits related to language. Damage to the surrounding areas (perisylvian region) may also result in Wernickes aphasia symptoms due to variation in individual neuroanatomical structure and any co-occurring damage in adjacent areas of the brain. Diagnosis Aphasia is usually first recognized by the physician who treats the person for his or her brain injury. Most individuals will undergo a magnetic resonance imaging (MRI) or computed tomography (CT) scan to confirm the presence of a brain injury and to identify its precise location. In circumstances where a person is showing possible signs of aphasia, the physician will refer him or her to a speech-language pathologist (SLP) for a comprehensive speech and language evaluation. SLPs will examine the individuals ability to express him or herself through speech, understand language in written and spoken forms, write independently, and perform socially.The American Speech, Language, Hearing Association (ASHA) states a comprehensive assessment should be conducted in order to analyze the patients communication functioning on multiple levels; as well as the effect of possible communication deficits on activities of daily living. Typical components of an aphasia assessment include: case history, self report, oral-motor examination, language skills, identification of environmental and personal factors, and the assessment results. A comprehensive aphasia assessment includes both formal and informal measures.Formal assessments include: Boston Diagnostic Aphasia Examination (BDAE): diagnoses the presence and type of aphasia, focusing on location of lesion and the underlying linguistic processes. Western Aphasia Battery – Revised (WAB): determines the presence, severity, and type of aphasia; and can also determine baseline abilities of patient. Communication Activities of Daily Living - Second Edition (CADL-2): measures functional communication abilities; focuses on reading, writing, social interactions, and varying levels of communication. Revised Token Test (RTT): assess receptive language and auditory comprehension; focuses on patients ability to follow directions.Informal assessments, which aid in the diagnosis of patients with suspected aphasia, include: Conversational speech and language sample Family interview Case history or medical chart review Behavioral observationsDiagnostic information should be scored and analyzed appropriately. Treatment plans and individual goals should be developed based on diagnostic information, as well as patient and caregiver needs, desires, and priorities. Treatment According to Bates et al. (2005), "the primary goal of rehabilitation is to prevent complications, minimize impairments, and maximize function". The topics of intensity and timing of intervention are widely debated across various fields. Results are contradictory: some studies indicate better outcomes with early intervention, while other studies indicate starting therapy too early may be detrimental to the patients recovery. Recent research suggests, that therapy be functional and focus on communication goals that are appropriate for the patients individual lifestyle.Specific treatment considerations for working with individuals with Wernickes aphasia (or those who exhibit deficits in auditory comprehension) include using familiar materials, using shorter and slower utterances when speaking, giving direct instructions, and using repetition as needed. Role of neuroplasticity in recovery Neuroplasticity is defined as the brains ability to reorganize itself, lay new pathways, and rearrange existing ones, as a result of experience. Neuronal changes after damage to the brain such as collateral sprouting, increased activation of the homologous areas, and map extension demonstrate the brains neuroplastic abilities. According to Thomson, "Portions of the right hemisphere, extended left brain sites, or both have been shown to be recruited to perform language functions after brain damage. All of the neuronal changes recruit areas not originally or directly responsible for large portions of linguistic processing. Principles of neuroplasticity have been proven effective in neurorehabilitation after damage to the brain. These principles include: incorporating multiple modalities into treatment to create stronger neural connections, using stimuli that evoke positive emotion, linking concepts with simultaneous and related presentations, and finding the appropriate intensity and duration of treatment for each individual patient. Auditory comprehension treatment Auditory comprehension is a primary focus in treatment for Wernickes aphasia, as it is the main deficit related to this diagnosis. Therapy activities may include: Single-word comprehension: A common treatment method used to support single-word comprehension skills is known as a pointing drill. Through this method, clinicians lay out a variety of images in front of a patient. The patient is asked to point to the image that corresponds to the word provided by the clinician. Understanding spoken sentences: "Treatment to improve comprehension of spoken sentences typically consists of drills in which patients answer questions, follow directions or verify the meaning of sentences". Understanding conversation: An effective treatment method to support comprehension of discourse includes providing a patient with a conversational sample and asking him or her questions about that sample. Individuals with less severe deficits in auditory comprehension may also be able to retell aspects of the conversation. Word retrieval Anomia is consistently seen in aphasia, so many treatment techniques aim to help patients with word finding problems. One example of a semantic approach is referred to as semantic feature analyses. The process includes naming the target object shown in the picture and producing words that are semantically related to the target. Through production of semantically similar features, participants develop more skilled in naming stimuli due to the increase in lexical activation. Restorative therapy approach Neuroplasticity is a central component to restorative therapy to compensate for brain damage. This approach is especially useful in Wernickes aphasia patients that have had a stroke to the left brain hemisphere.Schuells stimulation approach is a main method in traditional aphasia therapy that follows principles to retrieve function in the auditory modality of language and influence surrounding regions through stimulation. The guidelines to have the most effective stimulation are as follows: Auditory stimulation of language should be intensive and always present when other language modalities are stimulated. The stimulus should be presented at a difficulty level equal to or just below the patients ability. Sensory stimulation must be present and repeated throughout the treatment. Each stimulus applied should produce a response; if there is no response more stimulation cues should be provided. Response to stimuli should be maximized to create more opportunities for success and feedback for the speech-language pathologist. The feedback of the speech-language pathologist should promote further success and patient and encouragement. Therapy should follow an intensive and systemic method to create success by progressing in difficulty. Therapies should be varied and build off of mastered therapy tasks.Schuells stimulation utilizes stimulation through therapy tasks beginning at a simplified task and progressing to become more difficult including: Point to tasks. During these tasks the patient is directed to point to an object or multiple objects. As the skill is learned the level of complexity increases by increasing the number of objects the patient must point to.Simple: "Point to the book." Complex: "Point to the book and then to the ceiling after touching your ear." Following directions with objects. During these tasks the patient is instructed to follow the instruction of manually following directions that increase in complexity as the skill is learned.Simple: "Pick up the book." Complex: "Pick up the book and put it down on the bench after I move the cup." Yes or no questions – This task requires the patient to respond to various yes or no questions that can range from simple to complex.Paraphrasing and retelling – This task requires the patient to read a paragraph and, afterwards, paraphrase it aloud. This is the most complex of Schuells stimulation tasks because it requires comprehension, recall, and communication. Social approach to treatment The social approach involves a collaborative effort on behalf of patients and clinicians to determine goals and outcomes for therapy that could improve the patients quality of life. A conversational approach is thought to provide opportunities for development and the use of strategies to overcome barriers to communication. The main goals of this treatment method are to improve the patients conversational confidence and skills in natural contexts using conversational coaching, supported conversations, and partner training. Conversational coaching involves patients with aphasia and their speech language pathologists, who serve as a "coach" discussing strategies to approach various communicative scenarios. The "coach" will help the patient develop a script for a scenario (such as ordering food at a restaurant), and help the patient practice and perform the scenario in and out of the clinic while evaluating the outcome. Supported conversation also involves using a communicative partner who supports the patients learning by providing contextual cues, slowing their own rate of speech, and increasing their messages redundancy to promote the patients comprehension.Additionally, it is important to include the families of patients with aphasia in treatment programs. Clinicians can teach family members how to support one another, and how to adjust their speaking patterns to facilitate their loved ones treatment and rehabilitation. Prognosis Prognosis is strongly dependent on the location and extent of the lesion (damage) to the brain. Many personal factors also influence how a person will recover, which include age, previous medical history, level of education, gender, and motivation. All of these factors influence the brains ability to adapt to change, restore previous skills, and learn new skills. It is important to remember that all the presentations of Receptive Aphasia may vary. The presentation of symptoms and prognosis are both dependent on personal components related to the individuals neural organization before the stroke, the extent of the damage, and the influence of environmental and behavioral factors after the damage occurs. The quicker a diagnosis of a stroke is made by a medical team, the more positive the patients recovery may be. A medical team will work to control the signs and symptoms of the stroke and rehabilitation therapy will begin to manage and recover lost skills. The rehabilitation team may consist of a certified speech-language pathologist, physical therapist, occupational therapist, and the family or caregivers. The length of therapy will be different for everyone, but research suggests that intense therapy over a short amount of time can improve outcomes of speech and language therapy for patients with aphasia. Research is not suggesting the only way therapy should be administered, but gives insight on how therapy affects the patients prognosis. See also Agraphia Logorrhea (psychology) Paragrammatism References Further reading Klein, Stephen B., and Thorne. Biological Psychology. New York: Worth, 2007. Print. Saladin, Kenneth S. Anatomy & Physiology: the Unity of Form and Function. New York: McGraw-Hill Higher Education, 2010. Print. == External links ==
Ocular dysmetria	Ocular dysmetria is a form of dysmetria that involves the constant under- or over-shooting of the eyes when attempting to focus gaze on something.Ocular dysmetria indicates lesions in the cerebellum, which is the brain region responsible for coordinating movement. It is a symptom of several neurological conditions including multiple sclerosis. It is a condition that can cause symptoms similar to sea sickness. == References ==

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