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Spinocerebellar ataxia	Spinocerebellar ataxia (SCA) is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a neurological condition in its own right. An estimated 150,000 people in the United States have a diagnosis of spinocerebellar ataxia at any given time. SCA is hereditary, progressive, degenerative, and often fatal. There is no known effective treatment or cure. SCA can affect anyone of any age. The disease is caused by either a recessive or dominant gene. In many cases people are not aware that they carry a relevant gene until they have children who begin to show signs of having the disorder. Signs and symptoms Spinocerebellar ataxia (SCA) is one of a group of genetic disorders characterized by slowly progressive incoordination of gait and is often associated with poor coordination of hands, speech, and eye movements. A review of different clinical features among SCA subtypes was recently published describing the frequency of non-cerebellar features, like parkinsonism, chorea, pyramidalism, cognitive impairment, peripheral neuropathy, seizures, among others. As with other forms of ataxia, SCA frequently results in atrophy of the cerebellum, loss of fine coordination of muscle movements leading to unsteady and clumsy motion, and other symptoms. The symptoms of an ataxia vary with the specific type and with the individual patient. In many cases a person with ataxia retains full mental capacity but progressively loses physical control. Cause The hereditary ataxias are categorized by mode of inheritance and causative gene or chromosomal locus. The hereditary ataxias can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Many types of autosomal dominant cerebellar ataxias for which specific genetic information is available are now known. Synonyms for autosomal-dominant cerebellar ataxias (ADCA) used prior to the current understanding of the molecular genetics were Maries ataxia, inherited olivopontocerebellar atrophy, cerebello-olivary atrophy, or the more generic term "spinocerebellar degeneration." (Spinocerebellar degeneration is a rare inherited neurological disorder of the central nervous system characterized by the slow degeneration of certain areas of the brain. There are three forms of spinocerebellar degeneration: Types 1, 2, 3. Symptoms begin during adulthood.) There are five typical autosomal-recessive disorders in which ataxia is a prominent feature: Friedreich ataxia, ataxia-telangiectasia, ataxia with vitamin E deficiency, ataxia with oculomotor apraxia (AOA), spastic ataxia. Disorder subdivisions: Friedreichs ataxia, Spinocerebellar ataxia, Ataxia telangiectasia, Vasomotor ataxia, Vestibulocerebellar, Ataxiadynamia, Ataxiophemia, and Olivopontocerebellar atrophy. There have been reported cases where a polyglutamine expansion may lengthen when passed down, which often can result in an earlier age-of-onset and a more severe disease phenotype for individuals who inherit the disease allele. This falls under the category of genetic anticipation. Several types of SCA are characterized by repeat expansion of the trinucleotide sequence CAG in DNA that encodes a polyglutamine repeat tract in protein. The expansion of CAG repeats over successive generations appears to be due to slipped strand mispairing during DNA replication or DNA repair. Diagnosis Classification A few SCAs remain unspecified and can not be precisely diagnosed, but in the last decade genetic testing has allowed precise identification of dozens of different SCAs and more tests are being added each year. In 2008, a genetic ataxia blood test developed to test for 12 types of SCA, Friedreichs ataxia, and several others. However, since not every SCA has been genetically identified some SCAs are still diagnosed by neurological examination, which may include a physical exam, family history, MRI scanning of the brain and spine, and spinal tap.Many SCAs below fall under the category of polyglutamine diseases, which are caused when a disease-associated protein (i.e., ataxin-1, ataxin-3, etc.) contains a large number of repeats of glutamine residues, termed a polyQ sequence or a "CAG trinucleotide repeat" disease for either the one-letter designation or codon for glutamine respectively. The threshold for symptoms in most forms of SCA is around 35, though for SCA3 it extends beyond 50. Most polyglutamine diseases are dominant due to the interactions of resulting polyQ tail.The first ataxia gene was identified in 1993 and called "Spinocerebellar ataxia type 1" (SCA1); later genes were called SCA2, SCA3, etc. Usually, the "type" number of "SCA" refers to the order in which the gene was found. At this time, there are at least 29 different gene mutations that have been found.The following is a list of some of the many types of Spinocerebellar ataxia. Others include SCA18, SCA20, SCA21, SCA23, SCA26, SCA28, and SCA29. Four X-linked types have been described ( 302500, 302600, 301790, 301840), but only the first of these has so far been tied to a gene (SCAX1). Treatment Medication There is no cure for spinocerebellar ataxia, which is currently considered to be a progressive and irreversible disease, although not all types cause equally severe disability.In general, treatments are directed towards alleviating symptoms, not the disease itself. Many patients with hereditary or idiopathic forms of ataxia have other symptoms in addition to ataxia. Medications or other therapies might be appropriate for some of these symptoms, which could include tremor, stiffness, depression, spasticity, and sleep disorders, among others. Both onset of initial symptoms and duration of disease are variable. If the disease is caused by a polyglutamine trinucleotide repeat CAG expansion, a longer expansion may lead to an earlier onset and a more radical progression of clinical symptoms. Typically, a person with this disease will eventually be unable to perform daily tasks (ADLs). However, rehabilitation therapists can help patients to maximize their ability of self-care and delay deterioration to certain extent. Researchers are exploring multiple avenues for a cure including RNAi and the use of Stem Cells and several other avenues.On January 18, 2017, BioBlast Pharma announced completion of Phase 2a clinical trials of their medication, Trehalose, in the treatment of SCA3. BioBlast has received FDA Fast Track status and Orphan Drug status for their treatment. The information provided by BioBlast in their research indicates that they hope this treatment may prove efficacious in other SCA treatments that have similar pathology related to PolyA and PolyQ diseases.In addition, Dr. Beverly Davidson has been working on a methodology using RNAi technology to find a potential cure for over 2 decades. Her research began in the mid-1990s and progressed to work with mouse models about a decade later and most recently has moved to a study with non-human primates. The results from her most recent research "are supportive of clinical application of this gene therapy".Finally, another gene transfer technology discovered in 2011 has also been shown by Boudreau et al. to hold great promise and offers yet another avenue to a potential future cure. N-Acetyl-Leucine N-Acetyl-Leucine is an orally administered, modified amino acid that is being developed as a novel treatment for multiple rare and common neurological disorders by IntraBio Inc (Oxford, United Kingdom).N-Acetyl-Leucine has been granted multiple orphan drug designations from the U.S. Food & Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of various genetic diseases, including Spinocerebellar Ataxias. N-Acetyl-Leucine has also been granted Orphan Drug Designations in the US and EU for the related inherited cerebellar ataxia Ataxia-Telangiectasia U.S. Food & Drug Administration (FDA) and the European Medicines Agency (EMA).Published case series studies have demonstrated the effects of acute treatment with N-Acetyl-Leucine for the treatment of inherited cerebellar ataxias, including Spinocerebellar Ataxias. These studies further demonstrated that the treatment is well tolerated, with a good safety profile. A multinational clinical trial investigating N-Acetyl-L-Leucine for the treatment of a related inherited cerebellar ataxia, Ataxia-Telangiectasia, began in 2019.IntraBio is also conducting parallel clinical trials with N-Acetyl-L-Leucine for the treatment of Niemann-Pick disease type C and GM2 Gangliosidosis (Tay-Sachs and Sandhoff Disease). Future opportunities to develop N-Acetyl-Leucine include Lewy Body Dementia, Amyotrophic lateral sclerosis, Restless Leg Syndrome, Multiple Sclerosis, and Migraine. Rehabilitation Physical therapists can assist patients in maintaining their level of independence through therapeutic exercise programmes. One recent research report demonstrated a gain of 2 SARA points (Scale for the Assessment and Rating of Ataxia) from physical therapy. In general, physical therapy emphasises postural balance and gait training for ataxia patients. General conditioning such as range-of-motion exercises and muscle strengthening would also be included in therapeutic exercise programmes. Research showed that spinocerebellar ataxia 2 (SCA2) patients with a mild stage of the disease gained significant improvement in static balance and neurological indices after six months of a physical therapy exercise training program. Occupational therapists may assist patients with incoordination or ataxia issues through the use of adaptive devices. Such devices may include a cane, crutches, walker, or wheelchair for those with impaired gait. Other devices are available to assist with writing, feeding, and self care if hand and arm coordination are impaired. A randomised clinical trial revealed that an intensive rehabilitation program with physical and occupational therapies for patients with degenerative cerebellar diseases can significantly improve functional gains in ataxia, gait, and activities of daily living. Some level of improvement was shown to be maintained 24 weeks post-treatment. Speech language pathologists may use both behavioral intervention strategies as well as augmentative and alternative communication devices to help patients with impaired speech. References Further reading Nikonishyna, Yuliia V.; et al. (2022). ""Novel CACNA1A Variant p.Cys256Phe Disrupts Disulfide Bonds and Causes Spinocerebellar Ataxia."". Movement Disorders. Movement disorders: official journal of the Movement Disorder Society. 37 (2): 401–404. doi:10.1002/mds.28835. PMID 34647648. S2CID 238859984. External links ataxia at NINDS msa at NINDS opca_doc at NINDS MedlinePlus Encyclopedia: Olivopontocerebellar atrophy Spinocerebellar ataxia 27 at NIHs Office of Rare Diseases Spinocerebellar ataxia dysmorphism at NIHs Office of Rare Diseases
Peri-implant mucositis	Peri-implant mucositis is defined as an inflammatory lesion of the peri-implant mucosa in the absence of continuing marginal bone loss.The American Academy of Periodontology defines peri‐implant mucositis as a disease in which inflammation of the soft tissues surrounding a dental implant is present without additional bone loss after the initial bone remodeling that may occur during healing following the surgical placement of the implant.Peri-implant mucositis is largely accepted as the precursor of peri-implantitis and corresponds to gingivitis around natural teeth.Important criteria to defining peri-implant mucositis are, the inflammation of mucosa surrounding an endosseous implant and the absence of continuing marginal peri-implant bone loss. Aetiology A shift in bacterial biofilm composition, from uninterrupted plaque maturation, and the immune system disintegration causes peri-implant mucosa inflammation to occur. In peri-implant mucositis, there is an increase in proportion of bacteria from the orange complex: F. nucleatum, P. intermedia and Eubacterium species. A decrease in proportion of Streptococci and Actinomoyces species is also observed.Accumulation of bacteria around osseointegrated dental implants has been proven to be a cause of peri-implant mucositis by demonstrating this under experimental conditions and the development of an inflammatory response due to this has also been shown experimentally. When the surfaces of the implant in the mouth are colonised by pathogenic bacteria, plaque-induced inflammation can go on to cause destruction of the tissues around the implant. The presence of an inflammatory cell infiltrate in the connective tissue lateral to the junctional epithelium has been discovered in this condition, contributing to its development. The bacterial biofilm disrupts the host-microbe homeostasis, creating a dysbiosis which results in an inflammatory lesion. The inflammatory cell infiltrate has been found to increase in size as the peri-implant mucositis develops.Where peri-implant mucositis has been brought about by the accumulation of bacteria and their formation of a biofilm, it has been shown to be eventually reversible once the biofilm has been brought under control by regular cleaning by both patient and dental professional. This has been shown as studies display a clear reduction in redness, swelling and bleeding on probing in lesions of the peri-implant soft tissue after bacterial load has been minimised. This was shown in an experiment where bacteria were encouraged to accumulate for a period of time in which no oral hygiene was undertaken, allowing all of the patients to develop peri-implant mucositis. When oral hygiene was regularly commenced once again, all of the periodontal tissues eventually became healthy once more. However, the best management of peri-implant mucositis is not reversing it but preventing this from occurring in the first instance.The presence of excess luting cement has been demonstrated to contribute to causing peri-implant mucositis. One study gleaned results that suggested that in both patients with and without a history of periodontal problems, implants with extracoronal residual cement developed statistically significantly more cases of peri-implant mucositis as well as other periodontal problems. In this study 85% of implants in patients with previous periodontal conditions went on to develop peri-implant mucositis, which then progressed to peri-implantitis. In the group with no previous history of periodontal issues, 65% of implants still developed peri-implant mucositis, but significantly fewer of these implants then developed peri-implantitis. In contrast, the group with no extracoronal residual cement only had 30% of implants develop peri-implant mucositis. Therefore, cement remnants may be more likely to cause patients to develop peri-implant mucositis.Other causal factors of peri-implant mucositis include radiation and smoking, in addition to accretion of oral bacteria at the site. Other factors that are thought to contribute to the condition include lack of keratinised mucosa and diabetes mellitus, particularly poorly-controlled diabetes which will mean the patient will have a high level of blood glucose over longer periods. Understanding and controlling peri-implant mucositis is essential as it often leads to peri-implantitis. Signs and Symptoms Clinical signs and symptoms of peri-implant mucositis involves the localised surrounding gingival tissues (gum tissue) of a dental implant. These include:- Bleeding on probing with no supporting bone loss. Localised swelling Redness/erythema. Increased shininess of soft tissue surface. Soreness Risk Factors Risk Factors of PIM are categorised into General and Local Risk Factors General Risk Factors Smoking Radiation Therapy Poorly controlled Diabetes Mellitus (HbA1c >10.1)Local Risk Factors Oral Hygiene Poor compliance / access to regular supportive implant therapy Design of Implant-supported prostheses affecting accessibility for plaque removal Sub-mucosal restorations Dimension of Keratinized Peri-implant mucosa Excess CementPossible Risk Factors: Some other possible risk factors may include the location the implant is placed, type of implant placed and the age of the subject, as it was found that these factors had significant influences on bleeding on probing (BOP).Although it is uncertain whether increased abutment roughness will cause an increase in plaque accumulation and hence increase the risk of peri-implant mucositis, a 12-month comparative analysis in humans found that “a further reduction of the surface roughness, below a certain "threshold R(a)" (0.2 microns), has no major impact on the supra‐ and subgingival microbial composition.”Implants and abutments made of zirconium dioxide (ZrO2) were claimed to be more bio-compatible compared to those made of titanium but clinical studies show that there were slightly higher BOP scores or no significant difference in BOP scores around ZrO2 compared to titanium abutments. Diagnosis In order to diagnose peri-implant mucositis, it is essential to investigate probing parameters and complete a radiographic assessment. Correct diagnosis of peri-implant diseases is essential to allow appropriate management of the condition present. Failure to identify a peri-implant disease can lead to a complete loss of osseointegration and eventual loss of the implant.Though there are clear structural differences between dental implants and natural teeth, peri-implant health shares many common features with periodontal health around natural teeth. This is especially true with respect to their surrounding tissues and biological attachment.The diagnosis of peri-implant mucositis should be based on clinical signs of inflammatory disease, and radiographic assessment should be carried out to exclude bone level changes as this is an indication that peri-implant disease has already progressed to peri-implantitis stage. Clinical presentations to diagnose peri-implant mucositis include:-- Red, swollen and soft peri-implant tissues - Bleeding on probing (BoP) and/or suppuration on probing - Increased probing depths compared to baseline measurements - Absence of bone loss beyond crestal bone level changes as a result of initial remodelling following implant placement It has been suggested that the soft tissue cuff surrounding implants are less resistant to probing than the gingiva at adjacent teeth sites. This potentially leads to mechanically induced BoP on dental implants that are clinically healthy, as a result of trauma-induced BoP rather than a sign of biofilm-induced inflammation which represent the presence of peri-implant disease. Increased levels of bleeding on probing was present at 67% of sites where there is peri-implant mucositis as it is indicative of the presence of active disease and inflammation of the peri-implant mucosa. A light probing force of 0.25N should be used to probe the gingival margins so as not to damage the soft periodontal tissues. Bleeding on probing can be used in order to predict future loss of support from surrounding tissues. Microbiological testing was shown to improve the prognostic features compared to recording bleeding on probing alone as this was better for recognising the disease advancement around implants. Increased probing depths over time is linked to loss of attachment and a reduction in the supporting alveolar bone levels. When bone becomes involved, the disease has progressed to peri-implantitis and this site is no longer diagnosed with peri-implant mucositis. The presence of bleeding on probing, the probing depths measured to the base of any pocketing and suppuration should all be assessed regularly in order to correctly diagnose peri-implant mucositis. Mucosal recession, a draining sinus or fistula and swelling or hyperplasia of the gingivae surrounding the implant can all signify the presence of peri-implant disease and should all prompt further investigations to ascertain whether this is the case.Radiographs are required to distinguish between peri-implant mucositis and peri-implantitis as the supporting alveolar bone levels must be evaluated in order to decide on a diagnosis. Dental Panoramic Tomography or a variety of intra-oral radiographs can be used to monitor marginal bone levels and evaluate interproximal bone loss in particular, but most agree peri-apical radiographs show bone loss more comprehensively. Current radiographs can be compared to previous radiographs and the distance from a fixed point, such as the implant shoulder, used to measure the bone loss in mm over time. If an implant is mobile, this is indicative of a deficiency in osseointegration and at this point the implant should be removed. Therefore, this is not a valuable factor for early diagnosis of peri-implant mucositis. Alveolar bone loss following implant placement after first year in function should not exceed 2mm as generally between 0.5 – 2 mm of crestal bone height is lost during remodelling/healing process. As such changes ≥ 2mm during or after the first year should be considered as pathologic. Ie Peri-implant disease-induced. There are currently no biochemical diagnostic tests clinically available, as no sensitive diagnostic test has yet been found that can detect reversible changes before this is clinically visible and detectable. There are many salivary biomarkers and biomarkers in the crevicular fluid surrounding implants that are present in much higher levels when there is peri-implant mucositis or peri-implant disease but all these present after or at the same time as clinical signs and symptoms. Therefore, there is currently no benefit to assessing the peri-implant fluid or analysing the saliva. Research continues in this field, though there is also no biochemical diagnostic test clinically available to detect the progression of gingivitis or periodontitis as of yet. Prevention and Maintenance The best management of peri-implant mucositis is preventing it from occurring through maintenance of the implants. This involves regular cleaning from both the patient and a dental professional and antibacterial mouthwashes may help reduce plaque and bleeding around dental implants. Self-care Various mechanical ways of removing bacteria from around implants are available to be used by patients in their own homes, including but not limited to nylon-coated interdental brushes, soft-bristled toothbrushes and hard plastic cleaning instruments. These are all designed to prevent damage of the implant abutment, which would roughen the surface and lead to the accumulation of more bacteria on the surface which would contribute to the formation of more biofilms in the area. However, it was found that there were no statistically significant differences between some types of self administered antimicrobials, as they were all equally successful at maintaining the health of the soft tissues. One study was done comparing hyaluronic acid gel and chlorhexidine gel and another compared amine fluoride/stannous fluoride mouthwash to chlorhexidine mouthwash, but neither study showed either antimicrobial to be more effective at preventing peri-implant mucositis.It was found that there was no statistically significant difference between the effectiveness of using a powered/sonic toothbrush and using a manual toothbrush, although participants reported that they preferred the sonic toothbrush as they felt that it was better at keeping the areas around the implants clean. Dental Professional In terms of professionally administered treatment done by a dentist, there was no evidence to suggest that phosphoric acid etching gel is any more clinically advantageous than scaling or mechanical debridement and polishing or that enclosing chlorhexidine in the inner part of an implant is in any way superior to a physiological solution.It was also shown that a topical antibiotic inserted submucosally is no more successful at preventing peri-implant mucositis than a chlorhexidine gel.Debridement with manual curettes, followed by air polishing with glycine powder, and a prophylaxis brush, showed significant differences in BOP and peri-implant pocket depths. The use of manual curettes, sonic-driven scaler, and prophylaxis brush were found to be effective in maintaining the tissues around an implant, preventing inflammation. Applying chlorhexidine varnish in addition to debridement on implant surfaces had no significant additional benefit. Treatment When prevention of peri-implant mucositis fails, there are several options available to treat it. A similar study was conducted to assess if there was a difference between using sonic/powered toothbrushes and using manual toothbrushes in the treatment of peri-implant mucositis and it was found that there is no statistically significant difference between the two in terms of intervention either.Irrigants were also tested as part of a set of interventions administered by dental professionals but it was found that there was no statistically significant difference between chlorhexidine and physiologic solutions when used as irrigants at second state surgery to maintain health of soft tissues.Reduced mean plaque scores and reduced marginal bleeding scores were achieved more effectively from chlorhexidine irrigation than from the use of chlorhexidine mouthwash. Listerine mouthwash was found to be statistically significantly better than a placebo at attaining reduced mean plaque scores and reduced marginal bleeding scores. When Listerine mouthwash was used twice daily for 30 seconds in addition to routine oral hygiene, it was shown that a reduction of 54% in mean plaque and 34% in marginal bleeding compared to a placebo. Chlorhexidine irrigations reduced mean plaque by 20% and marginal bleeding by 35% in comparison to a chlorhexidine mouthwash. Chlorhexidine is the most effective antiplaque agent used in the mouth to date. Reducing the mean plaque scores and the marginal bleeding scores contributes to both the prevention and the treatment of peri-implant mucositis. Initially, the use of mouthwashes was only proposed for patients with physical disabilities which would result in decreased manual dexterity and hence make active cleaning difficult. However, it is now thought that this will lead to less peri-implant mucositis being caused in all implant patients. Despite this, there have been concerns about the link between mouthwashes containing alcohol and the incidence of oral cancer.Some studies looked solely at interventions which contribute to the reversal of peri-implant mucositis. One such study found no statistically significant difference between triclosan dentrifice in comparison to sodium fluoride dentrifice at recovering soft tissue health. There were also two trials conducted where patients with peri-implant mucositis were assessed after different interventions carried out by dental professionals. In these trials mechanical debridement being followed by minocycline or chlorhexidine gel had no statistically significant difference, nor did debridement with titanium curettes compared to an ultrasonic debridement tool. Nouveau interventions A double‐blind randomized controlled trial assessing the effect of subgingival ozone (O3, gaseous ozone, HealOzone MK II, KaVo) and/or hydrogen peroxide on the development of peri‐implant mucositis, found that ozone showed significant potential for management of peri-implant mucositis compared to oxygen and saline.Mechanical curettage with adjunct antimicrobial photodynamic therapy is more effective in reducing peri-implant inflammation in smokeless tobacco product users as compared to mechanical curettage alone in the short term (3 months). Further long-term studies will be needed to confirm long term efficacy.Current research found no evidence for use of systemic antibiotics in the treatment of peri-implant mucositis Further Discussion There is low quality evidence to suggest the most effective treatments for peri-implant mucositis, with no reliable evidence for which are more beneficial in the long term. All trials so far have had generally short follow-up periods and limited numbers of subjects. It is expected we will learn more about peri-implant mucositis as the number of patients opting to have implants continues to rise. There is little evidence for the most effective interventions for maintaining health and reversing the effects of peri-implant mucositis on the soft periodontal tissues. More RCTs should be conducted on implants and their potential failure and the inflammation of the periodontal tissues that can be caused by them, especially long term studies. Such trials will likely be difficult and expensive to carry out but there is definitely a need for them in order to find a definitive answer on how implants should be maintained and treated. Research is being continued into the investigations of peri-implant crevicular fluid and saliva in an attempt to find biomarkers that are diagnostic and will be indicative of peri-implant mucositis before the disease has started and other clinical signs and symptoms are visible. There are concerns with metal and ultrasonic instrumentation roughening implant surface and causing increased plaque retention. Studies in vitro have found that special coated scalers and ultrasonic tips (e.g. newly developed metallic tip and plastic hand curettes) were compatible with implant surfaces and caused minimal damage. However, this is yet to be confirmed in vivo. It was also found that plastic-coated scalers left plastic deposits on implant surfaces, hence more research is needed for evaluating their use in debriding implant. Studies on patient perception on comfort regarding hand scaling compared to ultrasonic scaling will be helpful in order to increase patient compliance, especially in the event that hand and ultrasonic instrumentation were found to be equally effective. == References ==
Mucous membrane pemphigoid	Mucous membrane pemphigoid is a rare chronic autoimmune subepithelial blistering disease characterized by erosive lesions of the mucous membranes and skin. It is one of the pemphigoid diseases that can result in scarring. Signs and symptoms The autoimmune reaction most commonly affects the oral mucosa in the mouth, causing lesions in the gums (gingiva), known as desquamative gingivitis. More severe cases can also affect areas of mucous membrane elsewhere in the body, such as the sinuses, genitals, anus, and cornea. When the cornea of the eye is affected, repeated scarring may result in blindness. Brunsting–Perry cicatricial pemphigoid is a rare variant of mucous membrane pemphigoid involving the scalp and the neck without mucosal involvement. It is proposed by some authors that this be called a variant of epidermolysis bullosa acquisita.Nikolskys sign (gentle lateral pressure) on unaffected mucosa or skin raises a bulla. If no lesions are present on examination it may be useful way of demonstrating reduced epithelial adhesion. In contrast, in Pemphigus, the epithelium tends to disintegrate rather than form a bulla. Nikolskys sign is present in pemphigus and mucous membrane pemphigoid, but not in bullous pemphigoid. Pathophysiology In mucous membrane pemphigoid, the autoimmune reaction occurs in the skin, specifically at the level of the basement membrane, which connects the lower skin layer (dermis) to the upper skin layer (epidermis) and keeps it attached to the body. When the condition is active, the basement membrane is dissolved by the antibodies produced, and areas of skin lift away at the base, causing hard blisters which scar if they burst. In other words, this is a desquamating/blistering disease in which the epithelium "unzips" from the underlying connective tissue, allowing fluid to gather that subsequently manifest as bullae, or blisters. Diagnosis Diagnostic techniques: antibodies (IgG) precipitate complement (C3) in the lamina lucida of the basement membrane. Circulating auto-antibodies to BP-1 antigen (located in hemidesmosome). 50% have BP-2. Positive Nikolsky sign. IgG, C3 deposition at BM creating smooth line in immunofluorescent analysis. Management The management depends upon the severity of the condition. For example, where there are lesions in the mouth alone, systemic drugs are less likely to be used. Where the condition is not limited to the mouth, or where there is poor response to Topical treatments, systemic drugs are more likely to be used. Conservative Simple measures that can be taken include avoidance of hard, sharp or rough foods, and taking care when eating. Good oral hygiene is also usually advised, and professional oral hygiene measures such as dental scaling. Medications Topical and intralesional (injected into the affected areas) corticosteroid drugs may be used, such as fluocinonide, clobetasol propionate or triamcinolone acetonide. Oral candidiasis may develop with long term topical steroid use, and sometimes antimycotics such as miconazole gel or chlorhexidine mouthwash are used to prevent this. Topical ciclosporin is sometimes used. Dapsone is sometimes used as a steroid sparing agent. The dose is often increased very slowly in order to minimize side effects. Systemic steroids, such as prednisone or prednisolone may be needed in severe cases. Many other drugs have been used to treat mucous membrane pemphoid, including azathioprine, cyclophosphamide, methotrexate, thalidomide, mycophenolate mofetil, leflunomide, sulphasalazine, sulphapuridine, sulphamethoxypiridazine, tetracyclines (e.g. minocycline, doxycycline) and nicotinamide. Other treatments Plasmapheresis appears to help some cases. Sometimes surgical procedures are required to repair scars, prevent complications such as blindness, upper airway stenosis or esophageal stricture. See also Gestational pemphigoid List of cutaneous conditions List of target antigens in pemphigoid List of immunofluorescence findings for autoimmune bullous conditions References == External links ==
Optic disc drusen	Optic disc drusen (ODD) are globules of mucoproteins and mucopolysaccharides that progressively calcify in the optic disc. They are thought to be the remnants of the axonal transport system of degenerated retinal ganglion cells. ODD have also been referred to as congenitally elevated or anomalous discs, pseudopapilledema, pseudoneuritis, buried disc drusen, and disc hyaline bodies. Anatomy The optic nerve is a cable connection that transmits images from the retina to the brain. It consists of over one million retinal ganglion cell axons. The optic nerve head, or optic disc is the anterior end of the nerve that is in the eye and hence is visible with an ophthalmoscope. It is located nasally and slightly inferior to the macula of the eye. There is a blind spot at the optic disc because there are no rods or cones beneath it to detect light. The central retinal artery and vein can be seen in the middle of the disc as it exits the scleral canal with the optic nerve to supply the retina. The vessels send branches out in all directions to supply the retina. Pathophysiology In children, optic disc drusen are usually buried and undetectable by fundoscopy except for a mild or moderate elevation of the optic disc. With age, the overlying axons become atrophied and the drusen become exposed and more visible. They may become apparent with an ophthalmoscope and some visual field loss at the end of adolescence. ODD can compress and eventually compromise the vasculature and retinal nerve fibers. Rarely, choroidal neovascularization may develop as the juxtapapillary nerve fibers are disrupted, with subsequent subretinal hemorrhage and retinal scarring. Even more rarely, vitreous hemorrhage may develop. Diagnosis Differential diagnosis In most patients, optic disc drusen are an incidental finding. It is important to differentiate them from other conditions that present with optic disc elevation, especially papilledema, which could imply raised intracranial pressure or tumors. True papilledema may present with exudates or cotton-wool spots, unlike ODD. The optic disc margins are characteristically irregular in ODD but not blurred as there is no swelling of the retinal nerve fibers. Spontaneous venous pulsations are present in about 80 percent of patients with ODD, but absent in cases of true disc edema. Other causes of disc elevation clinicians must exclude may be: hyaloid traction, epipapillary glial tissue, myelinated nerve fibres, scleral infiltration, vitreopapillary traction and high hyperopia. Disorders associated with disc elevation include: Alagille syndrome, Down syndrome, Kenny-Caffey syndrome, Leber Hereditary Optic Neuropathy and linear nevus sebaceous syndrome. Management Patients with optic disc drusen should be monitored periodically via ophthalmoscopy, Snellen acuity, contrast sensitivity, color vision, intraocular pressure and threshold visual fields. For those with visual field defects optical coherence tomography has been recommended for follow up of nerve fiber layer thickness. Associated conditions such as angioid streaks and retinitis pigmentosa should be screened for. Both the severity of optic disc drusen and the degree of intraocular pressure elevation have been associated with visual field loss. There is no widely accepted treatment for ODD, although some clinicians will prescribe eye drops designed to decrease the intra-ocular pressure and theoretically relieve mechanical stress on fibers of the optic disc. Rarely choroidal neovascular membranes may develop adjacent to the optic disc threatening bleeding and retinal scarring. Laser treatment or photodynamic therapy or other evolving therapies may prevent this complication. Prognosis Optic nerve damage is progressive and insidious. Some of patients will develop some peripheral field defects. These can include nasal step defects, enlarged blind spots, arcuate scotomas, sectoral field loss and altitudinal defects. Clinical symptoms correlate to visibility of the drusen. Central vision loss is a rare complication of bleeding from peripapillar choroidal neovascular membranes. Anterior ischemic optic neuropathy (AION) is a potential complication. Epidemiology Optic disc drusen are found clinically in about 1% of the population but this increases to 3.4% in individuals with a family history of ODD. About two thirds to three quarters of clinical cases are bilateral. A necropsy study of 737 cases showed a 2.4% incidence with 2 out of 15 (13%) bilateral, perhaps indicating the insidious nature of many cases. An autosomal dominant inheritance pattern with incomplete penetrance and associated inherited dysplasia of the optic disc and its blood supply is suspected. Males and females are affected at equal rates. Caucasians are the most susceptible ethnic group. Certain conditions have been associated with disc drusen such as retinitis pigmentosa, angioid streaks, Usher syndrome, Noonan syndrome and Alagille syndrome. Optic disc drusen are not related to Bruch membrane drusen of the retina which have been associated with age-related macular degeneration. See also Drusen References Further reading Online Mendelian Inheritance in Man (OMIM): Pseudopapilledema - 177800 Wirtschafter JD (1983). "Optic nerve axons and acquired alterations in the appearance of the optic disc". Trans Am Ophthalmol Soc. 81: 1034–91. PMC 1312472. PMID 6203209. == External links ==
Osteopathia striata	Osteopathia striata is a rare entity characterized by fine linear striations about 2- to 3-mm-thick, visible by radiographic examination, in the metaphyses and diaphyses of long or flat bones. It is often asymptomatic, and is often discovered incidentally. See also List of radiographic findings associated with cutaneous conditions == References ==
Endovascular aneurysm repair	Endovascular aneurysm repair (EVAR) is a type of minimally-invasive endovascular surgery used to treat pathology of the aorta, most commonly an abdominal aortic aneurysm (AAA). When used to treat thoracic aortic disease, the procedure is then specifically termed TEVAR for "thoracic endovascular aortic/aneurysm repair." EVAR involves the placement of an expandable stent graft within the aorta to treat aortic disease without operating directly on the aorta. In 2003, EVAR surpassed open aortic surgery as the most common technique for repair of AAA, and in 2010, EVAR accounted for 78% of all intact AAA repair in the United States. Medical uses Standard EVAR is appropriate for aneurysms that begin below the renal arteries, where there exists an adequate length of normal aorta (the "proximal aortic neck") for reliable attachment of the endograft without leakage of blood around the device ("endoleak"). If the proximal aortic neck is also involved with the aneurysm, the patient may be a candidate for complex visceral EVAR with a fenestrated or branched EVAR. Patients with aneurysms require elective repair of their aneurysm when it reaches a diameter large enough (typically greater than 5.5 cm) such that the risk of rupture is greater than the risk of surgery. Repair is also warranted for aneurysms that rapidly enlarge or those that have been the source of emboli (debris from the aneurysm that dislodges and travel into other arteries). Lastly, the repair is also indicated for aneurysms that are the source of pain and tenderness, which may indicate impending rupture. The options for repair include traditional open aortic surgery or endovascular repair.Endovascular procedures aim to reduce the morbidity and mortality of treating arterial disease in a patient population that is increasingly older and less fit than when major open repairs were developed and popularized. Even in the early days, significant risks were accepted in the understanding that the large open operation was the only option. That is not the case in most patients today.Studies that assign aneurysm patients to treatment with EVAR or traditional open surgery have demonstrated fewer early complications with the minimally invasive approach. Some studies have also observed a lower mortality rate with EVAR. The reduction in death, however, does not persist long-term. After a few years, the survival after repair is similar to EVAR or open surgery. This observation may be the result of durability problems with early endograft, with a corresponding need for additional procedures to repair endoleaks and other device-related issues. Newer, improved technology may reduce the need for such secondary procedures. If so, the results of EVAR may improve to the point where long-term survival benefit becomes evident.EVAR is also used for rupture of the abdominal and descending thoracic aorta, and in rare cases used to treat pathology of the ascending aorta. Aortic dissection Endografts have been used in patients with aortic dissection, noting the extremely complex nature of open surgical repair in these patients. In uncomplicated aortic dissections, no benefit has been demonstrated over medical management alone. In uncomplicated type B aortic dissection, TEVAR does not seem either to improve or compromise 2-year survival and adverse event rates. Its use in complicated aortic dissection is under investigation. In the Clinical Practice Guidelines of the European Society for Vascular Surgery, it is recommended that in patients with complicated acute type B aortic dissection, endovascular repair with thoracic endografting should be the first line intervention.Before people are deemed to be suitable candidates for this treatment, they have to go through a rigorous set of tests. These include a CT scan of the complete thorax/abdomen/pelvis and blood tests. The CT scan gives precise measurements of the aneurysm and the surrounding anatomy. In particular, the calibre/tortuosity of the iliac arteries and the relationship of the neck of the aneurysm to the renal arteries are important determinants of whether the aneurysm is amenable to endoluminal repair. In certain occasions where the renal arteries are too close to the aneurysm, the custom-made fenestrated graft stent is now an accepted alternative to doing open surgery. Relative contraindications A patients anatomy can be unsuitable for EVAR in several ways. Most commonly, in an infrarenal aneurysm, a potential EVAR candidate lacks adequate length of the normal-diameter aorta between the aneurysm and the takeoff of the renal arteries, the "infra-renal neck". Another relative contraindications include prohibitively small iliac arteries, aneurysmal iliac arteries, prohibitively small femoral arteries, or circumferential calcification of the femoral or iliac arteries.In addition to a short proximal aortic neck, the neck may be angulated, large in diameter, or shaped like a funnel (conical) where the neck diameter at the top is larger than the neck diameter at the bottom. Along with a short proximal aortic neck, necks with any of these characteristics are called "hostile necks" and endovascular repair can be either contraindicated or associated with early-late complications of endoleak, or endograft migration, or both.Many of the advances in EVAR technique aim to adapt EVAR for these situations, and advanced techniques allow EVAR to be employed in patients who previously were not candidates. Technique The procedure is carried out in a sterile environment under fluoroscopic guidance. It is usually carried out by a vascular surgeon, interventional radiologist or cardiac surgeon, and occasionally, general surgeon or interventional cardiologist. The procedure can be performed under general, regional (spinal or epidural) or even local anesthesia. Access to the patients femoral arteries can be with surgical incisions or percutaneously in the groin on both sides. Vascular sheaths are introduced into the patients femoral arteries, through which guidewires, catheters, and the endograft are passed.Diagnostic angiography images are captured of the aorta to determine the location of the patients renal arteries, so the stent-graft can be deployed without blocking these. Failure to achieve this will cause kidney failure. With most devices, the "main body" of the endograft is placed first, followed by the "limbs" which join the main body and extend to the iliac arteries, effectively protecting the aneurysm sac from blood pressure.The abdominal aneurysm extends down to the common iliac arteries in about 25%-30% of patients. In such cases, the iliac limbs can be extended into the external iliac artery to bypass a common iliac aneurysm. Alternatively, a specially designed endograft, (an iliac branch device) can be used to preserve flow to the internal iliac arteries. The preservation of the hypogastric (internal iliac) arteries is important to prevent buttock claudication and impotence, and every effort should be made to preserve flow to at least one hypogastric artery.The endograft acts as an artificial lumen for blood to flow through, protecting the surrounding aneurysm sac. This reduces the pressure in the aneurysm, which itself will usually thrombose and shrink in size over time.Staging such procedures is common, particularly to address aortic branch points near the diseased aortic segment. One example in the treatment of thoracic aortic disease is revascularization of the left common carotid artery and/or the left subclavian artery from the innominate artery or the right common carotid artery to allow treatment of a thoracic aortic aneurysm that encroaches proximally into the aortic arch. These "extra-anatomic bypasses" can be performed without an invasive thoracotomy. Another example in the abdominal aorta is the embolization of the internal iliac artery on one side prior to coverage by an iliac limb device. Continued improvement in stent-graft design, including branched endografts, will reduce but not eliminate multi-stage procedures. Percutaneous EVAR Standard EVAR involves a surgical cut-down on either the femoral or iliac arteries, with the creation of a 4–6 cm incision. Like many surgical procedures, EVAR has advanced to a more minimally invasive technique, by accessing the femoral arteries percutaneously In percutaneous EVAR (PEVAR), small, sub-centimeter incisions are made over the femoral artery, and endovascular techniques are used to place the device over a wire. Percutaneous EVAR has been systematically compared to the standard EVAR cut-down femoral artery approach. Moderate quality evidence suggests that there are no differences in short-term mortality, aneurysm sealing, long and short-term complications, or infections at the wound site. Higher quality evidence suggests that there are no differences in post-repair bleeding complications or haematoma between the two approaches. The percutaneous approach may have reduced surgical time. Fenestrated EVAR In certain circumstances, a specially designed custom-made graft, which has holes, or fenestrations, on the graft body to maintain the patency of the visceral arteries, is used for the procedure, which is called FEVAR (fenestrated endovascular aortic/aneurysm repair). When the aneurysm begins close to the renal arteries, standard EVAR may be contraindicated since there will be an inadequate length of suitable aorta for the endograft attachment. In these cases, a fenestrated endograft may be useful, where the attachment of the endograft to the aorta may be placed above the renal arteries with each fenestration aligned with a renal artery so that blood flow to the kidneys is maintained. Fenestrated EVAR has been in use in the United Kingdom for over a decade and early results were published in Jun 2012. Branched EVAR Thoracoabdominal aortic aneurysms (TAAA) involve the aorta in the chest and abdomen. As such, major branch arteries to the head, arms, spinal cord, intestines, and kidneys may originate from the aneurysm. An endovascular repair of a TAAA is only possible if blood flow to these critical arteries is preserved. Hybrid procedures offer one option, but a more direct approach involves the use of a branched endograft. However, the complex anatomy associated with the supra-aortic vessels is particularly difficult to accommodate with branched endograft devices. Dr. Timothy Chuter pioneered this approach, with a completely endovascular solution. After partial deployment of the main body of an endograft, separate endograft limbs are deployed from the main body to each major aortic branch. This procedure is long, technically difficult, and currently only performed in a few centers. When the aneurysm begins above the renal arteries, neither fenestrated endografts nor "EndoAnchoring" of an infrarenal endograft is useful (an open surgical repair may be necessary). Alternatively, a "branched" endograft may be used. A branched endograft has graft limbs that branch off of the main portion of the device to directly provide blood flow to the kidneys or the visceral arteries. Hybrid procedures On occasion, there is inadequate length or quality of the proximal or distal aortic neck. In these cases, a fully minimally invasive option is not possible. One solution, however, is a hybrid repair, which combines an open surgical bypass with EVAR or TEVAR. In hybrid procedures, the endograft is positioned over major aortic branches. While such a position would normally cause problems from disruption of blood flow to the covered branches (renal, visceral, or branches to the head or arms), the prior placement of bypass grafts to these critical vessels allowed the deployment of the endograft at a level that would otherwise not be possible.If a patient has calcified or narrow femoral arteries that prohibit the introduction of the endograft transfemorally, an iliac conduit may be used. This is typically a piece of PTFE that is sewn directly to the iliac arteries, which are exposed via an open retroperitoneal approach. The endograft is then introduced into the aorta through the conduit.In patients with thoracic aortic disease involving the arch and descending aorta, it is not always possible to perform a completely endovascular repair. This is because head vessels of the aortic arch supplying blood to the brain cannot be covered and for this reason, there is often an inadequate landing zone for stent-graft delivery. A hybrid repair strategy offers a reasonable choice for treating such patients. A commonly used hybrid repair procedure is the "frozen elephant trunk repair". This technique involves midline sternotomy. The aortic arch is transected and the stent-graft device is delivered in an ante-grade fashion in the descending aorta. The aortic arch is subsequently reconstructed and the proximal portion of the stent-graft device is then directly sutured into the surgical graft. Patients with anomalies of the arch and some disease extension into the descending aorta are often ideal candidates. Studies have reported successful use of hybrid techniques for treating Kommerell diverticulum and descending aneurysms in patients with previous coarctation repairs.In addition, hybrid techniques combining both open and endovascular repair are also used in managing emergency complications in the aortic arch, such as retrograde ascending dissection and endoleaks from previous stent grafting of descending aorta. A "reverse frozen elephant trunk repair" is shown to be particularly effective. Adjunctive procedures Snorkel: A covered stent placed into a visceral vessel adjacent to the main body of the EVAR device. The aortic lumen of the visceral stent is directed superiorly, resembling a snorkel. Chimney: In TEVAR, a covered stent placed from the ascending aorta to a great vessel (e.g., innominate artery) and adjacent to the main body of the EVAR is termed a chimney. In anatomic position, blood flows superiorly through a chimney-stent graft into the great vessel, just as smoke flows up a chimney. Periscope: Like a snorkel, a periscope stent graft provides flow to a visceral vessel, but in a retrograde fashion, with the aortic lumen inferior to the main body of the EVAR device. Stents: Large bare-metal stents have been used to treat proximal endoleaks, as have aortic extension cuffs to treat endograft migration. Glue: Trans-catheter embolic glue has been used to treat type I endoleaks, with inconsistent success. EndoAnchors: Small, helically shaped devices are screwed through the endograft and into the aortic wall. EndoAnchors have been used successfully to treat endoleaks and, in concert with an aortic extension endograft, to treat migration of the original endograft. Rigorous evaluations and long-term outcomes of this technique are not yet available. Risks The complications of EVAR can be divided into those that are related to the repair procedure and those related to the endograft device. For example, a myocardial infarction that occurs immediately after the repair is normally related to the procedure and not the device. By contrast, the development of an endoleak from degeneration of endograft fabric would be a device-related complication.Durability and problems such as endoleaks may require careful surveillance and adjuvant procedures to ensure the success of the EVAR or EVAR/hybrid procedure. CT angiography (CTA) imaging has, in particular, made a key contribution to planning, success, durability in this complex area of vascular surgery.A major cause of complications in EVAR is the failure of the seal between the proximal, infra-renal aneurysm neck and the endovascular graft. Risk of this form of failure is especially elevated in adverse or challenging proximal neck anatomies, where this seal could be compromised by unsuitable geometric fit between the graft and vessel wall, as well as instability of the anatomy. New recent techniques have been introduced to address these risks by utilizing a segment of the supra-renal portion of the aorta to increase the sealing zone, such as with fenestrated EVAR, chimneys and snorkels. These techniques may be suitable in certain patients with qualifying factors, e.g., configuration of renal arteries, renal function. However, these are more complex procedures than standard EVAR and may be subject to further complications.An approach that directly augments the fixation and sealing between the graft and aorta to mimic the stability of a surgical anastomosis is EndoAnchoring. EndoAnchors are small, helically shaped implants that directly lock the graft to the aortic wall with the goal to prevent complications of the seal, especially in adverse neck anatomies. These EndoAnchors may also be used to treat identified leaks between the graft and proximal neck. Procedure-related Arterial dissection, contrast-induced kidney failure, thromboembolizaton, ischemic colitis, groin hematoma, wound infection, type II endoleaks, myocardial infarction, congestive heart failure, cardiac arrhythmias, respiratory failure. Device-related Endograft migration, aneurysm rupture, graft limb stenosis/kinking, type I/III/IV endoleaks, stent graft thrombosis, or infection. Endoleaks An endoleak is a leak into the aneurysm sac after endovascular repair. Five types of endoleaks exist: Type I - Perigraft leakage at proximal or distal graft attachment sites (near the renal and iliac arteries) Type II - Retrograde flow to the aneurysm sac from branches such as the lumbar and inferior mesenteric arteries. Type II endoleaks are the most common, and least serious type of endoleak. Type II endoleaks do not require immediate treatment, as a portion will resolve spontaneously. Type III - Leakage between overlapping parts of the stent (i.e., the connection between overlapping components) or rupture through graft material. Type IV - Leakage through the graft wall due to the quality (porosity) of the graft material. As seen in first-generation grafts, changes in graft material in modern devices have decreased the prevalence of type IV leaks. Type V - Expansion of the aneurysm sac without an identifiable leak. Also called "endotension".Type I and III leaks are considered high-pressure leaks and are more concerning than other leak types. Depending on the aortic anatomy, they may require further intervention to treat. Type 2 leaks are common and often can be left untreated unless the aneurysm sac continues to expand after EVAR. Spinal cord injury Spinal cord injury is a devastating complication after aortic surgery, specifically for thoracoabdominal aortic aneurysm repair; severe injury could lead to urine and fecal incontinence, paresthesia and even paraplegia. The risk varies between studies with two metanalysis demonstrating a pooled incidence of spinal cord injury 2.2% and 11%. Predictive factors include increasing extent of coverage, hypogastric artery occlusion, prior aortic repair and perioperative hypotension. Spinal cord injury related to aortic repair occurs due to impaired blood flow to the spine after coverage of blood vessels, important to the blood circulation of the spine, namely intercostal- and lumbar arteries. A few methods exist for potentially reversing spinal cord injury, if it arises, elevated blood pressure, increased oxygenation, blood transfusion and cerebrospinal fluid drainage. Cerebrospinal fluid drainage Cerebrospinal fluid drainage is one of the adjunct methods used to reverse spinal cord injury. With increased drainage of spinal fluid, the intrathecal pressure decreases which allows for increase blood perfusion to the spine, possibly reversing the ischemic injury of the spinal tissue due to lessened blood supply. The benefits of this procedure have been established in open aortic repair and suggested in endovascular aortic repair. Recovery after EVAR Unlike traditional aortic repair, standard recovery after EVAR is remarkably straightforward. Patients who have undergone EVAR typically spend one night in the hospital to be monitored, although it has been suggested that EVAR can be performed as a same-day procedure.Patients are advised to slowly return to normal activity. There are no specific activity restrictions after EVAR, however, patients typically are seen by their surgeon within one month after EVAR to begin post-EVAR surveillance.There is limited research looking at patients experience of recovery after more complex and staged EVAR for thoracoabdominal aortic diseases. One qualitative study found that patients with complex aortic diseases struggle with physical and psychological setbacks, continuing years after their operations. History Dr. Juan C. Parodi introduced the minimally-invasive endovascular aneurysm repair (EVAR) to the world and performed the first successful endovascular repair of an abdominal aortic aneurysm on 7 September 1990 in Buenos Aires on a friend of Carlos Menem, the then President of Argentina. The first device was simple, according to Parodi: "It was a graft I designed with expandable ends, the extra-large Palmaz stent, a Teflon sheath with a valve, a wire, and the valvuloplasty balloon, which I took from the cardiologists." Parodis first patient lived for nine years after the procedure and died from pancreatic cancer. The first EVAR performed in the United States was in 1992 by Drs. Frank Veith, Michael Marin, Juan Parodi and Claudio Schonholz at Montefiore Medical Center affiliated with Albert Einstein College of Medicine.The modern endovascular device used to repair abdominal aortic aneurysms, which is bifurcated and modular, was pioneered and first employed by Dr. Timothy Chuter while a fellow at the University of Rochester. The first clinical series of his device was published from Nottingham in 1994. The first endovascular repair of a ruptured abdominal aortic aneurysm was also reported from Nottingham in 1994.By 2003, four devices were on the market in the United States. Each of these devices has since been either abandoned or further refined to improve its characteristics in vivo. Special populations Women Women are known to have smaller aortas on average than men, so are potential candidates for AAA treatment at smaller maximum aneurysm diameters than men. Transplant candidates As immunosuppressive medications are known to increase the rate of aneurysm growth, transplant candidates are AAA repair candidates at smaller maximum aneurysm diameters than the general population. Other animals Due to the expense associated with EVAR stent-graft devices and their specificity to human aortic anatomy, EVAR is not used in other animals. Videos == References ==
Centrifugal abdominal lipodystrophy	Centrifugal abdominal lipodystrophy is a skin condition characterized by areas of subcutaneous fat loss that slowly enlarge.: 496–7 See also Lipodystrophy List of cutaneous conditions Skin lesion == References ==
Hutchinsons triad	Hutchinsons triad is named after Sir Jonathan Hutchinson (1828–1913). It is a common pattern of presentation for congenital syphilis, and consists of three phenomena: interstitial keratitis, malformed teeth (Hutchinson incisors and mulberry molars), and eighth nerve deafness. There may also be a deformity on the nose known as saddle nose deformity. == References ==
Non-small-cell lung carcinoma	Non-small-cell lung carcinoma (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to small-cell carcinoma. When possible, they are primarily treated by surgical resection with curative intent, although chemotherapy has been used increasingly both preoperatively (neoadjuvant chemotherapy) and postoperatively (adjuvant chemotherapy). Types The most common types of NSCLC are squamous-cell carcinoma, large-cell carcinoma, and adenocarcinoma, but several other types occur less frequently. A few of the less common types are pleomorphic, carcinoid tumor, salivary gland carcinoma, and unclassified carcinoma. All types can occur in unusual histologic variants and as mixed cell-type combinations. Nonsquamous-cell carcinoma almost occupies the half of NSCLC. In the tissue classification, the central type contains about one-ninth.Sometimes, the phrase "not otherwise specified" (NOS) is used generically, usually when a more specific diagnosis cannot be made. This is most often the case when a pathologist examines a small number of malignant cells or tissue in a cytology or biopsy specimen.Lung cancer in people who have never smoked is almost universally NSCLC, with a sizeable majority being adenocarcinoma.On relatively rare occasions, malignant lung tumors are found to contain components of both SCLC and NSCLC. In these cases, the tumors are classified as combined small-cell lung carcinoma (c-SCLC), and are (usually) treated as "pure" SCLC. Lung adenocarcinoma Adenocarcinoma of the lung is currently the most common type of lung cancer in "never smokers" (lifelong nonsmokers). Adenocarcinomas account for about 40% of lung cancers. Historically, adenocarcinoma was more often seen peripherally in the lungs than SCLC and squamous-cell lung cancer, both of which tended to be more often centrally located. Recent studies, though, suggest that the "ratio of centrally to peripherally occurring" lesions may be converging toward unity for both adenocarcinoma and squamous-cell carcinoma. Squamous-cell lung carcinoma Squamous-cell carcinoma (SCC) of the lung is more common in men than in women. It is closely correlated with a history of tobacco smoking, more so than most other types of lung cancer. According to the Nurses Health Study, the relative risk of SCC is around 5.5, both among those with a previous duration of smoking of 1 to 20 years, and those with 20 to 30 years, compared to "never smokers" (lifelong nonsmokers). The relative risk increases to about 16 with a previous smoking duration of 30 to 40 years, and roughly 22 with more than 40 years. Large-cell lung carcinoma Large-cell lung carcinoma (LCLC) is a heterogeneous group of undifferentiated malignant neoplasms originating from transformed epithelial cells in the lung. LCLCs have typically comprised around 10% of all NSCLC in the past, although newer diagnostic techniques seem to be reducing the incidence of diagnosis of "classic" LCLC in favor of more poorly differentiated SCCs and adenocarcinomas. LCLC is, in effect, a "diagnosis of exclusion", in that the tumor cells lack light microscopic characteristics that would classify the neoplasm as a small-cell carcinoma, squamous-cell carcinoma, adenocarcinoma, or other more specific histologic type of lung cancer. LCLC is differentiated from SCLC primarily by the larger size of the anaplastic cells, a higher cytoplasmic-to-nuclear size ratio, and a lack of "salt-and-pepper" chromatin. Symptoms Many of the symptoms of NSCLC can be signs of other diseases, but having chronic or overlapping symptoms may be a signal of the presence of the disease. Some symptoms are indicators of less advanced cases, while some may signal that the cancer has spread. Some of the symptoms of less advanced cancer include chronic cough, coughing up blood, hoarseness, shortness of breath, wheezing, chest pain, weight loss, and loss of appetite. A few more symptoms associated with the early progression of the disease are feeling weak, being very tired, having trouble swallowing, swelling in the face or neck, and continuous or recurring infections such as bronchitis or pneumonia. Signs of more advanced cases include bone pain, nervous-system changes (headache, weakness, dizziness, balance problems, seizures), jaundice, lumps near the surface of the body, numbness of extremities due to Pancoast syndrome, and nausea, vomiting, and constipation brought on by hypercalcemia. Some more of the symptoms that indicate further progression of the cancer include shortness of breath, superior vena cava syndrome, trouble swallowing, large amounts of mucus, weakness, fatigue, and hoarseness. Cause Smoking is by far the leading risk factor for lung cancer. Cigarette smoke contains more than 6,000 components, many of which lead to DNA damage (see table of tobacco-related DNA damages in Tobacco smoking). Other causes include radon, exposure to secondhand smoke, exposure to substances such as asbestos, chromium, nickel, beryllium, soot, or tar, family history of lung cancer, and air pollution.Genetics can also play a role as a family history of lung cancer can contribute to an increased risk of developing the disease. Furthermore, research has revealed specific chromosome regions associated with increased risks of developing lung cancer. In general, DNA damage appears to be the primary underlying cause of cancer. Though most DNA damages are repairable, leftover unrepaired DNA damages from cigarette smoke are the likely cause of NSCLC. DNA replication past an unrepaired damage can give rise to a mutation because of inaccurate translesion synthesis. In addition, during repair of DNA double-strand breaks, or repair of other DNA damages, incompletely cleared sites of repair can lead to epigenetic gene silencing. DNA repair deficiency in NSCLC Deficiencies in DNA repair underlie many forms of cancer. If DNA repair is deficient, the frequency of unrepaired DNA damages increases, and these tend to cause inaccurate translesion synthesis leading to mutation. Furthermore, increased damages can elevate incomplete repair, leading to epigenetic alterations.As indicated as in the article Carcinogenesis, mutations in DNA repair genes occasionally occur in cancer, but deficiencies of DNA repair due to epigenetic alterations that reduce or silence DNA repair-gene expression occur much more frequently in cancer.Epigenetic gene silencing of DNA repair genes occurs frequently in NSCLC. At least nine DNA repair genes that normally function in relatively accurate DNA repair pathways are often repressed by promoter hypermethylation in NSCLC. One DNA repair gene, FEN1, that functions in an inaccurate DNA repair pathway, is expressed at an increased level due to hypo-, rather than hyper-, methylation of its promoter region (deficiency of promoter methylation) in NSCLC. The frequent deficiencies in accurate DNA repair, and the increase in inaccurate repair, likely cause the high level of mutation in lung cancer cells of more than 100,000 mutations per genome (see Whole genome sequencing). Staging Staging is a formal procedure to determine how developed the cancer is, which determines treatment options. The American Joint Committee on Cancer and the International Union Against Cancer recommend TNM staging, using a uniform scheme for NSCLC, SCLC, and bronchopulmonary carcinoid tumors. With TNM staging, the cancer is classified based on the size of the tumor and spread to lymph nodes and other organs. As the tumor grows in size and the areas affected become larger, the staging of the cancer becomes more advanced as well. Several components of NSCLC staging then influence physicians treatment strategies. The lung tumor itself is typically assessed both radiographically for overall size and by a pathologist under the microscope to identify specific genetic markers or to see if invasion into important structures within the chest (e.g., bronchus or pleural cavity) has occurred. Next, the patients nearby lymph nodes within the chest cavity, known as the mediastinum, are checked for disease involvement. Finally, the patient is evaluated for more distant sites of metastatic disease, most typically with brain imaging and or scans of the bones. Five-year survival rates The survival rates for stages I through IV decrease significantly due to the advancement of the disease. For stage I, the five-year survival rate is 47%, stage II is 30%, stage III is 10%, and stage IV is 1%. Treatment More than one kind of treatment is often used, depending on the stage of the cancer, the individuals overall health, age, response to chemotherapy, and other factors such as the likely side effects of the treatment. After full staging, the NSCLC patient can typically be classified in one of three different categories: patients with early, nonmetastatic disease (stages I and II, and select type III tumors), patients with locally advanced disease confined to the thoracic cavity (e.g., large tumors, tumors involving critical chest structures, or patients with positive mediastinal lymph nodes), or patients with distant metastasis outside of the thoracic cavity. Early/nonmetastatic NSCLC NSCLCs are usually not very sensitive to chemotherapy and/or radiation, so surgery (lung resection to remove the tumor) remains the treatment of choice if patients are diagnosed at an early stage.If the persons have a small, but inoperable tumor, they may undergo highly targeted, high-intensity radiation therapy. New methods of giving radiation treatment allow doctors to be more accurate in treating lung cancers. This means less radiation affects nearby healthy tissues. New methods include Cyberknife and stereotactic body radiation therapy. Certain people who are deemed to be higher risk may also receive adjuvant (ancillary) chemotherapy after initial surgery or radiation therapy. A number of possible chemotherapy agents can be selected, but most involve the platinum-based chemotherapy drug called cisplatin.Other treatments include percutaneous ablation and chemoembolization. The most widely used ablation techniques for lung cancer are radiofrequency ablation (RFA), cryoablation, and microwave ablation. Ablation may be an option for patients whose tumors are near the outer edge of the lungs. Nodules less than 1 cm from the trachea, main bronchi, oesophagus, and central vessels should be excluded from RFA given high risk of complications and frequent incomplete ablation. Additionally, lesions greater than 5 cm should be excluded and lesions 3 to 5 cm should be considered with caution given high risk of recurrence. As a minimally invasive procedure, it can be a safer alternative for patients who are poor candidates for surgery due to comorbidities or limited lung function. A study comparing thermal ablation to sublobar resection as treatment for early stage NSCLC in older people found no difference in overall survival of the patients. It is possible that RFA followed by radiation therapy has a survival benefit due to synergism of the two mechanisms of cell destruction. Advanced/metastatic NSCLC The treatment approach for people who have advanced NSCLC is first aimed at relieving pain and distress (palliative), but a wide variety of chemotherapy options exists. These agents include both traditional chemotherapies, such as cisplatin, which indiscriminately target all rapidly dividing cells, and newer targeted agents, which are more tailored to specific genetic aberrations found within a persons tumor. When choosing an appropriate chemotherapy approach, the toxicity profile (side effects of the drug) should be taken into account and balanced with the persons comorbidities (other conditions or side effects that the person is experiencing). Carboplatin is a chemotherapy agent that has a similar effect on a persons survival when compared to cisplatin, and has a different toxicity profile from cisplatin. Carboplatin may be associated with a higher risk of thrombocytopenia. Cisplatin may cause more nausea or vomiting when compared to carboplatin treatment.At present, two genetic markers are routinely profiled in NSCLC tumors to guide further treatment decision-making - mutations within epidermal growth factor (EGFR) and anaplastic lymphoma kinase. Also, a number of additional genetic markers are known to be mutated within NSCLC and may impact treatment in the future, including BRAF, HER2/neu, and KRAS. For advanced NSCLC, a combined chemotherapy treatment approach that includes cetuximab, an antibody that targets the EGFR signalling pathway, is more effective at improving a persons overall survival when compared to standard chemotherapy alone.Thermal ablations, i.e. RFA, cryoablation, and microwave ablation, are appropriate for palliative treatment of tumor-related symptoms or recurrences within treatment fields. People with severe pulmonary fibrosis and severe emphysema with a life expectancy less than a year should be considered poor candidates for this treatment. EGFR mutations Roughly 10–35% of people who have NSCLC will have drug-sensitizing mutations of the EGFR. The distribution of these mutations has been found to be race-dependent, with one study estimating that 10% of Caucasians, but 50% of Asians, will be found to have such tumor markers. A number of different EGFR mutations have been discovered, but certain aberrations result in hyperactive forms of the protein. People with these mutations are more likely to have adenocarcinoma histology and be nonsmokers or light smokers. These people have been shown to be sensitized to certain medications that block the EGFR protein known as tyrosine kinase inhibitors specifically, erlotinib, gefitinib, afatinib, or osimertinib. Reliable identification of mutations in lung cancer needs careful consideration due to the variable sensitivity of diagnostic techniques. ALK gene rearrangements Up to 7% of NSCLC patients have EML4-ALK translocations or mutations in the ROS1 gene; these patients may benefit from ALK inhibitors, which are now approved for this subset of patients. Crizotinib, which gained FDA approval in August 2011, is an inhibitor of several kinases, specifically ALK, ROS1, and MET. Crizotinib has been shown in clinical studies to have response rates around 60% if patients are shown to have ALK-positive disease. Several studies have also shown that ALK mutations and EGFR activating mutations are typically mutually exclusive. Thus, patients who fail crizotinib are not recommended to be switched to an EGFR-targeted drug such as erlotinib. Other treatment options NSCLC patients with advanced disease who are not found to have either EGFR or ALK mutations may receive bevacizumab, which is a monoclonal antibody medication targeted against the vascular endothelial growth factor (VEGF). This is based on an Eastern Cooperative Oncology Group study that found that adding bevacizumab to carboplatin and paclitaxel chemotherapy for certain patients with recurrent or advanced NSCLC (stage IIIB or IV) may increase both overall survival and progression-free survival. NSCLC cells expressing programmed death-ligand 1 (PD-L1) could interact with programmed death receptor 1 (PD-1) expressed on the surface of T cells, and result in decreased tumor cell kill by the immune system. Atezolizumab is an anti PD-L1 monoclonal antibody. Nivolumab and Pembrolizumab are anti PD-1 monoclonal antibodies. Ipilimumab is a monoclonal antibody that targets Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on the surface of T cells. Bevacizumab is a monoclonal antibody that targets Vascular Endothelial Growth Factor (VEGF) in the circulation and functions as an angiogenesis inhibitor. Multiple phase 3 clinical trials utilizing immunotherapy in the first line for treatment of NSCLC were published, including Pembrolizumab in KEYNOTE-024, KEYNOTE-042, KEYNOTE-189 and KEYNOTE-407; Nivolumab and Ipilimumab in CHECKMATE-227 and CHECKMATE 9LA; and Atezolizumab in IMpower110, IMpower130 and IMpower150.In 2015, the US Food and Drug Administration (FDA) approved the anti-PD-1 agent nivolumab for advanced or metastatic SCC.In 2015, FDA also approved the anti-EGFR drug necitumumab for metastatic SCC.2 October 2015, the FDA approved pembrolizumab for the treatment of metastatic NSCLC in patients whose tumors express PD-L1 and who have failed treatment with other chemotherapeutic agents.October 2016, pembrolizumab became the first immunotherapy to be used first line in the treatment of NSCLC if the cancer overexpresses PDL1 and the cancer has no mutations in EGFR or in ALK; if chemotherapy has already been administered, then pembrolizumab can be used as a second-line treatment, but if the cancer has EGFR or ALK mutations, agents targeting those mutations should be used first. Assessment of PDL1 must be conducted with a validated and approved companion diagnostic. The prognosis of patients with non-small-cell lung cancer improved significantly with the introduction of immunotherapy. People with tumor PDL-1 expressed over half or more of the tumor cells achieved a median overall survival of 30 months with pembrolizumab.Mobocertinib (Exkivity) was approved for medical use in the United States in September 2021, and it is indicated for adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. References External links MedlinePlus Encyclopedia: Lung cancer — non-small cell
Umbilical granuloma	Umbilical granuloma is the most common umbilical abnormality in newborn children or neonates, causing inflammation and drainage. It may appear in the first few weeks of newborn infants during the healing process of the umbilical cord due to an umbilical mass. It is the overgrowth of the umbilical tissue. It develops in about 1 out of 500 newborns. With appropriate treatment, it is expected to heal in 1~2 weeks. Causes Following umbilical cord clamping during delivery, the umbilicus base will spontaneously separate within 7-15 days. With routine cord care and proper hygienic conditions, the remaining umbilical base will heal and new skin tissue will form. In some instances, a mass of tissue, or granuloma, will form at the base.Umbilical granulomas occur after umbilical cord removal when the remaining ring of the umbilicus undergoes incomplete wound healing and there is excessive healing tissue, also known as granulation tissue.Delayed cord separation, mild infections and hygienic conditions are all factors which may contribute to the incidence of umbilical granuloma. Although the exact cause of umbilical granulomas is unknown, it is hypothesized that inflammation of the remaining umbilical stump drives skin cell division, resulting in a tissue mass, rather than proper healing at the site. Histophysiology An umbilical granuloma is a physiological response which surpasses the normal processes of skin restoration following umbilical cord clamping. Once the skin lesion is formed, there is an excess of fibroblast production. These fibroblasts, or connective tissue cells, are responsible for the production of collagen and additional fibers, resulting in the excess tissue mass found in the granuloma. Additional histological studies reveal an increase of cell division of vascular endothelial cells. These cells line our blood vessels and are further responsible for the growth and development of tissue and the formation of new blood vessels within the granuloma. Pathophysiology Inflammatory saprophytic microorganisms, involved with decomposition, may delay the healing process, and can lead to overproduction of fibroblasts that are involved in normal skin restoration. These microorganisms can interfere with the skin’s normal flora, and lead to increased pathogenic inflammation that leads to delayed epithelialization and the formation of granulomas with excessive blood vessels, fibroblasts, and mucus. Signs and symptoms Umbilical granulomas appear as round, pink lumps found at the base of the umbilicus after the removal of the umbilical cord. It appears small, pink/red, and moist due to cord separation. They are usually 1-10 mm in size, however grow in size if they are not treated. Umbilical granulomas are also painless since they do not contain nerve fibers. In some cases, they may contain an odorless discharge, or may be covered in a clear mucus. The surrounding skin of the infants umbilicus site will appear normal. Umbilical granulomas can become entry points for infectious agents. Symptoms such as edema, redness around the umbilical site, pain or discomfort when the area is touched, accompanied by a fever and purulent discharge, may indicate sepsis or a serious infection at the umbilicus site. Diagnosis Umbilical granuloma can be diagnosed from physical examination. If there is a discharge around the navel and the granulation tissue is large enough to be visible with the open eye, umbilical granuloma is the first to be suspected. Open eye inspection and/or dermoscopy is commonly used to recognize the granular tissue at the site. If the granuloma is not visible with the open eye, gentle pressure on the surrounding site or a surgical tweezer can be used to expose the small granuloma hidden within the umbilical pit. An otoscope may also be used by physicians in order to expose a small, sessile granuloma. Other additional tests are usually not required, but if continued, ultrasonography (US) can be used for initial diagnosis of umbilical lesions. Treatment Topical Although there is no singular method of treatment for umbilical granulomas, some treatment options available include common salt, silver nitrate, corticosteroids, and cleaning with alcohol. Home care following treatments include gentle cleaning the navel area with soap and sterile water, followed by open exposure of the belly button to air. Silver nitrate Silver nitrate is the most common treatment and practiced worldwide. Neonatology textbooks suggest silver nitrate as a first-line treatment option. The application of silver nitrate to granulomas was first noted in early 1800s as a cauterizing agent.Silver nitrate can be used as an antiseptic, an astringent, and as a caustic agent, depending on the indication. Its application requires medical personnel for treatment and may have unfavorable adverse effects if applied improperly. In the treatment of umbilical granulomas, silver nitrate is applied to the umbilical site to burn off the excess tissue. The absence of nerve endings within the granuloma make this a painless treatment for the newborn. While painless, contact of silver nitrate to the adjacent, healthy, normal tissue may result in burns. Silver nitrate application to the infected site should not exceed three applications with an interval of 3-4 days. In this event, alternative treatments should be considered Following treatment with silver nitrate, the granuloma is expected to shrink and resolve within 7 days. Double-ligature treatment In cases with deeply located umbilical granulomas, the double-ligature technique can be utilized to ligate the base of the granuloma. The procedure involves prepping and sterilizing the umbilical area with iodine solution, placing a silk suture around the base of the lesion to keep in place, and finally placing a more exact ligature around the granuloma. Much like the normal process of umbilical cord residue healing, the ligated granuloma will necrose due to lack of blood supply and will fall off naturally within 1 to 2 weeks. Minor complications of this technique include minimal bleeding and possibly requiring more ligatures than the original double ligation. Cryocautery Cryocautery can be utilized to freeze the umbilical granuloma by using cryogenic nitrous oxide along with other equipment. During cryocautery procedures, the umbilical site is first cleaned. The physician will then hold a cyroprobe with nitrous oxide as a refrigerant directly to the granuloma for 3 minutes. One risk of utilizing this technique is burning the skin surrounding the granuloma. Following the procedure, the naval site is cleansed, left exposed to the air and the infant is discharged. Cyrocautery is more commonly used for freezing for post hysterectomy granulation tissue. However, though more expensive and complex, cryosurgery is an effective treatment for the indication of umbilical granulomas in infants as well. Prevention Newborn naval care In order to reduce the possibility of an infection or inflammation at the umbilical site, the World Health Organization (WHO) has advocated for the use of dry umbilical cord care in high resource settings. Dry cord care includes keeping the newborns umbilical area clean and exposed to air or loosely covered by a clean cloth. The remainder of the umbilicus should be cleaned once daily with soap and sterile water. Chlorhexidine is recommended in substitute of sterile water for areas in which infection risks are high.Diaper positioning can also influence infection risk. Keeping the diaper area clean and reducing moisture at the site can reduce the chance of developing an infection. Aim to position the diaper by rolling the top portion down to sit under the navel, keeping the site open and exposed to air. Cord clamping technique The incidence of umbilical granuloma may be influenced by the method of cord clamping. It has been suggested that proximal cord clamping of the umbilical cord for 24 hours reduces the chance of infection at the naval site compared to other cord clamping practices. Timing Umbilical cord clamping timing can vary in time intervals. Early clamping is categorized as within the first 60 seconds after birth, whereas late umbilical cord clamping is classified as more than one minute after the birth. There is no evidence indicating that time to umbilical cord clamping has had an effect on umbilical granuloma formation or on additional neonatal morbidity outcomes. Complications If an infection occurs, omphalitis may occur. Recurrence risk The various treatment modalities of umbilical granuloma result in various recurrence risks. In a systematic review, following infants through weeks 1, 3 and 6 post-treatment for umbilical granuloma, newborns treated with silver nitrate presented with a 9% recurrence risk, whereas newborns treated with common salt presented null recurrence. See also Teratoma List of cutaneous conditions == References ==
Dissociative identity disorder	Dissociative identity disorder (DID), previously known as multiple personality disorder (MPD), and colloquially known as split personality disorder, is a mental disorder characterized by the maintenance of at least two distinct and relatively enduring personality states.The disorder is accompanied by memory gaps more severe than could be explained by ordinary forgetfulness. The personality states alternately show in a persons behavior; however, presentations of the disorder vary. Other conditions that often occur in people with DID include post-traumatic stress disorder, personality disorders (especially borderline and avoidant), depression, substance use disorders, conversion disorder, somatic symptom disorder, eating disorders, obsessive–compulsive disorder, and sleep disorders. Self-harm, non-epileptic seizures, flashbacks with amnesia for content of flashbacks, anxiety disorders, and suicidality are also common. Overview The following three subsections give brief overviews of the proposed cause of dissociative identity disorder (DID) and how it is recognized; conventional treatment of DID, and how frequently it occurs; and finally how it is perceived in present western culture. All of the topics are treated in greater detail in later sections. Cause and diagnosis DID is associated with overwhelming traumas or abuse during childhood.(p 294) In about 90% of cases, there is a history of neglect or abuse in childhood, while other cases are linked to experiences of war, or severe medical procedures during childhood. Genetic and biological factors are also believed to play a role. The diagnosis should not be made if the persons condition is better accounted for by substance use disorder, seizures, other mental health problems, imaginative play in children, or religious practices. Treatment and epidemiology Treatment generally involves supportive care and psychotherapy. The condition usually persists without treatment. It is believed to affect about 1.5% of the general population (based on a small US community sample) and 3% of those admitted to hospitals with mental health issues in Europe and North America. DID is diagnosed about six times more often in women than in men. The number of recorded cases increased significantly in the latter half of the 20th century, along with the number of identities reported by those affected. Society and culture DID is controversial within both the field of psychiatry and the legal system. Claims of DID have been used only rarely to argue criminal insanity in court.It is unclear whether increased rates of the disorder are due to better recognition or sociocultural factors such as mass media portrayals. The typical presenting symptoms in different regions of the world may also vary depending on culture, for example alter identities taking the form of possessing spirits, deities, ghosts, or mythical figures in cultures where normative possession states are common.(pp 295, 801) The possession form of dissociative identity disorder is involuntary and distressing, and occurs in a way that violates cultural or religious norms.(p 295) Definitions Dissociation, the term that underlies dissociative disorders including DID, lacks a precise, empirical, and generally agreed upon definition.A large number of diverse experiences have been termed dissociative, ranging from normal failures in attention to the breakdowns in memory processes characterized by the dissociative disorders. It is therefore unknown if there is a commonality between all dissociative experiences, or if the range of mild to severe symptoms is a result of different etiologies and biological structures. Other terms used in the literature, including personality, personality state, identity, ego state, and amnesia, also have no agreed upon definitions. Multiple competing models exist that incorporate some non-dissociative symptoms while excluding dissociative ones.Due to the lack of consensus regarding terminology in the study of DID, several terms have been proposed. One is ego state (behaviors and experiences possessing permeable boundaries with other such states but united by a common sense of self), while the other term is alters (each of which may have a separate autobiographical memory, independent initiative and a sense of ownership over individual behavior).Ellert Nijenhuis and colleagues suggest a distinction between personalities responsible for day-to-day functioning (associated with blunted physiological responses and reduced emotional reactivity, referred to as the "apparently normal part of the personality" or ANP) and those emerging in survival situations (involving fight-or-flight responses, vivid traumatic memories and strong, painful emotions – the "emotional part of the personality" or EP). "Structural dissociation of the personality" is used by Otto van der Hart and colleagues to distinguish dissociation they attribute to traumatic or pathological causes, which in turn is divided into primary, secondary and tertiary dissociation. According to this hypothesis, primary dissociation involves one ANP and one EP, while secondary dissociation involves one ANP and at least two EPs and tertiary dissociation, which is unique to DID, is described as having at least two ANPs and at least two EPs. Others have suggested dissociation can be separated into two distinct forms, detachment and compartmentalization, the latter of which, involving a failure to control normally controllable processes or actions, is most evident in DID. Efforts to psychometrically distinguish between normal and pathological dissociation have been made. Signs and symptoms According to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), symptoms of DID include "the presence of two or more distinct personality states" accompanied by the inability to recall personal information beyond what is expected through normal memory issues. Other DSM-5 symptoms include a loss of identity as related to individual distinct personality states, loss of ones subjective experience of the passage of time, and degradation of a sense of self and consciousness. In each individual, the clinical presentation varies and the level of functioning can change from severe impairment to minimal impairment. The symptoms of dissociative amnesia are subsumed under a DID diagnosis, and thus should not be diagnosed separately if DID criteria are met. Individuals with DID may experience distress from both the symptoms of DID (intrusive thoughts or emotions) and the consequences of the accompanying symptoms (dissociation rendering them unable to remember specific information). The majority of patients with DID report childhood sexual or physical abuse, though the accuracy of these reports is controversial. Amnesia between identities may be asymmetrical; identities may or may not be aware of what is known by another. Individuals with DID may be reluctant to discuss symptoms due to associations with abuse, shame, and fear. DID patients may also frequently and intensely experience time disturbances.Around half of people with DID have fewer than 10 identities and most have fewer than 100; although as many as 4,500 have been reported.(p 503) The average number of identities has increased over the past few decades, from two or three to now an average of approximately 16. However, it is unclear whether this is due to an actual increase in identities, or simply that the psychiatric community has become more accepting of a high number of compartmentalized memory components. Comorbid disorders The psychiatric history frequently contains multiple previous diagnoses of various disorders and treatment failures. The most common presenting complaint of DID is depression, with headaches being a common neurological symptom. Comorbid disorders can include substance use disorder, eating disorders, anxiety disorders, bipolar disorder, and personality disorders. A significant percentage of those diagnosed with DID have histories of borderline personality disorder and post-traumatic stress disorder (PTSD). Presentations of dissociation in people with schizophrenia differ from those with DID as not being rooted in trauma, and this distinction can be effectively tested, although both conditions share a high rate of dissociative auditory hallucinations. Other disorders that have been found to be comorbid with DID are somatization disorders, major depressive disorder, as well as history of a past suicide attempt, in comparison to those without a DID diagnosis. Individuals diagnosed with DID demonstrate the highest hypnotizability of any clinical population. Although DID has high comorbidity and its development is related to trauma, there exists evidence to suggest that DID merits a separate diagnosis from other conditions like PTSD. Borderline personality disorder The DSM-IV-TR states that self-harm, impulsivity, and rapid changes in interpersonal relationships "may warrant a concurrent diagnosis of borderline personality disorder." Steven Lynn and colleagues have suggested that the significant overlap between BPD and DID may be a contributing factor to the development of therapy induced DID, in that the suggestion of hidden alters by therapists who propose a diagnosis of DID provides an explanation to patients for the behavioral instability, self-mutilation, unpredictable mood changes and actions they experience. In 1993 a group of researchers reviewed both DID and borderline personality disorder (BPD), concluding that DID was an epiphenomenon of BPD, with no tests or clinical description capable of distinguishing between the two. Their conclusions about the empirical proof of DID were echoed by a second group, who still believed the diagnosis existed, but while the knowledge to date did not justify DID as a separate diagnosis, it also did not disprove its existence. Reviews of medical records and psychological tests indicated that the majority of DID patients could be diagnosed with BPD instead, though about a third could not, suggesting that DID does exist but may be over-diagnosed. Both groups also report higher rates of physical and sexual abuse than the general population, and patients with BPD also score highly on measures of dissociation. Even using strict diagnostic criteria, it can be difficult to distinguish between dissociative disorders and BPD (as well as bipolar disorder and schizophrenia), though the presence of comorbid anxiety disorders may help.}} Causes General DID is etiologically complex. Şar et al. state, "Dissociative identity disorder (DID) is multifactorial in its etiology. Whereas psychosocial etiologies of DID include developmental traumatization and sociocognitive sequelae, biological factors include trauma-generated neurobiological responses. Biologically derived traits and epigenetic mechanisms are also likely to be at play. At this point, no direct examination of genetics has occurred in DID. However, it is likely to exist, given the genetic link to dissociation in general and in relation to childhood adversity in particular." Stating that there is "a lack of understanding regarding the etiopathology of DID", Blihar adds that "many researchers and psychiatrists regard DID as the most severe form of a childhood onset post-traumatic stress disorder (PTSD) because it is virtually impossible to find a DID patient without a history of PTSD.... There are currently two competing theories regarding the relationship between trauma and dissociation: the trauma-related model and the fantasy-prone model."The DSM-5 diagnostic manual states that DID is "associated with overwhelming experiences, traumatic events, and/or abuse during childhood".(p 294) Other risk factors reported include childhood neglect, childhood medical procedures, war, terrorism, and childhood prostitution.(p 295) Dissociative disorders frequently occur after trauma, and the DSM5 places them after the trauma and stressor-related disorders to reflect this close relationship.(p 291) Disturbed and altered sleep has also been suggested as having a role in dissociative disorders in general and specifically in DID, alterations in environments also largely affecting the DID patient. Developmental trauma People diagnosed with DID often report that they have experienced physical or sexual abuse during childhood (although the accuracy of these reports has been disputed); others report overwhelming stress, serious medical illness or other traumatic events during childhood. They also report more historical psychological trauma than those diagnosed with any other mental illness. Severe sexual, physical, or psychological trauma in childhood has been proposed as an explanation for its development; awareness, memories and emotions of harmful actions or events caused by the trauma are removed from consciousness, and alternate personalities or subpersonalities form with differing memories, emotions and behavior. DID is attributed to extremes of stress or disorders of attachment. What may be expressed as post-traumatic stress disorder (PTSD) in adults may become DID when occurring in children, possibly due to their greater use of imagination as a form of coping.Possibly due to developmental changes and a more coherent sense of self past the age of six, the experience of extreme trauma may result in different, though also complex, dissociative symptoms and identity disturbances. A specific relationship between childhood abuse, disorganized attachment, and lack of social support are thought to be a necessary component of DID. Although what role a childs biological capacity to dissociate to an extreme level remains unclear, some evidence indicates a neurobiological impact of developmental stress.Delinking early trauma from the etiology of dissociation has been explicitly rejected by those supporting the early trauma model. However, a 2012 review article supports the hypothesis that current or recent trauma may affect an individuals assessment of the more distant past, changing the experience of the past and resulting in dissociative states. Giesbrecht et al. have suggested there is no actual empirical evidence linking early trauma to dissociation, and instead suggest that problems with neuropsychological functioning, such as increased distractibility in response to certain emotions and contexts, account for dissociative features. A middle position hypothesizes that trauma, in some situations, alters neuronal mechanisms related to memory. Evidence is increasing that dissociative disorders are related both to a trauma history and to "specific neural mechanisms". It has also been suggested that there may be a genuine but more modest link between trauma and DID, with early trauma causing increased fantasy-proneness, which may in turn render individuals more vulnerable to socio-cognitive influences surrounding the development of DID. Another suggestion made by Hart indicates that there are triggers in the brain that can be the catalyst for different self-states, and that victims of trauma are more susceptible to these triggers than non-victims of trauma; these triggers are said to be related to DID.Paris states that the trauma model of DID increased the appeal of the diagnosis among health care providers, patients and the public as it validated the idea that child abuse had lifelong, serious effects. Paris asserts that there is very little experimental evidence supporting the trauma-dissociation hypothesis, and no research showing that dissociation consistently links to long-term memory disruption. Therapist-induced The prevailing post-traumatic model of dissociation and dissociative disorders is contested. It has been hypothesized that symptoms of DID may be created by therapists using techniques to "recover" memories (such as the use of hypnosis to "access" alter identities, facilitate age regression or retrieve memories) on suggestible individuals. Referred to as the "sociocognitive model" (SCM), it proposes that DID is due to a person consciously or unconsciously behaving in certain ways promoted by cultural stereotypes, with unwitting therapists providing cues through improper therapeutic techniques. This model posits that behavior is enhanced by media portrayals of DID.Proponents of the SCM note that the bizarre dissociative symptoms are rarely present before intensive therapy by specialists in the treatment of DID who, through the process of eliciting, conversing with and identifying alters, shape or possibly create the diagnosis. While proponents note that DID is accompanied by genuine suffering and the distressing symptoms, and can be diagnosed reliably using the DSM criteria, they are skeptical of the traumatic etiology suggested by proponents. The characteristics of people diagnosed with DID (hypnotizability, suggestibility, frequent fantasization and mental absorption) contributed to these concerns and those regarding the validity of recovered memories of trauma. Skeptics note that a small subset of doctors are responsible for diagnosing the majority of individuals with DID. Psychologist Nicholas Spanos and others have suggested that in addition to therapy caused cases, DID may be the result of role-playing rather than alternative identities, though others disagree, pointing to a lack of incentive to manufacture or maintain separate identities and point to the claimed histories of abuse. Other arguments that therapy can cause DID, include the lack of children diagnosed with DID, the sudden spike in rates of diagnosis after 1980 (although DID was not a diagnosis until DSM-IV, published in 1994), the absence of evidence of increased rates of child abuse, the appearance of the disorder almost exclusively in individuals undergoing psychotherapy, particularly involving hypnosis, the presences of bizarre alternate identities (such as those claiming to be animals or mythological creatures) and an increase in the number of alternate identities over time (as well as an initial increase in their number as psychotherapy begins in DID-oriented therapy). These various cultural and therapeutic causes occur within a context of pre-existing psychopathology, notably borderline personality disorder, which is commonly comorbid with DID. In addition, presentations can vary across cultures, such as Indian patients who only switch alters after a period of sleep – which is commonly how DID is presented by the media within that country.Proponents of psychotherapy as a cause of DID state that DID is strongly linked to (possibly suggestive) psychotherapy, often involving recovered memories (memories that the person previously had amnesia for) or false memories, and that such therapy could cause additional identities. Such memories could be used to make an allegation of child sexual abuse. There is little agreement between those who see therapy as a cause and trauma as a cause. Supporters of therapy as a cause of DID suggest that a small number of clinicians diagnosing a disproportionate number of cases would provide evidence for their position though it has also been claimed that higher rates of diagnosis in specific countries like the United States may be due to greater awareness of DID. Lower rates in other countries may be due to artificially low recognition of the diagnosis. However, false memory syndrome per se is not regarded by mental health experts as a valid diagnosis, and has been described as "a non-psychological term originated by a private foundation whose stated purpose is to support accused parents," and critics argue that the concept has no empirical support, and further describe the False Memory Syndrome Foundation as an advocacy group that has distorted and misrepresented memory research. Children The rarity of DID diagnosis in children is cited as a reason to doubt the validity of DID, and proponents of both etiologies believe that the discovery of DID in a child who had never undergone treatment would critically undermine the SCM. Conversely, if children are found to develop DID only after undergoing treatment it would challenge the traumagenic model. As of 2011, approximately 250 cases of DID in children have been identified, though the data does not offer unequivocal support for either theory. While children have been diagnosed with DID before therapy, several were presented to clinicians by parents who were themselves diagnosed with DID; others were influenced by the appearance of DID in popular culture or due to a diagnosis of psychosis due to hearing voices – a symptom also found in DID. No studies have looked for children with DID in the general population, and the single study that attempted to look for children with DID not already in therapy did so by examining siblings of those already in therapy for DID. An analysis of diagnosis of children reported in scientific publications, 44 case studies of single patients were found to be evenly distributed (i.e., each case study was reported by a different author) but in articles regarding groups of patients, four researchers were responsible for the majority of the reports.The initial theoretical description of DID was that dissociative symptoms were a means of coping with extreme stress (particularly childhood sexual and physical abuse), but this belief has been challenged by the data of multiple research studies. Proponents of the traumagenic hypothesis claim the high correlation of child sexual and physical abuse reported by adults with DID corroborates the link between trauma and DID. However, the DID–maltreatment link has been questioned for several reasons. The studies reporting the links often rely on self-report rather than independent corroborations, and these results may be worsened by selection and referral bias. Most studies of trauma and dissociation are cross-sectional rather than longitudinal, which means researchers can not attribute causation, and studies avoiding recall bias have failed to corroborate such a causal link. In addition, studies rarely control for the many disorders comorbid with DID, or family maladjustment (which is itself highly correlated with DID). The popular association of DID with childhood abuse is relatively recent, occurring only after the publication of Sybil in 1973. Most previous examples of "multiples" such as Chris Costner Sizemore, whose life was depicted in the book and film The Three Faces of Eve, disclosed no history of child abuse. Pathophysiology Despite research on DID including structural and functional magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, event-related potential, and electroencephalography, no convergent neuroimaging findings have been identified regarding DID, making it difficult to hypothesize a biological basis for DID. In addition, many of the studies that do exist were performed from an explicitly trauma-based position, and did not consider the possibility of therapy as a cause of DID. There is no research to date regarding the neuroimaging and introduction of false memories in DID patients, though there is evidence of changes in visual parameters and support for amnesia between alters. DID patients also appear to show deficiencies in tests of conscious control of attention and memorization (which also showed signs of compartmentalization for implicit memory between alters but no such compartmentalization for verbal memory) and increased and persistent vigilance and startle responses to sound. DID patients may also demonstrate altered neuroanatomy. Experimental tests of memory suggest that patients with DID may have improved memory for certain tasks, which has been used to criticize the hypothesis that DID is a means of forgetting or suppressing memory. Patients also show experimental evidence of being more fantasy-prone, which in turn is related to a tendency to over-report false memories of painful events. Diagnosis General The fifth, revised edition of the American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnoses DID according to the diagnostic criteria found under code 300.14 (dissociative disorders). DID is often initially misdiagnosed because clinicians receive little training about dissociative disorders or DID, and often use standard diagnostic interviews that do not include questions about trauma, dissociation or post-traumatic symptoms.(p 118) This contributes to difficulties diagnosing the disorder and clinician bias.DID is rarely diagnosed in children, despite the average age of appearance of the first alter being three years old. The criteria require that an individual be recurrently controlled by two or more discrete identities or personality states, accompanied by memory lapses for important information that is not caused by alcohol, drugs or medications and other medical conditions such as complex partial seizures. In children the symptoms must not be better explained by "imaginary playmates or other fantasy play". Diagnosis is normally performed by a clinically trained mental health professional such as a psychiatrist or psychologist through clinical evaluation, interviews with family and friends, and consideration of other ancillary material. Specially designed interviews (such as the SCID-D) and personality assessment tools may be used in the evaluation as well. Since most of the symptoms depend on self-report and are not concrete and observable, there is a degree of subjectivity in making the diagnosis. People are often disinclined to seek treatment, especially since their symptoms may not be taken seriously; thus dissociative disorders have been referred to as "diseases of hiddenness".The diagnosis has been criticized by supporters of therapy as a cause or the sociocognitive hypothesis as they believe it is a culture-bound and often health care induced condition. The social cues involved in diagnosis may be instrumental in shaping patient behavior or attribution, such that symptoms within one context may be linked to DID, while in another time or place the diagnosis could have been something other than DID. Other researchers disagree and argue that the existence of the condition and its inclusion in the DSM is supported by multiple lines of reliable evidence, with diagnostic criteria allowing it to be clearly discriminated from conditions it is often mistaken for (schizophrenia, borderline personality disorder, and seizure disorder). That a large proportion of cases are diagnosed by specific health care providers, and that symptoms have been created in nonclinical research subjects given appropriate cueing has been suggested as evidence that a small number of clinicians who specialize in DID are responsible for the creation of alters through therapy. The condition may be under-diagnosed due to skepticism and lack of awareness from mental health professionals, made difficult due to the lack of specific and reliable criteria for diagnosing DID as well as a lack of prevalence rates due to the failure to examine systematically selected and representative populations. Differential diagnoses People with DID are diagnosed with five to seven comorbid disorders on average – much higher than other mental illnesses.Due to overlapping symptoms, the differential diagnosis includes schizophrenia, normal and rapid-cycling bipolar disorder, epilepsy, borderline personality disorder, and autism spectrum disorder. Delusions or auditory hallucinations can be mistaken for speech by other personalities. Persistence and consistency of identities and behavior, amnesia, measures of dissociation or hypnotizability and reports from family members or other associates indicating a history of such changes can help distinguish DID from other conditions. A diagnosis of DID takes precedence over any other dissociative disorders. Distinguishing DID from malingering is a concern when financial or legal gains are an issue, and factitious disorder may also be considered if the person has a history of help or attention-seeking. Individuals who state that their symptoms are due to external spirits or entities entering their bodies are generally diagnosed with dissociative disorder not otherwise specified rather than DID due to the lack of identities or personality states. Most individuals who enter an emergency department and are unaware of their names are generally in a psychotic state. Although auditory hallucinations are common in DID, complex visual hallucinations may also occur. Those with DID generally have adequate reality testing; they may have positive Schneiderian symptoms of schizophrenia but lack the negative symptoms. They perceive any voices heard as coming from inside their heads (patients with schizophrenia experience them as external). In addition, individuals with psychosis are much less susceptible to hypnosis than those with DID. Difficulties in differential diagnosis are increased in children.DID must be distinguished from, or determined if comorbid with, a variety of disorders including mood disorders, psychosis, anxiety disorders, PTSD, personality disorders, cognitive disorders, neurological disorders, epilepsy, somatoform disorder, factitious disorder, malingering, other dissociative disorders, and trance states. An additional aspect of the controversy of diagnosis is that there are many forms of dissociation and memory lapses, which can be common in both stressful and nonstressful situations and can be attributed to much less controversial diagnoses. Individuals faking or mimicking DID due to factitious disorder will typically exaggerate symptoms (particularly when observed), lie, blame bad behavior on symptoms and often show little distress regarding their apparent diagnosis. In contrast, genuine people with DID typically exhibit confusion, distress and shame regarding their symptoms and history.A relationship between DID and borderline personality disorder has been posited, with various clinicians noting overlap between symptoms and behaviors and it has been suggested that some cases of DID may arise "from a substrate of borderline traits". Reviews of DID patients and their medical records concluded that the majority of those diagnosed with DID would also meet the criteria for either borderline personality disorder or more generally borderline personality.The DSM-5 elaborates on cultural background as an influence for some presentations of DID.(p 295) Many features of dissociative identity disorder can be influenced by the individuals cultural background. Individuals with this disorder may present with prominent medically unexplained neurological symptoms, such as non-epileptic seizures, paralyses, or sensory loss, in cultural settings where such symptoms are common. Similarly, in settings where normative possession is common (e.g., rural areas in the developing world, among certain religious groups in the United States and Europe), the fragmented identities may take the form of possessing spirits, deities, demons, animals, or mythical figures. Acculturation or prolonged intercultural contact may shape the characteristics of other identities (e.g., identities in India may speak English exclusively and wear Western clothes). Possession-form dissociative identity disorder can be distinguished from culturally accepted possession states in that the former is involuntary, distressing, uncontrollable, and often recurrent or persistent; involves conflict between the individual and his or her surrounding family, social, or work milieu; and is manifested at times and in places that violate the norms of the culture or religion. Controversy DID is among the most controversial of the dissociative disorders and among the most controversial disorders found in the DSM-5. The primary dispute is between those who believe DID is caused by traumatic stresses forcing the mind to split into multiple identities, each with a separate set of memories, and the belief that the symptoms of DID are produced artificially by certain psychotherapeutic practices or patients playing a role they believe appropriate for a person with DID. The debate between the two positions is characterized by intense disagreement. Research into this hypothesis has been characterized by poor methodology. Psychiatrist Joel Paris notes that the idea that a personality is capable of splitting into independent alters is an unproven assertion that is at odds with research in cognitive psychology.Some believe that DID is caused by health care, i.e. symptoms of DID are created by therapists themselves via hypnosis. This belief also implies that those with DID are more susceptible to manipulation by hypnosis and suggestion than others. The iatrogenic model also sometimes states that treatment for DID is harmful. According to Brand, Loewenstein and Spiegel, "[t]he claims that DID treatment is harmful are based on anecdotal cases, opinion pieces, reports of damage that are not substant
Dissociative identity disorder	iated in the scientific literature, misrepresentations of the data, and misunderstandings about DID treatment and the phenomenology of DID". Their claim is evinced by the fact that only 5%–10% of people receiving treatment worsen in their symptoms.Psychiatrists August Piper and Harold Merskey have challenged the trauma hypothesis, arguing that correlation does not imply causation – the fact that people with DID report childhood trauma does not mean trauma causes DID – and point to the rareness of the diagnosis before 1980 as well as a failure to find DID as an outcome in longitudinal studies of traumatized children. They assert that DID cannot be accurately diagnosed because of vague and unclear diagnostic criteria in the DSM and undefined concepts such as "personality state" and "identities", and question the evidence for childhood abuse beyond self-reports, the lack of definition of what would indicate a threshold of abuse sufficient to induce DID and the extremely small number of cases of children diagnosed with DID despite an average age of appearance of the first alter of three years. Psychiatrist Colin Ross disagrees with Piper and Merskeys conclusion that DID cannot be accurately diagnosed, pointing to internal consistency between different structured dissociative disorder interviews (including the Dissociative Experiences Scale, Dissociative Disorders Interview Schedule and Structured Clinical Interview for Dissociative Disorders) that are in the internal validity range of widely accepted mental illnesses such as schizophrenia and major depressive disorder. In his opinion, Piper and Merskey are setting the standard of proof higher than they are for other diagnoses. He also asserts that Piper and Merskey have cherry-picked data and not incorporated all relevant scientific literature available, such as independent corroborating evidence of trauma.A study in 2018 revealed that the phenomena of pathological dissociation (including identity alteration) had been portrayed in the ancient Chinese medicine literature, suggesting that pathological dissociation is a cross-cultural condition. Screening Perhaps due to their perceived rarity, the dissociative disorders (including DID) were not initially included in the Structured Clinical Interview for DSM-IV (SCID), which is designed to make psychiatric diagnoses more rigorous and reliable. Instead, shortly after the publication of the initial SCID a freestanding protocol for dissociative disorders (SCID-D) was published. This interview takes about 30 to 90 minutes depending on the subjects experiences. An alternative diagnostic instrument, the Dissociative Disorders Interview Schedule, also exists but the SCID-D is generally considered superior. The Dissociative Disorders Interview Schedule (DDIS) is a highly structured interview that discriminates among various DSM-IV diagnoses. The DDIS can usually be administered in 30–45 minutes.Other questionnaires include the Dissociative Experiences Scale (DES), Perceptual Alterations Scale, Questionnaire on Experiences of Dissociation, Dissociation Questionnaire, and the Mini-SCIDD. All are strongly intercorrelated and except the Mini-SCIDD, all incorporate absorption, a normal part of personality involving narrowing or broadening of attention. The DES is a simple, quick, and validated questionnaire that has been widely used to screen for dissociative symptoms, with variations for children and adolescents. Tests such as the DES provide a quick method of screening subjects so that the more time-consuming structured clinical interview can be used in the group with high DES scores. Depending on where the cutoff is set, people who would subsequently be diagnosed can be missed. An early recommended cutoff was 15–20. The reliability of the DES in non-clinical samples has been questioned. Treatment Treatment aims to increase integrated functioning. The International Society for the Study of Trauma and Dissociation has published guidelines for phase-oriented treatment in adults as well as children and adolescents that are widely used in the field of DID treatment. The guidelines state that "a desirable treatment outcome is a workable form of integration or harmony among alternate identities". Some experts in treating people with DID use the techniques recommended in the 2011 treatment guidelines. The empirical research includes the longitudinal TOP DD treatment study, which found that patients showed "statistically significant reductions in dissociation, PTSD, distress, depression, hospitalisations, suicide attempts, self-harm, dangerous behaviours, drug use and physical pain" and improved overall functioning. Treatment effects have been studied for over thirty years, with some studies having a follow-up of ten years. Adult and child treatment guidelines exist that suggest a three-phased approach, and are based on expert consensus. Highly experienced therapists have few patients that achieve a unified identity.Common treatment methods include an eclectic mix of psychotherapy techniques, including cognitive behavioral therapy (CBT), insight-oriented therapy, dialectical behavioral therapy (DBT), hypnotherapy and eye movement desensitization and reprocessing (EMDR).Medications can be used for comorbid disorders or targeted symptom relief, for example antidepressants or treatments to improve sleep. Some behavior therapists initially use behavioral treatments such as only responding to a single identity, and then use more traditional therapy once a consistent response is established. Brief treatment due to managed care may be difficult, as individuals diagnosed with DID may have unusual difficulties in trusting a therapist and take a prolonged period to form a comfortable therapeutic alliance. Regular contact (at least weekly) is recommended, and treatment generally lasts years – not weeks or months. Sleep hygiene has been suggested as a treatment option, but has not been tested. In general there are very few clinical trials on the treatment of DID, none of which were randomized controlled trials.Therapy for DID is generally phase oriented. Different alters may appear based on their greater ability to deal with specific situational stresses or threats. While some patients may initially present with a large number of alters, this number may reduce during treatment – though it is considered important for the therapist to become familiar with at least the more prominent personality states as the "host" personality may not be the "true" identity of the patient. Specific alters may react negatively to therapy, fearing the therapists goal is to eliminate the alter (particularly those associated with illegal or violent activities). A more realistic and appropriate goal of treatment is to integrate adaptive responses to abuse, injury or other threats into the overall personality structure. There is debate over issues such as whether exposure therapy (reliving traumatic memories, also known as abreaction), engagement with alters and physical contact during therapy are appropriate and there are clinical opinions both for and against each option with little high-quality evidence for any position.Brandt et al., commenting on the lack of empirical studies of treatment effectiveness, conducted a survey of 36 clinicians expert in treating dissociative disorder (DD) who recommended a three-stage treatment. They agreed that skill building in the first stage is important so the patient can learn to handle high risk, potentially dangerous behavior, as well as emotional regulation, interpersonal effectiveness and other practical behaviors. In addition, they recommended "trauma-based cognitive therapy" to reduce cognitive distortions related to trauma; they also recommended that the therapist deal with the dissociated identities early in treatment. In the middle stage, they recommended graded exposure techniques, along with appropriate interventions as needed. The treatment in the last stage was more individualized; few with DD [sic] became integrated into one identity.The first phase of therapy focuses on symptoms and relieving the distressing aspects of the condition, ensuring the safety of the individual, improving the patients capacity to form and maintain healthy relationships, and improving general daily life functioning. Comorbid disorders such as substance use disorder and eating disorders are addressed in this phase of treatment. The second phase focuses on stepwise exposure to traumatic memories and prevention of re-dissociation. The final phase focuses on reconnecting the identities of disparate alters into a single functioning identity with all its memories and experiences intact.A study was conducted to develop an "expertise-based prognostic model for the treatment of complex post-traumatic stress disorder (PTSD) and dissociative identity disorder (DID)". Researchers constructed a two-stage survey and factor analyses performed on the survey elements found 51 factors common to complex PTSD and DID. The authors concluded from their findings: "The model is supportive of the current phase-oriented treatment model, emphasizing the strengthening of the therapeutic relationship and the patients resources in the initial stabilization phase. Further research is needed to test the models statistical and clinical validity." Prognosis Little is known about prognosis of untreated DID. It rarely, if ever, goes away without treatment, but symptoms may resolve from time to time or wax and wane spontaneously. Patients with mainly dissociative and post-traumatic symptoms face a better prognosis than those with comorbid disorders or those still in contact with abusers, and the latter groups often face lengthier and more difficult treatment. Suicidal ideation, suicide attempts, and self-harm also may occur. Duration of treatment can vary depending on patient goals, which can range from merely improving inter-alter communication and cooperation, to reducing inter-alter amnesia, to integration of all alters, but generally takes years. Epidemiology General According to the American Psychiatric Association, the 12-month prevalence of DID among adults in the US is 1.5%, with similar prevalence between women and men. Population prevalence estimates have been described to widely vary, with some estimates of DID in inpatient settings suggesting 1-9.6%." Reported rates in the community vary from 1% to 3% with higher rates among psychiatric patients. As of 2017, evidence suggested a prevalence of DID of 2–5% among psychiatric inpatients, 2–3% among outpatients, and 1% in the general population, with rates reported as high as 16.4% for teenagers in psychiatric outpatient services. Dissociative disorders in general have a prevalence of 12.0%–13.8% for psychiatric outpatients.As of 2012, DID was diagnosed 5 to 9 times more common in women than men during young adulthood, although this may have been due to selection bias as men meeting DID diagnostic criteria were suspected to end up in the criminal justice system rather than hospitals. In children, rates among men and women are approximately the same (5:4). DID diagnoses are extremely rare in children; much of the research on childhood DID occurred in the 1980s and 1990s and does not address ongoing controversies surrounding the diagnosis. DID occurs more commonly in young adults and declines in prevalence with age.There is a poor awareness of DID in the clinical settings and the general public. Poor clinical education (or lack thereof) for DID and other dissociative disorders has been described in literature: "most clinicians have been taught (or assume) that DID is a rare disorder with a florid, dramatic presentation." Symptoms in patients are often not easily visible, which complicates diagnosis. DID has a high correlation with, and has been described as a form of, complex post-traumatic stress disorder. There is a significant overlap of symptoms between borderline personality disorder and DID, although symptoms are understood to originate from different underlying causes. Historical prevalence Rates of diagnosed DID were increasing in the late 20th century, reaching a peak of diagnoses at approximately 40,000 cases by the end of the 20th century, up from less than 200 diagnoses before 1970. Initially DID along with the rest of the dissociative disorders were considered the rarest of psychological conditions, diagnosed in less than 100 by 1944, with only one further case reported in the next two decades. In the late 1970s and 80s, the number of diagnoses rose sharply. An estimate from the 1980s placed the incidence at 0.01%. Accompanying this rise was an increase in the number of alters, rising from only the primary and one alter personality in most cases, to an average of 13 in the mid-1980s (the increase in both number of cases and number of alters within each case are both factors in professional skepticism regarding the diagnosis). Others explain the increase as being due to the use of inappropriate therapeutic techniques in highly suggestible individuals, though this is itself controversial while proponents of DID claim the increase in incidence is due to increased recognition of and ability to recognize the disorder. Figures from psychiatric populations (inpatients and outpatients) show a wide diversity from different countries.A 1996 essay suggested three possible causes for the sudden increase of DID diagnoses, among which the author suspects the first being most likely: The result of therapist suggestions to suggestible people, much as Charcots hysterics acted in accordance with his expectations. Psychiatrists past failure to recognize dissociation being redressed by new training and knowledge. Dissociative phenomena are actually increasing, but this increase only represents a new form of an old and protean entity: "hysteria".Dissociative disorders were excluded from the Epidemiological Catchment Area Project. North America DID is considered a controversial diagnosis and condition, with much of the literature on DID still being generated and published in North America, to the extent that it was once regarded as a phenomenon confined to that continent though research has appeared discussing the appearance of DID in other countries and cultures. Although the condition has been described in non-English speaking nations and non-Western cultures, these reports all occur in English-language journals authored by international researchers who cite Western scientific literature and are therefore not isolated from Western influences. Etzel Cardena and David Gleaves believed the over-representation of DID in North America was the result of increased awareness and training about the condition which had formerly been missing. History Early references In the 19th century, "dédoublement", or "double consciousness", the historical precursor to DID, was frequently described as a state of sleepwalking, with scholars hypothesizing that the patients were switching between a normal consciousness and a "somnambulistic state".An intense interest in spiritualism, parapsychology and hypnosis continued throughout the 19th and early 20th centuries, running in parallel with John Lockes views that there was an association of ideas requiring the coexistence of feelings with awareness of the feelings. Hypnosis, which was pioneered in the late 18th century by Franz Mesmer and Armand-Marie Jacques de Chastenet, Marques de Puységur, challenged Lockes association of ideas. Hypnotists reported what they thought were second personalities emerging during hypnosis and wondered how two minds could coexist. In the 19th century, there were a number of reported cases of multiple personalities which Rieber estimated would be close to 100. Epilepsy was seen as a factor in some cases, and discussion of this connection continues into the present era.By the late 19th century, there was a general acceptance that emotionally traumatic experiences could cause long-term disorders which might display a variety of symptoms. These conversion disorders were found to occur in even the most resilient individuals, but with profound effect in someone with emotional instability like Louis Vivet (1863–?), who had a traumatic experience as a 17-year-old when he encountered a viper. Vivet was the subject of countless medical papers and became the most studied case of dissociation in the 19th century. Between 1880 and 1920, various international medical conferences devoted time to sessions on dissociation. It was in this climate that Jean-Martin Charcot introduced his ideas of the impact of nervous shocks as a cause for a variety of neurological conditions. One of Charcots students, Pierre Janet, took these ideas and went on to develop his own theories of dissociation. One of the first individuals diagnosed with multiple personalities to be scientifically studied was Clara Norton Fowler, under the pseudonym Christine Beauchamp; American neurologist Morton Prince studied Fowler between 1898 and 1904, describing her case study in his 1906 monograph, Dissociation of a Personality. 20th century In the early 20th century, interest in dissociation and multiple personalities waned for several reasons. After Charcots death in 1893, many of his so-called hysterical patients were exposed as frauds, and Janets association with Charcot tarnished his theories of dissociation. Sigmund Freud recanted his earlier emphasis on dissociation and childhood trauma.In 1908, Eugen Bleuler introduced the term "schizophrenia" to represent a revised disease concept for Emil Kraepelins dementia praecox. Whereas Kraepelins natural disease entity was anchored in the metaphor of progressive deterioration and mental weakness and defect, Bleuler offered a reinterpretation based on dissociation or "splitting" (Spaltung) and widely broadened the inclusion criteria for the diagnosis. A review of the Index medicus from 1903 through 1978 showed a dramatic decline in the number of reports of multiple personality after the diagnosis of schizophrenia became popular, especially in the United States. The rise of the broad diagnostic category of dementia praecox has also been posited in the disappearance of "hysteria" (the usual diagnostic designation for cases of multiple personalities) by 1910. A number of factors helped create a large climate of skepticism and disbelief; paralleling the increased suspicion of DID was the decline of interest in dissociation as a laboratory and clinical phenomenon.Starting in about 1927, there was a large increase in the number of reported cases of schizophrenia, which was matched by an equally large decrease in the number of multiple personality reports. With the rise of a uniquely American reframing of dementia praecox/schizophrenia as a functional disorder or "reaction" to psychobiological stressors – a theory first put forth by Adolf Meyer in 1906—many trauma-induced conditions associated with dissociation, including "shell shock" or "war neuroses" during World War I, were subsumed under these diagnoses. It was argued in the 1980s that DID patients were often misdiagnosed with schizophrenia.The public, however, was exposed to psychological ideas which took their interest. Mary Shelleys Frankenstein, Robert Louis Stevensons Strange Case of Dr Jekyll and Mr Hyde, and many short stories by Edgar Allan Poe, had a formidable impact. Book and film The Three Faces of Eve In 1957, with the publication of the bestselling book The Three Faces of Eve by psychiatrists Corbett H. Thigpen and Hervey M. Cleckley, based on a case study of their patient Chris Costner Sizemore, and the subsequent popular movie of the same name, the American publics interest in multiple personality was revived. More cases of dissociative identity disorder were diagnosed in the following years. The cause of the sudden increase of cases is indefinite, but it may be attributed to the increased awareness, which revealed previously undiagnosed cases or new cases may have been induced by the influence of the media on the behavior of individuals and the judgement of therapists. During the 1970s an initially small number of clinicians campaigned to have it considered a legitimate diagnosis. History in the DSM The DSM-II used the term hysterical neurosis, dissociative type. It described the possible occurrence of alterations in the patients state of consciousness or identity, and included the symptoms of "amnesia, somnambulism, fugue, and multiple personality". The DSM-III grouped the diagnosis with the other four major dissociative disorders using the term "multiple personality disorder". The DSM-IV made more changes to DID than any other dissociative disorder, and renamed it DID. The name was changed for two reasons: First, the change emphasizes the main problem is not a multitude of personalities, but rather a lack of a single, unified identity and an emphasis on "the identities as centers of information processing". Second, the term "personality" is used to refer to "characteristic patterns of thoughts, feelings, moods, and behaviors of the whole individual", while for a patient with DID, the switches between identities and behavior patterns is the personality. It is for this reason the DSM-IV-TR referred to "distinct identities or personality states" instead of personalities. The diagnostic criteria also changed to indicate that while the patient may name and personalize alters, they lack independent, objective existence. The changes also included the addition of amnesia as a symptom, which was not included in the DSM-III-R because despite being a core symptom of the condition, patients may experience "amnesia for the amnesia" and fail to report it. Amnesia was replaced when it became clear that the risk of false negative diagnoses was low because amnesia was central to DID.The ICD-10 places the diagnosis in the category of "dissociative disorders", within the subcategory of "other dissociative (conversion) disorders", but continues to list the condition as multiple personality disorder.The DSM-IV-TR criteria for DID have been criticized for failing to capture the clinical complexity of DID, lacking usefulness in diagnosing individuals with DID (for instance, by focusing on the two least frequent and most subtle symptoms of DID) producing a high rate of false negatives and an excessive number of DDNOS diagnoses, for excluding possession (seen as a cross-cultural form of DID), and for including only two "core" symptoms of DID (amnesia and self-alteration) while failing to discuss hallucinations, trance-like states, somatoform, depersonalization, and derealization symptoms. Arguments have been made for allowing diagnosis through the presence of some, but not all of the characteristics of DID rather than the current exclusive focus on the two least common and noticeable features. The DSM-IV-TR criteria have also been criticized for being tautological, using imprecise and undefined language and for the use of instruments that give a false sense of validity and empirical certainty to the diagnosis. The DSM-5 updated the definition of DID in 2013, summarizing the changes as: Several changes to the criteria for dissociative identity disorder have been made in DSM-5. First, Criterion A has been expanded to include certain possession-form phenomena and functional neurological symptoms to account for more diverse presentations of the disorder. Second, Criterion A now specifically states that transitions in identity may be observable by others or self-reported. Third, according to Criterion B, individuals with dissociative identity disorder may have recurrent gaps in recall for everyday events, not just for traumatic experiences. Other text modifications clarify the nature and course of identity disruptions. Between 1968 and 1980, the term that was used for dissociative identity disorder was "Hysterical neurosis, dissociative type". The APA wrote in the second edition of the DSM: "In the dissociative type, alterations may occur in the patients state of consciousness or in his identity, to produce such symptoms as amnesia, somnambulism, fugue, and multiple personality." The number of cases sharply increased in the late 1970s and throughout the 80s, and the first scholarly monographs on the topic appeared in 1986. Book and film Sybil In 1974, the highly influential book Sybil was published, and later made into a miniseries in 1976 and again in 2007. Describing what Robert Rieber called "the third most famous of multiple personality cases," it presented a detailed discussion of the problems of treatment of "Sybil Isabel Dorsett", a pseudonym for Shirley Ardell Mason. Though the book and subsequent films helped popularize the diagnosis and trigger an epidemic of the diagnosis, later analysis of the case suggested different interpretations, ranging from Masons problems having been caused by the therapeutic methods used by her psychiatrist, C.B. Wilbur, or an inadvertent hoax due in part to the lucrative publishing rights, though this conclusion has itself been challenged.David Spiegel, a Stanford psychiatrist whose father treated Shirley Ardell Mason on occasion, says that his father described Mason as "a brilliant hysteric. He felt that Wilbur tended to pressure her to exaggerate on the dissociation she already had." As media attention on DID increased, so too did the controversy surrounding the diagnosis. Re-classifications With the publication of the DSM-III, which omitted the terms "hysteria" and "neurosis" (and thus the former categories for dissociative disorders), dissociative diagnoses became "orphans" with their own categories with dissociative identity disorder appearing as "multiple personality disorder".In the opinion of McGill University psychiatrist Joel Paris, this inadvertently legitimized them by forcing textbooks, which mimicked the structure of the DSM, to include a separate chapter on them and resulted in an increase in diagnosis of dissociative conditions. Once a rarely occurring spontaneous phenomenon (research in 1944 showed only 76 cases), the diagnosis became "an artifact of bad (or naïve) psychotherapy" as patients capable of dissociating were accidentally encouraged to express their symptoms by "overly fascinated" therapists.In a 1986 book chapter (later reprinted in another volume), philosopher of science Ian Hacking focused on multiple personality disorder as an example of "making up people" through the untoward effects on individuals of the "dynamic nominalism" in medicine and psychiatry. With the invention of new terms entire new categories of "natural kinds" of people are assumed to be created, and those thus diagnosed respond by re-creating their identity in light of the new cultural, medical, scientific, political and moral expectations. Hacking argued that the process of "making up people" is historically contingent, hence it is not surprising to find the rise, fall, and resurrection of such categories over time. Hacking revisited his concept of "making up people" in a 2006."Interpersonality amnesia" was removed as a diagnostic feature from the DSM III in 1987, which may have contributed to the increasing frequency of the diagnosis. There were 200 reported cases of DID as of 1980, and 20,000 from 1980 to 1990. Joan Acocella reports that 40,000 cases were diagnosed from 1985 to 1995. Scientific publications regarding DID peaked in the mid-1990s then rapidly declined.There were several contributing factors to the rapid decline of reports of multiple personality disorder/dissociative identity disorder. One was the discontinuation in December 1997 of Dissociation: Progress in the Dissociative Disorders, the journal of The International Society for the Study of Multiple Personality and Dissociation. The society and its journal were perceived as uncritical sources of legitimacy for the extraordinary claims of the existence of intergenerational satanic cults responsible for a "hidden holocaust" of Satanic ritual abuse that was linked to the rise of MPD reports. In an effort to distance itself from the increasing skepticism regarding the clinical validity of MPD, the organization dropped "multiple personality" from its official name in 1993, and then in 1997 changed its name again to the International Society for the Study of Trauma and Dissociation.In 1994, the fourth edition of the DSM replaced the criteria again and changed the name of the condition from "multiple personality disorder" to the current "dissociative identity disorder" to emphasize the importance of changes to consciousness and identity rather than personality. The inclusion of interpersonality amnesia helped to distinguish DID from dissociative disorder not otherwise specified (DDNOS), but the condition retains an inherent subjectivity due to difficulty in defining terms such as personality, identity, ego-state, and even amnesia. The ICD-10 classified DID as a "Dissociative [conversion] disorder" and used the name "multiple personality disorder" with the classification number of F44.81. In the ICD-11, the World Health Organization have classified DID under the name "dissociative identity disorder" (code 6B64), and most cases formerly diagnosed as DDNOS are classified as "partial dissociative identity disorder" (code 6B65). 21st century A 2006 study compared scholarly research and publications on DID and dissociative amnesia to other mental health conditions, such as anorexia nervosa, alcohol use disorder, and schizophrenia from 1984 to 2003. The results were found to be unusually distributed, with a very low level of publications in the 1980s followed by a significant rise that peaked in the mid-1990s and subsequently rapidly declined in the decade following. Compared to 25 other diagnosis, the mid-1990s "bubble" of publications regarding DID was unique. In the opinion of the authors of the review, the publication results suggest a period of "fashion" that waned, and that the two diagnoses "[did] not command widespread scientific acceptance." Society and culture General The publics long fascination with DID has led to a number of different books and films,(p 169) with many representations described as increasing stigma by perpetuating the myth that people with mental illness are usually dangerous. Movies about DID have been also criticized for poor representation of both DID and its treatment, including "greatly overrepresenting" the role of hypnosis in therapy, showing a significantly smaller number of personalities than many people with DID have, and misrepresenting people with DID as having flamboyant and obvious personalities. Some movies are parodies and ridicule DID, for instance Me, Myself & Irene, which also incorrectly states that DID is schizophrenia. In some stories DID is used as
Dissociative identity disorder	a plot device, e.g. in Fight Club, and in whodunnit stories like Secret Window.United States of Tara was reported to be the first US television series with DID as its focus, and a professional commentary on each episode was published by the International Society for the Study of Trauma and Dissociation. More recently, the award winning Korean TV series Kill Me, Heal Me (Korean: 킬미, 힐미; RR: Kilmi, Hilmi) featured a wealthy young man with seven personalities, one of whom falls in love with the beautiful psychiatry resident who tries to help him.Most people with DID are believed to downplay or minimize their symptoms rather than seeking fame, often due to fear of the effects of stigma, or shame. Therapists may discourage them from media work due to concerns that they may feel exploited or traumatized, for example as a result of demonstrating switching between personality states to entertain others.(p 169)However, a number of people with DID have publicly spoken about their experiences, including comedian and talk show host Roseanne Barr, who interviewed Truddi Chase, author of When Rabbit Howls; Chris Costner Sizemore, the subject of The Three Faces of Eve, Cameron West, author of First Person Plural: My life as a multiple, and NFL player Herschel Walker, author of Breaking Free: My life with dissociative identity disorder.In The Three Faces of Eve (1957) hypnosis is used to identify a childhood trauma which then allows her to merge from three identities into just one. However, Sizemores own books Im Eve and A Mind of My Own revealed that this did not last; she later attempted suicide, sought further treatment, and actually had twenty-two personalities rather than three. Sizemore re-entered therapy and by 1974 had achieved a lasting recovery. Voices Within: The Lives of Truddi Chase portrays many of the 92 personalities Chase described in her book When Rabbit Howls, and is unusual in breaking away from the typical ending of integrating into one. Frankie & Alice (2010), starring Halle Berry; and the TV mini-series Sybil were also based on real people with DID. In popular culture dissociative identity disorder is often confused with schizophrenia, and some movies advertised as representing dissociative identity disorder may be more representative of psychosis or schizophrenia, for example Psycho (1960).In his book The C.I.A. Doctors: Human Rights Violations by American Psychiatrists, psychiatrist Colin A. Ross states that based on documents obtained through freedom of information legislation, a psychiatrist linked to Project MKULTRA reported being able to deliberately induce dissociative identity disorder using a variety of aversive or abusive techniques, creating a Manchurian Candidate for military purposes.A DID community exists on social media, including YouTube and TikTok. However, numerous high-profile members of this community have been criticized for faking their condition for views, or for portraying the disorder lightheartedly. Conversely, psychologist Naomi Torres-Mackie, head of research at The Mental Health Coalition, has stated "All of a sudden, all of my adolescent patients think that they have this, and they dont... Folks start attaching clinical meaning and feeling like, I should be diagnosed with this. I need medication for this, when actually a lot of these experiences are normative and dont need to be pathologized or treated."In the USA Network television production Mr. Robot, the protagonist Elliot Alderson is shown to have signs of DID and schizophrenia.In M. Night Shyamalans Unbreakable superhero film series (specifically the second film, Split), one character is diagnosed with DID, and that some of the personalities have super-human powers. Some advocates believe that the film is a negative portrayal.In Marvel Comics, the character of Moon Knight is shown to have DID. In the TV series Moon Knight based on the comic book character, protagonist Marc Spector is depicted with DID; the website for the National Alliance on Mental Illness appears in the series end credits. Another Marvel character, Legion, has DID in the comics, although he has schizophrenia in the TV show version. Legal issues People with dissociative identity disorder may be involved in legal cases as a witness, defendant, or as the victim/injured party. In the United States dissociative identity disorder has previously been found to meet the Frye test as a generally accepted medical condition, and the newer Daubert standard. Within legal circles, DID has been described as one of the most disputed psychiatric diagnoses and forensic assessments are needed. For defendants whose defense states they have a diagnosis of DID, courts must distinguish between those who genuinely have DID and those who are malingering to avoid responsibility, as shown in the fictional book and film Primal Fear. Expert witnesses are typically used to assess defendants in such cases, although some of the standard assessments like the MMPI-2 were not developed for people with a trauma history and the validity scales may incorrectly suggest malingering. The Multiscale Dissociation Inventory (Briere, 2002) is well suited to assessing malingering and dissociative disorders, unlike the self-report Dissociative Experiences Scale. In DID, evidence about the altered states of consciousness, actions of alter identities and episodes of amnesia may be excluded from a court if they not considered relevant, although different countries and regions have different laws. A diagnosis of DID may be used to claim a defense of not guilty by reason of insanity, but this very rarely succeeds, or of diminished capacity, which may reduce the length of a sentence. DID may also affect competency to stand trial. A not guilty by reason of insanity plea was first used successfully in an American court in 1978, in the State of Ohio v. Milligan case. However, a DID diagnosis is not automatically considered a justification for an insanity verdict, and since Milligan the few cases claiming insanity have largely been unsuccessful. Advocacy movement In the context of neurodiversity, the experience of dissociative identities has been called multiplicity and has led to advocacy for the recognition of positive plurality and the use of plural pronouns such as "we" and "our". Liz Fong-Jones states those with this condition might have fear in regard to "coming out" about their DID, as it could put them in a vulnerable position.In particular, advocates have challenged the necessity of integration. Timothy Baynes argues that alters have full moral status, just as their host does. He states that as integration may entail the (involuntary) elimination of such an entity, forcing people to undergo it as a therapeutic treatment is "seriously immoral".A DID (or Dissociative Identities) Awareness Day takes place on March 5 annually, and a multicolored awareness ribbon is used, based on the idea of a "crazy quilt". Footnotes References External links "International Society for the Study of Trauma and Dissociation".
Thyroid disease in pregnancy	Thyroid disease in pregnancy can affect the health of the mother as well as the child before and after delivery. Thyroid disorders are prevalent in women of child-bearing age and for this reason commonly present as a pre-existing disease in pregnancy, or after childbirth. Uncorrected thyroid dysfunction in pregnancy has adverse effects on fetal and maternal well-being. The deleterious effects of thyroid dysfunction can also extend beyond pregnancy and delivery to affect neurointellectual development in the early life of the child. Due to an increase in thyroxine binding globulin, an increase in placental type 3 deioidinase and the placental transfer of maternal thyroxine to the fetus, the demand for thyroid hormones is increased during pregnancy. The necessary increase in thyroid hormone production is facilitated by high human chorionic gonadotropin (hCG) concentrations, which bind the TSH receptor and stimulate the maternal thyroid to increase maternal thyroid hormone concentrations by roughly 50%. If the necessary increase in thyroid function cannot be met, this may cause a previously unnoticed (mild) thyroid disorder to worsen and become evident as gestational thyroid disease. Currently, there is not enough evidence to suggest that screening for thyroid dysfunction is beneficial, especially since treatment thyroid hormone supplementation may come with a risk of overtreatment. After women give birth, about 5% develop postpartum thyroiditis which can occur up to nine months afterwards. This is characterized by a short period of hyperthyroidism followed by a period of hypothyroidism; 20–40% remain permanently hypothyroid. The thyroid in pregnancy Fetal thyroxine is wholly obtained from maternal sources in early pregnancy since the fetal thyroid gland only becomes functional in the second trimester of gestation. As thyroxine is essential for fetal neurodevelopment it is critical that maternal delivery of thyroxine to the fetus is ensured early in gestation. In pregnancy, iodide losses through the urine and the feto-placental unit contribute to a state of relative iodine deficiency. Thus, pregnant women require additional iodine intake. A daily iodine intake of 250 µg is recommended in pregnancy but this is not always achieved even in iodine sufficient parts of the world.Thyroid hormone concentrations in blood are increased in pregnancy, partly due to the high levels of estrogen and due to the weak thyroid stimulating effects of human chorionic gonadotropin (hCG) that acts like TSH. Thyroxine (T4) levels rise from about 6–12 weeks, and peak by mid-gestation; reverse changes are seen with TSH. Gestation specific reference ranges for thyroid function tests are not widely in use although many centres are now preparing them. Hypothyroidism Clinical evaluation Hypothyroidism is common in pregnancy with an estimated prevalence of 2-3% and 0.3-0.5% for subclinical and overt hypothyroidism respectively. Endemic iodine deficiency accounts for most hypothyroidism in pregnant women worldwide while chronic autoimmune thyroiditis is the most common cause of hypothyroidism in iodine sufficient parts of the world. The presentation of hypothyroidism in pregnancy is not always classical and may sometimes be difficult to distinguish from the symptoms of normal pregnancy. A high index of suspicion is therefore required especially in women at risk of thyroid disease e.g. women with a personal or family history of thyroid disease, goitre, or co-existing primary autoimmune disorder like type 1 diabetes. Risks of hypothyroidism on fetal and maternal well-being Hypothyroidism is diagnosed by noting a high TSH associated with a subnormal T4 concentration. Subclinical hypothyroidism (SCH) is present when the TSH is high but the T4 level is in the normal range but usually low normal. SCH is the commonest form of hypothyroidism in pregnancy and is usually due to progressive thyroid destruction due to autoimmune thyroid disease.Several studies, mostly retrospective, have shown an association between overt hypothyroidism and adverse fetal and obstetric outcomes (e.g. Glinoer 1991). Maternal complications such as miscarriages, anaemia in pregnancy, pre-eclampsia, abruptio placenta and postpartum haemorrhage can occur in pregnant women with overt hypothyroidism. Also, the offspring of these mothers can have complications such as premature birth, low birth weight and increased neonatal respiratory distress. Similar complications have been reported in mothers with subclinical hypothyroidism. A three-fold risk of placental abruption and a two-fold risk of pre-term delivery were reported in mothers with subclinical hypothyroidism. Another study showed a higher prevalence of subclinical hypothyroidism in women with pre-term delivery (before 32 weeks) compared to matched controls delivering at term. An association with adverse obstetrics outcome has also been demonstrated in pregnant women with thyroid autoimmunity independent of thyroid function. Treatment of hypothyroidism reduces the risks of these adverse obstetric and fetal outcomes; a retrospective study of 150 pregnancies showed that treatment of hypothyroidism led to reduced rates of abortion and premature delivery. Also, a prospective intervention trial study showed that treatment of euthyroid antibody positive pregnant women led to fewer rates of miscarriage than non treated controls.It has long been known that cretinism (i.e. gross reduction in IQ) occurs in areas of severe iodine deficiency due to the fact that the mother is unable to make T4 for transport to the fetus, particularly in the first trimester. This neurointellectual impairment (on a more modest scale) has now been shown in an iodine sufficient area (USA) where a study showed that the IQ scores of 7- to 9-year-old children, born to mothers with undiagnosed and untreated hypothyroidism in pregnancy, were seven points lower than those of children of matched control women with normal thyroid function in pregnancy. Another study showed that persistent hypothyroxinaemia at 12 weeks gestation was associated with an 8-10 point deficit in mental and motor function scores in infant offspring compared to children of mothers with normal thyroid function. Even maternal thyroid peroxidase antibodies were shown to be associated with impaired intellectual development in the offspring of mothers with normal thyroid function. It has been shown that it is only the maternal FT4 levels that are associated with child IQ and brain morphological outcomes, as opposed to maternal TSH levels. Management of hypothyroidism in pregnancy Medications to treat hypothyroidism have been found to be safe during pregnancy. Levothyroxine is the treatment of choice for hypothyroidism in pregnancy. Thyroid function should be normalised prior to conception in women with pre-existing thyroid disease. Once pregnancy is confirmed the thyroxine dose should be increased by about 30-50% and subsequent titrations should be guided by thyroid function tests (FT4 and TSH) that should be monitored 4-6 weekly until euthyroidism is achieved. It is recommended that TSH levels are maintained below 2.5 mU/L in the first trimester of pregnancy and below 3 mU/L in later pregnancy. The recommended maintenance dose of thyroxine in pregnancy is about 2.0-2.4 µg/kg daily. Thyroxine requirements may increase in late gestation and return to pre-pregnancy levels in the majority of women on delivery. Pregnant patients with subclinical hypothyroidism (normal FT4 and elevated TSH) should be treated as well, since supplementation with levothyroxine in such cases results in a significantly higher delivery rate, with a pooled relative chance of 2.76. Hyperthyroidism Clinical evaluation Hyperthyroidism occurs in about 0.2-0.4% of all pregnancies. Most cases are due to Graves disease although less common causes (e.g. toxic nodules and thyroiditis) may be seen. Clinical assessment alone may occasionally be inadequate in differentiating hyperthyroidism from the hyperdynamic state of pregnancy. Distinctive clinical features of Graves disease include the presence of ophthalmopathy, diffuse goitre and pretibial myxoedema. Also, hyperthyroidism must be distinguished from gestational transient thyrotoxicosis, a self-limiting hyperthyroid state due to the thyroid stimulatory effects of beta-hCG . This distinction is important since the latter condition is typically mild and will not usually require specific antithyroid treatment. Red cell zinc may also be useful in differentiating the two. Hyperthyroidism due to Graves disease may worsen in the first trimester of pregnancy, remit in later pregnancy, and subsequently relapse in the postpartum. Risks of hyperthyroidism on fetal and maternal well-being Uncontrolled hyperthyroidism in pregnancy is associated with an increased risk of severe pre-eclampsia and up to a four-fold increased risk of low birth weight deliveries. Some of these unfavourable outcomes are more marked in women who are diagnosed for the first time in pregnancy. A recent study has also shown that already high normal maternal FT4 levels are associated with a decrease in child IQ and gray matter and cortex volumes, similar to the effects of hypothyroidism.Uncontrolled and inadequately treated maternal hyperthyroidism may also result in fetal and neonatal hyperthyroidism due to the transplacental transfer of stimulatory TSH receptor antibodies. Clinical neonatal hyperthyroidism occurs in about 1% of infants born to mothers with Graves disease. Rarely neonatal hypothyroidism may also be observed in the infants of mothers with Graves hyperthyroidism. This may result from transplacental transfer of circulating maternal anti-thyroid drugs, pituitary-thyroid axis suppression from transfer of maternal thyroxine. Management of hyperthyroidism in pregnancy Ideally, a woman who is known to have hyperthyroidism should seek pre-pregnancy advice, although as yet there is no evidence for its benefit. Appropriate education should allay fears that are commonly present in these women. She should be referred for specialist care for frequent checking of her thyroid status, thyroid antibody evaluation and close monitoring of her medication needs. Medical therapy with anti-thyroid medications is the treatment of choice for hyperthyroidism in pregnancy. Methimazole and propylthiouracil are effective in preventing pregnancy complications by hyperthyroidism. Surgery is considered for patients who have severe adverse reactions to anti-thyroid drugs and this is best performed in the second trimester of pregnancy. Radioactive iodine is absolutely contraindicated in pregnancy and the puerperium. If a woman is already receiving carbimazole, a change to propylthiouracil is recommended but this should be changed back to carbimazole after the first trimester. On occasion, Carbimazole is associated with skin and also mid-line defects in the fetus but propylthiouracil long term also can cause liver side effects in the adult. Carbimazole and propylthiouracil are both secreted in breast milk but evidence suggests that antithyroid drugs are safe during lactation. There are no adverse effects on IQ or psychomotor development in children whose mothers have received antithyroid drugs in pregnancy. Current guidelines suggest that a pregnant patient should be on propylthiouracil during the first trimester of pregnancy due to lower tetratogenic effect and then be switched to methimazole during the second and third trimester due to lower liver dysfunction side effects. Postpartum thyroiditis Postpartum thyroid dysfunction is a syndrome of thyroid dysfunction occurring within the first 12 months of delivery as a consequence of the postpartum immunological rebound that follows the immune tolerant state of pregnancy. Postpartum thyroid dysfunction is a destructive thyroiditis with similar pathogenetic features to Hashimotos thyroiditis.The disease is very common with a prevalence of 5-9% of unselected postpartum women. Typically there is a transient hyperthyroid phase that is followed by a phase of hypothyroidism. Permanent hypothyroidism occurs in as much as 30% of cases after 3 years, and in 50% at 7–10 years. The hyperthyroid phase will not usually require treatment but, rarely, propanolol may be used for symptom control in severe cases. The hypothyroid phase should be treated with thyroxine if patients are symptomatic, planning to get pregnant, or if TSH levels are above 10 mU/L. Long-term follow up is necessary due to the risk of permanent hypothyroidism.Nearly all the women with Postpartum thyroid dysfunction have anti-thyroid peroxidase antibodies. This marker can be a useful screening test in early pregnancy as 50% of women with antibodies will develop thyroid dysfunction postpartum. In addition, some but not all studies have shown an association between Postpartum thyroid dysfunction and depression so that thyroid function should be checked postpartum in women with mood changes. == References ==
Molybdenum deficiency	Molybdenum deficiency refers to the clinical consequences of inadequate supplies of molybdenum in the diet. The amount of molybdenum required is relatively small, and molybdenum deficiency usually does not occur in natural settings. However, it can occur in individuals receiving parenteral nutrition. Signs and symptoms Descriptions of human molybdenum deficiency are few. A patient receiving prolonged parenteral nutrition acquired a syndrome described as ‘acquired molybdenum deficiency.’ This syndrome, exacerbated by methionine administration, was characterized by high blood methionine, low blood uric acid, and low urinary uric acid and sulfate concentrations. The patient suffered mental disturbances that progressed to a coma. Pathological changes occurring in individuals with a genetic disease that results in a sulfite oxidase (a molybdoenzyme) deficiency include increased plasma and urine sulfite, sulfate, thiosulfate, S-sulfocysteine and taurine; seizures, and brain atrophy/lesions; dislocated lenses; and death at an early age.. Diagnosis Treatment 300 mcg Ammonium Molybdate per day can bring about recovery of “acquired molybdenum deficiency” [3] See also Molybdenum cofactor deficiency References Further reading == External links ==
Tick paralysis	Tick paralysis is the only tick-borne disease that is not caused by an infectious organism. The illness is caused by a neurotoxin produced in the ticks salivary gland. After prolonged attachment, the engorged tick transmits the toxin to its host. The incidence of tick paralysis is unknown. Patients can experience severe respiratory distress (similar to anaphylaxis). Signs and symptoms Tick paralysis results from injection of a toxin from tick salivary glands during a blood meal. The toxin causes symptoms within 2–7 days, beginning with weakness in both legs that progresses to paralysis. The paralysis ascends to the trunk, arms, and head within hours and may lead to respiratory failure and death. The disease can present as acute ataxia without muscle weakness. Patients may report minor sensory symptoms, such as local numbness, but constitutional signs are usually absent. Deep tendon reflexes are usually decreased or absent, and ophthalmoplegia and bulbar palsy can occur. Electromyographic (EMG) studies usually show a variable reduction in the amplitude of compound muscle action potentials, but no abnormalities of repetitive nerve stimulation studies. These appear to result from a failure of acetylcholine release at the motor nerve terminal level. There may be subtle abnormalities of motor nerve conduction velocity and sensory action potentials. Pathogenesis Tick paralysis is believed to be due to toxins found in the ticks saliva that enter the bloodstream while the tick is feeding. The two ticks most commonly associated with North American tick paralysis are the Rocky Mountain wood tick (Dermacentor andersoni) and the American dog tick (Dermacentor variabilis); however, 43 tick species have been implicated in human disease around the world. Most North American cases of tick paralysis occur from April to June, when adult Dermacentor ticks emerge from hibernation and actively seek hosts. In Australia, tick paralysis is caused by the tick Ixodes holocyclus. Prior to 1989, 20 fatal cases were reported in Australia.Although tick paralysis is of concern in domestic animals and livestock in the United States as well, human cases are rare and usually occur in children under the age of 10. Tick paralysis occurs when an engorged and gravid (egg-laden) female tick produces a neurotoxin in its salivary glands and transmits it to its host during feeding. Experiments have indicated that the greatest amount of toxin is produced between the fifth and seventh day of attachment (often initiating or increasing the severity of symptoms), although the timing may vary depending on the species of tick. Unlike Lyme disease, ehrlichiosis, and babesiosis, which are caused by the systemic proliferation and expansion of parasites in their hosts long after the offending tick is gone, tick paralysis is chemically induced by the tick and therefore usually only continues in its presence. Once the tick is removed, symptoms usually diminish rapidly. However, in some cases, profound paralysis can develop and even become fatal before anyone becomes aware of a ticks presence. Diagnosis Diagnosis is based on symptoms and upon finding an embedded tick, usually on the scalp. In the absence of a tick, the differential diagnosis includes Guillain–Barré syndrome. Early signs of tick poisoning could be a change of an animals ‘voice’, weakness in the back legs or vomiting. Prevention No human vaccine is currently available for any tick-borne disease, except for tick-borne encephalitis. Individuals should therefore take precautions when entering tick-infested areas, particularly in the spring and summer months. Preventive measures include avoiding trails that are overgrown with bushy vegetation, wearing light-coloured clothes that allow one to see the ticks more easily, and wearing long pants and closed-toe shoes. Tick repellents containing DEET (N,N, diethyl-m-toluamide) are only marginally effective and can be applied to skin or clothing. Rarely, severe reactions can occur in some people who use DEET-containing products. Young children may be especially vulnerable to these adverse effects. Permethrin, which can only be applied to clothing, is much more effective in preventing tick bites. Permethrin is not a repellent but rather an insecticide; it causes ticks to curl up and fall off the protected clothing. Treatment Removal of the offending tick usually results in resolution of symptoms within several hours to days. If the tick is not removed, the toxin can be fatal. A 1969 study of children reported mortality rates of 10 – 12 percent, mostly due to respiratory paralysis. The tick is best removed by grasping it as close to the skin as possible and pulling in a firm steady manner. Because the toxin lies in the ticks salivary glands, care must be taken to remove the entire tick (including the head), or symptoms may persist. It is important to note that, unlike the toxin of other tick species, the toxin of Ixodes holocyclus (Australian paralysis tick) may still be fatal even if the tick is removed. For affected animals, food and water intake can worsen the outcome, as the toxin can prevent the animal from swallowing properly. People who find a tick on their animal, are advised to remove it immediately and seek veterinary assistance if the animal shows any signs of illness. The tick can be placed in a tightly sealed plastic bag and taken to a veterinarian for identification. Research Although several attempts have been made to isolate and identify the neurotoxin since the first isolation in 1966, the exact structure of the toxin has still not been published. The 40-80 kDa protein fraction contains the toxin.The neurotoxin structure and gene, at least for the tick species Ixodes holocyclus have since been identified and are called holocyclotoxins after the species. At least three members (HT-1, HT-3, and HT-12) trigger paralysis by presynaptic inhibition of neurotransmitter release via a calcium dependent mechanism resulting in a reduction of quantal content, and loss of effective neuromuscular synaptic transmission. Culture In the TV show, Hart of Dixie, Season 1, Episode 2, a patient is diagnosed with tick paralysis who has been deer hunting. In the TV show, Emergency!, Season 5, Episode 4, "Equipment" (first aired Oct. 4, 1975), Dr. Joe Early diagnoses a young boy who has fallen from a tree with tick paralysis, after eliminating polio as a cause.In the TV show, House, Season 2, Episode 16, "Safe", Dr House diagnoses a patient (played by Michelle Trachtenberg) with tick paralysis.In the TV show, Remedy, Season 1 Episode 7, "Tomorrow, the Green Grass", Rebecca is diagnosed with tick paralysis. In the TV show, Royal Pains, Season 1 Episode 3, "Strategic Planning", a US Senators teenage son is diagnosed with and overcomes tick paralysis. In the TV show, Chicago Med, Season 3, Episode 5, "Mountains and Molehills", a young girl returning from Australia with increasing paralysis is diagnosed with tick paralysis. See also Polyneuropathy in dogs and cats for tick paralysis in dogs Tick-borne disease References == External links ==
Pyodermatitis vegetans	Pyodermatitis vegetans can refer to: Pyostomatitis vegetans Blastomycosis-like pyoderma
Renal cortical necrosis	Renal cortical necrosis (RCN) is a rare cause of acute kidney failure. The condition is "usually caused by significantly diminished arterial perfusion of the kidneys due to spasms of the feeding arteries, microvascular injury, or disseminated intravascular coagulation" and is the pathological progression of acute tubular necrosis. It is frequently associated with obstetric catastrophes such as abruptio placentae and septic shock, and is three times more common in developing nations versus industrialized nations (2% versus 6% in causes of acute kidney failure). Causes Adults Pregnancy related (>50% of cases) Placental abruption Infected abortion Prolonged intrauterine fetal death Severe eclampsia HIV Snake bites Binge drinking Shock Trauma Sickle cell disease Systemic lupus erythematosus (SLE) Sepsis SLE-associated antiphospholipid syndrome Vitamin deficiency Pancreatitis Malaria Meningococcemia Drug-induced toxicity (e.g. NSAIDs, Contrast Media, Quinine, or ATRA) Babies Congenital heart disease Fetal-maternal transfusion Dehydration Perinatal asphyxia Anemia Placental hemorrhage Severe hemolytic disease Sepsis Pathophysiology The exact pathologic mechanism for RCN is unclear, however the onset of small vessel pathology is likely an important aspect in the cause of this condition. In general the renal cortex is under greater oxygen tension and more prone to ischemic injury, especially at the level of the proximal collecting tubule, leading to its preferential damage in a sudden drop in perfusion. Rapidly corrected acute renal ischemia leads to acute tubular necrosis, from which complete recovery is possible, while more prolonged ischemia may lead to RCN. Pathologically, the cortex of the kidney is grossly atrophied with relative preservation of the gross structure of the medulla. The damage is usually bilateral owing to its underlying systemic causes, and is most frequently associated with pregnancy (>50% of cases). It accounts for 2% of all cases of acute kidney failure in adults and more than 20% of cases of acute kidney failure during late pregnancy. Diagnosis While the only diagnostic "gold standard" mechanism of diagnosis en vivo is via kidney biopsy, the clinical conditions and blood clotting disorder often associated with this disease may make it impractical in a clinical setting. Alternatively, it is diagnosed clinically, or at autopsy, with some authors suggesting diagnosis by contrast enhanced CT. Treatment Patients will require dialysis to compensate for the function of their kidneys. Prognosis Cortical necrosis is a severe and life-threatening condition, with mortality rates over 50%. Those mortality rates are even higher in neonates with the condition due to the overall difficult nature of neonatal care and an increased frequency of comorbid conditions. The extent of the necrosis is a major determinant of the prognosis, which in turn is dependent on the duration of ischemia, duration of oliguria, and the severity of the precipitating conditions. Of those that survive the initial event, there are varying degrees of recovery possible, depending on the extent of the damage. References == External links ==
Breast	The breast is one of two prominences located on the upper ventral region of a primates torso. Both females and males develop breasts from the same embryological tissues. In females, it serves as the mammary gland, which produces and secretes milk to feed infants. Subcutaneous fat covers and envelops a network of ducts that converge on the nipple, and these tissues give the breast its size and shape. At the ends of the ducts are lobules, or clusters of alveoli, where milk is produced and stored in response to hormonal signals. During pregnancy, the breast responds to a complex interaction of hormones, including estrogens, progesterone, and prolactin, that mediate the completion of its development, namely lobuloalveolar maturation, in preparation of lactation and breastfeeding. Humans are the only animals with permanent breasts. At puberty, estrogens, in conjunction with growth hormone, cause permanent breast growth in female humans. This happens only to a much lesser extent in other primates—breast development in other primates generally only occurs with pregnancy. Along with their major function in providing nutrition for infants, female breasts have social and sexual characteristics. Breasts have been featured in ancient and modern sculpture, art, and photography. They can figure prominently in the perception of a womans body and sexual attractiveness. A number of cultures associate breasts with sexuality and tend to regard bare breasts in public as immodest or indecent. Breasts, especially the nipples, are an erogenous zone. Etymology and terminology The English word breast derives from the Old English word brēost (breast, bosom) from Proto-Germanic *breustam (breast), from the Proto-Indo-European base bhreus– (to swell, to sprout). The breast spelling conforms to the Scottish and North English dialectal pronunciations. The Merriam-Webster Dictionary states that "Middle English brest, [comes] from Old English brēost; akin to Old High German brust..., Old Irish brú [belly], [and] Russian bryukho"; the first known usage of the term was before the 12th century.A large number of colloquial terms for breasts are used in English, ranging from fairly polite terms to vulgar or slang. Some vulgar slang expressions may be considered to be derogatory or sexist to women. Evolutionary development Humans are the only mammals whose breasts become permanently enlarged after sexual maturity (known in humans as puberty). The reason for this evolutionary change was unknown. Several hypotheses have been put forward: A link has been proposed to processes for synthesizing the endogenous steroid hormone precursor dehydroepiandrosterone which takes place in fat rich regions of the body like the buttocks and breasts. These contributed to human brain development and played a part in increasing brain size. Breast enlargement may for this purpose may have occurred as early as Homo ergaster (1.7-1.4 MYA). Other breast formation hypotheses may have then taken over as principal drivers.It has been suggested by zoologists Avishag and Amotz Zahavi that the size of the human breasts can be explained by the handicap theory of sexual dimorphism. This would see the explanation for larger breasts as them being an honest display of the womens health and ability to grow and carry them in her life. Prospective mates can then evaluate the genes of a potential mate for their ability to sustain her health even with the additional energy demanding burden she is carrying.The zoologist Desmond Morris describes a sociobiological approach in his popular science book The Naked Ape. He suggests, by making comparisons with the other primates, that breasts evolved to replace swelling buttocks as a sex signal, of ovulation. He notes how humans have, relatively speaking, large penises as well as large breasts. Furthermore, early humans adopted bipedalism and face-to-face coitus. He therefore suggested enlarged sexual signals helped maintain the bond between a mated male and female even though they performed different duties and therefore were separated for lengths of time.The study The Evolution of the Human Breast (2001) proposed that the rounded shape of a womans breast evolved to prevent the sucking infant offspring from suffocating while feeding at the teat; that is, because of the human infants small jaw, which did not project from the face to reach the nipple, he or she might block the nostrils against the mothers breast if it were of a flatter form (cf. common chimpanzee). Theoretically, as the human jaw receded into the face, the womans body compensated with round breasts.Ashley Montague (1965) proposed that breasts came about as an adaptation for infant feeding for a different reason as early human ancestors adopted bipedalism and the loss of body hair. Human upright stance meant infants must be carried at the hip or shoulder instead of on the back as in the apes. This gives the infant less opportunity to find the nipple or the purchase to cling on to the mothers body hair. The mobility of the nipple on a large breast in most human females gives the infant more ability to find grasp it and feed.Other suggestions include simply that permanent breasts attracted mates, that "pendulous" breasts gave infants something to cling to, or that permanent breasts shared the function of a camels hump, to store fat as an energy reserve. Anatomy In women, the breasts overlie the pectoralis major muscles and extend on average from the level of the second rib to the level of the sixth rib in the front of the rib cage; thus, the breasts cover much of the chest area and the chest walls. At the front of the chest, the breast tissue can extend from the clavicle (collarbone) to the middle of the sternum (breastbone). At the sides of the chest, the breast tissue can extend into the axilla (armpit), and can reach as far to the back as the latissimus dorsi muscle, extending from the lower back to the humerus bone (the bone of the upper arm). As a mammary gland, the breast is composed of differing layers of tissue, predominantly two types: adipose tissue; and glandular tissue, which affects the lactation functions of the breasts.: 115 Morphologically the breast is tear-shaped. The superficial tissue layer (superficial fascia) is separated from the skin by 0.5–2.5 cm of subcutaneous fat (adipose tissue). The suspensory Coopers ligaments are fibrous-tissue prolongations that radiate from the superficial fascia to the skin envelope. The female adult breast contains 14–18 irregular lactiferous lobes that converge at the nipple. The 2.0–4.5 mm milk ducts are immediately surrounded with dense connective tissue that support the glands. Milk exits the breast through the nipple, which is surrounded by a pigmented area of skin called the areola. The size of the areola can vary widely among women. The areola contains modified sweat glands known as Montgomerys glands. These glands secrete oily fluid that lubricate and protect the nipple during breastfeeding. Volatile compounds in these secretions may also serve as an olfactory stimulus for the newborns appetite.The dimensions and weight of the breast vary widely among women. A small-to-medium-sized breast weighs 500 grams (1.1 pounds) or less, and a large breast can weigh approximately 750 to 1,000 grams (1.7 to 2.2 pounds) or more. The tissue composition ratios of the breast also vary among women. Some womens breasts have a higher proportion of glandular tissue than of adipose or connective tissues. The fat-to-connective-tissue ratio determines the density or firmness of the breast. During a womans life, her breasts change size, shape, and weight due to hormonal changes during puberty, the menstrual cycle, pregnancy, breastfeeding, and menopause. Glandular structure The breast is an apocrine gland that produces the milk used to feed an infant. The nipple of the breast is surrounded by the areola (nipple-areola complex). The areola has many sebaceous glands, and the skin color varies from pink to dark brown. The basic units of the breast are the terminal duct lobular units (TDLUs), which produce the fatty breast milk. They give the breast its offspring-feeding functions as a mammary gland. They are distributed throughout the body of the breast. Approximately two-thirds of the lactiferous tissue is within 30 mm of the base of the nipple. The terminal lactiferous ducts drain the milk from TDLUs into 4–18 lactiferous ducts, which drain to the nipple. The milk-glands-to-fat ratio is 2:1 in a lactating woman, and 1:1 in a non-lactating woman. In addition to the milk glands, the breast is also composed of connective tissues (collagen, elastin), white fat, and the suspensory Coopers ligaments. Sensation in the breast is provided by the peripheral nervous system innervation by means of the front (anterior) and side (lateral) cutaneous branches of the fourth-, fifth-, and sixth intercostal nerves. The T-4 nerve (Thoracic spinal nerve 4), which innervates the dermatomic area, supplies sensation to the nipple-areola complex. Lymphatic drainage Approximately 75% of the lymph from the breast travels to the axillary lymph nodes on the same side of the body, whilst 25% of the lymph travels to the parasternal nodes (beside the sternum bone).: 116 A small amount of remaining lymph travels to the other breast and to the abdominal lymph nodes. The subareolar region has a lymphatic plexus known as the "subareolar plexus of Sappey". The axillary lymph nodes include the pectoral (chest), subscapular (under the scapula), and humeral (humerus-bone area) lymph-node groups, which drain to the central axillary lymph nodes and to the apical axillary lymph nodes. The lymphatic drainage of the breasts is especially relevant to oncology because breast cancer is common to the mammary gland, and cancer cells can metastasize (break away) from a tumour and be dispersed to other parts of the body by means of the lymphatic system. Shape, texture, and support The morphologic variations in the size, shape, volume, tissue density, pectoral locale, and spacing of the breasts determine their natural shape, appearance, and position on a womans chest. Breast size and other characteristics do not predict the fat-to-milk-gland ratio or the potential for the woman to nurse an infant. The size and the shape of the breasts are influenced by normal-life hormonal changes (thelarche, menstruation, pregnancy, menopause) and medical conditions (e.g. virginal breast hypertrophy). The shape of the breasts is naturally determined by the support of the suspensory Coopers ligaments, the underlying muscle and bone structures of the chest, and by the skin envelope. The suspensory ligaments sustain the breast from the clavicle (collarbone) and the clavico-pectoral fascia (collarbone and chest) by traversing and encompassing the fat and milk-gland tissues. The breast is positioned, affixed to, and supported upon the chest wall, while its shape is established and maintained by the skin envelope. In most women, one breast is slightly larger than the other. More obvious and persistent asymmetry in breast size occurs in up to 25% of women.While it is a common belief that breastfeeding causes breasts to sag, researchers have found that a womans breasts sag due to four key factors: cigarette smoking, number of pregnancies, gravity, and weight loss or gain.The base of each breast is attached to the chest by the deep fascia over the pectoralis major muscles. The space between the breast and the pectoralis major muscle, called retromammary space, gives mobility to the breast. The chest (thoracic cavity) progressively slopes outwards from the thoracic inlet (atop the breastbone) and above to the lowest ribs that support the breasts. The inframammary fold, where the lower portion of the breast meets the chest, is an anatomic feature created by the adherence of the breast skin and the underlying connective tissues of the chest; the IMF is the lower-most extent of the anatomic breast. Normal breast tissue typically has a texture that feels nodular or granular, to an extent that varies considerably from woman to woman. Development The breasts are principally composed of adipose, glandular, and connective tissues. Because these tissues have hormone receptors, their sizes and volumes fluctuate according to the hormonal changes particular to thelarche (sprouting of breasts), menstruation (egg production), pregnancy (reproduction), lactation (feeding of offspring), and menopause (end of menstruation). Puberty The morphological structure of the human breast is identical in males and females until puberty. For pubescent girls in thelarche (the breast-development stage), the female sex hormones (principally estrogens) in conjunction with growth hormone promote the sprouting, growth, and development of the breasts. During this time, the mammary glands grow in size and volume and begin resting on the chest. These development stages of secondary sex characteristics (breasts, pubic hair, etc.) are illustrated in the five-stage Tanner Scale.During thelarche the developing breasts are sometimes of unequal size, and usually the left breast is slightly larger. This condition of asymmetry is transitory and statistically normal in female physical and sexual development. Medical conditions can cause overdevelopment (e.g., virginal breast hypertrophy, macromastia) or underdevelopment (e.g., tuberous breast deformity, micromastia) in girls and women. Approximately two years after the onset of puberty (a girls first menstrual cycle), estrogen and growth hormone stimulate the development and growth of the glandular fat and suspensory tissues that compose the breast. This continues for approximately four years until the final shape of the breast (size, volume, density) is established at about the age of 21. Mammoplasia (breast enlargement) in girls begins at puberty, unlike all other primates in which breasts enlarge only during lactation. Changes during the menstrual cycle During the menstrual cycle, the breasts are enlarged by premenstrual water retention and temporary growth. Pregnancy and breastfeeding The breasts reach full maturity only when a womans first pregnancy occurs. Changes to the breasts are among the first signs of pregnancy. The breasts become larger, the nipple-areola complex becomes larger and darker, the Montgomerys glands enlarge, and veins sometimes become more visible. Breast tenderness during pregnancy is common, especially during the first trimester. By mid-pregnancy, the breast is physiologically capable of lactation and some women can express colostrum, a form of breast milk.Pregnancy causes elevated levels of the hormone prolactin, which has a key role in the production of milk. However, milk production is blocked by the hormones progesterone and estrogen until after delivery, when progesterone and estrogen levels plummet. Menopause At menopause, breast atrophy occurs. The breasts can decrease in size when the levels of circulating estrogen decline. The adipose tissue and milk glands also begin to wither. The breasts can also become enlarged from adverse side effects of combined oral contraceptive pills. The size of the breasts can also increase and decrease in response to weight fluctuations. Physical changes to the breasts are often recorded in the stretch marks of the skin envelope; they can serve as historical indicators of the increments and the decrements of the size and volume of a womans breasts throughout the course of her life. Breastfeeding The primary function of the breasts, as mammary glands, is the nourishing of an infant with breast milk. Milk is produced in milk-secreting cells in the alveoli. When the breasts are stimulated by the suckling of her baby, the mothers brain secretes oxytocin. High levels of oxytocin trigger the contraction of muscle cells surrounding the alveoli, causing milk to flow along the ducts that connect the alveoli to the nipple.Full-term newborns have an instinct and a need to suck on a nipple, and breastfed babies nurse for both nutrition and for comfort. Breast milk provides all necessary nutrients for the first six months of life, and then remains an important source of nutrition, alongside solid foods, until at least one or two years of age. Clinical significance The breast is susceptible to numerous benign and malignant conditions. The most frequent benign conditions are puerperal mastitis, fibrocystic breast changes and mastalgia. Lactation unrelated to pregnancy is known as galactorrhea. It can be caused by certain drugs (such as antipsychotic medications), extreme physical stress, or endocrine disorders. Lactation in newborns is caused by hormones from the mother that crossed into the babys bloodstream during pregnancy. Breast cancer Breast cancer is the most common cause of cancer death among women and it is one of the leading causes of death among women. Factors that appear to be implicated in decreasing the risk of breast cancer are regular breast examinations by health care professionals, regular mammograms, self-examination of breasts, healthy diet, and exercise to decrease excess body fat, and breastfeeding. Male breasts Both females and males develop breasts from the same embryological tissues. Normally, males produce lower levels of estrogens and higher levels of androgens, namely testosterone, which suppress the effects of estrogens in developing excessive breast tissue. In boys and men, abnormal breast development is manifested as gynecomastia, the consequence of a biochemical imbalance between the normal levels of estrogen and testosterone in the male body. Around 70% of boys temporarily develop breast tissue during adolescence. The condition usually resolves by itself within two years. When male lactation occurs, it is considered a symptom of a disorder of the pituitary gland. Plastic surgery Plastic surgery can be performed to augment or reduce the size of breasts, or reconstruct the breast in cases of deformative disease, such as breast cancer. Breast augmentation and breast lift (mastopexy) procedures are done only for cosmetic reasons, whereas breast reduction is sometimes medically indicated. In cases where a womans breasts are severely asymmetrical, surgery can be performed to either enlarge the smaller breast, reduce the size of the larger breast, or both.Breast augmentation surgery generally does not interfere with future ability to breastfeed. Breast reduction surgery more frequently leads to decreased sensation in the nipple-areola complex, and to low milk supply in women who choose to breastfeed. Implants can interfere with mammography (breast x-rays images). Society and culture General In Christian iconography, some works of art depict women with their breasts in their hands or on a platter, signifying that they died as a martyr by having their breasts severed; one example of this is Saint Agatha of Sicily. Femen is a feminist activist group which uses topless protests as part of their campaigns against sex tourism religious institutions, sexism, and homophobia. Femen activists have been regularly detained by police in response to their protests.There is a long history of female breasts being used by comedians as a subject for comedy fodder (e.g., British comic Benny Hills burlesque/slapstick routines). Art history In European pre-historic societies, sculptures of female figures with pronounced or highly exaggerated breasts were common. A typical example is the so-called Venus of Willendorf, one of many Paleolithic Venus figurines with ample hips and bosom. Artifacts such as bowls, rock carvings and sacred statues with breasts have been recorded from 15,000 BC up to late antiquity all across Europe, North Africa and the Middle East. Many female deities representing love and fertility were associated with breasts and breast milk. Figures of the Phoenician goddess Astarte were represented as pillars studded with breasts. Isis, an Egyptian goddess who represented, among many other things, ideal motherhood, was often portrayed as suckling pharaohs, thereby confirming their divine status as rulers. Even certain male deities representing regeneration and fertility were occasionally depicted with breast-like appendices, such as the river god Hapy who was considered to be responsible for the annual overflowing of the Nile. Female breasts were also prominent in Minoan art in the form of the famous Snake Goddess statuettes, and a few other pieces, though most female breasts are covered. In Ancient Greece there were several cults worshipping the "Kourotrophos", the suckling mother, represented by goddesses such as Gaia, Hera and Artemis. The worship of deities symbolized by the female breast in Greece became less common during the first millennium. The popular adoration of female goddesses decreased significantly during the rise of the Greek city states, a legacy which was passed on to the later Roman Empire.During the middle of the first millennium BC, Greek culture experienced a gradual change in the perception of female breasts. Women in art were covered in clothing from the neck down, including female goddesses like Athena, the patron of Athens who represented heroic endeavor. There were exceptions: Aphrodite, the goddess of love, was more frequently portrayed fully nude, though in postures that were intended to portray shyness or modesty, a portrayal that has been compared to modern pin ups by historian Marilyn Yalom. Although nude men were depicted standing upright, most depictions of female nudity in Greek art occurred "usually with drapery near at hand and with a forward-bending, self-protecting posture". A popular legend at the time was of the Amazons, a tribe of fierce female warriors who socialized with men only for procreation and even removed one breast to become better warriors (the idea being that the right breast would interfere with the operation of a bow and arrow). The legend was a popular motif in art during Greek and Roman antiquity and served as an antithetical cautionary tale. Body image Many women regard their breasts as important to their sexual attractiveness, as a sign of femininity that is important to their sense of self. A woman with smaller breasts may regard her breasts as less attractive. Clothing Because breasts are mostly fatty tissue, their shape can—within limits—be molded by clothing, such as foundation garments. Bras are commonly worn by about 90% of Western women, and are often worn for support. The social norm in most Western cultures is to cover breasts in public, though the extent of coverage varies depending on the social context. Some religions ascribe a special status to the female breast, either in formal teachings or through symbolism. Islam forbids free women from exposing their breasts in public. Many cultures, including Western cultures in North America, associate breasts with sexuality and tend to regard bare breasts as immodest or indecent. In some cultures, like the Himba in northern Namibia, bare-breasted women are normal. In some African cultures, for example, the thigh is regarded as highly sexualised and never exposed in public, but breast exposure is not taboo. In a few Western countries and regions female toplessness at a beach is acceptable, although it may not be acceptable in the town center.Social attitudes and laws regarding breastfeeding in public vary widely. In many countries, breastfeeding in public is common, legally protected, and generally not regarded as an issue. However, even though the practice may be legal or socially accepted, some mothers may nevertheless be reluctant to expose a breast in public to breastfeed due to actual or potential objections by other people, negative comments, or harassment. It is estimated that around 63% of mothers across the world have publicly breast-fed. Bare-breasted women are legal and culturally acceptable at public beaches in Australia and much of Europe. Filmmaker Lina Esco made a film entitled Free the Nipple, which is about "...laws against female toplessness or restrictions on images of female, but not male, nipples", which Esco states is an example of sexism in society. Sexual characteristic In some cultures, breasts play a role in human sexual activity. In Western culture, breasts have a "...hallowed sexual status, arguably more fetishized than either sexs genitalia". Breasts and especially the nipples are among the various human erogenous zones. They are sensitive to the touch as they have many nerve endings; and it is common to press or massage them with hands or orally before or during sexual activity. During sexual arousal, breast size increases, venous patterns across the breasts become more visible, and nipples harden. Compared to other primates, human breasts are proportionately large throughout adult females lives. Some writers have suggested that they may have evolved as a visual signal of sexual maturity and fertility.Many people regard bare female breasts to be aesthetically pleasing or erotic, and they can elicit heightened sexual desires in men in many cultures. In the ancient Indian work the Kama Sutra, light scratching of the breasts with nails and biting with teeth are considered erotic. Some people show a sexual interest in female breasts distinct from that of the person, which may be regarded as a breast fetish. A number of Western fashions include clothing which accentuate the breasts, such as the use of push-up bras and decollete (plunging neckline) gowns and blouses which show cleavage. While U.S. culture prefers breasts that are youthful and upright, some cultures venerate women with drooping breasts, indicating mothering and the wisdom of experience.Research conducted at the Victoria University of Wellington showed that breasts are often the first thing men look at, and for a longer time than other body parts. The writers of the study had initially speculated that the reason for this is due to endocrinology with larger breasts indicating higher levels of estrogen and a sign of greater fertility, but the researchers said that "Men may be looking more often at the breasts because they are simply aesthetically pleasing, regardless of the size."Some women report achieving an orgasm from nipple stimulation, but this is rare. Research suggests that the orgasms are genital orgasms, and may also be directly linked to "the genital area of the brain". In these cases, it seems that sensation from the nipples travels to the same part of the brain as sensations from the vagina, clitoris and cervix. Nipple stimulation may trigger uterine contractions, which then produce a sensation in the genital area of the brain. Anthropomorphic geography There are many mountains named after the breast because they resemble it in appearance and so are objects of religious and ancestral veneration as a fertility symbol and of well-being. In Asia, there was "Breast Mountain", which had a cave where the Buddhist monk Bodhidharma (Da Mo) spent much time in meditation. Other such breast mountains are Mount Elgon on the Uganda–Kenya border; Beinn Chìochan and the Maiden Paps in Scotland; the Bundok ng Susong Dalaga (Maidens breast mountains) in Talim Island, Philippines, the twin hills known as the Paps of Anu (Dá Chích Anann or the breasts of Anu), near Killarney in Ireland; the 2,086 m high Tetica de Bacares or La Tetica in the Sierra de Los Filabres, Spain; Khao Nom Sao in Thailand, Cerro Las Tetas in Puerto Rico; and the Breasts of Aphrodite in Mykonos, among many others. In the United States, the Teton Range is named after the French word for nipple. See also Medicine portal Human sexuality portal Udder References Bibliography Hollander, Anne (1993). Seeing through clothes. Berkeley: University of California Press. ISBN 978-0-520-08231-1. Morris, Desmond The Naked Ape: a zoologists study of the human animal Bantam Books, Canada. 1967 Yalom, Marilyn (1998). A history of the breast. London: Pandora. ISBN 978-0-86358-400-8. Venes, Donald (2013). Tabers cyclopedic medical dictionary. Philadelphia: F.A. Davis. ISBN 978-0-8036-2977-6. Lawrence, Ruth (2016). Breastfeeding : a guide for the medical profession, 8th edition. Philadelphia, PA: Elsevier. ISBN 978-0-323-35776-0. External links "Are Women Evolutionary Sex Objects?: Why Women Have Breasts". Archived from the original on 2 December 2011.
Acute exacerbation of chronic obstructive pulmonary disease	An acute exacerbation of chronic obstructive pulmonary disease, or acute exacerbations of chronic bronchitis (AECB), is a sudden worsening of chronic obstructive pulmonary disease (COPD) symptoms including shortness of breath, quantity and color of phlegm that typically lasts for several days. It may be triggered by an infection with bacteria or viruses or by environmental pollutants. Typically, infections cause 75% or more of the exacerbations; bacteria can roughly be found in 25% of cases, viruses in another 25%, and both viruses and bacteria in another 25%. Airway inflammation is increased during the exacerbation resulting in increased hyperinflation, reduced expiratory air flow and decreased gas exchange.Exacerbations can be classified as mild, moderate, and severe. As COPD progresses, exacerbations tend to become more frequent, the average being about three episodes per year. Signs and symptoms An acute exacerbation of COPD is associated with increased frequency and severity of coughing. It is often accompanied by worsened chest congestion and discomfort. Shortness of breath and wheezing are present in many cases. Exacerbations may be accompanied by increased amount of cough and sputum productions, and a change in appearance of sputum. An abrupt worsening in COPD symptoms may cause rupture of the airways in the lungs, which in turn may cause a spontaneous pneumothorax.In infection, there is often weakness, fever and chills. If due to a bacterial infection, the sputum may be slightly streaked with blood and coloured yellow or green. Causes As the lungs tend to be vulnerable organs due to their exposure to harmful particles in the air, several things can cause an acute exacerbation of COPD: Respiratory infection, being responsible for approximately half of COPD exacerbations. Approximately half of these are due to viral infections and another half appears to be caused by bacterial infections. Common bacterial pathogens of acute exacerbations include Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. Less common bacterial pathogens include Chlamydia pneumoniae and MRSA. Pathogens seen more frequently in patients with impaired lung function (FEV<35% of predicted) include Haemophilus parainfluenzae (after repeated use of antibiotics), Mycoplasma pneumoniae and gram-negative, opportunistic pathogens like Pseudomonas aeruginosa and Klebsiella pneumoniae. Allergens, e.g., pollens, wood or cigarette smoke, pollution Toxins, including a variety of different chemicals Air pollution Failing to follow a drug therapy program, e.g. improper use of an inhalerIn one-third of all COPD exacerbation cases, the cause cannot be identified. Diagnosis The diagnostic criteria for acute exacerbation of COPD generally include a production of sputum that is purulent and may be thicker than usual, but without evidence of pneumonia (which involves mainly the alveoli rather than the bronchi). Also, diagnostic criteria may include an increase in frequency and severity of coughing, as well as increased shortness of breath.A chest X-ray is usually performed on people with fever and, especially, hemoptysis (blood in the sputum), to rule out pneumonia and get information on the severity of the exacerbation. Hemoptysis may also indicate other, potentially fatal, medical conditions.A history of exposure to potential causes and evaluation of symptoms may help in revealing the cause the exacerbation, which helps in choosing the best treatment. A sputum culture can specify which strain is causing a bacterial AECB. An early morning sample is preferred.E-nose showed the ability to smell the cause of the exacerbation.The definition of a COPD exacerbation is commonly described as "lost in translation", meaning that there is no universally accepted standard with regard to defining an acute exacerbation of COPD. Many organizations consider it a priority to create such a standard, as it would be a major step forward in the diagnosis and quality of treatment of COPD. Prevention Acute exacerbations can be partially prevented. Some infections can be prevented by vaccination against pathogens such as influenza and Streptococcus pneumoniae. Regular medication use can prevent some COPD exacerbations; long acting beta-adrenoceptor agonists (LABAs), long-acting anticholinergics, inhaled corticosteroids and low-dose theophylline have all been shown to reduce the frequency of COPD exacerbations. Other methods of prevention include: Smoking cessation and avoiding dust, passive smoking, and other inhaled irritants Yearly influenza and 5-year pneumococcal vaccinations Regular exercise, appropriate rest, and healthy nutrition Avoiding people currently infected with e.g. cold and influenza Maintaining good fluid intake and humidifying the home, in order to help reduce the formation of thick sputum and chest congestion. Treatment Based on the severity different treatments may be used. Mild exacerbations are treated with short acting bronchodilators (SABDs). Moderate exacerbations are treated with SABDs together with antibiotics or oral corticosteroids, or both. Severe exacerbations need hospital treatment, and the prognosis is poor. Oxygen Oxygen therapy should be initiated if there is significantly low blood oxygen. High flow oxygen may be harmful in those with an acute exacerbation of COPD. In the prehospital environment those given high flow O2 rather than titrating their O2 saturations to 88% to 92% had worse outcomes. Antibiotics and steroids appear useful in mild to severe disease. Medications Inhaled bronchodilators open up the airways in the lungs. These include salbutamol and terbutaline (both β2-adrenergic agonists), and ipratropium (an anticholinergic). Medication can be administered via inhaler or nebuliser. There is no evidence to prefer a nebuliser over an inhaler. Antibiotics are used if a bacterial infection is the suspected cause. However, antibiotics will not treat exacerbations caused by viruses. Viral infections will usually be cured with time with the aid of proper rest and care. Still, other medications may be needed to control symptoms. Lipid-soluble antibiotics such as macrolides, tetracyclines, and fluoroquinolones penetrate the lung tissue well. Macrolides are more active against Streptococcus pneumoniae than the tetracyclines and the older fluoroquinolones. Within the macrolides, newer ones are more active against Haemophilus influenzae than the older erythromycin. Regimens should generally be given for five days. Choice of antibiotics is also dependent on the severity of the symptoms: "Simple" COPD is generally where a person 65 years or less, has fewer than four exacerbations per year, has minimal or moderate impairment in respiratory function and no comorbid disease. In patients with "simple" COPD, therapy should be targeted towards Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and possibly pathogens of atypical pneumonia. The first-line treatment is a beta-lactam antibiotic such as amoxicillin. The choice will depend on resistance patterns. In patients with penicillin allergy, doxycycline or trimethoprim are preferred. More complicated bronchitis may be when the patient is more than 65 years old, has four or more exacerbations per year, has an FEV1/FVC ratio of less than 50% on spirometry, has failed to respond to previous antibiotic treatment, and/or has comorbidity. In these cases, treatment should be aimed at Gram-negative bacteria and the possibility of high antibiotic resistance should be considered. Sputum culture results are of great value in determining antibiotic resistance. First-line treatment is cefuroxime or co-amoxiclav. Third-line treatment, as well as treatment in penicillin-allergic patients, is a fluoroquinolone such as ciprofloxacin. An agent active against Streptococcus pneumoniae may have to be added. Corticosteroids such as prednisolone reduce inflammation in the airways. According to a 2018 systematic review, a shorter, five-day course of systemic corticosteroids is likely comparable to longer (10–14 day) therapy for treatment of COPD exacerbation (Odds ratio (OR) 0.72, 95% confidence interval (CI) 0.36 to 1.46). Theophylline is generally not recommended.There should also be a "care plan" in case of future exacerbations. Patients may watch for symptoms, such as shortness of breath, change in character or amount of mucus, and start self-treatment as discussed with a health care provider. This allows for treatment right away until a doctor can be seen.The symptoms of acute exacerbations are treated using short-acting bronchodilators. A course of corticosteroids, usually in tablet or intravenous rather than inhaled form, can speed up recovery. The IV and oral forms of steroids have been found to be equivalent. Antibiotics are often used but will only help if the exacerbation is due to an infection. Antibiotics are indicated when a patient notes increased sputum production, purulent sputum, increased dyspnea, has an elevated white count, or is febrile. Examples of first-line antibiotics are amoxicillin, doxycycline, and co-trimoxazole. Mechanical ventilation Severe exacerbations can require hospital care where treatments such as oxygen and mechanical ventilation may be required. Mechanical ventilation can be invasive (endotracheal intubation) or non-invasive forms of ventilation such as continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP). Epidemiology The incidence varies depending on which definition is used, but definitions by Anthonisen et al. the typical COPD patient averages two to three AECB episodes per year. With a COPD prevalence of more than 12 million (possibly 24 million including undiagnosed ones) in the United States, there are at least 30 million incidences of AECB annually in the US. References == External links ==
Progressive retinal atrophy	Progressive retinal atrophy (PRA) is a group of genetic diseases seen in certain breeds of dogs and, more rarely, cats. Similar to retinitis pigmentosa in humans, it is characterized by the bilateral degeneration of the retina, causing progressive vision loss culminating in blindness. The condition in nearly all breeds is inherited as an autosomal recessive trait, with the exception of the Siberian Husky (inherited as an X chromosome linked trait) and the Bullmastiff (inherited as an autosomal dominant trait). There is no treatment. Types of PRA In general, PRAs are characterised by initial loss of rod photoreceptor cell function followed by that of the cones and for this reason night blindness is the first significant clinical sign for most dogs affected with PRA. As other retinal disorders, PRA can be divided into either dysplastic disease, where the cells develop abnormally, and degenerative, where the cells develop normally but then degenerate during the dogs lifetime.Generalized PRA is the most common type and causes atrophy of all the neural retinal structures. Central progressive retinal atrophy (CPRA) is a different disease from PRA involving the retinal pigment epithelium (RPE), and is also known as retinal pigment epithelial dystrophy (RPED). Generalized PRA Commonly affected breeds: Akita - Symptoms at one to three years old and blindness at three to five years old. Selective breeding has greatly reduced the incidence of this disease in this breed. Miniature longhaired Dachshund - Symptoms at six months old. Papillon - Slowly progressive with blindness at seven to eight years old. Tibetan Spaniel - Symptoms at three to five years old. Tibetan Terrier - PRA3/RCD4 disease of middle age dogs. http://www.ttca-online.org/html/Petersen-Jones_PRA_article.pdf Samoyed - Symptoms by three to five years old. Rod-cone dysplasia This type of PRA has an early onset of severe vision loss. It is caused by a defect in the gene for cGMP-phosphodiesterase, which leads to retinal levels of cyclic guanosine monophosphate ten times normal. Rod-cone dysplasia type 1 Irish Setter - Rod cell response is nearly absent. Night blindness by six to eight weeks old, often blind by one year old. Sloughi - A DNA test can identify whether Sloughis have the mutated recessive gene. This has enabled breeders to breed away from PRA, and the disease is now rare in the breed. Rod-cone dysplasia type 2 Collie - Rod cell response is nearly absent. Night blindness by six weeks old, blind by one to two years old. Rod-cone dysplasia type 3 Cardigan Welsh Corgi Rod dysplasia Norwegian Elkhound - Characterized by dysplasia of the rod cell unit and subsequent degeneration of the cone cell unit. Rod cell response is nearly absent. Night blindness by six months old, blind by three to five years old. Rod dysplasia has now been bred out of this breed. Early retinal degeneration Norwegian Elkhound - Night blindness by six weeks old, blind by twelve to eighteen months old. Photoreceptor dysplasia This is caused by an abnormal development of both rod and cone cells. Dogs are initially night blind and then progress to day blindness. Miniature Schnauzer - Slowly progressive, not seen until two to five years old. Belgian Shepherd Dog - Complete blindness by eight weeks old. Cone degeneration Alaskan Malamute - Temporary loss of vision in daylight (hemeralopia) at eight to ten weeks old. There is a purely rod cell retina by four years old. Cone-rod dystrophy Glen of Imaal Terrier - CRD3 results in gradual blindness with onset around 4 years of age (often detectable as retinal thinning as early as 3 years of age). Caused by a mutation in gene ADAM9, the disease is analogous to CRD9 in humans. A genetic test is now available from Optigen, LLC, that will identify whether a dog is affected, a carrier (heterozygous), or clear. Progressive rod-cone degeneration (PRCD) This is a disease with normal rod and cone cell development but late onset degeneration of the rod cells that progresses to the cone cells. It is inherited as an autosomal recessive trait and has been linked to the ninth canine chromosome. Poodle - Night blindness by three to five years old, blind by five to seven years old. English Cocker Spaniel - Occurs late in life, usually at four to eight years old. American Cocker Spaniel - Night blindness by three to five years old, blind one to two years later. Labrador Retriever - Night blindness by four to six years old, blind at six to eight years old. Portuguese Water Dog Chesapeake Bay Retriever Australian Cattle Dog American Eskimo Dog Nova Scotia Duck Tolling Retriever X-linked PRA This condition is linked to the X chromosome. Siberian Husky - Night blindness by two to four years old. Samoyed - More severe disease than the Husky. Dominant PRA Bullmastiff - Inherited as an autosomal dominant trait due to a mutation in the gene for rhodopsin. Feline PRA Abyssinian - Two forms exist. One is inherited as an autosomal dominant trait and has an early age onset. The other is inherited as an autosomal recessive trait and has a middle age onset. Early onset PRA has also been reported in the domestic shorthaired cat and Persian. The Siamese also likely has a hereditary form of PRA. Despite belief among breeders to the contrary, there is apparently no link between coat color in Persians and the development of PRA. Central progressive retinal atrophy (CPRA) CPRA is also known as retinal pigment epithelial dystrophy (RPED). The cause of this condition is the loss of the retinal pigment epitheliums ability to effectively process the photoreceptor outer segment (POS) and subsequent accumulation of POS material in the RPE and loss of function. The loss of function of the RPE leads to photoreceptor degeneration. Vitamin E deficiency may play a role in the development of CPRA. It is characterized by accumulation of pigment spots in the retina surrounded by retinal atrophy and a mottled appearance of the pigmented nontapetal fundus. The pigmented spots eventually coalesce and fade as the atrophy of the retina increases. It is an inherited condition (in the Labrador Retriever it is inherited as an autosomal dominant trait with variable penetrance). CPRA occurs in older dogs. Peripheral vision is retained for a long time. Vision is better in low light and better for moving or distant objects. Not all affected dogs go blind. Secondary cataracts are common. Commonly affected breeds Labrador Retriever Golden Retriever Border Collie Collie Shetland Sheepdog English Cocker Spaniel English Springer Spaniel Chesapeake Bay Retriever Cavalier King Charles Spaniel Briard - has an especially high frequency.It can also be found in the poodle varieties Hereditary retinal dysplasia There is another retinal disease in Briards known as hereditary retinal dysplasia. These dogs are night blind from birth, and day vision varies. Puppies affected often have nystagmus. It is also known as lipid retinopathy. Diagnosis Progressive vision loss in any dog in the absence of canine glaucoma or cataracts can be an indication of PRA. It usually starts with decreased vision at night, or nyctalopia. Other symptoms include dilated pupils and decreased pupillary light reflex. Fundoscopy to examine the retina will show shrinking of the blood vessels, decreased pigmentation of the nontapetal fundus, increased reflection from the tapetum due to thinning of the retina, and later in the disease a darkened, atrophied optic disc. Secondary cataract formation in the posterior portion of the lens can occur late in the disease. In these cases diagnosis of PRA may require electroretinography (ERG). For many breeds there are specific genetic tests of blood or buccal mucosa for PRA.Absent a genetic test, animals of breeds susceptible to PRA can be cleared of the disease only by the passage of time—that is, by living past the age at which PRA symptoms are typically apparent in their breed. Breeds in which the PRA gene is recessive may still be carriers of the gene and pass it on to their offspring, however, even if they lack symptoms, and it is also possible for onset of the disease to be later than expected, making this an imperfect test at best. Management There is no treatment for PRA. However, most dogs that suffer from this disease adjust remarkably well. To maximize the quality of the dogs life, follow these guidelines: Do not rearrange furniture, as the dog has memorized the layout of the environment Use a short leash when walking a dog with blindness from advanced PRA Erect safety barriers around pools or balconies See also Sudden acquired retinal degeneration References External links Article on PRA Article on Cataracts
Craniopagus twins	Craniopagus twins are conjoined twins that are fused at the cranium. The union may occur on any portion of the cranium, but does not primarily involve either the face or the foramen magnum; their brains are usually separate, but they may share some brain tissue. Conjoined twins are genetically identical and always share the same sex. The thorax and abdomen are separate and each twin has its own umbilicus and umbilical cord.The condition is extremely rare, with an incidence of approximately 1 in 2.5 million live births. An estimated 50 craniopagus twins born around the world every year as of 2021, with only 15 twins surviving beyond the first 30 days of life. Relatively few craniopagus twins survive the perinatal period; approximately 40% of conjoined twins are stillborn and an additional 33% die within the immediate perinatal period, usually from organ abnormalities and failure.However, 25% of craniopagus twins survive and may be considered for a surgical separation; several such attempts occur yearly worldwide. Advances in neuroimaging, neuroanesthesia, and neurosurgery have proven that a successful outcome is possible. Among all conjoined twins, craniopagus twins account for a mere 2% to 6%. Classification The first classification system was developed by OConnell in 1976, where craniopagus twins were classified as total and partial. In the former, twins shared an "extensive surface area with widely connected cranial cavities", while in the latter, only a "limited, superficial surface area" was connected.In 2006, Stone and Goodrich came up with a more nuanced classification system, which is the "most commonly used" system. Partial CPT was defined as "lacking substantial shared dural venous sinuses", whereas total CPT "share a large portion of their dural venous sinuses and present with pronounced brain compression, which leads to distortion within the cranium". Total Total craniopagus twins share a large portion of dural venous sinuses and present with pronounced brain compression, leading to distortion within the cranium. Stone and Goodrich also defined two main subtypes, based on whether the long-axis angle between the twins was angular or vertical. The angular subtype has a higher rate of comorbidities than the vertical subtype.Vertical craniopagus calvaria is continuous and is further subdivided on the basis of intertwin axial facial rotation: Type 1: both children face in the same general directional axis so that the angle between twins is less than 40 degrees. These twins show relatively symmetric superior bi-parietal or vertex compressional flattening. Type 2: both children face opposite directions so that the deformity shows an axial rotation between 140 and 180 degrees. Type 3: in this variety axial rotation is intermediate between the first two types with a rotation of being between 40 and 140.Another classification system divides total craniopagus twins into four categories: Frontal: twins are facing each other with the axis of the bodies forming an acute angle Temporoparietal: joined immediately above the external auditory meatus Occipital: twins are connected in the occipital lobe causing the twins to face away from each other Parietal: twins fuse at the vertex with the axis of the twins forming an obtuse angle; this leads to a situation where the twins share the most veins, lobes, and neural circuitry and thus is often described as one brain shared by two individuals Having this kind of juncture means that there would be one common continuous cranium housing four cerebral hemispheres. An incomplete dural septum typically separates the flattened cerebral hemispheres. In total vertical craniopagus, the major cerebral arterial supply is usually confined to each respective twin and in some cases conjoined brain tissue may contain a larger artery. Within this category there are three smaller subdivisions that basically outline the different rotational symmetry of the junction. Partial Stone and Goodrich define partial craniopagus twins as lacking substantial shared dural venous sinuses, with limited surface area involvement, with either intact crania or cranial defects. It is less common than total craniopagus twins. In partial craniopagus twins, the unions are usually frontal and less commonly occipital and vertical. Angular frontal junctions occur when the two twins are joined at any part of the forehead. Occipital twins are joined at the occipital lobe in the back of the head and vertical are joined on the top of the head and usually face opposite directions. The junctional diameter is often smaller in partial forms and occasionally an incomplete layer of bone may be present between the twins. Each child maintains independent calvarial convexities except at the common area of skull junction. The dura of both children may be intact or deficient and cortical gyri may interdigitate. Additionally, shared dural venous sinuses is usually absent, or, if it is present, negligible. These twins usually undergo successful separation and both twins may live to lead normal lives. Gestation and embryology The exact nature of how conjoined twins develop in utero remains unclear. Embryologists have traditionally attributed identical twinning as "splitting or fission" of either the inner cell mass of pleuripotential cells or early embryonic disc at 13–14 days of gestation just before the primitive streak. Some theorists suggested that conjoined twins develop as a result of the failed fusion of a single fertilized ovum. However a new hypothesis suggests that cranial fusion occurs between two separate embryos before the end of the 4th week of gestation. This can happen because the cranial neuropore is still open, which is responsible for the ultimate fusion and formation of the brain stem and central nervous system. Furthermore, this secondary fusion of embryonic discs could implicate that intact skin will not fuse to other intact skin, including the ectoderm of the embryo. This means that two embryonic discs could only unite in locations where the ectoderm is absent. Moreover, the fusion occurs from neural folds of two separate, dorsally oriented embryonic discs, and the union can occur only after the ectoderm is disrupted to allow the neural and surface ectodermal layers to separate from each other. The union in craniopagus twins may happen at any portion of the calvarium. The juncture can involve either the entire diameter of the head or any portion of the head and can be positioned at a multitude of rotational angles. In fact, craniopagus twins are rarely found in a symmetrical union. Apart from this, the vertebral axes may have a straight line. Despite this, the angle of the vertebrae is the ultimate dictator in how the individuals heads actually face. The majority of twins face either the same way or the exact opposite direction. Medical procedures Diagnosis Conjoined twins, including craniopagus twins, can be diagnosed using standard ultrasound procedures during a pregnancy. In part because treatment of conjoined twins varies largely, many parents make the decision to terminate pregnancy due to the prognosis and quality-of -life issues. If the parents choose to continue the pregnancy, mother and babies will be closely monitored. In almost all cases, a C-section delivery is planned, often two to three weeks before the due date. Separation surgeries After the twins are born, parents and doctors decide whether or not separation surgery is possible. The doctors also must consider the possibility of reconstructive surgery and the social and learning issues the twins may have to face after they are separated. Due to advances in neuroimaging, neuroanesthesia, and neurosurgical techniques, successful separation operations have become more common. Physical traits like joined brain tissue, shared arteries and veins, as well as defects in the skull and dura mater complicate a separation operation.Neuroimaging especially plays an important role because it is imperative in surgical planning to understand the shared vascular anatomy—including the brain parenchyma, calvaria, and dura mater—because separating shared vessels can lead to thrombosis, air embolism, cerebral infarction, and hemorrhage. Technologies such as CT scans, MRIs, and angiography are used to map the shared vascular structures. Cases Emilie and Elisabeth Stoll were born on January 17, 1912. Their parents exhibited them until their death in July 1912. Their cause of death is unknown, but they were probably weakened by the stress of travelling and exhibition. Rodney and Roger Brodie were born in Rock Island, Illinois, in 1951. In December 1952 a medical team led by neurosurgeon Oscar Sugar attempted to separate the 15-month old twins in a surgery that lasted 12 hours. During surgery, the doctors discovered that the twins shared the superior sagittal sinus, the canal that drains blood from the brain to the heart. This vessel was retained by Rodney Brodie. Both twins survived the surgery, although Roger did not regain consciousness and died 34 days later. Rodney recovered but suffered neurological damage; because his skull was never closed, he wore a helmet until his death at age 11. This was the first case where craniopagual twins were separated and one survived. Lotti and Rosemarie Knaack, who were born in Germany in 1951, were separated at age 6, with Lotti dying in surgery. Rosemarie survived until 2008. Lori and George Schappell, born in 1961, are believed to be the longest-surviving craniopagus twins still living. Ladan and Laleh Bijani, who were born in Iran, were separated in 2003 at age 29, only to die 90 minutes apart after surgery. Ahmed and Mohamed Ibrahim, who were born in Egypt, were successfully separated in Dallas, Texas, in October 2001, when they were 28 months old. Lea and Tabea Block, who were born in Germany in 2003, were separated in September 2004 at Johns Hopkins Hospital in Baltimore, Maryland. Tabea died of cardiac arrest an hour after separation. Anastasia and Tatiana Dogaru were born in 2004 with the crown of Tatianas head joined to the back of Anastasias. Doctors determined in 2007 that they could not be separated. Krista and Tatiana Hogan, born on October 25, 2006. After a series of tests doctors also determined these twins could also not be separated. Joseph and Luka Banda from Zambia, born in 1997, were separated successfully the same year in South Africa by a team of surgeons led by Ben Carson. Trishna and Krishna from Bangladesh born in December 2006, joined on the tops of their skulls and sharing a small amount of brain tissue. In 2009, they were separated in Melbourne, Australia. Ganga and Jamuna Shreshta, born in Kathmandu, Nepal in 2000, were successfully separated by Dr. Chumpon Chan and his team from the Singapore General Hospital in 2001 Rital and Ritaj Gaboura of Sudan, were separated at 11 months old in 2011 at the Great Ormond Street Hospital in London. As of 2019 they lived in Ireland. Jadon and Anias McDonald were separated at 13 months old in 2016 in a crowdfunded operation costing $2.5million (USD) at Montefiore Hospital in New York. Maria Ysadora and Maria Ysabelle, born in July 2016, were successfully separated on October 27, 2018, after a five-step surgery in São Paulo, Brazil by a multidisciplinary team of neurosurgeons and plastic surgeons led by Helio Machado and James Tait Goodrich. Safa and Marwa Bibi, born in Peshawar, Pakistan, on January 7, 2017, were separated in February 2019 during the third of three surgeries. Erin and Abby Delaney, born on July 24, 2016 in North Carolina, were successfully separated by a team led by Dr. Jesse Taylor and Dr. Gregory Heuer at the Childrens Hospital of Philadelphia on June 6, 2017. Jaga and Kalia, twins from Odisha, India, were separated successfully in September 2017 at All India Institutes of Medical Sciences in New Delhi and kept at SCB Medical College for monitoring. Kalia died on 25 November 2020 from cardiac arrest while Jaga continues to live. Rabeya and Rukaya Islam, born in Pabna, Bangladesh in July 2016, were successfully separated after a 33-hour surgery in Dhaka, Bangladesh, by a medical team from a Hungarian nonprofit called the Action for Defenseless People Foundation led by renowned neurosurgeon András Csókay. Two unnamed year-old twins conjoined at the back of their heads were separated successfully in a surgery performed by Dr. Mickey Gideon at the Soroka Medical Center in Beersheba, Israel, in September 2021. Bernado and Arthur Lima, three-year-old twins from Roraima, Brazil, were separated by a team led by Owase Jeelani in a Rio de Janeiro hospital. Seven surgeries were needed, the last of which alone took 27 hours. The operation was particularly notable in that Jeelani received assistance from Great Ormond Street Hospital in London via the use of virtual reality, as well as the twins being the oldest craniopagus twins to be separated. Tatiana and Krista Throughout history, the fascination about craniopagus twins has continually increased as neurobiology and the field of neuroscience has become more interesting to the public. In 2011, The New York Times Magazine covered a story of two craniopagus twin girls who share a brain and seem to show all different kinds of physiological and emotional responses due to their condition. Though Krista and Tatiana Hogan share a brain, the two girls showed distinct personalities and behavior. One example was when Krista started drinking her juice Tatiana felt it physically going through her body. In any other set of twins the natural conclusion about the two events would be that Kristas drinking and Tatianas reaction would be coincidental. But because Krista and Tatiana are connected at their heads, whatever the girls do they do it together. In this case, brain images revealed that there was an attenuated line stretching between the two brains and forming a "thalamic bridge", a bridge connecting the two thalami. Knowing that the thalamus acts as a major control panel within the body, it is believed that the girls share part of this control panel and so when one girl drinks the other one feels it. This along with many other cases, has advanced social media and neurological related research concerning this kind of link between craniopagus twins. Unfortunately, no controlled studies have been done because the twins are so young and their brains are still very malleable and plastic. Although there is not an overwhelming amount of research surrounding how the union between craniopagus twins leads to different personality, cognitive and motor traits, there have been some studies exploring what it actually means to share a brain. In the case of Tatiana and Krista, it is possible that the twins shared some conscious thought. Studies of the thalamus’ role in the brain provide neurological data that help explain these behavioral observations that these two twins experience. Thalamo-cortico-thalamic circuits are the looped neural pathways that connect the thalamus to the cerebral cortex, and then the cerebral cortex back to the thalamus. Because the thalamus is mainly responsible for relaying sensory messages from the body to the brain, it is possible that there is a lot of overlap between the twins’ sensory reception and the actual response it creates within the brain. One study examines this by studying the thalamus when it is at a persistent vegetative state that is when the patient is awake but not conscious. This study proved that the cortical activity on its own is not conscious and that all the activity between the loops of the thalamus, the cerebral cortex and the thalamus itself are all conscious actions. Another study of the thalamus reaffirms that the thalamus does not answer yes/no questions but instead acts as a mediator between different parts of the cerebral cortex and systemic sensory reception.These loops actually may account for the relationship between Tatiana and Krista. At the neuronal level, communication is dense network of neurons linked between themselves and the coordinator (in this case the thalamus) that finally sends a message to the cortex. On top of this, there are links between the cortex that send messages back through the coordinator and finally to the rest of the body. The brains ability to function through loops and circuits is a good model to explain why Tatiana “consciously” feels what Krista is “physically” experiencing. Additionally there is some level of synchronization between the two twins. Another study found that for craniopagus twins, their connection to each other is comparable to our normal appendages and that their bodies have obvious overlapping physically and psychologically. Because most cases of craniopagus twins are unique, the research outlining general connections between craniopagus twins is limited. However, this example provides insight into the effects of a union between twins who essentially share the same sensory relay system in the thalamus. History Conjoined twinning is one of the oldest known birth defects in history and examples with humans fascination with twins is extremely evident throughout historical literature. Although there are cases of conjoined twins dating back to as early as the 10th century, it was not until 1491 that the first case was documented. Apart from that, Sebastian Münster’s Cosmographia universalis provides the true first account of craniopagus twins who happened to live for ten years, exceeding many expectations during that time. He describes the set of twins as being a unique malformation and a punishment from their mothers mistake. In French barber surgeon Ambroise Paré’s 16th-century book, On Monsters and Marvels, various types of "supernatural" twinning are illustrated and described as "monstrous and marvelous creatures that proceed from the judgment of God", suggesting that conjoined twins and specifically craniopagus twins were viewed as literal monsters in the 16th century. See also Conjoined twins Parasitic twin Twin References == External links ==
Carcinoma	Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal or ectodermal germ layer during embryogenesis.Carcinomas occur when the DNA of a cell is damaged or altered and the cell begins to grow uncontrollably and become malignant. It is from the Greek: καρκίνωμα, romanized: karkinoma, lit. sore, ulcer, cancer (itself derived from karkinos meaning crab). Classification As of 2004, no simple and comprehensive classification system has been devised and accepted within the scientific community. Traditionally, however, malignancies have generally been classified into various types using a combination of criteria, including:The cell type from which they start; specifically: Epithelial cells ⇨ carcinoma Non-hematopoietic mesenchymal cells ⇨ sarcoma Hematopoietic cells Bone marrow-derived cells that normally mature in the bloodstream ⇨ leukemia Bone marrow-derived cells that normally mature in the lymphatic system ⇨ lymphoma Germ cells ⇨ germinomaOther criteria that play a role include: The degree to which the malignant cells resemble their normal, untransformed counterparts The appearance of the local tissue and stromal architecture The anatomical location from which tumors arise Genetic, epigenetic, and molecular features Histological types Adenocarcinoma (adeno = gland) Refers to a carcinoma featuring microscopic glandular-related tissue cytology, tissue architecture, and/or gland-related molecular products, e.g., mucin. Squamous cell carcinoma Refers to a carcinoma with observable features and characteristics indicative of squamous differentiation (intercellular bridges, keratinization, squamous pearls). Adenosquamous carcinoma Refers to a mixed tumor containing both adenocarcinoma and squamous cell carcinoma, wherein each of these cell types comprise at least 10% of the tumor volume. Anaplastic carcinoma Refers to a heterogeneous group of high-grade carcinomas that feature cells lacking distinct histological or cytological evidence of any of the more specifically differentiated neoplasms. These tumors are referred to as anaplastic or undifferentiated carcinomas. Large cell carcinoma Composed of large, monotonous rounded or overtly polygonal-shaped cells with abundant cytoplasm. Small cell carcinoma Cells are usually round and are less than approximately 3 times the diameter of a resting lymphocyte and with little evident cytoplasm. Occasionally, small cell malignancies may themselves have significant components of slightly polygonal and/or spindle-shaped cells.There are a large number of rare subtypes of anaplastic, undifferentiated carcinoma. Some of the more well known include the lesions containing pseudo-sarcomatous components: spindle cell carcinoma (containing elongated cells resembling connective tissue cancers), giant cell carcinoma (containing huge, bizarre, multinucleated cells), and sarcomatoid carcinoma (mixtures of spindle and giant cell carcinoma). Pleomorphic carcinoma contains spindle cell and/or giant cell components, plus at least a 10% component of cells characteristic of more highly differentiated types (i.e. adenocarcinoma and/or squamous cell carcinoma). Very rarely, tumors may contain individual components resembling both carcinoma and true sarcoma, including carcinosarcoma and pulmonary blastoma. A history of cigarette smoking is the most common cause of large cell carcinoma. Carcinoma of unknown primary site The term carcinoma has also come to encompass malignant tumors composed of transformed cells whose origin or developmental lineage is unknown (see cancer of unknown primary origin; CUP), but that possess certain specific molecular, cellular, and histological characteristics typical of epithelial cells. This may include the production of one or more forms of cytokeratin or other intermediate filaments, intercellular bridge structures, keratin pearls, and/or tissue architectural motifs such as stratification or pseudo-stratification. ICD-10 code (8010-8045) Epithelial neoplasms, NOS (8050-8080) Squamous cell neoplasms (M8070/3) Squamous cell carcinoma, NOS (8090-8110) Basal cell neoplasms (M8090/3) Basal cell carcinoma, NOS (8120-8130) Transitional cell carcinomas (8140-8380) Adenocarcinomas (M8140/3) Adenocarcinoma, NOS (M8142/3) Linitis plastica (M8155/3) Vipoma (M8160/3) Cholangiocarcinoma (M8170/3) Hepatocellular carcinoma, NOS (M8200/3) Adenoid cystic carcinoma (M8312/3) Renal cell carcinoma (M8312/3) Grawitz tumor (8390-8420) Adnexal and Skin appendage Neoplasms (8430-8439) Mucoepidermoid Neoplasms (8440-8490) Cystic, Mucinous and Serous Neoplasms (8500-8540) Ductal, Lobular and Medullary Neoplasms (8550-8559) Acinar cell neoplasms (8560-8580) Complex epithelial neoplasms Carcinoma In situ The term carcinoma in situ (or CIS) is a term for cells that are significantly abnormal but not cancer. They are thus not typically carcinomas. Pathogenesis Cancer occurs when a single progenitor cell accumulates mutations and other changes in the DNA, histones, and other biochemical compounds that make up the cells genome. The cell genome controls the structure of the cells biochemical components, the biochemical reactions that occur within the cell, and the biological interactions of that cell with other cells. Certain combinations of mutations in the given progenitor cell ultimately result in that cell (also called a cancer stem cell) displaying a number of abnormal, malignant cellular properties that, when taken together, are considered characteristic of cancer, including: the ability to continue to divide perpetually, producing an exponentially (or near-exponentially) increasing number of new malignant cancerous "daughter cells" (uncontrolled mitosis); the ability to penetrate normal body surfaces and barriers, and to bore into or through nearby body structures and tissues (local invasiveness); the ability to spread to other sites within the body (metastasize) by penetrating or entering into the lymphatic vessels (regional metastasis) and/or the blood vessels (distant metastasis).If this process of continuous growth, local invasion, and regional and distant metastasis is not halted via a combination of stimulation of immunological defenses and medical treatment interventions, the result is that the host has a continuously increasing burden of tumor cells throughout the body. Eventually, the tumor burden increasingly interferes with normal biochemical functions carried out by the hosts organs, and death ultimately ensues. Carcinoma is but one form of cancer—one composed of cells that have developed the cytological appearance, histological architecture, or molecular characteristics of epithelial cells. A progenitor carcinoma stem cell can be formed from any of a number of oncogenic combinations of mutations in a totipotent cell, a multipotent cell, or a mature differentiated cell. Invasion and metastasis The hallmark of a malignant tumor is its tendency to invade and infiltrate local and adjacent structures and, eventually, spread from the site of its origin to non-adjacent regional and distant sites in the body, a process called metastasis. If unchecked, tumor growth and metastasis eventually creates a tumor burden so great that the host succumbs. Carcinoma metastasizes through both the lymph nodes and the blood. Mutation Whole genome sequencing has established the mutation frequency for whole human genomes. The mutation frequency in the whole genome between generations for humans (parent to child) is about 70 new mutations per generation.Carcinomas, however, have much higher mutation frequencies. The particular frequency depends on tissue type, whether a mis-match DNA repair deficiency is present, and exposure to DNA damaging agents such as components of tobacco smoke. Tuna and Amos have summarized the mutation frequencies per megabase (Mb) in some carcinomas, as shown in the table (along with the indicated frequencies of mutations per genome). Cause of mutations The likely major underlying cause of mutations in carcinomas is DNA damage. For example, in the case of lung cancer, DNA damage is caused by agents in exogenous genotoxic tobacco smoke (e.g. acrolein, formaldehyde, acrylonitrile, 1,3-butadiene, acetaldehyde, ethylene oxide and isoprene). Endogenous (metabolically caused) DNA damage is also very frequent, occurring on average more than 60,000 times a day in the genomes of human cells. Externally and endogenously caused damages may be converted into mutations by inaccurate translesion synthesis or inaccurate DNA repair (e.g. by non-homologous end joining). High frequency The high frequency of mutations in the total genome within carcinomas suggests that, often, an early carcinogenic alteration may be a deficiency in DNA repair. For instance, mutation rates substantially increase (sometimes by 100-fold) in cells defective in DNA mismatch repairA deficiency in DNA repair, itself, can allow DNA damages to accumulate, and error-prone translesion synthesis past some of those damages may give rise to mutations. In addition, faulty repair of these accumulated DNA damages may give rise to epigenetic alterations or epimutations. While a mutation or epimutation in a DNA repair gene, itself, would not confer a selective advantage, such a repair defect may be carried along as a passenger in a cell when the cell acquires an additional mutation/epimutation that does provide a proliferative advantage. Such cells, with both proliferative advantages and one or more DNA repair defects (causing a very high mutation rate), likely give rise to the high frequency of total genome mutations seen in carcinomas. DNA repair In somatic cells, deficiencies in DNA repair sometimes arise by mutations in DNA repair genes, but much more often are due to epigenetic reductions in expression of DNA repair genes. Thus, in a sequence of 113 colorectal carcinomas, only four had somatic missense mutations in the DNA repair gene MGMT, while the majority of these cancers had reduced MGMT protein expression due to methylation of the MGMT promoter region. Diagnosis Carcinomas can be definitively diagnosed through biopsy, including fine-needle aspiration (FNA), core biopsy, or subtotal removal of single node,. Microscopic examination by a pathologist is then necessary to identify molecular, cellular, or tissue architectural characteristics of epithelial cells. Types Oral: Most oral cancers are squamous-cell carcinoma Lung: Carcinoma comprises >98% of all lung cancers. Breast: Nearly all breast cancers are ductal carcinoma. Prostate: The most common form of carcinoma of the prostate is adenocarcinoma. Colon and rectum: Nearly all malignancies of the colon and rectum are either adenocarcinoma or squamous cell carcinoma. Pancreas: Pancreatic carcinoma is almost always of the adenocarcinoma type and is highly lethal. Ovaries: One of the most deadly forms due to late detection.Some carcinomas are named for their or the putative cell of origin, (e.g.hepatocellular carcinoma, renal cell carcinoma). Staging Staging of carcinoma refers to the process of combining physical/clinical examination, pathological review of cells and tissues, surgical techniques, laboratory tests, and imaging studies in a logical fashion to obtain information about the size of the neoplasm and the extent of its invasion and metastasis. Carcinomas are usually staged with Roman numerals. In most classifications, Stage I and Stage II carcinomas are confirmed when the tumor has been found to be small and/or to have spread to local structures only. Stage III carcinomas typically have been found to have spread to regional lymph nodes, tissues, and/or organ structures, while Stage IV tumors have already metastasized through the blood to distant sites, tissues, or organs. In some types of carcinomas, Stage 0 carcinoma has been used to describe carcinoma in situ, and occult carcinomas detectable only via examination of sputum for malignant cells (in lung carcinomas). In more recent staging systems, substages (a, b, c) are becoming more commonly used to better define groups of patients with similar prognosis or treatment options. Carcinoma stage is the variable that has been most consistently and tightly linked to the prognosis of the malignancy. The criteria for staging can differ dramatically based upon the organ system in which the tumor arises. For example, the colon and bladder cancer staging system relies on depth of invasion, staging of breast carcinoma is more dependent on the size of the tumor, and in renal carcinoma, staging is based on both the size of the tumor and the depth of the tumor invasion into the renal sinus. Carcinoma of the lung has a more complicated staging system, taking into account a number of size and anatomic variables.The UICC/AJCC TNM systems are most often used. For some common tumors, however, classical staging methods (such as the Dukes classification for colon cancer) are still used. Grading Grading of carcinomas refers to the employment of criteria intended to semi-quantify the degree of cellular and tissue maturity seen in the transformed cells relative to the appearance of the normal parent epithelial tissue from which the carcinoma derives. Grading of carcinoma is most often done after a treating physician and/or surgeon obtains a sample of suspected tumor tissue using surgical resection, needle or surgical biopsy, direct washing or brushing of tumor tissue, sputum cytopathology, etc. A pathologist then examines the tumor and its stroma, perhaps utilizing staining, immunohistochemistry, flow cytometry, or other methods. Finally, the pathologist classifies the tumor semi-quantitatively into one of three or four grades, including: Grade 1, or well differentiated: there is a close, or very close, resemblance to the normal parent tissue, and the tumor cells are easily identified and classified as a particular malignant histological entity; Grade 2, or moderately differentiated: there is considerable resemblance to the parent cells and tissues, but abnormalities can commonly be seen and the more complex features are not particularly well-formed; Grade 3, or poorly differentiated: there is very little resemblance between the malignant tissue and the normal parent tissue, abnormalities are evident, and the more complex architectural features are usually rudimentary or primitive; Grade 4, or undifferentiated carcinoma: these carcinomas bear no significant resemblance to the corresponding parent cells and tissues, with no visible formation of glands, ducts, bridges, stratified layers, keratin pearls, or other notable characteristics consistent with a more highly differentiated neoplasm.Although there is definite and convincing statistical correlation between carcinoma grade and tumor prognosis for some tumor types and sites of origin, the strength of this association can be highly variable. It may be stated generally, however, that the higher the grade of the lesion, the worse is its prognosis. Epidemiology While cancer is generally considered a disease of old age, children can also develop cancer. In contrast to adults, carcinomas are exceptionally rare in children. Less than 1% of carcinoma diagnoses are in children.The two biggest risk factors for ovarian carcinoma are age and family history. References == External links ==
Lace bite	Lace bite is an irritation of the tibialis anterior and toe extensor tendons. The medical term for the condition is "tibialis anterior tendinopathy." This irritation, felt on the front of the foot or ankle, is often experienced by ice hockey players and figure skaters. It is caused by friction between the tendon and tongue of the ice skate.Common symptoms of lace bite include: Pain, tenderness, and swelling where the front of the ankle meets the foot Discomfort with ankle motion, especially when pulling the foot up or turning it inward A cracking sound when the front of the foot or ankle is moved or touchedTreatment options include adjusting tongue positioning, additional padding, alternative lacing, and placing an orthoplast between the leather of the boot and its padding. == References ==
Wolfram-like syndrome	Wolfram-like syndrome is a rare autosomal dominant genetic disorder which shares some of the features shown by those affected with the autosomal recessive Wolfram syndrome. It is a type of WFS1-related disorder. Signs and symptoms Individuals with this condition usually exhibit early-onset progressive hearing loss which starts around the age of 10 years old, early-onset optic atrophy which usually manifests in a persons mid teenage–late adulthood years of life, and adult-onset diabetes mellitus.Although rarely, psychiatric symptoms can also manifest in people with the condition, this group of symptoms consists of hallucinations, depression, anxiety, and sleep disorders.Psychosis and autism are sometimes seen as features of the disorder.Other symptoms include nephrocalcinosis, psychomotor delay, glaucoma, and megalocornea. Complications The psychiatric features that may appear in patients with this condition, particularly depression, can cause a patient to be live in a constantly miserable state of mind, which can lead some patients to develop suicidal tendencies and, which can ultimately lead to making the decision of commiting suicide. Genetics This condition is caused by mutations in the WFS1 gene, these mutations are inherited in an autosomal dominant manner, meaning that for a person to exhibit the symptoms of Wolfram-like syndrome, they must have at least one copy of the mutation that is responsible for the phenotype of the disorder, this mutation is usually inherited, but there are cases where the mutation is de novo, meaning that it wasnt inherited from either parent, but rather the result of a spontaneous error in cell division.This gene encodes a protein called wolframin, the mutations typically found in people with this condition cause the production of a protein that is either absent or has little to no function at all.Mutations in this gene are also associated with other disorders affecting vision or hearing, (aside from Wolfram syndrome) such as non-syndromic autosomal dominant deafness type 6., isolated autosomal dominant congenital cataract, etc. In rare cases, a mutation in the CDK13 gene instead of the WFS1 gene is responsible for the disorder, this genetic mutation has only been described in 3 affected children belonging to a consanguineous Pakistani family who, in addition to the typical symptoms of the disorder, also had anomalies affecting the gastrointestinal tract, congenital heart defects, and clinodactyly. Diagnosis The following diagnostic methods can be used to diagnose Wolfram-like syndrome Genetic mutation responsible for Wolfram-like syndrome Genetic testingWhole exome sequencing Whole genome sequencing Gene sequencing focused on the WFS1 gene Diabetes Blood testsBlood sugar test at a random time Fasting blood sugar test A1C test Oral glucose tolerance testing Hearing loss At-homeHearing loss screening mobile apps Whisper test In clinical settingAudiometer tests Tuning fork test Physical examination Optic atrophy OphthalmoscopyOptic disc examination, paleness strongly indicates optic atrophy Visual acuity examination Psychiatric symptoms Depression Use of the DSM-5 depression diagnosis criteria Physical examination Laboratory studies Psychiatric evaluation Anxiety Use of the DSM-5 criteria for anxiety disorder Psychological evaluation Hallucinations (with or without delusions and/or disconnection from reality) Hallucinations dont necessarily need to have an official clinical diagnosis (although one can be useful for treatment to be performed), but it can be used as a diagnostic method for other conditions such as psychosis or schizophrenia. Hallucinations can be auditory, visual, tactile, olfactory, or gustatory, and they involve a false perception of stimuli where there is none. The same (no necessary need for official clinical diagnosis but can be used as a diagnostic method for other conditions) goes for delusions, there are various types of delusions, including somatic, persecutory/paranoid, grandiose, etc. They involve a false, fixed, often irrational belief a person fully believes in and is hard to convince out of. Treatment There is no standard management method for Wolfram-like syndrome, however, the following treatment methods can be used to treat the symptoms Wolfram-like syndrome causes. Diabetes Insulin intake Regular blood sugar monitoring The use of metformin medication Healthy eating habits Regular physical activity Hearing loss Hearing aids Cochlear implants Surgical procedures Vision loss Optical aids Surgical procedures Medication Psychiatric symptoms Therapy (for depression, anxiety, etc.) Use of medication (antidepressants, antipsychotics, etc.) Prevalence According to OMIM, around 15-20 cases from 4 affected families with Wolfram-like syndrome have been described in medical lirerature. All of the families studied were European, both by ancestry and by nacionality, the countries said families originated from were Denmark, the Netherlands, France, and Sweden, respectively. History The disorder was seemingly first described in 1940 by Samuelson et al, their patients were 4 members from a Swedish family with an apparently never-described-before combination of autosomal dominant sensorineural deafness and optic atrophy. Said family was later re-examined in 2011 by Rendtorff et al In 2006, Eiberg et al. described 4 affected members from a 3-generation Danish family, said individuals showed a phenotype similar to that shown by patients with Wolfram syndrome, the pair of symptoms associated with the familys unique disorder was inherited following an autosomal dominant manner. All individuals had progressive hearing loss starting in childhood and optic atrophy with onset in either childhood or middle age. 3 out of the 4 individuals were found to have irregular glucose regulation, 1 had reduced glucose tolerance, another one was found to have diabetes which was previously undiagnosed, and yet another one of the patients was found to have decreased function of the pancreas beta cells. 1 out of the 4 individuals had a diagnosed anxiety disorder as well as a sleep disorder. Non-syndromic isolated congenital deafness was found in 2 other family members, although they were otherwise unaffected.The third case report was made by Valero et al in 2008, they described a 60-year old man and his 81-year-old mother from France. The both of them had noninsulin-dependent diabetes mellitus and childhood-onset hearing loss. Out of the 2 patients, the mother was the most affected, her phenotype consisted of additional features her son didnt suffer from including severe vision impairment, bilateral optic nerve atrophy. Even though both of them had hearing impairments, the son was the only one of the pair who wore a hearing aid, the mother didnt do so, and as a result she had very obvious difficulties comprehending speech.The fourth case report was made by Hogewind et al, their patients were 3 affected members of a 2-generation Dutch family (2 brothers and their mother). The three of them suffered from hearing loss ranging from moderate to severe and optic neuropathy but they didnt have any other symptoms, including the ones usually associated with both Wolfram syndrome and Wolfram-like syndrome (such as diabetes mellitus/insipidus or depression), but they did have red-green color deficiency. The elder sibling and the mother were found to have severe hearing loss which heavily diminished their ability at recognizing speech, while the younger brother was relatively okay at doing so. All three individuals were found to have ocular scotoma (also known as blind spot) and neuroretinal rim loss. They were the only affected people with the disorder in their family.The fifth case report was a re-examination of the Swedish family reported in 1940 by Samuelson et al. The phenotypical variability rate among affected family members was found to be high. Additional details were revealed in this reexamination of the family; the proband of the original study (whom had been long dead) was found to not only suffer from the typical deafness-visual impairment phenotype commonly associated with the syndrome, but they also had hallucinations and depression. 4 of their other family members had underwent therapy for anxiety and 1 of their family members had died as a result of suicide. Visual/ocular features included optic atrophy which resulted in progressively lower visual acuity among those with the condition and glaucoma, which was highly treatable. Relation with Wolfram syndrome Although both conditions are caused by a mutation in the WFS1 gene, they have different phenotypical features and different inheritance patterns, for example; while Wolfram syndrome tends to follow an autosomal recessive inheritance pattern, Wolfram-like syndrome follows an autosomal dominant inheritance pattern. Symptoms are another example of the difference between Wolfram syndrome and Wolfram-like syndrome; intellectual disabilities, ataxia, anosmia, ageusia, and/or sleep apnea, alongside other cardiac and/or endocrine symptoms are features that, while present in some to most cases of Wolfram syndrome, are absent in those with Wolfram-like syndrome, onset of certain symptoms also differs between patients with Wolfram syndrome and patients with Wolfram-like syndrome. Hearing impairments arent present in every person with Wolfram-like syndrome either. Wolfram-like syndrome is also known to be less severe than Wolfram syndrome itself. See also Delusional disorder == References ==
Ebullism	Ebullism is the formation of gas bubbles in bodily fluids due to reduced environmental pressure, for example at high altitude. It occurs because a system of liquid and gas at equilibrium will see a net conversion of liquid to gas as pressure lowers; for example, liquids reach their boiling point at lower temperatures when the pressure on them is lowered. Symptoms Symptoms of ebullism include bubbles in the membranes of the mouth and eyes, swelling of the skin, and bubbles in the blood. Blood circulation and breathing may be impaired or stopped. The brain tissue may be starved of oxygen because of blockage of arteries, and the lungs may swell and hemorrhage. Death results unless recompression is rapid enough to reduce the bubbles before tissue damage occurs. In 1960, Joseph Kittinger experienced localised ebullism during a 31 kilometres (19 mi) ascent in a helium-driven gondola. His right-hand glove failed to pressurise and his hand expanded to roughly twice its normal volume accompanied by disabling pain. His hand took about three hours to recover after his return to the ground. Tissue samples from the remains of the crew of Space Shuttle STS-107 Columbia revealed evidence of ebullism. Given the level of tissue damage, the crew could not have regained consciousness even with re-pressurization. Mechanism In the atmospheric pressure present at sea level, water boils at 100 °C (212 °F). At an altitude of 63,000 feet (19,000 m), it boils at only 37 °C (99 °F), the normal body temperature of humans. This altitude is known as Armstrongs Line. In practice bodily fluids do not boil off at this altitude. This is because the skin and outer organs have enough strength to withstand this pressure, thus pressure inside the body would be significantly higher—however, nitrogen bubbles are starting to form, creating a hazard. Prevention To prevent ebullism, a pure oxygen (O2) atmosphere was used in early space flights to eliminate nitrogen in the blood. There are major fire hazards associated with using pure O2 as a breathing gas, which was central to the death of three astronauts in a fire during a ground test with Apollo 1. Nonetheless, NASA continued to use a nominally pure oxygen atmosphere throughout the Apollo Program but switched to air for the follow-on Space Transport System "Space Shuttle". Russian cosmonauts used pure oxygen before changing to a higher-pressure nitrox mixture, leading to incompatibility problems in 1975 on the Apollo-Soyuz Test Project. Space suits are often pressurized to several psi lower than stations capsules or shuttles and since they still use pure O2, an acclimation period is common in the airlock to remove nitrogen and other gases from the bloodstream. Etymology The term "space ebullism" was introduced by Captain Julian E. Ward in his paper "The True Nature of the Boiling of Body Fluids in Space", published in Aviation Medicine in October 1956. It was suggested "because the word ebullism does not connote the addition of heat to produce vapor." It comes from Latin ebullire, meaning "to bubble out, or to boil up." See also Decompression sickness – Disorder caused by dissolved gases emerging from solution Uncontrolled decompression – Unplanned drop in the pressure of a sealed system == References ==
Caplans syndrome	Caplans syndrome (or Caplan disease or rheumatoid pneumoconiosis) is a combination of rheumatoid arthritis (RA) and pneumoconiosis that manifests as intrapulmonary nodules, which appear homogeneous and well-defined on chest X-ray. Signs and symptoms Caplan syndrome presents with cough and shortness of breath in conjunction with features of rheumatoid arthritis, such as painful joints and morning stiffness. Examination should reveal tender, swollen metacarpophalangeal joints and rheumatoid nodules; auscultation of the chest may reveal diffuse crackles that do not disappear on coughing or taking a deep breath. Caplan syndrome is a nodular condition of the lung occurring in dust-exposed persons with either a history of rheumatoid arthritis (RA) or who subsequently develop RA within the following 5–10 years. The nodules in the lung typically occur bilaterally and peripherally, on a background of simple coal workers pneumoconiosis. There are usually multiple nodules, varying in size from 0.5 to 5.0 cm. The nodules typically appear rapidly, often in only a few weeks. Nodules may grow, remain unchanged in size, resolve, or disappear and then reappear. They can cavitate, calcify, or develop air-fluid levels. Grossly, they can resemble a giant silicotic nodule. Histologically, they usually have a necrotic center surrounded by a zone of plasma cells and lymphocytes, and often with a peripheral inflammatory zone made of macrophages and neutrophils. Causes Caplan syndrome occurs only in patients with both RA and pneumoconiosis related to mining dust (coal, asbestos, silica). The condition occurs in miners (especially those working in anthracite coal-mines), asbestosis, silicosis and other pneumoconioses. There is probably also a genetic predisposition, and smoking is thought to be an aggravating factor. Pathophysiology The presence of rheumatoid arthritis alters how a persons immune system responds to foreign materials, such as dust from a coal mine. When a person with rheumatoid arthritis is exposed to such offensive materials, they are at an increased risk of developing pneumoconiosis. Diagnosis Chest radiology shows multiple, round, well defined nodules, usually 0.5-2.0 cm in diameter, which may cavitate and resemble tuberculosis. Lung function tests may reveal a mixed restrictive and obstructive ventilatory defect with a loss of lung volume. There may also be irreversible airflow limitation and a reduced DLCO. Rheumatoid factor, antinuclear antibodies, and non-organ specific antibodies may be present in the serum. Silicosis and asbestosis must be considered in the differential with TB. Management Once tuberculosis has been excluded, treatment is with steroids. All exposure to coal dust must be stopped, and smoking cessation should be attempted. Rheumatoid arthritis should be treated normally with early use of DMARDs. Prognosis The nodules may pre-date the appearance of rheumatoid arthritis by several years. Otherwise prognosis is as for RA; lung disease may remit spontaneously, but pulmonary fibrosis may also progress. Epidemiology Incidence is currently 1 in 100,000 people but is likely to fall as the coal mining industry declines. It has also been shown to occur in cases of complicated silicosis (marked by progressive massive pneumoconiosis). History The syndrome is named after Dr. Anthony Caplan, a physician on the Cardiff Pneumoconiosis Panel, who identified the constellation of findings as a distinct entity in a 1953 publication. He followed this with further articles exploring the disease. Caplan syndrome was originally described in coal miners with progressive massive fibrosis. References External links 00057 at CHORUS
Flat feet	Flat feet (also called pes planus or fallen arches) is a postural deformity in which the arches of the foot collapse, with the entire sole of the foot coming into complete or near-complete contact with the ground. Sometimes children are born with flat feet (congenital). There is a functional relationship between the structure of the arch of the foot and the biomechanics of the lower leg. The arch provides an elastic, springy connection between the forefoot and the hind foot so that a majority of the forces incurred during weight bearing on the foot can be dissipated before the force reaches the long bones of the leg and thigh.In pes planus, the head of the talus bone is displaced medially and distal from the navicular bone. As a result, the Plantar calcaneonavicular ligament (spring ligament) and the tendon of the tibialis posterior muscle are stretched to the extent that the individual with pes planus loses the function of the medial longitudinal arch (MLA). If the MLA is absent or nonfunctional in both the seated and standing positions, the individual has "rigid" flatfoot. If the MLA is present and functional while the individual is sitting or standing up on their toes, but this arch disappears when assuming a foot-flat stance, the individual has "supple" flatfoot. This latter condition is often treated with arch supports. However, a recent randomized controlled trial found no evidence for the efficacy of treatment of flat feet in children either from expensive prescribed orthotics (i.e., shoe inserts) or less expensive over-the-counter orthotics. Three studies (see citations below in Military performance section) of military recruits have shown no evidence of increased injury, or foot problems, due to flat feet, in a population of people who reach military service age without prior foot problems. However, these studies cannot be used to judge possible future damage from this condition when diagnosed at younger ages. They also cannot be applied to persons whose flat feet are associated with foot symptoms, or certain symptoms in other parts of the body (such as the leg or back) possibly referable to the foot. Children Studies have shown flat feet are a common occurrence in children and adolescents. The human arch develops in infancy and early childhood as part of normal muscle, tendon, ligament and bone growth. Flat arches in children usually become high arches as the child progresses through adolescence and into adulthood. Children with flat feet are at a higher risk of developing knee, hip, and back pain. A 2007 randomized controlled trial found no evidence for the efficacy of treatment of flat feet in children either from expensive prescribed orthotics (i.e. shoe inserts) or less expensive over-the-counter orthotics. As a symptom itself, flat feet usually accompany genetic musculoskeletal conditions such as dyspraxia, ligamentous laxity or hypermobility. Diagnosis Since children are unlikely to suspect or identify flat feet on their own, it is important for adult caregivers to check on this themselves. Besides visual inspection of feet and of the treadwear pattern on shoe soles, caregivers should notice when a childs gait is abnormal or the child seems to be in pain from walking. Children who complain about calf muscle pains, arch pain, or any other pains around the foot area may be developing or have developed flat feet. Treatment Training of the feet, utilizing foot gymnastics and going barefoot on varying terrain, can facilitate the formation of arches during childhood, with a developed arch occurring for most by the age of four to six years. Ligament laxity is also among the factors known to be associated with flat feet. One medical study in India with a large sample size of children who had grown up wearing shoes and others going barefoot found that the longitudinal arches of the bare-footers were generally strongest and highest as a group, and that flat feet were less common in children who had grown up wearing sandals or slippers than among those who had worn closed-toe shoes. Focusing on the influence of footwear on the prevalence of pes planus, the cross-sectional study performed on children noted that wearing shoes throughout early childhood can be detrimental to the development of a normal or a high medial longitudinal arch. The vulnerability for flat foot among shoe-wearing children increases if the child has an associated ligament laxity condition. The results of the study suggest that children be encouraged to play barefooted on various surfaces of terrain and that slippers and sandals are less harmful compared to closed-toe shoes. It appeared that closed-toe shoes greatly inhibited the development of the arch of the foot more so than slippers or sandals. This conclusion may be a result of the notion that intrinsic muscle activity of the arch is required to prevent slippers and sandals from falling off the childs foot. In children with few symptoms orthotics are not recommended. Adults Flat feet can also develop as an adult ("adult acquired flatfoot") due to injury, illness, unusual or prolonged stress to the foot, faulty biomechanics, or as part of the normal aging process. This is most common in women over 40 years of age. Known risk factors include obesity, hypertension and diabetes. Flat feet can also occur in pregnant women as a result of temporary changes, due to increased elastin (elasticity) during pregnancy. However, if developed by adulthood, flat feet generally remain flat permanently. If a youth or adult appears flatfooted while standing in a full weight bearing position, but an arch appears when the person plantarflexes, or pulls the toes back with the rest of the foot flat on the floor, this condition is called flexible flatfoot. This is not a true collapsed arch, as the medial longitudinal arch is still present and the windlass mechanism still operates; this presentation is actually due to excessive pronation of the foot (rolling inwards), although the term flat foot is still applicable as it is a somewhat generic term. Muscular training of the feet is helpful and will often result in increased arch height regardless of age. Pathophysiology Research has shown that tendon specimens from people who have adult-acquired flat feet show evidence of increased activity of proteolytic enzymes. These enzymes can break down the constituents of the involved tendons and cause the foot arch to fall. In the future, these enzymes may become targets for new drug therapies. Diagnosis Many medical professionals can diagnose a flat foot by examining the patient standing or just looking at them. On going up onto tip toe the deformity will correct when this is a flexible flat foot in a child with lax joints. Such correction is not seen in adults with a rigid flat foot. An easy and traditional home diagnosis is the "wet footprint" test, performed by wetting the feet in water and then standing on a smooth, level surface such as smooth concrete or thin cardboard or heavy paper. Usually, the more the sole of the foot that makes contact (leaves a footprint), the flatter the foot. In more extreme cases, known as a kinked flatfoot, the entire inner edge of the footprint may actually bulge outward, where in a normal to high arch this part of the sole of the foot does not make contact with the ground at all. On plain radiography, flat feet can be diagnosed and graded by several measures, the most important in adults being the talonavicular coverage angle, the calcaneal pitch, and the talar-1st metatarsal angle (Mearys angle). The talonavicular coverage angle is abnormally laterally rotated in flat feet. It is normally up to 7 degrees laterally rotated, so a greater rotation indicates flat feet. Radiographies generally need to be taken on weightbearing feet in order to detect misalignment. Treatment Most flexible flat feet are asymptomatic, and do not cause pain. In these cases, there is usually no cause for concern. Flat feet were formerly a physical-health reason for service-rejection in many militaries. However, three military studies on asymptomatic adults (see section below), suggest that persons with asymptomatic flat feet are at least as tolerant of foot stress as the population with various grades of arch. In a study performed to analyze the activation of the tibialis posterior muscle in adults with pes planus, it was noted that the tendon of this muscle may be dysfunctional and lead to disabling weightbearing symptoms associated with acquired flat foot deformity. The results of the study indicated that while barefoot, subjects activated additional lower-leg muscles to complete an exercise that resisted foot adduction. However, when the same subjects performed the exercise while wearing arch supporting orthotics and shoes, the tibialis posterior was selectively activated. Such discoveries suggest that the use of shoes with properly fitting, arch-supporting orthotics will enhance selective activation of the tibialis posterior muscle thus, acting as an adequate treatment for the undesirable symptoms of pes planus.Rigid flatfoot, a condition where the sole of the foot is rigidly flat even when a person is not standing, often indicates a significant problem in the bones of the affected feet, and can cause pain in about a quarter of those affected. Other flatfoot-related conditions, such as various forms of tarsal coalition (two or more bones in the midfoot or hindfoot abnormally joined) or an accessory navicular (extra bone on the inner side of the foot) should be treated promptly, usually by the very early teen years, before a childs bone structure firms up permanently as a young adult. Both tarsal coalition and an accessory navicular can be confirmed by X-ray. Rheumatoid arthritis can destroy tendons in the foot (or both feet) which can cause this condition, and untreated can result in deformity and early onset of osteoarthritis of the joint. Such a condition can cause severe pain and considerably reduced ability to walk, even with orthoses. Ankle fusion is usually recommended.Treatment of flat feet may also be appropriate if there is associated foot or lower leg pain, or if the condition affects the knees or the lower back. Treatment may include foot gymnastics or other exercises as recommended by a podiatrist or physical therapist. In cases of severe flat feet, orthoses should be used through a gradual process to lessen discomfort. Over several weeks, slightly more material is added to the orthosis to raise the arch. These small changes allow the foot structure to adjust gradually, as well as giving the patient time to acclimatise to the sensation of wearing orthoses. In some cases, surgery can provide lasting relief, and even create an arch where none existed before; it should be considered a last resort, as it is usually very time-consuming and costly. A minimally-invasive surgical intervention involving a small implant is also available. The implant is inserted into the sinus tarsi and prevents the calcaneus and talus from sliding relative to each other. This prevents the sinus tarsi from collapsing and thus prevents the external symptom of the fallen arch from occurring. Athletic performance The effects of flat feet fall under two categories, which are asymptomatic and symptomatic. Individuals with rigid flat feet tend to exhibit symptoms such as foot and knee tendinitis, and are recommended to consider surgical options when managing symptoms. Individuals with flexible flat generally exhibit asymptomatic effects in response to their flat feet.According to AAP news and journal gateway, being flexibly flat-footed does not impede athletic performance.It is generally assumed by running professionals (primarily including some physical trainers, podiatrists, and shoe manufacturers) that a person with flat feet tends to overpronate in the running form. However, some also assert that persons with flat feet may have an underpronating if they are not a neutral gait. With standard running shoes, these professionals claim, a person who overpronates in his or her running form may be more susceptible to shin splints, back problems, and tendonitis in the knee. Running in shoes with extra medial support or using special shoe inserts, orthoses, may help correct ones running form by reducing pronation and may reduce risk of injury. Military performance Studies analyzing the correlation between flat feet and physical injuries in soldiers have been inconclusive, but none suggest that flat feet are an impediment, at least in soldiers who reached the age of military recruitment without prior foot problems. A 2005 study of Royal Australian Air Force recruits that tracked the recruits over the course of their basic training found that neither flat feet nor high arched feet had any impact on physical capability, injury rates or bipedal aptitude. Although there have been results rendered from military trials that have shown those with flat feet to have fewer injuries. No current studies have been successful in fully ascertaining the chronic, long-term detriments to health that are caused by the overexertion (of which is necessary for athletes/soldiers performing with flat feet) and other compensating measures commonly enacted by the body during bipedal movement. Another divergent study of 295 Israel Defense Forces recruits found that those with high arches had almost four times as many stress fractures as those with the lowest arches. A later study of 449 U.S. Navy special warfare trainees found no significant difference in the incidence of stress fractures among sailors and Marines with different arch heights. See also Planovalgus deformity Marfan syndrome Ehlers-Danlos syndrome Comparison of orthotics Rocker-bottom feet References External links Can minimalist shoes help flat feet Best flat feet shoes solution Natural flat feet solution the details
Arthritis mutilans	Arthritis mutilans is a rare medical condition involving severe inflammation damaging the joints of the hands and feet, and resulting in deformation and problems with moving the affected areas; it can also affect the spine. As an uncommon arthropathy, arthritis mutilans was originally described as affecting the hands, feet, fingers, and/or toes, but can refer in general to severe derangement of any joint damaged by arthropathy. First described in modern medical literature by Marie and Leri in 1913, in the hands, arthritis mutilans is also known as opera glass hand (la main en lorgnette in French), or chronic absorptive arthritis. Sometimes there is foot involvement in which toes shorten and on which painful calluses develop in a condition known as opera glass foot, or pied en lorgnette. Signs and symptoms For a person with arthritis mutilans in the hands, the fingers become shortened by arthritis, and the shortening may become severe enough that the hand looks paw-like, with the first deformity occurring at the interphalangeal and metacarpophalangeal joints. The excess skin from the shortening of the phalanx bones becomes folded transversely, as if retracted into one another like opera glasses, hence the description la main en lorgnette. As the condition worsens, luxation, phalangeal and metacarpal bone absorption, and skeletal architecture loss in the fingers occurs. Cause Arthritis mutilans occurs mainly in people who have pre-existing psoriatic arthritis, but can occur, if less often, in advanced rheumatoid arthritis; it can also occur independently. Psoriasis and psoriatic arthritis are interrelated heritable diseases, occurring with greater heritable frequency than rheumatoid arthritis, primary Sjögren syndrome and thyroid disease. Psoriasis affects 2–3% of the Caucasian population, and psoriatic arthritis affects up to 30% of those. Arthritis mutilans presents in about 5–16% of psoriatic arthritis cases, involves osteolysis of the DIP and PIP joints, and can include bone edema, bone erosions, and new bone growth. Most often psoriatic arthritis is seronegative for rheumatoid factor (occurring in only about 13% of cases), and has genetic risk factor overlap with ankylosing spondylitis with HLA-B27, IL-23R77, and IL-1, however, as of 2016, immunopathogenesis is unclear. Diagnosis Enthesitis can assist in differentiating arthritis mutilans parent condition psoriatic arthritis from rheumatoid arthritis and osteoarthritis, with evidence in plain radiographs (x-rays) and MRI as periostitis, new bone formation, and bone erosions. Dactylitis, spondylitis and sacroiliitis are common with the parent condition psoriatic arthritis, but are not in rheumatoid arthritis. MRI bone edema scores are high in arthritis mutilans and correlate with radiographic measures of joint damage, although they may not correlate with disease activity. A source of significant pain, bone marrow edema (or lesions, using newer terminology), can be detected on MRI or with ultrasonography by signals of excessive water in bone marrow. Specifically, bone marrow edema can be detected within bone on T1-weighted images as poorly defined areas of low signal, with a high signal on T2-weighted fat-suppressed images. Comparatively, with arthritis mutilans in rheumatoid arthritis, bone marrow edema often involves the subchondral bone layer, while the condition as a subtype of psoriatic arthritis includes a greater extent of marrow edema, expanding to diaphysis. Treatment Medication The bone edema in arthritis mutilans can be treated with TNF inhibitors in the short term: a 2007 study found that the bone edema associated with psoriatic arthritis (of which arthritis mutilans is a subtype) responded to TNF inhibitors with "dramatic" improvement, but the study was not determinative of whether TNF inhibitors would prevent new bone formation, bone fusion, or osteolysis (bone resorption). Surgical Although a 2011 research article stated that disagreements between hand surgeons and rheumatologists remain regarding the indications, timing and effectiveness of rheumatoid hand surgery, arthritis mutilans may be successfully treated by iliac-bone graft and arthrodesis of the interphalangeal joints and the metacarpophalangeal joint in each finger. Outcomes Arthritis mutilans parent condition psoriatic arthritis leaves people with a mortality risk 60% higher than the general population, with premature death causes mirroring those of the general population, cardiovascular issues being most common. Life expectancy for people with psoriatic arthritis is estimated to be reduced by approximately 3 years. References == External links ==
Hemifacial hypertrophy	Hemifacial hypertrophy (also termed facial hemihypertrophy, facial hemihyperplasia, or Friedreichs disease) abbreviated as (HFH) is rare congenital disease characterized by unilateral enlargement of the head and teeth. It is classified as true HFH (THFH) with unilateral enlargement of the viscerocranium, and partial HFH (PHFH) in which not all structures are enlarged. Hemifacial hypertrophy can cause a wide spectrum of defects or may involve only muscle or bone. it is usually treated surgically. It is believed to be a minor form of hemihypertrophy. References == External links ==
Conjunctival concretion	Concretion in the palpebral conjunctiva, is called conjunctival concretion, that is a (or a cluster of) small, hard, yellowish-white calcified matter, superficially buried beneath the palpebral conjunctiva. Most of concretions in the eye form in the palpebral conjunctiva, which is a clear membrane to surround the inside of the eyelid; fewer can be located in the cornea and retina. Symptoms Conjunctival concretions are generally asymptomatic. Common symptoms include eye discomfort, eye irritation, and foreign body sensation. Sometimes, the larger, harder or multiple concretions make the rubbing off of the superficial layers of the conjunctiva or eyelids to cause conjunctival abrasion, especially prominent when blinking. In severe cases, dysfunction or inflammation of the Meibomian (Meibomianitis, an inflammation of the tarsal glands) glands may occur. Cause Chronic conjunctivitis (e.g. trachoma) and aging factor are two causes of conjunctival concretion, which will make the conjunctiva cellular degeneration to produce an epithelial inclusion cyst, filled with epithelial cells and keratin debris. After calcification, the conjunctival cyst hardens and forms a conjunctival concretion. Congenital conjunctival concretion condition is also more common. Clinical Statistics Conjunctival concretions can be single, also multiple, less confluent. There is no difference between the site of the occurrence on the upper and lower eyelid, nor right or left eye. The vast majority of concretions are in the conjunctival surface rather than deep. There is no difference in age for predilection or incidence of concretions, due to the causes of conjunctivitis, aging, and even congenital factor. For statistical purposes Conjunctival Concretion is classified under the World Health Organisations ICD-10 category of H11.129 and the ICD-11 category of 9A61.6. Treatment Conjunctival concretions can be seen easily by everting the eyelid. The projecting concretions can be removed if they are causing concerning symptoms. Removal can be performed by an eye doctor. Sometimes just a needle or a scalpel is used to remove the concretion under local light anesthesia of the conjunctiva in adults. == References ==
Lipoblastoma	Lipoblastoma is a type of rare, subcutaneous, benign, fatty tumor, found in infants, and children, more common in males with tendency of local recurrence. Local recurrence can happen in up to 80% of incompletely resected tumours. Therefore, complete surgical resection is required to prevent recurrence. It arises from embyronic white fat that is rapidly enlarging. Most common locations are at the trunk and extremities.Types include: Benign lipoblastomatosis, a tumor, also known as an embryonic lipoma, which usually occurs in children under three years old. This is the tumor of brown fat cells. Myxoid lipoblastoma, a cutaneous condition characterized by excess mucin Specimen Macroscopic Grossly, it has a pale yellow, myxoid cut surface with small cystic foci. Microscopic It has lobules consists of immature adipose tissue separated by fibrous septa and lipoblasts at different stages of maturation, without atypia or mitosis. Plexiform capillary network and mature adipose tissue are seen at the central part of the lobule. See also Lipoblast Lipoma == References ==
Cutis verticis gyrata	Cutis verticis gyrata is a medical condition usually associated with thickening of the scalp. The condition is identified by excessive thickening of the soft tissues of the scalp and characterized by ridges and furrows, which give the scalp a cerebriform appearance. Clinically, the ridges are hard and cannot be flattened on applying pressure. Patients show visible folds, ridges or creases on the surface of the top of the scalp. The number of folds can vary from two to roughly ten and are typically soft and spongy. The condition typically affects the central and rear regions of the scalp, but sometimes can involve the entire scalp. Hair loss can occur over time where the scalp thickens, though hair within any furrows remains normal. Thus far, due to the (apparent) rarity of the condition, limited research exists and causes are as yet undetermined. What is known, is that the condition is not exclusively congenital. The condition was first reported by Jean-Louis-Marc Alibert in 1837, who called it cutis sulcata. A clinical description of the condition was provided by Robert in 1843 and it was named by Paul Gerson Unna in 1907. It has also been called Robert-Unna syndrome, bulldog scalp, corrugated skin, cutis verticis plicata, and pachydermia verticis gyrata. Cause At this time, causes are unknown, but it is believed to not be congenital. Diagnosis There is no clinical diagnosis for CVG as cases are rarely seen and are often comorbid with other conditions. Classifications CVG is classified according to the presence, or lack of underlying cause. Studies suggest that CVG often occurs in individuals in a secondary form to other ailments. However, the condition can also be present on its own. CVG can be classified into two forms: ‘primary’ (essential and non-essential) and ‘secondary’.The classifications are: Primary essential Primary non-essential SecondaryPrimary essential CVG is where the cause of the condition in unknown. It has no other associated abnormalities. This occurs mainly in men, with a male:female ratio of 5:1 or 6:1, and develops during or soon after puberty. Because of the slow progression of the condition, which usually occurs without symptom, it often passes unnoticed in the early stage.Primary non-essential CVG can be associated with neuropsychiatric disorders including cerebral palsy, epilepsy, seizures, and ophthalmologic abnormalities, most commonly cataracts.Secondary CVG occurs as a consequence of a number of diseases or drugs that produce changes in scalp structure. These include: acromegaly (excessive growth hormone levels due to pituitary gland tumours), and theoretically, the use of growth hormone itself or the use of drugs that mimic the effect of growth hormone (such as GHRP-6 and CJC-1295). It may also arise in association with melanocytic naevi (moles), birthmarks (including connective tissue naevi, fibromas and naevus lipomatosus), and inflammatory processes (e.g. eczema, psoriasis, Darier disease, folliculitis, impetigo, atopic dermatitis, acne). Treatment Options for medical treatment for this condition have been limited to plastic surgery with excision of the folds by means of scalp reduction/surgical resection. Scalp subcision has also been suggested as a treatment. Additional suggestions also include injections of a dermal filler (e.g. (poly-L-lactic acid)).. More recently, two published medical journals appear to show Hyaluronidase injections (Hyaluronidase is an enzyme used to dissolve hyaluronic acid which is a component of our skin that contributes to its thickness) as a possible treatment with promising results. See also Skin lesion List of cutaneous conditions References Notes Bibliography Nguyen NQ (October 2003). "Cutis verticis gyrata". Dermatol. Online J. 9 (4): 32. doi:10.5070/D31DP6W6KS. PMID 14594605. == External links ==
Talaromycosis	Talaromycosis is a fungal infection that presents with painless skin lesions of face and neck, fever, anaemia, large lymph glands and liver.It is caused by the fungusTalaromyces marneffei, which is found in soil and decomposing organic matter. The infection is thought to be acquired by breathing in the fungus from the environment, however, the environmental source of the organism is not known. It typically occurs in people who are already sick and unable to fight infection such as HIV/AIDS, cancer, organ transplant, long-term steroid use, old age, malnutrition or autoimmune disease. It generally does not affect healthy people and does not spread from person to person. Diagnosis is usually made by identification of the fungus from clinical specimens, either by microscopy or culture. Biopsies of skin lesions, lymph nodes, and bone marrow demonstrate the presence of organisms on histopathology. Medical imaging may reveal shadows in the lungs. The disease can look similar to tuberculosis and histoplasmosis.Talaromycosis may be prevented in people at high risk, using the antifungal medication itraconazole, and is treatable with amphotericin B followed by itraconazole or voriconazole. The disease is fatal in 75% of those not given treatment.Talaromycosis is endemic exclusively to southeast Asia (including southern China and eastern India), and particularly in young farmers. The exact number of people in the world affected is not known. Men are affected more than women. The first natural human case of talaromycosis was reported in 1973 in an American minister with Hodgkins disease who lived in Southeast Asia. Signs and symptoms There may be no symptoms, or talaromycosis may present with small painless skin lesions. The head and neck are most often affected. Other features include: fever, general discomfort, weight loss, cough, difficulty breathing, diarrhoea, abdominal pain, swelling of the spleen (splenomegaly), liver swelling (hepatomegaly), swollen lymph nodes (lymphadenopathy), and anemia. There may be no symptoms.In those without HIV infection, the lungs, liver, and mouth are usually affected, with systemic infection rarely occurring. The skin lesions are also often smooth. The disease tends to present differently in those with HIV infection; they are more likely to experience widespread infection. Their skin lesions however, are usually dented in the centre and can appear similar to molluscum contagiosum. Cause Talaromycosis is usually caused by T. marneffei, however, other species of the Talaromyces genus are also known to cause the disease in rare cases. Risk factors Talaromycosis rarely affects healthy people and generally occurs in people who are already sick and unable to fight infection such as HIV/AIDS, cancer, organ transplant, long-term steroid use, old age, malnutrition or autoimmune disease. Mechanism The infection is thought to be acquired through breathing in the organism from the environment. However, the exact source of infection is not known. The infection is not spread person-to-person. In Thailand, talaromycosis is more common during the rainy season; rain may promote the proliferation of the fungus in the environment. Diagnosis There is no accurate fast serological test. Diagnosis relies on identifying Talaromyces marneffei in cultures from clinical specimens such as sputum, blood, skin scrapings, lymph node, and bone marrow, by which time the disease is in the late-stage. Fungi in blood are found in half of case.Non-specific laboratory findings may show evidence of the fungus invading tissue, such as low platelets due to bone marrow infiltration, and elevated transaminases due to liver involvement.Biopsies of skin lesions, lymph nodes, and bone marrow demonstrate the presence of organisms on histopathology. Intracellular and extracellular forms are oval and have a characteristic transverse septum. In culture, colonies are powdery green and produce red pigment; however, cultures are negative in a significant number of cases.Medical imaging may reveal shadows in the lungs. Differential diagnosis The disease can look similar to tuberculosis and histoplasmosis Treatment Talaromycosis may be prevented in people at high risk, using the antifungal medication itraconazole, and is treatable with amphotericin B followed by itraconazole or voriconazole. Outcomes With treatment, less than 25% of those affected die. Without treatment, more than 75% will die. Epidemiology The exact number of people in the world affected is not known. Once considered rare, its occurrence increased due to HIV/AIDS to become the third most common opportunistic infection (after extrapulmonary tuberculosis and cryptococcosis) in HIV-positive individuals within the endemic area of Southeast Asia. While incidence in those with HIV began to decrease due to antiretroviral treatment, the number of cases in those without HIV began to rise in some endemic areas since the mid-1990s, likely due to improved diagnosis and an increase in other conditions that reduce immunity. The disease has been found to be more common in young farmers. Men are affected more than women. History T. marneffei was first isolated from a bamboo rat in Vietnam in 1956. Three years later, it was described by Gabriel Segretain as a new species with disease potential. The first natural human case of talaromycosis was reported in 1973 in an American minister with Hodgkins disease who lived in Southeast Asia. Research An antigen assay has been developed to detect a key virulence factor Mp1p that has been shown to have a high specificity for Talaromyces marneffei. References == External links ==
Acute hemolytic transfusion reaction	An acute hemolytic transfusion reaction (AHTR), also called immediate hemolytic transfusion reaction, is a life-threatening reaction to receiving a blood transfusion. AHTRs occur within 24 hours of the transfusion and can be triggered by a few milliliters of blood. The reaction is triggered by host antibodies destroying donor red blood cells. AHTR typically occurs when there is an ABO blood group incompatibility, and is most severe when type A donor blood is given to a type O recipient. Signs and symptoms Early acute hemolytic transfusion reactions are typically characterized by fever, which may be accompanied by rigors (chills). Mild cases are also typically characterized by abdominal, back, flank, or chest pain. More severe cases may be characterized by shortness of breath, low blood pressure, hemoglobinuria, and may progress to shock and disseminated intravascular coagulation. In anesthetized or unconscious patients, hematuria (blood in the urine) may be the first sign of AHTR. Other symptoms include nausea, vomiting, and wheezing. Causes The most common cause of acute hemolytic transfusion reaction is ABO incompatibility, which is typically due to human error that results in a recipient receiving the incorrect blood product. Rarely, other blood type incompatibilities can cause AHTR, the most common of which is Kidd antigen incompatibility. Rh, Kell, and Duffy antigen incompatibility have also been implicated in AHTR. Mechanism Antibodies against A and B blood groups (isohemagglutinins) present in the recipients blood destroy the donor red blood cells. They also activate the coagulation cascade (blood clotting system) via factor XII, which can lead to disseminated intravascular coagulation and kidney damage. Isohemagglutinins also activate the complement cascade via C3a and C5a, which then promote inflammatory cytokine release from white blood cells. These inflammatory cytokines include IL-1, IL-6, IL-8, and TNF-alpha, which cause symptoms of low blood pressure, fever, chest pain, nausea, vomiting, and wheezing. Diagnosis The diagnosis of AHTR is made with microscopic examination of the recipients blood and a direct antiglobulin test. The donor and recipient blood can be re-tested with a type, crossmatch, and antibody screen to determine the cause of the reaction. Treatment Initial treatment for any type of transfusion reaction, including AHTR, is discontinuation of the transfusion. Fluid replacement and close monitoring of vital signs are important. People with AHTR are managed with supportive care, which may include diuretics, blood pressure support, and treatment of disseminated intravascular coagulation (with fresh frozen plasma, cryoprecipitate, and platelet transfusion). Furosemide is the diuretic of choice in treatment of AHTR with decreased urine output, because it increases the amount of blood that reaches the renal cortex. Mannitol may also be used. Dopamine is used for blood pressure support because it causes vasodilation (dilation of blood vessels) in the kidneys as well as increasing the cardiac output (amount of blood pumped by the heart each minute). Prognosis The severity and prognosis of acute hemolytic transfusion depends on the rate of blood administration and the total volume of the transfusion. Approximately 2% of cases are fatal. Reactions that begin sooner are typically more severe. Epidemiology Acute hemolytic transfusion reaction is estimated to occur in 1 in 38,000 to 1 in 70,000 transfusions. An estimated 41% of ABO-incompatible transfusions result in AHTR. == References ==
Transfusion hemosiderosis	Transfusional hemosiderosis is the accumulation of iron in the body due to frequent blood transfusions. Iron accumulates in the liver and heart, but also endocrine organs. Frequent blood transfusions may be given to many patients, such as those with thalassemia, sickle cell disease, leukemia, aplastic anemia, or myelodysplastic syndrome, among others. It is diagnosed with a blood transferrin test and a liver biopsy. It is treated with venipuncture, erythrocytapheresis, and iron chelation therapy. Signs and symptoms Transfusional hemosiderosis can cause cardiac arrhythmia and cardiomyopathy. Causes Transfusional hemosiderosis is a potential side effect of frequent blood transfusions. These may be given for a number of conditions, including: thalassemia. sickle cell disease. leukemia. aplastic anemia. myelodysplastic syndrome. Mechanism Hemoglobin, the oxygen-carrying molecule in a red blood cell, contains iron. The body has limited ways to store and remove iron. When red blood cells (RBCs) die, they are consumed by macrophages. Transfused RBCs have shorter lifespans that native ones, so they die and are consumed more frequently by the macrophages, which causes the latter to die from excess iron which is then released into the blood. Therefore, with frequent blood transfusions, iron builds up in the body over time. This can enter the liver, heart, pancreas, and endocrine organs. Free iron increases the production of oxygen radicals (mostly hydroxyl radicals) that cause damage to cells (particularly their DNA). Diagnosis Transfusional hemosiderosis can be inferred with a blood transferrin test. Blood ferritin may be increased with a number of other conditions, so is less reliable for diagnosis. A liver biopsy may be used, which is the most accurate diagnostic technique. The level of siderosis seen in a liver biopsy can be graded by severity. Treatment Transfusional hemosiderosis is treated with a number of therapies. Venipuncture (phlebotomy) removes blood. Erythrocytapheresis filters red blood cells from the blood. Chelation therapy removes iron from the blood. This involves delivering iron chelating agents such as deferoxamine, deferiprone or deferasirox. If iron overload has caused damage to end-organs, this is generally irreversible and may require transplantation. Prognosis Transfusion hemosiderosis can cause permanent damage to tissues that may lead to death. Tissue damage can remain even after chelation therapy. Outcomes are usually worse in patients who require blood transfusions compared to those who can have alternative therapies. Cardiomyopathy and cardiac arrhythmia are often a cause of death. Society Ted DeVita died of transfusional iron overload from too many blood transfusions. See also Hemosiderosis References Lu JP, Hayashi K (1994). "Selective iron deposition in pancreatic islet B cells of transfusional iron-overloaded autopsy cases". Pathol. Int. 44 (3): 194–9. doi:10.1111/j.1440-1827.1994.tb02592.x. PMID 8025661. S2CID 25357672.
Cortical desmoid	Cortical desmoid (also called tug lesion or periosteal desmoid) is an irregularity of the distal femoral cortex caused by repetitive stress at the attachment of the adductor magnus aponeurosis. It is most commonly seen in adolescents and is usually asymptomatic. It is a benign and self-limiting lesion. References Gould CF, Ly JQ, Lattin GE, Beall DP, Sutcliffe JB (2007). "Bone tumor mimics: avoiding misdiagnosis". Curr Probl Diagn Radiol. 36 (3): 124–41. doi:10.1067/j.cpradiol.2007.01.001. PMID 17484955.
Pancreatitis	Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types: acute pancreatitis, and chronic pancreatitis. Signs and symptoms of pancreatitis include pain in the upper abdomen, nausea and vomiting. The pain often goes into the back and is usually severe. In acute pancreatitis, a fever may occur, and symptoms typically resolve in a few days. In chronic pancreatitis weight loss, fatty stool, and diarrhea may occur. Complications may include infection, bleeding, diabetes mellitus, or problems with other organs.The two most common causes of acute pancreatitis are a gallstone blocking the common bile duct after the pancreatic duct has joined; and heavy alcohol use. Other causes include direct trauma, certain medications, infections such as mumps, and tumors. Chronic pancreatitis may develop as a result of acute pancreatitis. It is most commonly due to many years of heavy alcohol use. Other causes include high levels of blood fats, high blood calcium, some medications, and certain genetic disorders, such as cystic fibrosis, among others. Smoking increases the risk of both acute and chronic pancreatitis. Diagnosis of acute pancreatitis is based on a threefold increase in the blood of either amylase or lipase. In chronic pancreatitis, these tests may be normal. Medical imaging such as ultrasound and CT scan may also be useful.Acute pancreatitis is usually treated with intravenous fluids, pain medication, and sometimes antibiotics. Typically eating and drinking are disallowed, and a nasogastric tube is placed in the stomach. A procedure known as an endoscopic retrograde cholangiopancreatography (ERCP) may be done to examine the distal common bile duct and remove a gallstone if present. In those with gallstones the gallbladder is often also removed. In chronic pancreatitis, in addition to the above, temporary feeding through a nasogastric tube may be used to provide adequate nutrition. Long-term dietary changes and pancreatic enzyme replacement may be required. And occasionally surgery is done to remove parts of the pancreas.Globally, in 2015 about 8.9 million cases of pancreatitis occurred. This resulted in 132,700 deaths, up from 83,000 deaths in 1990. Acute pancreatitis occurs in about 30 per 100,000 people a year. New cases of chronic pancreatitis develop in about 8 per 100,000 people a year and currently affect about 50 per 100,000 people in the United States. It is more common in men than women. Often chronic pancreatitis starts between the ages of 30 and 40 while it is rare in children. Acute pancreatitis was first described on autopsy in 1882 while chronic pancreatitis was first described in 1946. Signs and symptoms The most common symptoms of pancreatitis are severe upper abdominal or left upper quadrant burning pain radiating to the back, nausea, and vomiting that is worse with eating. The physical examination will vary depending on severity and presence of internal bleeding. Blood pressure may be elevated by pain or decreased by dehydration or bleeding. Heart and respiratory rates are often elevated. The abdomen is usually tender but to a lesser degree than the pain itself. As is common in abdominal disease, bowel sounds may be reduced from reflex bowel paralysis. Fever or jaundice may be present. Chronic pancreatitis can lead to diabetes or pancreatic cancer. Unexplained weight loss may occur from a lack of pancreatic enzymes hindering digestion. Complications Early complications include shock, infection, systemic inflammatory response syndrome, low blood calcium, high blood glucose, and dehydration. Blood loss, dehydration, and fluid leaking into the abdominal cavity (ascites) can lead to kidney failure. Respiratory complications are often severe. Pleural effusion is usually present. Shallow breathing from pain can lead to lung collapse. Pancreatic enzymes may attack the lungs, causing inflammation. Severe inflammation can lead to intra-abdominal hypertension and abdominal compartment syndrome, further impairing renal and respiratory function and potentially requiring management with an open abdomen to relieve the pressure.Late complications include recurrent pancreatitis and the development of pancreatic pseudocysts—collections of pancreatic secretions that have been walled off by scar tissue. These may cause pain, become infected, rupture and bleed, block the bile duct and cause jaundice, or migrate around the abdomen. Acute necrotizing pancreatitis can lead to a pancreatic abscess, a collection of pus caused by necrosis, liquefaction, and infection. This happens in approximately 3% of cases or almost 60% of cases involving more than two pseudocysts and gas in the pancreas. Causes Eighty percent of cases of pancreatitis are caused by alcohol or gallstones. Gallstones are the single most common cause of acute pancreatitis. Alcohol is the single most common cause of chronic pancreatitis. Triglyceride levels greater than 1000 mg/dL (11.29 mmol/L) is another cause. Medications There are seven classes of medications associated with acute pancreatitis: statins, ACE inhibitors, oral contraceptives/hormone replacement therapy (HRT), diuretics, antiretroviral therapy, valproic acid, and oral hypoglycemic agents. Mechanisms of these drugs causing pancreatitis are not known exactly, but it is possible that statins have direct toxic effect on the pancreas or through the long-term accumulation of toxic metabolites. Meanwhile, ACE inhibitors cause angioedema of the pancreas through the accumulation of bradykinin. Birth control pills and HRT cause arterial thrombosis of the pancreas through the accumulation of fat (hypertriglyceridemia). Diuretics such as furosemide have a direct toxic effect on the pancreas. Meanwhile, thiazide diuretics cause hypertriglyceridemia and hypercalcemia, where the latter is the risk factor for pancreatic stones.HIV infection itself can cause a person to be more likely to get pancreatitis. Meanwhile, antiretroviral drugs may cause metabolic disturbances such as hyperglycemia and hypercholesterolemia, which predisposes to pancreatitis. Valproic acid may have direct toxic effect on the pancreas. There are various oral hypoglycemic agents that contributes to pancreatitis including metformin. But, glucagon-like peptide-1 (GLP-1) is more strongly associated with pancreatitis by promoting inflammation.Atypical antipsychotics such as clozapine, risperidone, and olanzapine can also cause pancreatitis. Infection A number of infectious agents have been recognized as causes of pancreatitis including: Viruses Coxsackie virus Cytomegalovirus Hepatitis B Herpes simplex virus Mumps Varicella-zoster virus Bacteria Legionella Leptospira Mycoplasma Salmonella Fungi Aspergillus Parasites Ascaris Cryptosporidium Toxoplasma Other Other common causes include trauma, autoimmune disease, high blood calcium, hypothermia, and endoscopic retrograde cholangiopancreatography (ERCP). Pancreas divisum is a common congenital malformation of the pancreas that may underlie some recurrent cases. Diabetes mellitus type 2 is associated with a 2.8-fold higher risk.Less common causes include pancreatic cancer, pancreatic duct stones, vasculitis (inflammation of the small blood vessels in the pancreas), and porphyria—particularly acute intermittent porphyria and erythropoietic protoporphyria.There is an inherited form that results in the activation of trypsinogen within the pancreas, leading to autodigestion. Involved genes may include trypsin 1, which codes for trypsinogen, SPINK1, which codes for a trypsin inhibitor, or cystic fibrosis transmembrane conductance regulator.The mnemonic GETSMASHED is often used to remember the common causes of pancreatitis: G—gallstones, E—ethanol, T—trauma, S—steroids, M—mumps, A—autoimmune pancreatitis, S—scorpion sting, H—hyperlipidemia, hypothermia, hyperparathyroidism, E—endoscopic retrograde cholangiopancreatography, D—drugs (commonly azathioprine, valproic acid, liraglutide). Diagnosis The differential diagnosis for pancreatitis includes but is not limited to cholecystitis, choledocholithiasis, perforated peptic ulcer, bowel infarction, small bowel obstruction, hepatitis, and mesenteric ischemia.Diagnosis requires 2 of the 3 following criteria: Characteristic acute onset of epigastric or vague abdominal pain that may radiate to the back (see signs and symptoms above) Serum amylase or lipase levels ≥ 3 times the upper limit of normal An imaging study with characteristic changes. CT, MRI, abdominal ultrasound or endoscopic ultrasound can be used for diagnosis.Amylase and lipase are 2 enzymes produced by the pancreas. Elevations in lipase are generally considered a better indicator for pancreatitis as it has greater specificity and has a longer half life. However, both enzymes can be elevated in other disease states. In chronic pancreatitis, the fecal pancreatic elastase-1 (FPE-1) test is a marker of exocrine pancreatic function. Additional tests that may be useful in evaluating chronic pancreatitis include hemoglobin A1C, immunoglobulin G4, rheumatoid factor, and anti-nuclear antibody.For imaging, abdominal ultrasound is convenient, simple, non-invasive, and inexpensive. It is more sensitive and specific for pancreatitis from gallstones than other imaging modalities. However, in 25–35% of patients the view of the pancreas can be obstructed by bowel gas making it difficult to evaluate.A contrast-enhanced CT scan is usually performed more than 48 hours after the onset of pain to evaluate for pancreatic necrosis and extrapancreatic fluid as well as predict the severity of the disease. CT scanning earlier can be falsely reassuring.ERCP or an endoscopic ultrasound can also be used if a biliary cause for pancreatitis is suspected. Treatment The treatment of pancreatitis is supportive and depends on severity. Morphine generally is suitable for pain control. There are no clinical studies to suggest that morphine can aggravate or cause pancreatitis or cholecystitis.The treatment for acute pancreatitis will depend on whether the diagnosis is for the mild form of the condition, which causes no complications, or the severe form, which can cause serious complications. Mild acute pancreatitis The treatment of mild acute pancreatitis is successfully carried out by admission to a general hospital ward. Traditionally, people were not allowed to eat until the inflammation resolved but more recent evidence suggests early feeding is safe and improves outcomes, and may result in an ability to leave the hospital sooner.Due to inflammation occurring in pancreatitis, proinflammatory cytokines secreted into the bloodstream can cause inflammation throughout the body, including the lungs and can manifest as ARDS. Because pancreatitis can cause lung injury and affect normal lung function, supplemental oxygen is occasionally delivered through breathing tubes that are connected via the nose (e.g., nasal cannulae) or via a mask. The tubes can then be removed after a few days once it is clear that the condition is improving. Dehydration may result during an episode of acute pancreatitis, so fluids will be provided intravenously. Opioids may be used for the pain. When the pancreatitis is due to gallstones, early gallbladder removal also appears to improve outcomes. Severe acute pancreatitis Severe pancreatitis can cause organ failure, necrosis, infected necrosis, pseudocyst, and abscess. If diagnosed with severe acute pancreatitis, people will need to be admitted to a high-dependency unit or intensive care unit. It is likely that the levels of fluids inside the body will have dropped significantly as it diverts bodily fluids and nutrients in an attempt to repair the pancreas. The drop in fluid levels can lead to a reduction in the volume of blood within the body, which is known as hypovolemic shock. Hypovolemic shock can be life-threatening as it can very quickly starve the body of the oxygen-rich blood that it needs to survive. To avoid going into hypovolemic shock, fluids will be administered intravenously. Oxygen will be supplied through tubes attached to the nose and ventilation equipment may be used to assist with breathing. Feeding tubes may be used to provide nutrients, combined with appropriate analgesia. As with mild acute pancreatitis, it will be necessary to treat the underlying cause—gallstones, discontinuing medications, cessation of alcohol, etc. If the cause is gallstones, it is likely that an ERCP procedure or removal of the gallbladder will be recommended. The gallbladder should be removed during the same hospital admission or within two weeks of pancreatitis onset so as to limit the risk of recurrent pancreatitis. If the cause of pancreatitis is alcohol, cessation of alcohol consumption and treatment for alcohol dependency may improve pancreatitis. Even if the underlying cause is not related to alcohol consumption, doctors recommend avoiding it for at least six months as this can cause further damage to the pancreas during the recovery process.Oral intake, especially fats, is generally restricted initially but early enteral feeding within 48 hours has been shown to improve clinical outcomes. Fluids and electrolytes are replaced intravenously. Nutritional support is initiated via tube feeding to surpass the portion of the digestive tract most affected by secreted pancreatic enzymes if there is no improvement in the first 72–96 hours of treatment. Prognosis Severe acute pancreatitis has mortality rates around 2–9%, higher where necrosis of the pancreas has occurred.Several scoring systems are used to predict the severity of an attack of pancreatitis. They each combine demographic and laboratory data to estimate severity or probability of death. Examples include APACHE II, Ranson, BISAP, and Glasgow. The Modified Glasgow criteria suggests that a case be considered severe if at least three of the following are true: Age > 55 years Blood levels: PO2 oxygen < 60 mmHg or 7.9 kPa White blood cells > 15,000/µlitre Calcium < 2 mmol/litre Blood urea nitrogen > 16 mmol/litre Lactate dehydrogenase (LDH) > 600iu/litre Aspartate transaminase (AST) > 200iu/litre Albumin < 32g/litre Glucose > 10 mmol/litreThis can be remembered using the mnemonic PANCREAS: PO2 oxygen < 60 mmHg or 7.9 kPa Age > 55 Neutrophilia white blood cells > 15,000/µlitre Calcium < 2 mmol/litre Renal function (BUN) > 16 mmol/litre Enzymes lactate dehydrogenase (LDH) > 600iu/litre aspartate transaminase (AST) > 200iu/litre Albumin < 32g/litre Sugar glucose > 10 mmol/litreThe BISAP score (blood urea nitrogen level >25 mg/dl (8.9 mmol/L), impaired mental status, systemic inflammatory response syndrome, age over 60 years, pleural effusion) has been validated as similar to other prognostic scoring systems. Epidemiology Globally the incidence of acute pancreatitis is 5 to 35 cases per 100,000 people. The incidence of chronic pancreatitis is 4–8 per 100,000 with a prevalence of 26–42 cases per 100,000. In 2013 pancreatitis resulted in 123,000 deaths up from 83,000 deaths in 1990. Costs In adults in the United Kingdom, the estimated average total direct and indirect costs of chronic pancreatitis is roughly £79,000 per person on an annual basis. Acute recurrent pancreatitis and chronic pancreatitis occur infrequently in children, but are associated with high healthcare costs due to substantial disease burden. Globally, the estimated average total cost of treatment for children with these conditions is approximately $40,500/person/year. Other animals Fatty foods may cause canine pancreatitis in dogs. See also Exocrine pancreatic insufficiency References External links Pancreatitis at Curlie GeneReviews/NCBI/NIH/UW entry on PRSS1-Related Hereditary Pancreatitis "Pancreatitis". MedlinePlus. U.S. National Library of Medicine.
Discrete papular lichen myxedematosus	Discrete papular lichen myxedematosus is a skin condition caused by fibroblasts producing abnormally large amounts of mucopolysaccharides characterized by the occurrence of waxy, flesh-colored papules.: 185 See also Papular mucinosis List of cutaneous conditions References == External links ==
Hajdu–Cheney syndrome	Hajdu–Cheney syndrome, also called acroosteolysis with osteoporosis and changes in skull and mandible, arthrodentoosteodysplasia and Cheney syndrome, is an extremely rare autosomal dominant congenital disorder of the connective tissue characterized by severe and excessive bone resorption leading to osteoporosis and a wide range of other possible symptoms. Mutations in the NOTCH2 gene, identified in 2011, cause HCS. HCS is so rare that only about 50 cases have been reported worldwide since the discovery of the syndrome in 1948 Signs and symptoms Hajdu–Cheney syndrome causes many issues with an individuals connective tissues. Some general characteristics of an individual with Hajdu–Cheney syndrome include bone flexibility and deformities, short stature, delayed acquisition of speech and motor skills, dolichocephalic skull, Wormian bone, small maxilla, hypoplastic frontal sinuses, basilar impression, joint laxity, bulbous finger tips and severe osteoporosis. Wormian bone occurs when extra bones appear between cranial sutures. Fetuses with Hajdu–Cheney syndrome often will not be seen to unclench their hands on obstetrical ultrasound. They may also have low-set ears and their eyes may be farther apart than on a usual child, called hypertelorism. Childrens heads can have some deformities in their shape and size (plagiocephaly). Early tooth loss and bone deformities, such as serpentine tibiae and fibulae, are also common in those affected. Genetics Hajdu–Cheney syndrome is a monogenic disorder. The disorder is inherited and controlled by a single pair of genes. A single copy of the mutant gene on an autosome causes HCS. HCS is an autosomal dominant disorder, only one parent with the defective gene is needed to pass the disorder to the offspring.Mutations within the last coding exon of NOTCH2 that remove the PEST domain and escape the nonsense-mediated mRNA decay have been shown to be the main cause of Hajdu–Cheney syndrome. The NOTCH2 gene plays a very important role in skeletogenesis. Mutations of NOTCH2 that seem to cause HCS occur in the last coding exon of the gene (exon 34). These mutations remove PEST domains, which mediate proteosomal destruction of the protein. These PEST domains are removed due to the premature stop codon in the amino acid sequence. All HCS alleles are observed to have premature protein destruction before the PEST sequence is fully translated. The result is a mature NOTCH2 gene with a partially completed PEST sequence. In some cases, no PEST sequence at all is seen. This leads to the no proteosomal destruction of the protein.The NOTCH2 gene is ubiquitously expressed in all embryonic tissue. When researching HCS in mice, the homozygous deletion of NOTCH2 leads to death. This observation is important because it explains how the HCS phenotype is not isolated to only one system of the body. NOTCH2 is also shown to regulate RANK-L osteoclastogenesis, which is the production of functional osteoclasts. Osteoclasts are the component that breaks bone down. This is why bone loss is observed in HCS patients, due to the overactivation of RANK-L. Pathogenesis The mechanism thought to cause HCS is an abnormality in osteoblast and osteoid function. These are major components of bone development, and the low function of each leads to the weak bones that characterize HCS. Diagnosis One of the main methods of pinpointing a NOTCH2 mutation that leads to HCS is through whole genome sequencing. This is then followed by exome capture by means of in-solution hybridization. The exome part of the genome consists of exons. Parallel sequencing follows the hybridization, which results in about 3.5 Gb of sequence data. These sequence data are then analyzed. Through sequence analysis and symptom presentation in HCS patients, this proves to be the most definitive method of diagnosis. Types Laboratory testing reveals multiple mutations of HCS. Two genetic variants result in sporadic HCS symptoms, which are HCS-02 and HCS-03. These mutations produce symptoms that come and go, but have been present de novo. HCS-03 was identified as the variant that is passed through affected family members and presents symptoms throughout the lifetime of the individual. All variants of HCS lead to the same premature termination of PEST sequences which compromise normal function of NOTCH2. NOTCH has four different receptors, which have an affinity for similar ligands. They are classified as single-pass transmembrane receptors. Treatment Since about 2002, some patients with this disorder have been offered drug therapy with bisphosphonates (a class of osteoporosis drugs) to treat problems with bone resorption associated with the bone breakdown and skeletal malformations that characterize this disorder. Brand names include Actonel (risedronate/alendronate), made by Merck Pharmaceuticals. Other drugs include Pamidronate, made by Novartis and Strontium Ranelate, made by Eli Lilly. However, for more progressive cases, surgery and bone grafting are necessary. Eponym It is named after Nicholas Hajdu (1908–1987), a Hungarian-English radiologist working in the UK and William D. Cheney, MD (1899–1985), a US radiologist. References Further reading External links OMIM entry on Hajdu–Cheney syndrome Acroosteolysis dominant type at Orphanet
VACTERL association	The VACTERL association (also VATER association, and less accurately VACTERL syndrome) refers to a recognized group of birth defects which tend to co-occur (see below). This pattern is a recognized association, as opposed to a syndrome, because there is no known pathogenetic cause to explain the grouped incidence. Each child with this condition can be unique. At present this condition is treated after birth with issues being approached one at a time. Some infants are born with symptoms that cannot be treated and they do not survive. Also, VACTERL association can be linked to other similar conditions such as Klippel Feil and Goldenhar syndrome including crossovers of conditions. No specific genetic or chromosome problem has been identified with VACTERL association. VACTERL can be seen with some chromosomal defects such as Trisomy 18 and is more frequently seen in babies of diabetic mothers. VACTERL association, however, is most likely caused by multiple factors.VACTERL association specifically refers to the abnormalities in structures derived from the embryonic mesoderm. Signs and symptoms The following features are observed with VACTERL association: V - Vertebral anomalies A - Anorectal malformations C - Cardiovascular anomalies T - Tracheoesophageal fistula E - Esophageal atresia R - Renal (Kidney) and/or radial anomalies L - Limb defectsAlthough it was not conclusive whether VACTERL should be defined by at least two or three component defects, it is typically defined by the presence of at least three of the above congenital malformations. Spine Vertebral anomalies, or defects of the spinal column, usually consist of small (hypoplastic) vertebrae or hemivertebra where only one half of the bone is formed. About 80 percent of patients with VACTERL association will have vertebral anomalies. In early life these rarely cause any difficulties, although the presence of these defects on a chest x-ray may alert the physician to other defects associated with VACTERL. Later in life these spinal column abnormalities may put the child at risk for developing scoliosis, or curvature of the spine. Anal defects Anal atresia or imperforate anus is seen in about 55 to 90 percent of patients with VACTERL association. These anomalies are usually noted at birth. It often require surgery in the first days of life. Sometimes babies will require several surgeries to fully reconstruct the intestine and anal canal. Cardiac defects Up to 75 percent of patients with VACTERL association have been reported to have congenital heart disease. The most common heart defects seen with VACTERL association are ventricular septal defect (VSD), atrial septal defects and tetralogy of Fallot. Less common defects are truncus arteriosus and transposition of the great arteries. It is subsequently thought that cardiac defects should be considered an extension of VACTERL. Trachea and oesophagus Oesophageal atresia with tracheoesophageal fistula (TO fistula or TOF) is seen in about 70 percent of patients with VACTERL association, although it can frequently occur as an isolated defect. 15 to 33 percent of patients with TO fistulas will also have congenital heart disease. However these babies usually have uncomplicated heart defects, like a ventricular septal defect, which may not require any surgery. Kidneys Kidney defects are seen in approximately 50 percent of patients with VACTERL association. In addition, up to 35 percent of patients with VACTERL association have a single umbilical artery (there are usually two arteries and one vein) which is often associated with additional kidney or urologic problems. Renal abnormalities in VACTERL association can be severe, with incomplete formation of one or both kidneys or urologic abnormalities such as obstruction of outflow of urine from the kidneys or severe reflux (backflow) of urine into the kidneys from the bladder. These problems can cause kidney failure early in life and may require kidney transplant. Many of these problems can be corrected surgically before any damage can occur. Limbs Limb defects occur in up to 70 percent of babies with VACTERL association and include a displaced or hypoplastic thumb, extra digits (polydactyly), fusion of digits (syndactyly) and forearm defects such as radial aplasia. Babies with limb defects on both sides tend to have kidney or urologic defects on both sides, while babies with limb defects on only one side of the body tend to have kidney problems on that same side. Extension Features secondary to VACTERL components are frequent enough to be considered an extension of VACTERL. These include: single umbilical artery, ambiguous genitalia, abdominal wall defects, diaphragmatic hernia, intestinal and respiratory anomalies, and oligohydramnios sequence defects. Cardiac defects are thought to fit in this category. Growth Many babies with VACTERL are born small and have difficulty with gaining weight. Babies with VACTERL association, however, do tend to have normal development and normal intelligence. Pathology Patients with abnormal cardiac and kidney function may be more at risk for hemolytic uremic syndrome Diagnosis Differential diagnosis Baller–Gerold syndrome CHARGE syndrome Currarino syndrome DiGeorge syndrome Fanconi anemia Feingold syndrome Fryns syndrome MURCS association Oculo-auriculo-vertebral syndrome Opitz G/BBB syndrome Holt–Oram syndrome Pallister–Hall syndrome Townes–Brocks syndrome VACTERL with hydrocephalus Management Epidemiology The incidence of VACTERL association is estimated to be approximately 1 in 10,000 to 1 in 40,000 live-born infants. It is seen more frequently in infants born to diabetic mothers. While most cases are sporadic, there are clearly families who present with multiple involved members. History The acronym VATER association was first described by Linda Quan, an emergency room physician, and David Smith, a man who was considered the father of dysmorphology in 1972, to define a non-random co-occurrence of the listed defects. Years later, research revealed that cardiac and renal abnormalities were common in the association, and the acronym was changed to VACTERL. However, no single cause was identified that links all these conditions together. Therefore, this VACTERL is termed as "association" instead of a "syndrome". The differentiation of the acronyms VACTERL and VATER is due to the variation in defects determined at or prior to birth. VACTERL contains vertebral, anal, cardiac, trachea-esophageal, renal/kidney, and limb defects where as VATER only has vertebral, anal, trachea-esophogeal, and renal defects. The "R" in VATER represented radial dysplasia. Though the differences are clear, the physical defects vary from case to case. See also 22q11 deletion syndrome Absent radius CHARGE Association Holt–Oram syndrome Feingold syndrome Pallister–Hall syndrome Townes–Brocks syndrome References Further reading McMullen, KP; Karnes, PS; Moir, CR; Michels, VV (Jun 28, 1996). "Familial recurrence of tracheoesophageal fistula and associated malformations". American Journal of Medical Genetics. 63 (4): 525–8. doi:10.1002/(sici)1096-8628(19960628)63:4<525::aid-ajmg3>3.0.co;2-n. PMID 8826429. == External links ==
Diaphragmatic hernia	Diaphragmatic hernia is a defect or hole in the diaphragm that allows the abdominal contents to move into the chest cavity. Treatment is usually surgical. Types Congenital diaphragmatic hernia Morgagnis hernia Bochdalek hernia Hiatal hernia Iatrogenic diaphragmatic hernia Traumatic diaphragmatic hernia Signs and symptoms A scaphoid abdomen (sucked inwards) may be the presenting symptom in a newborn. Diagnosis Diagnosis can be made by either CT or X-ray. Treatment Treatment for a diaphragmatic hernia usually involves surgery, with acute injuries often repaired with monofilament permanent sutures. Other animals Peritoneopericardial diaphragmatic hernia is a type of hernia more common in other mammals. This is usually treated with surgery. References Bibliography Eren S, Ciris F (2005). "Diaphragmatic hernia: diagnostic approaches with review of the literature". Eur J Radiol. 54 (3): 448–59. doi:10.1016/j.ejrad.2004.09.008. PMID 15899350. == External links ==
Myotonia congenita	Myotonia congenita is a congenital neuromuscular channelopathy that affects skeletal muscles (muscles used for movement). It is a genetic disorder. The hallmark of the disease is the failure of initiated contraction to terminate, often referred to as delayed relaxation of the muscles (myotonia) and rigidity. Symptoms include delayed relaxation of the muscles after voluntary contraction (myotonia), and may also include stiffness, hypertrophy (enlargement), transient weakness in some forms of the disorder (from certain genetic mutations), severe masseter spasm, and cramping. The condition is sometimes referred to as fainting goat syndrome, as it is responsible for the eponymous fainting seen in fainting goats when presented with a sudden stimulus. Of note, myotonia congenita has no association with malignant hyperthermia (MH). Symptoms and signs The prolonged muscle contractions, which occur most commonly in the leg muscles in recessive mutations, and more commonly in the hands, face, and eyelids in dominant mutations, are often enhanced by inactivity, and in some forms are relieved by repetitive movement known as "the warm-up effect". This effect often diminishes quickly with rest. Some individuals with myotonia congenita are prone to falling as a result of hasty movements or an inability to stabilize themselves after a loss of balance. During a fall, a person with myotonia congenita may experience partial or complete rigid paralysis that will quickly resolve once the event is over. However, a fall into cold water may render the person unable to move for the duration of submergence. As with myotonic goats, children are more prone to falling than adults, due to their impulsivity.The two major types of myotonia congenita are distinguished by the severity of their symptoms and their patterns of inheritance. Becker disease usually appears later in childhood than Thomsen disease, and causes more severe myotonia, muscle stiffness and transient weakness. Although myotonia in itself is not normally associated with pain, cramps or myalgia may develop. People with Becker disease often experience temporary attacks of muscle weakness, particularly in the arms and hands, brought on by movement after periods of rest. They may also develop mild, permanent muscle weakness over time. This muscle weakness is not observed in people with Thomsen disease. However, in recent times, as more of the individual mutations that cause myotonia congenita are identified, these limited disease classifications are becoming less widely used.Early symptoms in a child may include: Difficulty swallowing Gagging Stiff movements that improve when they are repeated Frequent falling Difficulties opening eyelids after strenuous contraction or crying (von Graefes sign)Possible complications may include: Aspiration pneumonia (caused by swallowing difficulties) Frequent choking or gagging in infants (also caused by swallowing difficulties) Abdominal muscle weakness Chronic joint problems Injury due to falls Phenotypic variability Both Thomsen and Becker myotonia have high phenotype variability. Severity of symptoms can vary greatly between individuals and throughout the lives of the individuals themselves. This may be partly because there are over 130 currently known different mutations that can cause the disorder, each with their own specifics, and also because myotonia congenita is an ion channel disorder, and ion channels are sensitive to internal and external environmental factors. It has been shown that pregnancy and the use of diuretics aggravate myotonia, and both these conditions are linked to the loss of divalent cations such as magnesium and calcium. It has further been shown that in chemically-induced myotonia in isolated rat muscle, myotonia could be dampened by increasing the magnesium and calcium content of the extracellular medium. This has also been shown for isolated human muscle.Adrenaline/epinephrine is well known to make myotonia worse in most individuals with the disorder, and a person with myotonia congenita may experience a sudden increase in difficulty with mobility in a particularly stressful situation during which adrenaline is released.Due to the invisible nature of the disorder, the fact that those with myotonia congenita often appear very fit and able bodied, the general lack of knowledge about the disorder by the general and medical community, and often by the individual themselves, and the potential for inconsistency with the symptoms, many people with myotonia congenita have experienced a degree of social persecution at one time or another because of the effects of their disorder. The warm-up phenomenon This phenomenon was described along with the disease by Thomsen in 1876 but its etiology remains unclear.Patients report that myotonia congenita may present itself in the following ways (this is from first hand experience). If the person is sedentary and then decides to walk up a set of stairs, by the third or fourth step their leg muscles begin to stiffen significantly, requiring them to slow down almost to a complete stop. But as the muscles loosen up, a few steps later, they can once again begin to climb the steps at a normal pace. If this person plays any kind of a sport, a good warm-up is mandatory. Otherwise if they need to quickly and intensively use their muscles, such as in a sprint race or a basketball game, their muscles will freeze up, causing them to slow down or almost come to a complete stop. But once the muscles are warmed up, they can once again function normally. This can happen in various muscles, even in muscles such as the tongue. For example, if a person has not spoken for awhile and then wants to speak, their tongue may be stiff at first causing the words to come out a little garbled, but after a few seconds of trying to speak, the tongue muscle will loosen up and then they can speak normally for the remainder of the time that they are conversing.Patients report that repeated contraction of muscle alleviates present myotonia with each contraction, such that myotonia is almost absent after a few contractions of the same muscle. The effect lasts about five minutes. There have been several proposed mechanisms for this phenomenon, but none have been demonstrated conclusively; one hypothesis is that the Na+/K+-ATPase is stimulated during the myotonic activity by increased intracellular Na+ in the cytosol of the muscle cell, increasing the activity of the Na+/K+-ATPase. However, in experiments with patients where the Na+/K+-ATPase had been blocked in the underarm by infusion of the Na+/K+-ATPase-blocker Ouabain, no effect on warm-up was observed. Another hypothesis states that the few remaining functional chloride channels in muscle may become more active with increased muscle activity.It has been proposed that inactivation of sodium channel protein type 4 subunit alpha, residing in skeletal muscle, could play an important role in the warm-up phenomenon. In particular, slow inactivation of the channel is believed to have a spatial and temporal extent that is correlated to warm-up and therefore may provide a plausible cause. Causes The disorder is caused by mutations in part of a gene (CLCN1) encoding the ClC-1 chloride channel, resulting in muscle fiber membranes having an unusually exaggerated response to stimulation (hyperexcitability).Three cases have been reported who were diagnosed with Thomsens myotonia and proved on genetic testing not to have mutations in the chloride gene but rather in the alpha-subunit of the voltage gated sodium channel (SCN4A). Like chloride channel mutations, patients with sodium channel mutations may have a very varied phenotype, making a diagnosis more difficult. Mechanisms Myotonia congenita is caused in humans by loss-of-function mutations in the gene CLCN1. This is the gene encoding the protein CLCN1, that forms the ClC-1 chloride channel, critical for the normal function of skeletal muscle cells. This gene is also associated with the condition in horses, goats, and dogs. In short, in lack of sufficient functional chloride channels, the muscle fiber membrane becomes hyper-excitable and continues to be electrically active (firing action potentials) when stimulated, for longer periods of time, than a normal muscle fiber. This results in prolonged contraction/delayed relaxation of the muscle.The dysfunctional Cl− channels are located in the muscle fiber membrane and do not affect the motor nerve innervating the muscle. However, many studies have shown that denervation of muscle fibers alter the resting membrane conductance, but whether this affects myotonia in the muscle has been subject to heavy debate, and results from experiments are inconclusive.In skeletal muscle fibers, a large transverse tubule system with a high surface-area to volume ratio exists. The onset of skeletal muscle activity is associated with the initiation and propagation of action potentials again associated with an efflux of K+ to the extracellular fluid and transverse tubule system. When many action potentials are elicited subsequently more K+ is expelled from the cell into the transverse tubular system. As K+ accumulates in the transverse tubular system the equilibrium potential for K+ (EK+) normally around -80 mV, becomes more depolarized (depolarization), according to the Nernst equation. In skeletal muscle fibers the equilibrium potential for Cl− is around -80 mV, equal to that of K+ at rest. Cl− moves towards its equilibrium potential around -80 mV, while potassium moves towards its equilibrium potential more depolarized than -80 mV during activity. This results in a slightly more depolarized membrane potential of the fiber during repeated action potentials, see Goldman equation. The Na+ conductance is only elevated shortly compared to the K+ conductance during each action potential, which is why K+ largely determines the membrane potential (Cl− is passively distributed during rest). In the case of myotonia congenita, the chloride channels that allow Cl− to move across the membrane towards its equilibrium potential are defective, thus K+ is the only ion determining the membrane potential, and as more and more K+ accumulates in the transverse tubular system with each subsequent action potential the fiber depolarizes until the membrane potential comes close enough to the action potential threshold for spontaneous activity to ensue Spontaneous action potentials can arise for several seconds, leading to the delayed relaxation that is the hallmark of myotonia. Cessation of spontaneous activity is associated with sodium channel inactivation (Nav1.4). Diagnosis Types Two types of myotonia congenita exist, an autosomal dominant form and an autosomal recessive form. Autosomal dominant myotonia congenita (OMIM #160800) is also called Thomsen disease, after Danish/German physician Asmus Julius Thomas Thomsen (1815–1896), who himself had the disease and who wrote the first description of it in the medical literature (in 1876). Autosomal recessive myotonia congenita (OMIM #255700) is also called generalized myotonia, recessive generalized myotonia (RGM), Becker disease, and Becker myotonia, after the German professor Peter Emil Becker, who discovered its recessive nature.The term congenital in its sense of "clinically apparent from birth" applies only to Thomsen disease, as the clinical onset of Becker myotonia may be delayed up to the age of 4 to 6 years. But in either form of myotonia congenita, the terms strictest sense reflects that the disease is genetically present from birth, although the clinical onset may be delayed.With the advent of genetic testing, it has recently been found that some typically recessive mutations may occur in a dominant fashion in some individuals. The reason for this is not known.Because several CLCN1 mutations can cause either Becker disease or Thomsen disease, doctors usually rely on characteristic signs and symptoms to distinguish the two forms of myotonia congenita. However, myotonia caused by CLCN1 mutations can occasionally be clinically indistinguishable from myotonia caused by sodium channel mutations (SCN4A mutations) resulting in the similar disease paramyotonia congenita.A so-called Finnish heritage disease, congenital myotonia is more common in Finland and among ethnic Finns. A molecular study of the CLCN1 gene in 24 families in northern Finland, including 46 affected individuals, showed that although the inheritance appeared to be dominant (Thomsen type), in fact it is recessive (Becker type). Differential diagnosis Sodium channel myotonias (SCN4A) Potassium-aggravated myotonia (acetazolamide responsive myotonia) Paramyotonia congenita Hyperkalemic periodic paralysisDystrophies Myotonic dystrophy (myotonic muscular dystrophy: Type 1 and Type 2)Potassium channel disorders (KCNJ2) Andersen-Tawil syndromeOther disorders Thyroid disorders Neuromyotonia (Isaacs Syndrome) Schwartz–Jampel syndrome Stiff person syndrome Brody myopathy (Brody Disease, Brodys Disease, Brodys Myopathy) Treatment Some cases of myotonia congenita do not require treatment, or it is determined that the risks of the medication outweigh the benefits. If necessary, however, symptoms of the disorder may be relieved with quinine, ranolazine, procainamide, flecainide, phenytoin, carbamazepine, mexiletine and other anticonvulsant drugs. Physical therapy and other rehabilitative measures may also be used to help muscle function. Genetic counseling is available. Epidemiology In northern Scandinavia, the prevalence of myotonia congenita has been estimated at 1:10,000.Myotonia congenita is estimated to affect 1 in 100,000 people worldwide. Research The name Thomsen’s disease refers to the Danish physician Julius Thomsen (1815–1896) who described the condition in himself and his family.Myotonia can be achieved in preparations of intact isolated muscle by the administration of 9-Anthracenecarboxylic acid, a blocker of chloride channels. It is also possible to achieve myotonia in preparations of intact isolated muscle by greatly lowering or removing the extracellular content of chloride in the bathing medium.During the 1970s several murine models of myotonia appeared. One in particular has been used widely, the adr mouse or "arrested development of righting response". This model is often used in scientific work with muscular dystrophy, and displays myotonia due to lack of functional chloride channels. See also Fainting goat Tonic immobility New Forest pony References External links GeneReview/NCBI/NIH/UW entry on myotonia congenita NINDS: Myotonia congenita National Library of Medicine: Myotonia congenita
Infantile neuronal ceroid lipofuscinosis	Infantile neuronal ceroid lipofuscinoses (INCL) or Santavuori disease or Hagberg-Santavuori disease or Santavuori-Haltia disease or Infantile Finnish type neuronal ceroid lipofuscinosis or Balkan disease is a form of NCL and inherited as a recessive autosomal genetic trait. The disorder is progressive, degenerative and fatal, extremely rare worldwide – with approximately 60 official cases reported by 1982, perhaps 100 with the condition in total today – but relatively common in Finland due to the local founder effect. Presentation The development of children born with INCL is normal for the first 8–18 months, but will then flounder and start to regress both physically and mentally. Motor skills and speech are lost, and optic atrophy causes blindness. A variety of neurological symptoms, such as epilepsy and myoclonic seizures, appear. The senses of hearing and touch remain unaffected. The average lifespan of an INCL child is 9–11 years. Causes It has been associated with palmitoyl-protein thioesterase. Diagnosis Treatment Treatment is limited. Drugs can alleviate the symptoms, such as sleep difficulties and epilepsy. Physiotherapy helps affected children retain the ability to remain upright for as long as possible, and prevents some of the pain. Recent attempts to treat INCL with cystagon have been unsuccessful. See also FAIDD (The Finnish Association on Intellectual and Developmental Disabilities) References External links GeneReviews/NCBI/NIH/UW entry on Neuronal Ceroid-Lipofuscinosis An overview (in Finnish) The INCL organization of Finland (in Finnish)
Murine typhus	Murine typhus, also known as endemic typhus or flea-borne typhus, is a form of typhus transmitted by fleas (Xenopsylla cheopis), usually on rats, in contrast to epidemic typhus which is usually transmitted by lice. Murine typhus is an under-recognized entity, as it is often confused with viral illnesses. Most people who are infected do not realize that they have been bitten by fleas. Historically the term "hunger-typhus" was used in accounts by British POWs in Germany at the end of World War I when they described conditions in Germany. Signs and symptoms Symptoms of endemic typhus include headache, fever, muscle pain, joint pain, nausea and vomiting. 40–50% of patients will develop a discrete rash six days after the onset of signs. Up to 45% will develop neurological signs such as confusion, stupor, seizures or imbalance. Symptoms may resemble those of measles, rubella, or possibly Rocky Mountain spotted fever. These symptoms are likely caused by a vasculitis caused by the rickettsia. Causes It is caused by the bacterium Rickettsia typhi, and is transmitted by the fleas that infest rats. While rat fleas are the most common vectors, cat fleas and mouse fleas are less common modes of transmission. These fleas are not affected by the infection. Human infection occurs because of flea-fecal contamination of the bites on human skin. Rats, cats, and opossums maintain the rickettsia colonization by providing it with a host for its entire life cycle. Rats can develop the infection, and help spread the infection to other fleas that bite them, and help multiply the number of infected fleas that can then infect humans. Less often, endemic typhus is caused by Rickettsia felis and transmitted by fleas carried by cats or opossums. In the United States of America, murine typhus is found most commonly in southern California, Texas and Hawaii. In some studies, up to 13% of children were found to have serological evidence of infection. Diagnosis As of 2014, early diagnosis continued to be based on clinical suspicion, and treatment of the disease is indicated even before laboratory results confirm its presence. Because of the lag between the onset of infection and the appearance of antibodies in a blood test, serologic tests are merely confirmatory and retrospective. Weil-Felix agglutination reactions are not sensitive to the disease. Indirect fluorescence antibody assays that are specific to R. typhi antigens are the recommended route for detection and diagnosis: diagnostic titers are present in half of all cases within the first week of infection and in nearly all cases by day-15. The sharing of antigens by rickettsiae means routine serologic evaluation will not distinguish between murine typhus and epidemic typhus. Bacterial cultures are rarely performed because although they are highly accurate for diagnosis, the biohazard risk of generating them is often considered too high. Treatment The disease can be fatal if left untreated, but endemic typhus is highly treatable with antibiotics. Most people recover fully, but death may occur in the elderly, severely disabled or patients with a depressed immune system. The most effective antibiotics include tetracycline and chloramphenicol. In the United States, the CDC recommends solely doxycycline. See also List of mites associated with cutaneous reactions References == External links ==
Piezogenic papules	Painful fat herniation is foot pain caused by the herniation of fat through the thin fascial layers of the weight-bearing parts of the heel. The herniation results in small bumps called piezogenic pedal papules or piezogenic papules. Though piezogenic papules are most commonly found on the heel, they can also be found on the wrist and palm.Piezogenic papules are relatively common; in one population-based study, the prevalence was found to be 76%. They occur more frequently in runners, triathletes, and individuals exposed to long periods of standing. They are also common in individuals with connective tissue disorders, especially Ehlers–Danlos syndrome. However, due to their preponderance in the general population, the presence of piezogenic papules alone does not automatically indicate the presence of Ehlers–Danlos syndrome. In most cases, piezogenic papules are of little clinical significance. See also Skin lesion Tennis toe List of cutaneous conditions References == External links ==
Psoriasis	Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, or purple on some people with darker skin, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete body coverage. Injury to the skin can trigger psoriatic skin changes at that spot, which is known as the Koebner phenomenon.The five main types of psoriasis are plaque, guttate, inverse, pustular, and erythrodermic. Plaque psoriasis, also known as psoriasis vulgaris, makes up about 90% of cases. It typically presents as red patches with white scales on top. Areas of the body most commonly affected are the back of the forearms, shins, navel area, and scalp. Guttate psoriasis has drop-shaped lesions. Pustular psoriasis presents as small, noninfectious, pus-filled blisters. Inverse psoriasis forms red patches in skin folds. Erythrodermic psoriasis occurs when the rash becomes very widespread, and can develop from any of the other types. Fingernails and toenails are affected in most people with psoriasis at some point in time. This may include pits in the nails or changes in nail color.Psoriasis is generally thought to be a genetic disease that is triggered by environmental factors. If one twin has psoriasis, the other twin is three times more likely to be affected if the twins are identical than if they are nonidentical. This suggests that genetic factors predispose to psoriasis. Symptoms often worsen during winter and with certain medications, such as beta blockers or NSAIDs. Infections and psychological stress can also play a role. The underlying mechanism involves the immune system reacting to skin cells. Diagnosis is typically based on the signs and symptoms.There is no known cure for psoriasis, but various treatments can help control the symptoms. These treatments include steroid creams, vitamin D3 cream, ultraviolet light, and immunosuppressive drugs, such as methotrexate. About 75% of skin involvement improves with creams alone. The disease affects 2–4% of the population. Men and women are affected with equal frequency. The disease may begin at any age, but typically starts in adulthood. Psoriasis is associated with an increased risk of psoriatic arthritis, lymphomas, cardiovascular disease, Crohns disease, and depression. Psoriatic arthritis affects up to 30% of individuals with psoriasis.The word "psoriasis" is from Greek ψωρίασις, meaning "itching condition" or "being itchy" from psora, "itch", and -iasis, "action, condition". Signs and symptoms Plaque psoriasis Psoriasis vulgaris (also known as chronic stationary psoriasis or plaque-like psoriasis) is the most common form and affects 85–90% of people with psoriasis. Plaque psoriasis typically appears as raised areas of inflamed skin covered with silvery-white, scaly skin. These areas are called plaques and are most commonly found on the elbows, knees, scalp, and back. Other forms Additional types of psoriasis comprise about 10% of cases. They include pustular, inverse, napkin, guttate, oral, and seborrheic-like forms. Pustular psoriasis Pustular psoriasis appears as raised bumps filled with noninfectious pus (pustules). The skin under and surrounding the pustules is red and tender. Pustular psoriasis can either be localized or more widespread throughout the body. Two types of localized pustular psoriasis include psoriasis pustulosa palmoplantaris and acrodermatitis continua of Hallopeau; both forms are localized to the hands and feet. Inverse psoriasis Inverse psoriasis (also known as flexural psoriasis) appears as smooth, inflamed patches of skin. The patches frequently affect skin folds, particularly around the genitals (between the thigh and groin), the armpits, in the skin folds of an overweight abdomen (known as panniculus), between the buttocks in the intergluteal cleft, and under the breasts in the inframammary fold. Heat, trauma, and infection are thought to play a role in the development of this atypical form of psoriasis. Napkin psoriasis Napkin psoriasis is a subtype of psoriasis common in infants characterized by red papules with silver scale in the diaper area that may extend to the torso or limbs. Napkin psoriasis is often misdiagnosed as napkin dermatitis (diaper rash). Guttate psoriasis Guttate psoriasis is characterized by numerous small, scaly, red or pink, droplet-like lesions (papules). These numerous spots of psoriasis appear over large areas of the body, primarily the trunk, but also the limbs and scalp. Guttate psoriasis is often triggered by a streptococcal infection, typically streptococcal pharyngitis. Erythrodermic psoriasis Psoriatic erythroderma (erythrodermic psoriasis) involves widespread inflammation and exfoliation of the skin over most of the body surface, often involving greater than 90% of the body surface area. It may be accompanied by severe dryness, itching, swelling, and pain. It can develop from any type of psoriasis. It is often the result of an exacerbation of unstable plaque psoriasis, particularly following the abrupt withdrawal of systemic glucocorticoids. This form of psoriasis can be fatal as the extreme inflammation and exfoliation disrupt the bodys ability to regulate temperature and perform barrier functions. Mouth Psoriasis in the mouth is very rare, in contrast to lichen planus, another common papulosquamous disorder that commonly involves both the skin and mouth. When psoriasis involves the oral mucosa (the lining of the mouth), it may be asymptomatic, but it may appear as white or grey-yellow plaques. Fissured tongue is the most common finding in those with oral psoriasis and has been reported to occur in 6.5–20% of people with psoriasis affecting the skin. The microscopic appearance of oral mucosa affected by geographic tongue (migratory stomatitis) is very similar to the appearance of psoriasis. However, modern studies have failed to demonstrate any link between the two conditions. Seborrheic-like psoriasis Seborrheic-like psoriasis is a common form of psoriasis with clinical aspects of psoriasis and seborrheic dermatitis, and it may be difficult to distinguish from the latter. This form of psoriasis typically manifests as red plaques with greasy scales in areas of higher sebum production such as the scalp, forehead, skin folds next to the nose, the skin surrounding the mouth, skin on the chest above the sternum, and in skin folds. Psoriatic arthritis Psoriatic arthritis is a form of chronic inflammatory arthritis that has a highly variable clinical presentation and frequently occurs in association with skin and nail psoriasis. It typically involves painful inflammation of the joints and surrounding connective tissue, and can occur in any joint, but most commonly affects the joints of the fingers and toes. This can result in a sausage-shaped swelling of the fingers and toes known as dactylitis. Psoriatic arthritis can also affect the hips, knees, spine (spondylitis), and sacroiliac joint (sacroiliitis). About 30% of individuals with psoriasis will develop psoriatic arthritis. Skin manifestations of psoriasis tend to occur before arthritic manifestations in about 75% of cases. Nail changes Psoriasis can affect the nails and produces a variety of changes in the appearance of fingers and toenails. Nail psoriasis occurs in 40–45% of people with psoriasis affecting the skin, and has a lifetime incidence of 80–90% in those with psoriatic arthritis. These changes include pitting of the nails (pinhead-sized depressions in the nail is seen in 70% with nail psoriasis), whitening of the nail, small areas of bleeding from capillaries under the nail, yellow-reddish discoloration of the nails known as the oil drop or salmon spots, dryness, thickening of the skin under the nail (subungual hyperkeratosis), loosening and separation of the nail (onycholysis), and crumbling of the nail. Medical signs In addition to the appearance and distribution of the rash, specific medical signs may be used by medical practitioners to assist with diagnosis. These may include Auspitzs sign (pinpoint bleeding when scale is removed), Koebner phenomenon (psoriatic skin lesions induced by trauma to the skin), and itching and pain localized to papules and plaques. Causes The cause of psoriasis is not fully understood, but many theories exist. Genetics Around one-third of people with psoriasis report a family history of the disease, and researchers have identified genetic loci associated with the condition. Identical twin studies suggest a 70% chance of a twin developing psoriasis if the other twin has the disorder. The risk is around 20% for nonidentical twins. These findings suggest both a genetic susceptibility and an environmental response in developing psoriasis.Psoriasis has a strong hereditary component, and many genes are associated with it, but how those genes work together is unclear. Most of the identified genes relate to the immune system, particularly the major histocompatibility complex (MHC) and T cells. Genetic studies are valuable due to their ability to identify molecular mechanisms and pathways for further study and potential medication targets.Classic genome-wide linkage analysis has identified nine loci on different chromosomes associated with psoriasis. They are called psoriasis susceptibility 1 through 9 (PSORS1 through PSORS9). Within those loci are genes on pathways that lead to inflammation. Certain variations (mutations) of those genes are commonly found in psoriasis. Genome-wide association scans have identified other genes that are altered to characteristic variants in psoriasis. Some of these genes express inflammatory signal proteins, which affect cells in the immune system that are also involved in psoriasis. Some of these genes are also involved in other autoimmune diseases.The major determinant is PSORS1, which probably accounts for 35–50% of psoriasis heritability. It controls genes that affect the immune system or encode skin proteins that are overabundant with psoriasis. PSORS1 is located on chromosome 6 in the MHC, which controls important immune functions. Three genes in the PSORS1 locus have a strong association with psoriasis vulgaris: HLA-C variant HLA-Cw6, which encodes an MHC class I protein; CCHCR1, variant WWC, which encodes a coiled coil protein overexpressed in psoriatic epidermis; and CDSN, variant allele 5, which encodes corneodesmosin, a protein expressed in the granular and cornified layers of the epidermis and upregulated in psoriasis.Two major immune system genes under investigation are interleukin-12 subunit beta (IL12B) on chromosome 5q, which expresses interleukin-12B; and IL23R on chromosome 1p, which expresses the interleukin-23 receptor, and is involved in T cell differentiation. Interleukin-23 receptor and IL12B have both been strongly linked with psoriasis. T cells are involved in the inflammatory process that leads to psoriasis. These genes are on the pathway that upregulate tumor necrosis factor-α and nuclear factor κB, two genes involved in inflammation. The first gene directly linked to psoriasis was identified as the CARD14 gene located in the PSORS2 locus. A rare mutation in the gene encoding for the CARD14-regulated protein plus an environmental trigger was enough to cause plaque psoriasis (the most common form of psoriasis). Lifestyle Conditions reported as worsening the disease include chronic infections, stress, and changes in season and climate. Others factors that might worsen the condition include hot water, scratching psoriasis skin lesions, skin dryness, excessive alcohol consumption, cigarette smoking, and obesity. The effects of stopping cigarette smoking or alcohol misuse have yet to be studied as of 2019. HIV The rate of psoriasis in human immunodeficiency virus-positive (HIV) individuals is comparable to that of HIV-negative individuals, but psoriasis tends to be more severe in people infected with HIV. A much higher rate of psoriatic arthritis occurs in HIV-positive individuals with psoriasis than in those without the infection. The immune response in those infected with HIV is typically characterized by cellular signals from Th2 subset of CD4+ helper T cells, whereas the immune response in psoriasis vulgaris is characterized by a pattern of cellular signals typical of Th1 subset of CD4+ helper T cells and Th17 helper T cells. The diminished CD4+-T cell presence is thought to cause an overactivation of CD8+-T cells, which are responsible for the exacerbation of psoriasis in HIV-positive people. Psoriasis in those with HIV/AIDS is often severe and may be untreatable with conventional therapy. In those with long-term, well-controlled psoriasis, new HIV infection can trigger a severe flare-up of psoriasis and/or psoriatic arthritis. Microbes Psoriasis has been described as occurring after strep throat, and may be worsened by skin or gut colonization with Staphylococcus aureus, Malassezia spp., and Candida albicans. Guttate psoriasis often affects children and adolescents and can be triggered by a recent group A streptococcal infection (tonsillitis or pharyngitis). Medications Drug-induced psoriasis may occur with beta blockers, lithium, antimalarial medications, nonsteroidal anti-inflammatory drugs, terbinafine, calcium channel blockers, captopril, glyburide, granulocyte colony-stimulating factor, interleukins, interferons, lipid-lowering medications,: 197 and paradoxically TNF inhibitors such as infliximab or adalimumab. Withdrawal of corticosteroids (topical steroid cream) can aggravate psoriasis due to the rebound effect. Pathophysiology Psoriasis is characterized by an abnormally excessive and rapid growth of the epidermal layer of the skin. Abnormal production of skin cells (especially during wound repair) and an overabundance of skin cells result from the sequence of pathological events in psoriasis. The sequence of pathological events in psoriasis is thought to start with an initiation phase in which an event (skin trauma, infection, or drugs) leads to activation of the immune system and then the maintenance phase consisting of chronic progression of the disease. Skin cells are replaced every 3–5 days in psoriasis rather than the usual 28–30 days. These changes are believed to stem from the premature maturation of keratinocytes induced by an inflammatory cascade in the dermis involving dendritic cells, macrophages, and T cells (three subtypes of white blood cells). These immune cells move from the dermis to the epidermis and secrete inflammatory chemical signals (cytokines) such as interleukin-36γ, tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-22. These secreted inflammatory signals are believed to stimulate keratinocytes to proliferate. One hypothesis is that psoriasis involves a defect in regulatory T cells, and in the regulatory cytokine interleukin-10. The inflammatory cytokines found in psoriatic nails and joints (in the case of psoriatic arthritis) are similar to those of psoriatic skin lesions, suggesting a common inflammatory mechanism.Gene mutations of proteins involved in the skins ability to function as a barrier have been identified as markers of susceptibility for the development of psoriasis.Deoxyribonucleic acid (DNA) released from dying cells acts as an inflammatory stimulus in psoriasis and stimulates the receptors on certain dendritic cells, which in turn produce the cytokine interferon-α. In response to these chemical messages from dendritic cells and T cells, keratinocytes also secrete cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor-α, which signal downstream inflammatory cells to arrive and stimulate additional inflammation.Dendritic cells bridge the innate immune system and adaptive immune system. They are increased in psoriatic lesions and induce the proliferation of T cells and type 1 helper T cells (Th1). Targeted immunotherapy, as well as psoralen and ultraviolet A (PUVA) therapy, can reduce the number of dendritic cells and favors a Th2 cell cytokine secretion pattern over a Th1/Th17 cell cytokine profile. Psoriatic T cells move from the dermis into the epidermis and secrete interferon-γ and interleukin-17. Interleukin-23 is known to induce the production of interleukin-17 and interleukin-22. Interleukin-22 works in combination with interleukin-17 to induce keratinocytes to secrete neutrophil-attracting cytokines. Diagnosis A diagnosis of psoriasis is usually based on the appearance of the skin. Skin characteristics typical for psoriasis are scaly, erythematous plaques, papules, or patches of skin that may be painful and itch. No special blood tests or diagnostic procedures are usually required to make the diagnosis.The differential diagnosis of psoriasis includes dermatological conditions similar in appearance such as discoid eczema, seborrheic eczema, pityriasis rosea (may be confused with guttate psoriasis), nail fungus (may be confused with nail psoriasis) or cutaneous T cell lymphoma (50% of individuals with this cancer are initially misdiagnosed with psoriasis). Dermatologic manifestations of systemic illnesses such as the rash of secondary syphilis may also be confused with psoriasis.If the clinical diagnosis is uncertain, a skin biopsy or scraping may be performed to rule out other disorders and to confirm the diagnosis. Skin from a biopsy shows clubbed epidermal projections that interdigitate with dermis on microscopy. Epidermal thickening is another characteristic histologic finding of psoriasis lesions. The stratum granulosum layer of the epidermis is often missing or significantly decreased in psoriatic lesions; the skin cells from the most superficial layer of skin are also abnormal as they never fully mature. Unlike their mature counterparts, these superficial cells keep their nuclei. Inflammatory infiltrates can typically be seen on microscopy when examining skin tissue or joint tissue affected by psoriasis. Epidermal skin tissue affected by psoriatic inflammation often has many CD8+ T cells, while a predominance of CD4+ T cells makes up the inflammatory infiltrates of the dermal layer of skin and the joints. Classification Morphological Psoriasis is classified as a papulosquamous disorder and is most commonly subdivided into different categories based on histological characteristics. Variants include plaque, pustular, guttate, and flexural psoriasis. Each form has a dedicated ICD-10 code. Psoriasis can also be classified into nonpustular and pustular types. Pathogenetic Another classification scheme considers genetic and demographic factors. Type 1 has a positive family history, starts before the age of 40, and is associated with the human leukocyte antigen, HLA-Cw6. Conversely, type 2 does not show a family history, presents after age 40, and is not associated with HLA-Cw6. Type 1 accounts for about 75% of persons with psoriasis.The classification of psoriasis as an autoimmune disease has sparked considerable debate. Researchers have proposed differing descriptions of psoriasis and psoriatic arthritis; some authors have classified them as autoimmune diseases while others have classified them as distinct from autoimmune diseases and referred to them as immune-mediated inflammatory diseases. Severity No consensus exists about how to classify the severity of psoriasis. Mild psoriasis has been defined as a percentage of body surface area (BSA)≤10, a Psoriasis Area and Severity Index (PASI) score ≤10, and a Dermatology Life Quality Index (DLQI) score ≤10. Moderate to severe psoriasis was defined by the same group as BSA >10 or PASI score >10 and a DLQI score >10.The DLQI is a 10-question tool used to measure the impact of several dermatologic diseases on daily functioning. The DLQI score ranges from 0 (minimal impairment) to 30 (maximal impairment) and is calculated with each answer being assigned 0–3 points with higher scores indicating greater social or occupational impairment.The PASI is the most widely used measurement tool for psoriasis. It assesses the severity of lesions and the area affected and combines these two factors into a single score from 0 (no disease) to 72 (maximal disease). Nevertheless, the PASI can be too unwieldy to use outside of research settings, which has led to attempts to simplify the index for clinical use. Management While no cure is available for psoriasis, many treatment options exist. Topical agents are typically used for mild disease, phototherapy for moderate disease, and systemic agents for severe disease. There is no evidence to support the effectiveness of conventional topical and systemic drugs, biological therapy, or phototherapy for acute guttate psoriasis or an acute guttate flare of chronic psoriasis. Topical agents Topical corticosteroid preparations are the most effective agents when used continuously for eight weeks; retinoids and coal tar were found to be of limited benefit and may be no better than placebo. Greater benefit has been observed with very potent corticosteroids when compared to potent corticosteroids. Vitamin D analogues such as paricalcitol are superior to placebo. Combination therapy with vitamin D and a corticosteroid are superior to either treatment alone and vitamin D is superior to coal tar for chronic plaque psoriasis.For psoriasis of the scalp, a 2016 review found dual therapy (vitamin D analogues and topical corticosteroids) or corticosteroid monotherapy to be more effective and safer than topical vitamin D analogues alone. Due to their similar safety profiles and minimal benefit of dual therapy over monotherapy, corticosteroid monotherapy appears to be an acceptable treatment for short-term treatment.Moisturizers and emollients such as mineral oil, petroleum jelly, calcipotriol, and decubal (an oil-in-water emollient) were found to increase the clearance of psoriatic plaques. Some emollients have been shown to be even more effective at clearing psoriatic plaques when combined with phototherapy. Certain emollients, though, have no impact on psoriasis plaque clearance or may even decrease the clearance achieved with phototherapy, e.g. the emollient salicylic acid is structurally similar to para-aminobenzoic acid, commonly found in sunscreen, and is known to interfere with phototherapy in psoriasis. Coconut oil, when used as an emollient in psoriasis, has been found to decrease plaque clearance with phototherapy. Medicated creams and ointments applied directly to psoriatic plaques can help reduce inflammation, remove built-up scale, reduce skin turnover, and clear affected skin of plaques. Ointment and creams containing coal tar, dithranol, corticosteroids (i.e. desoximetasone), fluocinonide, vitamin D3 analogues (for example, calcipotriol), and retinoids are routinely used. (The use of the finger tip unit may be helpful in guiding how much topical treatment to use.)Vitamin D analogues may be useful with steroids; steroids alone have a higher rate of side effects. Vitamin D analogues may allow less steroids to be used.Another topical therapy used to treat psoriasis is a form of balneotherapy, which involves daily baths in the Dead Sea. This is usually done for four weeks with the benefit attributed to sun exposure and specifically UVB light. This is cost-effective and it has been propagated as an effective way to treat psoriasis without medication. Decreases of PASI scores greater than 75% and remission for several months have commonly been observed. Side effects may be mild such as itchiness, folliculitis, sunburn, poikiloderma, and a theoretical risk of nonmelanoma cancer or melanoma has been suggested. Some studies indicate no increased risk of melanoma in the long term. Data are inconclusive with respect to nonmelanoma skin cancer risk, but support the idea that the therapy is associated with an increased risk of benign forms of sun-induced skin damage such as, but not limited to, actinic elastosis or liver spots. Dead Sea balneotherapy is also effective for psoriatic arthritis. Tentative evidence indicates that balneophototherapy, a combination of salt bathes and exposure to ultraviolet B-light (UVB), in chronic plaque psoriasis is better than UVB alone. UV phototherapy Phototherapy in the form of sunlight has long been used for psoriasis. UVB wavelengths of 311–313 nanometers are most effective, and special lamps have been developed for this application. The exposure time should be controlled to avoid overexposure and burning of the skin. The UVB lamps should have a timer that turns off the lamp when the time ends. The amount of light used is determined by a persons skin type. Increased rates of cancer from treatment appear to be small. Narrowband UVB therapy has been demonstrated to have similar efficacy to psoralen and ultraviolet A phototherapy (PUVA). A 2013 meta-analysis found no difference in efficacy between NB-UVB and PUVA in the treatment of psoriasis, but NB-UVB is usually more convenient.One of the problems with clinical phototherapy is the difficulty many people have gaining access to a facility. Indoor tanning resources are almost ubiquitous today and could be considered as a means for people to get UV exposure when dermatologist-provided phototherapy is not available. Indoor tanning is already used by many people as a treatment for psoriasis; one indoor facility reported that 50% of its clients were using the center for psoriasis treatment; another reported 36% were doing the same thing. However, a concern with the use of commercial tanning is that tanning beds that primarily emit UVA might not effectively treat psoriasis. One study found that plaque psoriasis is responsive to erythemogenic doses of either UVA or UVB, as exposure to either can cause dissipation of psoriatic plaques. It does require more energy to reach erythemogenic dosing with UVA.UV light therapies all have risks; tanning beds are no exception, being listed by the World Health Organization as carcinogens. Exposure to UV light is known to increase the risks of melanoma and squamous cell and basal cell carcinomas; younger people with psoriasis, particularly those under age 35, are at increased risk from melanoma from UV light treatment. A review of studies recommends that people who are susceptible to skin cancers exercise caution when using UV light therapy as a treatment.A major mechanism of NB-UVB is the induction of DNA damage in the form of pyrimidine dimers. This type of phototherapy is useful in the treatment of psoriasis because the formation of these dimers interferes with the cell cycle and stops it. The interruption of the cell cycle induced by NB-UVB opposes the characteristic rapid division of skin cells seen in psoriasis. The activity of many types of immune cells found in the skin is also effectively suppressed by NB-UVB phototherapy treatments. The most common short-term side effect of this form of phototherapy is redness of the skin; less common side effects of NB-UVB phototherapy are itching and blistering of the treated skin, irritation of the eyes in the form of conjunctival inflammation or inflammation of the cornea, or cold sores due to reactivation of the herpes simplex virus in the skin surrounding the lips. Eye protection is usually given during phototherapy treatments.PUVA combines the oral or topical administration of psoralen with exposure to ultraviolet A (UVA) light. The mechanism of action of PUVA is unknown, but probably involves activation of psoralen by UVA light, which inhibits the abnormally rapid production of the cells in psoriatic skin. There are multiple mechanisms of action associated with PUVA, including effects on the skins immune system. PUVA is associated with nausea, headache, fatigue, burning, and itching. Long-term treatment is associated with squamous cell carcinoma (but not with melan
Psoriasis	oma). A combination therapy for moderate to severe psoriasis using PUVA plus acitretin resulted in benefit, but acitretin use has been associated with birth defects and liver damage. Systemic agents Psoriasis resistant to topical treatment and phototherapy may be treated with systemic therapies including medications by mouth or injectable treatments. People undergoing systemic treatment must have regular blood and liver function tests to check for medication toxicities. Pregnancy must be avoided for most of these treatments. The majority of people experience a recurrence of psoriasis after systemic treatment is discontinued. Non-biologic systemic treatments frequently used for psoriasis include methotrexate, ciclosporin, hydroxycarbamide, fumarates such as dimethyl fumarate, and retinoids. Methotrexate and ciclosporin are medications that suppress the immune system; retinoids are synthetic forms of vitamin A. These agents are also regarded as first-line treatments for psoriatic erythroderma. Oral corticosteroids should not be used, for they can severely flare psoriasis upon their discontinuation.Biologics are manufactured proteins that interrupt the immune process involved in psoriasis. Unlike generalized immunosuppressive medical therapies such as methotrexate, biologics target specific aspects of the immune system contributing to psoriasis. These medications are generally well-tolerated, and limited long-term outcome data have demonstrated biologics to be safe for long-term use in moderate to severe plaque psoriasis. However, due to their immunosuppressive actions, biologics have been associated with a small increase in the risk for infection.Guidelines regard biologics as third-line treatment for plaque psoriasis following inadequate response to topical treatment, phototherapy, and non-biologic systemic treatments. The safety of biologics during pregnancy has not been assessed. European guidelines recommend avoiding biologics if a pregnancy is planned; anti-TNF therapies such as infliximab are not recommended for use in chronic carriers of the hepatitis B virus or individuals infected with HIV.Several monoclonal antibodies target cytokines, the molecules that cells use to send inflammatory signals to each other. TNF-α is one of the main executor inflammatory cytokines. Four monoclonal antibodies (MAbs) (infliximab, adalimumab, golimumab, and certolizumab pegol) and one recombinant TNF-α decoy receptor, etanercept, have been developed to inhibit TNF-α signaling. Additional monoclonal antibodies, such as ixekizumab, have been developed against pro-inflammatory cytokines and inhibit the inflammatory pathway at a different point than the anti-TNF-α antibodies. IL-12 and IL-23 share a common domain, p40, which is the target of the FDA-approved ustekinumab. In 2017 the US FDA approved guselkumab for plaque psoriasis. There have been few studies of the efficacy of anti-TNF medications for psoriasis in children. One randomized control study suggested that 12 weeks of etanercept treatment reduced the extent of psoriasis in children with no lasting adverse effects.Two medications that target T cells are efalizumab and alefacept. Efalizumab is a monoclonal antibody that specifically targets the CD11a subunit of LFA-1. It also blocks the adhesion molecules on the endothelial cells that line blood vessels, which attract T cells. Efalizumab was voluntarily withdrawn from the European market in February 2009, and from the U.S. market in June 2009, by the manufacturer due to the medications association with cases of progressive multifocal leukoencephalopathy. Alefacept also blocks the molecules that dendritic cells use to communicate with T cells and even causes natural killer cells to kill T cells as a way of controlling inflammation. Apremilast may also be used.Individuals with psoriasis may develop neutralizing antibodies against monoclonal antibodies. Neutralization occurs when an antidrug antibody prevents a monoclonal antibody such as infliximab from binding antigen in a laboratory test. Specifically, neutralization occurs when the anti-drug antibody binds to infliximabs antigen binding site instead of TNF-α. When infliximab no longer binds tumor necrosis factor alpha, it no longer decreases inflammation, and psoriasis may worsen. Neutralizing antibodies have not been reported against etanercept, a biologic medication that is a fusion protein composed of two TNF-α receptors. The lack of neutralizing antibodies against etanercept is probably secondary to the innate presence of the TNF-α receptor, and the development of immune tolerance.A 2021 meta-analysis found that ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab were the most effective biologics for treating psoriasis. In general, anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha biologics were found to be more effective than traditional systemic treatments. The immunologic pathways of psoriasis involve Th9, Th17, Th1 lymphocytes, and IL-22. The aforementioned biologic agents hinder different aspects of these pathways.Another treatment for moderate to severe psoriasis is fumaric acid esters (FAE) which may be similar in effectiveness to methotrexate.It has been theorized that antistreptococcal medications may improve guttate and chronic plaque psoriasis; however, the limited studies do not show that antibiotics are effective. Surgery Limited evidence suggests removal of the tonsils may benefit people with chronic plaque psoriasis, guttate psoriasis, and palmoplantar pustulosis. Diet Uncontrolled studies have suggested that individuals with psoriasis or psoriatic arthritis may benefit from a diet supplemented with fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A low-calorie diet appears to reduce the severity of psoriasis. Diet recommendations include consumption of cold water fish (preferably wild fish, not farmed) such as salmon, herring, and mackerel; extra virgin olive oil; legumes; vegetables; fruits; and whole grains; and avoid consumption of alcohol, red meat, and dairy products (due to their saturated fat). The effect of consumption of caffeine (including coffee, black tea, mate, and dark chocolate) remains to be determined.Many patients report improvements after consuming less tobacco, caffeine, sugar, nightshades (tomatoes, eggplant, peppers, paprika and white potatoes) and taking probiotics and oral Vitamin D.There is a higher rate of celiac disease among people with psoriasis. When adopting a gluten-free diet, disease severity generally decreases in people with celiac disease and those with anti-gliadin antibodies. Prognosis Most people with psoriasis experience nothing more than mild skin lesions that can be treated effectively with topical therapies.Psoriasis is known to hurt the quality of life of both the affected person and the individuals family members. Depending on the severity and location of outbreaks, individuals may experience significant physical discomfort and some disability. Itching and pain can interfere with basic functions, such as self-care and sleep. Participation in sporting activities, certain occupations, and caring for family members can become difficult activities for those with plaques located on their hands and feet. Plaques on the scalp can be particularly embarrassing, as flaky plaque in the hair can be mistaken for dandruff.Individuals with psoriasis may feel self-conscious about their appearance and have a poor self-image that stems from fear of public rejection and psychosexual concerns. Psoriasis has been associated with low self-esteem and depression is more common among those with the condition. People with psoriasis often feel prejudiced against due to the commonly held incorrect belief that psoriasis is contagious. Psychological distress can lead to significant depression and social isolation; a high rate of thoughts about suicide has been associated with psoriasis. Many tools exist to measure the quality of life of people with psoriasis and other dermatological disorders. Clinical research has indicated individuals often experience a diminished quality of life. Children with psoriasis may encounter bullying.Several conditions are associated with psoriasis. These occur more frequently in older people. Nearly half of individuals with psoriasis over the age of 65 have at least three comorbidities (concurrent conditions), and two-thirds have at least two comorbidities. Cardiovascular disease Psoriasis has been associated with obesity and several other cardiovascular and metabolic disturbances. The number of new cases per year of diabetes is 27% higher in people affected by psoriasis than in those without the condition. Severe psoriasis may be even more strongly associated with the development of diabetes than mild psoriasis. Younger people with psoriasis may also be at increased risk for developing diabetes. Individuals with psoriasis or psoriatic arthritis have a slightly higher risk of heart disease and heart attacks when compared to the general population. Cardiovascular disease risk appeared to be correlated with the severity of psoriasis and its duration. There is no strong evidence to suggest that psoriasis is associated with an increased risk of death from cardiovascular events. Methotrexate may provide a degree of protection for the heart.The odds of having hypertension are 1.58 times ( i.e. 58%) higher in people with psoriasis than those without the condition; these odds are even higher with severe cases of psoriasis. A similar association was noted in people who have psoriatic arthritis—the odds of having hypertension were found to be 2.07 times ( i.e. 107%) greater when compared to odds of the general population. The link between psoriasis and hypertension is not currently understood. Mechanisms hypothesized to be involved in this relationship include the following: dysregulation of the renin–angiotensin system, elevated levels of endothelin 1 in the blood, and increased oxidative stress. The number of new cases of the heart rhythm abnormality atrial fibrillation is 1.31 times ( i.e. 31%) higher in people with mild psoriasis and 1.63 times ( i.e. 63%) higher in people with severe psoriasis. There may be a slightly increased risk of stroke associated with psoriasis, especially in severe cases. Treating high levels of cholesterol with statins has been associated with decreased psoriasis severity, as measured by PASI score, and has also been associated with improvements in other cardiovascular disease risk factors such as markers of inflammation. These cardioprotective effects are attributed to ability of statins to improve blood lipid profile and because of their anti-inflammatory effects. Statin use in those with psoriasis and hyperlipidemia was associated with decreased levels of high-sensitivity C-reactive protein and TNFα as well as decreased activity of the immune protein LFA-1. Compared to individuals without psoriasis, those affected by psoriasis are more likely to satisfy the criteria for metabolic syndrome. Other diseases The rates of Crohn disease and ulcerative colitis are increased when compared with the general population, by a factor of 3.8 and 7.5 respectively. People with psoriasis also have a higher risk of celiac disease. Few studies have evaluated the association of multiple sclerosis with psoriasis, and the relationship has been questioned. Psoriasis has been associated with a 16% increase in overall relative risk for non-skin cancer, thought to be attributed to systemic therapy, particularly methotrexate. People treated with long term systemic therapy for psoriasis have a 52% increased risk cancers of the lung and bronchus, a 205% increase in the risk of developing cancers of the upper gastrointestinal tract, a 31% increase in the risk of developing cancers of the urinary tract, a 90% increase in the risk of developing liver cancer, and a 46% increase in the risk of developing pancreatic cancer. The risk for development of non-melanoma skin cancers is also increased. Psoriasis increases the risk of developing squamous cell carcinoma of the skin by 431% and increases the risk of basal cell carcinoma by 100%. There is no increased risk of melanoma associated with psoriasis. People with psoriasis have a higher risk of developing cancer. Epidemiology Psoriasis is estimated to affect 2–4% of the population of the western world. The rate of psoriasis varies according to age, region and ethnicity; a combination of environmental and genetic factors is thought to be responsible for these differences. It can occur at any age, although it most commonly appears for the first time between the ages of 15 and 25 years. Approximately one third of people with psoriasis report being diagnosed before age 20. Psoriasis affects both sexes equally.Psoriasis affects about 6.7 million Americans and occurs more frequently in adults.Psoriasis is about five times more common in people of European descent than in people of Asian descent.People with inflammatory bowel disease such as Crohn disease or ulcerative colitis are at an increased risk of developing psoriasis. Psoriasis is more common in countries farther from the equator. Persons of white European ancestry are more likely to have psoriasis and the condition is relatively uncommon in African Americans and extremely uncommon in Native Americans. History Scholars believe psoriasis to have been included among the various skin conditions called tzaraath (translated as leprosy) in the Hebrew Bible, a condition imposed as a punishment for slander. The person was deemed "impure" (see tumah and taharah) during their affected phase and is ultimately treated by the kohen. However, it is more likely that this confusion arose from the use of the same Greek term for both conditions. The Greeks used the term lepra (λεπρα) for scaly skin conditions. They used the term psora to describe itchy skin conditions. It became known as Willans lepra in the late 18th century when English dermatologists Robert Willan and Thomas Bateman differentiated it from other skin diseases. Leprosy, they said, is distinguished by the regular, circular form of patches, while psoriasis is always irregular. Willan identified two categories: leprosa graecorum and psora leprosa.Psoriasis is thought to have first been described in Ancient Rome by Cornelius Celsus. The British dermatologist Thomas Bateman described a possible link between psoriasis and arthritic symptoms in 1813.The history of psoriasis is littered with treatments of dubious effectiveness and high toxicity. In the 18th and 19th centuries, Fowlers solution, which contains a poisonous and carcinogenic arsenic compound, was used by dermatologists as a treatment for psoriasis. Mercury was also used for psoriasis treatment during this time period. Sulfur, iodine, and phenol were also commonly used treatments for psoriasis during this era when it was incorrectly believed that psoriasis was an infectious disease. Coal tars were widely used with ultraviolet light irradiation as a topical treatment approach in the early 1900s. During the same time period, psoriatic arthritis cases were treated with intravenously administered gold preparations in the same manner as rheumatoid arthritis. Society and culture The International Federation of Psoriasis Associations (IFPA) is the global umbrella organization for national and regional psoriasis associations and also gathers the leading experts in psoriasis and psoriatic arthritis research for scientific conferences every three years. The Psoriasis International Network, a program of the Fondation René Touraine, gathers dermatologists, rheumatologists and other caregivers involved in the management of psoriasis. Non-profit organizations like the National Psoriasis Foundation in the United States, the Psoriasis Association in the United Kingdom, and Psoriasis Australia offer advocacy and education about psoriasis in their respective countries. Cost The annual cost for treating psoriasis in the United States is estimated as high as $32.5 billion, including $12.2 billion in direct costs. Pharmacy costs are the main source of direct expense, with biologic therapy the most prevalent. These costs increase significantly when co-morbid conditions such as heart disease, hypertension, diabetes, lung disease and psychiatric disorders are factored in. Expenses linked to co-morbidities are estimated at an additional $23,000 per person per year. Research The role of insulin resistance in the pathogenesis of psoriasis is under investigation. Preliminary research has suggested that antioxidants such as polyphenols may have beneficial effects on the inflammation characteristic of psoriasis.Many novel medications being researched during the 2010s target the Th17/IL-23 axis, particularly IL-23p19 inhibitors, as IL-23p19 is present in increased concentrations in psoriasis skin lesions while contributing less to protection against opportunistic infections. Other cytokines such as IL-17 and IL-22 also have been targets for inhibition as they play important roles in the pathogenesis of psoriasis. Another avenue of research has focused on the use of vascular endothelial growth factor inhibitors to treat psoriasis. Oral agents being investigated during the 2010s as alternatives to medications administered by injection include Janus kinase inhibitors, protein kinase C inhibitors, mitogen-activated protein kinase inhibitors, and phosphodiesterase 4 inhibitors, all of which have proven effective in various phase 2 and 3 clinical trials. These agents have potentially severe side-effects due to their immunosuppressive mechanisms. References Further reading External links "Psoriatic arthritis". Genetics Home Reference. "Psoriasis". MedlinePlus. U.S. National Library of Medicine.
Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly	Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly is a rare hereditary autosomal recessive malformation syndrome of the central nervous system characterized by profound motor delays and intellectual disabilities, progressive microcephaly, hypertonia, spasticity, clonus and epilepsy. MRI findings include severe cerebellar and cerebral deterioration (atrophy) and impaired myelination. This condition is an example of consequences from the Founder effect, especially that of Jewish populations.It has been described in 5 infants from 4 Israeli families of ethnic Caucasus Jewish descent. The genetic cause was found to be a homozygous mutation of the MED17 gene, located in chromosome 11, this mutation is called L371P.In vitro functional expression assays of the L371P mutation showed that it results in a functionally inactive MED17 protein. == References ==
Guillain–Barré syndrome	Guillain–Barré syndrome (GBS) is a rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system. Typically, both sides of the body are involved, and the initial symptoms are changes in sensation or pain often in the back along with muscle weakness, beginning in the feet and hands, often spreading to the arms and upper body. The symptoms may develop over hours to a few weeks. During the acute phase, the disorder can be life-threatening, with about 15% of people developing weakness of the breathing muscles and, therefore, requiring mechanical ventilation. Some are affected by changes in the function of the autonomic nervous system, which can lead to dangerous abnormalities in heart rate and blood pressure.Although the cause is unknown, the underlying mechanism involves an autoimmune disorder in which the bodys immune system mistakenly attacks the peripheral nerves and damages their myelin insulation. Sometimes this immune dysfunction is triggered by an infection or, less commonly, by surgery, and rarely, by vaccination. The diagnosis is usually based on the signs and symptoms through the exclusion of alternative causes and supported by tests such as nerve conduction studies and examination of the cerebrospinal fluid. There are a number of subtypes based on the areas of weakness, results of nerve conduction studies, and the presence of certain antibodies. It is classified as an acute polyneuropathy.In those with severe weakness, prompt treatment with intravenous immunoglobulins or plasmapheresis, together with supportive care, will lead to good recovery in the majority of cases. Recovery may take weeks to years, with about a third having some permanent weakness. Globally, death occurs in approximately 7.5% of those affected. Guillain–Barré syndrome is rare, at 1 or 2 cases per 100,000 people every year. Both sexes and all parts of the world have similar rates of disease.The syndrome is named after the French neurologists Georges Guillain and Jean Alexandre Barré, who, together with French physician André Strohl, described the condition in 1916. Signs and symptoms The first symptoms of Guillain–Barré syndrome are numbness, tingling, and pain, alone or in combination. This is followed by weakness of the legs and arms that affects both sides equally and worsens over time. The weakness can take half a day to over two weeks to reach maximum severity, and then becomes steady. In one in five people, the weakness continues to progress for as long as four weeks. The muscles of the neck may also be affected, and about half experience involvement of the cranial nerves that supply the head and face; this may lead to weakness of the muscles of the face, swallowing difficulties and sometimes weakness of the eye muscles. In 8%, the weakness affects only the legs (paraplegia or paraparesis). Involvement of the muscles that control the bladder and anus is unusual. In total, about a third of people with Guillain–Barré syndrome continue to be able to walk. Once the weakness has stopped progressing, it persists at a stable level ("plateau phase") before improvement occurs. The plateau phase can take between two days and six months, but the most common duration is a week. Pain-related symptoms affect more than half, and include back pain, painful tingling, muscle pain, and pain in the head and neck relating to irritation of the lining of the brain.Many people with Guillain–Barré syndrome have experienced the signs and symptoms of an infection in the 3–6 weeks before the onset of the neurological symptoms. This may consist of upper respiratory tract infection (rhinitis, sore throat), or diarrhea. In children, particularly those younger than six years old, the diagnosis can be difficult and the condition is often initially mistaken (sometimes for up to two weeks) for other causes of pains and difficulty walking, such as viral infections, or bone and joint problems.On neurological examination, characteristic features are the reduced strength of muscles and reduced or absent tendon reflexes (hypo- or areflexia, respectively). However, a small proportion have normal reflexes in affected limbs before developing areflexia, and some may have exaggerated reflexes. In the Miller Fisher variant of Guillain–Barré syndrome (see below), a triad of weakness of the eye muscles, abnormalities in coordination, as well as absent reflexes can be found. The level of consciousness is normally unaffected in Guillain–Barré syndrome, but the Bickerstaff brainstem encephalitis subtype may feature drowsiness, sleepiness, or coma. Respiratory failure A quarter of all people with Guillain–Barré syndrome develop weakness of the breathing muscles leading to respiratory failure, the inability to breathe adequately to maintain healthy levels of oxygen, and/or carbon dioxide in the blood. This life-threatening scenario is complicated by other medical problems such as pneumonia, severe infections, blood clots in the lungs, and bleeding in the digestive tract in 60% of those who require artificial ventilation. Autonomic dysfunction The autonomic or involuntary nervous system, which is involved in the control of body functions such as heart rate and blood pressure, is affected in two-thirds of people with Guillain–Barré syndrome, but the impact is variable. Twenty percent may experience severe blood-pressure fluctuations and irregularities in the heart beat, sometimes to the point that the heart beat stops and requires pacemaker-based treatment. Other associated problems are abnormalities in perspiration and changes in the reactivity of the pupils. Autonomic nervous system involvement can affect even those who do not have severe muscle weakness. Causes Infection onset Two-thirds of people with Guillain–Barré syndrome have experienced an infection before the onset of the condition. Most commonly, these are episodes of gastroenteritis or a respiratory tract infection. In many cases, the exact nature of the infection can be confirmed. Approximately 30% of cases are provoked by Campylobacter jejuni bacteria, which cause diarrhea. A further 10% are attributable to cytomegalovirus (CMV, HHV-5). Despite this, only very few people with Campylobacter or CMV infections develop Guillain–Barré syndrome (0.25–0.65 per 1000 and 0.6–2.2 per 1000 episodes, respectively). The strain of Campylobacter involved may determine the risk of GBS; different forms of the bacteria have different lipopolysaccharides on their surface, and some may induce illness (see below) while others will not.Links between other infections and GBS are less certain. Two other herpes viruses (Epstein–Barr virus/HHV-4 and varicella zoster virus/HHV-3) and the bacterium Mycoplasma pneumoniae have been associated with GBS. GBS is known to occur after influenza, and influenza vaccination has been demonstrated to be associated with a reduced risk. The tropical flaviviral infections dengue fever and Zika virus have also been associated with episodes of GBS. Previous hepatitis E virus infection has been found to be more common in people with GBS. Vaccine onset An increased incidence of Guillain–Barré syndrome followed influenza immunization that followed the 1976 swine flu outbreak (H1N1 A/NJ/76); 8.8 cases per million (0.0088 per 1000) recipients developed it as a complication. GBS cases occurred in 362 patients during the 6 weeks after influenza vaccination of 45 million persons, an 8.8-fold increase over normal rates. The 1976 swine flu vaccination-induced GBS was an outlier; small increases in incidence have been observed in subsequent vaccination campaigns, but not to the same extent. The 2009 flu pandemic vaccine against pandemic swine flu virus H1N1/PDM09 did not cause a significant increase in cases. In fact, "studies found a small increase of approximately 1 case per million vaccines above the baseline rate, which is similar to that observed after administration of seasonal influenza vaccines over the past several years." The benefits to the population as a whole of vaccination in preventing influenza outweigh the small risks to individuals of that group of GBS after vaccination. Natural influenza infection is a stronger risk factor for the development of GBS than is influenza vaccination and the vaccination reduced the risk of GBS overall by lowering the risk of catching influenza.In the United States, GBS after seasonal influenza vaccination is listed on the federal governments vaccine injury table. On March 24, 2021, after reviewing several post-marketing observational studies, where an increased risk of Guillain–Barré syndrome was observed after 42 days following vaccination with the Zoster vaccine Shingrix, the FDA required safety label changes from the manufacturer GlaxoSmithKline to include warnings for risk of Guillain–Barré syndrome. COVID-19 infection or vaccine related GBS has been reported in association with COVID-19, and may be a potential neurological complication of the disease. GBS has been reported as a very rare side effect of the Janssen and the Oxford–AstraZeneca COVID-19 vaccine for COVID-19 and European Medicines Agency (EMA) had issued warning to the patients and healthcare providers. The incidence of GBS following the vaccination with the Oxford-AstraZeneca vaccine was originally reported as being lower than the incidence of GBS following a COVID-19 infection. More recent studies, however, found no measurable link between COVID-19 infection and GBS, while correlations with a first dose of AstraZeneca or Janssen vaccines were still positive.COVID-19 has been reported as causing peripheral neuropathy and more recently some evidence of aggravation of autoimmune disorders including GBS. Some studies are now finding Parkinsons Disease is more common in infection survivors. Drug induced Zimelidine, an antidepressant, had a very favorable safety profile but as a result of rare case reports of Guillain–Barré syndrome was withdrawn from the market. Mechanism The nerve dysfunction in Guillain–Barré syndrome is caused by an immune attack on the nerve cells of the peripheral nervous system and their support structures. The nerve cells have their body (the soma) in the spinal cord and a long projection (the axon) that carries electrical nerve impulses to the neuromuscular junction, where the impulse is transferred to the muscle. Axons are wrapped in a sheath of Schwann cells that contain myelin. Between Schwann cells are gaps (nodes of Ranvier) where the axon is exposed. Different types of Guillain–Barré syndrome feature different types of immune attack. The demyelinating variant (AIDP, see below) features damage to the myelin sheath by white blood cells (T lymphocytes and macrophages); this process is preceded by activation of a group of blood proteins known as complement. In contrast, the axonal variant is mediated by IgG antibodies and complement against the cell membrane covering the axon without direct lymphocyte involvement.Various antibodies directed at nerve cells have been reported in Guillain–Barré syndrome. In the axonal subtype, these antibodies have been shown to bind to gangliosides, a group of substances found in peripheral nerves. A ganglioside is a molecule consisting of ceramide bound to a small group of hexose-type sugars and containing various numbers of N-acetylneuraminic acid groups. The key four gangliosides against which antibodies have been described are GM1, GD1a, GT1a, and GQ1b, with different antiganglioside antibodies being associated with particular features; for instance, GQ1b antibodies have been linked with Miller Fisher variant GBS and related forms including Bickerstaff encephalitis. The production of these antibodies after an infection probably is the result of molecular mimicry, where the immune system is reacting to microbial substances, but the resultant antibodies also react with substances occurring naturally in the body. After a Campylobacter infection, the body produces antibodies of the IgA class; only a small proportion of people also produce IgG antibodies against bacterial substance cell wall substances (e.g. lipooligosaccharides) that cross react with human nerve cell gangliosides. It is not currently known how this process escapes central tolerance to gangliosides, which is meant to suppress the production of antibodies against the bodys own substances. Not all antiganglioside antibodies cause disease, and it has recently been suggested that some antibodies bind to more than one type of epitope simultaneously (heterodimeric binding) and that this determines the response. Furthermore, the development of pathogenic antibodies may depend on the presence of other strains of bacteria in the bowel.It has been suggested that a poor injection technique may also cause a direct injury to the axillary nerves adjacent to the injection site in deltoid muscle that may lead to peripheral neuropathy. The consequent vaccine transfection and translation in the nerves may spur an immune response against nerve cells potentially causing an autoimmune nerve damage, leading to conditions like Guillain–Barré syndrome. Diagnosis The diagnosis of Guillain–Barré syndrome depends on findings such as rapid development of muscle paralysis, absent reflexes, absence of fever, and absence of a likely cause. Cerebrospinal fluid analysis (through a lumbar spinal puncture) and nerve conduction studies are supportive investigations commonly performed in the diagnosis of GBS. Testing for antiganglioside antibodies is often performed, but their contribution to diagnosis is usually limited. Blood tests are generally performed to exclude the possibility of another cause for weakness, such as a low level of potassium in the blood. An abnormally low level of sodium in the blood is often encountered in Guillain–Barré syndrome. This has been attributed to the inappropriate secretion of antidiuretic hormone, leading to relative retention of water.In many cases, magnetic resonance imaging of the spinal cord is performed to distinguish between Guillain–Barré syndrome and other conditions causing limb weakness, such as spinal cord compression. If an MRI scan shows enhancement of the nerve roots, this may be indicative of GBS. In children, this feature is present in 95% of scans, but it is not specific to Guillain–Barré syndrome, so other confirmation is also needed. Spinal fluid Cerebrospinal fluid envelops the brain and the spine, and lumbar puncture or spinal tap is the removal of a small amount of fluid using a needle inserted between the lumbar vertebrae. Characteristic findings in Guillain–Barré syndrome are an elevated protein level, usually greater than 0.55 g/L, and fewer than 10 white blood cells per cubic millimeter of fluid ("albuminocytological dissociation"). This pattern distinguishes Guillain–Barré syndrome from other conditions (such as lymphoma and poliomyelitis) in which both the protein and the cell count are elevated. Elevated CSF protein levels are found in approximately 50% of patients in the first 3 days after onset of weakness, which increases to 80% after the first week.Repeating the lumbar puncture during the disease course is not recommended. The protein levels may rise after treatment has been administered. Neurophysiology Directly assessing nerve conduction of electrical impulses can exclude other causes of acute muscle weakness, as well as distinguish the different types of Guillain–Barré syndrome. Needle electromyography (EMG) and nerve conduction studies may be performed. In the first two weeks, these investigations may not show any abnormality. Neurophysiology studies are not required for the diagnosis.Formal criteria exist for each of the main subtypes of Guillain–Barré syndrome (AIDP and AMAN/AMSAN, see below), but these may misclassify some cases (particularly where there is reversible conduction failure) and therefore changes to these criteria have been proposed. Sometimes, repeated testing may be helpful. Clinical subtypes A number of subtypes of Guillain–Barré syndrome are recognized. Despite this, many people have overlapping symptoms that can make the classification difficult in individual cases. All types have partial forms. For instance, some people experience only isolated eye-movement or coordination problems; these are thought to be a subtype of Miller Fisher syndrome and have similar antiganglioside antibody patterns. Other diagnostic entities are often included in the spectrum of Guillain–Barré syndrome. Bickerstaffs brainstem encephalitis (BBE), for instance, is part of the group of conditions now regarded as forms of Miller Fisher syndrome (anti-GQ1b antibody syndrome), as well as a related condition labelled "acute ataxic hypersomnolence" where coordination problems and drowsiness are present but no muscle weakness can be detected. BBE is characterized by the rapid onset of ophthalmoplegia, ataxia, and disturbance of consciousness, and may be associated with absent or decreased tendon reflexes and as well as Babinskis sign. The course of the disease is usually monophasic, but recurrent episodes have been reported. MRI abnormalities in the brainstem have been reported in 11%.Whether isolated acute sensory loss can be regarded as a form of Guillain–Barré syndrome is a matter of dispute; this is a rare occurrence compared to GBS with muscle weakness but no sensory symptoms. Treatment Immunotherapy Plasmapheresis and intravenous immunoglobulins (IVIG) are the two main immunotherapy treatments for GBS. Plasmapheresis attempts to reduce the bodys attack on the nervous system by filtering antibodies out of the bloodstream. Similarly, administration of IVIG neutralizes harmful antibodies and inflammation. These two treatments are equally effective, but a combination of the two is not significantly better than either alone. Plasmapheresis speeds recovery when used within four weeks of the onset of symptoms. IVIG works as well as plasmapheresis when started within two weeks of the onset of symptoms, and has fewer complications. IVIG is usually used first because of its ease of administration and safety; the risks include occasionally causing liver inflammation, or in rare cases, kidney failure. Glucocorticoids alone have not been found to be effective in speeding recovery and could potentially delay recovery. Respiratory failure Respiratory failure may require intubation of the trachea and breathing support through mechanical ventilation, generally on an intensive care unit. The need for ventilatory support can be anticipated by measurement of two spirometry-based breathing tests: the forced vital capacity (FVC) and the negative inspiratory force (NIF). An FVC of less than 15 mL per kilogram body weight or an NIF of less than 60 cmH2O are considered markers of severe respiratory failure. Pain While pain is common in people with Guillain–Barré syndrome, studies comparing different types of pain medication are insufficient to make a recommendation as to which should be used. Rehabilitation Following the acute phase, around 40% of people require intensive rehabilitation with the help of a multidisciplinary team to focus on improving activities of daily living (ADLs). Studies into the subject have been limited, but it is likely that intensive rehabilitation improves long-term symptoms. Teams may include physical therapists, occupational therapists, speech language pathologists, social workers, psychologists, other allied health professionals and nurses. The team usually works under the supervision of a neurologist or rehabilitation physician directing treatment goals.Physiotherapy interventions include strength, endurance, and gait training with graduated increases in mobility, maintenance of posture and alignment as well as joint function. Occupational therapy aims to improve everyday function with domestic and community tasks as well as driving and work. Home modifications, gait aids, orthotics, and splints may be provided. Speech-language pathology input may be required in those with speech and swallowing problems, as well as to support communication in those who require ongoing breathing support (often through a tracheostomy). Nutritional support may be provided by the team and by dietitians. Psychologists may provide counseling and support. Psychological interventions may also be required for anxiety, fear, and depression. Prognosis Guillain–Barré syndrome can lead to death as a result of many complications: severe infections, blood clots, and cardiac arrest likely due to autonomic neuropathy. Despite optimum care, this occurs in about 5% of cases.There is a variation in the rate and extent of recovery. The prognosis of Guillain–Barré syndrome is determined mainly by age (those over 40 may have a poorer outcome), and by the severity of symptoms after two weeks. Furthermore, those who experienced diarrhea before the onset of the disease have a worse prognosis. On the nerve conduction study, the presence of conduction block predicts poorer outcome at 6 months. In those who have received intravenous immunoglobulins, a smaller increase in IgG in the blood two weeks after administration is associated with poorer mobility outcomes at six months than those whose IgG level increased substantially. If the disease continues to progress beyond four weeks, or there are multiple fluctuations in the severity (more than two in eight weeks), the diagnosis may be chronic inflammatory demyelinating polyneuropathy, which is treated differently.In research studies, the outcome from an episode of Guillain–Barré syndrome is recorded on a scale from 0 to 6, where 0 denotes completely healthy; 1 very minor symptoms but able to run; 2 able to walk but not to run; 3 requiring a stick or other support; 4 confined to bed or chair; 5 requiring long-term respiratory support; 6 death.The health-related quality of life (HRQL) after an attack of Guillain–Barré syndrome can be significantly impaired. About a fifth are unable to walk unaided after six months, and many experience chronic pain, fatigue and difficulty with work, education, hobbies and social activities. HRQL improves significantly in the first year. Epidemiology In Western countries, the number of new episodes per year has been estimated to be between 0.89 and 1.89 cases per 100,000 people. Children and young adults are less likely to be affected than the elderly: the relative risk increases by 20% for every decade of life. Men are more likely to develop Guillain–Barré syndrome than women; the relative risk for men is 1.78 compared to women.The distribution of subtypes varies between countries. In Europe and the United States, 60–80% of people with Guillain–Barré syndrome have the demyelinating subtype (AIDP), and AMAN affects only a small number (6–7%). In Asia and Central and South America, that proportion is significantly higher (30–65%). This may be related to the exposure to different kinds of infection, but also the genetic characteristics of that population. Miller Fisher variant is thought to be more common in Southeast Asia. History Jean-Baptiste Octave Landry first described the disorder in 1859. In 1916, Georges Guillain, Jean Alexandre Barré, and André Strohl diagnosed two soldiers with the illness and described the key diagnostic abnormality—albuminocytological dissociation—of increased spinal fluid protein concentration but a normal cell count.C. Miller Fisher described the variant that bears his name in 1956. British neurologist Edwin Bickerstaff described the encephalitis type in 1951 and made further contributions with another paper in 1957. Guillain had reported on some of these features before their full description in 1938. Further subtypes have been described since then, such as the form featuring pure ataxia and the type causing pharyngeal-cervical-brachial weakness. The axonal subtype was first described in 1986.Diagnostic criteria were developed in the late 1970s after the series of cases associated with swine flu vaccination. These were refined in 1990. The case definition was revised by the Brighton Collaboration for vaccine safety in 2009, but is mainly intended for research. Plasma exchange was first used in 1978, and its benefit was confirmed in larger studies in 1985. Intravenous immunoglobulins were introduced in 1988, and studies in the early 1990s demonstrated that they were no less effective than plasma exchange. Research directions The understanding of the disease mechanism of Guillain–Barré syndrome has evolved in recent years. Development of new treatments has been limited since immunotherapy was introduced in the 1980s and 1990s. Current research is aimed at demonstrating whether some people who have received IVIg might benefit from a second course if the antibody levels measured in blood after treatment have shown only a small increase. Studies of the immunosuppressive drugs mycophenolate mofetil, brain-derived neurotrophic factor and interferon beta (IFN-β) have not demonstrated benefit to support their widespread use.An animal model (experimental autoimmune neuritis in rats) is often used for studies, and some agents have shown promise: glatiramer acetate, quinpramine, fasudil (an inhibitor of the Rho-kinase enzyme), and the heart drug flecainide. An antibody targeted against the anti-GD3 antiganglioside antibody has shown benefit in laboratory research. Given the role of the complement system in GBS, it has been suggested that complement inhibitors (such as the drug eculizumab) may be effective. In animals it is called acute polyradiculoneuritis or "coonhound paralysis", and may onset in the coonhound 7 to 10 days after transmission from raccoons. If the coonhound has not been around raccoons, the disease is called acute idiopathic polyradiculoneuritis. References Further reading Steinberg GJ, Parry JS (2006). Guillain–Barré syndrome: from diagnosis to recovery. New York: Demos; ANN Press (American Academy of Neurology). ISBN 9781932603569. == External links ==
Phacodonesis	Phacodonesis (; from Ancient Greek φακός (phakos) lens, and δονέω (doneo) to shake) is the tremulousness or vibration of the lens with eye movement. This is often due to lens subluxation, the incomplete or partial dislocation of the lens, caused by an injury to the eye in which some or most of the zonular fibers are broken. See also Iridodonesis References External links An example of phacodonesis on YouTube
Trisomy 22	Trisomy 22 is a chromosomal disorder in which three copies of chromosome 22 are present rather than two. It is a frequent cause of spontaneous abortion during the first trimester of pregnancy. Progression to the second trimester and live birth are rare. This disorder is found in individuals with an extra copy or a variation of chromosome 22 in some or all cells of their bodies. Associated disorders Many kinds of disorders are associated with trisomy 22: Emanuel syndrome is named after the genetic contributions made by researcher Dr. Beverly Emanuel. This condition is assigned to individuals born with an unbalanced 11/22 translocation. That is, a fragment of chromosome 11 is moved, or translocated, to chromosome 22. 22q11 deletion syndrome is a rare condition which occurs in about one in 4000 births. This condition is identified when a band in the q11.2 section of the arm of chromosome 22 is missing or deleted. This condition has several different names: 22q11.2 deletion syndrome, velocardiofacial syndrome, DiGeorge syndrome, conotruncal anomaly face syndrome, Opitz G/BBB syndrome, and Cayler cardiofacial syndrome. The effects of this disorder are different in each individual, but similarities exist, such as heart defects, immune system problems, a distinctive facial appearance, learning challenges, cleft palate, hearing loss, kidney problems, hypocalcemia, and sometimes psychiatric issues. 22q11 microduplication syndrome is the opposite of the 22q11 deletion syndrome; in this condition, a band of q.11.2 section of chromosome 22 is duplicated. Individuals carrying this deficiency are relatively "normal", as in they do not possess any major birth defects or major medical illnesses. This microduplication is more common than the deletion; this might relate to the milder phenotype of the individuals. 22q13 deletion syndrome (Phelan–McDermid syndrome) is a condition caused by the deletion of the tip of the q arm on chromosome 22. Most individuals with this disorder experience cognitive delays, low muscle tone, and sleeping, eating, and behavioural issues. Chromosome ring 22 is a rare disorder caused by the break and rejoining of both ends of chromosome 22, forming a ring. The effects on the individual with this disorder are dependent on the amount of genetic information lost during the process. Major characteristics for this disorder are intellectual disability, muscle weakness, and lack of coordination. Cat eye syndrome (Schmid Fraccaro syndrome) is a condition caused by a partial trisomy or tetrasomy in chromosome 22. A small extra chromosome is found, made up of the top half of chromosome 22 and a portion of the q arm at the q11.2 break. This chromosome can be found three or four times. This syndrome is referred as "cat eye" due to the eye appearance of reported affected individuals who have coloboma of the iris, but this feature is only seen in about half of the cases. Mosaic trisomy 22 is a disorder in which an extra chromosome 22 is found only in some cells of the body. The severity of each case is determined by the number of cells with this extra copy. Some characteristics of individuals with this condition are cardiac abnormalities, growth retardation, mental delay, etc. Complete trisomy 22, in contrast with mosaic trisomy 22, is characterized by an extra copy of chromosome 22 found in each cell of the body of the affected individual. As of 2014, 29 live-born human cases have been reported, with all of them dying before the age of 12 months. References Further reading Mokate T, Leask K, Mehta S, et al. (2006). "Non-mosaic trisomy 22: a report of 2 cases". Prenat. Diagn. 26 (10): 962–5. doi:10.1002/pd.1537. PMID 16906599. S2CID 43499352. External links Humpath 6236
Aortopulmonary window	Aortopulmonary window (APW) refers to a congenital heart defect similar in some ways to persistent truncus arteriosus. Persistent truncus arteriosus involves a single valve; aortopulmonary window is a septal defect.A large number of patients with a large APW usually die within 1 year of age. It is extremely rare to find cases of APW surviving till adult age and it is still rare to surgically treat such patients who are incidentally detected in adult age because such subsets of patients invariably have associated pulmonary vascular obstructive disease in advanced stage and thus there is therapeutic dilemma to surgically correct these patients.Although cases of uncorrected APW presenting in adulthood have been reported but literature on surgically treated AP window in adult populations is limited. A rare case of successful surgical management of an incidentally detected large APW with reversible pulmonary arterial hypertension has been reported as isolated case reports. See also Aortic window Major aortopulmonary collateral artery, developes when native pulmonary circulation is underdeveloped References == External links ==
Carnosinemia	Carnosinemia is a rare autosomal recessive metabolic disorder caused by a deficiency of carnosinase, a dipeptidase (a type of enzyme that splits dipeptides into their two amino acid constituents).Carnosine is a dipeptide composed of beta-alanine and histidine, and is found in skeletal muscle and cells of the nervous system. This disorder results in an excess of carnosine in the urine, cerebrospinal fluid, blood, and nervous tissue. Neurological disorders associated with a deficiency of carnosinase, and the resulting carnosinemia ("carnosine in the blood") are common. Symptoms and signs A variety of neurological symptoms have been associated with carnosinemia. They include: hypotonia, developmental delay, intellectual disability, degeneration of axons, sensory neuropathy, tremors, demyelinization, gray matter anomalies, myoclonic seizures, and loss of purkinje fibers. Genetics The gene for carnosinase is located on chromosome 18, an autosome. The carnosine dipeptidase-1 gene (CNDP1) controls tissue and serum carnosinase. Mutations in CNDP1 are responsible for carnosinase deficiency, resulting in carnosinemia.Carnosinemia is an autosomal recessive disorder, which means the defective gene is located on an autosome, and two copies of the defective gene - one from each parent - are required to inherit 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 Types Carnosinase in humans has two forms:1. Cellular, or tissue carnosinase: This form of the enzyme is found in every bodily tissue. It is a dimer, and hydrolyzes both carnosine and anserine, preferring dipeptides that have a histidine monomer in the C-terminus position. Tissue carnosinase is often considered a "nonspecific dipeptidase", based in part on its ability to hydrolyze a range of dipeptide substrates, including those belonging to prolinase.2. Serum carnosinase: This is the carnosinase found in the blood plasma. Deficiency of this form of carnosinase, along with carnosinuria ("carnosine in the urine"), is the usual metabolic indicator of systemic carnosinase deficiency. Serum carnosinase is a glycoprotein, and splits free carnosine and anserine in the blood. This form of the dipeptidase is not found in human blood until late infancy, slowly rising to adult levels by age 15. Unlike tissue carnosinase, serum carnosinase also hydrolyzes the GABA metabolite homocarnosine. Homocarnosinosis, a neurological disorder resulting in an excess of homocarnosine in the brain, though unaffected by tissue carnosinase, is caused by a deficiency of serum carnosinase in its ability to hydrolyze homocarnosine.A deficiency of tissue and serum carnosinase, with serum being an indicator, is the underlying metabolic cause of carnosinemia. Treatment See also Histidinemia Hyperprolinemia Inborn errors of metabolism Proline References == External links ==
Tenosynovitis	Tenosynovitis is the inflammation of the fluid-filled sheath (called the synovium) that surrounds a tendon, typically leading to joint pain, swelling, and stiffness. Tenosynovitis can be either infectious or noninfectious. Common clinical manifestations of noninfectious tenosynovitis include de Quervain tendinopathy and stenosing tenosynovitis (more commonly known as trigger finger) Signs and symptoms Infectious tenosynovitis occurs between 2.5% and 9.4% of all hand infections. Kanavels cardinal signs is used to diagnose infectious tenosynovitis. They are: tenderness to touch along the flexor aspect of the finger, fusiform enlargement of the affected finger, the finger being held in slight flexion at rest, and severe pain with passive extension. Fever may also be present but is uncommon. Pathogenesis Infectious tenosynovitis is the infection of closed synovial sheaths in the flexor tendons of the fingers. It is usually caused by trauma, but bacteria can spread from other sites of the body. Although tenosynovitis usually affects the flexor tendon of the fingers, the disease can also affect the extensor tendons occasionally. The clinical presentation is therefore as acute infection following trauma. The infection can be mono- or polymicrobial and can vary depending on the nature of the trauma. The most common pathogenic agent is Staphylococcus aureus introduced from the skin. Other bacteria linked to infectious tenosynovitis include Pasteurella multocida (associated with animal bites), Eikenella spp. (associated with IV drug use), and Mycobacterium marinum (associated with wounds exposed to fresh or salt water). Additionally, sexually active patients are at risk for hematogenous spread due to Neisseria gonorrhoeae (see infectious arthritis). Common noninfectious tenosynovitis are: stenosing tenosynovitis, intersection syndrome, extensor pollicis longus (EPL) tenosynovitis, de Quervains and fourth compartment tenosynovitis. Diagnosis Diagnosis of tenosynovitis is typically made clinically after a thorough patient history and physical exam. Aspirated fluid can also be cultured to identify the infectious organism. X-rays are typically unremarkable but can help rule out a broken bone or a foreign body Treatment The mainstay of treatment for infectious tenosynovitis includes symptom relief, antibiotic therapy, and surgery. Early recognition of the disease with early initiation of antibiotics are important for better range of movement of the affected finger. Minimally invasive procedures into the flexor tendon sheath such as catheter irrigation give better outcomes (74% chance of good outcome) when compared to open surgery (26% chance of good outcome). However, wound irrigation with antibiotics has no clear benefits. Most infectious tenosynovitis cases should be managed with tendon sheath irrigation and drainage, with or without debridement of surrounding necrotic tissue, along with treatment with broad-spectrum antibiotics. In severe cases, amputation may even be necessary to prevent the further spread of infection. Following surgical intervention, antibiotic therapy is continued and adjusted based on the results of the fluid culture. Prognosis The earlier the condition is identified, the better the chance of getting full range of motion of the finger. However, finger stiffness, Boutonniere deformity, deep space infection, tendon necrosis, adhesions, persistent infection, and need for amputation of the finger can occur. Tendon adhesion and finger stiffness are caused by the violation of the flexor tendon sheath. See also Synovitis DeQuervains syndrome Remitting seronegative symmetrical synovitis with pitting edema Notes External links http://orthoinfo.aaos.org MediLine Plus
Chromosome abnormality	A chromosomal abnormality, chromosomal anomaly, chromosomal aberration, chromosomal mutation, or chromosomal disorder, is a missing, extra, or irregular portion of chromosomal DNA. These can occur in the form of numerical abnormalities, where there is an atypical number of chromosomes, or as structural abnormalities, where one or more individual chromosomes are altered. Chromosome mutation was formerly used in a strict sense to mean a change in a chromosomal segment, involving more than one gene. Chromosome anomalies usually occur when there is an error in cell division following meiosis or mitosis. Chromosome abnormalities may be detected or confirmed by comparing an individuals karyotype, or full set of chromosomes, to a typical karyotype for the species via genetic testing. Numerical abnormality An abnormal number of chromosomes is called aneuploidy, and occurs when an individual is either missing a chromosome from a pair (resulting in monosomy) or has more than two chromosomes of a pair (trisomy, tetrasomy, etc.). Aneuploidy can be full, involving a whole chromosome missing or added, or partial, where only part of a chromosome is missing or added. Aneuploidy can occur with sex chromosomes or autosomes.An example of trisomy in humans is Down syndrome, which is a developmental disorder caused by an extra copy of chromosome 21; the disorder is therefore also called trisomy 21.An example of monosomy in humans is Turner syndrome, where the individual is born with only one sex chromosome, an X. Sperm aneuploidy Exposure of males to certain lifestyle, environmental and/or occupational hazards may increase the risk of aneuploid spermatozoa. In particular, risk of aneuploidy is increased by tobacco smoking, and occupational exposure to benzene, insecticides, and perfluorinated compounds. Increased aneuploidy is often associated with increased DNA damage in spermatozoa. Structural abnormalities When the chromosomes structure is altered, this can take several forms: Deletions: A portion of the chromosome is missing or has been deleted. Known disorders in humans include Wolf–Hirschhorn syndrome, which is caused by partial deletion of the short arm of chromosome 4; and Jacobsen syndrome, also called the terminal 11q deletion disorder. Duplications: A portion of the chromosome has been duplicated, resulting in extra genetic material. Known human disorders include Charcot–Marie–Tooth disease type 1A, which may be caused by duplication of the gene encoding peripheral myelin protein 22 (PMP22) on chromosome 17. Inversions: A portion of the chromosome has broken off, turned upside down, and reattached, therefore the genetic material is inverted. Insertions: A portion of one chromosome has been deleted from its normal place and inserted into another chromosome. Translocations: A portion of one chromosome has been transferred to another chromosome. There are two main types of translocations: Reciprocal translocation: Segments from two different chromosomes have been exchanged. Robertsonian translocation: An entire chromosome has attached to another at the centromere - in humans, these only occur with chromosomes 13, 14, 15, 21, and 22. Rings: A portion of a chromosome has broken off and formed a circle or ring. This can happen with or without the loss of genetic material. Isochromosome: Formed by the mirror image copy of a chromosome segment including the centromere.Chromosome instability syndromes are a group of disorders characterized by chromosomal instability and breakage. They often lead to an increased tendency to develop certain types of malignancies. Inheritance Most chromosome abnormalities occur as an accident in the egg cell or sperm, and therefore the anomaly is present in every cell of the body. Some anomalies, however, can happen after conception, resulting in Mosaicism (where some cells have the anomaly and some do not). Chromosome anomalies can be inherited from a parent or be "de novo". This is why chromosome studies are often performed on parents when a child is found to have an anomaly. If the parents do not possess the abnormality it was not initially inherited; however, it may be transmitted to subsequent generations. Acquired chromosome abnormalities Most cancers, if not all, could cause chromosome abnormalities, with either the formation of hybrid genes and fusion proteins, deregulation of genes and overexpression of proteins, or loss of tumor suppressor genes (see the "Mitelman Database" and the Atlas of Genetics and Cytogenetics in Oncology and Haematology,). Furthermore, certain consistent chromosomal abnormalities can turn normal cells into a leukemic cell such as the translocation of a gene, resulting in its inappropriate expression. DNA damage during spermatogenesis During the mitotic and meiotic cell divisions of mammalian gametogenesis, DNA repair is effective at removing DNA damages. However, in spermatogenesis the ability to repair DNA damages decreases substantially in the latter part of the process as haploid spermatids undergo major nuclear chromatin remodeling into highly compacted sperm nuclei. As reviewed by Marchetti et al., the last few weeks of sperm development before fertilization are highly susceptible to the accumulation of sperm DNA damage. Such sperm DNA damage can be transmitted unrepaired into the egg where it is subject to removal by the maternal repair machinery. However, errors in maternal DNA repair of sperm DNA damage can result in zygotes with chromosomal structural aberrations.Melphalan is a bifunctional alkylating agent frequently used in chemotherapy. Meiotic inter-strand DNA damages caused by melphalan can escape paternal repair and cause chromosomal aberrations in the zygote by maternal misrepair. Thus both pre- and post-fertilization DNA repair appear to be important in avoiding chromosome abnormalities and assuring the genome integrity of the conceptus. Detection Depending on the information one wants to obtain, different techniques and samples are needed. For the prenatal diagnosis of a foetus, amniocentesis, chorionic villus sampling or circulating foetal cells would be collected and analysed in order to detect possible chromosomal abnormalities. For the preimplantational diagnosis of an embryo, a blastocyst biopsy would be performed. For a lymphoma or leukemia screening the technique used would be a bone marrow biopsy. See also Aneuploidy Chromosome segregation Genetic disorder List of genetic disorders Gene therapy Nondisjunction Obstetrical complications References External links Chromosome+disorders at the US National Library of Medicine Medical Subject Headings (MeSH)
Trematoda	Trematoda is a class within the phylum Platyhelminthes. It includes two groups of parasitic flatworms, known as flukes. They are internal parasites of molluscs and vertebrates. Most trematodes have a complex life cycle with at least two hosts. The primary host, where the flukes sexually reproduce, is a vertebrate. The intermediate host, in which asexual reproduction occurs, is usually a snail. Taxonomy and biodiversity The trematodes or flukes include 18,000 to 24,000 species, divided into two subclasses. Nearly all trematodes are parasites of mollusks and vertebrates. The smaller Aspidogastrea, comprising about 100 species, are obligate parasites of mollusks and may also infect turtles and fish, including cartilaginous fish. The Digenea, the majority of trematodes, are obligate parasites of both mollusks and vertebrates, but rarely occur in cartilaginous fish. Two other parasitic classes, the Monogenea and Cestoda, are sister classes in the Neodermata, a group of Rhabditophoran Platyhelminthes.Flukes can be classified into two groups based on, the system in which they infect their vertebrate host. They may also be classified according to the environment in which they are found. For instance, pond flukes infect fish in ponds. Tissue flukes infect the bile ducts, lungs, or other biological tissues. This group includes the lung fluke, Paragonimus westermani, and the liver flukes, Clonorchis sinensis and Fasciola hepatica. Blood flukes inhabit the blood in some stages of their life cycle. Blood flukes include species of the genus Schistosoma.Lung flukes: there are eight species of lung flukes that infect humans: Paragonimus westermani, P. heterotremus, P. skryabini, P. miyazakii, P. africanus, P. uterobilateralis, P. kellicotti, and P. mexicanus. Paragonimus westermani needs three different hosts in order to survive, reproduce, and complete its life cycle. The completion of a lung flukes life cycle follows the cycle of first, second, and final hosts. The first intermediate host of the lung fluke is a snail, the second intermediate host is a crab or crayfish, and the final host for lung flukes is an animal or human host.Liver flukes: include Clonorchis, Opisthorchis, and Fasciola. Clonorchis and Opisthorchis are considered the most important human pathogens because they are classified as class 1 carcinogens. Liver flukes are commonly found within bile ducts, liver, and gallbladder in mammalian and avian species. There are high numbers of human infection with all three of these liver flukes.Blood flukes: include five species of Schistosoma: Schistosoma japonicum, S. mekongi, S. mansoni, S. haematobium, and S. intercalatum. Humans get infected by the cercariae, which are the larval forms of trematodes. Any contact with water can cause potential human infection. Adult blood flukes can live indefinitely in human or animal reservoir hosts. Anatomy Trematodes are flattened oval or worm-like animals, usually no more than a few centimeters in length, although species as small as 1 millimetre (0.039 in) are known. Their most distinctive external feature is the presence of two suckers, one close to the mouth, and the other on the underside of the animal.The body surface of trematodes comprises a tough syncytial tegument, which helps protect against digestive enzymes in those species that inhabit the gut of larger animals. It is also the surface of gas exchange; there are no respiratory organs.The mouth is located at the forward end of the animal, and opens into a muscular, pumping pharynx. The pharynx connects, via a short oesophagus, to one or two blind-ending caeca, which occupy most of the length of the body. In some species, the caeca are themselves branched. As in other flatworms, there is no anus, and waste material must be egested through the mouth.Although the excretion of nitrogenous waste occurs mostly through the tegument, trematodes do possess an excretory system, which is instead mainly concerned with osmoregulation. This consists of two or more protonephridia, with those on each side of the body opening into a collecting duct. The two collecting ducts typically meet up at a single bladder, opening to the exterior through one or two pores near the posterior end of the animal.The brain consists of a pair of ganglia in the head region, from which two or three pairs of nerve cords run down the length of the body. The nerve cords running along the ventral surface are always the largest, while the dorsal cords are present only in the Aspidogastrea. Trematodes generally lack any specialized sense organs, although some ectoparasitic species do possess one or two pairs of simple ocelli. Reproductive system Most trematodes are simultaneous hermaphrodites, having both male and female organs. Blood flukes are the only form of trematodes that are not hermaphrodites, meaning they have both a male and female sex. Blood flukes are unique in the way that they can reproduce sexually and asexually. In order for the reproduction of blood flukes to occur asexually, infecting a freshwater snail must happen to act as an intermediate host. Acting as an intermediate host, an organism that supports non-reproductive parasites, allows for the blood flukes to gather nourishment to reproduce. The asexual reproduction takes place in the hepatopancreas of the snail. Reproduction of blood flukes sexually involves finding a mammal host to act as an intermediate host to support their nutritional needs.The reproductive system of trematodes usually consist of having two testes, which are found posterior and dorsal to the ventral sucker. Having sperm ducts that join together on the underside of the front half of the animal. This final part of the male system varies considerably in structure between species, but may include sperm storage sacs and accessory glands, in addition to the copulatory organ, which is either eversible, and termed a cirrus, or non-eversible, and termed a penis.There is usually only a single ovary. Eggs pass from it into an oviduct. The distal part of the oviduct, called ootype, is dilated. It is connected via a pair of ducts to a number of vitelline glands on either side of the body, that produce yolk cells. After the egg is surrounded by yolk cells, its shell is formed from the secretion of another gland called Mehlis gland or shell gland, the duct of which also opens in the ootype. The ootype is connected to an elongated uterus that opens to the exterior in the genital pore, close to the male opening. Most commonly found in trematodes, the sperm cells travel through the uterus to reach the ootype, where fertilization occurs. The ovary is sometimes also associated with a storage sac for sperm, and a copulatory duct termed Laurers canal. Laurer’s canal is described to be the primitive vagina but it is a vestigial organ in some species. In some instances it can serve as a tube outside the worm for potential waste products from the egg-formation system. Organ morphology Body wall musculature: Formed of three different muscle layers: circular, longitudinal, and diagonal. The outermost layer is formed by the circular muscle fibers, directly behind that are the longitudinal muscle fibers. The inner layer is formed by the diagonal muscle fibers. Together these muscle fibers form the segmented body wall of trematodes.Oral sucker and acetabulum: In some species of Trematoda, such as T. bragai, there is an acetabulum. This saucer-shaped organ is attached to the oral sucker in some Trematodes and other parasitic worms. This allows for parasitic worms to attach to their host by penetrating the host’s tissue with spines lining the acetabulum organ. In trematodes, the oral sucker is linked to the pharynx via a canal composed of meridional, equatorial, and radial muscle fibers. Together, the mouth, pharynx, and esophagus form the foregut in Trematodes.Male reproductive system: The male reproductive system generally includes two testes, while some species may have more. Along with this, the size and position of the testes in the body may vary depending on the species. Due to this species-level variation, the male reproductive system can be very useful in species identification. Sperm production, or spermatogenesis, occurs in the testes. Spermatogenesis in Trematodes produces biflagellate sperm or sperm with two tails. This phenomenon occurs across very few invertebrate and vertebrate species. Sperm is stored in the seminal vesicle, this organ is connected to the testes by the vas deferens.Female reproductive system: The female reproductive system consists of one ovary in Trematodes. The location of the ovary varies between species, making the female reproductive system useful in species identification. The oocytes are released from the ovary via the oocapt, from here, the stored sperm in the seminal vesicles will meet with the oocyte. In the Mehlis’ gland, the oocyte and sperm will be joined and start developing. As the embryo is forming, the vitelline ducts will begin to release materials that will be used to create the eggshell around the embryo. Finally, the Laurers’ canal will lead outside of the body. The egg can be released from the body, this canal can also serve as a way to expel excess stored sperm. Life cycles Trematodes have a very complex life cycle and depending on what taxa they belong to, their life cycles can be completed with as little as one host compared to the typical three hosts. When there is one host, this is normally a specific species of snail of the family Lymnaeidae. Almost all trematodes infect molluscs as the first host in the life cycle, and most have a complex life cycle involving other hosts. Most trematodes are monoecious and alternately reproduce sexually and asexually. The two main exceptions to this are the Aspidogastrea, which have no asexual reproduction, and the schistosomes, which are dioecious. In the definitive host, in which sexual reproduction occurs, eggs are commonly shed along with host feces. Eggs shed in water release free-swimming larval forms (Miracidia) that are infective to the intermediate host, in which asexual reproduction occurs. A species that exemplifies the remarkable life history of the trematodes is the bird fluke, Leucochloridium paradoxum. The definitive hosts, in which the parasite reproduces, are various woodland birds, while the hosts in which the parasite multiplies (intermediate host) are various species of snail. The adult parasite in the birds gut produces eggs and these eventually end up on the ground in the birds feces. Some eggs may be swallowed by a snail and hatch into larvae (miracidia). These larvae grow and take on a sac-like appearance. This stage is known as the sporocyst and it forms a central body in the snails digestive gland that extends into a brood sac in the snails head, muscular foot and eye-stalks. It is in the central body of the sporocyst where the parasite replicates itself, producing many tiny embryos (redia). These embryos move to the brood sac and mature into cercaria. Life cycle adaptations Trematodes have a large variation of forms throughout their life cycles. Individual trematode parasites life cycles may vary from this list. They have five larval stages along with the cystic and fully matured adult phases. Trematodes are released from the definitive host as eggs, which have evolved to withstand the harsh environment Released from the egg which hatches into the miracidium. This infects the first intermediate host in one of two ways, either active or passive transmission. The first host is normally a mollusk. a) Active transmission has adapted for dispersal in space as a free swimming ciliated miracidium with adaptations for recognizing and penetrating the first intermediate host. b) Passive transmission has adapted for dispersal in time and infects the first intermediate host contained within the egg. The sporocyst forms inside the snail first intermediate host and feeds through diffusion across the tegument. The rediae also forms inside the snail first intermediate host and feeds through a developed pharynx. Either the rediae or the sporocyst develops into the cercariae through polyembryony in the snail. The cercariae are adapted for dispersal in space and exhibit a large variety in morphology. They are adapted to recognize and penetrate the second intermediate host, and contain behavioral and physiological adaptations not present in earlier life stages. The metacercariae are an adapted cystic form dormant in the secondary intermediate host. The adult is the fully developed form which infects the definitive host.The first stage is the miracidium that is triangular in shape and covered by a ciliated ectoderm which is the outermost layer of the three germ layers. The epidermis and epidemic tissues of the parasite are going to evolve from the miracidium. They also have an anterior spin which helps them drill into the snail. The miracidium develops into the sporocyst, which is a sac-like structure, and in this sac the larvae begin to develop. The cells multiply. The rediae and cercariae develop from the larvae which are then released and encyst as metacercariae on aquatic plants. Humans as well as larger sea creatures then get infected when they eat these plants. When they infect humans, it takes 3–4 months for the metacercariae to mature into adult flukes and lay eggs. Life cycle of liver flukes Liver flukes, one of the different species, are responsible for causing liver fluke disease which is also known as fasciolosis. They are hermaphroditic internal parasites. They are caused by the migration of a large number of immature flukes through the liver passageway or by adult flukes that migrate to the bile ducts. Liver flukes infect all grazing animals and are passed from human to human when they eat raw or undercooked fish. Like other flukes, the liver flukes need intermediate hosts and as a result, the transmission from animals to humans happens in three phases. The first phase is the infection of the snail (the first intermediate host) via feces. They complete their gestation and hatch as cercariae. They leave their snail hosts and infect fish who are their second intermediate host. Lastly, humans ingest the metacercariae in raw and undercooked fish. In humans, the metacercariae complete their life cycle and become full grown liver flukes. Infections Human infections are most common in Asia, Africa and Latin America. However, trematodes can be found anywhere where untreated human waste is used as fertilizer. Humans can be infected by trematodes either by consuming undercooked contaminated fish or plants, or by ingesting contaminated water. The metacercariae of trematodes attach to fish and plants. In addition, humans can be infected by certain species through swimming in contaminated water. Humans cannot get infected by trematodes directly, trematodes require an intermediate host to do so.Schistosomiasis (also known as bilharzia, bilharziosis or snail fever) is an example of a parasitic disease caused by one of the species of trematodes (platyhelminth infection, or "flukes"), a parasitic worm of the genus Schistosoma. Clonorchis, Opisthorchis, Fasciola and Paragonimus species, the foodborne trematodes, are another. Other diseases are caused by members of the genus Choledocystus. Medically, trematodes are often classed by which organ they invade, which can include blood vessels, the gastrointestinal tract, lungs, or liver. In many cases, eggs from the trematodes can often be found in stool months after infection.Depending on the type of infection, the drugs Ppraziquantel and Ttriclabendazole are used to eradicate the trematodes in humans. Animal infections Humans are not the only creatures that can be infected with trematodes. They can infect dogs, cats, reptiles, and many more vertebrates. One of the most common victims of trematodes are ruminants. Similarly to humans, cattle and sheep can get infected by trematodes by eating contaminated food. When a ruminant is infected by a trematode, the infection leads to less milk or meat production, which has become an issue in cattle and other livestock industries. Etymology Trematodes are commonly referred to as flukes. This term can be traced back to the Old English name for flounder, and refers to the flattened, rhomboidal shape of the worms. The flukes can be classified into two groups based on, on the basis of the system in which they infect their in the vertebrate host. They may also be classified according to the environment in which they are found. For instance, pond flukes infect fish in ponds. Tissue flukes infect the bile ducts, lungs, or other biological tissues. This group includes the lung fluke, Paragonimus westermani, and the liver flukes, Clonorchis sinensis and Fasciola hepatica. Blood flukes inhabit the blood in some stages of their life cycle. Blood flukes include species of the genus Schistosoma. References External links Earthlife BioLib ZipcodeZoo
Pneumonic plague	Pneumonic plague is a severe lung infection caused by the bacterium Yersinia pestis. Symptoms include fever, headache, shortness of breath, chest pain, and coughing. They typically start about three to seven days after exposure. It is one of three forms of plague, the other two being septicemic plague and bubonic plague.The pneumonic form may occur following an initial bubonic or septicemic plague infection. It may also result from breathing in airborne droplets from another person or animal infected with pneumonic plague. The difference between the forms of plague is the location of infection; in pneumonic plague the infection is in the lungs, in bubonic plague the lymph nodes, and in septicemic plague within the blood. Diagnosis is by testing the blood, sputum, or fluid from a lymph node.While vaccines are being developed, in most countries they are not yet commercially available. Prevention is by avoiding contact with infected rodents, people, or cats. It is recommended that those infected be isolated from others. Treatment of pneumonic plague is with antibiotics.Plague is present among rodents in Africa, the Americas, and Asia. Pneumonic plague is more serious and less common than bubonic plague. The total reported number of cases of all types of plague in 2013 was 783. Left untreated, pneumonic plague is nearly always fatal. Some hypothesize that the pneumonic version of the plague was mainly responsible for the Black Death that resulted in approximately 75 - 200 million deaths in the 1300s. Signs and symptoms The most apparent symptom of pneumonic plague is coughing, often with hemoptysis (coughing up blood). With pneumonic plague, the first signs of illness are fever, headache, weakness and rapidly developing pneumonia with shortness of breath, chest pain, cough and sometimes bloody or watery sputum.The pneumonia progresses for two to four days and may cause respiratory failure and shock. Patients will die without early treatment, some within 36 hours. Initial pneumonic plague symptoms can often include the following: Fever Weakness Headaches NauseaRapidly developing pneumonia with: Shortness of breath Chest pain Cough Bloody or watery sputum (saliva and discharge from respiratory passages). Causes Pneumonic plague can be caused in two ways: primary, which results from the inhalation of aerosolized plague bacteria, or secondary, when septicemic plague spreads into lung tissue from the bloodstream. Pneumonic plague is not exclusively vector-borne like bubonic plague; instead, it can be spread from person to person. There have been cases of pneumonic plague resulting from the dissection or handling of contaminated animal tissue. This is one of the types of plague formerly known as the Black Death. Treatment Pneumonic plague is a very aggressive infection requiring early treatment, which must be given within 24 hours of first symptoms to reduce the risk of death. Streptomycin, gentamicin, tetracyclines and chloramphenicol are all able to kill the causative bacterium. Antibiotic treatment for seven days will protect people who have had direct, close contact with infected patients. Wearing a close-fitting surgical mask also protects against infection.The mortality rate from untreated pneumonic plague approaches 100%. Modern outbreaks Since 2002, the World Health Organization (WHO) has reported seven plague outbreaks, though some may go unreported because they often happen in remote areas. Between 1998 and 2009, nearly 24,000 cases have been reported, including about 2,000 deaths, in Africa, Asia, the Americas, and Eastern Europe. Ninety-eight percent of the worlds cases occur in Africa. Democratic Republic of the Congo Two outbreaks occurred in the Democratic Republic of the Congo in 2005 and 2006. The outbreak in 2005 was only detected by looking back at blood samples. India In September 1994, India experienced an outbreak of plague that killed 50 and caused travel to New Delhi by air to be suspended until the outbreak was brought under control. The outbreak was feared to be much worse because the plague superficially resembles other common diseases such as influenza and bronchitis; over 200 people that had been quarantined were released when they did not test positive for the plague. All but two of the deaths occurred around the city of Surat. China A major outbreak of the pneumonic plague occurred in Manchuria from 1910 to 1911, in what became known as the Manchurian plague, killing around 60,000 people. The Qing court dispatched Wu Lien-teh, a doctor educated at Cambridge University, to oversee disease control and treatment efforts. He made the novel observation that the disease was transmitted by air, and developed prototypical respirators to help prevent its spread. A second, less deadly outbreak occurred in 1920–21, killing approximately 9,300 people.The Peoples Republic of China has eradicated pneumonic plague from most parts of the country, but still reports occasional cases in remote western areas, where the disease is carried by rats and the marmots that live across the Himalayan plateau. Outbreaks can be caused when a person eats an infected marmot or comes into contact with fleas carried by rats. A 2006 WHO report from an international meeting on plague cited a Chinese government disease expert as saying that most cases of the plague in Chinas northwest occur when hunters are contaminated while skinning infected animals.The expert said at the time that, due to the regions remoteness, the disease killed more than half the infected people. The report also said that since the 1990s, there was a rise in plague cases in humans—from fewer than 10 in the 1980s to nearly 100 cases in 1996 and 254 in 2000. In September 2008, two people in East Tibet died of pneumonic plague.An outbreak of the disease in China began in August 2009 in Ziketan Town located in Qinghai Province. The town was sealed off and several people died as a result of the disease. According to spokesperson Vivian Tan of the WHO office in Beijing, "In cases like this [in August 2009], we encourage the authorities to identify cases, to investigate any suspicious symptoms among close contacts, and to treat confirmed cases as soon as possible. So far, they have done exactly that. There have been sporadic cases reported around the country in the last few years so the authorities do have the experience to deal with this."In September 2010, five cases of pneumonic plague were reported in Tibet.In July 2014, Chinese media reported one case found in Gansu.On 12 November 2019, It was announced that two people from the Chinese province of Inner Mongolia were diagnosed with pneumonic plague. They received treatment in Chaoyang District, Beijing, and authorities implemented preventative control measures. Later in November, a third case of plague was confirmed. A 55-year-old man was diagnosed with bubonic plague after eating wild rabbit in Inner Mongolia. The regions health commission says it has no evidence to suggest that this case is linked to the previous two. By the end of November, a fourth case was confirmed. Chinese health authorities reported a fresh case of bubonic plague in the countrys northern Inner Mongolia region, bringing the total number of reported plague cases originating from Inner Mongolia to four. Peru In August 2010, Perus health minister Oscar Ugarte announced that an outbreak of plague had killed a 14-year-old boy and had infected at least 31 people in a northern coastal province. The boy died of bubonic plague on 26 July 2010. Ugarte stated that authorities were screening sugar and fish meal exports from Ascope Province, located about 325 miles (520 km) northwest of Lima, not far from the popular Chicama beach. Most of the infections in Peru were bubonic plague, with four cases of pneumonic plague.The first recorded plague outbreak in Peru was in 1903. Prior to the above case, the last known outbreak was in 1994, killing 35 people. Madagascar In November 2013, an outbreak of plague occurred in the African island nation of Madagascar. As of 16 December, at least 89 people were infected, with 39 deaths with at least two cases involving pneumonic plague. However, as many as 90% of cases were later reported to have involved pneumonic plague.From 23 August to 30 September 2017, a total of 73 suspected, probable, and confirmed cases of pneumonic plague, including 17 deaths, were reported in Madagascar. The diagnosis was confirmed by the Institut Pasteur de Madagascar by a polymerase chain reaction test, while field health workers used a Rapid Diagnostic Test. The WHO and Institut Pasteur de Madagascar were both involved in administering antibiotic compounds and attempting to stop the spread of the disease. By mid-October, there were an estimated 684 confirmed cases of plague with 474 pneumonic, 156 bubonic and one septicemic. The remainder were not classified. At least 74 deaths have been ascribed to pneumonic plague.The outbreak officially ended on 26 November 2017 with 2,348 cases and 202 deaths officially reported. United States In the fall of 1924, an outbreak occurred in Los Angeles that killed 30 people. On 2 November 2007, wildlife biologist Eric York died of pneumonic plague in Grand Canyon National Park. York was exposed to the bacteria while conducting a necropsy on a cougar carcass.In 2014, the Colorado Department of Public Health and Environment confirmed that a Colorado man had been diagnosed with pneumonic plague, the first confirmed human case in Colorado in more than 10 years, and one of only 60 cases since 1957. The man was found to have the disease after the family dog died unexpectedly and a necropsy revealed that the disease was the cause. Three additional pneumonic plague cases were confirmed in Colorado before the outbreak ended. References External links Media related to Pneumonic plague at Wikimedia Commons Frequently Asked Questions \| Plague \| CDC. Centers for Disease Control and Prevention.
Congenital erosive and vesicular dermatosis	Congenital erosive and vesicular dermatosis is a cutaneous condition characterized by generalized erosions, vesicles, crusting and ‘scalded skin-like’ erythematous areas affecting up to 75% of the body surface area. See also Melanotic neuroectodermal tumor of infancy List of cutaneous conditions == References ==
Hypertropia	Hypertropia is a condition of misalignment of the eyes (strabismus), whereby the visual axis of one eye is higher than the fellow fixating eye. Hypotropia is the similar condition, focus being on the eye with the visual axis lower than the fellow fixating eye. Dissociated vertical deviation is a special type of hypertropia leading to slow upward drift of one or rarely both eyes, usually when the patient is inattentive. Presentation Associated defects Refractive errors such as hyperopia and anisometropia may be associated abnormalities found in patients with vertical strabismus. The vertical miscoordination between the two eyes may lead to Strabismic amblyopia, (due to deprivation / suppression of the deviating eye) cosmetic defect (most noticed by parents of a young child and in photographs) Face turn, depending on presence of binocular vision in a particular gaze diplopia or double vision - more seen in adults (maturity / plasticity of neural pathways) and suppression mechanisms of the brain in sorting out the images from the two eyes. cyclotropia, a cyclotorsional deviation of the eyes (rotation around the visual axis), particularly when the root cause is an oblique muscle paresis causing the hypertropia. Causes Hypertropia may be either congenital or acquired, and misalignment is due to imbalance in extraocular muscle function. The superior rectus, inferior rectus, superior oblique, and inferior oblique muscles affect the vertical movement of the eyes. These muscles may be either paretic, restrictive (fibrosis) or overactive effect of the muscles. Congenital cases may have developmental abnormality due to abnormal muscle structure, usually muscle atrophy / hypertrophy or rarely, absence of the muscle and incorrect placement. Specific & common causes include: Superior oblique Palsy / Congenital fourth nerve palsy Inferior oblique overaction Browns syndrome Duanes retraction syndrome Double elevator palsy Fibrosis of rectus muscle in Graves Disease (most commonly inferior rectus is involved) Surgical trauma to the vertical muscles (e.g. during scleral buckling surgery or cataract surgery causing iatrogenic trauma to the vertical muscles).Sudden onset hypertropia in a middle aged or elderly adult may be due to compression of the trochlear nerve and mass effect from a tumor, requiring urgent brain imaging using MRI to localise any space occupying lesion. It could also be due to infarction of blood vessels supplying the nerve, due to diabetes and atherosclerosis. In other instances it may be due to an abnormality of neuromuscular transmission, i.e., Myasthenia Gravis. Treatment In general, strabismus can be approached and treated with a variety of procedures. Depending on the individual case, treatment options include: Correction of refractive errors by glasses Prism therapy (if tolerated, to manage diplopia) Vision Therapy Patching (mainly to manage amblyopia in children and diplopia in adults) Botulinum toxin injection Surgical correctionSurgical correction of the hypertropia is desired to achieve binocularity, manage diplopia and/or correct the cosmetic defect. Steps to achieve the same depend on mechanism of the hypertropia and identification of the offending muscles causing the misalignment. Various surgical procedures have been described and should be offered after careful examination of eyes, including a detailed orthoptic examination focussing on the disturbances in ocular motility and visual status. Specialty fellowship trained pediatric ophthalmologists and strabismus surgeons are best equipped to deal with these complex procedures. See also List of systemic diseases with ocular manifestations References == External links ==
Peripheral ulcerative keratitis	Peripheral Ulcerative Keratitis (PUK) is a group of destructive inflammatory diseases involving the peripheral cornea in human eyes. The symptoms of PUK include pain, redness of the eyeball, photophobia, and decreased vision accompanied by distinctive signs of crescent-shaped damage of the cornea. The causes of this disease are broad, ranging from injuries, contamination of contact lenses, to association with other systemic conditions. PUK is associated with different ocular and systemic diseases. Moorens ulcer is a common form of PUK. The majority of PUK is mediated by local or systemic immunological processes, which can lead to inflammation and eventually tissue damage. Standard PUK diagnostic test involves reviewing the medical history and a completing physical examinations. Two major treatments are the use of medications such as corticosteroids or other immunosuppressive agents and surgical resection of the conjunctiva. The prognosis of PUK is unclear with one study providing potential complications. PUK is a rare condition with an estimated incidence of 3 per million annually. Signs and symptoms The most easily identifiable sign is a visible lesion of the cornea presented usually in a crescent shape. Common reasons for destruction are stromal degradation and epithelial defects on the inflammatory cells. There would be a change in conformation of the peripheral cornea, depending on the severity of corneal thinning. This process is usually accompanied by the possibility of concealing perforation. The formation of an oval-shaped ulcer at the margin of the cornea is also a sign.Symptoms of PUK include pain, redness, tearing, increased sensitivity to bright light, impaired or blurred vision, and the feeling of foreign objects trapped in the eyes. Association There are several associations of PUK to ocular and systemic diseases. Rheumatoid arthritis (RA), Wegners granulomatosis (WG), and Polyarteritis Nodosa (PAN) are the most common systemic conditions. Rheumatoid arthritis: Approximately 50% of PUK are related to collagen vascular diseases, in which RA is the most common category. Around 34-42% of PUK patients have RA. Wegners granulomatosis: WG is a rare autoimmune disease associated with PUK. It causes vasculitis of the lower and upper respiratory tracts, and it also affects multiple organs, including eyes. Without timely initiation of systemic therapy, WG patients will develop conjunctival and scleral inflammations. The inflammation will eventually cause corneal thinning and worsen PUK. Polyarteritis Nodosa: PAN is another autoimmune disease in which the bodys immune system attacks small and medium-sized arteries of its own by mistake. PUK is one of the predominant ocular inflammatory manifestations of PAN. Causes There are three major causes for PUK. One possible cause is injury due to any kind of scratches by sharp or hard objects on the surface of the cornea. The scratched area forms an opening in the cornea, allowing microorganisms to access the cornea and lead to infection. Contamination of contact lenses is another cause as fungi, bacteria and parasites, microscopic parasite acanthamoeba, in particular, could inhabit the surface of the carrying case of the contact lens. When placing the contact lens to ones eyes, invisible microorganisms may contaminate the cornea resulting in PUK. An extended period of wearing contact lenses could also cause damage on the cornea surface, allowing the entry of microorganisms to the cornea. Other than contamination of contact lenses, contamination occurring in water could also cause PUK. Especially in places like the ocean, rivers, lakes and hot tubs, massive amounts of bacteria, fungi, and parasites exist. When there is an injury on the cornea surface, contact with contaminated water could transfer unwanted microorganisms into the cornea resulting in PUK. Virus and bacteria are sources of infection to the cornea. Herpes virus and bacteria that cause gonorrhea are some examples. Anatomy and pathogenesis The corneal epithelium consists of five to six layers of cells with a total thickness of around 0.52mm. The cornea thickens to 0.65mm towards the periphery of the cornea. Stroma, which accounts for 90% of the corneal thickness, refers to the middle layer between epithelium and endothelium. It is present in the peripheral cornea to act as a transitional zone between the sclera and cornea. Limbal vasculature, deriving from capillaries that surround the peripheral cornea, supplies the stroma. Various molecules normally diffuse from these capillaries at the periphery to the central cornea. With limited diffusion, there is a higher concentration of IgM, factor C1 of the complement cascade, and Langerhans cells. Any kind of inflammatory stimulus present in the peripheral cornea results in recruitment of neutrophil and activation of both classical and alternative pathways of immune response, namely the humoral and cell-mediated autoimmune responses. These responses will lead to the formation of antigen-specific antibodies to combat foreign antigens. However, antigen-antibody complexes formed may deposit in the vascular endothelium and activate complements leading to severe local inflammation. Under this circumstance, inflammatory cells, such as macrophages and neutrophils, enter the peripheral cornea. These inflammatory cells release enzymes protease and collagenases, causing potential disruption of the corneal stroma. The additional release of cytokines, for example, interleukin-1, from these cells further accelerates the process of stromal destruction. Moorens ulcer and relevant classification Moorens ulcer is a common form of PUK. One classification of Moorens ulcer, based on the clinical presentation, includes bilateral indolent moorens ulcer, bilateral aggressive moorens ulcer and unilateral moorens ulcer. Unilateral moorens ulcer, meaning ulcer of one eye, mainly affects elderly above 60 years old. Rapid onset with redness and severe pain of the affected eye and either slow or extremely quick progression are some typical characteristics of unilateral moorens ulcer. Bilateral aggressive moorens ulcer is prevalent in Indian between age 14 to 40. The common presentation includes the appearance of lesions in one eye, followed by the development of lesions in another eye. Finally, bilateral indolent moorens ulcer is common in patients of at least 50-year-old. It usually progresses slowly and causes little or no pain.Other classification methods also exist. The first one is classifying Moorens ulcers based on clinical presentation and prognosis into two categories. The first type is usually presented unilaterally, accompanied by symptoms ranging from mild to moderate. Therefore, it has a more effective response to treatment. In contrast, type II appears in a bilateral manner, with severe symptoms and poor outcome of treatment. The second classification is based on severity. Grade I refers to corneal thinning, grade II describes impending corneal perforation, and grade III is corneal perforation with a diameter greater than 2mm. Diagnosis There are many investigative modalities available for diagnosing PUK, including history review and physical examination. A thorough history of ocular infections, contact lens usage, other medication, or surgery is necessary to identify possible presence of associated diseases. An ophthalmic examination helps identify whether it is due to local pathogenesis. Physical examinations allow more understanding of the underlying systemic process.A standard testing procedure includes hematological investigations, immunological testing, followed by chest X-ray. Hematological investigations are blood tests estimating hemoglobin, platelet counts, total white blood cell counts, erythrocyte sedimentation rate and viscosity. Other common body checks include urinalysis and liver and renal function tests. The selection of immunological testing for various markers is based on numerous additional medical examinations and clinical history of the patient. Possible markers are antinuclear antibodies, anti-rheumatoid antibodies, and antibodies to cyclic citrullinated peptides. Finally, a chest X-ray helps distinguish whether there are complications, such as pulmonary diseases, due to systemic conditions associated with PUK.One of the common causes of PUK is ocular infections by microorganisms such as bacteria, viruses, and fungi. To detect the causative microorganism, doctors usually collect samples before the commencement of therapy and send them to laboratories. Laboratory personnel then perform smear examination, inoculate the samples on culture media, and perform serological testing. Serological testing is an antibody test providing information on PUK etiology. The diagnosis of PUK due to systemic conditions requires a combination of serological and hematological testing, together with imaging techniques such as radiography and CT scanning. Treatments Various PUK therapies are of different objectives, for example, inflammation control, halting of disease progression, stroma repairment, avoidance of secondary complications, and vision restoration. A thorough understanding of PUK and different therapies is important. Medical and surgical treatments are two major approaches to manage PUK. Medical therapy As for medical therapy, there are several types of drugs available for PUK. Topical corticosteroids usually serve as therapy for milder unilateral cases of RA-associated PUK. Systemic corticosteroids in the form of an oral dose are the acute management of more severe cases. However, there are side effects with prolonged usage of oral corticosteroids. Immunosuppressive agents, such as azathioprine, cyclophosphamide, and methotrexate, have demonstrated efficacy in treating inflammatory eye diseases, including PUK. The combined therapy of systemic corticosteroids up to 100 mg/day and immunosuppressive agents are used for severe cases of PUK. Biological agents, such as anti-tissue necrosis factors (anti-TNF), is a well-established treatment of systemic inflammatory diseases, Infliximab and Adalimumab are TNF blockers for treating RA-associated PUK. However, the high cost and uncertainty of long-term side effects are the possible drawbacks. Surgical treatment In terms of surgical treatment, conjunctival resection is a common procedure, which can temporarily remove local inflammatory mediators and collagenases and therefore slow down the disease progression. Other surgical management includes corneal gluing, or keratoplasty procedures. Corneal transplantation is a management option when there is severe corneal melting or perforation although one possible disadvantage is the risk of rejection.Surgical treatment helps maintain the integrity of the globe, but it is usually complementary because it alone cannot influence the underlying immunological process. Therefore, medical and surgical treatments are commonly used in conjunction. Choice of treatment The choice of treatment may be different depending on the nature of PUK, infectious or noninfectious. Selection of the right targeted antimicrobial therapy for infectious PUK is based on clinical judgement and culture results. For example, the appropriate treatment for bacterial infections is antibiotics, such as fluoroquinolones. As for Moorens ulcers, 56% of unilateral PUK and 50% of bilateral PUK in one eye showed recovery with intensive topical steroids. Only 18% of patients with bilateral ulcers occurring simultaneously in both eyes show improvements with topical steroids alone; therefore a combination of immunosuppressive agents and systemic steroids should be given in early courses of management. Corticosteroids are the first line of therapy, but side effects may arise from long-term usage. In addition, conjunctival resection can be performed to temporarily remove local inflammatory mediators, followed by the use of immunosuppressants. Prognosis Currently, there are limited studies regarding the prognosis of PUK. However, one study has pointed out possible complications surrounding PUK include moderate to severe vision loss, corneal perforation and increased risk of recurrence. Epidemiology PUK is a rare condition with an estimated incidence of 3 per million annually. Studies have reported that most patients with PUK are older than 60 years of age (32%). Among them, men have a higher occurrence rate in men (60%). Most patients live in rural areas (66%) and are in the lower socioeconomic groups. The age of those with PUK ranges from 5 to 89 years, with a mean age of 45.5 years.The mortality rate after PUK diagnosis in an investigation of 34 patients with and without immunosuppressive medication is 53% and 5%, respectively. Another single-centre study involving 46 patients with RA reported a mortality rate of 15%. Reports have also shown a possibility of PUK occurrence after any ocular surgery. In a retrospective study of 771 eyes, 1.4% of participants reported developing late-onset PUK at an average of 3–6 months after surgery. == References ==
Aplasia cutis congenita	Aplasia cutis congenita is a rare disorder characterized by congenital absence of skin. Frieden classified ACC in 1986 into 9 groups on the basis of location of the lesions and associated congenital anomalies. The scalp is the most commonly involved area with lesser involvement of trunk and extremities. Frieden classified ACC with fetus papyraceus as type 5. This type presents as truncal ACC with symmetrical absence of skin in stellate or butterfly pattern with or without involvement of proximal limbs. It is the most common congenital cicatricial alopecia, and is a congenital focal absence of epidermis with or without evidence of other layers of the skin.The exact etiology of ACC is still unclear but intrauterine infection by varicella or herpes virus, drugs such as methimazole, misoprostol, valproate, cocaine, marijuana etc., fetus papyraceus, feto-fetal transfusion, vascular coagulation defects, amniotic membrane adherence, abnormal elastic fiber biomechanical forces and trauma are implicated. It can be associated with Johanson–Blizzard syndrome, Adams–Oliver syndrome, trisomy 13, and Wolf–Hirschhorn syndrome. It can also seen with exposure to methimazole and carbimazole in utero. This dermatological manifestation has been linked to Peptidase D haploinsufficiency and a deletion in Chromosome 19. Signs and symptoms Genetics This condition has been linked to mutations in the ribosomal GTPase BMS1 gene. Diagnosis Treatment Skin grafting is a solution to fix aplasia cutis congenita. See also List of cutaneous conditions References External links Aplasia cutis congenita (ACC) on emedicine
Transient hypogammaglobulinemia of infancy	Transient hypogammaglobulinemia of infancy is a form of hypogammaglobulinemia appearing after birth, leading to a reduction in the level of IgG, and also sometimes IgA and IgM. (The ratios of immunoglobulins vary rapidly in all infants, and the term dysgammaglobulinemia, although theoretically applicable, is not usually used in this context.) It can result in increased infections, but it can also present without symptoms. Pathophysiology Normally, a newborns immunoglobulins come from the mother during pregnancy and wane after birth until 3-6 months of age, when the infant begins to start to produce their own IgG. However, in transient hypogammaglobulinemia of infancy, the IgG synthesis is delayed, and the hypogammaglobulinemia is prolonged beyond age 6 months. See also List of cutaneous conditions References == External links ==
Trichofolliculoma	Trichofolliculoma is a cutaneous condition characterized by a benign, highly structured tumor of the pilosebaceous unit.: 671 See also Multiple familial trichoepithelioma Pilomatricoma Skin lesion List of cutaneous conditions References == External links ==
Pseudoporphyria	Pseudoporphyria is a bullous photosensitivity that clinically and histologically mimics porphyria cutanea tarda.: 524 The difference is that no abnormalities in urine or serum porphyrin is noted on laboratories. Pseudoporphyria has been reported in patients with chronic kidney failure treated with hemodialysis and in those with excessive exposure to ultraviolet A (UV-A) by tanning beds. Presentation Pseudoporphyria is clinically characterized by increased skin fragility; erythema; and the appearance of tense bullae and erosions on sun-exposed skin, which are identical to those seen in patients with PCT. However, a clinical pearl that may prove helpful in differentiating between pseudoporphyria and PCT is that the classic features of hypertrichosis, hyperpigmentation, and sclerodermoid changes found with PCT are unusual with pseudoporphyria. A second clinical pattern of pseudoporphyria has a similar presentation to erythropoietic protoporphyria (EPP), an autosomal dominant porphyria resulting from a reduced activity of ferrochelatase.In contrast to PCT, EPP usually begins in childhood with a history of photosensitivity, often described as a burning sensation immediately after sunlight exposure. Clinically, EPP is characterized by erythema, edema, shallow scars, and waxy induration of the skin, particularly on the face. Pseudoporphyria that clinically mimics EPP has been described almost exclusively in children taking naproxen for juvenile rheumatoid arthritis. Naproxen-induced pseudoporphyria seems to have a dimorphic presentation with the PCT-like pattern more often seen in the adult population and the EPP-like pattern more commonly seen in children, although some overlap has been documented. Race Although pseudoporphyria has no predilection toward any one race, it has been shown that fair-skinned children who are highly prone to sunburn are more likely to develop naproxen-induced pseudoporphyria than those children with skin types III or higher. Wallace et al. demonstrated that even in the absence of a history of blistering, children with light skin and blue or green eyes are at an increased risk of developing shallow scars on the face while taking naproxen. Causes Pseudoporphyria can be induced by a wide range of medications, excessive UV-A exposure, and hemodialysis. One frequently reported drug is naproxen. A frequent source of UV-A exposure is tanning booths. As recognition of pseudoporphyria increases and the number of new medications expands, the list of etiologic agents associated with pseudoporphyria will most likely continue to grow. Agents associated with pseudoporphyria are as follows: Propionic acid derivatives (NSAIDs) - naproxen, diflunisal, ketoprofen, oxaprozin, mefenamic acid, rofecoxib Ketone NSAID-nabumetone Antibiotics - nalidixic acid, tetracycline, oxytetracycline, ampicillin-sulbactam, cefepime, fluoroquinolones (M Poh, personal communication, June 1999) Antifungals - voriconazole Diuretics - furosemide, chlorthalidone, butamide, triamterene/hydrochlorothiazide Antiarrhythmics - amiodarone Chemotherapy - 5-fluorouracil Immunosuppressants - cyclosporine Sulfones - dapsone Vitamins - brewers yeast, pyridoxine Vitamin A derivatives - etretinate, isotretinoin Muscle relaxants - carisoprodol/aspirin Nonsteroidal antiandrogens - flutamide Other - hemodialysis, excessive UV-A, cola, oral contraceptive pills (levonorgestrel and ethinylestradiol), narrowband UV-B phototherapy (rarely) Pathophysiology The precise pathophysiologic mechanism of pseudoporphyria is not fully understood. Some drugs, especially non steroidal anti-inflammatory drugs, can trigger pseudoporphyria in the presence of ultraviolet light. The pathophysiology of pseudoporphyria associated with hemodialysis has not been fully explained. Aluminum hydroxide has been implicated in hemodialysis-associated pseudoporphyria. Aluminum hydroxide is found in dialysis solution and has been shown to produce a porphyrialike disorder after long-term administration in rats. Diagnosis Treatment Sun avoidance, avoidance of tanning booths, and usage of broad spectrum sunscreen that blocks both UVA and UVB. Identification and avoidance of the offending drug. Frequency Although fewer than 100 cases are documented in English language literature, pseudoporphyria is most likely underreported in the literature because it is only a symptom of some other condition, e.g. side effect of medicine or symptom of liver problems. As the symptoms of pseudoporhphyra have other names, those symptoms are mentioned. The rarity of porphyria in modern times also makes the use of the term pseudoporphyria obscure. History A careful history is of utmost importance when the diagnosis of pseudoporphyria is being considered. A personal and family history of hepatitis, porphyria, or photosensitivity disorder must be sought. Although a genetic factor has not been considered in pseudoporphyria, one case of monozygotic twins developing pseudoporphyria after excessive UV-A exposure from long-term tanning bed use has been documented. The patient should be thoroughly questioned regarding any symptoms of connective tissue disorder, which may be the underlying pathology of the photosensitivity. Recent reports suggest that a connective tissue disorder may be a predisposing factor in patients using nonsteroidal anti-inflammatory drugs (NSAIDs) who develop pseudoporphyria. References == External links ==
Brody myopathy	Brody myopathy, also called Brody disease, is a rare disorder that affects skeletal muscle function. BD was first characterized in 1969 by Dr. Irwin A. Brody at Duke University Medical Center. Individuals with BD have difficulty relaxing their muscles after exercise. This difficulty in relaxation leads to symptoms including cramps, stiffness, and discomfort in the muscles of the limbs and face. Symptoms are heightened by exercise and commonly progress in severity throughout adulthood. Signs and symptoms Symptoms include stiffness and sometimes muscle cramping after exercise and especially when exposed to cold. The most commonly affected muscles are in the arms, legs, and eyelids. Individuals with Brody myopathy also sometimes experience weakness, myalgia, and rhabdomyolysis. Cause Most cases of BD are inherited through autosomal recessive mutations in ATP2A1, where each copy of the affected individuals gene contain a mutation. The gene involved in BD encodes the fast-twitch skeletal muscle ATPase, SERCA1. SERCA1 is a protein pump that uses ATP to pump Ca2+ ions from the cytosol to the sarcoplasmic reticulum in skeletal muscle. In those with BD, SERCA1 pumps are unable to effectively move Ca2+ across the membrane, leading to increased levels of cytoplasmic Ca2+. Increases in cytoplasmic Ca2+ levels interfere with muscle contraction, leading to the characteristic symptoms of BD.In some cases of BD, no mutations in ATP2A1 have been observed. Disease transmission in cases of non-ATP2A1 BD have been characterized as autosomal dominant pattern of inheritance. These cases have revealed that the cause of the disease likely exhibits genetic heterogeneity, meaning the disease involves mutations in other locations within the genome (although no other loci have been identified in the development of BD as of now). Diagnosis Diagnosis of BD begins with clinical evaluation of individuals for characteristic symptoms of cramping and stiffness of exercised muscles. A few techniques are involved in confirming a diagnosis of BD.Blood testing may be used to measure serum creatine kinase, which ranges from normal to slightly elevated in those with BD. Skeletal muscle biopsies are used to examine muscle fibers. Biopsies in individuals with BD often show variation in muscle fiber size, atrophied fast-twitch muscle fibers, and increased nuclei number. Electromyography (EMG) can be used in diagnosis to rule out myotonia, or muscle stiffness that is detected by EMG. Individuals with BD have stiff muscles but normal EMG results (pseudo-myotonia), where no myotonic discharges are detected. Genetic testing may also be used in the diagnosis of BD to look for mutations in ATP2A1. Since only some forms of the disease are associated with ATP2A1, results of genetic testing do not always confirm a diagnosis of BD, but are useful to rule out other similar disorders. Treatment There is no cure for BD, although treatment options are available for reducing the negative symptoms of BD. The drugs dantrolene and verapamil are used in BD treatment due to their effects on Ca2+. Dantrolene is a muscle relaxer that decreases the symptoms of BD by inhibiting Ca2+ release channels in the sarcoplasmic reticulum, while verapamil sequesters Ca2+ in the sarcoplasmic reticulum of muscle cells by functioning as a Ca2+ channel blocker.These drugs act by limiting the amount of Ca2+ from being released from the sarcoplasmic reticulum. When a muscle is stimulated, Ca2+ is released from the sarcoplasmic reticulum into the cytoplasm where it binds to a protein called troponin. This event allows the muscle fibers to overlap, causing a contraction. In BD, Ca2+ levels are high in the cytoplasm, which means Ca2+ can readily bind troponin, leading to muscles that are in an extended state of contraction. References == External links ==
Subungual exostosis	Subungual exostoses are a type of non-cancerous bone tumor of the chondrogenic type, and consists of bone and cartilage. It usually projects from the upper surface of the big toe underlying the nailbed, giving rise to a painful swelling that destroys the nail. Subsequent ulceration and infection may occur.There is an association with trauma and infection. Diagnosis involves medical imaging to exclude other similar conditions, particularly osteochondroma. X-ray appearance may reveal a bony protuberance attached to the top or side surface of a toe bone.Treatment is by surgical excision and is effective.More than half are under the age of 18 years and males are affected equally to females. Combined with bizarre parosteal osteochondromatous proliferation, they comprise <5% of cartilage tumors. Signs and symptoms They tend to be painful due to the pressure applied to the nail bed and plate. They can involve destruction of the nail bed. These lesions are not true osteochondromas, rather it is a reactive cartilage metaplasia. The reason it occurs on the dorsal aspect is because the periosteum is loose dorsally but very tightly adherent volarly. Diagnosis Diagnosis involves medical imaging.Differential diagnosis includes mainly bizarre parosteal osteochondromatous proliferation (BPOP), which is more irregular and tends to involve the middle of the finger or toe rather than the end near the nail. They are distinct from subungual osteochondroma. Treatment Treatment is by surgical excision and is effective. Epidemiology It tends to occur in children and adolescents. Combined with BPOP, they account for less than 5% of cartilage tumors. See also Sternal cleft List of cutaneous conditions References == External links ==
Rectal prolapse	A rectal prolapse occurs when walls of the rectum have prolapsed to such a degree that they protrude out of the anus and are visible outside the body. However, most researchers agree that there are 3 to 5 different types of rectal prolapse, depending on whether the prolapsed section is visible externally, and whether the full or only partial thickness of the rectal wall is involved.Rectal prolapse may occur without any symptoms, but depending upon the nature of the prolapse there may be mucous discharge (mucus coming from the anus), rectal bleeding, degrees of fecal incontinence and obstructed defecation symptoms.Rectal prolapse is generally more common in elderly women, although it may occur at any age and in either sex. It is very rarely life-threatening, but the symptoms can be debilitating if left untreated. Most external prolapse cases can be treated successfully, often with a surgical procedure. Internal prolapses are traditionally harder to treat and surgery may not be suitable for many patients. Classification The different kinds of rectal prolapse can be difficult to grasp, as different definitions are used and some recognize some subtypes and others do not. Essentially, rectal prolapses may be: full thickness (complete), where all the layers of the rectal wall prolapse, or involve the mucosal layer only (partial) external if they protrude from the anus and are visible externally, or internal if they do not circumferential, where the whole circumference of the rectal wall prolapse, or segmental if only parts of the circumference of the rectal wall prolapse present at rest, or occurring during straining.External (complete) rectal prolapse (rectal procidentia, full thickness rectal prolapse, external rectal prolapse) is a full thickness, circumferential, true intussusception of the rectal wall which protrudes from the anus and is visible externally.Internal rectal intussusception (occult rectal prolapse, internal procidentia) can be defined as a funnel shaped infolding of the upper rectal (or lower sigmoid) wall that can occur during defecation. This infolding is perhaps best visualised as folding a sock inside out, creating "a tube within a tube". Another definition is "where the rectum collapses but does not exit the anus". Many sources differentiate between internal rectal intussusception and mucosal prolapse, implying that the former is a full thickness prolapse of rectal wall. However, a publication by the American Society of Colon and Rectal Surgeons stated that internal rectal intussusception involved the mucosal and submucosal layers separating from the underlying muscularis mucosa layer attachments, resulting in the separated portion of rectal lining "sliding" down. This may signify that authors use the terms internal rectal prolapse and internal mucosal prolapse to describe the same phenomena. Mucosal prolapse (partial rectal mucosal prolapse) refers to prolapse of the loosening of the submucosal attachments to the muscularis propria of the distal rectummucosal layer of the rectal wall. Most sources define mucosal prolapse as an external, segmental prolapse which is easily confused with prolapsed (3rd or 4th degree) hemorrhoids (piles). However, both internal mucosal prolapse (see below) and circumferential mucosal prolapse are described by some. Others do not consider mucosal prolapse a true form of rectal prolapse.Internal mucosal prolapse (rectal internal mucosal prolapse, RIMP) refers to prolapse of the mucosal layer of the rectal wall which does not protrude externally. There is some controversy surrounding this condition as to its relationship with hemorrhoidal disease, or whether it is a separate entity. The term "mucosal hemorrhoidal prolapse" is also used.Solitary rectal ulcer syndrome (SRUS, solitary rectal ulcer, SRU) occurs with internal rectal intussusception and is part of the spectrum of rectal prolapse conditions. It describes ulceration of the rectal lining caused by repeated frictional damage as the internal intussusception is forced into the anal canal during straining. SRUS can be considered a consequence of internal intussusception, which can be demonstrated in 94% of cases. Mucosal prolapse syndrome (MPS) is recognized by some. It includes solitary rectal ulcer syndrome, rectal prolapse, proctitis cystica profunda, and inflammatory polyps. It is classified as a chronic benign inflammatory disorder. Rectal prolapse and internal rectal intussusception has been classified according to the size of the prolapsed section of rectum, a function of rectal mobility from the sacrum and infolding of the rectum. This classification also takes into account sphincter relaxation: Grade I: nonrelaxation of the sphincter mechanism (anismus) Grade II: mild intussusception Grade III: moderate intussusception Grade IV: severe intussusception Grade V: rectal prolapseRectal internal mucosal prolapse has been graded according to the level of descent of the intussusceptum, which was predictive of symptom severity: first degree prolapse is detectable below the anorectal ring on straining second degree when it reached the dentate line third degree when it reached the anal verge The most widely used classification of internal rectal prolapse is according to the height on the rectal/sigmoid wall from which they originate and by whether the intussusceptum remains within the rectum or extends into the anal canal. The height of intussusception from the anal canal is usually estimated by defecography.Recto-rectal (high) intussusception (intra-rectal intussusception) is where the intussusception starts in the rectum, does not protrude into the anal canal, but stays within the rectum. (i.e. the intussusceptum originates in the rectum and does not extend into the anal canal. The intussuscipiens includes rectal lumen distal to the intussusceptum only). These are usually intussusceptions that originate in the upper rectum or lower sigmoid.Recto-anal (low) intussusception (intra-anal intussusception) is where the intussusception starts in the rectum and protrudes into the anal canal (i.e. the intussusceptum originates in the rectum, and the intussuscipiens includes part of the anal canal) An Anatomico-Functional Classification of internal rectal intussusception has been described, with the argument that other factors apart from the height of intussusception above the anal canal appear to be important to predict symptomology. The parameters of this classification are anatomic descent, diameter of intussuscepted bowel, associated rectal hyposensitivity and associated delayed colonic transit: Type 1: Internal recto-rectal intussusception Type 1W Wide lumen Type 1N Narrowed lumen Type 2: Internal recto-anal intussusception Type 2W Wide Lumen Type 2N Narrowed lumen Type 2M Narrowed internal lumen with associated rectal hyposensitivity or early megarectum Type 3: Internal-external recto-anal intussusception Diagnosis History Patients may have associated gynecological conditions which may require multidisciplinary management. History of constipation is important because some of the operations may worsen constipation. Fecal incontinence may also influence the choice of management. Physical examination Rectal prolapse may be confused easily with prolapsing hemorrhoids. Mucosal prolapse also differs from prolapsing (3rd or 4th degree) hemorrhoids, where there is a segmental prolapse of the hemorrhoidal tissues at the 3, 7 and 11 oclock positions. Mucosal prolapse can be differentiated from a full thickness external rectal prolapse (a complete rectal prolapse) by the orientation of the folds (furrows) in the prolapsed section. In full thickness rectal prolapse, these folds run circumferential. In mucosal prolapse, these folds are radially. The folds in mucosal prolapse are usually associated with internal hemorrhoids. Furthermore, in rectal prolapse, there is a sulcus present between the prolapsed bowel and the anal verge, whereas in hemorrhoidal disease there is no sulcus. Prolapsed, incarcerated hemorrhoids are extremely painful, whereas as long as a rectal prolapse is not strangulated, it gives little pain and is easy to reduce.The prolapse may be obvious, or it may require straining and squatting to produce it. The anus is usually patulous, (loose, open) and has reduced resting and squeeze pressures. Sometimes it is necessary to observe the patient while they strain on a toilet to see the prolapse happen (the perineum can be seen with a mirror or by placing an endoscope in the bowl of the toilet). A phosphate enema may need to be used to induce straining.The perianal skin may be macerated (softening and whitening of skin that is kept constantly wet) and show excoriation. Proctoscopy/sigmoidoscopy/colonoscopy These may reveal congestion and edema (swelling) of the distal rectal mucosa, and in 10-15% of cases there may be a solitary rectal ulcer on the anterior rectal wall. Localized inflammation or ulceration can be biopsied and may lead to a diagnosis of SRUS or colitis cystica profunda. Rarely, a neoplasm (tumour) may form on the leading edge of the intussusceptum. In addition, patients are frequently elderly and therefore have increased incidence of colorectal cancer. Full length colonoscopy is usually carried out in adults prior to any surgical intervention. These investigations may be used with contrast media (barium enema) which may show the associated mucosal abnormalities. Videodefecography This investigation is used to diagnose internal intussusception, or demonstrate a suspected external prolapse that could not be produced during the examination. It is usually not necessary with obvious external rectal prolapse. Defecography may demonstrate associated conditions like cystocele, vaginal vault prolapse or enterocele. Colonic transit studies Colonic transit studies may be used to rule out colonic inertia if there is a history of severe constipation. Continent prolapse patients with slow transit constipation, and who are fit for surgery may benefit from subtotal colectomy with rectopexy. Anorectal manometry This investigation objectively documents the functional status of the sphincters. However, the clinical significance of the findings are disputed by some. It may be used to assess for pelvic floor dyssenergia, (anismus is a contraindication for certain surgeries, e.g. STARR), and these patients may benefit from post-operative biofeedback therapy. Decreased squeeze and resting pressures are usually the findings, and this may predate the development of the prolapse. Resting tone is usually preserved in patients with mucosal prolapse. In patients with reduced resting pressure, levatorplasty may be combined with prolapse repair to further improve continence. Anal electromyography/pudendal nerve testing It may be used to evaluate incontinence, but there is disagreement about what relevance the results may show, as rarely do they mandate a change of surgical plan. There may be denervation of striated musculature on the electromyogram. Increased nerve conduction periods (nerve damage), this may be significant in predicting post-operative incontinence. Complete rectal prolapse Rectal prolapse is a "falling down" of the rectum so that it is visible externally. The appearance is of a reddened, proboscis-like object through the anal sphincters. Patients find the condition embarrassing. The symptoms can be socially debilitating without treatment, but it is rarely life-threatening.The true incidence of rectal prolapse is unknown, but it is thought to be uncommon. As most affected people are elderly, the condition is generally under-reported. It may occur at any age, even in children, but there is peak onset in the fourth and seventh decades. Women over 50 are six times more likely to develop rectal prolapse than men. It is rare in men over 45 and in women under 20. When males are affected, they tend to be young and report significant bowel function symptoms, especially obstructed defecation, or have a predisposing disorder (e.g., congenital anal atresia). When children are affected, they are usually under the age of 3. 35% of women with rectal prolapse have never had children, suggesting that pregnancy and labour are not significant factors. Anatomical differences such as the wider pelvic outlet in females may explain the skewed gender distribution.Associated conditions, especially in younger patients include autism, developmental delay syndromes and psychiatric conditions requiring several medications. Signs and symptoms Signs and symptoms include: history of a protruding mass. degrees of fecal incontinence, (50-80% of patients) which may simply present as a mucous discharge. constipation (20-50% of patients) also described as tenesmus (a sensation of incomplete evacuation of stool) and obstructed defecation. a feeling of bearing down. rectal bleeding diarrhea and erratic bowel habits.Initially, the mass may protrude through the anal canal only during defecation and straining, and spontaneously return afterwards. Later, the mass may have to be pushed back in following defecation. This may progress to a chronically prolapsed and severe condition, defined as spontaneous prolapse that is difficult to keep inside, and occurs with walking, prolonged standing, coughing or sneezing (Valsalva maneuvers). A chronically prolapsed rectal tissue may undergo pathological changes such as thickening, ulceration and bleeding.If the prolapse becomes trapped externally outside the anal sphincters, it may become strangulated and there is a risk of perforation. This may require an urgent surgical operation if the prolapse cannot be manually reduced. Applying granulated sugar on the exposed rectal tissue can reduce the edema (swelling) and facilitate this. Cause The precise cause is unknown, and has been much debated. In 1912 Moschcowitz proposed that rectal prolapse was a sliding hernia through a pelvic fascial defect.This theory was based on the observation that rectal prolapse patients have a mobile and unsupported pelvic floor, and a hernia sac of peritoneum from the Pouch of Douglas and rectal wall can be seen. Other adjacent structures can sometimes be seen in addition to the rectal prolapse. Although a pouch of Douglas hernia, originating in the cul de sac of Douglas, may protrude from the anus (via the anterior rectal wall), this is a different situation from rectal prolapse. Shortly after the invention of defecography, In 1968 Broden and Snellman used cinedefecography to show that rectal prolapse begins as a circumferential intussusception of the rectum, which slowly increases over time. The leading edge of the intussusceptum may be located at 6–8 cm or at 15–18 cm from the anal verge. This proved an older theory from the 18th century by John Hunter and Albrecht von Haller that this condition is essentially a full-thickness rectal intussusception, beginning about 3 inches above the dentate line and protruding externally.Since most patients with rectal prolapse have a long history of constipation, it is thought that prolonged, excessive and repetitive straining during defecation may predispose to rectal prolapse. Since rectal prolapse itself causes functional obstruction, more straining may result from a small prolapse, with increasing damage to the anatomy. This excessive straining may be due to predisposing pelvic floor dysfunction (e.g. obstructed defecation) and anatomical factors: Abnormally low descent of the peritoneum covering the anterior rectal wall poor posterior rectal fixation, resulting in loss of posterior fixation of the rectum to the sacral curve loss of the normal horizontal position of the rectum with lengthening (redundant rectosigmoid) and downward displacement of the sigmoid and rectum long rectal mesentery a deep cul-de-sac levator diastasis a patulous, weak anal sphincterSome authors question whether these abnormalities are the cause, or secondary to the prolapse. Other predisposing factors/associated conditions include: pregnancy (although 35% of women who develop rectal prolapse are nulliparous) (have never given birth) previous surgery (30-50% of females with the condition underwent previous gynecological surgery) pelvic neuropathies and neurological disease high gastrointestinal helminth loads (e.g. Whipworm) COPD cystic fibrosis The association with uterine prolapse (10-25%) and cystocele (35%) may suggest that there is some underlying abnormality of the pelvic floor that affects multiple pelvic organs. Proximal bilateral pudendal neuropathy has been demonstrated in patients with rectal prolapse who have fecal incontinence. This finding was shown to be absent in healthy subjects, and may be the cause of denervation-related atrophy of the external anal sphincter. Some authors suggest that pudendal nerve damage is the cause for pelvic floor and anal sphincter weakening, and may be the underlying cause of a spectrum of pelvic floor disorders.Sphincter function in rectal prolapse is almost always reduced. This may be the result of direct sphincter injury by chronic stretching of the prolapsing rectum. Alternatively, the intussuscepting rectum may lead to chronic stimulation of the rectoanal inhibitory reflex (RAIR - contraction of the external anal sphincter in response to stool in the rectum). The RAIR was shown to be absent or blunted. Squeeze (maximum voluntary contraction) pressures may be affected as well as the resting tone. This is most likely a denervation injury to the external anal sphincter.The assumed mechanism of fecal incontinence in rectal prolapse is by the chronic stretch and trauma to the anal sphincters and the presence of a direct conduit (the intussusceptum) connecting rectum to the external environment which is not guarded by the sphincters.The assumed mechanism of obstructed defecation is by disruption to the rectum and anal canals ability to contract and fully evacuate rectal contents. The intussusceptum itself may mechanically obstruct the rectoanal lumen, creating a blockage that straining, anismus and colonic dysmotility exacerbate.Some believe that internal rectal intussusception represents the initial form of a progressive spectrum of disorders the extreme of which is external rectal prolapse. The intermediary stages would be gradually increasing sizes of intussusception. However, internal intussusception rarely progresses to external rectal prolapse. The factors that result in a patient progressing from internal intussusception to a full thickness rectal prolapse remain unknown. Defecography studies demonstrated that degrees of internal intussusception are present in 40% of asymptomatic subjects, raising the possibility that it represents a normal variant in some, and may predispose patients to develop symptoms, or exacerbate other problems. Treatment Conservative Surgery is thought to be the only option to potentially cure a complete rectal prolapse. For people with medical problems that make them unfit for surgery, and those who have minimal symptoms, conservative measures may be beneficial. Dietary adjustments, including increasing dietary fiber may be beneficial to reduce constipation, and thereby reduce straining. A bulk forming agent (e.g. psyllium) or stool softener can also reduce constipation. Surgical Surgery is often required to prevent further damage to the anal sphincters. The goals of surgery are to restore the normal anatomy and to minimize symptoms. There is no globally agreed consensus as to which procedures are more effective, and there have been over 50 different operations described.Surgical approaches in rectal prolapse can be either perineal or abdominal. A perineal approach (or trans-perineal) refers to surgical access to the rectum and sigmoid colon via an incision around the anus and perineum (the area between the genitals and the anus). Abdominal approach (trans-abdominal approach) involves the surgeon cutting into the abdomen and gaining surgical access to the pelvic cavity. Procedures for rectal prolapse may involve fixation of the bowel (rectopexy), or resection (a portion removed), or both. Trans-anal (endo-anal) procedures are also described where access to the internal rectum is gained through the anus itself. Abdominal procedures are associated with lower risk of postoperative recurrence of the prolapse, compared with perineal procedures (6.1% vs 16.3% in patients who are younger than 65 years of age at the time of surgery). Abdominal procedures The abdominal approach carries a small risk of impotence in males (e.g. 1-2% in abdominal rectopexy). Abdominal operations may be open or laparoscopic (keyhole surgery).Laparoscopic procedures Recovery time following laparoscopic surgery is shorter and less painful than following traditional abdominal surgery. Instead of opening the pelvic cavity with a wide incision (laparotomy), a laparoscope (a thin, lighted tube) and surgical instruments are inserted into the pelvic cavity via small incisions. Rectopexy and anterior resection have been performed laparoscopically with good results. Perineal procedures The perineal approach generally results in less post-operative pain and complications, and a reduced length of hospital stay. These procedures generally carry a higher recurrence rate and poorer functional outcome. The perineal procedures include perineal rectosigmoidectomy and Delorme repair. Elderly, or other medically high-risk patients are usually treated by perineal procedures, as they can be performed under a regional anesthetic, or even local anesthetic with intravenous sedation, thus avoid the risks of a general anesthetic. Alternatively, perineal procedures may be selected to reduce risk of nerve damage, for example in young male patients for whom sexual dysfunction may be a major concern.Perineal rectosigmoidectomy The goal of Perineal rectosigmoidectomy is to resect or remove the redundant bowel. This is done through the perineum. The lower rectum is anchored to the sacrum through fibrosis in order to prevent future prolapse. The full thickness of the rectal wall is incised at a level just above the dentate line. Redundant rectal and sigmoid wall is removed and the new edge of colon is reconnected (anastomosed) with the anal canal with stitches or staples. This procedure may be combined with levatorplasty, to tighten the pelvic muscles. A combined a perineal proctosigmoidectomy with anterior levatorplasty is also called an Altemeier procedure. Levatorplasty is performed to correct levator diastasis which is commonly associated with rectal prolapse. Perineal rectosigmoidectomy was first introduced by Mikulicz in 1899, and it remained the preferred treatment in Europe for many years. It was Popularized by Altemeier. The procedure is simple, safe and effective. Continence levatorplasty may enhance restoration of continence (2/3 of patients). Complications occur in less than 10% of cases, and include pelvic bleeding, pelvic abscess and anastomotic dehiscence (splitting apart of the stitches inside), bleeding or leak at a dehiscence Mortality is low. Recurrence rates are higher than for abdominal repair, 16-30%, but more recent studies give lower recurrence rates. Additional levatorplasty can reduce recurrence rates to 7%.Delorme Procedure This is a modification of the perineal rectosigmoidectomy, differing in that only the mucosa and submucosa are excised from the prolapsed segment, rather than full thickness resection. The prolapse is exposed if it is not already present, and the mucosal and submucosal layers are stripped from the redundant length of bowel. The muscle layer that is left is plicated (folded) and placed as a buttress above the pelvic floor. The edges of the mucosal are then stitched back together. "Mucosal proctectomy" was first discussed by Delorme in 1900, now it is becoming more popular again as it has low morbidity and avoids an abdominal incision, while effectively repairing the prolapse. The procedure is ideally suited to those patients with full-thickness prolapse limited to partial circumference (e.g., anterior wall) or less-extensive prolapse (perineal rectosigmoidectomy may be difficult in this situation). Fecal incontinence is improved following surgery (40%–75% of patients). Post operatively, both mean resting and squeeze pressures were increased. Constipation is improved in 50% of cases, but often urgency and tenesmus are created. Complications, including infection, urinary retention, bleeding, anastomotic dehiscence (opening of the stitched edges inside), stricture (narrowing of the gut lumen), diarrhea, and fecal impaction occur in 6-32% of cases. Mortality occurs in 0–2.5% cases. There is a higher recurrence rate than abdominal approaches (7-26% cases).Anal encirclement (Thirsch procedure) This procedure can be carried out under local anaesthetic. After reduction of the prolapse, a subcutaneous suture (a stich under the skin) or other material is placed encircling the anus, which is then made taut to prevent further prolapse. Placing silver wire around the anus first described by Thiersch in 1891. Materials used include nylon, silk, silastic rods, silicone, Marlex mesh, Mersilene mesh, fascia, tendon, and Dacron. This operation does not correct the prolapse itself, it merely supplements the anal sphincter, narrowing the anal canal with the aim of preventing the prolapse from becoming external, meaning it remains in the rectum. This goal is achieved in 54-100% cases. Complications include breakage of the encirclement material, fecal impaction, sepsis, and erosion into the skin or anal canal. Recurrence rates are higher than the other perineal procedures. This procedure is most often used for people who have a severe condition or who have a high risk of adverse effects from general anesthetic, and who may not tolerate other perineal procedures. Internal rectal intussusception Internal rectal intussusception (rectal intussusception, internal intussusception, internal rectal prolapse, occult rectal prolapse, internal rectal procidentia and rectal invagination) is a medical condition defined as a funnel shaped infolding of the rectal wall that can occur during defecation.This phenomenon was first described in the late 1960s when defecography was first developed and became widespread. Degrees of internal intussusception have been demonstrated in 40% of asymptomatic subjects, raising the possibility that it represents a normal variant in some, and may predispose patients to develop symptoms, or exacerbate other problems. Symptoms Internal intussusception may be asymptomatic, but common symptoms include: Fecal leakage Sensation of obstructed defecation (tenesmus). Pelvic pain. Rectal bleeding.Recto-rectal intussusceptions may be asymptomatic, apart from mild obstructed defecation. "interrupted defaecation" in the morning is thought by some to be characteristic.Recto-anal intussusceptions commonly give more severe symptoms of straining, incomplete evacuation, need for digital evacuation of stool, need for support of the perineum during defecation, urgency, frequency or intermittent fecal incontinence.It has been observed that intussusceptions of thickness ≥3 mm, and those that appear to cause obstruction to rectal evacuation may give clinical symptoms. Cause There are two schools of thought regarding the nature of internal intussusception,
Rectal prolapse	viz: whether it is a primary phenomenon, or secondary to (a consequence of) another condition. Some believe that it represents the initial form of a progressive spectrum of disorders the extreme of which is external rectal prolapse. The intermediary stages would be gradually increasing sizes of intussusception. The folding section of rectum can cause repeated trauma to the mucosa, and can cause solitary rectal ulcer syndrome. However, internal intussusception rarely progress to external rectal prolapse.Others argue that the majority of patients appear to have rectal intussusception as a consequence of obstructed defecation rather than a cause, possibly related to excessive straining in patients with obstructed defecation. Patients with other causes of obstructed defecation (outlet obstruction) like anismus also tend to have higher incidence of internal intussusception. Enteroceles are coexistent in 11% of patients with internal intussusception. Symptoms of internal intussusception overlap with those of rectocele, indeed the 2 conditions can occur together.Patients with solitary rectal ulcer syndrome combined with internal intussusception (as 94% of SRUS patients have) were shown to have altered rectal wall biomechanics compared to patients with internal intussusception alone. The presumed mechanism of the obstructed defecation is by telescoping of the intussusceptum, occluding the rectal lumen during attempted defecation. One study analysed resected rectal wall specimens in patients with obstructed defecation associated with rectal intussusception undergoing stapled trans-anal rectal resection. They reported abnormalities of the enteric nervous system and estrogen receptors. One study concluded that intussusception of the anterior rectal wall shares the same cause as rectocele, namely deficient recto-vaginal ligamentous support. Comorbidities and complications The following conditions occur more commonly in patients with internal rectal intussusception than in the general population: Rectocele Solitary rectal ulcer syndrome. Diagnosis Unlike external rectal prolapse, internal rectal intussusception is not visible externally, but it may still be diagnosed by digital rectal examination, while the patient strains as if to defecate. Imaging such as a defecating proctogram or dynamic MRI defecography can demonstrate the abnormal folding of the rectal wall. Some have advocated the use of anorectal physiology testing (anorectal manometry). Treatment Non surgical measures to treat internal intussusception include pelvic floor retraining, a bulking agent (e.g. psyllium), suppositories or enemas to relieve constipation and straining. If there is incontinence (fecal leakage or more severe FI), or paradoxical contraction of the pelvic floor (anismus), then biofeedback retraining is indicated. Some researchers advise that internal intussusception be managed conservatively, compared to external rectal prolapse which usually requires surgery.As with external rectal prolapse, there are a great many different surgical interventions described. Generally, a section of rectal wall can be resected (removed), or the rectum can be fixed (rectopexy) to its original position against the sacral vertebrae, or a combination of both methods. Surgery for internal rectal prolapse can be via the abdominal approach or the transanal approach.It is clear that there is a wide spectrum of symptom severity, meaning that some patients may benefit from surgery and others may not. Many procedures receive conflicting reports of success, leading to a lack of any consensus about the best way to manage this problem. Relapse of the intussusception after treatment is a problem. Two of the most commonly employed procedures are discussed below. laparoscopic ventral (mesh) rectopexy (LVR) This procedure aims to "[correct] the descent of the posterior and middle pelvic compartments combined with reinforcement of the rectovaginal septum".Rectopexy has been shown to improve anal incontinence (fecal leakage) in patients with rectal intussusception. The operation has been shown to have low recurrence rate (around 5%). It also improves obstructed defecation symptoms.Complications include constipation, which is reduced if the technique does not use posterior rectal mobilization (freeing the rectum from its attached back surface).The advantage of the laparoscopic approach is decreased healing time and less complications. Stapled trans-anal rectal resection (STARR) This operation aims to "remove the anorectal mucosa circumferential and reinforce the anterior anorectal junction wall with the use of a circular stapler". In contrast to other methods, STARR does not correct the descent of the rectum, it removes the redundant tissue. The technique was developed from a similar stapling procedure for prolapsing hemorrhoids. Since, specialized circular staplers have been developed for use in external rectal prolapse and internal rectal intussusception.Complications, sometimes serious, have been reported following STARR, but the procedure is now considered safe and effective. STARR is contraindicated in patients with weak sphincters (fecal incontinence and urgency are a possible complication) and with anismus (paradoxical contraction of the pelvic floor during attempted defecation). The operation has been shown to improve rectal sensitivity and decrease rectal volume, the reason thought to create urgency. 90% of patients do not report urgency 12 months after the operation. The anal sphincter may also be stretched during the operation. STARR was compared with biofeedback and found to be more effective at reducing symptoms and improving quality of life. Mucosal prolapse Rectal mucosal prolapse (mucosal prolapse, anal mucosal prolapse) is a sub-type of rectal prolapse, and refers to abnormal descent of the rectal mucosa through the anus. It is different to an internal intussusception (occult prolapse) or a complete rectal prolapse (external prolapse, procidentia) because these conditions involve the full thickness of the rectal wall, rather than only the mucosa (lining).Mucosal prolapse is a different condition to prolapsing (3rd or 4th degree) hemorrhoids, although they may look similar. Rectal mucosal prolapse can be a cause of obstructed defecation (outlet obstruction). and rectal malodor. Symptoms Symptom severity increases with the size of the prolapse, and whether it spontaneously reduces after defecation, requires manual reduction by the patient, or becomes irreducible. The symptoms are identical to advanced hemorrhoidal disease, and include: Fecal leakage causing staining of undergarments Rectal bleeding Mucous rectal discharge Rectal pain Pruritus ani Cause The condition, along with complete rectal prolapse and internal rectal intussusception, is thought to be related to chronic straining during defecation and constipation. Mucosal prolapse occurs when the results from loosening of the submucosal attachments (between the mucosal layer and the muscularis propria) of the distal rectum. The section of prolapsed rectal mucosa can become ulcerated, leading to bleeding. Diagnosis Mucosal prolapse can be differentiated from a full thickness external rectal prolapse (a complete rectal prolapse) by the orientation of the folds (furrows) in the prolapsed section. In full thickness rectal prolapse, these folds run circumferential. In mucosal prolapse, these folds are radially. The folds in mucosal prolapse are usually associated with internal hemorrhoids. Treatment EUA (examination under anesthesia) of anorectum and banding of the mucosa with rubber bands. Solitary rectal ulcer syndrome and colitis cystica profunda Solitary rectal ulcer syndrome (SRUS, SRU), is a disorder of the rectum and anal canal, caused by straining and increased pressure during defecation. This increased pressure causes the anterior portion of the rectal lining to be forced into the anal canal (an internal rectal intussusception). The lining of the rectum is repeatedly damaged by this friction, resulting in ulceration. SRUS can therefore be considered to be a consequence of internal intussusception (a sub type of rectal prolapse), which can be demonstrated in 94% of cases. It may be asymptomatic, but it can cause rectal pain, rectal bleeding, rectal malodor, incomplete evacuation and obstructed defecation (rectal outlet obstruction). Symptoms Symptoms include: Straining during defecation Mucous rectal discharge Rectal bleeding Sensation of incomplete evacuation (tenesmus) constipation, or more rarely diarrhea fecal incontinence (rarely) Prevalence The condition is thought to be uncommon. It usually occurs in young adults, but children can be affected too. Cause The essential cause of SRUS is thought to be related to too much straining during defecation. Overactivity of the anal sphincter during defecation causes the patient to require more effort to expel stool. This pressure is produced by the modified valsalva manovoure (attempted forced exhalation against a closed glottis, resulting in increased abdominal and intra-rectal pressure). Patiest with SRUS were shown to have higher intra-rectal pressures when straining than healthy controls. SRUS is also associated with prolonged and incomplete evacuation of stool.More effort is required because of concomitant anismus, or non-relaxation/paradoxical contraction of puborectalis (which should normally relax during defecation). The increased pressure forces the anterior rectal lining against the contracted puborectalis and frequently the lining prolapses into the anal canal during straining and then returns to its normal position afterwards. The repeated trapping of the lining can cause the tissue to become swollen and congested. Ulceration is thought to be caused by resulting poor blood supply (ischemia), combined with repeated frictional trauma from the prolapsing lining, and exposure to increased pressure are thought to cause ulceration. Trauma from hard stools may also contribute. The site of the ulcer is typically on the anterior wall of the rectal ampulla, about 7–10 cm from the anus. However, the area may of ulceration may be closer to the anus, deeper inside, or on the lateral or posterior rectal walls. The name "solitary" can be misleading since there may be more than one ulcer present. Furthermore, there is a "preulcerative phase" where there is no ulcer at all.Pathological specimens of sections of rectal wall taken from SRUS patients show thickening and replacement of muscle with fibrous tissue and excess collagen. Rarely, SRUS can present as polyps in the rectum.SRUS is therefore associated and with internal, and more rarely, external rectal prolapse. Some believe that SRUS represents a spectrum of different diseases with different causes.Another condition associated with internal intussusception is colitis cystica profunda (also known as CCP, or proctitis cystica profunda), which is cystica profunda in the rectum. Cystica profunda is characterized by formation of mucin cysts in the muscle layers of the gut lining, and it can occur anywhere along the gastrointestinal tract. When it occurs in the rectum, some believe to be an interchangeable diagnosis with SRUS since the histologic features of the conditions overlap. Indeed, CCP is managed identically to SRUS.Electromyography may show pudendal nerve motor latency. Complications Complications are uncommon, but include massive rectal bleeding, ulceration into the prostate gland or formation of a stricture. Very rarely, cancer can arise on the section of prolapsed rectal lining. Diagnosis and investigations SRUS is commonly misdiagnosed, and the diagnosis is not made for 5–7 years. Clinicians may not be familiar with the condition, and treat for Inflammatory bowel disease, or simple constipation.The thickened lining or ulceration can also be mistaken for types of cancer.The differential diagnosis of SRUS (and CCP) includes: polyps endometriosis inflammatory granulomas infectious disorders drug-induced colitis mucus-producing adenocarcinomaDefecography, sigmoidoscopy, transrectal ultrasound, mucosal biopsy, anorectal manometry and electromyography have all been used to diagnose and study SRUS. Some recommend biopsy as essential for diagnosis since ulcerations may not always be present, and others state defecography as the investigation of choice to diagnose SRUS. Treatment Although SRUS is not a medically serious disease, it can be the cause of significantly reduced quality of life for patients. It is difficult to treat, and treatment is aimed at minimizing symptoms. Stopping straining during bowel movements, by use of correct posture, dietary fiber intake (possibly included bulk forming laxatives such as psyllium), stool softeners (e.g. polyethylene glycol, and biofeedback retraining to coordinate pelvic floor during defecation.Surgery may be considered, but only if non surgical treatment has failed and the symptoms are severe enough to warrant the intervention. Improvement with surgery is about 55-60%.Ulceration may persist even when symptoms resolve. Mucosal prolapse syndrome A group of conditions known as Mucosal prolapse syndrome (MPS) has now been recognized. It includes SRUS, rectal prolapse, proctitis cystica profunda, and inflammatory polyps. It is classified as a chronic benign inflammatory disorder. The unifying feature is varying degrees of rectal prolapse, whether internal intussusception (occult prolapse) or external prolapse. Epidemiology Rectal prolapse affects less than 0.5% of the general population. It affects women more commonly, with a female to male ratio of 9:1. Pornography Rosebud pornography and Prolapse pornography (or rosebudding or rectal prolapse pornography) is an anal sex practice that occurs in some extreme anal pornography wherein a pornographic actor or actress performs a rectal prolapse wherein the walls of the rectum slip out of the anus. Rectal prolapse is a serious medical condition that requires the attention of a medical professional. However, in rosebud pornography, it is performed deliberately. Michelle Lhooq, writing for VICE, argues that rosebudding is an example of producers making extreme content due to the easy availability of free pornography on the internet. She also argues that rosebudding is a way for pornographic actors and actresses to distinguish themselves. Repeated rectal prolapses can cause bowel problems and anal leakage and therefore risk the health of pornographic actors or actresses who participate in them. Lhooq also argues that some who participate in this form of pornography are unaware of the consequences. Terminology Prolapse refers to "the falling down or slipping of a body part from its usual position or relations". It is derived from the Latin pro- - "forward" + labi - "to slide". "Prolapse". Merriam-Webster Dictionary. Prolapse can refer to many different medical conditions other than rectal prolapse. procidentia has a similar meaning to prolapse, referring to "a sinking or prolapse of an organ or part". It is derived from the Latin procidere - "to fall forward". Procidentia usually refers to uterine prolapse, but rectal procidentia can also be a synonym for rectal prolapse. Intussusception is defined as invagination (infolding), especially referring to "the slipping of a length of intestine into an adjacent portion". It is derived from the Latin intus - "within" and susceptio - "action of undertaking", from suscipere - "to take up". "Intussusception". Merriam-Webster Dictionary. Rectal intussusception is not to be confused with other intussusceptions involving colon or small intestine, which can sometimes be a medical emergency. Rectal intussusception by contrast is not life-threatening. Intussusceptum refers to the proximal section of rectal wall, which telescopes into the lumen of the distal section of rectum (termed the intussuscipiens). What results is 3 layers of rectal wall overlaid. From the lumen outwards, the first layer is the proximal wall of the intussusceptum, the middle is the wall of the intussusceptum folded back on itself, and the outer is the distal rectal wall, the intussuscipiens. See also Fecal incontinence Obstructed defecation Rectal discharge Anismus References == External links ==
Renal medullary carcinoma	Renal medullary carcinoma is a rare type of cancer that affects the kidney. It tends to be aggressive, difficult to treat, and is often metastatic at the time of diagnosis. Most individuals with this type of cancer have sickle cell trait or rarely sickle cell disease, suggesting that the sickle cell trait may be a risk factor for this type of cancer. Signs and symptoms In a case series of 34 patients, Davis and colleagues reported the following signs and symptoms: macroscopically visible (gross) hematuria (60%) abdominal or back/flank pain (50%) significant weight loss (25%)Other researchers have reported a palpable renal mass or enlarged lymph nodes. Causes The etiology of renal medullary carcinoma is still not completely understood. However, the majority of individuals diagnosed with this type of cancer have had sickle cell trait, in which the person carries one normal copy of the hemoglobin A gene (HbA) and one copy of the hemoglobin A gene harboring the genetic mutation found in sickle cell disease (HbS). These individuals do not have sickle cell disease but can manifest symptoms such as kidney damage over the course of their lives. The other genetic or environmental factors that contribute to the risk of renal medullary carcinoma are unknown. Mechanism The finding that virtually all people affected by renal medullary carcinoma carry at least one copy of the HbS mutation suggests that sickle cell trait somehow predisposes to this type of cancer. The precise mechanism is unknown, but red blood cells with a sickle cell configuration have been identified in pathology specimens. Diagnosis The diagnosis of renal medullary carcinoma is typically made after individuals with sickle cell trait present with the typical signs and symptoms outlined above, in combination with radiographic imaging (usually abdominal/pelvic CT scan) studies and ultimately surgical biopsy and pathological examination of the tumor. Findings on radiographic examination are non-specific and can reveal a mass deep within the kidney. Histopathology studies show a distinctive pattern that can be distinguished from other renal tumors. Classification Renal medullary carcinoma has been termed "the seventh sickle cell nephropathy" because it is found almost exclusively in individuals with sickle cell trait or occasionally in those with sickle cell disease. Prevention Renal medullary carcinoma is extremely rare and it is not currently possible to predict those individuals with sickle cell trait who will eventually develop this cancer. It is hoped that early detection could result in better outcomes but screening is not feasible. Management This cancer is typically aggressive, presents at an advanced stage when the cancer has already metastasized, and is resistant to chemotherapy. It therefore poses a significant management challenge. Current treatment options include surgical resection and chemotherapy with a variety of agents, including (but not limited to) ifosfamide, etoposide, carboplatin, and topotecan. A recent study looked at the use of methotrexate, vinblastine, doxorubicin, and cisplatin in 3 patients and saw a partial response and longer survival than historical reports. Carboplatin, gemcitibine, and paclitaxel provided a complete response in a patient with advanced disease. The role of radiation is unclear; some tumors have shown a response to radiation. Due to the apparent propensity for the tumor to spread to the central nervous system, it has been suggested that prophylactic craniospinal irradiation should be considered. Prognosis Since the cancer most often presents at an advanced stage, prognosis is generally very poor, with median survival times of 3 months (range 1–7 months). Longer survival of beyond one year was reported in one patient and of up to eight years in one individual whose tumor was well circumscribed and non-metastatic at the time of diagnosis, suggesting that early detection could dramatically improve survival. Epidemiology As of 2009, there have been approximately 120 reported cases of renal medullary carcinoma. In every instance except for one, the patients were positive for cell sickling. Wilms tumor, the most common renal tumor of childhood, is responsible for 6-7% of childhood cancer whereas all remaining primary renal tumors (among which is included renal medullary carcinoma) collectively account for less than 1% of all childhood cancer and less than 10% of primary kidney tumors in childhood. History Renal medullary carcinoma was first described as a clinicopathologic entity in 1995. References == External links ==
Mees lines	Mees lines or Aldrich–Mees lines, also called leukonychia striata, are white lines of discoloration across the nails of the fingers and toes (leukonychia). Presentation They are typically white bands traversing the width of the nail. As the nail grows they move towards the end, and finally disappear when trimmed. Causes Mees lines appear after an episode of poisoning with arsenic, thallium or other heavy metals or selenium, opioid MT-45, and can also appear if the subject is suffering from kidney failure. They have been observed in chemotherapy patients. Eponym and history Although the phenomenon is named after Dutch physician R. A. Mees, who described the abnormality in 1919, earlier descriptions of the same abnormality were made by Englishman E. S. Reynolds in 1901 and by American C. J. Aldrich in 1904. See also Leukonychia List of cutaneous conditions Muehrckes nails – a similar condition, except the lines are underneath the nails and so do not move as the nail grows References == External links ==
Problem gambling	Problem gambling or ludomania is repetitive gambling behavior despite harm and negative consequences. Problem gambling may be diagnosed as a mental disorder according to DSM-5 if certain diagnostic criteria are met. Pathological gambling is a common disorder that is associated with both social and family costs. The DSM-5 has re-classified the condition as an addictive disorder, with those affected exhibiting many similarities to those who have substance addictions. The term gambling addiction has long been used in the recovery movement. Pathological gambling was long considered by the American Psychiatric Association to be an impulse-control disorder rather than an addiction. However, data suggest a closer relationship between pathological gambling and substance use disorders than exists between PG and obsessive-compulsive disorder, largely because the behaviors in problem gambling and most primary substance use disorders (i.e. those not resulting from a desire to "self-medicate" for another condition such as depression) seek to activate the brains reward mechanisms while the behaviors characterizing obsessive-compulsive disorder are prompted by overactive and misplaced signals from the brains fear mechanisms.Problem gambling is an addictive behavior with a high comorbidity with alcohol problems. A common tendency shared by people who have a gambling addiction is impulsivity. Signs and symptoms Research by governments in Australia led to a universal definition for that country which appears to be the only research-based definition not to use diagnostic criteria: "Problem gambling is characterized by many difficulties in limiting money and/or time spent on gambling which leads to adverse consequences for the gambler, others, or for the community." The University of Maryland Medical Center defines pathological gambling as "being unable to resist impulses to gamble, which can lead to severe personal or social consequences".Most other definitions of problem gambling can usually be simplified to any gambling that causes harm to the gambler or someone else in any way; however, these definitions are usually coupled with descriptions of the type of harm or the use of diagnostic criteria. The DSM-V has since reclassified pathological gambling as "gambling disorder" and has listed the disorder under substance-related and addictive disorders rather than impulse-control disorders. This is due to the symptomatology of the disorder resembling an addiction not dissimilar to that of a substance use disorder. In order to be diagnosed, an individual must have at least four of the following symptoms in a 12-month period: Needs to gamble with increasing amounts of money in order to achieve the desired excitement Is restless or irritable when attempting to cut down or stop gambling Has made repeated unsuccessful efforts to control, cut back, or stop gambling Is often preoccupied with gambling (e.g., having persistent thoughts of reliving past gambling experiences, handicapping or planning the next venture, thinking of ways to get money with which to gamble) Often gambles when feeling distressed (e.g., helpless, guilty, anxious, depressed) After losing money gambling, often returns another day to get even ("chasing" ones losses) Lies to conceal the extent of involvement with gambling Has jeopardized or lost a significant relationship, job, education, or career opportunity because of gambling Relies on others to provide money to relieve desperate financial situations caused by gambling Factors that lead to gambling addiction Mayo Clinic specialists state that compulsive gambling may be result from biological, genetic, and environmental factors, such as: mental health disorders (the presence of substance use disorders, personality disorders, emotional states) age and sex (usually found in youth or middle-aged people, and more common to men than women) impact on family or friends personality traits drugs with rare side-effects (for example, antipsychotic medications or dopamine agonists).Other studies add the following triggers to the mentioned above: traumatic conditions job-related stress solitude other addictionsIf not treated, problem gambling may cause very serious and lasting effects on an individuals life: relationship related issues problems with money, bankruptcy legal problems, imprisonment health problems suicide, including suicidal thoughts and attempts Suicide rates A gambler who does not receive treatment for pathological gambling when in a desperation phase may contemplate suicide. Problem gambling is often associated with increased suicidal ideation and attempts compared to the general population.Early onset of problem gambling may increase lifetime risk of suicide. Both comorbid substance use and comorbid mental disorders increase the risk of suicide in people with problem gambling. A 2010 Australian hospital study found that 17% of suicidal patients admitted to the Alfred Hospitals emergency department were problem gamblers. Mechanisms Biology According to the Illinois Institute for Addiction Recovery, evidence indicates that pathological gambling is an addiction similar to chemical addiction. It has been observed that some pathological gamblers have lower levels of norepinephrine than normal gamblers. According to a study conducted by Alec Roy, formerly at the National Institute on Alcohol Abuse and Alcoholism, norepinephrine is secreted under stress, arousal, or thrill, so pathological gamblers gamble to make up for their under-dosage.Studies have compared pathological gamblers to substance addicts, concluding that addicted gamblers display more physical symptoms during withdrawal.Deficiencies in serotonin might also contribute to compulsive behavior, including a gambling addiction. There are three important points discovered after these antidepressant studies: Antidepressants can reduce pathological gambling in case when there is an effect on serotonergic reuptake inhibitors and 5-HT1/5-HT2 receptor antagonists. Pathological gambling, as the part of obsessive-compulsive disorder, requires the higher doses of antidepressants as is usually required for depressive disorders. In cases where participants do not have or have minimal symptoms of anxiety or depression, antidepressants still have those effect.A limited study was presented at a conference in Berlin, suggesting opioid release differs in problem gamblers from the general population, but in a very different way from people who have a substance use disorder.The findings in one review indicated the sensitization theory is responsible. Dopamine dysregulation syndrome has been observed in the aforementioned theory in people with regard to such activities as gambling.Some medical authors suggest that the biomedical model of problem gambling may be unhelpful because it focuses only on individuals. These authors point out that social factors may be a far more important determinant of gambling behavior than brain chemicals and they suggest that a social model may be more useful in understanding the issue. For example, an apparent increase in problem gambling in the UK may be better understood as a consequence of changes in legislation which came into force in 2007 and enabled casinos, bookmakers, and online betting sites to advertise on TV and radio for the first time and which eased restrictions on the opening of betting shops and online gambling sites.Pathological gambling is similar to many other impulse-control disorders such as kleptomania. According to evidence from both community- and clinic-based studies, individuals who are pathological gamblers are highly likely to exhibit other psychiatric problems concurrently, including substance use disorders, mood and anxiety disorders, or personality disorders.Pathological gambling shows several similarities with substance use disorders. There is a partial overlap in diagnostic criteria; pathological gamblers are also likely to have a substance use disorder. The "telescoping phenomenon" reflects the rapid development from initial to problematic behavior in women compared with men. This phenomenon was initially described for alcoholism, but it has also been applied to pathological gambling. Also biological data provide a support for a relationship between pathological gambling and substance use disorder. A comprehensive UK Gambling Commission study from 2018 has also hinted at the link between gambling addiction and a reduction in physical activity, poor diet and overall well-being. The study links problem gambling to a myriad of issues affecting relationships, and social stability. Psychological Several psychological mechanisms are thought to be implicated in the development and maintenance of problem gambling. First, reward processing seems to be less sensitive with problem gamblers. Second, some individuals use problem gambling as an escape from the problems in their lives (an example of negative reinforcement). Third, personality factors play a role, such as narcissism, risk-seeking, sensation-seeking, and impulsivity. Fourth, problem gamblers have a number of cognitive biases, including the illusion of control, unrealistic optimism, overconfidence and the gamblers fallacy (the incorrect belief that a series of random events tends to self-correct so that the absolute frequencies of each of various outcomes balance each other out). Fifth, problem gamblers represent a chronic state of a behavioral spin process, a gambling spin, as described by the criminal spin theory.Spains gambling watchdog has made an update to its 2019–2020 Responsible Gaming Program, classifying problem gambling as a mental disorder. Diagnosis The most common instrument used to screen for "probable pathological gambling" behavior is the South Oaks Gambling Screen (SOGS) developed by Lesieur and Blume (1987) at the South Oaks Hospital in New York City. In recent years the use of SOGS has declined due to a number of criticisms, including that it overestimates false positives (Battersby, Tolchard, Thomas & Esterman, 2002). The DSM-IV diagnostic criteria presented as a checklist is an alternative to SOGS, it focuses on the psychological motivations underpinning problem gambling and was developed by the American Psychiatric Association. It consists of ten diagnostic criteria. One frequently used screening measure based upon the DSM-IV criteria is the National Opinion Research Center DSM Screen for Gambling Problems (NODS). The Canadian Problem Gambling Inventory (CPGI) and the Victorian Gambling Screen (VGS) are newer assessment measures. The Problem Gambling Severity Index, which focuses on the harms associated with problem gambling, is composed of nine items from the longer CPGI. The VGS is also harm based and includes 15 items. The VGS has proven validity and reliability in population studies as well as Adolescents and clinic gamblers. Treatment Most treatment for problem gambling involves counseling, step-based programs, self-help, peer-support, medication, or a combination of these. However, no one treatment is considered to be most efficacious and, in the United States, no medications have been approved for the treatment of pathological gambling by the U.S. Food and Drug Administration (FDA). Gamblers Anonymous (GA) is a commonly used treatment for gambling problems. Modeled after Alcoholics Anonymous, GA is a twelve-step program that emphasizes a mutual-support approach. There are three in-patient treatment centers in North America. One form of counseling, cognitive behavioral therapy (CBT) has been shown to reduce symptoms and gambling-related urges. This type of therapy focuses on the identification of gambling-related thought processes, mood and cognitive distortions that increase ones vulnerability to out-of-control gambling. Additionally, CBT approaches frequently utilize skill-building techniques geared toward relapse prevention, assertiveness and gambling refusal, problem solving and reinforcement of gambling-inconsistent activities and interests.As to behavioral treatment, some recent research supports the use of both activity scheduling and desensitization in the treatment of gambling problems. In general, behavior analytic research in this area is growing There is evidence that the SSRI paroxetine is efficacious in the treatment of pathological gambling. Additionally, for patients with both pathological gambling and a comorbid bipolar spectrum condition, sustained-release lithium has shown efficacy in a preliminary trial. The opioid antagonist drug nalmefene has also been trialled quite successfully for the treatment of compulsive gambling. Group concepts based on CBT, such as the metacognitive training for problem gambling have also proven effective. Step-based programs 12 Step-based programs such as Gamblers Anonymous are specific to gambling and generic to healing addiction, creating financial health, and improving mental wellness. Commercial alternatives that are designed for clinical intervention, using the best of health science and applied education practices, have been used as patient-centered tools for intervention since 2007. They include measured efficacy and resulting recovery metrics. Motivational interviewing Motivational interviewing is one of the treatments of compulsive gambling. The motivational interviewers basic goal is promoting readiness to change through thinking and resolving mixed feelings. Avoiding aggressive confrontation, argument, labeling, blaming, and direct persuasion, the interviewer supplies empathy and advice to compulsive gamblers who define their own goal. The focus is on promoting freedom of choice and encouraging confidence in the ability to change. Peer support A growing method of treatment is peer support. With the advancement of online gambling, many gamblers experiencing issues use various online peer-support groups to aid their recovery. This protects their anonymity while allowing them to attempt recovery on their own, often without having to disclose their issues to loved ones. Self-help Research into self-help for problem gamblers has shown benefits. A study by Wendy Slutske of the University of Missouri concluded one-third of pathological gamblers overcome it by natural recovery. Anti-addiction drugs Self-exclusion Gambling self-exclusion (voluntary exclusion) programs are available in the US, the UK, Canada, Australia, South Africa, France, and other countries. They seem to help some (but not all) problem gamblers to gamble less often.Some experts maintain that casinos in general arrange for self-exclusion programs as a public relations measure without actually helping many of those with problem gambling issues. A campaign of this type merely "deflects attention away from problematic products and industries", according to Natasha Dow Schull, a cultural anthropologist at New York University and author of the book Addiction by Design.There is also a question as to the effectiveness of such programs, which can be difficult to enforce. In the province of Ontario, Canada, for example, the Self-Exclusion program operated by the governments Ontario Lottery and Gaming Corporation (OLG) is not effective, according to investigation conducted by the television series, revealed in late 2017. \|"Gambling addicts ... said that while on the ... self-exclusion list, they entered OLG properties on a regular basis" in spite of the facial recognition technology in place at the casinos, according to the Canadian Broadcasting Corporation. As well, a CBC journalist who tested the system found that he was able to enter Ontario casinos and gamble on four distinct occasions, in spite of having been registered and photographed for the self-exclusion program. An OLG spokesman provided this response when questioned by the CBC: "We provide supports to self-excluders by training our staff, by providing disincentives, by providing facial recognition, by providing our security officers to look for players. No one element is going to be foolproof because it is not designed to be foolproof". Impact (Australia) According to the Productivity Commissions 2010 final report into gambling, the social cost of problem gambling is close to 4.7 billion dollars a year. Some of the harms resulting from problem gambling include depression, suicide, lower work productivity, job loss, relationship breakdown, crime and bankruptcy. A survey conducted in 2008 found that the most common motivation for fraud was problem gambling, with each incident averaging a loss of $1.1 million. According to Darren R. Christensen. Nicki A. Dowling, Alun C. Jackson and Shane A.Thomas a survey done from 1994 to 2008 in Tasmania gave results that gambling participation rates have risen rather than fallen over this period. Prevalence Europe In Europe, the rate of problem gambling is typically 0.5 to 3 percent. The "British Gambling Prevalence Survey 2007", conducted by the United Kingdom Gambling Commission, found approximately 0.6 percent of the adult population had problem gambling issues—the same percentage as in 1999. The highest prevalence of problem gambling was found among those who participated in spread betting (14.7%), fixed odds betting terminals (11.2%), and betting exchanges (9.8%). In Norway, a December 2007 study showed the amount of current problem gamblers was 0.7 percent.With gambling addiction on the rise worldwide and across Europe in particular, those calling gambling a disease have been gaining grounds. The UK Gambling Commission announced a significant shift in their approach to gambling through their reclassification of gambling as a disease, and therefore, it should be addressed adequately by the NHS. The World Health Organization has also classified gambling a disease. In its 72nd World Health Assembly held on Saturday, May 25, 2019, ‘gaming disorder’ was recognized as an official illness. The 194-member meet added excessive gaming to a classified list of diseases as it revised its International Statistical Classification of Diseases and Related Health Problems (ICD-11). North America In the United States, the percentage of pathological gamblers was 0.6 percent, and the percentage of problem gamblers was 2.3 percent in 2008. Studies commissioned by the National Gambling Impact Study Commission Act has shown the prevalence rate ranges from 0.1 percent to 0.6 percent. Nevada has the highest percentage of pathological gambling; a 2002 report estimated 2.2 to 3.6 percent of Nevada residents over the age of 18 could be called problem gamblers. Also, 2.7 to 4.3 percent could be called probable pathological gamblers.According to a 1997 meta-analysis by Harvard Medical Schools division on addictions, 1.1 percent of the adult population of the United States and Canada could be called pathological gamblers. A 1996 study estimated 1.2 to 1.9 percent of adults in Canada were pathological. In Ontario, a 2006 report showed 2.6 percent of residents experienced "moderate gambling problems" and 0.8 percent had "severe gambling problems". In Quebec, an estimated 0.8 percent of the adult population were pathological gamblers in 2002. Although most who gamble do so without harm, approximately 6 million American adults are addicted to gambling.Signs of a gambling problem include: Using income or savings to gamble while letting bills go unpaid Repeated unsuccessful attempts to stop gambling Chasing losses Losing sleep over thoughts of gambling Arguing with friends or family about gambling behavior Feeling depressed or suicidal because of gambling losses Oceania (Australia) Casinos and poker machines in pubs and clubs facilitate problem gambling in Australia. The building of new hotels and casinos has been described as "one of the most active construction markets in Australia"; for example, AUD$860 million was allocated to rebuild and expand the Star Complex in Sydney.A 2010 study, conducted in the Northern Territory by researchers from the Australian National University (ANU) and Southern Cross University (SCU), found that the proximity of a persons residence to a gambling venue is significant in terms of prevalence. Harmful gambling in the study was prevalent among those living within 100 metres of any gambling venue, and was over 50% higher than among those living ten kilometres from a venue. The studys data stated: Specifically, people who lived 100 metres from their favourite venue visited an estimated average of 3.4 times per month. This compared to an average of 2.8 times per month for people living one kilometre away, and 2.2 times per month for people living ten kilometres away. According to the Productivity Commissions 2016 report into gambling, 0.5% to 1% (80,000 to 160,000) of the Australian adult population had significant problems resulting from gambling. A further 1.4% to 2.1% (230,000 to 350,000) of the Australian adult population experienced moderate risks making them likely to be vulnerable to problem gambling. Estimates show that problem gamblers account for an average of 41% of the total gaming machine spending. See also Gamblers Anonymous Gamblers Lament, an ancient poem about gambling Gambling Commission (Great Britain) GamCare Gaming law National Council on Problem Gambling (Singapore) National Council on Problem Gambling (United States) Problem Gambling Foundation of New Zealand Video game addiction References == External links ==
Naxos syndrome	Naxos disease (also known as "diffuse non-epidermolytic palmoplantar keratoderma with woolly hair and cardiomyopathy" or "diffuse palmoplantar keratoderma with woolly hair and arrhythmogenic right ventricular cardiomyopathy", first described on the island of Naxos by Nikos Protonotarios) is a cutaneous condition characterized by a palmoplantar keratoderma. The prevalence of the syndrome is up to 1 in every 1000 people in the Greek islands.It has been associated with mutations in the genes encoding the proteins desmoplakin, plakoglobin, desmocollin-2, and SRC-interacting protein (SIP). Naxos disease has the same cutaneous phenotype as the Carvajal syndrome. Symptoms Between 80 and 99% of those with Naxos disease will display some of the following symptoms: Disease of the heart muscle Thickening of palms and soles Sudden increased heart rate Dizzy spells Kinked hair See also Olmsted syndrome List of cutaneous conditions List of conditions caused by problems with junctional proteins References == External links ==
Amish lethal microcephaly	Amish lethal microcephaly is a rare genetic disorder which is characterized by severe microcephaly (small head) from birth, brain hypoplasia (underdeveloped brain), micrognathia (small chin), irritability (at second or third month of age), seizures, problems controlling their body temperature, high levels of alpha-ketogluraic acid in their urine, and less commonly hepatomegaly (large liver). Babies with this condition typically die when they are 6 months old. This disorder was named after the Amish since, in Old Order Amish communities in Pennsylvania, it affects 1 in 500 babies, while 1 in 11 people in the same communities are unaffected carriers of the (recessive) mutation that causes the disorder, it has not been found outside this population.This disorder is caused by mutations in the SLC25A19 gene in chromosome 17q25, it follows an autosomal recessive inheritance pattern == References ==
Webbed neck	A webbed neck, or pterygium colli, is a congenital skin fold that runs along the sides of the neck down to the shoulders. There are many variants. Signs and symptoms On babies, webbed neck may look like loose folds of skin on the neck. As the child grows, the skin may stretch out to look like there is little or no neck. Associated conditions It is a feature of Turner syndrome (only found in girls) and Noonan syndrome, as well as the rarer Klippel–Feil syndrome, or Diamond–Blackfan anemia References == External links ==
Fibrocystic breast changes	Fibrocystic breast changes is a condition of the breasts where there may be pain, breast cysts, and breast masses. The breasts may be described as "lumpy" or "doughy". Symptoms may worsen during certain parts of the menstrual cycle due to hormonal stimulation. These are normal breast changes, not associated with cancer.Risk factors include an early age at first menstrual period and either having children at a late age or not at all. It is not a disease but represents normal breast changes. Diagnosis involves ruling out breast cancer. Fibrocystic changes include fibroadenomas, fibrosis, and papillomas of the breast.Management may involve education about the condition, using a well fitting bra, and pain medication, if needed. Occasionally danazol or tamoxifen may be used for pain. It is estimated that up to 60% of women are affected. Most commonly between the ages of 30 and 50 years. Signs and symptoms The changes in fibrocystic breast disease are characterised by the appearance of fibrous tissue and a lumpy, cobblestone texture in the breasts. These lumps are smooth with well defined edges, and free-moving regarding adjacent structures. These lumps can sometimes be obscured by irregularities in the breast associated with the condition. Theyre often found in the upper, outer sections of the breast (nearest to the armpit), but can be found throughout the breast. Women with fibrocystic changes may experience a persistent or intermittent aching or breast tenderness related to periodic swelling. Breasts and nipples may also be tender or itchy. Symptoms follow a periodic trend closely tied to the menstrual cycle. Symptoms tend to peak in the days to weeks before each period and decrease afterwards. At peak, breasts may feel full, heavy, swollen, and tender to the touch. No complications related to breastfeeding have been found. Pathophysiology The exact mechanism of the condition is not fully understood, though it is known to be tied to hormone level fluctuation, the condition usually subsides after menopause and is closely related to the menstrual cycle. Post-menopausal under hormone replacement therapy have also reported symptoms of fibrocystic breast changes indicating hormones may play a major role. This condition is an accumulative process, partly caused by the normal hormonal variation during a womans monthly cycle. The most important of these hormones include: estrogen, progesterone and prolactin. These hormones directly affect the breast tissue by causing cells to grow and multiply. Other hormones such as TSH, insulin, growth hormone and growth factors such as TGF-beta exert both direct and indirect effects by amplifying or regulating cell growth. Chronic hormonal fluctuations eventually produce small cysts and/or areas of dense or fibrotic tissue over the years. By the age of 30, multiple small cysts and breast pain may arise. Larger cysts usually do not occur until after the age of 35. Over time, presumably driven by aberrant growth signals, such lesions may accumulate epigenetic, genetic and karyotypic changes such as modified expression of hormone receptors and loss of heterozygosity. Several variants of fibrocystic breast changes may be distinguished and may vary in cause and genetic predisposition. Adenosis involves an abnormal count and density of lobular units, while other lesions appear to mainly arise from ductal epithelial origins. Theres evidence that iodine deficiency contributes to fibrocystic breast changes by enhancing breast tissue sensitivity to estrogen. Diagnosis This is an exclusion diagnosis, mostly done based on the clinical presentation after ruling out breast cancer. Nipple fluid aspiration can be used as a classification cyst type method (and to some extent improve breast cancer risk prediction) but its rarely used in practice. Biopsy or fine needle aspiration are rarely warranted.Fibrocystic breast disease is primarily diagnosed based on the symptoms, clinical breast exam and physical exam. During this examination, the doctor looks for unusual breast areas, both visually and manually. Also, the lymph nodes located in the axilla and lower neck are examined. A complete and accurate medical history is also helpful in the diagnosing process. If the patients medical history and physical exam findings are consistent with normal breast changes, no additional tests are needed; otherwise the patient will be asked to return a few weeks later for reassessment. Women may detect lumps in their breasts during self-examination, if this happens its strongly advised to visit a health professional right away. Imaging In order to establish whether the lump is a cyst or not, several imaging tests may be performed, these may include: mammography, X-rays, MRIs and ultrasound studies. Mammography is usually the first imaging test to be ordered when unusual breast changes are found during a clinical breast examination. A diagnostic mammography consists of X-ray series that provide clear and specific visualization areas in the breast. Ultrasounds and MRIs are commonly performed in conjunction with mammographies as they produce clear images of the breast that clearly distinguish between solid masses and fluid-filled breast cysts. These can better evaluate dense breast tissue; specially in young patients, under 30 years. Biopsy Breast biopsy is a test used to confirm the suspected diagnosis, only after imaging tests have already been performed and revealed unusual looking areas. The procedure consists in removing a sample of breast tissue which is then studied by a pathologist under a microscope. The specialist analyzing the tissue sample will be able to conclude if the breast changes are benign or malignant. There are four main types of procedures for breast biopsy that may be performed, these include: fine-needle, core-needle, stereotactic biopsy and surgical approach. A fine-needle aspiration biopsy is usually ordered when the doctor is almost certain that the lump is a cyst. This test is generally performed in conjunction with an ultrasound which is helpful in guiding the needle into a small or hard to find lump. The procedure consists in inserting a thin needle into the breast tissue while the lump is palpated and seen live under sonographic ultrasound waves. The core-needle biopsy is normally performed under local anesthesia and in a physicians office. The needle used in this procedure is slightly larger than the one used in a fine-needle biopsy because the procedure is intended to remove a small cylinder of tissue that will be sent to the laboratory for further examination. A newer type of breast biopsy technique is the stereotactic biopsy which relies on a three-dimensional X-ray to guide the needle of non-palpable mass. The biopsy is performed in a similar manner, by using a needle to remove tissue sample but locating the specific area of the breast is done by X-raying the breast in two different angles. Surgical biopsy is performed to remove the entire lump or a part of it. It may be painful and is done under local anesthesia. Treatment Most women with fibrocystic changes who are asymptomatic do not need treatment, only a closer follow-up may be advised. Theres no widely accepted treatment or prevention strategy for this condition. When the patient is symptomatic treatment may be necessary, same guidelines as treatment for cyclical breast pain are followed. Theres still controversy whether benign breast conditions improve or worsen with the use of oral contraceptives or hormone replacement therapy.Small-scale studies have indicated that fibrocystic breast changes may improve by making dietary changes (especially by reducing caffeine intake and related methylxanthines found in chocolate or tea) and usage of vitamin supplements. Tentative evidence has shown beneficial effects of iodine supplementation in women with fibrocystic breast changes. Prognosis There are usually no adverse side effects associated with this condition. In almost all cases it subsides after menopause. A possible complication arises through the fact that cancerous tumors may be more difficult to detect in women with fibrocystic changes. Breast cancer risk Breast cancer risk is elevated in a defined fraction of the lesions. Except for people with a strong family history of breast cancer, where the risk is two-fold, nonproliferative lesions have no increased risk. Proliferative lesions also have approximately a two-fold risk. In particular, atypical hyperplasia which is associated with an increased risk of developing breast cancer. Theres two types of atypical hyperplasia: lobular and ductal; the lobular type is associated a greater cancer risk of approximately 5-fold and especially high relative risk in premenopausal women. Atypical ductal hyperplasia is associated with 2.4-fold risk. In contrast, a New England Journal of Medicine article states that for women with a strong familial history of breast cancer, the risk of future breast cancer is roughly doubled, independent of histological status. The article further states "The relative risk of breast cancer for the cohort was 1.56 (95 percent confidence interval, 1.45 to 1.68), and this increased risk persisted for at least 25 years after biopsy. The relative risk associated with atypia was 4.24 (95 percent confidence interval, 3.26 to 5.41), as compared with a relative risk of 1.88 (95 percent confidence interval, 1.66 to 2.12) for proliferative changes without atypia and of 1.27 (95 percent confidence interval, 1.15 to 1.41) for nonproliferative lesions. The strength of the family history of breast cancer, available for 4808 women, was a risk factor that was independent of histologic findings. No increased risk was found among women with no family history and nonproliferative findings. In the first 10 years after the initial biopsy, an excess of cancers occurred in the same breast, especially in women with atypia." It is not well understood whether the lesions are precursors of breast cancer or only an indication of increased risk, for most types of lesions the chance of developing breast cancer is nearly the same in the affected and unaffected breast (side) indicating only coincidence of risk factors. For atypical lobular hyperplasia there is high incidence of ipsilateral breast cancers indicating a possible direct carcinogenetic link. Epidemiology The estimated prevalence of fibrocystic breast changes in women over their lifetime vary widely in the literature, ranging from 30 to 60% over about 50 to 60% to about 60 to 75% of all women.The condition is most common among women between 30 and 50 years of age. Terminology In ICD-10 the condition is called diffuse cystic mastopathy, or, if there is epithelial proliferation, fibrosclerosis of breast. Other names for this condition include chronic cystic mastitis, fibrocystic mastopathy and mammary dysplasia. The condition has also been named after several people (see eponyms below). Since it is a very common disorder, some authors have argued that it should not be termed a "disease", whereas others feel that it meets the criteria for a disease. It is not a classic form of mastitis (breast inflammation). Eponyms This entity has historically also been termed Bloodgood’s disease, Coopers disease (after Sir Astley Paston Cooper, 1st baronet), Phocas disease, Reclus’ disease and Reclus’ syndrome (after Paul Reclus), Reclus-Schimmelbusch disease, Schimmelbusch disease and Tillaux-Phocas disease. References == External links ==
Familial cutaneous collagenoma	Familial cutaneous collagenoma is an autosomal dominant genetic disorder characterized by the presence of multiple symmetric nodules on the trunk and upper arms in multiple members of the same family. The nodules are flesh-colored, asymptomatic, and they start appearing during adolescent years.It has been described in 10 families worldwide.These nodules are caused by an overgrowth of collagen fibers with an accompanying decreased number of elastic fibers.In some cases, this condition is associated with anomalies in other parts of the body. Genetics In a 2-generation Israeli Jewish family (whose affected members were two biological cousins), Hershkovitz et al. found a heterozygous mutation in the LEMD3 gene in both cousins and in the unaffected father of one of them. Possibly related complications In 1968, Henderson et al. described 3 American brothers with the condition, and found that each one of them had health complications: the first brother suffered from idiopathic cardiomyopathy, the second suffered from iris atrophy of the left eye with accompanying severe high-frequency deafness, and the third suffered from recurrent vasculitis. == References ==
Breast engorgement	Breast engorgement occurs in the mammary glands due to expansion and pressure exerted by the synthesis and storage of breast milk. It is also a main factor in altering the ability of the infant to latch-on. Engorgement changes the shape and curvature of the nipple region by making the breast inflexible, flat, hard, and swollen. The nipples on an engorged breast are flat or inverted. Sometimes it may lead to striae on nipples, mainly a preceding symptom of septation mastitis.Engorgement usually happens when the breasts switch from colostrum to mature milk (often referred to as when the milk "comes in"). However, engorgement can also happen later if lactating women miss several nursings and not enough milk is expressed from the breasts. It can be exacerbated by insufficient breastfeeding and/or blocked milk ducts. When engorged the breasts may swell, throb, and cause mild to extreme pain. Engorgement may lead to mastitis (inflammation of the breast) and untreated engorgement puts pressure on the milk ducts, often causing a plugged duct. The woman will often feel a lump in one part of the breast, and the skin in that area may be red and/or warm. If it continues unchecked, the plugged duct can become a breast infection, at which point she may have a fever or flu-like symptoms. Signs and symptoms Symptoms include the breasts being swollen and oedematous, and the skin appearing shiny and diffusely red. Usually the whole of both breasts are affected, and they are painful. The woman may have a fever that usually subsides in 24 hours. The nipples may become stretched tight and flat which makes it difficult for the baby to attach and remove the milk. The milk does not flow well.A fever may occur in 15 percent, but is typically less than 39 degrees C and lasts for less than one day. Causes Failure to remove breast milk, especially in the first few days after delivery when the milk comes in and fills the breast, and at the same time blood flow to the breasts increases, causing congestion. The common reasons why milk is not removed adequately are delayed initiation of breastfeeding, infrequent feeds, poor attachment, ineffective suckling, a sudden change in breastfeeding routine, suddenly stopping breastfeeding, or if a baby suddenly starts breastfeeding less than usual. Treatment The mother must remove the breast milk. If the baby can attach well and suckle, then she should breastfeed as frequently as the baby is willing. If the baby is not able to attach and suckle effectively, she should express her milk by hand or with a pump a few times until the breasts are softer, so that the baby can attach better, and then get them to breastfeed frequently. She can apply warm compresses to the breast or take a warm shower before expressing, which helps the milk to flow. She can use cold compresses after feeding or expressing, which helps to reduce the oedema. Engorgement occurs less often in baby-friendly hospitals which practise the Ten Steps and which help mothers to start breastfeeding soon after delivery.Regular breastfeeding can and should be continued. The treatment for breast engorgement can be divided into non-medical and medical methods. The non-medical methods include hot/cold packs, Gua-Sha (scraping therapy), acupuncture and drinking specialized herbal teas whereas medical methods are proteolytic enzymes such as serrapeptase, protease, and subcutaneous oxytocin. Cabbage leaves are often cited as a possible treatment but studies have found they provide "no overall benefit" on breast engorgement. Evidence from published clinical trials on the effectiveness of treatment options is of weak quality and is not strong enough to justify a clinical recommendation. See also Galactorrhea Mammoplasia References External links Breast Engorgement
Homocystinuria	Homocystinuria or HCU is an inherited disorder of the metabolism of the amino acid methionine due to a deficiency of cystathionine beta synthase or methionine synthase. It is an inherited autosomal recessive trait, which means a child needs to inherit a copy of the defective gene from both parents to be affected. Symptoms of homocystinuria can also be caused by a deficiency of vitamins B6, B12, or folate. Signs and symptoms This defect leads to a multi-systemic disorder of the connective tissue, muscles, central nervous system (CNS), and cardiovascular system. Homocystinuria represents a group of hereditary metabolic disorders characterized by an accumulation of the amino acid homocysteine in the serum and an increased excretion of homocysteine in the urine. Infants appear to be normal and early symptoms, if any are present, are vague.Signs and symptoms of homocystinuria that may be seen include the following: Cause It is usually caused by the deficiency of the enzyme cystathionine beta synthase, mutations of other related enzymes such as methionine synthase, or the deficiency of folic acid, vitamin B12 and/or pyridoxine (vitamin B6). Diagnosis The term homocystinuria describes an increased excretion of the thiol amino acid homocysteine in urine (and incidentally, also an increased concentration in plasma). The source of this increase may be one of many metabolic factors, only one of which is CBS deficiency. Others include the re-methylation defects (cobalamin defects, methionine synthase deficiency, MTHFR) and vitamin deficiencies including riboflavin (vitamin B2), pyridoxal phosphate (vitamin B6), folate (vitamin B9), and cobalamin (vitamin B12). In light of this, a combined approach to laboratory diagnosis is required to reach a differential diagnosis.CBS deficiency may be diagnosed by routine metabolic biochemistry. Genetic testing may be used to screen for known SNPs (mutations). In the first instance, plasma or urine amino acid analysis will frequently show an elevation of methionine and the presence of homocysteine. Many neonatal screening programs include methionine as a metabolite. The disorder may be distinguished from the re-methylation defects (e.g., MTHFR, methionine synthase deficiency, or the cobalamin defects) in lieu of the elevated methionine concentration. Additionally, organic acid analysis or quantitative determination of methylmalonic acid should help to exclude cobalamin (vitamin B12) defects and vitamin B12 deficiency giving a differential diagnosis.The laboratory analysis of homocysteine itself is complicated because most homocysteine (possibly above 85%) is bound to other thiol amino acids and proteins in the form of disulphides (e.g., cysteine in cystine-homocysteine, homocysteine in homocysteine-homocysteine) via disulfide bonds. Since as an equilibrium process the proportion of free homocystene is variable a true value of total homocysteine (free + bound) is useful for confirming diagnosis and particularly for monitoring of treatment efficacy. To this end it is prudent to perform total homocyst(e)ine analysis in which all disulphide bonds are subject to reduction prior to analysis, traditionally by HPLC after derivatisation with a fluorescent agent, thus giving a true reflection of the quantity of homocysteine in a plasma sample. Treatment No specific cure has been discovered for homocystinuria; however, many people are treated using high doses of vitamin B6 (also known as pyridoxine). Slightly less than 50% respond to this treatment and need to take supplemental vitamin B6 for the rest of their lives. Those who do not respond require a Low-sulfur diet (especially monitoring methionine), and most will need treatment with trimethylglycine. A normal dose of folic acid supplement and occasionally adding cysteine to the diet can be helpful, as glutathione is synthesized from cysteine (so adding cysteine can be important to reduce oxidative stress). Riboflavin, a cofactor for the MTHFR enzyme pathway and multiple glutathione-related pathways, may also be used.Betaine (N,N,N-trimethylglycine) is used to reduce concentrations of homocysteine by promoting the conversion of homocysteine back to methionine, i.e., increasing flux through the re-methylation pathway independent of folate derivatives (which is mainly active in the liver and in the kidneys). The re-formed methionine is then gradually removed by incorporation into body protein. The methionine that is not converted into protein is converted to S-adenosyl-methionine which goes on to form homocysteine again. Betaine is, therefore, only effective if the quantity of methionine to be removed is small. Hence treatment includes both betaine and a diet low in methionine. In classical homocystinuria (CBS, or cystathione beta synthase deficiency), the plasma methionine level usually increases above the normal range of 30 micromoles/L and the concentrations should be monitored as potentially toxic levels (more than 400 micromoles/L) may be reached. Recommended diet Low-protein food is recommended for this disorder, which requires food products low in particular types of amino acids (e.g., methionine). Prognosis The life expectancy of patients with homocystinuria is reduced only if untreated. It is known that before the age of 30, almost one quarter of patients die as a result of thrombotic complications (e.g., heart attack). Society and culture One theory suggests that Akhenaten, a pharaoh of the eighteenth dynasty of Egypt, may have had homocystinuria. See also Cystinuria Hyperhomocysteinemia References Further reading GeneReview/NIH/UW entry on Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency == External links ==
Pterygium inversum unguis	Pterygium inversum unguis or ventral pterygium is characterized by the adherence of the distal portion of the nailbed to the ventral surface of the nail plate.: 788 The condition may be present at birth or acquired, and may cause pain with manipulation of small objects, typing, and close manicuring of the nail.: 788 secondary due to connective tissue disorders See also Pterygium unguis Nail List of cutaneous conditions == References ==
Flashback	Flashback(s) or Flash Back may refer to: Flashback (narrative), in literature and drama, a scene that takes the narrative back in time Flashback (psychology), in which a memory is suddenly and unexpectedly revisited Acid flashback, a reported psychological effect of LSD use Flashback (welding), a hazard of using an oxyacetylene torch Flashback arrestor, a safety device used in oxy-fuel welding and cutting Computing Flashback (Trojan), computer malware that infects computers running Mac OS X Atari Flashback series, a line of video-game consoles that emulate 1980s-era Atari games Oracle Flashback, a means of retrieving data as it existed in an Oracle database at an earlier time Film, television and radio Flashback (1969 film), an Italian film by Raffaele Andreassi Flashback (1990 film), an American film by Franco Amurri Flashback (2020 film), a Canadian film by Christopher MacBride Flashback (2021 film), a French film by Caroline Vigneaux Flashback (TV series), a 1962–1968 Canadian quiz show Flashback (radio program), an American syndicated radio program Flashback, a Flash animation using a song from the Shpongle album Are You Shpongled? Television episodes "Flashback" (Desperate Housewives) "Flash Back" (The Flash) "Flashback" (Star Trek: Voyager) "Flashback" (Static Shock) "Flashback: Mike and Glorias Wedding", two episodes of All in the Family "Flashbacks" (South Park), or "City on the Edge of Forever" Literature Flashback (comics), a mutant character in Marvel Comics Flashback, a 2011 novel by Dan Simmons Flashback, a member of the Blood Syndicate in Milestone Comics Flashback Media Group, a Swedish publishing group and Internet forum host Flashbacks (book), a 1983 autobiography by Timothy Leary Music Flashback Records (disambiguation) Albums Flashback (Darin album) or the title song, 2008 Flashback (Don Friedman album) or the title song, 1963 Flashback (Electric Light Orchestra album), 2000 Flashback (Ivy Queen album), 2005 Flashback (Joan Jett album), 1993 Flashback (Pernilla Wahlgren album) or the title song, 1989 Flashback (single album), by After School, or the title song, 2012 Flashback: The Best of 38 Special, 1987 Flashback! Rock Classics Of The 70s, a charity compilation, 1991 Flash Back, by Capsule, or the title song, 2007 Flashbacks (album), by the Fuzztones, 1996 Flashbacks (EP), by Contemplate, 2018 Flashback: The Best of The J. Geils Band, by the J. Geils Band, 1985 Flash Back 1979-1986, by Aerodrom, 1996 Songs "Flashback" (Calvin Harris song), 2009 "Flashback"/"Komorebi no Uta", by High and Mighty Color, 2008 "Flashbacks" (song), by Inna, 2021 "Flashback", by Ashford & Simpson from Is It Still Good to Ya, 1978 "Flashback", by Ghali, 2019 "Flashback", by Icona Pop from Icona Pop, 2012 "Flashback", by Imagination from Body Talk, 1981 "Flashback", by Kelly Rowland from Ms. Kelly, 2007 "Flashback", by Laurent Garnier, 1997 "Flashback", by Ministry from The Land of Rape and Honey, 1988 "Flashback", by Simon Webbe from Smile, 2017 "Flashback", by Sonic Syndicate from Only Inhuman, 2007 "Flashback", by Tina Arena from In Deep, 1997 "Flash Back", by Ivy Queen from The Original Rude Girl, 1998 "Flash Back", by Kelis from Wanderland, 2001 "Flash Back", by Rustie from Glass Swords, 2011 "Flashbacks", by Chris Brown from Indigo, 2019 "Flashbacks", by Marshmello from Joytime II, 2018 Roller coasters Flashback (Six Flags Magic Mountain), a steel roller coaster at Six Flags Magic Mountain, US Flashback (Six Flags New England), a steel roller coaster at Six Flags New England, US Flashback (Six Flags Over Texas), a steel boomerang roller coaster at Six Flags Over Texas, US Video games Flashback (1992 video game), a science fiction cinematic platform game Flashback (2013 video game), a remake of the 1992 game See also All pages with titles beginning with Flashback All pages with titles containing Flashback All pages with titles beginning with Flash Back All pages with titles containing Flash back Backflash (disambiguation)
Muenke syndrome	Muenke syndrome, also known as FGFR3-related craniosynostosis, is a human specific condition characterized by the premature closure of certain bones of the skull during development, which affects the shape of the head and face. First described by Maximilian Muenke, the syndrome occurs in about 1 in 30,000 newborns. This condition accounts for an estimated 8 percent of all cases of craniosynostosis. Signs and symptoms Many people with this disorder have a premature fusion of skull bones along the coronal suture. Not every case has had craniosynostosis however. Other parts of the skull may be malformed as well. This will usually cause an abnormally shaped head, wide-set eyes, low set ears and flattened cheekbones in these patients. About 5 percent of affected individuals have an enlarged head (macrocephaly). There may also be associated hearing loss in 10–33% of cases and it is important for affected individuals to have hearing tests to check on the possibility of a problem. They can lose about 33-100% of hearing.Most people with this condition have normal intellect, but developmental delay and learning disabilities are possible. The signs and symptoms of Muenke syndrome vary among affected people, and some findings overlap with those seen in other craniosynostosis syndromes. Between 6 percent and 7 percent of people with the gene mutation associated with Muenke syndrome do not have any of the characteristic features of the disorder. Other Implications of Muenke Syndrome Apart from craniosynostosis, it has been suggested that hearing loss, and learning difficulties are common in Muenke syndrome. According to Ulster Medical Journal, most individuals with Muenke syndrome may have limb findings. The most common ocular finding in Muenke syndrome is strabismus as studied by Dr. Agochukwu-Nwubah and her researching team. Approximately 20% of people with Muenke Syndrome will also be affected by epilepsy. Causes Muenke syndrome is caused by a specific gene mutation in the FGFR3 gene. The mutation arises randomly; there is no full understanding for what causes this mutation. This mutation causes the FGFR3 protein to be overly active; it interferes with normal bone growth, and allows skull bones to fuse prematurely. There is no connection between anything mother did (or did not do) to activate the syndrome. If neither of the parents have Muenke syndrome, chances of having another child with the syndrome are minimal. This condition is inherited in an autosomal dominant pattern. This means if a parent has Muenke syndrome, every newborn has a 50% chance of inheriting the syndrome. Genetics Muenke syndrome is inherited in an autosomal dominant pattern. In some cases, an affected person inherits the mutation from one affected parent. If a patient is shown to have Muenke, they have a 50/50 chance of passing it on to their children. Not all cases of Muenke however is obvious. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family. A single mutation in the FGFR3 gene cause this syndrome. The FGFR3 gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. This mutation causes the FGFR3 protein to be overly active, which interferes with normal bone growth and allows the bones of the skull to fuse before they should.As stated by researchers at the University of Washington, Muenke syndrome is inherited in an autosomal dominant manner with incomplete penetrance and variable expressivity.” Prenatal diagnosis for pregnancies at increased risk is possible if the defining mutation has been identified in the family (Agochukwu et.al. 2006). According to the article Craniosynostosis: Molecular Genetics, penetrance is higher in females (87%) than in males (76%). Muenke syndrome is estimated to account for 25%-30% of all genetic causes of craniosynostosis according to the Journal of Anatomy. Diagnosis The diagnosis of Muenke syndrome is suspected bases on abnormal skull shape and a diagnosis of coronal craniosynostosis. In 2006, Agochukwu and her colleagues concluded that “A distinct Muenke syndrome phenotype includes: uni or bilateral coronal synostosis, midface hypoplasia, broad toes, and brachydactyly.” Due to phenotypic overlap and/or mild phenotypes, clinical differentiation of this syndrome may be difficult. The suspected diagnosis is confirmed by a blood test to check for gene mutation. To establish the extent of disease in an individual diagnosed with Muenke syndrome, various evaluations are recommended. Treatment The treatment of Muenke syndrome is focused on the correction of the abnormal skull shape and mirrors the treatment of coronal craniosynostosis. The abnormal growth patterns continue throughout the growing years; therefore, intervention, accurate diagnosis, and a customized, expertly carried-out treatment plan should be a primary concern. Although the timing of surgery can be highly individualized, surgical correction of the bicoronal craniosynostosis is most often done between 6 and 12 months of age. Surgery is usually performed through a scalp incision that lies concealed within the hair of the head. Your craniofacial surgeon will work in concert with a pediatric neurosurgeon in order to safely remove the bones of the skull. Then, the craniofacial surgeon reshapes and repositions those bones to give a more normal skull shape. References Rannan-Eliya SV, Taylor IB, De Heer IM, Van Den Ouweland AM, Wall SA, Wilkie AO (August 2004). "Paternal origin of FGFR3 mutations in Muenke-type craniosynostosis". Hum. Genet. 115 (3): 200–7. doi:10.1007/s00439-004-1151-5. PMID 15241680. S2CID 24791706. Agochukwu NB, Doherty ES, Muenke M (December 7, 2010). "Muenke Syndrome". Gene Reviews. PMID 20301588. Hughes J, Nevin NC, Morrison PJ (2001). "Familial craniosynostosis due to Pro250Arg mutation in the fibroblast growth factor receptor 3 gene". Ulster Med J. 70 (70): 47–50. PMC 2449219. PMID 11428324. Morris-Kay GM, Wilkie AO (2005). "Growth of the normal skull vault and its alteration in craniosynostosis: Insights from human genetics and experimental studies". Journal of Anatomy. 207 (5): 637–653. doi:10.1111/j.1469-7580.2005.00475.x. PMC 1571561. PMID 16313397. Solomon BD, Muenke M (2010). "Craniosynostosis: Molecular Genetics". Principles of Diagnosis and Treatment. 19: 89–97. External links National Institute of Healths Reference GeneReview/NIH/UW entry on Muenke Syndrome
Linear gingival erythema	Linear gingival erythema (LGE) is a periodontal disorder diagnosed based on distinct clinical characteristics. It was originally thought that LGE was directly associated with HIV, and it was thus called HIV-associated gingivitis (HIV-G). Later research confirmed that LGE also occurs in HIV negative immunocompromised patients, and it was thus renamed. Presentation LGE is limited to the soft tissue of the periodontium, appearing as a red line 2–3 mm in width adjacent to the free gingival margin. Unlike conventional periodontal disease, though, LGE is not significantly associated with increased levels of dental plaque.The prevalence of LGE remains unclear and there is no known treatment. == References ==
Herpetic whitlow	A herpetic whitlow is a lesion (whitlow) on a finger or thumb caused by the herpes simplex virus. It is a painful infection that typically affects the fingers or thumbs. Occasionally infection occurs on the toes or on the nail cuticle. Herpes whitlow can be caused by infection by HSV-1 or HSV-2. HSV-1 whitlow is often contracted by health care workers that come in contact with the virus; it is most commonly contracted by dental workers and medical workers exposed to oral secretions. It is also often observed in thumb-sucking children with primary HSV-1 oral infection (autoinoculation) prior to seroconversion, and in adults aged 20 to 30 following contact with HSV-2-infected genitals. Symptoms and signs Symptoms of herpetic whitlow include swelling, reddening and tenderness of the skin of infected finger. This may be accompanied by fever and swollen lymph nodes. Small, clear vesicles initially form individually, then merge and become cloudy, unlike in bacterial whitlow when there is pus. Associated pain often seems largely relative to the physical symptoms. The herpes whitlow lesion usually heals in two to three weeks. It may reside in axillary sensory ganglia to cause recurrent herpetic lesions on that arm or digits. Blistering can occur in severe cases. Causes In children the primary source of infection is the orofacial area, and it is commonly inferred that the virus (in this case commonly HSV-1) is transferred by the cutting, chewing or sucking of fingernail or thumbnail.In adults, it is more common for the primary source to be the genital region, with a corresponding preponderance of HSV-2. It is also seen in adult health care workers such as dentists because of increased exposure to the herpes virus.Contact sports are also a potential source of infection with herpetic whitlows. Treatment Although it is a self-limited illness, oral or intravenous antiviral treatments, particularly acyclovir, have been used in the management of immunocompromised or severely infected patients. It is usually given when the condition fails to improve on its own. Topical acyclovir has not been shown to be effective in management of herpetic whitlow. Famciclovir has been demonstrated to effectively treat and prevent recurrent episodes. Lancing or surgically debriding the lesion may make it worse by causing a superinfection or encephalitis. Prognosis Even though the disease is self-limiting, as with many herpes infections, the virus lies dormant in the peripheral nervous system. The disease recurs in about 20-50% of people. The most severe infection is usually the first one, with recurrences subsequently getting milder. The lesions the disease makes will either dry out, or burst, followed by healing. If the infected area is not touched, scars usually do not occur. The immunocompromised may have a hard time recovering, and have more frequent recurrences. Gallery See also Herpes simplex List of cutaneous conditions References External links Herpetic Whitlow Medscape Klotz, R. W. (Feb 1990). "Herpetic whitlow: an occupational hazard" (PDF). AANA J. 58 (1): 8–13. PMID 2316323. Archived from the original (PDF) on 2016-06-05. Retrieved 2014-05-12.
Fibrochondrogenesis	Fibrochondrogenesis is a rare autosomal recessive form of osteochondrodysplasia, causing abnormal fibrous development of cartilage and related tissues.It is a lethal rhizomelic (malformations which result in short, underdeveloped limbs) form of dwarfism, exhibiting both skeletal dysplasia (malformations of bone) and fibroblastic dysplasia (abnormal development of fibroblasts, specialized cells that make up fibrous connective tissue, which plays a role in the formation of cellular structure and promotes healing of damaged tissues). Death caused by complications of fibrochondrogenesis occurs in infancy. Presentation Fibrochondrogenesis is a congenital disorder presenting several features and radiological findings, some which distinguish it from other osteochondrodysplasias. These include: fibroblastic dysplasia and fibrosis of chondrocytes (cells which form cartilage); and flared, widened long bone metaphyses (the portion of bone that grows during childhood).Other prominent features include dwarfism, shortened ribs that have a concave appearance, micrognathism (severely underdeveloped jaw), macrocephaly (enlarged head), thoracic hypoplasia (underdeveloped chest), enlarged stomach, platyspondyly (flattened spine), and the somewhat uncommon deformity of bifid tongue (in which the tongue appears split, resembling that of a reptile). Cause The cause of platyspondyly in fibrochondrogenesis can be attributed in part to odd malformations and structural flaws found in the vertebral bodies of the spinal column in affected infants.Fibrochondrogenesis alters the normal function of chondrocytes, fibroblasts, metaphyseal cells and others associated with cartilage, bone and connective tissues. Overwhelming disorganization of cellular processes involved in the formation of cartilage and bone (ossification), in combination with fibroblastic degeneration of these cells, developmental errors and systemic skeletal malformations describes the severity of this lethal osteochondrodysplasia. Genetics Fibrochondrogenesis is inherited in an autosomal recessive pattern. This means that the defective gene responsible for the disorder is located on an autosome, and two copies of the gene — one copy inherited from each parent — are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder each carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder. Currently, no specific genetic mutation has been established as the cause of fibrochondrogenesis.Omphalocele is a congenital feature where the abdominal wall has an opening, partially exposing the abdominal viscera (typically, the organs of the gastrointestinal tract). Fibrochondrogenesis is believed to be related to omphalocele type III, suggesting a possible genetic association between the two disorders. Diagnosis Treatment Epidemiology Fibrochondrogenesis is quite rare. A 1996 study from Spain determined a national minimal prevalence for the disorder at 8 cases out of 1,158,067 live births.A United Arab Emirates (UAE) University report, from early 2003, evaluated the results of a 5-year study on the occurrence of a broad range of osteochondrodysplasias. Out of 38,048 newborns in Al Ain, over the course of the study period, fibrochondrogenesis was found to be the most common of the recessive forms of osteochondrodysplasia, with a prevalence ratio of 1.05:10,000 births.While these results represented the most common occurrence within the group studied, they do not dispute the rarity of fibrochondrogenesis. The study also included the high rate of consanguinous marriages as a prevailing factor for these disorders, as well as the extremely low rate of diagnosis-related pregnancy terminations throughout the region. Research The fibrocartilaginous effects of fibrochondrogenesis on chondrocytes has shown potential as a means to produce therapeutic cellular biomaterials via tissue engineering and manipulation of stem cells, specifically human embryonic stem cells.Utilization of these cells as curative cartilage replacement materials on the cellular level has shown promise, with beneficial applications including the repair and healing of damaged knee menisci and synovial joints; temporomandibular joints, and vertebra. See also Fibrocyte Boomerang dysplasia Cystic fibrosis References == External links ==
Galactocele	A galactocele (also called lacteal cyst or milk cyst) is a retention cyst containing milk or a milky substance that is usually located in the mammary glands. They can occur in women during or shortly after lactation. They present as a firm mass, often subareolar, and are caused by the obstruction of a lactiferous duct. Clinically, they appear similar to a cyst on examination. The duct becomes more distended over time by epithelial cells and milk. It may rarely be complicated by a secondary infection and result in abscess formation. These cysts may rupture leading to formation of inflammatory reaction and may mimic malignancy. Once lactation has ended the cyst should resolve on its own without intervention. A galactocele is not normally infected as the milk within is sterile and has no outlet through which to become contaminated. Treatment is by aspiration of the contents or by excision of the cyst. Antibiotics are given to prevent infection.Galactoceles may be associated with oral contraceptive use. They have been known to present, although rarely, after Breast augmentation and Breast reduction. References External links Case description and discussion at Harvard.edu
Quadricuspid aortic valve	A quadricuspid aortic valve (QAV) is a rare congenital heart defect characterized by the presence of four cusps, instead of the usual three found normally in the aortic valve. It is a defect that occurs during embryological development of the aortic trunk during gestation. There is an increased risk of developing post-natal aortic regurgitations and other heart-related diseases; therefore patients with the condition should be carefully monitored. Signs and symptoms Complications The most common complications of QAV are aortic regurgitations. This is caused by the inadequate closing of the four cusps at the end of systole. The fourth dysplastic cusp is incapable of fully closing the aortic annulus, which causes a backflow of blood through the aortic valve. Using transthoracic echocardiograms, 3-D TEE and ECG traces, it is also possible to find left ventricular hypertrophy, bundle branch blocks, and abnormal displacement of the ostium in the right coronary artery in association with QAV. Some research has shown increased incidences of atrial fibrillation to be associated but this relationship is not yet clearly established. Diagnosis Previously, diagnosis was usually done through autopsy. Advances in imaging technologies allow for early detection and thus ample treatment and monitoring of the affected patient. A short-axis ultrasound of the aortic valve allows for the best view of the aortic valve, and gives a clear indication of the adduction pattern of the aortic valves.If an “X” shape is seen, then the patient can be diagnosed with having a quadricuspid aortic valve. A transthoracic echocardiogram (TTE) indicates if there is an aortic regurgitation, but a 3-D transesophageal echocardiogram can give a better view of the aortic valve.Multidetector coronary CT angiography has been indicated as a single competent diagnostic imaging tool capable of delineating valvular anatomy, severity of regurgitation, and high risk coronary problems. Classification There have been seven described variations of the quadricuspid aortic valve. They are classified on a scale from A to G and describe the variations in size of the four cusps. The most common variation is that of B – three equal-sized cusps and one smaller cusp. There is no correlation between the anatomy and functional status of the aortic cusps. Treatment The typical method of treatment is through surgery such as aortic valve reconstruction surgery (AVRS) and aortic valve replacement, usually with a synthetic valve. Incidence Quadricuspid aortic valves are very rare cardiac valvular anomalies with a prevalence of 0.013% to 0.043% of cardiac cases and a prevalence of 1 in 6000 patients that undertake aortic valve surgery. There is a slight male predominance in all of the cases, and the mean age is 50.7. == References ==
Neutrophil-specific granule deficiency	Neutrophil-specific granule deficiency ( previously known as lactoferrin deficiency) is a rare congenital immunodeficiency characterized by an increased risk for pyogenic infections due to defective production of specific granules and gelatinase granules in patient neutrophils. Symptoms and signs Atypical infections are the key clinical manifestation of SGD. Within the first few years of life, patients will experience repeated pyogenic infections by species such as Staphylococcus aureus, Pseudomonas aeruginosa or other Enterobacteriaceae, and Candida albicans. Cutaneous ulcers or abscesses and pneumonia and chronic lung disease are common. Patients may also develop sepsis, mastoiditis, otitis media, and lymphadenopathy. Infants may present with vomiting, diarrhea, and failure to thrive.Diagnosis can be made based upon CEBPE gene mutation or a pathognomonic finding of a blood smear showing lack of specific granules. Neutrophils and eosinophils will contain hyposegmented nuclei (a pseudo-Pelger–Huet anomaly). Genetics A majority of patients with SGD have been found to have mutations in the CEBPE (CCAAT/enhancer-binding protein epsilon) gene, a transcription factor primarily active in myeloid cells. Almost all patients have been found to be homozygous for the mutation, suggesting the disease is autosomal recessive. One patient, heterozygous for the mutation, was found to be deficient in GFI1, a related gene. Pathophysiology The defect in CEBPE appears to block the ability of neutrophils to mature past the promyelocyte stage in bone marrow. Since specific (secondary) and gelatinase (tertiary) granules are only produced past the promyelocyte stage of development, these are deficient in SGD. Lactoferrin is the major enzyme found in specific granules, and will be largely absent in the granulocytes of these patients, along with defensins (despite these also being found in azurophilic (primary) granules). The other major components of azurophilic granules, such as lysozyme, cathepsin, and elastase will be normal, however a lack of defensins and lactoferrin drastically weakens the neutrophil innate ability to fight infection. Neutrophils will also display abnormal chemotaxis, such as a decreased response to fMLP, due to a lack of chemotactic receptors typically found in the specific granules. Diagnosis Treatment Treatment consists mainly of high dose antibiotics for active infections and prophylactic antibiotics for prevention of future infections. GM-CSF therapy or bone marrow transplant might be considered for severe cases. Prognosis is difficult to predict, but patients receiving treatment are generally able to survive to adulthood. Epidemiology Estimation of the frequency of SGD is difficult, as it is an extremely rare disease with few cases reported in literature. The condition was first reported in 1980, and since only a handful more cases have been published. References == External links ==
Hyperthyroidism	Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism. It is noted that thyrotoxicosis is related to hyper-kinetic movement disorders including chorea and myoclonus. Some, however, use the terms interchangeably. Signs and symptoms vary between people and may include irritability, muscle weakness, sleeping problems, a fast heartbeat, heat intolerance, diarrhea, enlargement of the thyroid, hand tremor, and weight loss. Symptoms are typically less severe in the elderly and during pregnancy. An uncommon complication is thyroid storm in which an event such as an infection results in worsening symptoms such as confusion and a high temperature and often results in death. The opposite is hypothyroidism, when the thyroid gland does not make enough thyroid hormone.Graves disease is the cause of about 50% to 80% of the cases of hyperthyroidism in the United States. Other causes include multinodular goiter, toxic adenoma, inflammation of the thyroid, eating too much iodine, and too much synthetic thyroid hormone. A less common cause is a pituitary adenoma. The diagnosis may be suspected based on signs and symptoms and then confirmed with blood tests. Typically blood tests show a low thyroid stimulating hormone (TSH) and raised T3 or T4. Radioiodine uptake by the thyroid, thyroid scan, and TSI antibodies may help determine the cause.Treatment depends partly on the cause and severity of disease. There are three main treatment options: radioiodine therapy, medications, and thyroid surgery. Radioiodine therapy involves taking iodine-131 by mouth which is then concentrated in and destroys the thyroid over weeks to months. The resulting hypothyroidism is treated with synthetic thyroid hormone. Medications such as beta blockers may control the symptoms, and anti-thyroid medications such as methimazole may temporarily help people while other treatments are having an effect. Surgery to remove the thyroid is another option. This may be used in those with very large thyroids or when cancer is a concern. In the United States hyperthyroidism affects about 1.2% of the population. It occurs between two and ten times more often in women. Onset is commonly between 20 and 50 years of age. Overall the disease is more common in those over the age of 60 years. Signs and symptoms Hyperthyroidism may be asymptomatic or present with significant symptoms. Some of the symptoms of hyperthyroidism include nervousness, irritability, increased perspiration, heart racing, hand tremors, anxiety, trouble sleeping, thinning of the skin, fine brittle hair, and muscular weakness—especially in the upper arms and thighs. More frequent bowel movements may occur, and diarrhea is common. Weight loss, sometimes significant, may occur despite a good appetite (though 10% of people with a hyperactive thyroid experience weight gain), vomiting may occur, and, for women, menstrual flow may lighten and menstrual periods may occur less often, or with longer cycles than usual.Thyroid hormone is critical to normal function of cells. In excess, it both overstimulates metabolism and disrupts the normal functioning of sympathetic nervous system, causing "speeding up" of various body systems and symptoms resembling an overdose of epinephrine (adrenaline). These include fast heartbeat and symptoms of palpitations, nervous system tremor such as of the hands and anxiety symptoms, digestive system hypermotility, unintended weight loss, and, in lipid panel blood tests, a lower and sometimes unusually low serum cholesterol.Major clinical signs of hyperthyroidism include weight loss (often accompanied by an increased appetite), anxiety, heat intolerance, hair loss (especially of the outer third of the eyebrows), muscle aches, weakness, fatigue, hyperactivity, irritability, high blood sugar, excessive urination, excessive thirst, delirium, tremor, pretibial myxedema (in Graves disease), emotional lability, and sweating. Panic attacks, inability to concentrate, and memory problems may also occur. Psychosis and paranoia, common during thyroid storm, are rare with milder hyperthyroidism. Many persons will experience complete remission of symptoms 1 to 2 months after a euthyroid state is obtained, with a marked reduction in anxiety, sense of exhaustion, irritability, and depression. Some individuals may have an increased rate of anxiety or persistence of affective and cognitive symptoms for several months to up to 10 years after a euthyroid state is established. In addition, those with hyperthyroidism may present with a variety of physical symptoms such as palpitations and abnormal heart rhythms (the notable ones being atrial fibrillation), shortness of breath (dyspnea), loss of libido, amenorrhea, nausea, vomiting, diarrhea, gynecomastia and feminization. Long term untreated hyperthyroidism can lead to osteoporosis. These classical symptoms may not be present often in the elderly.Neurological manifestations can include tremors, chorea, myopathy, and in some susceptible individuals (in particular of Asian descent) periodic paralysis. An association between thyroid disease and myasthenia gravis has been recognized. Thyroid disease, in this condition, is autoimmune in nature and approximately 5% of people with myasthenia gravis also have hyperthyroidism. Myasthenia gravis rarely improves after thyroid treatment and the relationship between the two entities is not well understood.In Graves disease, ophthalmopathy may cause the eyes to look enlarged because the eye muscles swell and push the eye forward. Sometimes, one or both eyes may bulge. Some have swelling of the front of the neck from an enlarged thyroid gland (a goiter).Minor ocular (eye) signs, which may be present in any type of hyperthyroidism, are eyelid retraction ("stare"), extraocular muscle weakness, and lid-lag. In hyperthyroid stare (Dalrymple sign) the eyelids are retracted upward more than normal (the normal position is at the superior corneoscleral limbus, where the "white" of the eye begins at the upper border of the iris). Extraocular muscle weakness may present with double vision. In lid-lag (von Graefes sign), when the person tracks an object downward with their eyes, the eyelid fails to follow the downward moving iris, and the same type of upper globe exposure which is seen with lid retraction occurs, temporarily. These signs disappear with treatment of the hyperthyroidism.Neither of these ocular signs should be confused with exophthalmos (protrusion of the eyeball), which occurs specifically and uniquely in hyperthyroidism caused by Graves disease (note that not all exophthalmos is caused by Graves disease, but when present with hyperthyroidism is diagnostic of Graves disease). This forward protrusion of the eyes is due to immune-mediated inflammation in the retro-orbital (eye socket) fat. Exophthalmos, when present, may exacerbate hyperthyroid lid-lag and stare. Thyroid storm Thyroid storm is a severe form of thyrotoxicosis characterized by rapid and often irregular heart beat, high temperature, vomiting, diarrhea, and mental agitation. Symptoms may not be typical in the young, old, or pregnant. It usually occurs due to untreated hyperthyroidism and can be provoked by infections. It is a medical emergency and requires hospital care to control the symptoms rapidly. Even with treatment, death occurs in 20% to 50% of cases. Hypothyroidism Hyperthyroidism due to certain types of thyroiditis can eventually lead to hypothyroidism (a lack of thyroid hormone), as the thyroid gland is damaged. Also, radioiodine treatment of Graves disease often eventually leads to hypothyroidism. Such hypothyroidism may be diagnosed with thyroid hormone testing and treated by oral thyroid hormone supplementation. Causes There are several causes of hyperthyroidism. Most often, the entire gland is overproducing thyroid hormone. Less commonly, a single nodule is responsible for the excess hormone secretion, called a "hot" nodule. Thyroiditis (inflammation of the thyroid) can also cause hyperthyroidism. Functional thyroid tissue producing an excess of thyroid hormone occurs in a number of clinical conditions. The major causes in humans are: Graves disease. An autoimmune disease (usually, the most common cause with 50–80% worldwide, although this varies substantially with location- i.e., 47% in Switzerland (Horst et al., 1987) to 90% in the USA (Hamburger et al. 1981)). Thought to be due to varying levels of iodine in the diet. It is eight times more common in females than males and often occurs in young females, around 20 – 40 years of age. Toxic thyroid adenoma (the most common cause in Switzerland, 53%, thought to be atypical due to a low level of dietary iodine in this country) Toxic multinodular goiterHigh blood levels of thyroid hormones (most accurately termed hyperthyroxinemia) can occur for a number of other reasons: Inflammation of the thyroid is called thyroiditis. There are several different kinds of thyroiditis including Hashimotos thyroiditis (Hypothyroidism immune-mediated), and subacute thyroiditis (de Quervains). These may be initially associated with secretion of excess thyroid hormone but usually progress to gland dysfunction and, thus, to hormone deficiency and hypothyroidism. Oral consumption of excess thyroid hormone tablets is possible (surreptitious use of thyroid hormone), as is the rare event of eating ground beef or pork contaminated with thyroid tissue, and thus thyroid hormones (termed hamburger thyrotoxicosis or alimentary thyrotoxicosis). Pharmacy compounding errors may also be a cause. Amiodarone, an antiarrhythmic drug, is structurally similar to thyroxine and may cause either under-or overactivity of the thyroid. Postpartum thyroiditis (PPT) occurs in about 7% of women during the year after they give birth. PPT typically has several phases, the first of which is hyperthyroidism. This form of hyperthyroidism usually corrects itself within weeks or months without the need for treatment. A struma ovarii is a rare form of monodermal teratoma that contains mostly thyroid tissue, which leads to hyperthyroidism. Excess iodine consumption notably from algae such as kelp.Thyrotoxicosis can also occur after taking too much thyroid hormone in the form of supplements, such as levothyroxine (a phenomenon known as exogenous thyrotoxicosis, alimentary thyrotoxicosis, or occult factitial thyrotoxicosis).Hypersecretion of thyroid stimulating hormone (TSH), which in turn is almost always caused by a pituitary adenoma, accounts for much less than 1 percent of hyperthyroidism cases. Diagnosis Measuring the level of thyroid-stimulating hormone (TSH), produced by the pituitary gland (which in turn is also regulated by the hypothalamuss TSH Releasing Hormone) in the blood is typically the initial test for suspected hyperthyroidism. A low TSH level typically indicates that the pituitary gland is being inhibited or "instructed" by the brain to cut back on stimulating the thyroid gland, having sensed increased levels of T4 and/or T3 in the blood. In rare circumstances, a low TSH indicates primary failure of the pituitary, or temporary inhibition of the pituitary due to another illness (euthyroid sick syndrome) and so checking the T4 and T3 is still clinically useful.Measuring specific antibodies, such as anti-TSH-receptor antibodies in Graves disease, or anti-thyroid peroxidase in Hashimotos thyroiditis—a common cause of hypothyroidism—may also contribute to the diagnosis. The diagnosis of hyperthyroidism is confirmed by blood tests that show a decreased thyroid-stimulating hormone (TSH) level and elevated T4 and T3 levels. TSH is a hormone made by the pituitary gland in the brain that tells the thyroid gland how much hormone to make. When there is too much thyroid hormone, the TSH will be low. A radioactive iodine uptake test and thyroid scan together characterizes or enables radiologists and doctors to determine the cause of hyperthyroidism. The uptake test uses radioactive iodine injected or taken orally on an empty stomach to measure the amount of iodine absorbed by the thyroid gland. Persons with hyperthyroidism absorb much more iodine than healthy persons which includes radioactive iodine which is easy to measure. A thyroid scan producing images is typically conducted in connection with the uptake test to allow visual examination of the over-functioning gland.Thyroid scintigraphy is a useful test to characterize (distinguish between causes of) hyperthyroidism, and this entity from thyroiditis. This test procedure typically involves two tests performed in connection with each other: an iodine uptake test and a scan (imaging) with a gamma camera. The uptake test involves administering a dose of radioactive iodine (radioiodine), traditionally iodine-131 (131I), and more recently iodine-123 (123I). Iodine-123 may be the preferred radionuclide in some clinics due to its more favorable radiation dosimetry (i.e. less radiation dose to the person per unit administered radioactivity) and a gamma photon energy more amenable to imaging with the gamma camera. For the imaging scan, I-123 is considered an almost ideal isotope of iodine for imaging thyroid tissue and thyroid cancer metastasis.Typical administration involves a pill or liquid containing sodium iodide (NaI) taken orally, which contains a small amount of iodine-131, amounting to perhaps less than a grain of salt. A 2-hour fast of no food prior to and for 1 hour after ingesting the pill is required. This low dose of radioiodine is typically tolerated by individuals otherwise allergic to iodine (such as those unable to tolerate contrast mediums containing larger doses of iodine such as used in CT scan, intravenous pyelogram (IVP), and similar imaging diagnostic procedures). Excess radioiodine that does not get absorbed into the thyroid gland is eliminated by the body in urine. Some people with hyperthyroidism may experience a slight allergic reaction to the diagnostic radioiodine and may be given an antihistamine.The person returns 24 hours later to have the level of radioiodine "uptake" (absorbed by the thyroid gland) measured by a device with a metal bar placed against the neck, which measures the radioactivity emitting from the thyroid. This test takes about 4 minutes while the uptake % (i.e., percentage) is accumulated (calculated) by the machine software. A scan is also performed, wherein images (typically a center, left and right angle) are taken of the contrasted thyroid gland with a gamma camera; a radiologist will read and prepare a report indicating the uptake % and comments after examining the images. People with hyperthyroid will typically "take up" higher than normal levels of radioiodine. Normal ranges for RAI uptake are from 10 to 30%. In addition to testing the TSH levels, many doctors test for T3, Free T3, T4, and/or Free T4 for more detailed results. Free T4 is unbound to any protein in the blood. Adult limits for these hormones are: TSH (units): 0.45 – 4.50 uIU/mL; T4 Free/Direct (nanograms): 0.82 – 1.77 ng/dl; and T3 (nanograms): 71 – 180 ng/dl. Persons with hyperthyroidism can easily exhibit levels many times these upper limits for T4 and/or T3. See a complete table of normal range limits for thyroid function at the thyroid gland article. In hyperthyroidism CK-MB (Creatine kinase) is usually elevated. Subclinical In overt primary hyperthyroidism, TSH levels are low and T4 and T3 levels are high. Subclinical hyperthyroidism is a milder form of hyperthyroidism characterized by low or undetectable serum TSH level, but with a normal serum free thyroxine level. Although the evidence for doing so is not definitive, treatment of elderly persons having subclinical hyperthyroidism could reduce the number of cases of atrial fibrillation. There is also an increased risk of bone fractures (by 42%) in people with subclinical hyperthyroidism; there is insufficient evidence to say whether treatment with antithyroid medications would reduce that risk.A 2022 meta-analysis found subclinical hyperthyroidism to be associated with cardiovascular death. Screening In those without symptoms who are not pregnant there is little evidence for or against screening. Treatment Antithyroid drugs Thyrostatics (antithyroid drugs) are drugs that inhibit the production of thyroid hormones, such as carbimazole (used in the UK) and methimazole (used in the US, Germany and Russia), and propylthiouracil. Thyrostatics are believed to work by inhibiting the iodination of thyroglobulin by thyroperoxidase and, thus, the formation of tetraiodothyronine (T4). Propylthiouracil also works outside the thyroid gland, preventing the conversion of (mostly inactive) T4 to the active form T3. Because thyroid tissue usually contains a substantial reserve of thyroid hormone, thyrostatics can take weeks to become effective and the dose often needs to be carefully titrated over a period of months, with regular doctor visits and blood tests to monitor results.A very high dose is often needed early in treatment, but, if too high a dose is used persistently, people can develop symptoms of hypothyroidism. This titrating of the dose is difficult to do accurately, and so sometimes a "block and replace" attitude is taken. In block and replace treatments thyrostatics are taken in sufficient quantities to completely block thyroid hormones, and the person treated as though they have complete hypothyroidism. Beta-blockers Many of the common symptoms of hyperthyroidism such as palpitations, trembling, and anxiety are mediated by increases in beta-adrenergic receptors on cell surfaces. Beta blockers, typically used to treat high blood pressure, are a class of drugs that offset this effect, reducing rapid pulse associated with the sensation of palpitations, and decreasing tremor and anxiety. Thus, a person with hyperthyroidism can often obtain immediate temporary relief until the hyperthyroidism can be characterized with the Radioiodine test noted above and more permanent treatment take place. Note that these drugs do not treat hyperthyroidism or any of its long-term effects if left untreated, but, rather, they treat or reduce only symptoms of the condition.Some minimal effect on thyroid hormone production however also comes with propranolol—which has two roles in the treatment of hyperthyroidism, determined by the different isomers of propranolol. L-propranolol causes beta-blockade, thus treating the symptoms associated with hyperthyroidism such as tremor, palpitations, anxiety, and heat intolerance. D-propranolol inhibits thyroxine deiodinase, thereby blocking the conversion of T4 to T3, providing some though minimal therapeutic effect. Other beta-blockers are used to treat only the symptoms associated with hyperthyroidism. Propranolol in the UK, and metoprolol in the US, are most frequently used to augment treatment for people with hyperthyroid. Diet People with autoimmune hyperthyroidism (such as in Graves disease) should not eat foods high in iodine, such as edible seaweed and kelps.From a public health perspective, the general introduction of iodized salt in the United States in 1924 resulted in lower disease, goiters, as well as improving the lives of children whose mothers would not have eaten enough iodine during pregnancy which would have lowered the IQs of their children. Surgery Surgery (thyroidectomy to remove the whole thyroid or a part of it) is not extensively used because most common forms of hyperthyroidism are quite effectively treated by the radioactive iodine method, and because there is a risk of also removing the parathyroid glands, and of cutting the recurrent laryngeal nerve, making swallowing difficult, and even simply generalized staphylococcal infection as with any major surgery. Some people with Graves may opt for surgical intervention. This includes those that cannot tolerate medicines for one reason or another, people that are allergic to iodine, or people that refuse radioiodine.If people have toxic nodules treatments typically include either removal or injection of the nodule with alcohol. Radioiodine In iodine-131 (radioiodine) radioisotope therapy, which was first pioneered by Dr. Saul Hertz, radioactive iodine-131 is given orally (either by pill or liquid) on a one-time basis, to severely restrict, or altogether destroy the function of a hyperactive thyroid gland. This isotope of radioactive iodine used for ablative treatment is more potent than diagnostic radioiodine (usually iodine-123 or a very low amount of iodine-131), which has a biological half-life from 8–13 hours. Iodine-131, which also emits beta particles that are far more damaging to tissues at short range, has a half-life of approximately 8 days. People not responding sufficiently to the first dose are sometimes given an additional radioiodine treatment, at a larger dose. Iodine-131 in this treatment is picked up by the active cells in the thyroid and destroys them, rendering the thyroid gland mostly or completely inactive.Since iodine is picked up more readily (though not exclusively) by thyroid cells, and (more important) is picked up even more readily by over-active thyroid cells, the destruction is local, and there are no widespread side effects with this therapy. Radioiodine ablation has been used for over 50 years, and the only major reasons for not using it are pregnancy and breastfeeding (breast tissue also picks up and concentrates iodine). Once the thyroid function is reduced, replacement hormone therapy (levothyroxine) taken orally each day replaces the thyroid hormone that is normally produced by the body.There is extensive experience, over many years, of the use of radioiodine in the treatment of thyroid overactivity and this experience does not indicate any increased risk of thyroid cancer following treatment. However, a study from 2007 has reported an increased number of cancer cases after radioiodine treatment for hyperthyroidism.The principal advantage of radioiodine treatment for hyperthyroidism is that it tends to have a much higher success rate than medications. Depending on the dose of radioiodine chosen, and the disease under treatment (Graves vs. toxic goiter, vs. hot nodule etc.), the success rate in achieving definitive resolution of the hyperthyroidism may vary from 75 to 100%. A major expected side-effect of radioiodine in people with Graves disease is the development of lifelong hypothyroidism, requiring daily treatment with thyroid hormone. On occasion, some people may require more than one radioactive treatment, depending on the type of disease present, the size of the thyroid, and the initial dose administered.People with Graves disease manifesting moderate or severe Graves ophthalmopathy are cautioned against radioactive iodine-131 treatment, since it has been shown to exacerbate existing thyroid eye disease. People with mild or no ophthalmic symptoms can mitigate their risk with a concurrent six-week course of prednisone. The mechanisms proposed for this side effect involve a TSH receptor common to both thyrocytes and retro-orbital tissue.As radioactive iodine treatment results in the destruction of thyroid tissue, there is often a transient period of several days to weeks when the symptoms of hyperthyroidism may actually worsen following radioactive iodine therapy. In general, this happens as a result of thyroid hormones being released into the blood following the radioactive iodine-mediated destruction of thyroid cells that contain thyroid hormone. In some people, treatment with medications such as beta blockers (propranolol, atenolol, etc.) may be useful during this period of time. Most people do not experience any difficulty after the radioactive iodine treatment, usually given as a small pill. On occasion, neck tenderness or a sore throat may become apparent after a few days, if moderate inflammation in the thyroid develops and produces discomfort in the neck or throat area. This is usually transient, and not associated with a fever, etc.It is recommended that breastfeeding be stopped at least six weeks before radioactive iodine treatment and that it not be resumed, although it can be done in future pregnancies. It also shouldnt be done during pregnancy, and pregnancy should be put off until at least 6–12 months after treatment.A common outcome following radioiodine is a swing from hyperthyroidism to the easily treatable hypothyroidism, which occurs in 78% of those treated for Graves thyrotoxicosis and in 40% of those with toxic multinodular goiter or solitary toxic adenoma. Use of higher doses of radioiodine reduces the number of cases of treatment failure, with penalty for higher response to treatment consisting mostly of higher rates of eventual hypothyroidism which requires hormone treatment for life.There is increased sensitivity to radioiodine therapy in thyroids appearing on ultrasound scans as more uniform (hypoechogenic), due to densely packed large cells, with 81% later becoming hypothyroid, compared to just 37% in those with more normal scan appearances (normoechogenic). Thyroid storm Thyroid storm presents with extreme symptoms of hyperthyroidism. It is treated aggressively with resuscitation measures along with a combination of the above modalities including: an intravenous beta blockers such as propranolol, followed by a thioamide such as methimazole, an iodinated radiocontrast agent or an iodine solution if the radiocontrast agent is not available, and an intravenous steroid such as hydrocortisone. Alternative medicine In countries such as China, herbs used alone or with antithyroid medications are used to treat hyperthyroidism. Very low quality evidence suggests that traditional Chinese herbal medications may be beneficial when taken along with routine hyperthyroid medications, however, there is no reliable evidence to determine the effectiveness of Chinese herbal medications for treating hyperthyroidism. Epidemiology In the United States hyperthyroidism affects about 1.2% of the population. About half of these cases have obvious symptoms while the other half do not. It occurs between two and ten times more often in women. The disease is more common in those over the age of 60 years.Subclinical hyperthyroidism modestly increases the risk of cognitive impairment and dementia. History Caleb Hillier Parry first made the association between the goiter and protrusion of the eyes in 1786, however, did not publish his findings until 1825. In 1835, Irish doctor Robert James Graves discovered a link between the protrusion of the eyes and goiter, giving his name to the autoimmune disease now known as Graves Disease. Pregnancy Recognizing and evaluating hyperthyroidism in pregnancy is a diagnostic challenge. Thyroid hormones are naturally elevated during pregnancy. Thyroid function generally normalizes in by the second trimester without treatment. Hyperthyroidism must also be distinguished from gestational transient thyrotoxicosis; as it can increase the risk of complications for mother and child. Such risks include pregnancy-related hypertension, pregnancy loss, low-birth weight, still birth and behavioral disorders later in the childs life. Nonetheless, high maternal FT4 levels during pregnancy have been associated with impaired brain developmental outcomes of the offspring and this was independent of for example hCG levels. Other animals Cats Hyperthyroidism is one of the most common endocrine conditions affecting older domesticated housecats. In the United States, up to 10% of cats over ten years old have hyperthyroidism. The disease has become significantly more common since the first reports of feline hyperthyroidism in the 1970s. The most common cause of hyperthyroidism in cats is the presence of benign tumors called adenomas. 98% of cases are caused by the presence of an adenoma, but the reason these cats develop such tumors continues to be studied. The most common presenting symptoms are: rapid weight loss, tachycardia (rapid heart rate), vomiting, diarrhea, increased consumption of fluids (polydipsia),
Hyperthyroidism	increased appetite (polyphagia), and increased urine production (polyuria). Other symptoms include hyperactivity, possible aggression, an unkempt appearance, and large, thick claws. Heart murmurs and a gallop rhythm can develop due to secondary hypertrophic cardiomyopathy. About 70% of affected cats also have enlarged thyroid glands (goiter). 10% of cats exhibit "apathetic hyperthyroidism", which is characterized by anorexia and lethargy.The same three treatments used with humans are also options in treating feline hyperthyroidism (surgery, radioiodine treatment, and anti-thyroid drugs). There is also a special low iodine diet available that will control the symptoms providing no other food is fed; Hills y/d formula, when given exclusively, decreases T4 production by limiting the amount of iodine needed for thyroid hormone production. It is the only available commercial diet that focuses on managing feline hyperthyroidism. Medical and dietary management using methimazole and Hills y/d cat food will give hyperthyroid cats an average of 2 years before dying due to secondary conditions such as heart and kidney failure. Drugs used to help manage the symptoms of hyperthyroidism are methimazole and carbimazole. Drug therapy is the least expensive option, even though the drug must be administered daily for the remainder of the cats life. Carbimazole is only available as a once daily tablet. Methimazole is available as an oral solution, a tablet, and compounded as a topical gel that is applied using a finger cot to the hairless skin inside a cats ear. Many cat owners find this gel a good option for cats that dont like being given pills. Radioiodine treatment, however, is not available in all areas, as this treatment requires nuclear radiological expertise and facilities that not only board the cat, but are specially equipped to manage the cats urine, sweat, saliva, and stool, which are radioactive for several days after the treatment, usually for a total of 3 weeks (the cat spends the first week in total isolation and the next two weeks in close confinement). In the United States, the guidelines for radiation levels vary from state to state; some states such as Massachusetts allow hospitalization for as little as two days before the animal is sent home with care instructions. Dogs Hyperthyroidism is much less common in dogs compared to cats. Hyperthyroidism may be caused by a thyroid tumor. This may be a thyroid carcinoma. About 90% of carcinomas are very aggressive; they invade the surrounding tissues and metastasize (spread) to other tissues, particularly the lungs. This has a poor prognosis. Surgery to remove the tumor is often very difficult due to metastasis into arteries, the esophagus, or the windpipe. It may be possible to reduce the size of the tumor, thus relieving symptoms and allowing time for other treatments to work. About 10% of thyroid tumors are benign; these often cause few symptoms.In dogs treated for hypothyroidism (lack of thyroid hormone), iatrogenic hyperthyroidism may occur as a result of an overdose of the thyroid hormone replacement medication, levothyroxine; in this case, treatment involves reducing the dose of levothyroxine. Dogs which display coprophagy, the consumption of feces, and also live in a household with a dog receiving levothyroxine treatment, may develop hyperthyroidism if they frequently eat the feces from the dog receiving levothyroxine treatment.Hyperthyroidism may occur if a dog eats an excessive amount of thyroid gland tissue. This has occurred in dogs fed commercial dog food. See also High-output cardiac failure Jod-Basedow phenomenon Hashitoxicosis Further reading 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis, Thyroid. Oct 2016.1343-1421. References Further reading External links Merck Manual article about hyperthyroidism "Hyperthyroidism". MedlinePlus. U.S. National Library of Medicine.
Kuru	Kuru may refer to: Anthropology and history Kuru (disease), a type of transmissible spongiform encephalopathy associated with the cannibalistic funeral practices of the Fore people Kuru (mythology), part of Meithei mythology Kuru Kingdom, a powerful Indo-Aryan tribe and kingdom during the Vedic period (Early Iron Age) and later a republic during the Mahajanapada period in India King Kuru (Vedic Hindu era), the imputed ancestral king of Indo-Aryan Kuru tribe Kuru (sport), a traditional Bhutanese sport Kuru, also called sintak, a traditional game of stones from the Philippines Places Kuru River, a river in South Sudan Kuru, Finland, municipality Kuru, Iran Kuru, Nigeria Kuru, Ida-Viru County, village in Iisaku Parish, Ida-Viru County, Estonia Kuru, Lääne-Viru County, village in Tapa Parish, Lääne-Viru County, Estonia Kuru block, a community development block in Jharkhand, India Kuru, Lohardaga, a village in Jhankhand, India Transport HMAS Kuru, an Australian patrol boat operational between 1938 and 1943 S/S Kuru, a Finnish lake steamer People Ahmet Kuru (born 1982), Turkish footballer Bartoloměj Kuru (born 1987), Austrian footballer Büşra Kuru (born 2001), German-born Turkish womens footballer Taygun Kuru (born 1990), Turkish-German footballer Uğur Arslan Kuru (born 1989), Turkish footballer Kuruvilla Pandikattu (born 1957), Indian philosopher Other uses Kuru (film), a Japanese supernatural horror film KURU (FM), a radio station (89.1 FM) licensed to serve Silver City, New Mexico, United States Kuru kulla, a genus dromaeosaurid theropod See also Kourou (disambiguation) Kurus (disambiguation) Kuru Kuru (disambiguation) Kurultai, a political and military council of ancient Mongol and Turkic chiefs and khans
Mitochondrial disease	Mitochondrial disease is a group of disorders caused by mitochondrial dysfunction. Mitochondria are the organelles that generate energy for the cell and are found in every cell of the human body except red blood cells. They convert the energy of food molecules into the ATP that powers most cell functions. Mitochondrial diseases take on unique characteristics both because of the way the diseases are often inherited and because mitochondria are so critical to cell function. A subclass of these diseases that have neuromuscular symptoms are known as mitochondrial myopathies. Types Examples of mitochondrial diseases include: Mitochondrial myopathy Diabetes mellitus and deafness (DAD) this combination at an early age can be due to mitochondrial disease Diabetes mellitus and deafness can be found together for other reasons Lebers hereditary optic neuropathy (LHON) visual loss beginning in young adulthood eye disorder characterized by progressive loss of central vision due to degeneration of the optic nerves and retina affects 1 in 50,000 people in Finland Leigh syndrome, subacute necrotizing encephalomyelopathyafter normal development the disease usually begins late in the first year of life, although onset may occur in adulthood a rapid decline in function occurs and is marked by seizures, altered states of consciousness, dementia, ventilatory failure Neuropathy, ataxia, retinitis pigmentosa, and ptosis (NARP) progressive symptoms as described in the acronym dementia Myoneurogenic gastrointestinal encephalopathy (MNGIE) gastrointestinal pseudo-obstruction neuropathy MERRF syndrome progressive myoclonic epilepsy "Ragged Red Fibers" are clumps of diseased mitochondria that accumulate in the subsarcolemmal region of the muscle fiber and appear when muscle is stained with modified Gömöri trichrome stain short stature hearing loss lactic acidosis exercise intolerance MELAS syndrome Mitochondrial DNA depletion syndromeConditions such as Friedreichs ataxia can affect the mitochondria but are not associated with mitochondrial proteins. Presentation Associated conditions Acquired conditions in which mitochondrial dysfunction has been involved are: diabetes Huntingtons disease cancer Alzheimers disease, Parkinsons disease bipolar disorder, schizophrenia, aging and senescence, anxiety disorders cardiovascular disease sarcopenia chronic fatigue syndromeThe body, and each mutation, is modulated by other genome variants; the mutation that in one individual may cause liver disease might in another person cause a brain disorder. The severity of the specific defect may also be great or small. Some defects include exercise intolerance. Defects often affect the operation of the mitochondria and multiple tissues more severely, leading to multi-system diseases.It has also been reported that drug tolerant cancer cells have an increased number and size of mitochondria, which suggested an increase in mitochondrial biogenesis. Interestingly, a recent study in Nature Nanotechnology has reported that cancer cells can hijack the mitochondria from immune cells via physical tunneling nanotubes.As a rule, mitochondrial diseases are worse when the defective mitochondria are present in the muscles, cerebrum, or nerves, because these cells use more energy than most other cells in the body. Although mitochondrial diseases vary greatly in presentation from person to person, several major clinical categories of these conditions have been defined, based on the most common phenotypic features, symptoms, and signs associated with the particular mutations that tend to cause them.An outstanding question and area of research is whether ATP depletion or reactive oxygen species are in fact responsible for the observed phenotypic consequences.Cerebellar atrophy or hypoplasia has sometimes been reported to be associated. Causes Mitochondrial disorders may be caused by mutations (acquired or inherited), in mitochondrial DNA (mtDNA), or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondrial dysfunction due to adverse effects of drugs, infections, or other environmental causes. Oxalate may enter cells where it is known to cause mitochondrial dysfunction. Nuclear DNA has two copies per cell (except for sperm and egg cells), one copy being inherited from the father and the other from the mother. Mitochondrial DNA, however, is inherited from the mother only (with some exceptions) and each mitochondrion typically contains between 2 and 10 mtDNA copies. During cell division the mitochondria segregate randomly between the two new cells. Those mitochondria make more copies, normally reaching 500 mitochondria per cell. As mtDNA is copied when mitochondria proliferate, they can accumulate random mutations, a phenomenon called heteroplasmy. If only a few of the mtDNA copies inherited from the mother are defective, mitochondrial division may cause most of the defective copies to end up in just one of the new mitochondria (for more detailed inheritance patterns, see human mitochondrial genetics). Mitochondrial disease may become clinically apparent once the number of affected mitochondria reaches a certain level; this phenomenon is called "threshold expression". Mitochondria possess many of the same DNA repair pathways as nuclei do—but not all of them; therefore, mutations occur more frequently in mitochondrial DNA than in nuclear DNA (see Mutation rate). This means that mitochondrial DNA disorders may occur spontaneously and relatively often. Defects in enzymes that control mitochondrial DNA replication (all of which are encoded for by genes in the nuclear DNA) may also cause mitochondrial DNA mutations. Most mitochondrial function and biogenesis is controlled by nuclear DNA. Human mitochondrial DNA encodes 13 proteins of the respiratory chain, while most of the estimated 1,500 proteins and components targeted to mitochondria are nuclear-encoded. Defects in nuclear-encoded mitochondrial genes are associated with hundreds of clinical disease phenotypes including anemia, dementia, hypertension, lymphoma, retinopathy, seizures, and neurodevelopmental disorders.A study by Yale University researchers (published in the February 12, 2004, issue of the New England Journal of Medicine) explored the role of mitochondria in insulin resistance among the offspring of patients with type 2 diabetes. Other studies have shown that the mechanism may involve the interruption of the mitochondrial signaling process in body cells (intramyocellular lipids). A study conducted at the Pennington Biomedical Research Center in Baton Rouge, Louisiana showed that this, in turn, partially disables the genes that produce mitochondria. Mechanisms The effective overall energy unit for the available body energy is referred to as the daily glycogen generation capacity, and is used to compare the mitochondrial output of affected or chronically glycogen-depleted individuals to healthy individuals. This value is slow to change in a given individual, as it takes between 18 and 24 months to complete a full cycle.The glycogen generation capacity is entirely dependent on, and determined by, the operating levels of the mitochondria in all of the cells of the human body; however, the relation between the energy generated by the mitochondria and the glycogen capacity is very loose and is mediated by many biochemical pathways. The energy output of full healthy mitochondrial function can be predicted exactly by a complicated theoretical argument, but this argument is not straightforward, as most energy is consumed by the brain and is not easily measurable. Diagnosis Mitochondrial diseases are usually detected by analysing muscle samples, where the presence of these organelles is higher. The most common tests for the detection of these diseases are: Southern blot to detect big deletions or duplications Polymerase chain reaction and specific mutation testing Sequencing Treatments Although research is ongoing, treatment options are currently limited; vitamins are frequently prescribed, though the evidence for their effectiveness is limited.Pyruvate has been proposed in 2007 as a treatment option. N-acetyl cysteine reverses many models of mitochondrial dysfunction. In the case of mood disorders, specifically bipolar disorder, it is hypothesized that N-acetyl-cysteine (NAC), acetyl-L-carnitine (ALCAR), S-adenosylmethionine (SAMe), coenzyme Q10 (CoQ10), alpha-lipoic acid (ALA), creatine monohydrate (CM), and melatonin could be potential treatment options. Gene therapy prior to conception Mitochondrial replacement therapy (MRT), where the nuclear DNA is transferred to another healthy egg cell leaving the defective mitochondrial DNA behind, is an IVF treatment procedure. Using a similar pronuclear transfer technique, researchers at Newcastle University led by Douglass Turnbull successfully transplanted healthy DNA in human eggs from women with mitochondrial disease into the eggs of women donors who were unaffected. In such cases, ethical questions have been raised regarding biological motherhood, since the child receives genes and gene regulatory molecules from two different women. Using genetic engineering in attempts to produce babies free of mitochondrial disease is controversial in some circles and raises important ethical issues. A male baby was born in Mexico in 2016 from a mother with Leigh syndrome using MRT.In September 2012 a public consultation was launched in the UK to explore the ethical issues involved. Human genetic engineering was used on a small scale to allow infertile women with genetic defects in their mitochondria to have children. In June 2013, the United Kingdom government agreed to develop legislation that would legalize the three-person IVF procedure as a treatment to fix or eliminate mitochondrial diseases that are passed on from mother to child. The procedure could be offered from 29 October 2015 once regulations had been established.Embryonic mitochondrial transplant and protofection have been proposed as a possible treatment for inherited mitochondrial disease, and allotopic expression of mitochondrial proteins as a radical treatment for mtDNA mutation load. In June 2018 Australian Senates Senate Community Affairs References Committee recommended a move towards legalising Mitochondrial replacement therapy (MRT). Research and clinical applications of MRT were overseen by laws made by federal and state governments. State laws were, for the most part, consistent with federal law. In all states, legislation prohibited the use of MRT techniques in the clinic, and except for Western Australia, research on a limited range of MRT was permissible up to day 14 of embryo development, subject to a license being granted. In 2010, the Hon. Mark Butler MP, then Federal Minister for Mental Health and Ageing, had appointed an independent committee to review the two relevant acts: the Prohibition of Human Cloning for Reproduction Act 2002 and the Research Involving Human Embryos Act 2002. The committees report, released in July 2011, recommended the existing legislation remain unchanged Currently, human clinical trials are underway at GenSight Biologics (ClinicalTrials.gov # NCT02064569) and the University of Miami (ClinicalTrials.gov # NCT02161380) to examine the safety and efficacy of mitochondrial gene therapy in Lebers hereditary optic neuropathy. Epidemiology About 1 in 4,000 children in the United States will develop mitochondrial disease by the age of 10 years. Up to 4,000 children per year in the US are born with a type of mitochondrial disease. Because mitochondrial disorders contain many variations and subsets, some particular mitochondrial disorders are very rare. The average number of births per year among women at risk for transmitting mtDNA disease is estimated to approximately 150 in the United Kingdom and 800 in the United States. History The first pathogenic mutation in mitochondrial DNA was identified in 1988; from that time to 2016, around 275 other disease-causing mutations were identified.: 37 Notable cases Notable people with mitochondrial disease include: Mattie Stepanek, a poet, peace advocate, and motivational speaker who had dysautonomic mitochondrial myopathy, and who died at age 13. Rocco Baldelli, a coach and former center fielder in Major League Baseball who had to retire from active play at age 29 due to mitochondrial channelopathy. Charlie Gard, a British boy who had mitochondrial DNA depletion syndrome; decisions about his care were taken to various law courts. References External links Mitochondrial disease at Curlie International Mito Patients (IMP)
Hair disease	Hair diseases are disorders primarily associated with the follicles of the hair. A few examples are Alopecia Bubble hair deformity Hair casts Hair loss hypertrichosis Ingrown hair Monilethrix Premature greying of hair Pattern hair loss Trichorrhexis invaginataMany hair diseases can be associated with distinct underlying disorders. Piedra are fungal diseases. Hair disease may refer to excessive shedding or baldness (or both). Balding can be localised or diffuse, scarring or non-scarring. Increased hair can be due to hormonal factors (hirsutism) or non-hormonal (hypertrichosis). Scalp disorders may or may not be associated with hair loss. See also List of cutaneous conditions References External links https://www.nlm.nih.gov/medlineplus/hairdiseasesandhairloss.html
Grain itch	Grain itch is a cutaneous condition caused by several types of mites, and characterized by intense pruritus.: 454 See also Grocers itch List of cutaneous conditions List of mites associated with cutaneous reactions == References ==
Infantile neuroaxonal dystrophy	Infantile neuroaxonal dystrophy is a rare pervasive developmental disorder that primarily affects the nervous system. Individuals with infantile neuroaxonal dystrophy typically do not have any symptoms at birth, but between the ages of about 6 and 18 months they begin to experience delays in acquiring new motor and intellectual skills, such as crawling or beginning to speak. Eventually they lose previously acquired skills. Cause This condition is inherited in an autosomal recessive pattern, which means two copies of the gene (PLA2G6) in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene but do not show signs and symptoms of the disorder. Pathophysiology Mutations in the PLA2G6 gene have been identified in most individuals with infantile neuroaxonal dystrophy. The PLA2G6 gene provides instructions for making an enzyme called an A2 phospholipase. This enzyme family is involved in metabolizing phospholipids. Phospholipid metabolism is important for many body processes, including helping to keep the cell membrane intact and functioning properly. Specifically, the A2 phospholipase produced from the PLA2G6 gene, sometimes called PLA2 group VI, helps to regulate the levels of a compound called phosphatidylcholine, which is abundant in the cell membrane.Mutations in the PLA2G6 gene impair the function of the PLA2 group VI enzyme. This impairment of enzyme function may disrupt cell membrane maintenance and contribute to the development of spheroid bodies in the nerve axons. Although it is unknown how changes in this enzymes function lead to the signs and symptoms of infantile neuroaxonal dystrophy, phospholipid metabolism problems have been seen in both this disorder and a related disorder called pantothenate kinase-associated neurodegeneration. These disorders, as well as the more common Alzheimer disease and Parkinson disease, also are associated with changes in brain iron metabolism. Researchers are studying the links between phospholipid defects, brain iron, and damage to nerve cells, but have not determined how the iron accumulation that occurs in some individuals with infantile neuroaxonal dystrophy may contribute to the features of this disorder.A few individuals with infantile neuroaxonal dystrophy have not been found to have mutations in the PLA2G6 gene. The genetic cause of the condition in these cases is unknown; there is evidence that at least one other gene may be involved.Mutations in the NAGA gene, resulting in alpha-N-acetylgalactosaminidase deficiency, cause an infantile neuroaxonal dystrophy known as Schindler disease. Diagnosis In some cases, signs and symptoms of infantile neuroaxonal dystrophy first appear later in childhood or during the teenage years and progress more slowly. Children with infantile neuroaxonal dystrophy experience progressive difficulties with movement. Generally they have muscles that are at first weak and "floppy" (hypotonic), and then gradually become very stiff (spastic). Eventually, affected children lose the ability to move independently. Lack of muscle strength causes difficulty with feeding and breathing problems that can lead to frequent infections, such as pneumonia. Seizures occur in some affected children.Rapid, involuntary eye movements (nystagmus), eyes that do not look in the same direction (strabismus), and vision loss due to deterioration (atrophy) of the optic nerve are characteristic of infantile neuroaxonal dystrophy. Hearing loss may also develop. Children with this disorder experience progressive deterioration of cognitive functions (dementia), and eventually lose awareness of their surroundings.Infantile neuroaxonal dystrophy is characterized by the development of swellings called spheroid bodies in the axons, the fibers that extend from nerve cells (neurons) and transmit impulses to muscles and other neurons. A part of the brain called the cerebellum, which helps to control movements, may also be damaged. In some individuals with infantile neuroaxonal dystrophy, abnormal amounts of iron accumulate in a specific region of the brain called the basal ganglia. Management Currently, only palliative treatment is available: alleviation of spasticity and seizures, baclofen for relieving dystonia, physiotherapeutic treatment and measures such as gastric feeding tube or tracheostomy to prevent aspirational pneumonia. Research An open-label clinical study for long-term evaluation of efficacy, safety, tolerability, and pharmacokinetics of a deuterium-enhanced polyunsaturated fatty acid RT001, which, when taken with food, can protect the neuronal cells from degeneration, started in the Summer 2018.The loss of iPLA2-VIA, the fly homolog of PLA2G6, reduces lifespan, impairs synaptic transmission, and causes neurodegeneration. Phospholipases typically hydrolyze glycerol phospholipids, but loss of iPLA2-VIA does not affect the phospholipid composition of brain tissue but rather causes an elevation in ceramides. Reducing ceramides with drugs, including myriocin or desipramine, alleviates lysosomal stress and suppresses neurodegeneration. References Further reading GeneReview/NIH/UW entry on Infantile Neuroaxonal Dystrophy National Library of Medicine. Genetics Home Reference - Infantile neuroaxonal dystrophy == External links ==
Endemic goitre	Endemic goiter is a type of goitre that is associated with dietary iodine deficiency. Cause Some inland areas where soil and water lacks in iodine compounds and consumption of marine foods is low are known for higher incidence of goitre. In such areas goitre is said to be "endemic". Prevention This type of goiter is easily preventable. In most developed countries regulations have been put into force by health policy institutions requiring salt, flour or water to be fortified with iodine. Treatment Treatment of endemic goiter is medical with iodine and thyroxine preparations. Surgery is only necessary in cases where complicated by significant compression of nearby structures. References == External links ==
Desmosterolosis	Desmosterolosis in medicine and biology is a defect in cholesterol biosynthesis. It results in an accumulation of desmosterol and a variety of associated symptoms. Only two cases have been reported as of 2007. The condition is due to inactivating mutations in 24-dehydrocholesterol reductase. Certain anticholesterolemic and antiestrogenic drugs such as triparanol, ethamoxytriphetol, and clomifene have been found to inhibit conversion of desmosterol into cholesterol and to induce desmosterolosis, for instance cataracts. References == External links ==
Factitious disorder imposed on another	Factitious disorder imposed on another (FDIA), also called Munchausen syndrome by proxy (MSbP), is a condition in which a caregiver creates the appearance of health problems in another person, typically their child. This may include injuring the child or altering test samples. The caregiver then presents the person as being sick or injured. Permanent injury or death of the victim may occur as a result of the disorder. The behaviour occurs without a specific benefit to the caregiver.The cause of FDIA is unknown. The primary motive may be to gain attention and manipulate physicians. Risk factors for FDIA include pregnancy related complications and a mother who was abused as a child or has factitious disorder imposed on self. Diagnosis is supported when removing the child from the caregiver results in improvement of symptoms or video surveillance without the knowledge of the caregiver finds concerns. Those affected by the disorder have been subjected to a form of physical abuse and medical neglect.Management of FDIA may require putting the child in foster care. It is not known how effective therapy is for FDIA; it is assumed it may work for those who admit they have a problem. The prevalence of FDIA is unknown, but it appears to be relatively rare. More than 95% of cases involve a persons mother.The prognosis for the caregiver is poor. However, there is a burgeoning literature on possible courses of therapy.The condition was first named, as "Munchausen syndrome by proxy", in 1977 by British pediatrician Roy Meadow. Some aspects of FDIA may represent criminal behavior. Signs and symptoms In factitious disorder imposed on another, a caregiver makes a dependent person appear mentally or physically ill in order to gain attention. To perpetuate the medical relationship, the caregiver systematically misrepresents symptoms, fabricates signs, manipulates laboratory tests, or even purposely harms the dependent (e.g. by poisoning, suffocation, infection, physical injury). It is important to note the caregiver is not performing this behavior for obvious external reward, such as money. Studies have shown a mortality rate of between six and ten percent, making it perhaps the most lethal form of abuse.In one study, the average age of the affected individual at the time of diagnosis was four years old. Slightly over 50% were aged 24 months or younger, and 75% were under six years old. The average duration from onset of symptoms to diagnosis was 22 months. By the time of diagnosis, six percent of the affected persons were dead, mostly from apnea (a common result of smothering) or starvation, and seven percent had long-term or permanent injury. About half of the affected had siblings; 25% of the known siblings were dead, and 61% of siblings had symptoms similar to the affected or that were otherwise suspicious. The mother was the perpetrator in 76.5% of the cases, the father in 6.7%.Most present about three medical problems in some combination of the 103 different reported symptoms. The most-frequently reported problems are apnea (26.8% of cases), anorexia or feeding problems (24.6% of cases), diarrhea (20%), seizures (17.5%), cyanosis (blue skin) (11.7%), behavior (10.4%), asthma (9.5%), allergy (9.3%), and fevers (8.6%). Other symptoms include failure to thrive, vomiting, bleeding, rash, and infections. Many of these symptoms are easy to fake because they are subjective. A parent reporting that their child had a fever in the past 24 hours is making a claim that is impossible to prove or disprove. The number and variety of presented symptoms contribute to the difficulty in reaching a proper diagnosis. Aside from the motive (most commonly attributed to be a gain in attention or sympathy), another feature that differentiates FDIA from "typical" physical child abuse is the degree of premeditation involved. Whereas most physical abuse entails lashing out at a child in response to some behavior (e.g., crying, bedwetting, spilling food), assaults on the FDIA victim tend to be unprovoked and planned.Also unique to this form of abuse is the role that health care providers play by actively, albeit unintentionally, enabling the abuse. By reacting to the concerns and demands of perpetrators, medical professionals are manipulated into a partnership of child maltreatment. Challenging cases that defy simple medical explanations may prompt health care providers to pursue unusual or rare diagnoses, thus allocating even more time to the child and the abuser. Even without prompting, medical professionals may be easily seduced into prescribing diagnostic tests and therapies that may be painful, costly, or potentially injurious to the child. If the health practitioner resists ordering further tests, drugs, procedures, surgeries, or specialists, the FDIA abuser makes the medical system appear negligent for refusing to help a sick child and their selfless parent. Like those with Munchausen syndrome, FDIA perpetrators are known to switch medical providers frequently until they find one that is willing to meet their level of need; this practice is known as "doctor shopping" or "hospital hopping". The perpetrator continues the abuse because maintaining the child in the role of patient satisfies the abusers needs. The cure for the victim is to separate the child completely from the abuser. When parental visits are allowed, sometimes there is a disastrous outcome for the child. Even when the child is removed, the perpetrator may then abuse another child: a sibling or other child in the family.Factitious disorder imposed on another can have many long-term emotional effects on a child. Depending on their experience of medical interventions, a percentage of children may learn that they are most likely to receive the positive parental attention they crave when they are playing the sick role in front of health care providers. Several case reports describe Munchausen syndrome patients suspected of themselves having been FDIA victims. Seeking personal gratification through illness can thus become a lifelong and multi-generational disorder in some cases. In stark contrast, other reports suggest survivors of FDIA develop an avoidance of medical treatment with post-traumatic responses to it.The adult caregiver who has abused the child often seems comfortable and not upset over the childs hospitalization. While the child is hospitalized, medical professionals must monitor the caregivers visits to prevent an attempt to worsen the childs condition. In addition, in many jurisdictions, medical professionals have a duty to report such abuse to legal authorities. Diagnosis Munchausen syndrome by proxy is a controversial term. In the World Health Organizations International Statistical Classification of Diseases, 10th Revision (ICD-10), the official diagnosis is factitious disorder (301.51 in ICD-9, F68.12 in ICD-10). Within the United States, factitious disorder imposed on another (FDIA or FDIoA) was officially recognized as a disorder in 2013, while in the United Kingdom, it is known as fabricated or induced illness by carers (FII).In DSM-5, the diagnostic manual published by the American Psychiatric Association in 2013, this disorder is listed under 300.19 Factitious disorder. This, in turn, encompasses two types: Factitious Disorder Imposed on Self Factitious Disorder Imposed on Another (Previously Factitious Disorder by Proxy); the diagnosis is assigned to the perpetrator; the person affected may be assigned an abuse diagnosis (e.g. child abuse).Both types include an optional specifier to identify if the observed behavior was a single episode or part of recurrent episodes. Warning signs Warning signs of the disorder include: A child who has one or more medical problems that do not respond to treatment or that follow an unusual course that is persistent, puzzling, and unexplained. Physical or laboratory findings that are highly unusual, discrepant with patients presentation or history, or physically or clinically impossible. A parent who appears medically knowledgeable, fascinated with medical details and hospital gossip, appears to enjoy the hospital environment, and expresses interest in the details of other patients problems. A highly attentive parent who is reluctant to leave their childs side and who themselves seem to require constant attention. A parent who appears unusually calm in the face of serious difficulties in their childs medical course while being highly supportive and encouraging of the physician, or one who is angry, devalues staff, and demands further intervention, more procedures, second opinions, and transfers to more sophisticated facilities. The suspected parent may work in the health-care field themselves or profess an interest in a health-related job. The signs and symptoms of a childs illness may lessen or simply vanish in the parents absence (hospitalization and careful monitoring may be necessary to establish this causal relationship). A family history of similar or unexplained illness or death in a sibling. A parent with symptoms similar to their childs own medical problems or an illness history that itself is puzzling and unusual. A suspected emotionally distant relationship between parents; the spouse often fails to visit the patient and has little contact with physicians even when the child is hospitalized with a serious illness. A parent who reports dramatic, negative events, such as house fires, burglaries, or car accidents, that affect them and their family while their child is undergoing treatment. A parent who seems to have an insatiable need for adulation or who makes self-serving efforts for public acknowledgment of their abilities. A child who inexplicably deteriorates whenever discharge is planned. A child that looks for cueing from a parent in order to feign illness when medical personnel are present. A child that is overly articulate regarding medical terminology and their own disease process for their age. A child that presents to the Emergency Department with a history of repeat illness, injury, or hospitalization. Epidemiology FDIA is rare. Incidence rate estimates range from 1 to 28 per million children, although some assume that it may be much more common.One study showed that in 93 percent of FDIA cases, the abuser is the mother or another female guardian or caregiver. A psychodynamic model of this kind of maternal abuse exists.Fathers and other male caregivers have been the perpetrators in only seven percent of the cases studied. When they are not actively involved in the abuse, the fathers or male guardians of FDIA victims are often described as being distant, emotionally disengaged, and powerless. These men play a passive role in FDIA by being frequently absent from the home and rarely visiting the hospitalized child. Usually, they vehemently deny the possibility of abuse, even in the face of overwhelming evidence or their childs pleas for help.Overall, male and female children are equally likely to be the victim of FDIA. In the few cases where the father is the perpetrator, however, the victim is three times more likely to be male.One study in Italy found that 4 out of more than 700 children admitted to the hospital met the criteria (0.53%). In this study, stringent diagnostic criteria were used, which required at least one test outcome or event that could not possibly have occurred without deliberate intervention by the FDIA person. Society and culture Terminology The term "Munchausen syndrome by proxy", in the United States, has never officially been included as a discrete mental disorder by the American Psychiatric Association, which publishes the Diagnostic and Statistical Manual of Mental Disorders (DSM), now in its fifth edition. Although the DSM-III (1980) and DSM-III-R (1987) included Munchausen syndrome, they did not include MSbP. DSM-IV (1994) and DSM-IV-TR (2000) added MSbP as a proposal only, and although it was finally recognized as a disorder in DSM-5 (2013), each of the last three editions of the DSM designated the disorder by a different name. FDIA has been given different names in different places and at different times. What follows is a partial list of alternative names that have been either used or proposed (with approximate dates): Factitious Disorder Imposed on Another (current) (U.S., 2013) American Psychiatric Association, DSM-5 Factitious Disorder by Proxy (FDP, FDbP) (proposed) (U.S., 2000) American Psychiatric Association, DSM-IV-TR Fictitious Disorder by Proxy (FDP, FDbP) (proposed) (U.S., 1994) American Psychiatric Association, DSM-IV Fabricated or Induced Illness by Carers (FII) (U.K., 2002) The Royal College of Pediatrics and Child Health Factitious Illness by Proxy (1996) World Health Organization Pediatric Condition Falsification (PCF) (proposed) (U.S., 2002) American Professional Society on the Abuse of Children proposed this term to diagnose the victim (child); the perpetrator (caregiver) would be diagnosed "factitious disorder by proxy"; MSbP would be retained as the name applied to the disorder that contains these two elements, a diagnosis in the child and a diagnosis in the caretaker. Induced Illness (Munchausen Syndrome by Proxy) (Ireland, 1999–2002) Department of Health and Children Munchausen Syndrome by Proxy (2002) Professor Roy Meadow. Meadows Syndrome (1984–1987) named after Roy Meadow. This label, however, had already been in use since 1957 to describe a completely unrelated and rare form of cardiomyopathy. Polle Syndrome (1977–1984) coined by Burman and Stevens, from the then-common belief that Baron Münchhausens second wife gave birth to a daughter named Polle during their marriage. The baron declared that the baby was not his, and the child died from "seizures" at the age of 10 months. The name fell out of favor after 1984, when it was discovered that Polle was not the babys name, but rather was the name of her mothers hometown.While it initially included only the infliction of harmful medical care, the term has subsequently been extended to include cases in which the only harm arose from medical neglect, noncompliance, or even educational interference. The term is derived from Munchausen syndrome, a psychiatric factitious disorder wherein those affected feign disease, illness, or psychological trauma to draw attention, sympathy, or reassurance to themselves. Munchausen syndrome by proxy perpetrators, by contrast, are willing to fulfill their need for positive attention by hurting their own child, thereby assuming the sick role onto their child, by proxy. These proxies then gain personal attention and support by taking on this fictitious "hero role" and receive positive attention from others, by appearing to care for and save their so-called sick child. They are named after Baron Munchausen, a literary character based on Hieronymus Karl Friedrich, Freiherr von Münchhausen (1720–1797), a German nobleman and well-known storyteller. In 1785, writer and con artist Rudolf Erich Raspe anonymously published a book in which a fictional version of "Baron Munchausen" tells fantastic and impossible stories about himself, establishing a popular literary archetype of a bombastic exaggerator. Initial description "Munchausen syndrome" was first described by R. Asher in 1951 as when someone invents or exaggerates medical symptoms, sometimes engaging in self-harm, to gain attention or sympathy. The term "Munchausen syndrome by proxy" was first coined by John Money and June Faith Werlwas in a 1976 paper titled Folie à deux in the parents of psychosocial dwarfs: Two cases to describe the abuse-induced and neglect-induced symptoms of the syndrome of abuse dwarfism. That same year, Sneed and Bell wrote an article titled The Dauphin of Munchausen: factitious passage of renal stones in a child.According to other sources, the term was created by the British pediatrician Roy Meadow in 1977. In 1977, Meadow – then professor of pediatrics at the University of Leeds, England – described the extraordinary behavior of two mothers. According to Meadow, one had poisoned her toddler with excessive quantities of salt. The other had introduced her own blood into her babys urine sample. This second case occurred during a series of Outpatient visits to the Paediatric Clinic of Dr. Bill Arrowsmith at Doncaster Royal Infirmary. He referred to this behavior as Munchausen syndrome by proxy (MSbP).The medical community was initially skeptical of FDIAs existence, but it gradually gained acceptance as a recognized condition. Controversy During the 1990s and early 2000s, Roy Meadow was an expert witness in several murder cases involving MSbP/FII. Meadow was knighted for his work for child protection, though later, his reputation, and consequently the credibility of MSbP, became damaged when several convictions of child killing, in which he acted as an expert witness, were overturned. The mothers in those cases were wrongly convicted of murdering two or more of their children, and had already been imprisoned for up to six years.One case was that of Sally Clark. Clark was a lawyer wrongly convicted in 1999 of the murder of her two baby sons, largely on the basis of Meadows evidence. As an expert witness for the prosecution, Meadow asserted that the odds of there being two unexplained infant deaths in one family were one in 73 million. That figure was crucial in sending Clark to jail but was hotly disputed by the Royal Statistical Society, who wrote to the Lord Chancellor to complain. It was subsequently shown that the true odds were much greater once other factors (e.g. genetic or environmental) were taken into consideration, meaning that there was a significantly higher likelihood of two deaths happening as a chance occurrence than Meadow had claimed during the trial. Those odds in fact range from a low of 1:8500 to as high as 1:200. It emerged later that there was clear evidence of a Staphylococcus aureus infection that had spread as far as the childs cerebrospinal fluid. Clark was released in January 2003 after three judges quashed her convictions in the Court of Appeal in London, but suffering from catastrophic trauma of the experience, she later died from alcohol poisoning. Meadow was involved as a prosecution witness in three other high-profile cases resulting in mothers being imprisoned and subsequently cleared of wrongdoing: Trupti Patel, Angela Cannings and Donna Anthony.In 2003, Lord Howe, the Opposition spokesman on health, accused Meadow of inventing a "theory without science" and refusing to produce any real evidence to prove that Munchausen syndrome by proxy actually exists. It is important to distinguish between the act of harming a child, which can be easily verified, and motive, which is much harder to verify and which FDIA tries to explain. For example, a caregiver may wish to harm a child out of malice and then attempt to conceal it as illness to avoid detection of abuse, rather than to draw attention and sympathy. The distinction is often crucial in criminal proceedings, in which the prosecutor must prove both the act and the mental element constituting a crime to establish guilt. In most legal jurisdictions, a doctor can give expert witness testimony as to whether a child was being harmed but cannot speculate regarding the motive of the caregiver. FII merely refers to the fact that illness is induced or fabricated and does not specifically limit the motives of such acts to a caregivers need for attention and/or sympathy. In all, around 250 cases resulting in conviction in which Meadow was an expert witness were reviewed, with few changes, but all where the only evidence was Meadows expert testimony were overturned. Meadow was investigated by the British General Medical Council (GMC) over evidence he gave in the Sally Clark trial. In July 2005, the GMC declared Meadow guilty of "serious professional misconduct", and he was struck off the medical register for giving "erroneous" and "misleading" evidence. At appeal, High Court judge Mr. Justice Collins said that the severity of his punishment "approaches the irrational" and set it aside.Collinss judgment raises important points concerning the liability of expert witnesses – his view is that referral to the GMC by the losing side is an unacceptable threat and that only the Court should decide whether its witnesses are seriously deficient and refer them to their professional bodies.In addition to the controversy surrounding expert witnesses, an article appeared in the forensic literature that detailed legal cases involving controversy surrounding the murder suspect. The article provides a brief review of the research and criminal cases involving Munchausen syndrome by proxy in which psychopathic mothers and caregivers were the murderers. It also briefly describes the importance of gathering behavioral data, including observations of the parents who commit the criminal acts. The article references the 1997 work of Southall, Plunkett, Banks, Falkov, and Samuels, in which covert video recorders were used to monitor the hospital rooms of suspected FDIA victims. In 30 out of 39 cases, a parent was observed intentionally suffocating their child; in two they were seen attempting to poison a child; in another, the mother deliberately broke her three-month-old daughters arm. Upon further investigation, those 39 patients, ages 1 month to 3 years old, had 41 siblings; 12 of those had died suddenly and unexpectedly. The use of covert video, while apparently extremely effective, raises controversy in some jurisdictions over privacy rights. Legal status In most legal jurisdictions, doctors are allowed to give evidence only in regard to whether the child is being harmed. They are not allowed to give evidence in regard to the motive. Australia and the UK have established the legal precedent that FDIA does not exist as a medico-legal entity. In a June 2004 appeal hearing, the Supreme Court of Queensland, Australia, stated: As the term factitious disorder (Munchausens Syndrome) by proxy is merely descriptive of a behavior, not a psychiatrically identifiable illness or condition, it does not relate to an organized or recognized reliable body of knowledge or experience. Dr. Reddans evidence was inadmissible. The Queensland Supreme Court further ruled that the determination of whether or not a defendant had caused intentional harm to a child was a matter for the jury to decide and not for the determination by expert witnesses: The diagnosis of Doctors Pincus, Withers, and OLoughlin that the appellant intentionally caused her children to receive unnecessary treatment through her own acts and the false reporting of symptoms of the factitious disorder (Munchausen Syndrome) by proxy is not a diagnosis of a recognized medical condition, disorder, or syndrome. It is simply placing her within the medical term used in the category of people exhibiting such behavior. In that sense, their opinions were not expert evidence because they related to matters that could be decided on the evidence by ordinary jurors. The essential issue as to whether the appellant reported or fabricated false symptoms or did acts to intentionally cause unnecessary medical procedures to injure her children was a matter for the jurys determination. The evidence of Doctors Pincus, Withers, and OLoughlin that the appellant was exhibiting the behavior of factitious disorder (Munchausen syndrome by proxy) should have been excluded. Principles of law and implications for legal processes that may be deduced from these findings are that: Any matters brought before a Court of Law should be determined by the facts, not by suppositions attached to a label describing a behavior, i.e., MSBP/FII/FDBP; MSBP/FII/FDBP is not a mental disorder (i.e., not defined as such in DSM IV), and the evidence of a psychiatrist should not therefore be admissible; MSBP/FII/FDBP has been stated to be a behavior describing a form of child abuse and not a medical diagnosis of either a parent or a child. A medical practitioner cannot therefore state that a person "suffers" from MSBP/FII/FDBP, and such evidence should also therefore be inadmissible. The evidence of a medical practitioner should be confined to what they observed and heard and what forensic information was found by recognized medical investigative procedures; A label used to describe a behavior is not helpful in determining guilt and is prejudicial. By applying an ambiguous label of MSBP/FII to a woman is implying guilt without factual supportive and corroborative evidence; The assertion that other people may behave in this way, i.e., fabricate and/or induce illness in children to gain attention for themselves (FII/MSBP/FDBY), contained within the label is not factual evidence that this individual has behaved in this way. Again therefore, the application of the label is prejudicial to fairness and a finding based on fact.The Queensland Judgment was adopted into English law in the High Court of Justice by Mr. Justice Ryder. In his final conclusions regarding Factitious Disorder, Ryder states that: I have considered and respectfully adopt the dicta of the Supreme Court of Queensland in R v. LM [2004] QCA 192 at paragraph 62 and 66. I take full account of the criminal law and foreign jurisdictional contexts of that decision but I am persuaded by the following argument upon its face that it is valid to the English law of evidence as applied to children proceedings.The terms "Munchausen syndrome by proxy" and "factitious (and induced) illness (by proxy)" are child protection labels that are merely descriptions of a range of behaviors, not a pediatric, psychiatric or psychological disease that is identifiable. The terms do not relate to an organized or universally recognized body of knowledge or experience that has identified a medical disease (i.e. an illness or condition) and there are no internationally accepted medical criteria for the use of either label.In reality, the use of the label is intended to connote that in the individual case there are materials susceptible of analysis by pediatricians and of findings of fact by a court concerning fabrication, exaggeration, minimization or omission in the reporting of symptoms and evidence of harm by act, omission or suggestion (induction). Where such facts exist the context and assessments can provide an insight into the degree of risk that a child may face and the court is likely to be assisted as to that aspect by psychiatric and/or psychological expert evidence.All of the above ought to be self evident and has in any event been the established teaching of leading pediatricians, psychiatrists and psychologists for some while. That is not to minimize the nature and extent of professional debate about this issue which remains significant, nor to minimize the extreme nature of the risk that is identified in a small number of cases.In these circumstances, evidence as to the existence of MSBP or FII in any individual case is as likely to be evidence of mere propensity which would be inadmissible at the fact finding stage (see Re CB and JB supra). For my part, I would consign the label MSBP to the history books and however useful FII may apparently be to the child protection practitioner I would caution against its use other than as a factual description of a series of incidents or behaviors that should then be accurately set out (and even then only in the hands of the pediatrician or psychiatrist/psychologist). I cannot emphasis too strongly that my conclusion cannot be used as a reason to re-open the many cases where facts have been found against a carer and the label MSBP or FII has been attached to that carers behavior. What I seek to caution against is the use of the label as a substitute for factual analysis and risk assessment. In his book Playing Sick (2004), Marc Feldman notes that such findings have been in the minority among U.S. and even Australian courts. Pediatricians and other physicians have banded together to oppose limitations on child-abuse professionals whose work includes FII detection. The April 2007 issue of the journal Pediatrics specifically mentions Meadow as an individual who has been inappropriately maligned. In the context of child protection (a child being removed from the custody of a parent), the Australian state of New South Wales uses a "on the balance of probabilities" test, rather than a "beyond reasonable doubt" test. Therefore, in the case "The Secretary, Department of Family and Community Services and the Harper Children [2016] NSWChC 3", the expert testimony of Professor David Isaacs that a certain blood test result was "highly unlikely" to occur naturally or accidentally (without any speculation about motive), was sufficient to refuse the return of the affected child and his younger siblings to the mother. The children had initially been removed from the mothers custody after the blood test results became known. The fact that the affected child quickly improved both medically and behaviourly after being removed was also a factor. Notable cases Beverley Allitt, a British nurse who murdered four children and injured a further nine in 1991 at Grantham and Kesteven Hospital, Lincolnshire, was diagnosed with Munchausen syndrome by proxy.Wendi Michelle Scott is a Frederick, Maryland, mother who was charged with sickening her four-year-old daughter.The book Sickened, by Julie Gregory, details her life growing up with a mother who had Munchausen by proxy, who took her to various
Factitious disorder imposed on another	doctors, coached her to act sicker than she was and to exaggerate her symptoms, and who demanded increasingly invasive procedures to diagnose Gregorys enforced imaginary illnesses.Lisa Hayden-Johnson of Devon was jailed for three years and three months after subjecting her son to a total of 325 medical actions – including being forced to use a wheelchair and being fed through a tube in his stomach. She claimed her son had a long list of illnesses including diabetes, food allergies, cerebral palsy, and cystic fibrosis, describing him as "the most ill child in Britain" and receiving numerous cash donations and charity gifts, including two cruises.In the mid-1990s, Kathy Bush gained public sympathy for the plight of her daughter, Jennifer, who by the age of 8 had undergone 40 surgeries and spent over 640 days in hospitals for gastrointestinal disorders. The acclaim led to a visit with first lady Hillary Clinton, who championed the Bushs plight as evidence of need for medical reform. However, in 1996, Kathy Bush was arrested and charged with child abuse and Medicaid fraud, accused of sabotaging Jennifers medical equipment and drugs to agitate and prolong her illness. Jennifer was moved to foster care where she quickly regained her health. The prosecutors claimed Kathy was driven by Munchausen Syndrome by Proxy, and she was convicted to a five-year sentence in 1999. Kathy was released after serving three years in 2005, always maintaining her innocence, and having gotten back in contact with Jennifer via correspondence.In 2014, 26-year-old Lacey Spears was charged in Westchester County, New York, with second-degree depraved murder and first-degree manslaughter. She fed her son dangerous amounts of salt after she conducted research on the Internet about its effects. Her actions were allegedly motivated by the social media attention she gained on Facebook, Twitter, and blogs. She was convicted of second-degree murder on March 2, 2015, and sentenced to 20 years to life in prison.Dee Dee Blanchard was a Missouri mother who was murdered by her daughter and a boyfriend in 2015 after having claimed for years that her daughter, Gypsy Rose, was sick and disabled; to the point of shaving her head, making her use a wheelchair in public, and subjecting her to unnecessary medication and surgery. Gypsy possessed no outstanding illnesses. Feldman said it is the first case he is aware of in a quarter-century of research where the victim killed the abuser. Their story was shown on HBOs documentary film Mommy Dead and Dearest and is featured in the Hulu limited series The Act. Gypsy Rose pleaded guilty to second-degree murder and is serving a ten-year sentence, her boyfriend was convicted of first-degree murder and is sentenced to life in prison without parole. Rapper Eminem has spoken about how his mother would frequently take him to hospitals to receive treatment for illnesses that he did not have. His song "Cleanin Out My Closet" includes a lyric regarding the illness, "...going through public housing systems victim of Münchausen syndrome. My whole life I was made to believe I was sick, when I wasn’t ‘til I grew up and blew up..." His mothers illness resulted in Eminem receiving custody of his younger brother, Nathan.In 2013, when Justina Pelletier was 14, her parents took her to the emergency room at Boston Childrens Hospital where doctors diagnosed her problems as psychiatric, but when her parents rejected the diagnosis and attempted to have her released, the hospital filed a report with Massachusetts Department of Children and Families alleging medical child abuse. This resulted in her being housed for 18 months in the psychiatric hospital, with her parents having limited access, until a judge ordered her returned to her parents. In 2016 her parents sued Boston Childrens for medical malpractice, alleging that their civil rights were violated. At the trial, Pelletiers treating neurologist stated that several of her doctors suspected factitious disorder by proxy, and wanted her parents to stop encouraging her to be sick. Her parents lost the lawsuit, with one juror stating that Pelletiers parents thought of psychiatry as "psychological baloney". Directed towards animals Medical literature describes a subset of FDIA caregivers, where the proxy is a pet rather than another person. These cases are labeled Munchausen syndrome by proxy: pet (MSbP:P). In these cases, pet owners correspond to caregivers in traditional FDIA presentations involving human proxies. No extensive survey has yet been made of the extant literature, and there has been no speculation as to how closely FDIA:P tracks with human FDIA. See also List of Munchausen by proxy cases Folie à deux Hypochondria Munchausen by Internet Psychosomatic illness Run (2020 American film) == References ==
Tenonitis	Tenonitis is a rare eye disease that is represented by inflammation of Tenons capsule. Tenons capsule, also known as the fascial sheath of the eyeball, is a structure surrounding the eyeball, and when it becomes inflamed it may cause issues in regards to vision. Also known as orbital tenonitis, tenonitis is associated with the SLC26A3 gene. The inflammation of the Tenon capsule resulting from heightened blood flow may also affect the lacrimal gland and the extraocular muscles. Signs and Symptoms Signs and symptoms depend on the severity of the case with tenonitis. In mild cases it may just be an uncomfortable sensation in the eye socket. In extreme cases it may cause permanent blindness or eye removal is needed. Swelling Intraocular pressure Blindness Causes There are no specific causes of this disease. With this being so rare not enough research has been allocated to pinpoint a specific cause of this disease. The main thing that we know about this disease is that the inflammation of the Tenon capsule may be related to macular retinal edema and intraocular pressure quantitative trait locus. Mechanism With the lack of research and understanding about this specific disease it is hard to come up with a mechanism that outlines how this arises in the body. Although we cannot pinpoint specifically how it occurs, there are some findings that may help us get to that point in the future. A gene that is associated with orbital tenonitis is the SLC26A3 gene. This gene mediates chloride and bicarbonate exchange and additionally transports sulfate and other anions at the apical membrane, part of the plasma membrane of enterocytes. It is also known that related phenotypes are Increased shRNA abundance (Z-score > 2). Diagnosis Tenonitis can be identified and diagnosed a few different ways. Tenons capsule may have inflammation from a disease called idiopathic orbital inflammation syndrome. There is no history of trauma or adjacent focus of infection with this disease. In order to diagnose tenonitis some type of imaging is needed, such as a CT or MRI. The imaging is used to capture the inflammation and to spot any possible chance of infection. For chronic diseases a biopsy may be needed to determine an underlying condition that may be causing the recurring inflammation. Treatment The main course of treatment for this specific disease would be to surgically excise the capsule. There is no info that implies the inflammation of this capsule will go down over time so the known course of action would be to have it surgically removed in order to relieve discomfort and to prevent further irritation to this area. Prognosis Although this may not be a lethal disease, it will progressively get worse over time. Depending on the severity of the disease, this may have months of progression. When going past 3 months of having issues, the main course of action would be to surgically relieve the pain or total excision of the affected area. Epidemiology This disease has no specific population it targets more. With the information that is provided by previous research, this is a typically universal disease that can affect any population. Research Directions Currently there havent been many studies conducted in regards to Tenons capsule. In one study the objective was to see the efficacy of excision of the capsule by way of trabeculectomy alone, and also combined with partial tenonectomy. There is further research needed to be done to determine the cause of this specific disease, what happens during the progression of it, and treatment plans that need to be put in place. == References ==

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