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Medulloepithelioma

Medulloepithelioma is a rare, primitive, fast-growing brain tumour thought to stem from cells of the embryonic medullary cavity. Tumours originating in the ciliary body of the eye are referred to as embryonal medulloepitheliomas, or diktyomas.A highly malignant undifferentiated primitive neuroepithelial tumour of children, medulloepithelioma may contain bone, cartilage, skeletal muscle, and tends to metastasize extracranially. Signs and symptoms Medulloepithelioma have been reported to occur in the cerebral hemispheres, brainstem, cerebellum, and peripheral sites.Due to rapid growth of the tumour, patients typically present with increased intracranial pressure, seizures, and focal neurologic signs. Diagnosis Imaging studies such as Computerized Tomography (CT) and Magnetic Resonance Imaging (MRI) can aid diagnosis. Medulloepithelioma appears isodense or hypodense with variable heterogeneity and calcification on non-contrast CT scan, and enhances with contrast. This radiographical finding is consistent with a primitive neuroectodermal tumour, especially in children. Blood studies and imaging studies of the abdomen may be used to detect metastases.Needle aspiration biopsy can be used to aid diagnosis. Definitive diagnosis requires histopathological examination of surgically excised tumour tissues.Histologically, medulloepithelioma resemble a primitive neural tube and with neuronal, glial and mesenchymal elements. Flexner-Wintersteiner rosettes may also be observed.Immunohistochemically, neural tube-like structures are vimentin positive in the majority of medulloepitheliomas. Poorly differentiated medulloepitheliomas are vimentin negative. Classification Medulloepithelioma was originally classified as the most primitive neoplasm of the Central Nervous System (CNS) by Bailey and Cushing in 1926. Rorke et al. classified this tumour into two subtypes: 1) medulloepithelioma not otherwise specified 2) medulloepithelioma with differentiation into astrocytes, oligodendrocytes; ependymal cells; neuronal cells; others (melanin, mesenchymal cells); and mixed cellular elements. Treatment Total resection of the tumour, followed by radiation therapy is the standard treatment modality. Medulloepithelioma of the ciliary body may necessitate enucleation of the eye. Radiation therapy alone may prolong survival. Aggressive chemotherapy with autologous bone marrow transplant is used for metastatic medulloepitheliomas. Prognosis Medulloepithelioma carries a dismal prognosis with a median survival of 5 months. Epidemiology Medulloepithelioma most commonly affect children between 6 months and 5 years; rarely, this tumour may occur congenitally or beyond this age range. Incidence is equal in males and females. References == External links ==

Metastatic calcification

Metastatic calcification is deposition of calcium salts in otherwise normal tissue, because of elevated serum levels of calcium, which can occur because of deranged metabolism as well as increased absorption or decreased excretion of calcium and related minerals, as seen in hyperparathyroidism. In contrast, dystrophic calcification is caused by abnormalities or degeneration of tissues resulting in mineral deposition, though blood levels of calcium remain normal. These differences in pathology also mean that metastatic calcification is often found in many tissues throughout a person or animal, whereas dystrophic calcification is localized. Metastatic calcification can occur widely throughout the body but principally affects the interstitial tissues of the vasculature, kidneys, lungs, and gastric mucosa. For the latter three, acid secretions or rapid changes in pH levels contribute to the formation of salts. Causes Hypercalcemia, elevated blood calcium, has numerous causes, including Elevated levels of parathyroid hormone due to hyperparathyroidism, leading to bone resorption and subsequent hypercalcemia by reducing phosphate concentration. Secretion of parathyroid hormone-related protein by certain tumors. Resorption of bone due to Primary bone marrow tumors (e.g. multiple myeloma and leukemia) Metastasis of other tumors, breast cancer for example, to bone. Paget disease Immobilization Vitamin D related disorders Vitamin D intoxication Williams syndrome (increased sensitivity to vitamin D) Sarcoidosis Kidney failure == References ==

Hereditary breast–ovarian cancer syndrome

Hereditary breast–ovarian cancer syndromes (HBOC) are cancer syndromes that produce higher than normal levels of breast cancer, ovarian cancer and additional cancers in genetically related families (either one individual had both, or several individuals in the pedigree had one or the other disease). It accounts for 90% of the hereditary cancers. The hereditary factors may be proven or suspected to cause the pattern of breast and ovarian cancer occurrences in the family. The name HBOC may be misleading because it implies that this genetic susceptibility to cancer is mainly in women. In reality, both sexes have the same rates of gene mutations and HBOC can predispose to other cancers including prostate cancer and pancreatic cancer. For this reason, the term "King syndrome" has recently come into use. The new name references Mary-Claire King who identified the genes BRCA1 and BRCA2. Causes A number of genes are associated with HBOC. The most common of the known causes of HBOC are: BRCA mutations: Harmful mutations in the BRCA1 and BRCA2 genes can produce very high rates of breast and ovarian cancer, as well as increased rates of other cancers. Mutations in BRCA1 are associated with a 39-46% risk of ovarian cancer and mutations in BRCA2 are associated with a 10-27% risk of ovarian cancer.Other identified genes include: MLH1, MSH2, MSH6, PMS2: mutations in genes that lead to Lynch Syndrome put individuals at risk for ovarian cancer. TP53: Mutations cause Li-Fraumeni syndrome. It produces particularly high rates of breast cancer among younger women with mutated genes, and despite being rare, 4% of women with breast cancer under age 30 have a mutation in this gene. PTEN: Mutations cause Cowden syndrome, which produces hamartomas (benign polyps) in the colon, skin growths, and other clinical signs, as well as an increased risk for many cancers. CDH1: Mutations are associated with lobular breast cancer and gastric cancer. STK11: Mutations produce Peutz–Jeghers syndrome. It is extremely rare, and creates a predisposition to breast cancer, intestinal cancer, and pancreatic cancer. CHEK2: Approximately one out of 40 northern Europeans have a mutation in this gene, making it a common mutation. It is also one of the most frequently mutated genes after BRCA among Hispanics in the United States. Considered a moderate-risk mutation, it may double or triple the carriers lifetime risk of breast cancer, and also increase the risk of colon cancer and prostate cancer. ATM: Mutations cause ataxia telangectasia; female carriers have approximately double the normal risk of developing breast cancer. PALB2: Studies vary in their estimate of the risk from mutations in this gene and the frequency of mutations in this gene may be different among different populations. It may be moderate risk, or as high as BRCA2.Approximately 45% of HBOC cases involve unidentified genes, or multiple genes. Prevention People with BRCA1 and BRCA2 mutations are recommended to have a transvaginal ultrasound 1-2 times per year. Screening with CA-125 is also recommended. Prophylactic salpingo-oophorectomy (removal of the ovaries and Fallopian tubes to prevent cancer) is recommended at age 35-40 for people with BRCA1 mutations and at age 40-45 for people with BRCA2 mutations. References == External links ==

Punctate epithelial erosions

Punctate epithelial erosions are a pathology affecting the cornea. Signs and symptoms It is a characterized by a breakdown or damage of the epithelium of the cornea in a pinpoint pattern, which can be seen with examination with a slit-lamp. Patients may present with non-specific symptoms such as red eye, tearing, foreign body sensation, photophobia and burning. Cause Punctate epithelial erosions may be seen with different disorders: Rosacea Dry-eye syndrome Blepharitis Acute bacterial conjunctivitis Trauma Exposure keratopathy from poor eyelide closure Ultraviolet or chemical burn Contact lens-related disorder such as toxicity or tight lens syndrome Trichiasis Entropion or ectropion Floppy eyelid syndrome Chemotherapy i.e. cytosine arabinoside Thygesons Superficial Punctate Keratopathy Diagnosis Slit lamp examination Treatment Due to the different underlying causes, proper diagnosis, treatment, and prognosis can only be determined by an eye care professional. Punctate epithelial erosions may be treated with artificial tears. In some disorders, topical antibiotic is added to the treatment. Patients should discontinue contact lens wear until recovery. == References ==

Retinitis pigmentosa

Retinitis pigmentosa (RP) is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision (side and upper or lower visual field). As peripheral vision worsens, people may experience "tunnel vision". Complete blindness is uncommon. Onset of symptoms is generally gradual and often begins in childhood.Retinitis pigmentosa is generally inherited from one or both parents or rarely it can be newly evolved from a miscoding during DNA division. It is caused by genetic miscoding of proteins in one of more than 300 genes involved. The underlying mechanism involves the progressive loss of rod photoreceptor cells that line the retina of the eyeball. The rod cells secrete a neuroprotective substance (Rod-derived cone viability factor, RdCVF) that protects the cone cells from apoptosis (cell death). However, when the rod cells die, this substance is no longer provided. This is generally followed by the loss of cone photoreceptor cells. Diagnosis is by eye examination of the retina finding dark pigment deposits caused by the rupture of the underlying retinal pigmented epithelial cells, given that these cells contain a pigment known as melanin. Other supportive testing may include the electroretinogram (ERG), visual field testing (VFT), ocular coherence tomography (OCT) and DNA testing to determine the gene responsible for a persons particular type of RP (now called Inherited Retinal Dystrophy (IRD).There is currently no cure for retinitis pigmentosa. Efforts to manage the problem may include the use of low vision aids, portable lighting, or orientation and mobility training. Vitamin A palmitate supplements may be useful to slow worsening. A visual prosthesis may be an option in certain people with severe disease.Currently there is only one FDA-approved gene therapy that is commercially available to RP patients with Leber congenital amaurosis type 2. It replaces the miscoded RPE65 protein that is produced within the retinal pigmented epithelium. It has been found to effectively work in about 50% of the patients who receive the therapy. The earlier the child receives the RPE65 therapy the better the chances for a positive outcome. There are many other therapies being researched at this time with the goal of being approved in the next few years. It is estimated to affect 1 in 4,000 people. Signs and symptoms The initial retinal degenerative symptoms of retinitis pigmentosa are characterized by decreased night vision (nyctalopia) and the loss of the mid-peripheral visual field. The rod photoreceptor cells, which are responsible for low-light vision and are orientated mainly in the retinal periphery, are the retinal processes affected first during non-syndromic (without other conditions) forms of this disease. Visual decline progresses relatively quickly to the far peripheral field, eventually extending into the central visual field as tunnel vision increases. Visual acuity and color vision can become compromised due to accompanying loss of the cone photoreceptor cells, which are responsible for color vision, visual acuity, and sight in the central visual field. The progression of disease occurs in both eyes in a similar but not identical pattern. A variety of indirect symptoms characterize retinitis pigmentosa along with the direct effects of the initial rod photoreceptor degeneration and later cone photoreceptor decline. Phenomena such as photophobia, which describes the event in which light is perceived as an intense glare, and photopsia, the presence of blinking, swirling or shimmering lights spontaneously occurring within the visual field, often manifest during the later stages of RP. Findings related to RP have often been characterized in the fundus (back layer) of the eye as the "ophthalmic triad". This includes the development of (1) a mottled appearance of the retina and retinal pigment epithelium (RPE) that gives the same visual appearance of Bone Spicule patterns (but are not Bone Spicules), (2) a waxy yellow appearance of the optic disk, and (3) the attenuation of blood vessels in size and Arterial/Venous ratio as they enter and exit the Optic Disk of the retina and transverse it.Non-syndromic RP (RP appears alone without other co-morbidities) usually presents a variety of the following symptoms: Night blindness Tunnel vision (due to loss of peripheral vision) Latticework vision(due to patchy loss of peripheral vision) loss of depth perception Photopsia (Spontaneously occurring flashes/blinking/swirling/shimmering lights) Photophobia (aversion to bright lights) Development of the appearance of melanin pigment in a bone spicule pattern in the fundus (not bone tissue) Slow adjustment from dark to light environments and vice versa Blurring of vision Poor color separation Loss of central vision is the last to go, because this is a disease of the rods and not the cones which are the highest in number in the Central Vision (Macula and Fovea) Eventual blindness (legally defined as 20 degrees or less in the best seeing eye or visual acuity of 20/200 or worse. Majority of patients do not go totally Blind, they quite often retain limited non-functional vision. Causes RP may be: (1) non-syndromic, that is, it occurs alone, without any other clinical findings, (2) syndromic, with other neurosensory disorders, developmental abnormalities, or complex clinical findings, or (3) secondary to other systemic diseases. RP combined with deafness (congenital or progressive) is called Usher syndrome. Alports syndrome is associated with RP and an abnormal glomerular-basement membrane leading to nephrotic syndrome. It is inherited as X-linked dominant. RP combined with ophthalmoplegia, dysphagia, ataxia, and cardiac conduction defects is seen in the mitochondrial DNA disorder Kearns–Sayre syndrome (also known as Ragged Red Fiber Myopathy) RP combined with retardation, peripheral neuropathy, acanthotic (spiked) RBCs, ataxia, steatorrhea, and absence of VLDL is seen in abetalipoproteinemia. RP is seen clinically in association with several other rare genetic disorders (including muscular dystrophy and chronic granulomatous disease) as part of McLeod syndrome. This is an X-linked recessive phenotype characterized by a complete absence of XK cell surface proteins, and therefore markedly reduced expression of all Kell red blood cell antigens. For transfusion purposes, these patients are considered completely incompatible with all normal and K0/K0 donors. RP associated with hypogonadism, and developmental delay with an autosomal recessive inheritance pattern is seen with Bardet–Biedl syndromeOther conditions include neurosyphilis, toxoplasmosis and Refsums disease. Genetics Retinitis pigmentosa (RP) is one of the most common forms of inherited retinal degeneration.There are multiple genes that code for proteins needed in the visual pathway, when mutated, they can cause the retinitis pigmentosa phenotype. Inheritance patterns of RP have been identified as autosomal dominant, autosomal recessive, X-linked, and maternally (mitochondrially) acquired, and are dependent on the specific RP gene mutations present in the parental generation. (Of note, Autosomal Dominant RP Type 11 (PRPF-31) can be inherited as a genotype only, because of incomplete penetrance, thus coded for in the DNA but, does not manifest the disease as a phenotype.) In 1989, a mutation of the gene for rhodopsin, a pigment that plays an essential part in the visual transduction cascade enabling vision in low-light conditions, was identified. The rhodopsin gene encodes a principal protein of photoreceptor outer segments. Mutations in this gene most commonly presents as missense mutations or misfolding of the rhodopsin protein, and most frequently follow autosomal dominant inheritance patterns. Since the discovery of the rhodopsin gene, more than 100 RHO mutations have been identified, accounting for 15% of all types of retinal degeneration, and approximately 25% of autosomal dominant forms of RP.Over 100 mutations have been reported to date in the opsin gene associated with the RP since the Pro23His mutation in the intradiscal domain of the protein was first reported in 1990. These mutations are found throughout the opsin gene and are distributed along the three domains of the protein (the intradiscal, transmembrane, and cytoplasmic domains). One of the main biochemical causes of RP in the case of rhodopsin mutations is protein misfolding, and the disruption of molecular chaperones. It was found that the mutation of codon 23 in the rhodopsin gene, in which proline is changed to histidine, accounts for the largest fraction of rhodopsin mutations in the United States. Several other studies have reported various codon mutations associated with retinitis pigmentosa, including Thr58Arg, Pro347Leu, Pro347Ser, as well as deletion of Ile-255. In 2000, a rare mutation in codon 23 was reported causing autosomal dominant retinitis pigmentosa, in which proline changed to alanine. However, this study showed that the retinal dystrophy associated with this mutation was characteristically mild in presentation and course. Furthermore, there was greater preservation in electroretinography amplitudes than the more prevalent Pro23His mutation.Autosomal recessive inheritance patterns of RP have been identified in at least 45 genes. This means that two unaffected individuals who are carriers of the same RP-inducing gene mutation in diallelic form can produce offspring with the RP phenotype. A mutation on the USH2A gene is known to cause 10-15% of a syndromic form of RP known as Ushers Syndrome when inherited in an autosomal recessive fashion.Mutations in four pre-mRNA splicing factors are known to cause autosomal dominant retinitis pigmentosa. These are PRPF3 (human PRPF3 is HPRPF3; also PRP3), PRPF8, PRPF31 and PAP1. These factors are ubiquitously expressed and it is proposed that defects in a ubiquitous factor (a protein expressed everywhere) should only cause disease in the retina because the retinal photoreceptor cells have a far greater requirement for protein processing (rhodopsin) than any other cell type.The somatic, or X-linked inheritance patterns of RP are currently identified with the mutations of six genes, the most common occurring at specific loci in the RPGR and RP2 genes.Types include: Pathophysiology A variety of retinal molecular pathway defects have been matched to multiple known RP gene mutations. Mutations in the rhodopsin gene (RHO), which is responsible for the majority of autosomal-dominantly inherited RP cases, disrupts the rhodopsin protein essential for translating light into decipherable electrical signals within the phototransduction cascade of the central nervous system. Defects in the activity of this G-protein-coupled receptor are classified into distinct classes that depend on the specific folding abnormality and the resulting molecular pathway defects. The Class I mutant proteins activity is compromised as specific point mutations in the protein-coding amino acid sequence affect the pigment proteins transport to the outer segment of the eye, where the phototransduction cascade is localized. Additionally, the misfolding of Class II rhodopsin gene mutations disrupts the proteins conjunction with 11-cis-retinal to induce proper chromophore formation. Additional mutants in this pigment-encoding gene affect protein stability, disrupt mRNA integrity post-translationally, and affect the activation rates of transducin and opsin optical proteins.Additionally, animal models suggest that the retinal pigment epithelium fails to phagocytose the outer rod segment discs that have been shed, leading to an accumulation of outer rod segment debris. In mice that are homozygous recessive for retinal degeneration mutation, rod photoreceptors stop developing and undergo degeneration before cellular maturation completes. A defect in cGMP-phosphodiesterase has also been documented; this leads to toxic levels of cGMP. Diagnosis An accurate diagnosis of retinitis pigmentosa relies on the documentation of the progressive loss of photoreceptor cell function, confirmed by a combination of visual field and visual acuity tests, fundus and optical coherence imagery, and electroretinography (ERG).Visual field and acuity tests measure and compare the size of the patients field of vision and the clarity of their visual perception with the standard visual measurements associated with healthy 20/20 vision. Clinical diagnostic features indicative of retinitis pigmentosa include a substantially small and progressively decreasing visual area in the visual field test, and compromised levels of clarity measured during the visual acuity test. Additionally, optical tomography such as fundus and retinal (optical coherence) imagery provide further diagnostic tools when determining an RP diagnosis. Photographing the back of the dilated eye allows the confirmation of bone spicule accumulation in the fundus, which presents during the later stages of RP retinal degeneration. Combined with cross-sectional imagery of optical coherence tomography, which provides clues into photoreceptor thickness, retinal layer morphology, and retinal pigment epithelium physiology, fundus imagery can help determine the state of RP progression.While visual field and acuity test results combined with retinal imagery support the diagnosis of retinitis pigmentosa, additional testing is necessary to confirm other pathological features of this disease. Electroretinography (ERG) confirms the RP diagnosis by evaluating functional aspects associated with photoreceptor degeneration, and can detect physiological abnormalities before the initial manifestation of symptoms. An electrode lens is applied to the eye as photoreceptor response to varying degrees of quick light pulses is measured. Patients exhibiting the retinitis pigmentosa phenotype would show decreased or delayed electrical response in the rod photoreceptors, as well as possibly compromised cone photoreceptor cell response. The patients family history is also considered when determining a diagnosis due to the genetic mode of inheritance of retinitis pigmentosa. At least 35 different genes or loci are known to cause "nonsyndromic RP" (RP that is not the result of another disease or part of a wider syndrome). Indications of the RP mutation type can be determine through DNA testing, which is available on a clinical basis for: RLBP1 (autosomal recessive, Bothnia type RP) RP1 (autosomal dominant, RP1) RHO (autosomal dominant, RP4) RDS (autosomal dominant, RP7) PRPF8 (autosomal dominant, RP13) PRPF3 (autosomal dominant, RP18) CRB1 (autosomal recessive, RP12) ABCA4 (autosomal recessive, RP19) RPE65 (autosomal recessive, RP20)For all other genes (e.g. DHDDS), molecular genetic testing is available on a research basis only. RP can be inherited in an autosomal dominant, autosomal recessive, X-linked or Y-linked manner. X-linked RP can be either recessive, affecting primarily only males, or dominant, affecting both males and females, although males are usually more mildly affected. Some digenic (controlled by two genes) and mitochondrial forms have also been described. Genetic counseling depends on an accurate diagnosis, determination of the mode of inheritance in each family, and results of molecular genetic testing. Treatment There is currently no cure for retinitis pigmentosa, but the efficacy and safety of various prospective treatments are currently being evaluated. The efficiency of various supplements, such as vitamin A, DHA, NAC, and lutein, in delaying disease progression remains an unresolved, yet prospective treatment option. Clinical trials investigating optic prosthetic devices, gene therapy mechanisms, and retinal sheet transplantations are active areas of study in the partial restoration of vision in retinitis pigmentosa patients. Stalling of disease Studies have demonstrated the delay of rod photoreceptor degeneration by the daily intake of 15000 IU (equivalent to 4.5 mg) of vitamin A palmitate; thus, stalling disease progression in some patients. Recent investigations have shown that proper vitamin A supplementation can postpone blindness by up to 10 years (by reducing the 10% loss pa to 8.3% pa) in some patients in certain stages of the disease. Bone marrow derived stem cells (BMSC) MD Stem Cells, a clinical research company using autologous bone marrow derived stem cells (BMSC) in the treatment of retinal and optic nerve disease, published results from the Retinitis Pigmentosa cohort within their ongoing NIH registered Stem Cell Ophthalmology Study II (SCOTS2) clinical trial (NCT 03011541). Outcomes were encouraging with 45.5% of eyes showing an average of 7.9 lines of improvement (40.9% LogMAR improvement over baseline) and 45.5% of eyes showing stable acuity over the follow up. Results were statistically significant(p=0.016). Retinitis Pigmentosa continues to be treated and evaluated in the study. Argus retinal prosthesis The Argus retinal prosthesis became the first approved treatment for the disease in February 2011, and is currently available in Germany, France, Italy, and the UK. Interim results on 30 patients long term trials were published in 2012. The Argus II retinal implant has also received market approval in the US. The device may help adults with RP who have lost the ability to perceive shapes and movement to be more mobile and to perform day-to-day activities. In June 2013, twelve hospitals in the US announced they would soon accept consultation for patients with RP in preparation for the launch of Argus II later that year. The Alpha-IMS is a subretinal implant involving the surgical implantation of a small image-recording chip beneath the optic fovea. Measures of visual improvements from Alpha-IMS studies require the demonstration of the devices safety before proceeding with clinical trials and granting market approval. Gene therapy The goal of gene therapy studies is to virally supplement retinal cells expressing mutant genes associated with the retinitis pigmentosa phenotype with healthy forms of the gene; thus, allowing the repair and proper functioning of retinal photoreceptor cells in response to the instructions associated with the inserted healthy gene. Clinical trials investigating the insertion of the healthy RPE65 gene in retinas expressing the LCA2 retinitis pigmentosa phenotype measured modest improvements in vision; however, the degradation of retinal photoreceptors continued at the disease-related rate. Likely, gene therapy may preserve remaining healthy retinal cells while failing to repair the earlier accumulation of damage in already diseased photoreceptor cells. Response to gene therapy would theoretically benefit young patients exhibiting the shortest progression of photoreceptor decline; thus, correlating to a higher possibility of cell rescue via the healthy inserted gene. Drugs Drug named Disulfiram has shown reversing of the disease in rats. Prognosis The progressive nature of and lack of a definitive cure for retinitis pigmentosa contribute to the inevitably discouraging outlook for patients with this disease. While complete blindness is rare, the persons visual acuity and visual field will continue to decline as initial rod photoreceptor and later cone photoreceptor degradation proceeds.Studies indicate that children carrying the disease genotype benefit from presymptomatic counseling in order to prepare for the physical and social implications associated with progressive vision loss. While the psychological prognosis can be slightly alleviated with active counseling the physical implications and progression of the disease depend largely on the age of initial symptom manifestation and the rate of photoreceptor degradation, rather than access to prospective treatments. Corrective visual aids and personalized vision therapy provided by Low Vision Specialists may help patients correct slight disturbances in visual acuity and optimize their remaining visual field. Support groups, vision insurance, and lifestyle therapy are additional useful tools for those managing progressive visual decline. Epidemiology Retinitis pigmentosa is the leading cause of inherited blindness, with approximately 1/4,000 individuals experiencing the non-syndromic form of their disease within their lifetime. It is estimated that 1.5 million people worldwide are currently affected. Early onset RP occurs within the first few years of life and is typically associated with syndromic disease forms, while late onset RP emerges from early to mid-adulthood. Autosomal dominant and recessive forms of retinitis pigmentosa affect both male and female populations equally; however, the less frequent X-linked form of the disease affects male recipients of the X-linked mutation, while females usually remain unaffected carriers of the RP trait. The X-linked forms of the disease are considered severe, and typically lead to complete blindness during later stages. In rare occasions, a dominant form of the X-linked gene mutation will affect both males and females equally.Due to the genetic inheritance patterns of RP, many isolate populations exhibit higher disease frequencies or increased prevalence of a specific RP mutation. Pre-existing or emerging mutations that contribute to rod photoreceptor degeneration in retinitis pigmentosa are passed down through familial lines; thus, allowing certain RP cases to be concentrated to specific geographical regions with an ancestral history of the disease. Several hereditary studies have been performed to determine the varying prevalence rates in Maine (USA), Birmingham (England), Switzerland (affects 1/7000), Denmark (affects 1/2500), and Norway. Navajo Indians display an elevated rate of RP inheritance as well, which is estimated as affecting 1 in 1878 individuals. Despite the increased frequency of RP within specific familial lines, the disease is considered non-discriminatory and tends to equally affect all world populations. Research Future treatments may involve retinal transplants, artificial retinal implants, gene therapy, stem cells, nutritional supplements, and/or drug therapies. 2012: Scientists at the University of Miami Bascom Palmer Eye Institute presented data showing protection of photoreceptors in an animal model when eyes were injected with mesencephalic astrocyte-derived neurotrophic factor (MANF). Researchers at the University of California, Berkeley were able to restore vision to blind mice by exploiting a "photoswitch" that activates retinal ganglion cells in animals with damaged rod and cone cells.2015: A study by Bakondi et al. at Cedars-Sinai Medical Center showed that CRISPR/Cas9 can be used to treat rats with the autosomal dominant form of retinitis pigmentosa. Researchers find that two molecules, rod-derived cone viability factor (RdCVF) and Nrf2, can protect cone photoreceptors in mouse models of retinitis pigmentosa.2016: RetroSense Therapeutics aimed to inject viruses with DNA from light-sensitive algae into the eyes of several blind people (who have retinitis pigmentosa). If successful, they will be able to see in black and white.In 2017 the FDA approved the gene therapy voretigene neparvovec to treat people with biallelic RPE65 mutation-associated retinal dystrophy.In 2020, a literature review estimated the experimental therapeutic technique called transcorneal electrical stimulation as "probably effective" (level B) in retinitis pigmentosa, based on the evidence available at that time.In 2021 an optogenetics application of the protein Channelrhodopsin in a human patient was reported with partial recovery of non-functional vision in a series of one patient only. They did not use standard protocol to measure visual improvement, but created their own criteria. The serendipitous discovery of the novel algal channelrhodopsin used came out of the 1000 Plant Genomes Project. Notable cases Jennifer L. Armentrout, American author of YA paranormal and Science Fiction Willie Brown, 41st Mayor of San Francisco, California Alex Bulmer, Canadian playwright Molly Burke, Canadian YouTuber and motivational speaker Neil Fachie, British paralympic cyclist William (Bill) Fulton, urban planner, author, and former Mayor of Ventura, California Gordon Gund, American businessman and professional sports team owner Rigo Tovar, Mexican musician, singer and actor Lindy Hou, Australian tandem cyclist and triathlete Akbar Khan, musician and disability activist from India Amar Latif, entrepreneur, television personality and professional traveller Rachael Leahcar, Australian singer/songwriter, actress and motivational speaker Steve Lonegan, Mayor of Bogota, New Jersey; Republican candidate for U.S. Senate Chris McCausland, British stand-up comedian and actor Woody Shaw, American jazz trumpeter Regina Sorenson, Australian television personality Shel Talmy, American record producer, songwriter and arranger Danelle Umstead, American Paralympic alpine skier, Dancing with the Stars contestant Jon Wellner, American actor Steve Wynn, American business magnate and Las Vegas casino developer See also References External links Retinitis pigmentosa at Curlie GeneReviews/NCBI/NIH/UW entry on Retinitis Pigmentosa Overview NCBI/Molecular diagnosis of retinitis pigmentosa

Metabolic acidosis

Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the bodys acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidneys to excrete excess acids. Metabolic acidosis can lead to acidemia, which is defined as arterial blood pH that is lower than 7.35. Acidemia and acidosis are not mutually exclusive – pH and hydrogen ion concentrations also depend on the coexistence of other acid-base disorders; therefore, pH levels in people with metabolic acidosis can range from low to high. Acute metabolic acidosis, lasting from minutes to several days, often occurs during serious illnesses or hospitalizations, and is generally caused when the body produces an excess amount of organic acids (ketoacids in ketoacidosis, or lactic acid in lactic acidosis). A state of chronic metabolic acidosis, lasting several weeks to years, can be the result of impaired kidney function (chronic kidney disease) and/or bicarbonate wasting. The adverse effects of acute versus chronic metabolic acidosis also differ, with acute metabolic acidosis impacting the cardiovascular system in hospital settings, and chronic metabolic acidosis affecting muscles, bones, kidney and cardiovascular health. Signs and symptoms Acute metabolic acidosis Symptoms are not specific, and diagnosis can be difficult unless patients present with clear indications for arterial blood gas sampling. Symptoms may include palpitations, headache, altered mental status such as severe anxiety due to hypoxia, decreased visual acuity, nausea, vomiting, abdominal pain, altered appetite and weight gain, muscle weakness, bone pain, and joint pain. People with acute metabolic acidosis may exhibit deep, rapid breathing called Kussmaul respirations which is classically associated with diabetic ketoacidosis. Rapid deep breaths increase the amount of carbon dioxide exhaled, thus lowering the serum carbon dioxide levels, resulting in some degree of compensation. Overcompensation via respiratory alkalosis to form an alkalemia does not occur. Extreme acidemia can also lead to neurological and cardiac complications: Neurological: lethargy, stupor, coma, seizures Cardiac: Abnormal heart rhythms (e.g., ventricular tachycardia) and decreased response to epinephrine, both leading to low blood pressurePhysical examination can occasionally reveal signs of the disease, but is often otherwise normal. Cranial nerve abnormalities are reported in ethylene glycol poisoning, and retinal edema can be a sign of methanol intoxication. Chronic metabolic acidosis Chronic metabolic acidosis has non-specific clinical symptoms but can be readily diagnosed by testing serum bicarbonate levels in patients with Chronic Kidney Disease (CKD) as part of a comprehensive metabolic panel. Patients with CKD Stages G3-G5 should be routinely screened for metabolic acidosis. Diagnostic approach and causes Metabolic acidosis is defined as a reduced serum pH, and an abnormal serum bicarbonate concentration of <22 mEq/L, below the normal range of 22 to 29 mEq/L. However, if a patient has other coexisting acid-base disorders, the pH level may be low, normal or high in the setting of metabolic acidosis. In the absence of chronic respiratory alkalosis, metabolic acidosis can be clinically diagnosed by measuring serum bicarbonate levels in the blood, which is generally a standard component of blood panels. Imperatively, when weighing a metabolic acidosis diagnosis, the change in serum bicarbonate levels over time should be considered; if baseline bicarbonate results are unknown, a single set of values may be misinterpreted. Causes Generally, metabolic acidosis occurs when the body produces too much acid (e.g., lactic acidosis, see below section), there is a loss of bicarbonate from the blood, or when the kidneys are not removing enough acid from the body. Chronic metabolic acidosis is most often caused by a decreased capacity of the kidneys to excrete excess acids through renal ammoniagenesis. The typical Western diet generates 75-100 mEq of acid daily, and individuals with normal kidney function increase the production of ammonia to get rid of this dietary acid. As kidney function declines, the tubules lose the ability to excrete excess acid, and this results in buffering of acid using serum bicarbonate, as well as bone and muscle stores.There are many causes of acute metabolic acidosis, and thus it is helpful to group them by the presence or absence of a normal anion gap. Increased anion gap Causes of increased anion gap include: Lactic acidosis Ketoacidosis (e.g., Diabetic, alcoholic, or starvation) Chronic kidney failure Transient 5-oxoprolinemia due to long-term ingestion of high-doses of acetaminophen (often seen with sepsis, liver failure, kidney failure, or malnutrition) Intoxication: Salicylates, methanol, ethylene glycol Organic acids, paraldehyde, ethanol, formaldehyde Carbon monoxide, cyanide, ibuprofen, metformin Propylene glycol (metabolized to L and D-lactate and is often found in infusions for certain intravenous medications used in the intensive care unit) Massive rhabdomyolysis Isoniazid, iron, phenelzine, tranylcypromine, valproic acid, verapamil Topiramate SulfatesNormal anion gap Causes of normal anion gap include Inorganic acid addition Infusion/ingestion of HCl, NH4Cl Gastrointestinal base loss Diarrhea Small bowel fistula/drainage Surgical diversion of urine into gut loops Renal base loss/acid retention: Proximal renal tubular acidosis Distal renal tubular acidosisHyperalimentation Addison disease Acetazolamide Spironolactone Saline infusionTo distinguish between the main types of metabolic acidosis, a clinical tool called the anion gap is considered very useful. It is calculated by subtracting the sum of the chloride and bicarbonate levels from the sum of the sodium and potassium levels. As sodium is the main extracellular cation, and chloride and bicarbonate are the main anions, the result should reflect the remaining anions. Normally, this concentration is about 8–16 mmol/L (12±4). An elevated anion gap (i.e. > 16 mmol/L) can indicate particular types of metabolic acidosis, such as types caused by certain poisons, lactate acidosis, and ketoacidosis. It is important to note that the anion gap can be spuriously normal in sampling errors of the sodium level, e.g. in extreme hypertriglyceridemia. The anion gap can also be increased due to relatively low levels of cations other than sodium and potassium (e.g. calcium or magnesium).As a differential diagnosis is made, other tests may be necessary, including toxicological screening and imaging of the kidneys, along with testing of electrolytes (including chloride), glucose, kidney function, and a full blood count. Urinalysis can reveal acidity (salicylate poisoning) or alkalinity (renal tubular acidosis type I). In addition, it can show ketones in ketoacidosis. It is also important to differentiate between acidosis-induced hyperventilation and asthma; otherwise, treatment could lead to inappropriate bronchodilation. Pathophysiology Compensatory mechanisms Metabolic acidosis is characterized by a low concentration of bicarbonate (HCO−3), which can happen with increased generation of acids (such as ketoacids or lactic acid), excess loss of HCO−3 by the kidneys or gastrointestinal tract, or an inability to generate sufficient HCO−3. Thus demonstrating the importance of maintaining balance between acids and bases in the body for maintaining optimal functioning of organs, tissues and cells. The body regulates the acidity of the blood by four buffering mechanisms. Bicarbonate buffering system Intracellular buffering by absorption of hydrogen atoms by various molecules, including proteins, phosphates and carbonate in bone. Respiratory compensation. Hyperventilation will cause more carbon dioxide to be removed from the body and thereby increases pH. Kidney compensation Buffer The decreased bicarbonate that distinguishes metabolic acidosis is therefore due to two separate processes: the buffer (from water and carbon dioxide) and additional renal generation. The buffer reactions are: H + + HCO 3 − ↽ − − ⇀ H 2 CO 3 ↽ − − ⇀ CO 2 + H 2 O {\displaystyle {\ce {H+ + HCO3- <=> H2CO3 <=> CO2 + H2O}}} The Henderson-Hasselbalch equation mathematically describes the relationship between blood pH and the components of the bicarbonate buffering system: pH = pK a + L o g ⁡ [ HCO 3 − ] [ CO 2 ] {\displaystyle {\text{pH}}={\text{pK}}_{a}+\mathop {\mathrm {Log} } {\frac {\left[{\text{HCO}}_{3}^{-}\right]}{\left[{\text{CO}}_{2}\right]}}} Using Henrys law, we can say that [CO2] = 0.03 × PaCO2 (PaCO2 is the pressure of CO2 in arterial blood) Adding the other normal values, we get pH = 6.1 + L o g ⁡ [ 24 0.03 × 40 ] {\displaystyle {\text{pH}}=6.1+\mathop {\mathrm {Log} } \left[{\frac {24}{0.03\times 40}}\right]} = 6.1 + 1.3 {\displaystyle =6.1+1.3} = 7.4 {\displaystyle =7.4} Consequences Acute Metabolic Acidosis Acute Metabolic Acidosis most often occurs during hospitalizations, and acute critical illnesses. It is often associated with poor prognosis, with a mortality rate as high as 57% if the pH remains untreated at 7.20. At lower pH levels, acute metabolic acidosis can lead to impaired circulation and end organ function. Chronic Metabolic Acidosis Chronic metabolic acidosis commonly occurs in people with Chronic Kidney Disease with an eGFR of less than 45 ml/min/1.73m2, most often with mild to moderate severity; however, metabolic acidosis can manifest earlier on in the course of Chronic Kidney Disease. Multiple animal and human studies have shown that metabolic acidosis in Chronic Kidney Disease, given its chronic nature, has a profound adverse impact on cellular function, overall contributing to high morbidities in patients. The most adverse consequences of chronic metabolic acidosis in people with Chronic Kidney Disease and in particular, for those who have end-stage renal disease (ESRD), are detrimental changes to the bones and muscles. Acid buffering leads to loss of bone density, resulting in an increased risk of bone fractures, renal osteodystrophy, and bone disease; as well, increased protein catabolism leads to muscle wasting. Furthermore, metabolic acidosis in Chronic Kidney Disease is also associated with a reduction in eGFR; it is both a complication of Chronic Kidney Disease, as well as an underlying cause of Chronic Kidney Disease progression. Treatment Treatment of metabolic acidosis depends on the underlying cause, and should target reversing the main process. When considering course of treatment, it is important to distinguish between acute versus chronic forms. Acute Metabolic Acidosis Bicarbonate therapy is generally administered In patients with severe acute acidemia (pH < 7.11), or with less severe acidemia (pH 7.1-7.2) who have severe acute kidney injury. Bicarbonate therapy is not recommended for people with less severe acidosis (pH ≥ 7.1), unless severe acute kidney injury is present. In the BICAR-ICU trial, bicarbonate therapy for maintaining a pH >7.3 had no overall effect on the composite outcome of all-cause mortality and the presence of at least one organ failure at day 7. However, amongst the sub-group of patients with severe acute kidney injury, bicarbonate therapy significantly decreased the primary composite outcome, and 28-day mortality, along with the need for dialysis. Chronic Metabolic Acidosis For people with Chronic Kidney Disease, treating metabolic acidosis slows the progression of chronic kidney disease. Dietary interventions for treatment of chronic metabolic acidosis include base-inducing fruits and vegetables that assist with reducing the urine net acid excretion, and increase TCO2. Recent research has also suggested that dietary protein restriction, through ketoanalogue-supplemented vegetarian very low protein diets are also a nutritionally safe option for correction of metabolic acidosis in people with Chronic Kidney Disease.Currently, the most commonly used treatment for chronic metabolic acidosis is oral bicarbonate. The NKF/KDOQI guidelines recommend starting treatment when serum bicarbonate levels are <22 mEq/L, in order to maintain levels ≥ 22 mEq/L. Studies investigating the effects of oral alkali therapy demonstrated improvements in serum bicarbonate levels, resulting in a slower decline in kidney function, and reduction in proteinuria – leading to a reduction in the risk of progressing to kidney failure. However, side effects of oral alkali therapy include gastrointestinal intolerance, worsening edema, and worsening hypertension. Furthermore, large doses of oral alkali are required to treat chronic metabolic acidosis, and the pill burden can limit adherence.Veverimer (TRC 101) is a promising investigational drug designed to treat metabolic acidosis by binding with the acid in the gastrointestinal tract and removing it from the body through excretion in the feces, in turn decreasing the amount of acid in the body, and increasing the level of bicarbonate in the blood. Results from a Phase 3, double-blind placebo-controlled 12-week clinical trial in people with CKD and metabolic acidosis demonstrated that Veverimer effectively and safely corrected metabolic acidosis in the short-term, and a blinded, placebo-controlled, 40-week extension of the trial assessing long-term safety, demonstrated sustained improvements in physical function and a combined endpoint of death, dialysis, or 50% decline in eGFR. See also Delta ratio Metabolic alkalosis Respiratory acidosis Respiratory alkalosis Trauma triad of death Winters formula Intravenous bicarbonate References == External links ==

Placental site nodule

A placental site nodule (PSN) is benign remnant from a previous pregnancy. Presentation They are typically asymptomatic and found incidentally. Pathology PSNs are intermediate trophoblastic remnants. Diagnosis PSN are diagnosed by examining the tissue under a microscope, usually obtained with a dilation and curettage. Typically, they consist of pink (hyaline) material using the standard stain and contain few cells. Bizarre multinucleated cells may be present; however, there is no mitotic activity. The differential diagnosis includes (cervical) squamous cell carcinoma, gestational trophoblastic disease, and exaggerated placental site. Prognosis PSN are benign. Once removed, they do not require any treatment and do not recur. See also Gestational trophoblastic disease Placental site trophoblastic tumour References == External links ==

Spondylosis

Spondylosis is the degeneration of the vertebral column from any cause. In the more narrow sense it refers to spinal osteoarthritis, the age-related wear and tear of the spinal column, which is the most common cause of spondylosis. The degenerative process in osteoarthritis chiefly affects the vertebral bodies, the neural foramina and the facet joints (facet syndrome). If severe, it may cause pressure on the spinal cord or nerve roots with subsequent sensory or motor disturbances, such as pain, paresthesia, imbalance, and muscle weakness in the limbs. When the space between two adjacent vertebrae narrows, compression of a nerve root emerging from the spinal cord may result in radiculopathy (sensory and motor disturbances, such as severe pain in the neck, shoulder, arm, back, or leg, accompanied by muscle weakness). Less commonly, direct pressure on the spinal cord (typically in the cervical spine) may result in myelopathy, characterized by global weakness, gait dysfunction, loss of balance, and loss of bowel or bladder control. The patient may experience shocks (paresthesia) in hands and legs because of nerve compression and lack of blood flow. If vertebrae of the neck are involved it is labelled cervical spondylosis. Lower back spondylosis is labeled lumbar spondylosis. The term is from Ancient Greek σπόνδυλος spóndylos, "a vertebra", in plural "vertebrae – the backbone". Signs and symptoms Complications A rare but severe complication of this disease is vertebrobasilar insufficiency. This is a result of the vertebral artery becoming occluded as it passes up in the transverse foramen. The spinal joints become stiff in cervical spondylosis. Thus the chondrocytes which maintain the disc become deprived of nutrition and die. Secondary osteophytes may cause stenosis for spinal nerves, manifesting as radiculopathy. Causes Spondylosis is caused from years of constant abnormal pressure, caused by joint subluxation, stress induced by sports, acute and/or repetitive trauma, or poor posture, being placed on the vertebrae and the discs between them. The abnormal stress causes the body to form new bone in order to compensate for the new weight distribution. This abnormal weight bearing from bone displacement will cause spondylosis to occur. Poor postures and loss of the normal spinal curves can lead to spondylosis as well. Spondylosis can affect a person at any age; however, older people are more susceptible. Diagnosis There are multiple techniques used in the diagnosis of spondylosis, these are; Cervical Compression Test, a variant of Spurlings test, is performed by laterally flexing the patients head and placing downward pressure on it. Neck or shoulder pain on the ipsilateral side (i.e., the side to which the head is flexed) indicates a positive result for this test. A positive test result is not necessarily a positive result for spondylosis and as such additional testing is required. Lhermitte sign: feeling of electrical shock with patient neck flexion Reduced range of motion of the neck, the most frequent objective finding on physical examination MRI and CT scans are helpful for pain diagnosis but generally are not definitive and must be considered together with physical examinations and history. Treatment Many of the treatments for cervical spondylosis have not been subjected to rigorous, controlled trials. Surgery is advocated for cervical radiculopathy in patients who have intractable pain, progressive symptoms, or weakness that fails to improve with conservative therapy. Surgical indications for cervical spondylosis with myelopathy (CSM) remain somewhat controversial, but "most clinicians recommend operative therapy over conservative therapy for moderate-to-severe myelopathy" (Baron, M. E.). Physical therapy may be effective for restoring range of motion, flexibility and core strengthening. Decompressive therapies (i.e., manual mobilization, mechanical traction) may also help alleviate pain. However, physical therapy and osteopathy cannot "cure" the degeneration, and some people view that strong compliance with postural modification is necessary to realize maximum benefit from decompression, adjustments and flexibility rehabilitation. Surgery Current surgical procedures used to treat spondylosis aim to alleviate the signs and symptoms of the disease by decreasing pressure in the spinal canal (decompression surgery) and/or by controlling spine movement (fusion surgery).Decompression surgery: The vertebral column can be operated on from both an anterior and posterior approach. The approach varies depending on the site and cause of root compression. Commonly, osteophytes and portions of intervertebral disc are removed.Fusion surgery: Performed when there is evidence of spinal instability or mal-alignment. Use of instrumentation (such as pedicle screws) in fusion surgeries varies across studies. See also Laminectomy References Further reading Thomas, Clayton L. (1985). Tabers Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, Pennsylvania. ISBN 0-8036-8309-X. Middleton, K., & Fish, D. E. (2009). Lumbar spondylosis: clinical presentation and treatment approaches. Current Reviews in Musculoskeletal Medicine, 2(2), 94–104. == External links ==

Xanthoma

A xanthoma (pl. xanthomas or xanthomata) (condition: xanthomatosis), from Greek ξανθός (xanthós) yellow, is a deposition of yellowish cholesterol-rich material that can appear anywhere in the body in various disease states. They are cutaneous manifestations of lipidosis in which lipids accumulate in large foam cells within the skin. They are associated with hyperlipidemias, both primary and secondary types.Tendon xanthomas are associated with type II hyperlipidemia, chronic biliary tract obstruction, primary biliary cirrhosis, sitosterolemia and the rare metabolic disease cerebrotendineous xanthomatosis. Palmar xanthomata and tuberoeruptive xanthomata (over knees and elbows) occur in type III hyperlipidemia. Types Xanthelasma A xanthelasma is a sharply demarcated yellowish collection of cholesterol underneath the skin, usually on or around the eyelids. Strictly, a xanthelasma is a distinct condition, being called a xanthoma only when becoming larger and nodular, assuming tumorous proportions. Still, it is often classified simply as a subtype of xanthoma. Xanthoma tuberosum Xanthoma tuberosum (also known as tuberous xanthoma) is characterized by xanthomas located over tuberosity of the joints.: 530 Xanthoma tendinosum Xanthoma tendinosum (also tendon xanthoma or tendinous xanthoma) is clinically characterized by papules and nodules found in the tendons of the hands, feet, and heel.: 531  Also associated with familial hypercholesterolemia (FH). Eruptive xanthoma Eruptive xanthoma (ILDS E78.220) is clinically characterized by small, yellowish-orange to reddish-brown papules surrounded by an erythematous halo that appear suddenly all over the body, especially the hands, buttocks, and the extensor surfaces of the extremities.: 531  It tends to be associated with elevated triglycerides. Xanthoma planum Xanthoma planum (ILDS D76.370), also known as plane xanthoma, is clinically characterized by bands or rectangular plates (macules) and plaques in the dermis spread diffusely over large areas of the body.: 531 Palmar xanthoma Palmar xanthoma is clinically characterized by yellowish plaques that involve the palms and flexural surfaces of the fingers.: 531  Plane xanthomas are characterised by yellowish to orange, flat macules or slightly elevated plaques, often with a central white area which may be localised or generalised. They often arise in the skin folds, especially the palmar creases. They occur in hyperlipoproteinaemia type III and type IIA, and in association with biliary cirrhosis. The presence of palmar xanthomata, like the presence of tendinous xanthomata, is indicative of hypercholesterolaemia. Tuberoeruptive xanthoma Tuberoeruptive xanthoma (ILDS E78.210) is clinically characterized by red papules and nodules that appear inflamed and tend to coalesce.: 532  Tuberous xanthomata are considered similar, and within the same disease spectrum as eruptive xanthomata. Other types Other types of xanthoma identified in the Medical Dictionary include: Xanthoma diabeticorum: a type of eruptive xanthoma, often with severe diabetes. Xanthoma disseminatum: a rare xanthoma consisting of non-X histiocytes on flexural (folded) surfaces, associated with diabetes insipidus. Verrucous xanthoma, or histiocytosis Y: a papilloma of the oral mucosa and skin whereby the connective tissue under the epithelium contains histiocytes. See also Xanthelasma List of xanthoma variants associated with hyperlipoproteinemia subtypes References External links Media related to xanthoma at Wikimedia Commons MedlinePlus Encyclopedia: Xanthoma

List of skin conditions

Many conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle and glands. The major function of this system is as a barrier against the external environment. The skin weighs an average of four kilograms, covers an area of two square metres, and is made of three distinct layers: the epidermis, dermis, and subcutaneous tissue. The two main types of human skin are: glabrous skin, the hairless skin on the palms and soles (also referred to as the "palmoplantar" surfaces), and hair-bearing skin. Within the latter type, the hairs occur in structures called pilosebaceous units, each with hair follicle, sebaceous gland, and associated arrector pili muscle. In the embryo, the epidermis, hair, and glands form from the ectoderm, which is chemically influenced by the underlying mesoderm that forms the dermis and subcutaneous tissues.The epidermis is the most superficial layer of skin, a squamous epithelium with several strata: the stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale. Nourishment is provided to these layers by diffusion from the dermis since the epidermis is without direct blood supply. The epidermis contains four cell types: keratinocytes, melanocytes, Langerhans cells, and Merkel cells. Of these, keratinocytes are the major component, constituting roughly 95 percent of the epidermis. This stratified squamous epithelium is maintained by cell division within the stratum basale, in which differentiating cells slowly displace outwards through the stratum spinosum to the stratum corneum, where cells are continually shed from the surface. In normal skin, the rate of production equals the rate of loss; about two weeks are needed for a cell to migrate from the basal cell layer to the top of the granular cell layer, and an additional two weeks to cross the stratum corneum.The dermis is the layer of skin between the epidermis and subcutaneous tissue, and comprises two sections, the papillary dermis and the reticular dermis. The superficial papillary dermis interdigitates with the overlying rete ridges of the epidermis, between which the two layers interact through the basement membrane zone. Structural components of the dermis are collagen, elastic fibers, and ground substance. Within these components are the pilosebaceous units, arrector pili muscles, and the eccrine and apocrine glands. The dermis contains two vascular networks that run parallel to the skin surface—one superficial and one deep plexus—which are connected by vertical communicating vessels. The function of blood vessels within the dermis is fourfold: to supply nutrition, to regulate temperature, to modulate inflammation, and to participate in wound healing.The subcutaneous tissue is a layer of fat between the dermis and underlying fascia. This tissue may be further divided into two components, the actual fatty layer, or panniculus adiposus, and a deeper vestigial layer of muscle, the panniculus carnosus. The main cellular component of this tissue is the adipocyte, or fat cell. The structure of this tissue is composed of septal (i.e. linear strands) and lobular compartments, which differ in microscopic appearance. Functionally, the subcutaneous fat insulates the body, absorbs trauma, and serves as a reserve energy source.Conditions of the human integumentary system constitute a broad spectrum of diseases, also known as dermatoses, as well as many nonpathologic states (like, in certain circumstances, melanonychia and racquet nails). While only a small number of skin diseases account for most visits to the physician, thousands of skin conditions have been described. Classification of these conditions often presents many nosological challenges, since underlying etiologies and pathogenetics are often not known. Therefore, most current textbooks present a classification based on location (for example, conditions of the mucous membrane), morphology (chronic blistering conditions), etiology (skin conditions resulting from physical factors), and so on. Clinically, the diagnosis of any particular skin condition is made by gathering pertinent information regarding the presenting skin lesion(s), including the location (such as arms, head, legs), symptoms (pruritus, pain), duration (acute or chronic), arrangement (solitary, generalized, annular, linear), morphology (macules, papules, vesicles), and color (red, blue, brown, black, white, yellow). Diagnosis of many conditions often also requires a skin biopsy which yields histologic information that can be correlated with the clinical presentation and any laboratory data. Acneiform eruptions Acneiform eruptions are caused by changes in the pilosebaceous unit.Acne aestivalis (Mallorca acne) Acne conglobata Acne cosmetica (cosmetic acne) Acne fulminans (acute febrile ulcerative acne) Acne keloidalis nuchae (acne keloidalis, dermatitis papillaris capillitii, folliculitis keloidalis, folliculitis keloidis nuchae, nuchal keloid acne) Acne mechanica Acne medicamentosa Acne miliaris necrotica (acne varioliformis) Acne vulgaris (acne simplex) Acne with facial edema (solid facial edema) Blepharophyma Erythrotelangiectatic rosacea (erythematotelangiectatic rosacea, vascular rosacea) Excoriated acne (acne excoriée des jeunes filles, Pickers acne) Glandular rosacea Gnathophyma Gram-negative rosacea Granulomatous facial dermatitis Granulomatous perioral dermatitis Halogen acne Hidradenitis suppurativa (acne inversa, pyoderma fistulans significa, Verneuils disease) Idiopathic facial aseptic granuloma Infantile acne Lupoid rosacea (granulomatous rosacea, micropapular tuberculid, rosacea-like tuberculid of Lewandowsky) Lupus miliaris disseminatus faciei Metophyma Neonatal acne (acne infantum, acne neonatorum, neonatal cephalic pustulosis) Occupational acne Oil acne Ocular rosacea (ophthalmic rosacea, ophthalmorosacea) Otophyma Periorificial dermatitis Persistent edema of rosacea (chronic upper facial erythematous edema, Morbihans disease, rosaceous lymphedema) Phymatous rosacea Pomade acne Papulopustular rosacea (inflammatory rosacea) Perifolliculitis capitis abscedens et suffodiens (dissecting cellulitis of the scalp, dissecting folliculitis, perifolliculitis capitis abscedens et suffodiens of Hoffman) Perioral dermatitis Periorbital dermatitis (periocular dermatitis) Pyoderma faciale (rosacea fulminans) Rhinophyma Rosacea (acne rosacea) Rosacea conglobata Synovitis–acne–pustulosis–hyperostosis–osteomyelitis syndrome (SAPHO syndrome) Steroid rosacea Tar acne Tropical acne Autoinflammatory syndromes Autoinflammatory syndromes are a group of inherited disorders characterized by bouts of inflammatory skin lesions and periodic fevers. Blau syndrome Chronic infantile neurologic cutaneous and articular syndrome Familial cold urticaria (familial cold autoinflammatory syndrome) Familial Mediterranean fever Hyper-IgD syndrome Majeed syndrome Muckle–Wells syndrome TNF receptor associated periodic syndrome (familial Hibernian fever, TRAPS, tumor necrosis factor receptor associated periodic syndrome) Chronic blistering Chronic blistering cutaneous conditions have a prolonged course and present with vesicles and bullae. Adult linear IgA disease Bullous pemphigoid Bullous lupus erythematosus Childhood linear IgA disease (chronic bullous disease of childhood) Cicatricial pemphigoid (benign mucosal pemphigoid, benign mucous membrane pemphigoid, ocular pemphigus, scarring pemphigoid) Dermatitis herpetiformis (Duhring disease) Endemic pemphigus (endemic pemphigus foliaceus, fogo selvagem) Epidermolysis bullosa acquisita Grovers disease (benign papular acantholytic dermatosis, persistent acantholytic dermatosis, transient acantholytic dermatosis) IgA pemphigus Intraepidermal neutrophilic IgA dermatosis Localized cicatricial pemphigoid (Brunsting–Perry cicatricial pemphigoid) Paraneoplastic pemphigus Pemphigus erythematosus (Senear–Usher syndrome) Pemphigus foliaceus Pemphigus herpetiformis (acantholytic herpetiform dermatitis, herpetiform pemphigus, mixed bullous disease, pemphigus controlled by sulfapyridine) Pemphigoid nodularis Pemphigus vegetans Pemphigus vegetans of Hallopeau Pemphigus vegetans of Neumann Pemphigus vulgaris Vesicular pemphigoid Vulvar childhood pemphigoid Conditions of the mucous membranes Conditions of the mucous membranes involve the moist linings of the eyes, nose, mouth, genitals, and anus. Acatalasia (acatalasemia, Takaharas disease) Acquired dyskeratotic leukoplakia Actinic cheilitis (actinic cheilosis) Acute necrotizing ulcerative gingivitis (acute membranous gingivitis, acute necrotizing ulcerative gingivostomatitis, fusospirillary gingivitis, fusospirillosis, fusospirochetal gingivitis, necrotizing gingivitis, phagedenic gingivitis, trench mouth, ulcerative gingivitis, Vincent gingivitis, Vincent infection, Vincent stomatitis, Vincents disease) Allergic contact cheilitis Angina bullosa haemorrhagica Angular cheilitis (perlèche) Behçets disease (Behçets syndrome, oculo-oral-genital syndrome) Black hairy tongue (hairy tongue, lingua villosa nigra) Caviar tongue Cheilitis exfoliativa Cheilitis glandularis Cheilitis granulomatosa (granulomatous cheilitis, orofacial granulomatosis) Cutaneous sinus of dental origin (dental sinus) Cyclic neutropenia Desquamative gingivitis Drug-induced ulcer of the lip Epidermization of the lip Epulis Epulis fissuratum (granuloma fissuratum) Eruptive lingual papillitis Erythroplakia (erythroplasia) Fissured tongue (furrowed tongue, lingua plicata, plicated tongue, scrotal tongue) Geographic tongue (benign migratory glossitis, benign migratory stomatitis, glossitis areata exfoliativa, glossitis areata migrans, lingua geographica, stomatitis areata migrans, transitory benign plaques of the tongue) Gingival fibroma Gingival hypertrophy Hairy leukoplakia (oral hairy leukoplakia) Intraoral dental sinus Linea alba Leukoplakia Leukoplakia with tylosis and esophageal carcinoma Major aphthous ulcer (periadenitis mucosa necrotica recurrens) Median rhomboid glossitis (central papillary atrophy) Melanocytic oral lesion Melkersson–Rosenthal syndrome Morsicatio buccarum (chronic cheek biting, chronic cheek chewing) Mucosal squamous cell carcinoma Mucous cyst of the oral mucosa (mucocele) Nagayamas spots Oral Crohns disease Oral florid papillomatosis Oral melanosis Osseous choristoma of the tongue Peripheral ameloblastoma Plasma cell cheilitis (plasma cell gingivitis, plasma cell orificial mucositi) Plasmoacanthoma Proliferative verrucous leukoplakia Pyogenic granuloma (eruptive hemangioma, granulation tissue-type hemangioma, granuloma gravidarum, lobular capillary hemangioma, pregnancy tumor, tumor of pregnancy) Pyostomatitis vegetans Recurrent aphthous stomatitis (aphthosis, canker sores, recurrent oral aphthae) Recurrent intraoral herpes simplex infection Smooth tongue (atrophic glossitis, bald tongue, hunter glossitis, moeller) Stomatitis nicotina (nicotine stomatitis, smokers keratosis, smokers patches) Torus palatinus Trumpeters wart Vestibular papillomatosis White sponge nevus (white sponge nevus of Cannon) Conditions of the skin appendages Conditions of the skin appendages are those affecting the glands of the skin, hair, nails, and arrector pili muscles. Acne necrotica Acquired generalized hypertrichosis (acquired hypertrichosis lanuginosa, hypertrichosis lanuginosa acquisita) Acquired perforating dermatosis (acquired perforating collagenosis) Acrokeratosis paraneoplastica of Bazex (acrokeratosis neoplastica, Bazex syndrome) Acroosteolysis Acute paronychia Alopecia areata Alopecia neoplastica Anagen effluvium Androgenic alopecia (androgenetic alopecia) Anhidrosis (hypohidrosis) Anonychia Apparent leukonychia Beaus lines Blue nails Bromidrosis (apocrine bromhidrosis, fetid sweat, malodorous sweating, osmidrosis) Bubble hair deformity Central centrifugal cicatricial alopecia (follicular degeneration syndrome, pseudopelade of the central scalp) Chevron nail (herringbone nail) Chromhidrosis (colored sweat) Chronic paronychia Cicatricial alopecia Clubbing (drumstick fingers, Hippocratic fingers, watch-glass nails) Congenital onychodysplasia of the index fingers Disseminate and recurrent infundibulofolliculitis Erosive pustular dermatitis of the scalp (erosive pustular dermatosis of the scalp) Erythromelanosis follicularis faciei et colli Folliculitis decalvans Folliculitis nares perforans Fox–Fordyce disease Frontal fibrosing alopecia Generalized congenital hypertrichosis (congenital hypertrichosis lanuginosa) Generalized hyperhidrosis Graham-Little syndrome Granulosis rubra nasi Green nails Gustatory hyperhidrosis Hair casts (pseudonits) Hair follicle nevus (vellus hamartoma) Hairy palms and soles Half and half nails (Lindsays nails) Hangnail Hapalonychia Hematidrosis Hirsutism Hook nail Hot comb alopecia Hypertrichosis cubiti (hairy elbow syndrome) Hypertrichosis simplex of the scalp Intermittent hair–follicle dystrophy Keratosis pilaris atrophicans Kinking hair (acquired progressive kinking) Koenens tumor (Koenens periungual fibroma, periungual fibroma) Koilonychia (spoon nails) Kyrle disease Leukonychia (white nails) Lichen planopilaris (acuminatus, follicular lichen planus, lichen planus follicularis, peripilaris) Lichen planus of the nails Lichen spinulosus (keratosis spinulosa) Lipedematous alopecia (lipedematous scalp) Localized acquired hypertrichosis Localized congenital hypertrichosis Longitudinal erythronychia Longitudinal melanonychia Loose anagen syndrome (loose anagen hair syndrome) Lupus erythematosus Madarosis Malalignment of the nail plate Male-pattern baldness Marie–Unna hereditary hypotrichosis (Marie–Unna hypotrichosis) Median nail dystrophy (dystrophia unguis mediana canaliformis, median canaliform dystrophy of Heller, solenonychia) Mees lines Melanonychia Menkes kinky hair syndrome (kinky hair disease, Menkes disease) Monilethrix (beaded hair) Muehrckes nails (Muehrckes lines) Nail–patella syndrome (Fong syndrome, hereditary osteoonychodysplasia, HOOD syndrome) Neoplasms of the nailbed Nevoid hypertrichosis Noncicatricial alopecia Onychauxis Onychoatrophy Onychocryptosis (ingrown nail, unguis incarnatus) Onychogryphosis (rams horn nails) Onycholysis Onychomadesis Onychomatricoma Onychophagia (nail biting) Onychophosis Onychoptosis defluvium (alopecia unguium) Onychorrhexis (brittle nails) Onychoschizia Onychotillomania Ophiasis Palmoplantar hyperhidrosis (emotional hyperhidrosis) Parakeratosis pustulosa Patterned acquired hypertrichosis Perforating folliculitis Pili annulati (ringed hair) Pili bifurcati Pili multigemini Pili pseudoannulati (pseudo pili annulati) Pili torti (twisted hairs) Pincer nails (omega nails, trumpet nails) Pityriasis amiantacea (tinea amiantacea) Platonychia Plica neuropathica (felted hair) Plummers nail Premature greying of hair Prepubertal hypertrichosis Pressure alopecia (postoperative alopecia, pressure-induced alopecia) Pseudofolliculitis barbae (barbers itch, folliculitis barbae traumatica, razor bumps, scarring pseudofolliculitis of the beard, shave bumps) Pseudopelade of Brocq (alopecia cicatrisata) Psoriatic nails Pterygium inversum unguis (pterygium inversus unguis, ventral pterygium) Pterygium unguis (dorsal pterygium) Purpura of the nail bed Racquet nail (brachyonychia, nail en raquette, racquet thumb) Recurrent palmoplantar hidradenitis (idiopathic palmoplantar hidradenitis, idiopathic plantar hidradenitis, painful plantar erythema, palmoplantar eccrine hidradenitis, plantar panniculitis) Red lunulae Ross syndrome Rubinstein–Taybi syndrome Setleis syndrome Shell nail syndrome Short anagen syndrome Splinter hemorrhage Spotted lunulae Staining of the nail plate Stippled nails Subungual hematoma Telogen effluvium Terrys nails Traction alopecia Traumatic alopecia Traumatic anserine folliculosis Triangular alopecia (temporal alopecia, temporal triangular alopecia) Trichomegaly Trichomycosis axillaris Trichorrhexis invaginata (bamboo hair) Trichorrhexis nodosa Trichostasis spinulosa Tufted folliculitis Tumor alopecia Twenty-nail dystrophy (sandpapered nails, trachyonychia) Uncombable hair syndrome (cheveux incoiffable, pili trianguli et canaliculi, spun-glass hair) Wooly hair nevus (woolly hair nevus) X-linked hypertrichosis Conditions of the subcutaneous fat Conditions of the subcutaneous fat are those affecting the layer of adipose tissue that lies between the dermis and underlying fascia. Acquired generalized lipodystrophy (Lawrence syndrome, Lawrence–Seip syndrome) Adiposis dolorosa (Dercums disease) Alpha-1 antitrypsin deficiency panniculitis (alpha1-protease deficiency panniculitis, alpha1-proteinase deficiency panniculitis) Atrophic connective tissue panniculitis Barraquer–Simons syndrome (acquired partial lipodystrophy, cephalothoracic lipodystrophy, progressive lipodystrophy) Benign symmetric lipomatosis (benign symmetric lipomatosis of Launois–Bensaude, Madelungs disease) Centrifugal abdominal lipodystrophy (centrifugal lipodystrophy, lipodystrophia centrifugalis abdominalis infantalis) Chronic erythema nodosum (erythema nodosum migrans, subacute migratory panniculitis of Vilanova and Piñol, subacute nodular migratory panniculitis) Cold panniculitis (popsicle panniculitis) Congenital generalized lipodystrophy (Berardinelli–Seip syndrome) Cytophagic histiocytic panniculitis Drug-induced lipodystrophy Factitial panniculitis Familial partial lipodystrophy (Köbberling–Dunnigan syndrome) Gouty panniculitis Hemihyperplasia–multiple lipomatosis syndrome HIV-associated lipodystrophy Involutional lipoatrophy Lipoatrophia annularis (Ferreira–Marques lipoatrophia) Lipoatrophia semicircularis (semicircular lipoatrophy) Lipodermatosclerosis (chronic panniculitis with lipomembranous changes, hypodermitis sclerodermiformis, sclerosing panniculitis, stasis panniculitis) Lipohypertrophy Localized lipodystrophy Neutrophilic lobular panniculitis Nodular vasculitis Non-progressive late-onset linear hemifacial lipoatrophy Pancreatic panniculitis (enzymatic panniculitis, pancreatic fat necrosis, subcutaneous fat necrosis) Polands syndrome Post-steroid panniculitis Sclerema neonatorum Sclerosing lipogranuloma (paraffinoma) Septal panniculitis Subcutaneous fat necrosis of the newborn Traumatic panniculitis Tumor lysis syndrome Weber–Christian disease (relapsing febrile nonsuppurative panniculitis) Congenital anomalies Cutaneous congenital anomalies are a diverse group of disorders that result from faulty morphogenesis, the biological process that forms the shape of a human body. Accessory nail of the fifth toe Accessory tragus (ear tag, preauricular appendage, preauricular tag) Amniotic band syndrome (ADAM complex, amniotic band sequence, congenital constriction bands, pseudoainhum) Aplasia cutis congenita (cutis aplasia, congenital absence of skin, congenital scars) Arteriovenous fistula Benign neonatal hemangiomatosis Branchial cyst (branchial cleft cyst) Bronchogenic cyst Capillary hemangioma (infantile hemangioma, nevus maternus, strawberry hemangioma, strawberry nevus) Cavernous venous malformation Congenital cartilaginous rest of the neck (cervical accessory tragus, wattle) Congenital erosive and vesicular dermatosis Congenital hypertrophy of the lateral fold of the hallux Congenital lip pit (congenital sinus of the lower lip, lip sinus, midline sinus of the upper lip) Congenital malformations of the dermatoglyphs Congenital smooth muscle hamartoma Cystic lymphatic malformation Dermoid cyst Diffuse neonatal hemangiomatosis Encephalocele Focal facial dermal dysplasia Hutchinsons teeth Hyperkeratotic cutaneous capillary-venous malformation Intrauterine epidermal necrosis Limb–mammary syndrome Lowry–MacLean syndrome Macrocheilia Macrocystic lymphatic malformation Malignant pilomatricoma (pilomatrical carcinoma, pilomatrix carcinoma) Maternal autoimmune bullous disease Median raphe cyst Melanotic neuroectodermal tumor of infancy Membranous aplasia cutis Microcystic lymphatic malformation Midline cervical cleft Mongolian spot (congenital dermal melanocytosis, dermal melanocytosis) Mulberry molar Nager acrofacial dysostosis Nasal glioma (brain-like heterotopia, cephalic brain-like heterotopia, glial hamartoma, heterotopic neuroglial tissue, nasal cerebral heterotopia, nasal heterotopic brain tissue) Nasolacrimal duct cyst Nevus psiloliparus Non-involuting congenital hemangioma Omphalomesenteric duct cyst (omphalomesenteric duct remnant, vitelline cyst) PELVIS syndrome Pilomatricoma (calcifying epithelioma of Malherbe, Malherbe calcifying epithelioma, pilomatrixoma) Poland anomaly Posterior fossa malformations–hemangiomas–arterial anomalies–cardiac defects–eye abnormalities–sternal cleft and supraumbilical raphe syndrome (PHACE association, PHACES syndrome) Preauricular sinus and cyst (ear pit, congenital auricular fistula, congenital preauricular fistula, preauricular cyst) Rapidly involuting congenital hemangioma (congenital nonprogressive hemangioma) Rosenthal–Kloepfer syndrome Rudimentary supernumerary digit (rudimentary polydactyly) SACRAL syndrome Sinus pericranii Skin dimple (skin fossa) Superficial lymphatic malformation (lymphangioma circumscriptum) Supernumerary nipple (accessory nipple, pseudomamma) Thyroglossal duct cyst Verrucous vascular malformation (angiokeratoma circumscriptum naeviforme) Connective tissue diseases Connective tissue diseases are caused by a complex array of autoimmune responses that target or affect collagen or ground substance. Acute cutaneous lupus erythematosus Atrophoderma of Pasini and Pierini (dyschromic and atrophic variation of scleroderma, morphea plana atrophica, sclérodermie atrophique demblée) Calcinosis–Raynaud phenomenon–esophageal dysmotility–sclerodactyly–telangiectasia syndrome (CREST syndrome) Chilblain lupus erythematosus (chilblain lupus erythematosus of Hutchinson) Childhood dermatomyositis Childhood discoid lupus erythematosus Childhood systemic lupus erythematosus Complement deficiency syndromes Dermatomyositis Ehlers–Danlos syndrome Eosinophilia–myalgia syndrome Frontal linear scleroderma (en coup de sabre, morphea en coup de sabre) Generalized discoid lupus erythematosus Generalized morphea Interstitial granulomatous dermatitis Juvenile rheumatoid arthritis (juvenile idiopathic arthritis, Stills disease) Keloid morphea Linear atrophoderma of Moulin (Moulin atrophoderma linearis) Linear scleroderma Localized discoid lupus erythematosus Localized morphea Lupus erythematosus panniculitis (lupus erythematosus profundus, lupus panniculitis, lupus profundus, subcutaneous lupus erythematosus) Lupus erythematosus–lichen planus overlap syndrome (lichen planus–lupus erythematosus overlap syndrome) Methotrexate-induced papular eruption Mixed connective tissue disease (Sharps syndrome, undifferentiated connective tissue disease) Morphea profunda Morphea–lichen sclerosus et atrophicus overlap Mouth and genital ulcers with inflamed cartilage syndrome (MAGIC syndrome) Neonatal lupus erythematosus Nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy) Nicolau–Balus syndrome Nodulosis–arthropathy–osteolysis syndrome Normophosphatemic familial tumoral calcinosis Palisaded neutrophilic and granulomatous dermatitis Pansclerotic morphea Parry–Romberg syndrome (progressive hemifacial atrophy) Progressive systemic sclerosis Relapsing polychondritis (atrophic polychondritis, systemic chondromalacia) Rheumatoid arthritis Rheumatoid nodulosis (accelerated rheumatoid nodulosis) Rheumatoid vasculitis Rowells syndrome Scleredema adultorum (Bushke disease, scleredema diabeticorum, scleredema adultorum of Buschke, scleredema of Buschke) Silicosis Sjögrens syndrome (Mikulicz disease, Sicca syndrome) Subacute cutaneous lupus erythematosus Systemic lupus erythematosus Toxic oil syndrome Tumid lupus erythematosus (lupus erythematosus tumidus) Tuzun syndrome Verrucous lupus erythematosus (hypertrophic lupus erythematosus) Winchester syndrome Abnormalities of dermal fibrous and elastic tissue Abnormalities of dermal fibrous and elastic tissue are caused by problems in the regulation of collagen synthesis or degradation. Acrodermatitis chronica atrophicans (Herxheimer disease, primary diffuse atrophy) Actinic elastosis (solar elastosis) Anetoderma (anetoderma maculosa, anetoderma maculosa cutis, atrophia maculosa cutis, macular atrophy) Blepharochalasis Cutis laxa (chalazoderma, dermatochalasia, dermatolysis, dermatomegaly, generalized elastolysis, generalized elastorrhexis, pachydermatocele) Cutis rhomboidalis nuchae Ehlers–Danlos syndrome (cutis hyperelastica, elastic skin, India rubber skin) Elastosis perforans serpiginosa Homocystinuria Jadassohn–Pellizzari anetoderma Linear focal elastosis (elastotic striae) Loeys–Dietz syndrome Marfan syndrome Occipital horn syndrome Osteogenesis imperfecta (Lobstein syndrome) Perforating calcific elastosis (localized acquired cutaneous pseudoxanthoma elasticum, perforating periumbilical calcific elastosis, periumbilical perforating pseudoxanthoma elasticum) Pseudoxanthoma elasticum (Grönblad–Strandberg syndrome) Reactive perforating collagenosis Schweninger–Buzzi anetoderma Sclerotic fibroma Striae atrophicans Striae distensae Ullrich disease Verrucous perforating collagenoma Wrinkly skin syndrome Dermal and subcutaneous growths Dermal and subcutaneous growths result from (1) reactive or neoplastic proliferation of cellular components of the dermis or subcutaneous tissue, or (2) neoplasms invading or aberrantly present in the dermis. Acquired progressive lymphangioma (benign lymphangioendothelioma) Acral arteriolar ectasia Acral fibrokeratoma (acquired digital fibrokeratoma, acquired periungual fibrokeratoma) Acrochordon (cutaneous papilloma, cutaneous tag, fibroepithelial polyp, fibroma molluscum, fibroma pendulum, papilloma colli, skin tag, soft fibroma, Templeton skin tag) Adenoma sebaceum Adult type of generalized eruption of cutaneous mastocytosis African cutaneous Kaposi sarcoma African lymphadenopathic Kaposi sarcoma Aggressive infantile fibromatosis AIDS-associated Kaposi sarcoma Ainhum (bankokerend, dactylolysis spontanea, sukhapakla) Angiofibroma Angiokeratoma Angiokeratoma of Fordyce (angiokeratoma of the scrotum and vulva) Angiokeratoma of Mibelli (Mibellis angiokeratoma, telangiectatic warts) Angioleiomyoma (vascular leiomyoma) Angiolipoleiomyoma Angiolipoma Angioma serpiginosum Angiosarcoma Aponeurotic fibroma (calcifying aponeurotic fibroma, juvenile aponeurotic fibroma) Atypical fibroxanthoma Benign lipoblastomatosis (embryonic lipoma) Buschke–Ollendorff syndrome (dermatofibrosis lenticularis disseminata) Capillary aneurysms Carcinoid Cellular angiofibroma Cherry angioma (De Morgan spot, senile angioma) Chondrodermatitis nodularis chronica helicis (chondrodermatitis nodularis helicis) Chondroid lipoma Chordoma Classic Kaposi sarcoma Collagenous fibroma (desmoplastic fibroblastoma) Composite hemangioendothelioma Connective tissue nevus (collagenoma, elastoma, shagreen patch) Cutaneous endometriosis Cutaneous meningioma (heterotopic meningeal tissue, rudimentary meningocele) Cutaneous myelofibrosis Cutaneous myxoma Cutis marmorata telangiectatica congenita (congenital generalized phlebectasia, Van Lohuizen syndrome) Dermal dendrocyte hamartoma Dermatofibroma (benign fibrous histiocytoma, dermal dendrocytoma, fibrous dermatofibroma, fibrous histiocytoma, fibroma simplex, histiocytoma, nodular subepidermal fibrosis, sclerosing hemangioma) Dermatofibrosarcoma protuberans Desmoid tumor Diffuse cutaneous mastocytosis Diffuse infantile fibromatosis Dupuytrens contracture (Dupuytrens diathesis, Dupuytrens disease, palmar fibromatosis) Eccrine angiomatous hamartoma Elastofibroma dorsi Endovascular papillary angioendothelioma (Dabska tumor, Dabska-type hemangioendothelioma, hobnail hemangioendothelioma, malignant endovascular papillary angioendothelioma, papillary intralymphatic angioendothelioma) Epithelioid cell histiocytoma Epithelioid hemangioendothelioma Epithelioid sarcoma Erythrodermic mastocytosis Extraskeletal chondroma (chondroma of soft parts) Familial myxovascular fibromas Fascial hernia Fibroma of tendon sheath Fibromatosis colli (sternomastoid tumor of infancy) Fibrous hamartoma of infancy Fibrous papule of the nose (benign solitary fibrous papule, fibrous papule of the face) Folded skin with scarring (Michelin tire baby syndrome) Fordyces spot (Fordyces disease) Ganglion cyst Ganglioneuroma Gardner fibroma Genital leiomyoma (dartoic leiomyoma) Giant cell fibroblastoma Giant cell tumor of the tendon sheath (giant cell synovioma, localized nodular tenosynovitis, pigmented villonodular synovitis) Glomeruloid hemangioma Glomus tumor (glomangioma, solid glomus tumor, solitary glomus tumor) Granular cell tumor (Abrikossoffs tumor, Abrikossovs tumor, granular cell myoblastoma, granular cell nerve sheath tumor, granular cell schwannoma) Hamartoma Hemangiopericytoma Hemangiosarcoma Hibernoma (fetal lipoma, lipoma of embryonic fat, lipoma of immature adipose tissue) Hypertrophic scar Immunosuppression-associated Kaposi sarcoma Infantile digital fibromatosis (inclusion body fibromatosis, infantile digital myofibroblastoma, Reye tumor) Infantile hemangiopericytoma (congenital hemangiopericytoma) Infantile myofibromatosis (congenital generalized fibromatosis, congenital multicentric fibromatosis) Infantile systemic hyalinosis (juvenile systemic hyalinosis) Intradermal spindle cell lipoma Intravascular papillary endothelial hyperplasia (Massons hemangio-endotheliome vegetant intravasculaire, Massons lesion, Massons pseudoangiosarcoma, Massons tumor, papillary endothelial hyperplasia) Juvenile hyaline fibromatosis (fibromatosis hyalinica multiplex juvenilis, Murray–Puretic–Drescher syndrome) Kaposiform hemangioendothelioma (infantile kaposiform hemangioendothelioma) Kasabach–Merritt syndrome (hemangioma with thrombocytopenia) Keloid (Keloidal scar) Keratinizing metaplasia Keratocyst Klippel–Trenaunay syndrome (angioosteohypertrophy syndrome, hemangiectatic hypertrophy) Knuckle pads (heloderma) Leiomyosarcoma Lipoma Liposarcoma (atypical lipoma, atypical lipomatous tumor) Lymphangiectasis (lymphangioma) Lymphangiomatosis Malignant fibrous histiocytoma Malignant peripheral nerve sheath tumor (malignant schwannoma, neurofibrosarcoma, neurosarcoma) Mast cell sarcoma Meningocele Metastatic carcinoma Microvenular hemangioma (microcapillary hemangioma) Midline nevus flammeus (angels kiss, salmon patch) Multifocal lymphangioendotheliomatosis (congenital cutaneovisceral angiomatosis with thrombocytopenia, multifocal lymphangioendotheliomatosis with thrombocytopenia) Multinucleate cell angiohistocytoma Multiple cutaneous and uterine leiomyomatosis syndrome (leiomyomatosis cutis et uteri, multiple leiomyomatosis, Reeds syndrome) Multiple cutaneous leiomyoma (pilar leiomyoma) Neural fibrolipoma Neuroblastoma (infantile neuroblastoma, neuroepithelioma) Neuroma cutis Neurothekeoma (bizarre cutaneous neurofibroma, cutaneous lobular neuromyxoma, myxoma of the nerve sheath, myxomatous perineurioma, nerve sheath myxoma) Nevus flammeus (capillary malformation, port-wine stain) Nevus flammeus nuchae (stork bite) Nevus lipomatosus superficialis (nevus lipomatosis of Hoffman and Zurhelle) Nevus oligemicus Nodular fasciitis (nodular pseudosarcomatous fasciits, pseudosarcomatous fasciitis, subcutaneous pseudosarcomatous fibromatosis) Oral submucous fibrosis Pachydermodactyly Palisaded encapsulated neuroma Paraneoplastic syndrome Pearly penile papules (hirsuties coronae glandis, hirsutoid papillomas) Peyronies disease (induratio penis plastica) Phakomatosis pigmentovascularis Piloleiomyoma Plantar fibromatosis (Ledderhoses disease) Pleomorphic fibroma Pleomorphic lipoma Plexiform fibrohistiocytic tumor Porokeratotic eccrine ostial and dermal duct nevus Progressive nodular histiocytoma Proliferating angioendotheliomatosis Prominent inferior labial artery Pseudo-ainhum Retiform hemangioendothelioma (hobnail hemangioendothelioma) Schwannoma (acoustic neuroma, neurilemmoma, neurinoma, neurolemmoma, Schwann cell tumor) Solitary angiokeratoma Solitary cutaneous leiomyoma Solitary mastocytoma Solitary neurofibroma (plexiform neurofibroma, solitary nerve sheath tumor, sporadic neurofibroma) Spider angioma (nevus araneus, spider telangiectasia, spider nevus, vascular spider) Spindle cell hemangioendothelioma (spindle cell hemangioma) Spindle cell lipoma Sternal cleft Subungual exostosis Superficial acral fibromyxoma Systemic mastocytosis Targetoid hemosiderotic hemangioma (hobnail hemangioma) Telangiectasia Telangiectasia macularis eruptiva perstans Teratoma Tufted angioma (acquired tufted angioma, angioblastoma, angioblastoma of Nakagawa, hypertrophic hemangioma, progressive capillary hemangioma, tufted hemangioma) Umbilical granuloma Universal angiomatosis (generalized telangiectasia) Urticaria pigmentosa (childhood type of generalized eruption of cutaneous mastocytosis) Venous lake (phlebectasis) Wildervanck syndrome Xanthelasmoidal mastocytosis Zosteriform metastasis Dermatitis Dermatitis is a general term for "inflammation of the skin". Childhood granulomatous periorificial dermatitis Essential dermatitis Atopic Atopic dermatitis is a chronic dermatitis associated with a hereditary tendency to develop allergies to food and inhalant substances. Atopic dermatitis (atopic eczema, disseminated neurodermatitis, flexural eczema, infantile eczema, prurigo diathsique) Contact Contact dermatitis is caused by certain substances coming in contact with the skin. Abietic acid dermatitis Acid-induced Acrylic monomer dermatitis Adhesive dermatitis African blackwood dermatitis Airbag dermatitis (airbag burn) Alkali-induced Allergic Antifungal agent-induced Antimicrobial agent-induced Arsenic dermatitis Artificial nail-induced Axillary antiperspirant-induced Axillary deodorant-induced Baboon syndrome Black dermatographism Bleaching cream-induced Capsaisin-induced Chemical burn Chloracne Chrome dermatitis Clothing-induced Cobalt dermatitis Contact stomatitis (contact lichenoid reaction, lichenoid amalgam reaction, oral mucosal cinnamon reaction) Contact urticaria Corticosteroid-induced Cosmetic dermatitis Cosmetic intolerance syndrome Dentifrice-induced Dermatitis from metals and metal salts Dust-induced Epoxy resin dermatitis Ethylenediamine-induced Eye makeup-induced Fiberglass dermatitis Flower-induced Formaldehyde-induced Formaldehyde-releasing agent-induced Fragrance-induced Gold dermatitis Hair bleach-induced Hair dye-induced Hair lotion-induced Hair spray-induced Hair straightener-induced Hair tonic-induced Houseplant-induced Hydrocarbon-induced Irritant folliculitis Lacquer dermatitis (lacquer sensitivity) Lanolin-induced Lipstick-induced Local anesthetic-induced Makassar ebony dermatitis Marine plant-induced Mechanical irritant dermatitis Mercury dermatitis Mouthwash-induced Nail lacquer-induced Nail polish remover-induced Nickel dermatitis Occupation-induced p-Chloro-meta-xylenol-induced Paraben-induced Paraphenylenediamine dermatitis Permanent wave preparation-induced Phenothiazine drug-induced Photoallergic Photoirritant Plant derivative-induced Pollen-induced Polyester resin dermatitis Propylene glycol-induced Protein contact dermatitis Quaternium-15 hypersensitivity Reed dermatitis Rosewood dermatitis Rosin dermatitis Rubber dermatitis Seed-induced Shoe dermatitis Solvent-induced Sorbic acid-induced Subjective irritant contact dermatitis (sensory irritant contact dermatitis) Sunscreen-induced Systemic contact dermatitis Tear gas dermatitis Textile dermatitis Traumatic irritant contact dermatitis Tree-associated plant-induced Tree-induced Tulip fingers Urshiol-induced Vegetable-induced Eczema Eczema refers to a broad range of conditions that begin as spongiotic dermatitis and may progress to a lichenified stage. Autoimmune estrogen dermatitis Autoimmune progesterone dermatitis Autosensitization dermatitis Breast eczema (nipple eczema) Chronic vesiculobullous hand eczema Circumostomy eczema Dyshidrosis (acute vesiculobullous hand eczema, cheiropompholyx, dyshidrotic eczema, pompholyx, podopompholyx) Ear eczema Eyelid dermatitis Hand eczema Hyperkeratotic hand dermatitis Id reaction (disseminated eczema, generalized eczema) Irritant diaper dermatitis (diaper dermatitis, napkin dermatitis) Juvenile plantar dermatosis (atopic winter feet, dermatitis plantaris sicca, forefoot dermatitis, moon-boot foot syndrome, sweaty sock dermatitis) Molluscum dermatitis Nummular dermatitis (discoid eczema, microbial eczema, nummular eczema, nummular neurodermatitis) Nutritional deficiency eczema Sulzberger–Garbe syndrome (oid-oid disease) Xerotic eczema (asteatotic eczema, desiccation dermatitis, eczema craquelé, pruritus hiemalis, winter eczema, winter itch) Pustular Pustular dermatitis is an inflammation of the skin that presents with pustular lesions. Eosinophilic pustular folliculitis (Ofujis disease, sterile eosinophilic pustulosis) Reactive arthritis Subcorneal pustular dermatosis (Sneddon–Wilkinson disease) Seborrheic Seborrheic dermatitis is a chronic, superficial, inflammatory disease characterized by scaling on an erythematous base. Infantile seborrheic dermatitis Leiners disease Pityriasis simplex capillitii (dandruff) Seborrheic dermatitis (seborrheic eczema) Disturbances of pigmentation Disturbances of human pigmentation, either loss or reduction, may be related to loss of melanocytes or the inability of melanocytes to produce melanin or transport melanosomes correctly. Albinism–black lock–cell migration disorder of the neurocytes of the gut–deafness syndrome (ABCD syndrome) Albinism–deafness syndrome (Woolf syndrome, Ziprkowski–Margolis syndrome) Alezzandrini syndrome Argyria Arsenic poisoning Berlin syndrome Canthaxanthin Chédiak–Higashi syndrome Chrysiasis Cross–McKusick–Breen syndrome (Cross syndrome, oculocerebral-hypopigmentation syndrome) Dermatopathia pigmentosa reticularis (dermatopathia pigmentosa reticularis hyperkeratotica et mutilans, dermatopathia pigmentosa reticularis hypohidotica et atrophica, dermatopathic pigmentosa reticularis) Dyschromatosis symmetrica hereditaria (reticulate acropigmentation of Dohi, symmetrical dyschromatosis of the extremities) Dyschromatosis universalis hereditaria Elejalde syndrome (Griscelli syndrome type 1) Eruptive hypomelanosis Familial progressive hyperpigmentation Galli–Galli disease Griscelli syndrome type 2 (partial albinism with immunodeficiency) Griscelli syndrome type 3 Hemochromatosis (bronze diabetes) Hemosiderin hyperpigmentation Hermansky–Pudlak syndrome Idiopathic guttate hypomelanosis (leukopathia symmetrica progressiva) Iron metallic discoloration Klein–Waardenburg syndrome Lead poisoning Leukoderma Melanoma-associated leukoderma Melasma (chloasma faciei, mask of pregnancy) Mukamel syndrome Necklace of Venus Nevus anemicus Nevus depigmentosus (nevus achromicus) Ocular albinism Oculocutaneous albinism Pallister–Killian syndrome Periorbital hyperpigmentation Photoleukomelanodermatitis of Kobori Phylloid hypomelanosis Piebaldism Pigmentatio reticularis faciei et colli Pityriasis alba Poikiloderma of Civatte Poikiloderma vasculare atrophicans Postinflammatory hyperpigmentation (postinflammatory hypermelanosis) Postinflammatory hypopigmentation Progressive macular hypomelanosis Quadrichrome vitiligo Reticular pigmented anomaly of the flexures (dark dot disease, Dowling–Degos disease) Reticulate acropigmentation of Kitamura Revesz syndrome Riehl melanosis Scratch dermatitis (flagellate pigmentation from bleomycin) Segmental vitiligo Shah–Waardenburg syndrome Shiitake mushroom dermatitis (flagellate mushroom dermatitis, mushroom workers disease, shiitake-induced toxicoderma) Tar melanosis (melanodermatitis toxica lichenoides) Tietz syndrome Titanium metallic discoloration Transient neonatal pustular melanosis (transient neonatal pustulosis, lentigines neonatorum) Trichrome vitiligo Vagabonds leukomelanoderma Vasospastic macule Vitiligo Vitiligo ponctué Vogt–Koyanagi–Harada syndrome Waardenburg syndrome Wende–Bauckus syndrome (Pegum syndrome) Woronoffs ring X-linked reticulate pigmentary disorder (familial cutaneous amyloidosis, Partington amyloidosis, Partington cutaneous amyloidosis, Partington syndrome type II, reticulate pigmentary disorder, X-linked reticulate pigmentary disorder with systemic manifestations) Yemenite deaf-blind hypopigmentation syndrome Drug eruptions Drug eruptions are adverse drug reactions that present with cutaneous manifestations. Acrodynia (calomel disease, erythredemic polyneuropathy, pink disease) Acute generalized exanthematous pustulosis (pustular drug eruption, toxic pustuloderma) Adverse reaction to biologic agents Adverse reaction to cytokines Allopurinol hypersensitivity syndrome Anticoagulant-induced skin necrosis Anticonvulsant hypersensitivity syndrome Bromoderma Bullous drug reaction (bullous drug eruption, generalized bullous fixed drug eruption, multilocular bullous fixed drug eruption) Chemotherapy-induced acral erythema (palmoplantar erythrodysesthesia syndrome) Chemotherapy-induced hyperpigmentation Drug-induced acne Drug-induced angioedema Drug-related gingival hyperplasia Drug-induced lichenoid reaction (drug-induced lichen planus, lichenoid drug eruption) Drug-induced lupus erythematosus Drug-induced nail changes Drug-induced pigmentation Drug-induced pseudolymphoma Drug-induced urticaria Erythema multiforme major (erythema multiforme minor–erythema multiforme von Hebra) Exudative hyponychial dermatitis Fixed drug reaction Halogenoderma Heparin necrosis HIV disease-related drug reaction Hydroxyurea dermopathy Injection site reaction Iododerma Leukotriene receptor antagonist-associated Churg–Strauss syndrome Linear IgA bullous dermatosis (linear IgA dermatosis) Photosensitive drug reaction Red man syndrome Severe cutaneous adverse reactions (includes DRESS syndrome, Steven Johnson syndrome, Toxic epidermal necrolysis, Stevens-Johnson/toxic epidermal necrolysis overlap syndrome, and Acute generalized exanthematous pustulosis) Scleroderma-like reaction to taxanes Serum sickness-like reaction Steroid acne Steroid folliculitis Stevens–Johnson syndrome Sulfonamide hypersensitivity syndrome Texiers disease Toxic epidermal necrolysis (Lyells syndrome) Urticarial erythema multiforme Vitamin K reaction Warfarin necrosis Endocrine-related Endocrine conditions often present with cutaneous findings as the skin interacts with the endocrine system in many ways. Acanthosis nigricans associated with malignancy (acanthosis nigricans type I) Acanthosis nigricans associated with obesity, insulin-resistant states, and endocrinopathy (acanthosis nigricans type III) Acral acanthosis nigricans (acral acanthotic anomaly) Acral dry gangrene Acromegaly Addisons disease Adrenal adenoma Adrenal carcinoma Adrenal hyperplasia Alopecia–nail dystrophy–ophthalmic complications–thyroid dysfunction–hypohidrosis–ephelides and enteropathy–respiratory tract infections syndrome (ANOTHER syndrome) Arrhenoblastoma Cretinism Cushings syndrome Excess ovarian androgen release syndrome (ovarian SAHA syndrome) Familial acanthosis nigricans (acanthosis nigricans type II) Growth hormone deficiency Hyperandrogenism–insulin resistance–acanthosis nigricans syndrome (HAIR-AN syndrome) Hyperparathyroidism Hyperprolactinemic SAHA syndrome Hyperthyroidism Hypoparathyroidism Hypothyroidism Leydig cell tumor Multiple endocrine neoplasia type 1 (Wermer syndrome) Multiple endocrine neoplasia type 2 (multiple endocrine neoplasia type 2A, pheochromocytoma and amyloid-producing medullary thyroid carcinoma, PTC syndrome, Sipple syndrome) Multiple endocrine neoplasia type 3 (mucosal neuromata with endocrine tumors, multiple endocrine neoplasia type 2B, multiple mucosal neuroma syndrome, Wagenmann–Froboese syndrome) Myxedema Panhypopituitarism Persistent adrenarche syndrome (adrenal SAHA syndrome) Polycystic ovarian syndrome Seborrhoea–acne–hirsutism–alopecia (SAHA syndrome) Thyroid acropachy Eosinophilic Eosinophilic cutaneous conditions encompass a wide variety of diseases that are characterized histologically by the presence of eosinophils in the inflammatory infiltrate, or evidence of eosinophil degranulation. Angiolymphoid hyperplasia with eosinophilia (epithelioid hemangioma, histiocytoid hemangioma, inflammatory angiomatous nodule, inflammatory arteriovenous hemangioma, intravenous atypical vascular proliferation, papular angioplasia, pseudopyogenic granuloma) Annular erythema of infancy Arthropod assault Eosinophilic cellulitis (Wells syndrome) Eosinophilic fasciitis (Shulmans syndrome) Eosinophilic granuloma Eosinophilic granulomatosis with polyangiitis Eosinophilic pustular folliculitis of infancy (eosinophilic pustular folliculitis in infancy, infantile eosinophilic pustular folliculitis, neonatal eosinophilic pustular folliculitis) Eosinophilic ulcer of the oral mucosa (eosinophilic ulcer of the tongue, Riga–Fede disease, traumatic eosinophilic granuloma) Eosinophilic vasculitis Erythema toxicum neonatorum (erythema toxicum, toxic erythema of the newborn) Granuloma faciale Hypereosinophilia Hypereosinophilic syndrome Incontinentia pigmenti (Bloch–Siemens syndrome, Bloch–Sulzberger disease, Bloch–Sulzberger syndrome) Itchy red bump disease (papular dermatitis) Juvenile xanthogranuloma Kimuras disease Nodules–eosinophilia–rheumatism–dermatitis–swelling syndrome Pachydermatous eosinophilic dermatitis Papular eruption of blacks Papuloerythroderma of Ofuji Pruritic papular eruption of HIV disease Epidermal nevi, neoplasms, and cysts Epidermal nevi, neoplasms, and cysts are skin lesions that develop from the epidermal layer of the skin. Aberrant basal cell carcinoma Acanthoma fissuratum (granuloma fissuratum, spectacle frame acanthoma) Acrospiroma (clear cell hidradenoma, dermal duct tumor, hidroacanthoma simplex, nodular hidradenoma, poroma) Actinic keratosis (senile keratosis, solar keratosis) Adenoid squamous cell carcinoma (pseudoglandular squamous cell carcinoma) Aggressive digital papillary adenocarcinoma (digital papillary adenocarcinoma, papillary adenoma) Apocrine gland carcinoma Apocrine nevus Arsenical keratosis Atrophic actinic keratosis Balanitis plasmacellularis (balanoposthitis chronica circumscripta plasmacellularis, balanitis circumscripta plasmacellularis, plasma cell balanitis, plasma cell vulvitis, vulvitis circumscripta plasmacellularis, Zoons balanitis, Zoons erythroplasia, Zoons vulvitis) Basal cell carcinoma Basaloid follicular hamartoma Basaloid squamous cell carcinoma Birt–Hogg–Dubé syndrome Bowens disease (squamous cell carcinoma in situ) Brooke–Fordyce syndrome Ceruminoma Cicatricial basal cell carcinoma (morpheaform basal cell carcinoma, morphoeic basal cell carcinoma) Ciliated cyst of the vulva (cutaneous Müllerian cyst, paramesonephric mucinous cyst of the vulva) Clear cell acanthoma (acanthome cellules claires of Degos and Civatte, Degos acanthoma, pale cell acanthoma) Clear cell squamous cell carcinoma (clear cell carcinoma of the skin) Chronic scar keratosis (chronic cicatrix keratosis) Clonal seborrheic keratosis Common seborrheic keratosis (basal cell papilloma, solid seborrheic keratosis) Cowden syndrome (Cowdens disease, multiple hamartoma syndrome) Cutaneous ciliated cyst Cutaneous columnar cyst Cutaneous horn (Cornu cutaneum) Cystic basal cell carcinoma Dermal eccrine cylindroma (cylindroma) Dermatosis papulosa nigra Desmoplastic trichoepithelioma Dilated pore (dilated pore of Winer) Eccrine carcinoma (syringoid carcinoma) Eccrine nevus Epidermal cyst (epidermal inclusion cyst, epidermoid cyst, infundibular cyst, keratin cyst) Epidermal nevus syndrome (Feuerstein and Mims syndrome, Solomons syndrome) Epidermolytic acanthoma Epithelioma cuniculatum (Ackerman tumor, carcinoma cuniculatum) Eruptive vellus hair cyst Erythroplasia of Queyrat Extramammary Pagets disease Fibroepithelioma Fibroepithelioma of Pinkus Fibrofolliculoma Follicular hybrid cyst (Hybrid cyst) Folliculosebaceous-apocrine hamartoma (follicular-apocrine hamartoma) Folliculosebaceous cystic hamartoma Generalized eruptive keratoacanthoma (generalized eruptive keratoacanthoma of Grzybowski) Giant solitary trichoepithelioma Hidradenoma Hidradenocarcinoma Hidrocystoma (cystadenoma, Molls gland cyst, sudoriferous cyst) Hydrocarbon keratosis (pitch keratosis, tar keratosis, tar wart) Hyperkeratosis lenticularis perstans (Flegels disease) Hyperkeratosis of the nipple and areola Hyperkeratotic actinic keratosis Ichthyosis hystrix (ichthyosis hystrix gravior type Lambert, porcupine man, systematized verrucous nevus) Ichthyosis hystrix of Curth–Macklin Infiltrative basal cell carcinoma Inflammatory linear verrucous epidermal nevus Inverted follicular keratosis Irritated seborrheic keratosis (basosquamous cell acanthoma, inflamed seborrheic keratosis) Isthmicoma (infundibuloma, tumor of the follicular infundibulum) Juvenile myelomonocytic leukemia Keratin implantation cyst Keratoacanthoma Keratoacanthoma centrifugum marginatum Large cell acanthoma Lichenoid actinic keratosis Lichenoid keratosis (benign lichenoid keratosis, lichen planus-like keratosis, solitary lichen planus, solitary lichenoid keratosis) Linear verrucous epidermal nevus (linear epidermal nevus, verrucous epidermal nevus) Malignant acrospiroma (spiradenocarcinoma) Malignant mixed tumor (malignant chondroid syringoma) Malignant trichilemmal cyst Mantleoma Marjolins ulcer Melanoacanthoma (pigmented seborrheic keratosis) Merkel cell carcinoma (cutaneous apudoma, primary neuroendocrine carcinoma of the skin, primary small cell carcinoma of the skin, trabecular carcinoma of the skin) Microcystic adnexal carcinoma (sclerosing sweat duct carcinoma) Micronodular basal cell carcinoma Milia en plaque Milium Mixed tumor (chondroid syringoma) Mucinous carcinoma Mucinous nevus (nevus mucinosus) Muir–Torre syndrome Multiple familial trichoepithelioma (Brooke–Spiegler syndrome, epithelioma adenoides cysticum) Multiple keratoacanthomas (Ferguson–Smith syndrome, Ferguson-Smith type of multiple self-healing keratoacanthomas, multiple keratoacanthomas of the Ferguson–Smith type) Multiple minute digitate hyperkeratosis (digitate keratoses, disseminated spiked hyperkeratosis, familial disseminated piliform hyperkeratosis, minute aggregate keratosis) Nevoid basal cell carcinoma syndrome (basal cell nevus syndrome, Gorlin syndrome, Gorlin–Goltz syndrome) Nevus comedonicus (comedo nevus) Nevus comedonicus syndrome Nevus sebaceous (nevus sebaceous of Jadassohn, organoid nevus) Nevus unius lateris Nodular basal cell carcinoma (classic basal cell carcinoma) Pagets disease of the breast Papillary eccrine adenoma (tubular apocrine adenoma) Papillary hidradenoma (hidradenoma papilliferum) Papillomatosis cutis carcinoides (Gottrons carcinoid papillomatosis, papillomatosis cutis carcinoides of Gottron–Eisenlohr) Patch blue nevus (acquired dermal melanocytosis, dermal melanocyte hamartoma) Perifollicular fibroma Phakomatosis pigmentokeratotica Pigmented actinic keratosis Pigmented basal cell carcinoma Pigmented hairy epidermal nevus syndrome Pilar sheath acanthoma Pilonidal sinus (Barbers interdigital pilonidal sinus, pilonidal cyst, pilonidal disease) Porocarcinoma (malignant poroma, eccrine porocarcinoma) Polypoid basal cell carcinoma Pore-like basal cell carcinoma Primary cutaneous adenoid cystic carcinoma Proliferating epidermoid cyst (proliferating epithelial cyst) Proliferating trichilemmal cyst (pilar tumor, proliferating follicular cystic neoplasm, proliferating pilar tumor, proliferating trichilemmal tumor) Pseudocyst of the auricle (auricular endochondrial pseudocyst, cystic chondromalacia, endochondral pseudocyst, intracartilaginous cyst) Pseudoepitheliomatous keratotic and micaceous balanitis PUVA keratosis Rasmussen syndrome Reactional keratosis Reticulated seborrheic keratosis (adenoid seborrheic keratosis) Rodent ulcer (Jacobi ulcer) Schimmelpenning syndrome (Schimmelpenning–Feuerstein–Mims syndrome) Sebaceoma (sebaceous epithelioma) Sebaceous adenoma Sebaceous carcinoma Sebaceous hyperplasia Sebaceous nevus syndrome Seboacanthoma Seborrheic keratosis (seborrheic verruca, senile wart) Seborrheic keratosis with squamous atypia Signet-ring cell squamous cell carcinoma Solitary keratoacanthoma (subungual keratoacanthoma) Solitary trichoepithelioma Spindle cell squamous cell carcinoma (spindle cell carcinoma) Spiradenoma Squamous cell carcinoma Steatocystoma multiplex (epidermal polycystic disease, sebocystomatosis) Steatocystoma simplex (simple sebaceous duct cyst, solitary steatocystoma) Stucco keratosis (digitate seborrheic keratosis, hyperkeratotic seborrheic keratosis, keratosis alba, serrated seborrheic keratosis, verrucous seborrheic keratosis) Superficial basal cell carcinoma (superficial multicentric basal cell carcinoma) Syringadenoma papilliferum (syringocystadenoma papilliferum) Syringofibroadenoma (acrosyringeal nevus of Weedon and Lewis) Syringoma Systematized epidermal nevus Thermal keratosis Trichilemmal carcinoma Trichilemmal cyst (isthmus-catagen cyst, pilar cyst) Trichilemmoma Trichoadenoma (trichoadenoma of Nikolowski) Trichoblastoma Trichoblastic fibroma Trichodiscoma Trichofolliculoma Unilateral palmoplantar verrucous nevus Urethral caruncle Verrucous carcinoma Verrucous cyst (cystic papilloma) Viral keratosis Warty dyskeratoma (isolated dyskeratosis follicularis) Waxy keratosis of childhood (kerinokeratosis papulosa) Zoons vulvitis Zosteriform speckled lentiginous nevus Erythemas Erythemas are reactive skin conditions in which there is blanchable redness. Erythema annulare centrifugum (deep gyrate erythema, erythema perstans, palpable migrating erythema, superficial gyrate erythema) Erythema gyratum repens (Gammels disease) Erythema migrans (erythema chronicum migrans) Erythema multiforme Erythema multiforme minor (herpes simplex-associated erythema multiforme) Erythema palmare Generalized erythema Necrolytic acral erythema Necrolytic migratory erythema (glucagonoma syndrome) Genodermatoses Genodermatoses are inherited genetic skin conditions often grouped into three categories: chromosomal, single gene, and polygenetic. 18q deletion syndrome Acrodermatitis enteropathica Acrogeria (Gottron syndrome) Acrokeratosis verruciformis (acrokeratosis verruciformis of Hopf) Adams–Oliver syndrome Adducted thumbs syndrome Albrights hereditary osteodystrophy Angelman syndrome Apert syndrome (acrocephalosyndactyly) Arthrogryposis–renal dysfunction–cholestasis syndrome Ataxia telangiectasia (Louis–Bar syndrome) Atrichia with papular lesions (papular atrichia) Atrophodermia vermiculata (acne vermoulante, acne vermoulanti, atrophoderma reticulata symmetrica faciei, atrophoderma reticulatum, atrophoderma vermiculata, atrophoderma vermiculatum, atrophodermia reticulata symmetrica faciei, atrophodermia ulerythematosa, atrophodermie vermiculée des joues avec kératoses folliculaires, folliculitis ulerythema reticulata, folliculitis ulerythematous reticulata, folliculitis ulerythemosa, honeycomb atrophy, ulerythema acneforme, ulerythema acneiforme) Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy syndrome Bart syndrome Bazex–Dupré–Christol syndrome (Bazex syndrome, follicular atrophoderma and basal cell carcinomas) Beare–Stevenson cutis gyrata syndrome Bloom syndrome (Bloom–Torre–Machacek syndrome) Blue rubber bleb nevus syndrome Brittle hair–intellectual impairment–decreased fertility–short stature syndrome Cantú syndrome Cardio-facio-cutaneous syndrome (cardiofaciocutaneous syndrome) Cartilage–hair hypoplasia (McKusick type metaphyseal chondrodysplasia) Cerebral dysgenesis–neuropathy–ichthyosis–keratoderma syndrome Childhood tumor syndrome Chondrodysplasia punctata Cicatricial junctional epidermolysis bullosa Craniosynostosis–anal anomalies–porokeratosis syndrome Cockayne syndrome Colobomas of the eye–heart defects–ichthyosiform dermatosis–mental retardation–ear defects syndrome (CHIME syndrome, Zunich neuroectodermal syndrome, Zunich–Kaye syndrome) Congenital hemidysplasia with ichthyosiform erythroderma and limb defects syndrome (CHILD syndrome) Conradi–Hünermann syndrome (Conradi–Hünermann–Happle syndrome, Happle syndrome, X-linked dominant chondrodysplasia punctata) Costello syndrome Cronkhite–Canada syndrome Crouzon syndrome Cutis verticis gyrata Dariers disease (Darier–White disease, dyskeratosis follicularis, keratosis follicularis) DeSanctis–Cacchione syndrome Disseminated superficial actinic porokeratosis Disseminated superficial porokeratosis Dolichol kinase deficiency Dominant dystrophic epidermolysis bullosa Dyskeratosis congenita (Zinsser–Cole–Engman syndrome) Dystrophic epidermolysis bullosa Ectodermal dysplasia Ectodermal dysplasia with corkscrew hairs Ectrodactyly–ectodermal dysplasia–cleft syndrome (EEC syndrome, split hand–split foot–ectodermal dysplasia–cleft syndrome) Epidermolysis bullosa herpetiformis (Dowling–Meara epidermolysis bullosa simplex) Epidermolysis bullosa simplex Epidermolysis bullosa simplex of Ogna Epidermolysis bullosa simplex with mottled pigmentation Epidermolysis bullosa simplex with muscular dystrophy Epidermolytic hyperkeratosis (bullous congenital ichthyosiform erythroderma, bullous ichthyosiform erythroderma) Erythrokeratodermia with ataxia (Giroux–Barbeau syndrome) Familial benign chronic pemphigus (familial benign pemphigus, Hailey–Hailey disease) Fanconi syndrome (familial pancytopenia, familial panmyelophthisis) Fibrodysplasia ossificans progressiva Focal dermal hypoplasia (Goltz syndrome) Follicular atrophoderma Franceschetti–Klein syndrome (mandibulofacial dysostosis) Gardners syndrome (familial colorectal polyposis) Gastrocutaneous syndrome Generalized atrophic benign epidermolysis bullosa Generalized epidermolysis bullosa simplex (Koebner variant of generalized epidermolysis bullosa simplex) Generalized trichoepithelioma Giant axonal neuropathy with curly hair Gingival fibromatosis with hypertrichosis Haber syndrome Hallerman–Streiff syndrome Harlequin-type ichthyosis (harlequin baby, harlequin fetus, harlequin ichthyosis, ichthyosis congenita, ichthyosis congenita gravior) Hay–Wells syndrome (AEC syndrome, ankyloblepharon filiforme adnatum–ectodermal dysplasia–cleft palate syndrome, ankyloblepharon–ectodermal defects–cleft lip and palate syndrome, ankyloblepharon–ectodermal dysplasia–clefting syndrome) Hereditary sclerosing poikiloderma Heterochromia iridum Holocarboxylase synthetase deficiency Hypohidrotic ectodermal dysplasia (anhidrotic ectodermal dysplasia, Christ–Siemens–Touraine syndrome) Hypotrichosis–acro-osteolysis–onychogryphosis–palmoplantar keratoderma–periodontitis syndrome Hypotrichosis–lymphedema–telangiectasia syndrome Ichthyosis–brittle hair–impaired intelligence–decreased fertility–short stature syndrome (IBIDS syndrome, sulfur-deficient brittle hair syndrome, Tays syndrome, trichothiodystrophy, trichothiodystrophy with ichthyosis) Ichthyosis bullosa of Siemens (ichthyosis exfoliativa) Ichthyosis follicularis (ichthyosis follicularis with alopecia and photophobia syndrome) Ichthyosis linearis circumflexa Ichthyosis prematurity syndrome Ichthyosis vulgaris (autosomal dominant ichthyosis, ichthyosis simplex) Ichthyosis with confetti Neonatal ichthyosis–sclerosing cholangitis syndrome (ichthyosis–sclerosing cholangitis syndrome, NISCH syndrome) Incontinentia pigmenti achromians (hypomelanosis of Ito) Immune dysfunction–polyendocrinopathy–enteropathy–X-linked syndrome Jaffe–Campanacci syndrome Johanson–Blizzard syndrome Johnson–McMillin syndrome Joubert syndrome Junctional epidermolysis bullosa Junctional epidermolysis bullosa gravis (epidermolysis bullosa letalis, Herlitz disease, Herlitz epidermolysis bullosa, Herlitz syndrome, lethal junctional epidermolysis bullosa) Junctional epidermolysis bullosa with pyloric atresia Kabuki syndrome (Kabuki makeup syndrome, Niikawa–Kuroki syndrome) Keratolytic winter erythema (erythrokeratolysis hiemalis, Oudtshoorn disease, Oudtshoorn skin) Keratosis follicularis spinulosa decalvans (Siemens-1 syndrome) Keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome Keratosis pilaris atrophicans faciei (folliculitis rubra, keratosis pilaris rubra atrophicans faciei, lichen pilare, lichen pilaire ou xerodermie pilaire symmetrique de la face, ulerythema ophryogenes, xerodermi pilaire symmetrique de la face) Keratosis pilaris Kindler syndrome (acrokeratotic poikiloderma, bullous acrokeratotic poikiloderma of Kindler and Weary, congenital poikiloderma with blisters and keratoses, congenital poikiloderma with bullae and progressive cutaneous atrophy, hereditary acrokeratotic poikiloderma, hyperkeratosis–hyperpigmentation syndrome, Weary–Kindler syndrome) Klinefelter syndrome Klippel–Feil syndrome Lamellar ichthyosis (collodion baby) Legius syndrome (neurofibromatosis type 1-like syndrome) Lelis syndrome Lenz–Majewski syndrome Leschke syndrome Lethal acantholytic epidermolysis bullosa Lhermitte–Duclos disease Linear and whorled nevoid hypermelanosis (linear nevoid hyperpigmentation, progressive cribriform and zosteriform hyperpigmentation, reticulate and zosteriform hyperpigmentation, reticulate hyperpigmentation of Iijima and Naito and Uyeno, zebra-like hyperpigmentation in whorls and streaks, zebra-line hyperpigmentation) Linear Darier disease (acantholytic dyskeratotic epidermal nevus) Linear porokeratosis Localized epidermolysis bullosa simplex (Weber–Cockayne syndrome, Weber–Cockayne variant of generalized epidermolysis bullosa simplex) Mandibuloacral dysplasia Marinesco–Sjögren syndrome McCune–Albright syndrome McCusick syndrome Metageria Microphthalmia–dermal aplasia–sclerocornea syndrome Mitis junctional epidermolysis bullosa (nonlethal junctional epidermolysis bullosa) Mitochondrial myopathy–encephalopathy–lactic acidosis–stroke syndrome Multiple lentigines syndrome (cardiocutaneous syndrome, Gorlin syndrome II, lentiginosis profusa syndrome, LEOPARD syndrome, progressive cardiomyopathic lentiginosis) Multiple pterygium syndrome Multiple sulfatase deficiency (Austin disease, mucosulfatidosis) Naegeli–Franceschetti–Jadassohn syndrome (chromatophore nevus of Naegeli) Netherton syndrome Neurofibromatosis type 1 (von Recklinghausens disease) Neurofibromatosis type 3 (neurofibromatosis mixed type) Neurofibromatosis type 4 (neurofibromatosis variant type) Neutral lipid storage disease (Dorfman–Chanarin syndrome) Nonbullous congenital ichthyosiform erythroderma (congenital ichthyosiform erythroderma) Noonan syndrome Oculocerebrocutaneous syndrome (Delleman–Oorthuys syndrome) Oculodentodigital dysplasia Odonto–Tricho–Ungual–Digital–Palmar syndrome Oliver–McFarlane syndrome Orofaciodigital syndrome Pachydermoperiostosis (idiopathic hypertrophic osteoathorpathy, Touraine–Solente–Gole syndrome) Peeling skin syndrome (acral peeling skin syndrome, continual peeling skin syndrome, familial continual skin peeling, idiopathic deciduous skin, keratolysis exfoliativa congenita) Pfeiffer syndrome Photosensitivity–ichthyosis–brittle sulfur-deficient hair–impaired intelligence–decreased fertility–short stature syndrome Pityriasis rotunda (pityriasis circinata, tinea circinata) Plate-like osteoma cutis Plaque-type porokeratosis (classic porokeratosis, porokeratosis of Mibelli) Polyneuropathy–organomegaly–endocrinopathy–monoclonal gammopathy–skin changes syndrome (Crow–Fukase syndrome) Polyostotic fibrous dysplasia (Albrights disease) Popliteal pterygium syndrome Porokeratosis Porokeratosis palmaris et plantaris disseminata Prader–Willi syndrome Progeria (Hutchinson–Gilford progeria syndrome, Hutchinson–Gilford syndrome, progeria syndrome) Progressive osseous heteroplasia Progressive symmetric erythrokeratodermia (erythrokeratodermia progressiva symmetrica) Proteus syndrome Proteus-like syndrome Punctate porokeratosis Rapp–Hodgkin syndrome (Rapp–Hodgkin ectodermal dysplasia syndrome) Recessive dystrophic epidermolysis bullosa (Hallopeau–Siemens variant of epidermolysis bullosa, Hallopeau–Siemens disease) Refsums disease (heredopathia atactica polyneuritiformis, phytanic acid storage disease) Relapsing linear acantholytic dermatosis Restrictive dermopathy Rhizomelic chondrodysplasia punctata (autosomal recessive chondrodysplasia punctata type 1, chondrodystrophia calcificans punctata, peroxisomal biogenesis disorder complementation group 11) Rombo syndrome Rothmund–Thomson syndrome (poikiloderma congenitale) Rud syndrome Say syndrome Scalp–ear–nipple syndrome (Finlay–Marks syndrome) Schindler disease (Kanzaki disease, alpha-N-acetylgalactosaminidase deficiency) Schinzel–Giedion syndrome Scleroatrophic syndrome of Huriez (Huriez syndrome, palmoplantar keratoderma with scleroatrophy, palmoplantar keratoderma with sclerodactyly, scleroatrophic and keratotic dermatosis of the limbs, sclerotylosis) Segmental neurofibromatosis Senter syndrome (Desmons syndrome) Shabbir syndrome (laryngo–onycho–cutaneous syndrome) Silver–Russell syndrome Sjögren–Larsson syndrome Skin fragility syndrome (plakophilin 1 deficiency) Smith–Lemli–Opitz syndrome Sturge–Weber syndrome Supernumerary nipples–uropathies–Beckers nevus syndrome Terminal osseous dysplasia with pigmentary defects Tooth and nail syndrome (hypodontia with nail dysgenesis, Witkop syndrome) Townes–Brocks syndrome Transient bullous dermolysis of the newborn Treacher Collins syndrome (Treacher Collins–Franceschetti syndrome) Tricho–dento–osseous syndrome Tricho–rhino–phalangeal syndrome Tuberous sclerosis (Bourneville disease, epiloia) Turner syndrome Ulnar–mammary syndrome Van Der Woude syndrome Von Hippel–Lindau syndrome Watson syndrome Werner syndrome (adult progeria) Westerhof syndrome Whistling syndrome (craniocarpotarsal syndrome, distal arthrogryposis type 2, Freeman–Sheldon syndrome, Windmill–Vane–Hand syndrome) Wilson–Turner syndrome Wolf–Hirschhorn syndrome (4p- syndrome) X-linked ichthyosis (steroid sulfatase deficiency, X-linked recessive ichthyosis) X-linked recessive chondrodysplasia punctata Xeroderma pigmentosum (Cockayne syndrome complex) XXYY genotype Zimmermann–Laband syndrome Infection-related Infection-related cutaneous conditions may be caused by bacteria, fungi, yeast, viruses, or parasites. Bacterium-related Bacterium-related cutaneous conditions often have distinct morphologic characteristics that may be an indication of a generalized systemic process or simply an isolated superficial infection. Aeromonas infection African tick bite fever American tick bite fever (Rickettsia parkeri infection) Arcanobacterium haemolyticum infection Bacillary angiomatosis Bejel (endemic syphilis) Blastomycosis-like pyoderma (pyoderma vegetans) Blistering distal dactylitis Botryomycosis Brill–Zinsser disease Brucellosis (Bangs disease, Malta fever, undulant fever) Bubonic plague Bullous impetigo Cat scratch disease (cat scratch fever, English–Wear infection, inoculation lymphoreticulosis, subacute regional lymphadenitis) Cellulitis Chancre Chancroid (soft chancre, ulcus molle) Chlamydial infection Chronic lymphangitis Chronic recurrent erysipelas Chronic undermining burrowing ulcers (Meleney gangrene) Chromobacteriosis infection Condylomata lata Cutaneous actinomycosis Cutaneous anthrax infection Cutaneous C. diphtheriae infection (Barcoo rot, diphtheric desert sore, septic sore, Veldt sore) Cutaneous group B streptococcal infection Cutaneous Pasteurella hemolytica infection Cutaneous Streptococcus iniae infection Dermatitis gangrenosa (gangrene of the skin) Ecthyma Ecthyma gangrenosum Ehrlichiosis ewingii infection Elephantiasis nostras Endemic typhus (murine typhus) Epidemic typhus (epidemic louse-borne typhus) Erysipelas (ignis sacer, Saint Anthonys fire) Erysipeloid of Rosenbach Erythema marginatum Erythrasma External otitis (otitis externa, swimmers ear) Felon Flea-borne spotted fever Flinders Island spotted fever Flying squirrel typhus Folliculitis Fournier gangrene (Fournier gangrene of the penis or scrotum) Furunculosis (boil) Gas gangrene (clostridial myonecrosis, myonecrosis) Glanders (equinia, farcy, malleus) Gonococcemia (arthritis–dermatosis syndrome, disseminated gonococcal infection) Gonorrhea (clap) Gram-negative folliculitis Gram-negative toe web infection Granuloma inguinale (Donovanosis, granuloma genitoinguinale, granuloma inguinale tropicum, granuloma venereum, granuloma venereum genitoinguinale, lupoid form of groin ulceration, serpiginous ulceration of the groin, ulcerating granuloma of the pudendum, ulcerating sclerosing granuloma) Green nail syndrome Group JK Corynebacterium sepsis Haemophilus influenzae cellulitis Helicobacter cellulitis Hospital furunculosis Hot tub folliculitis (Pseudomonas aeruginosa folliculitis) Human granulocytotropic anaplasmosis Human monocytotropic ehrlichiosis Impetigo contagiosa Japanese spotted fever Leptospirosis (Fort Bragg fever, pretibial fever, Weils disease) Listeriosis Ludwigs angina Lupoid sycosis Lyme disease (Afzelius disease, Lyme borreliosis) Lymphogranuloma venereum (climatic bubo, Durand–Nicolas–Favre disease, lymphogranuloma inguinale, poradenitis inguinale, strumous bubo) Malakoplakia (malacoplakia) Mediterranean spotted fever (Boutonneuse fever) Melioidosis (Whitmores disease) Meningococcemia Missouri Lyme disease Mycoplasma infection Necrotizing fasciitis (flesh-eating bacteria syndrome) Neonatal toxic shock-like exanthematous disease Nocardiosis Noma neonatorum North Asian tick typhus Ophthalmia neonatorum Oroya fever (Carrions disease) Pasteurellosis Perianal cellulitis (perineal dermatitis, streptococcal perianal disease) Periapical abscess Pinta Pitted keratolysis (keratolysis plantare sulcatum, keratoma plantare sulcatum, ringed keratolysis) Plague Primary gonococcal dermatitis Pseudomonal pyoderma Pseudomonas hot-foot syndrome Pyogenic paronychia Pyomyositis Q fever Queensland tick typhus Rat-bite fever Recurrent toxin-mediated perineal erythema Rhinoscleroma Rickettsia aeschlimannii infection Rickettsialpox Rocky Mountain spotted fever Saber shin (anterior tibial bowing) Saddle nose Salmonellosis Scarlet fever Scrub typhus (Tsutsugamushi fever) Shigellosis Staphylococcal scalded skin syndrome (pemphigus neonatorum, Ritters disease) Streptococcal intertrigo Superficial pustular folliculitis (impetigo of Bockhart, superficial folliculitis) Sycosis vulgaris (barbers itch, sycosis barbae) Syphilid Syphilis (lues) Tick-borne lymphadenopathy Toxic shock syndrome (streptococcal toxic shock syndrome, streptococcal toxic shock-like syndrome, toxic streptococcal syndrome) Trench fever (five-day fever, quintan fever, urban trench fever) Tropical ulcer (Aden ulcer, jungle rot, Malabar ulcer, tropical phagedena) Tularemia (deer fly fever, Oharas disease, Pahvant Valley plague, rabbit fever) Verruga peruana Vibrio vulnificus infection Yaws (bouba, frambösie, parangi, pian) Mycobacterium-related Mycobacterium-related cutaneous conditions are caused by Mycobacterium infections. Aquarium granuloma (fish-tank granuloma, swimming-pool granuloma) Borderline lepromatous leprosy Borderline leprosy Borderline tuberculoid leprosy Buruli ulcer (Bairnsdale ulcer, Searl ulcer, Searles ulcer) Erythema induratum (Bazin disease) Histoid leprosy Lepromatous leprosy Leprosy (Hansens disease) Lichen scrofulosorum (tuberculosis cutis lichenoides) Lupus vulgaris (tuberculosis luposa) Miliary tuberculosis (disseminated tuberculosis, tuberculosis cutis acuta generalisata, tuberculosis cutis disseminata) Mycobacterium avium-intracellulare complex infection Mycobacterium haemophilum infection Mycobacterium kansasii infection Papulonecrotic tuberculid Primary inoculation tuberculosis (cutaneous primary complex, primary tuberculous complex, tuberculous chancre) Rapid-growing Mycobacterium infection Scrofuloderma (tuberculosis cutis colliquativa) Tuberculosis cutis orificialis (acute tuberculous ulcer, orificial tuberculosis) Tuberculosis verrucosa cutis (lupus verrucosus, prosectors wart, warty tuberculosis) Tuberculous cellulitis Tuberculous gumma (metastatic tuberculous abscess, metastatic tuberculous ulcer) Tuberculoid leprosy Mycosis-related Mycosis-related cutaneous conditions are caused by fungi or yeasts, and may present as either a superficial or deep infection of the skin, hair, or nails. African histoplasmosis Alternariosis Antibiotic candidiasis (iatrogenic candidiasis) Black piedra Candidal intertrigo Candidal onychomycosis Candidal paronychia Candidal vulvovaginitis Candidid Chromoblastomycosis (chromomycosis, cladosporiosis, Fonsecas disease, Pedrosos disease, phaeosporotrichosis, verrucous dermatitis) Chronic mucocutaneous candidiasis Coccidioidomycosis (California disease, desert rheumatism, San Joaquin Valley fever, valley fever) Congenital cutaneous candidiasis Cryptococcosis Dermatophytid Diaper candidiasis Disseminated coccidioidomycosis (coccidioidal granuloma) Distal subungual onychomycosis Entomophthoromycosis Erosio interdigitalis blastomycetica Favus Fungal folliculitis (majocchi granuloma) Fusariosis Geotrichosis Granuloma gluteale infantum Histoplasmosis (cave disease, Darlings disease, Ohio Valley disease, reticuloendotheliosis) Hyalohyphomycosis Kerion Lobomycosis (keloidal blastomycosis, lacaziosis, Lobos disease) Mucormycosis Mycetoma (Madura foot, maduromycosis) North American blastomycosis (blastomycetic dermatitis, blastomycosis, Gilchrists disease) Onychomycosis (dermatophytic onychomycosis, ringworm of the nail, tinea unguium) Oral candidiasis (thrush) Otomycosis Perianal candidiasis Perlèche (angular cheilitis) Phaeohyphomycosis Piedra (trichosporosis) Pityrosporum folliculitis Primary cutaneous aspergillosis Primary cutaneous coccidioidomycosis Primary cutaneous histoplasmosis Primary pulmonary coccidioidomycosis Primary pulmonary histoplasmosis Progressive disseminated histoplasmosis Proximal subungual onychomycosis Rhinosporidiosis South American blastomycosis (Brazilian blastomycosis, paracoccidioidal granuloma, paracoccidioidomycosis) Sporotrichosis (rose-gardeners disease) Systemic candidiasis Tinea barbae (barbers itch, ringworm of the beard, tinea sycosis) Tinea capitis (herpes tonsurans, ringworm of the hair, ringworm of the scalp, scalp ringworm, tinea tonsurans) Tinea corporis (ringworm, tinea circinata, tinea glabrosa) Tinea corporis gladiatorum Tinea cruris (crotch itch, eczema marginatum, gym itch, jock itch, ringworm of the groin) Tinea faciei Tinea imbricata (tokelau) Tinea incognito Tinea manuum Tinea nigra (superficial phaeohyphomycosis, tinea nigra palmaris et plantaris) Tinea pedis (athletes foot, ringworm of the foot) Tinea versicolor (dermatomycosis furfuracea, pityriasis versicolor, tinea flava) White piedra White superficial onychomycosis Zygomycosis (phycomycosis) Parasitic infestations, stings, and bites Parasitic infestations, stings, and bites in humans are caused by several groups of organisms belonging to the following phyla: Annelida, Arthropoda, Bryozoa, Chordata, Cnidaria, Cyanobacteria, Echinodermata, Nemathelminthes, Platyhelminthes, and Protozoa. Acanthamoeba infection Amebiasis cutis Ant sting Arachnidism Bakers itch Balamuthia infection Bedbug infestation (bedbug bite, cimicosis) Bee and wasp stings Blister beetle dermatitis Bombardier beetle burn Bristleworm sting Centipede bite Cheyletiella dermatitis Chigger bite Coolie itch Copra itch Coral dermatitis Creeping eruption (cutaneous larva migrans) Cutaneous leishmaniasis (Aleppo boil, Baghdad boil, bay sore, Biskra button, Chiclero ulcer, Delhi boil, Kandahar sore, Lahore sore, leishmaniasis tropica, oriental sore, pian bois, uta) Cysticercosis cutis Demodex folliculitis, usually caused by the Demodex folliculorum mite Dogger Bank itch Dracunculiasis (dracontiasis, guinea worm disease, Medina worm) Echinococcosis (hydatid disease) Elephantiasis tropica (elephantiasis arabum) Elephant skin Enterobiasis (oxyuriasis, pinworm infection, seatworm infection) Erisipela de la costa Feather pillow dermatitis Funnel web spider bite Gamasoidosis Gnathostomiasis (larva migrans profundus) Grain itch (barley itch, mattress itch, prairie itch, straw itch) Grocers itch Head lice infestation (cooties, pediculosis capitis) Hookworm disease (ancylostomiasis, ground itch, necatoriasis, uncinariasis) Human trypanosomiasis Hydroid dermatitis Irukandji syndrome Jellyfish dermatitis Ked itch Larva currens Latrodectism (widow spider bite) Leech bite Leopard skin Lepidopterism (Caripito itch, caterpillar dermatitis, moth dermatitis) Lizard skin Loaiasis (Calabar swelling, fugitive swelling, loa loa, tropical swelling) Loxoscelism (brown recluse spider bite, necrotic cutaneous loxoscelism) Mal morando Millipede burn Mosquito bite Mucocutaneous leishmaniasis (espundia, leishmaniasis americana) Myiasis Nairobi fly dermatitis (Kenya fly dermatitis, Nairobi eye) Nematode dermatitis Norwegian scabies (crusted scabies) Onchocerciasis Ophthalmia nodosa Paederus dermatitis Pediculosis corporis (pediculosis vestimenti, Vagabonds disease) Pediculosis pubis (crabs, phthirus pubis, phthirus pubis, pubic lice) Pneumocystosis (often classified as fungal) Portuguese man-of-war dermatitis Post-kala-azar dermal leishmaniasis (post-kala-azar dermatosis) Protothecosis Pulicosis (flea bites) Reduviid bite Scabies (itch mite infestation, seven-year itch) Scorpion sting Sea anemone dermatitis Seabathers eruption (sea lice) Sea urchin injury Seaweed dermatitis Snake bite Sowda Sparganosis Spider bite Stingray injury Swimmers itch (cercarial dermatitis, schistosome cercarial dermatitis) Tarantula bite Tick bite Toxoplasmosis Trichinosis Trichomoniasis Tungiasis (bicho de pie, chigoe flea bite, jigger bite, nigua, pique) Visceral leishmaniasis (dumdum fever, kala-azar) Visceral schistosomiasis (bilharziasis) Viscerotropic leishmaniasis Wheat warehouse itch Virus-related Virus-related cutaneous conditions are caused by two main groups of viruses–DNA and RNA types–both of which are obligatory intracellular parasites. Alphavirus infection Asymmetric periflexural exanthem of childhood (unilateral laterothoracic exanthem) B virus infection Boston exanthem disease Bovine papular stomatitis Bowenoid papulosis Buffalopox Butchers wart Chikungunya fever Condylomata acuminata Congenital rubella syndrome Cowpox Cytomegalic inclusion disease Dengue (Break-bone fever) Disseminated herpes zoster Eczema herpeticum (Kaposis varicelliform eruption) Eczema vaccinatum Epidermodysplasia verruciformis Eruptive pseudoangiomatosis Erythema infectiosum (fifth disease, slapped cheek disease) Exanthem of primary HIV infection (acute retroviral syndrome) Farmyard pox Generalized vaccinia Genital herpes (herpes genitalis, herpes progenitalis) Gianotti–Crosti syndrome (infantile papular acrodermatitis, papular acrodermatitis of childhood, papulovesicular acrolocated syndrome) Giant condyloma acuminatum (Buschke–Löwenstein tumor, giant condyloma of Buschke–Löwenstein tumor) Hand-foot-and-mouth disease Hecks disease (focal epithelial hyperplasia) Hemorrhagic fever with renal syndrome Hepatitis B Hepatitis C Herpangina Herpes gladiatorum (scrum pox) Herpes simplex Herpes zoster oticus (Ramsay–Hunt syndrome) Herpetic keratoconjunctivitis Herpetic sycosis Herpetic whitlow HIV-associated pruritus Human monkeypox Human T-lymphotropic virus 1 infection Human tanapox Immune reconstitution inflammatory syndrome (immune recovery syndrome) Infectious mononucleosis (glandular fever) Inflammatory skin lesions following zoster infection (isotopic response) Intrauterine herpes simplex Kaposi sarcoma Lassa fever Lipschütz ulcer (ulcus vulvae acutum) Measles (rubeola, morbilli) Milkers nodule Modified varicella-like syndrome Molluscum contagiosum Myrmecia Neonatal herpes simplex Ophthalmic zoster Orf (contagious pustular dermatosis, ecthyma contagiosum, infectious labial dermatitis, sheep pox) Orf-induced immunobullous disease Orolabial herpes (herpes labialis) Papular purpuric gloves and socks syndrome Pigmented wart Postherpetic neuralgia (zoster-associated pain) Post-vaccination follicular eruption Progressive vaccinia (vaccinia gangrenosum, vaccinia necrosum) Pseudocowpox Recurrent respiratory papillomatosis (laryngeal papillomatosis) Rift Valley fever Roseola infantum (exanthem subitum, exanthema subitum, sixth disease) Roseola vaccinia Rubella (German measles) Sandfly fever (Pappataci fever, phlebotomus fever) Sealpox Varicella (chickenpox) Variola major (smallpox) Verruca plana (flat wart) Verruca plantaris (plantar wart) Verruca vulgaris (wart) Verrucae palmares et plantares Viral-associated trichodysplasia (ciclosporin-induced folliculodystrophy) Wasting syndrome West Nile virus infection Zoster (herpes zoster, shingles) Zoster sine herpete Lichenoid eruptions Lichenoid eruptions are dermatoses related to the unique, common inflammatory disorder lichen planus, which affects the skin, mucous membranes, nails, and hair. Annular lichen planus Atrophic lichen planus Bullous lichen planus (vesiculobullous lichen planus) Erosive lichen planus Erythema dyschromicum perstans (ashy dermatosis, dermatosis cinecienta) Giant cell lichenoid dermatitis Hepatitis-associated lichen planus Hypertrophic lichen planus (lichen planus verrucosus) Idiopathic eruptive macular pigmentation Inverse lichen planus Keratosis lichenoides chronica (Nékams disease) Kraurosis vulvae Lichen nitidus Lichen planus actinicus (actinic lichen niditus, actinic lichen planus, lichen planus atrophicus annularis, lichen planus subtropicus, lichen planus tropicus, lichenoid melanodermatitis, lichenoid melanodermatosis, summertime actinic lichenoid eruption) Lichen planus pemphigoides Lichen planus pigmentosus Lichen planus–lichen sclerosus overlap syndrome Lichen ruber moniliformis Lichen sclerosus (lichen sclerosus et atrophicus) Lichen striatus (Blaschko linear acquired inflammatory skin eruption, linear lichenoid dermatosis) Lichen verrucosus et reticularis Lichenoid trikeratosis Lichenoid dermatitis Lichenoid reaction of graft-versus-host disease Linear lichen planus Mucosal lichen planus Peno-gingival syndrome Ulcerative lichen planus Vulvovaginal gingival syndrome Vulvovaginal lichen planus Lymphoid-related Lymphoid-related cutaneous conditions are a group of disorders characterized by collections of lymphocyte cells within the skin. Adult T-cell leukemia/lymphoma Angiocentric lymphoma (extranodal natural killer cell lymphoma, nasal-type NK lymphoma, NK/T-cell lymphoma, polymorphic/malignant midline reticulosis) Angioimmunoblastic T-cell lymphoma (angioimmunoblastic lymphadenopathy with dysproteinemia) Blastic NK-cell lymphoma CD30+ cutaneous T-cell lymphoma (primary cutaneous anaplastic large cell lymphoma) Cutaneous lymphoid hyperplasia (borrelial lymphocytoma, lymphadenosis benigna cutis, lymphocytoma cutis, pseudolymphoma, pseudolymphoma of Spiegler and Fendt, sarcoidosis of Spiegler and Fendt, Spiegler–Fendt lymphoid hyperplasia, Spiegler–Fendt sarcoid) Cutaneous lymphoid hyperplasia with bandlike and perivascular patterns Cutaneous lymphoid hyperplasia with nodular pattern (nodular pattern of cutaneous lymphoid hyperplasia) Diffuse large B-cell lymphoma (primary cutaneous large B-cell lymphoma) Granulocytic sarcoma (chloroma, myeloid sarcoma) Granulomatous slack skin Hairy-cell leukemia Hodgkins disease Ichthyosis acquisita (acquired ichthyosis) IgG4-related skin disease Intravascular large B-cell lymphoma (angiotropic large cell lymphoma, intralymphatic lymphomatosis, intravascular lymphomatosis, malignant angioendotheliomatosis) Jessner lymphocytic infiltrate of the skin (benign lymphocytic infiltration of the skin, Jessner lymphocytic infiltration of the skin, Jessner–Kanof lymphocytic infiltration of the skin, lymphocytic infiltrate of Jessner) Kikuchis disease (histiocytic necrotizing lymphadenitis) Large plaque parapsoriasis (parapsoriasis en plaques) Lennert lymphoma (lymphoepitheliod lymphoma) Leukemia cutis Lymphoma cutis Lymphomatoid granulomatosis Lymphomatoid papulosis Malignant histiocytosis (histiocytic medullary reticulosis) Marginal zone B-cell lymphoma Mucosa-associated lymphoid tissue lymphoma Mycosis fungoides Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma Nonspecific cutaneous conditions associated with leukemia (leukemid) Pagetoid reticulosis (acral mycoses fungoides, localized epidermotropic reticulosis, mycosis fungoides palmaris et plantaris, unilesional mycosis fungoides, Woringer–Kolopp disease) Pityriasis lichenoides chronica (chronic guttate parapsoriasis, chronic pityriasis lichenoides, dermatitis psoriasiformis nodularis, parapsoriasis chronica, parapsoriasis lichenoides chronica) Pityriasis lichenoides et varioliformis acuta (acute guttate parapsoriasis, acute parapsoriasis, acute pityriasis lichenoides, Mucha–Habermann disease, parapsoriasis acuta, parapsoriasis lichenoides et varioliformis acuta, parapsoriasis varioliformis) Plasmacytoma Plasmacytosis Pleomorphic T-cell lymphoma (non-mycosis fungoides CD30− pleomorphic small/medium-sized cutaneous T-cell lymphoma) Polycythemia vera (erythremia) Primary cutaneous follicular lymphoma (follicular center cell lymphoma, follicular center lymphoma) Primary cutaneous immunocytoma Primary cutaneous marginal zone lymphoma Retiform parapsoriasis Secondary cutaneous CD30+ large cell lymphoma Sézary syndrome Sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease) Subcutaneous T-cell lymphoma (panniculitis-like T-cell lymphoma) Vesiculopustular eruption and leukemoid reaction in Down syndrome Melanocytic nevi and neoplasms Melanocytic nevi and neoplasms are caused by either a proliferation of (1) melanocytes, or (2) nevus cells, a form of melanocyte that lack dendritic processes. Acral nevus (melanocytic nevus of acral skin, melanocytic nevus with intraepidermal ascent of cells) Amelanotic blue nevus (hypomelanotic blue nevus) Balloon cell nevus Bannayan–Riley–Ruvalcaba syndrome Beckers nevus (Beckers melanosis, Beckers pigmentary hamartoma, nevoid melanosis, pigmented hairy epidermal nevus) Benign melanocytic nevus (banal nevus, common acquired melanocytic nevus, mole, nevocellular nevus, nevocytic nevus) Blue nevus (blue neuronevus, dermal melanocytoma, nevus bleu) Blue nevus of Jadassohn–Tièche (common blue nevus, nevus ceruleus) Carney complex (LAMB syndrome, NAME syndrome) Cellular blue nevus Centrofacial lentiginosis Congenital melanocytic nevus Deep penetrating nevus Dysplastic nevus (atypical mole, atypical nevus, B-K mole, Clarks nevus, dysplastic melanocytic nevus, nevus with architectural disorder) Dysplastic nevus syndrome (B-K mole syndrome, familial atypical multiple mole–melanoma syndrome, familial melanoma syndrome) Ephelis (freckle) Epithelioid blue nevus Generalized lentiginosis Giant pigmented nevus (bathing trunk nevus, congenital nevomelanocytic nevus, garment nevus, giant hairy nevus, nevus pigmentosus et pilosus) Halo nevus (leukoderma acquisitum centrifugum, perinevoid vitiligo, Sutton nevus) Horis nevus (acquired bilateral nevus of Ota-like macules) Inherited patterned lentiginosis in black persons Ink spot lentigo (sunburn lentigo) Laugier–Hunziker syndrome Lentigo simplex (simple lentigo) Malignant blue nevus Medium-sized congenital nevocytic nevus Melanoacanthoma Melanocytic tumors of uncertain malignant potential Moynahan syndrome Mucosal lentigines (labial and penile and vulvar melanosis, melanotic macules) Nevus of Ito (nevus fuscoceruleus acromiodeltoideus) Nevus of Ota (congenital melanosis bulbi, melanosis bulborum and aberrant dermal melanocytosis, nevus fuscoceruleus ophthalmomaxillaris, oculodermal melanocytosis, oculomucodermal melanocytosis) Nevus spilus (speckled lentiginous nevus, zosteriform lentiginous nevus) Partial unilateral lentiginosis (segmental lentiginosis) Peutz–Jeghers syndrome Pigmented spindle cell nevus (pigmented spindle cell tumor of Reed, pigmented variant of Spitz nevus) Pseudomelanoma (recurrent melanocytic nevus, recurrent nevus) PUVA lentigines Small-sized congenital nevocytic nevus Spitz nevus (benign juvenile melanoma, epithelioid and spindle cell nevus, Spitzs juvenile melanoma) Solar lentigo (lentigo senilis, liver spot, old age spot, senile freckle) Melanoma Melanoma is a malignant proliferation of melanocytes and the most aggressive type of skin cancer. Acral lentiginous melanoma Amelanotic melanoma Animal-type melanoma Desmoplastic melanoma (neurotropic melanoma, spindled melanoma) Lentigo maligna (lentiginous melanoma on sun-damaged skin) Lentigo maligna melanoma Melanoma with features of a Spitz nevus (Spitzoid melanoma) Melanoma with small nevus-like cells (small cell melanoma) Mucosal melanoma Nevoid melanoma Nodular melanoma Polypoid melanoma Seborrheic keratosis-like melanoma Soft-tissue melanoma (clear-cell sarcoma, melanoma of the soft parts) Superficial spreading melanoma (superficially spreading melanoma) Uveal melanoma Monocyte- and macrophage-related Monocyte- and macrophage-related cutaneous conditions are characterized histologically by infiltration of the skin by monocyte or macrophage cells, often divided into several categories, including granulomatous disease, histiocytoses, and sarcoidosis. Actinic granuloma (OBrien granuloma) Annular elastolytic giant cell granuloma (giant cell elastophagocytosis, Meischers granuloma, Mieschers granuloma of the face) Annular sarcoidosis Benign cephalic histiocytosis (histiocytosis with intracytoplasmic worm-like bodies) Congenital self-healing reticulohistiocytosis (Hashimoto–Pritzker disease, Hashimoto–Pritzker syndrome) Erythrodermic sarcoidosis Generalized eruptive histiocytoma (eruptive histiocytoma, generalized eruptive histiocytosis) Generalized granuloma annulare Giant cell reticulohistiocytoma (solitary reticulohistiocytoma, solitary reticulohistiocytosis) Granuloma annulare in HIV disease Granuloma multiforme (Mkar disease, granuloma multiforme (Leiker)) Hand–Schüller–Christian disease Heerfordts syndrome Hereditary progressive mucinous histiocytosis Hypopigmented sarcoidosis Ichthyosiform sarcoidosis Indeterminate cell histiocytosis Interstitial granulomatous drug reaction Langerhans cell histiocytosis (histiocytosis X) Letterer–Siwe disease Localized granuloma annulare Löfgren syndrome Lupus pernio Morpheaform sarcoidosis Mucosal sarcoidosis Multicentric reticulohistiocytosis Necrobiotic xanthogranuloma (necrobiotic xanthogranuloma with paraproteinemia) Non-X histiocytosis Papular sarcoid Papular xanthoma Patch-type granuloma annulare (macular granuloma annulare) Perforating granuloma annulare Progressive nodular histiocytosis Reticulohistiocytoma Scar sarcoid (sarcoidosis in scars) Sea-blue histiocytosis Subcutaneous granuloma annulare (deep granuloma annulare, pseudorheumatoid nodule) Subcutaneous sarcoidosis (Darier–Roussy disease, Darier–Roussy sarcoid) Systemic sarcoidosis Ulcerative sarcoidosis Xanthoma disseminatum (disseminated xanthosiderohistiocytosis, Montgomery syndrome) Mucinoses Mucinoses are a group of conditions caused by dermal fibroblasts producing abnormally large amounts of mucopolysaccharides. Acral persistent papular mucinosis Atypical lichen myxedematosus (intermediate lichen myxedematosus) Atypical tuberous myxedema (Jadassohn–Dosseker syndrome) Cutaneous focal mucinosis Cutaneous lupus mucinosis (papular and nodular mucinosis in lupus erythematosus, papular and nodular mucinosis of Gold, papulonodular mucinosis in lupus erythematosus) Discrete papular lichen myxedematosus Eccrine mucinosis Follicular mucinosis (alopecia mucinosa, mucinosis follicularis, Pinkus follicular mucinosis, Pinkus follicular mucinosis–benign primary form) Localized lichen myxedematosus Myxoid cyst (digital mucous cyst, mucous cyst) Myxoid lipoblastoma Neuropathia mucinosa cutanea Nodular lichen myxedematosus Papular mucinosis (generalized lichen myxedematosus, sclerodermoid lichen myxedematosus, scleromyxedema) Papular mucinosis of infancy (cutaneous mucinosis of infancy) Perifollicular mucinosis Reticular erythematous mucinosis (midline mucinosis, plaque-like cutaneous mucinosis, REM syndrome) Scleroderma Self-healing juvenile cutaneous mucinosis Self-healing papular mucinosis Stiff skin syndrome (congenital fascial dystrophy) Neurocutaneous Neurocutaneous conditions are due organic nervous system disease or are psychiatric in etiology. Atypical chronic pain syndrome Body dysmorphic disorder (dysmorphic syndrome, dysmorphophobia) Brachioradial pruritus Bromidrosiphobia Complex regional pain syndrome (reflex sympathetic dystrophy) Congenital insensitivity to pain with anhidrosis Delusional parasitosis (delusions of parasitosis, Ekbom syndrome, monosymptomatic hypochondriacal psychosis) Dermatothlasia Factitious dermatitis (dermatitis artefacta, factitial dermatitis) Glossodynia (burning mouth syndrome, burning tongue, orodynia) Levator ani syndrome Malum perforans pedis (neurotrophic ulcer, perforating ulcer of the foot) Meralgia paresthetica (Roth–Bernhardt disease) Neurotic excoriations Notalgia paresthetica (hereditary localized pruritus, posterior pigmented pruritic patch, subscapular pruritus) Postencephalitic trophic ulcer Psychogenic pruritus Riley–Day syndrome (familial dysautonomia) Scalp dysesthesia Sciatic nerve injury Scrotodynia Syringomyelia (Morvans disease) Traumatic neuroma (amputation neuroma) Trichotillomania (trichotillosis) Trigeminal neuralgia (tic douloureux) Trigeminal trophic lesion (trigeminal trophic syndrome) Vulvodynia (vestibulodynia) Noninfectious immunodeficiency-related Noninfectious immunodeficiency-related cutaneous conditions are caused by T-cell or B-cell dysfunction. Bare lymphocyte syndrome Chronic granulomatous disease (Bridges–Good syndrome, chronic granulomatous disorder, Quie syndrome) Common variable immunodeficiency (acquired hypogammaglobulinemia) Complement deficiency DiGeorge syndrome (DiGeorge anomaly, thymic hypoplasia) Graft-versus-host disease Griscelli syndrome Hyper-IgE syndrome (Buckley syndrome, Job syndrome) Immunodeficiency with hyper-IgM Immunodeficiency–centromeric instability–facial anomalies syndrome (ICF syndrome) Isolated IgA deficiency Isolated primary IgM deficiency Janus kinase 3 deficiency Leukocyte adhesion molecule deficiency LIG4 syndrome Myeloperoxidase deficiency Neutrophil immunodeficiency syndrome Nezelof syndrome (thymic dysplasia with normal immunoglobulins) Omenn syndrome Purine nucleoside phosphorylase deficiency Severe combined immunodeficiency (alymphocytosis, Glanzmann–Riniker syndrome, severe mixed immunodeficiency syndrome, thymic alymphoplasia) Shwachman–Bodian–Diamond syndrome Thymoma with immunodeficiency (Good syndrome) Transient hypogammaglobulinemia of infancy Warts–hypogammaglobulinemia–infections–myelokathexis syndrome (WHIM syndrome) Wiskott–Aldrich syndrome X-linked agammaglobulinemia (Bruton syndrome, sex-linked agammaglobulinemia) X-linked hyper-IgM syndrome X-linked hypogammaglobulinemia X-linked lymphoproliferative disease (Duncans disease) X-linked neutropenia Nutrition-related Nutrition-related cutaneous conditions are caused by malnutrition due to an improper or inadequate diet. Biotin deficiency Carotenemia Essential fatty acid deficiency Folic acid deficiency Hypervitaminosis A Hypovitaminosis A (phrynoderma) Iron deficiency Kwashiorkor Lycopenemia Maple syrup urine disease Marasmus Niacin deficiency (pellagra, vitamin B3 deficiency) Selenium deficiency Vitamin B1 deficiency (beriberi, thiamine deficiency) Vitamin B12 deficiency (cyanocobalamin deficiency) Vitamin B2 deficiency (ariboflavinosis, riboflavin deficiency) Vitamin B6 deficiency (pyridoxine deficiency) Vitamin B6 excess (pyridoxine excess) Vitamin C deficiency (scurvy) Vitamin K deficiency Zinc deficiency Papulosquamous hyperkeratotic Papulosquamous hyperkeratotic cutaneous conditions are those that present with papules and scales caused by a thickening of the stratum corneum. Confluent and reticulated papillomatosis (confluent and reticulated papillomatosis of Gougerot and Carteaud, familial cutaneous papillomatosis, familial occurrence of confluent and reticulated papillomatosis) Digitate dermatosis Drug-induced keratoderma Exfoliative dermatitis (dermatitis exfoliativa, erythroderma, red man syndrome) Florid cutaneous papillomatosis Granular parakeratosis (axillary granular parakeratosis, intertriginous granular parakeratosis) Keratolysis exfoliativa (lamellar dyshidrosis, recurrent focal palmar peeling, recurrent palmar peeling) Keratosis punctata of the palmar creases (hyperkeratosis penetrans, hyperkeratosis punctata, keratodermia punctata, keratosis punctata, keratotic pits of the palmar creases, lenticular atrophia of the palmar creases, punctate keratosis of the palmar creases) Meesmann corneal dystrophy Paraneoplastic keratoderma Pityriasis rosea (pityriasis rosea Gibert) Pityriasis rubra pilaris (Devergies disease, lichen ruber acuminatus, lichen ruber pilaris) Pure hair-nail type ectodermal dysplasia Small plaque parapsoriasis (chronic superficial dermatitis) Tripe palms Xanthoerythrodermia perstans Palmoplantar keratodermas Palmoplantar keratodermas are a diverse group of hereditary and acquired keratodermas in which there is hyperkeratosis of the skin of the palms and soles. Acrokeratoelastoidosis of Costa (keratoelastoidosis marginalis) Aquagenic keratoderma (acquired aquagenic palmoplantar keratoderma, aquagenic syringeal acrokeratoderma, aquagenic wrinkling of the palms, transient reactive papulotranslucent acrokeratoderma) Bart–Pumphrey syndrome (palmoplantar keratoderma with knuckle pads and leukonychia and deafness) Camisa disease Carvajal syndrome (striate palmoplantar keratoderma with woolly hair and cardiomyopathy, striate palmoplantar keratoderma with woolly hair and left ventricular dilated cardiomyopathy) Corneodermatoosseous syndrome (CDO syndrome) Diffuse epidermolytic palmoplantar keratoderma (palmoplantar keratoderma cum degeneratione granulosa Vörner, Vörners epidermolytic palmoplantar keratoderma, Vörner keratoderma) Diffuse nonepidermolytic palmoplantar keratoderma (diffuse orthohyperkeratotic keratoderma, hereditary palmoplantar keratoderma, keratosis extremitatum progrediens, keratosis palmoplantaris diffusa circumscripta, tylosis, Unna–Thost disease, Unna–Thost keratoderma) Erythrokeratodermia variabilis (erythrokeratodermia figurata variabilis, keratosis extremitatum progrediens, keratosis palmoplantaris transgrediens et progrediens, Mendes da Costa syndrome, Mendes da Costa type erythrokeratodermia, progressive symmetric erythrokeratoderma) Focal acral hyperkeratosis (acrokeratoelastoidosis lichenoides, degenerative collagenous plaques of the hand) Focal palmoplantar and gingival keratosis Focal palmoplantar keratoderma with oral mucosal hyperkeratosis (focal epidermolytic palmoplantar keratoderma, hereditary painful callosities, hereditary painful callosity syndrome, keratosis follicularis, keratosis palmoplantaris nummularis, nummular epidermolytic palmoplantar keratoderma) Haim–Munk syndrome (palmoplantar keratoderma with periodontitis and arachnodactyly and acro-osteolysis) Hidrotic ectodermal dysplasia (alopecia congenita with keratosis palmoplantaris, Clouston syndrome, Cloustons hidrotic ectodermal dysplasia, Fischer–Jacobsen–Clouston syndrome, keratosis palmaris with drumstick fingers, palmoplantar keratoderma and clubbing) Howel–Evans syndrome (familial keratoderma with carcinoma of the esophagus, focal non-epidermolytic palmoplantar keratoderma with carcinoma of the esophagus, palmoplantar ectodermal dysplasia type III, palmoplantar keratoderma associated with esophageal cancer, tylosis, tylosis–esophageal carcinoma) Hystrix-like ichthyosis–deafness syndrome (HID syndrome) Keratoderma climactericum (acquired plantar keratoderma, climacteric keratoderma, Haxthausens disease) Keratosis punctata palmaris et plantaris (Buschke–Fischer–Brauer disease, Davis Colley disease, keratoderma disseminatum palmaris et plantaris, keratosis papulosa, keratoderma punctatum, keratodermia punctata, keratoma hereditarium dissipatum palmare et plantare, palmar and plantar seed dermatoses, palmar keratoses, papulotranslucent acrokeratoderma, punctate keratoderma, punctate keratoses of the palms and soles, maculosa disseminata) Keratitis–ichthyosis–deafness syndrome (erythrokeratodermia progressiva Burns, ichthyosiform erythroderma with corneal involvement and deafness, KID syndrome) Mal de Meleda (acral keratoderma, Gamborg–Nielsen keratoderma, mutilating palmoplantar keratoderma of the Gamborg–Nielsen type, palmoplantar ectodermal dysplasia type VIII, palmoplantar keratoderma of the Norrbotten type) Naxos syndrome (diffuse non-epidermolytic palmoplantar keratoderma with woolly hair and cardiomyopathy, diffuse palmoplantar keratoderma with woolly hair and arrythmogenic right ventricular cardiomyopathy of Naxos, Naxos disease) Olmsted syndrome (mutilating palmoplantar keratoderma with periorificial keratotic plaques, mutilating palmoplantar keratoderma with periorificial plaques, polykeratosis of Touraine) Pachyonychia congenita type I (Jadassohn–Lewandowsky syndrome) Pachyonychia congenita type II (Jackson–Lawler pachyonychia congenita, Jackson–Sertoli syndrome) Palmoplantar keratoderma and spastic paraplegia (Charcot–Marie–Tooth disease with palmoplantar keratoderma and nail dystrophy) Palmoplantar keratoderma of Sybert (Greither palmoplantar keratoderma, Greither syndrome, keratosis extremitatum hereditaria progrediens, keratosis palmoplantaris transgrediens et progrediens, Sybert keratoderma, transgrediens and progrediens palmoplantar keratoderma) Papillon–Lefèvre syndrome (palmoplantar keratoderma with periodontitis) Porokeratosis plantaris discreta Punctate palmoplantar keratoderma Schöpf–Schulz–Passarge syndrome (eyelid cysts with palmoplantar keratoderma and hypodontia and hypotrichosis) Scleroatrophic syndrome of Huriez (Huriez syndrome, palmoplantar keratoderma with scleroatrophy, palmoplantar keratoderma with sclerodactyly, scleroatrophic and keratotic dermatosis of the limbs, sclerotylosis) Striate palmoplantar keratoderma (acral keratoderma, Brünauer–Fuhs–Siemens type of palmoplantar keratoderma, focal non-epidermolytic palmoplantar keratoderma, keratosis palmoplantaris varians, palmoplantar keratoderma areata, palmoplantar keratoderma striata, Wachter keratoderma, Wachters palmoplantar keratoderma) Spiny keratoderma (porokeratosis punctata palmaris et plantaris, punctate keratoderma, punctate porokeratosis of the palms and soles) Tyrosinemia type II (oculocutaneous tyrosinemia, Richner–Hanhart syndrome) Vohwinkel syndrome (keratoderma hereditaria mutilans, keratoma hereditaria mutilans, mutilating keratoderma of Vohwinkel, mutilating palmoplantar keratoderma) Pregnancy-related Pregnancy-related cutaneous conditions are a group of skin changes observed during pregnancy. Impetigo herpetiformis Intrahepatic cholestasis of pregnancy (cholestasis of pregnancy, jaundice of pregnancy, obstetric cholestasis, prurigo gravidarum) Linea nigra Pemphigoid gestationis (gestational pemphigoid, herpes gestationis) Prurigo gestationis (Besnier prurigo, early-onset prurigo of pregnancy, linear IgM dermatosis of pregnancy, papular dermatitis of pregnancy, prurigo of pregnancy, Spanglers papular dermatitis of pregnancy) Pruritic folliculitis of pregnancy Pruritic urticarial papules and plaques of pregnancy (late-onset prurigo of pregnancy, polymorphic eruption of pregnancy, PUPPP syndrome, toxemic rash of pregnancy, toxic erythema of pregnancy) Striae gravidarum Pruritic Pruritus, commonly known as itchiness, is a sensation exclusive to the skin, and characteristic of many skin conditions. Adult blaschkitis Aquadynia Aquagenic pruritus Biliary pruritus Cholestatic pruritus Drug-induced pruritus Hydroxyethyl starch-induced pruritus Lichen simplex chronicus (neurodermatitis) Prion pruritus Prurigo nodularis Prurigo pigmentosa Prurigo simplex Pruritus ani Pruritus scroti Pruritus vulvae Puncta pruritica (itchy points) Scalp pruritus Senile pruritus Uremic pruritus (renal pruritus) Psoriasis Psoriasis is a common, chronic, and recurrent inflammatory disease of the skin characterized by circumscribed, erythematous, dry, scaling plaques. Annular pustular psoriasis Drug-induced psoriasis Exanthematic pustular psoriasis Generalized pustular psoriasis (pustular psoriasis of von Zumbusch) Guttate psoriasis (eruptive psoriasis) Inverse psoriasis Keratoderma blennorrhagica (keratoderma blennorrhagicum) Localized pustular psoriasis Napkin psoriasis Psoriasis vulgaris (chronic stationary psoriasis, plaque-like psoriasis) Psoriatic arthritis Psoriatic erythroderma (erythrodermic psoriasis) Seborrheic-like psoriasis (sebopsoriasis, seborrhiasis) Reactive neutrophilic Reactive neutrophilic cutaneous conditions constitute a spectrum of disease mediated by neutrophils, and typically associated with underlying diseases, such as inflammatory bowel disease and hematologic malignancy. Acute erythema nodosum Bowel-associated dermatosis–arthritis syndrome (bowel bypass syndrome, bowel bypass syndrome without bowel bypass, intestinal bypass arthritis–dermatitis syndrome) Marshall syndrome Neutrophilic dermatosis of the dorsal hands (pustular vasculitis of the dorsal hands) Neutrophilic eccrine hidradenitis Pyoderma gangrenosum Pyogenic arthritis–pyoderma gangrenosum–acne syndrome (PAPA syndrome) Rheumatoid neutrophilic dermatitis (rheumatoid neutrophilic dermatosis) Superficial granulomatous pyoderma Sweets syndrome (acute febrile neutrophilic dermatosis) Sweets syndrome-like dermatosis Vesicopustular dermatosis Recalcitrant palmoplantar eruptions Recalcitrant palmoplantar eruptions are skin conditions of the palms and soles which are resistant to treatment. Dermatitis repens (acrodermatitis continua, acrodermatitis continua of Hallopeau, acrodermatitis continua suppurativa Hallopeau, acrodermatitis perstans, dermatitis repens Crocker, Hallopeaus acrodermatitis, Hallopeaus acrodermatitis continua, pustular acrodermatitis) Infantile acropustulosis (acropustulosis of infancy) Palmoplantar pustulosis (persistent palmoplantar pustulosis, pustular psoriasis of the Barber type, pustular psoriasis of the extremities, pustulosis of palms and soles, pustulosis palmaris et plantaris) Pustular bacterid Resulting from errors in metabolism Skin conditions resulting from errors in metabolism are caused by enzymatic defects that lead to an accumulation or deficiency of various cellular components, including, but not limited to, amino acids, carbohydrates, and lipids. Acute intermittent porphyria Adrenoleukodystrophy (Schilders disease) Alkaptonuria Aminolevulinic acid dehydratase deficiency porphyria (Doss porphyria, plumboporphyria) B-mannosidase deficiency Carotenosis Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy syndrome (CADASIL syndrome) Cerebrotendinous xanthomatosis Citrullinemia Congenital erythropoietic porphyria (Gunthers disease) Diabetic bulla (bullosis diabeticorum, bullous eruption of diabetes mellitus) Diabetic cheiroarthropathy Diabetic dermopathy (shin spots) Dystrophic calcinosis cutis Eruptive xanthoma Erythropoietic protoporphyria Fabry disease (Anderson–Fabry disease, angiokeratoma corporis diffusum) Familial alpha-lipoprotein deficiency (Tangier disease) Familial amyloid polyneuropathy Familial apoprotein CII deficiency Familial combined hyperlipidemia (multiple-type hyperlipoproteinemia) Familial defective apolipoprotein B-100 Familial dysbetalipoproteinemia (broad beta disease, remnant removal disease) Familial hypertriglyceridemia Farber disease (fibrocytic dysmucopolysaccharidosis, lipogranulomatosis) Fucosidosis Gauchers disease Gout (podagra, urate crystal arthropathy, urate deposition disease) Hartnup disease (pellagra-like dermatosis) Hemodialysis-associated amyloidosis Hepatoerythropoietic porphyria Hereditary coproporphyria Hereditary gelsolin amyloidosis Heredofamilial amyloidosis Hunter syndrome Hurler syndrome (gargoylism, mucopolysaccharidosis type I) Hurler–Scheie syndrome (mucopolysaccharidosis type I H-S) Hyaluronidase deficiency (mucopolysaccharidosis type IX) Iatrogenic calcinosis cutis Idiopathic scrotal calcinosis (idiopathic calcified nodules of the scrotum) Lafora disease Lesch–Nyhan syndrome (juvenile gout) Lichen amyloidosis Limited joint mobility Lipoid proteinosis (hyalinosis cutis et mucosae, Urbach–Wiethe disease) Lipoprotein lipase deficiency (chylomicronemia, chylomicronemia syndrome) Macular amyloidosis Maroteaux–Lamy syndrome (mucopolysaccharidosis type VI) Medication-induced hyperlipoproteinemia Metastatic calcinosis cutis Milia-like calcinosis Morquios disease (mucopolysaccharidosis type IV) Necrobiosis lipoidica (necrobiosis lipoidica diabeticorum) Niemann–Pick disease Nodular amyloidosis Nodular xanthoma Normolipoproteinemic xanthomatosis Obstructive liver disease (xanthomatous biliary cirrhosis) Ochronosis Osteoma cutis Palmar xanthoma Phenylketonuria Phytosterolemia (sitosterolemia) Porphyria cutanea tarda Primary cutaneous amyloidosis Primary systemic amyloidosis Prolidase deficiency Pseudoporphyria (pseudoporphyria cutanea tarda) Sanfilippo syndrome Scheie syndrome (mucopolysaccharidosis type I S) Secondary cutaneous amyloidosis Secondary systemic amyloidosis Sialidosis Sly syndrome (mucopolysaccharidosis type VII) Subepidermal calcified nodule (solitary congenital nodular calcification, Winers nodular calcinosis) Transient erythroporphyria of infancy (purpuric phototherapy-induced eruption) Traumatic calcinosis cutis Tuberoeruptive xanthoma (tuberous xanthoma) Tumoral calcinosis Variegate porphyria (mixed hepatic porphyria, mixed porphyria, South African genetic porphyria, South African porphyria) Verruciform xanthoma Waxy skin Wilsons disease (hepatolenticular degeneration) Xanthelasma palpebrarum (xanthelasma) Xanthoma diabeticorum Xanthoma planum (plane xanthoma) Xanthoma striatum palmare Xanthoma tendinosum (tendinous xanthoma) Xanthoma tuberosum Resulting from physical factors Skin conditions resulting from physical factors occur from a number of causes, including, but not limited to, hot and cold temperatures, friction, and moisture. Abrasion Acrocyanosis Actinic prurigo (familial polymorphous light eruption of American Indians, hereditary polymorphous light eruption of American Indians, Hutchinsons summer prurigo, hydroa aestivale) Aerosol burn Benign summer light eruption Beryllium granuloma Black heel and palm (black heel, calcaneal petechiae, chromidrose plantaire, post-traumatic punctate intraepidermal hemorrhage, tache noir, talon noir) Callus (callosity, clavus, corn, heloma, heloma durum, heloma molle, intractable plantar keratosis, tyloma) Carbon stain Chilblains (pernio, perniosis) Chronic actinic dermatitis (actinic reticuloid, chronic photosensitivity dermatitis, persistent light reactivity, photosensitive eczema) Colloid milium Coma blister Coral cut Delayed blister Dermatosis neglecta Edema blister (edema bulla, hydrostatic bulla, stasis blister) Electrical burn Equestrian perniosis Erythema ab igne (fire stains, toasted skin syndrome) Erythrocyanosis crurum Favre–Racouchot syndrome (Favre–Racouchot disease, nodular cutaneous elastosis with cysts and comedones) Foreign body reaction Fracture blister Friction blister Frostbite Garrods pad (violinists viola pad) Harpists finger Heel stick wound Heat edema Hot tar burn Hunan hand syndrome (chili burn) Hydroa vacciniforme (Bazins hydroa vacciniforme) Joggers nipple Juvenile spring eruption Kairo cancer Kang cancer Kangri ulcer Lightning burn Loop mark Magnetic resonance imaging burn (MRI burn) Mercury granuloma Miliaria crystallina (miliaria crystalline, sudamina) Miliaria profunda (mammillaria) Miliaria pustulosa Miliaria rubra (heat rash, prickly heat) Narcotic dermopathy Occlusion miliaria Painful fat herniation (painful piezogenic pedal papules, piezogenic papules) Peat fire cancer Photoaging (dermatoheliosis) Photosensitivity with HIV infection Phototoxic tar dermatitis Photosenitization Phytophotodermatitis (Berloque dermatitis) Pinch mark Polymorphous light eruption (polymorphic light eruption) Postmiliarial hypohidrosis Postoperative hematoma Pressure ulcer (decubitus ulcer) Pseudoacanthosis nigricans Pseudoverrucous papules and nodules Pulling boat hands PUVA-induced acrobullous dermatosis Runners rump Sclerosing lymphangiitis Silica granuloma Silicone granuloma Skin pop scar Skin track Slap mark Solar erythema Soot tattoo Subcutaneous emphysema Sucking blister Sunburn Surfers knots Tattoo Tennis toe Thermal burn Traumatic asphyxia Trench foot Tropical anhidrotic asthenia Tropical immersion foot (paddy foot, paddy-field foot) Turf toe Uranium dermatosis UV-sensitive syndrome Vibration white finger (dead finger, hand–arm vibration syndrome) Warm water immersion foot Weathering nodule of ear Wrestlers ear (cauliflower ear, traumatic auricular hematoma) Zirconium granuloma Ionizing radiation-induced Ionizing radiation-induced cutaneous conditions result from exposure to ionizing radiation. Acute radiodermatitis Chronic radiation keratosis Chronic radiodermatitis Eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy Fluoroscopy burn Radiation acne Radiation cancer Radiation dermatitis (radiodermatitis) Radiation recall reaction Radiation-induced erythema multiforme Radiation-induced hypertrophic scar Radiation-induced keloid Radiation-induced morphea Urticaria and angioedema Urticaria is a vascular reaction of the skin characterized by the appearance of wheals, which are firm, elevated swellings of the skin. Angioedema, which can occur alone or with urticaria, is characterized by a well-defined, edematous swelling that involves subcutaneous tissues, abdominal organs, or upper airway. Acquired C1 esterase inhibitor deficiency Acute urticaria Adrenergic urticaria Anaphylaxis Aquagenic urticaria Cholinergic urticaria Chronic urticaria (ordinary urticaria) Cold urticaria Dermatographism (dermographism) Episodic angioedema with eosinophilia (Gleichs syndrome) Exercise urticaria (exercise-induced urticaria) Galvanic urticaria Heat urticaria Hereditary angioedema (Quinckes edema) Localized heat contact urticaria Mast cell-independent urticaria Physical urticaria Primary cold contact urticaria Pressure urticaria (delayed pressure urticaria) Reflex cold urticaria Schnitzler syndrome Secondary cold contact urticaria Solar urticaria Systemic capillary leak syndrome Urticarial allergic eruption Urticaria-like follicular mucinosis Vibratory angioedema Vascular-related Vascular-related cutaneous conditions result from dysfunction of the blood or blood vessels in the dermis, or lymphatics in the subcutaneous tissues. Aagenaes syndrome Acroangiodermatitis (acroangiodermatitis of Mali, Mali acroangiodermatitis, Pseudo-Kaposis sarcoma) Acrocyanosis Acute hemorrhagic edema of infancy (acute hemorrhagic edema of childhood, Finkelsteins disease, infantile postinfectious iris-like purpura and edema, medallion-like purpura, purpura en cocarde avec oedema, Seidlmayer syndrome) Arterial insufficiency ulcer (ischemic ulcer) Arteriosclerosis obliterans Bier spots Blueberry muffin baby Bonnet–Dechaume–Blanc syndrome (Wyburn–Mason syndrome) Bullous lymphedema Bullous small vessel vasculitis (bullous variant of small vessel vasculitis) Calciphylaxis Caput succedaneum Cholesterol embolus (warfarin blue toe syndrome) Cobb syndrome Corona phlebectatica Cryofibrinogenemic purpura Cryoglobulinemic purpura Cryoglobulinemic vasculitis Cutaneous small-vessel vasculitis (cutaneous leukocytoclastic angiitis, cutaneous leukocytoclastic vasculitis, cutaneous necrotizing venulitis, hypersensitivity angiitis) Deep venous thrombosis Disseminated intravascular coagulation Doucas and Kapetanakis pigmented purpura Drug-induced purpura Drug-induced thrombocytopenic purpura Eczematid-like purpura of Doucas and Kapetanakis Epidemic dropsy Erythema elevatum diutinum Erythromelalgia (acromelalgia, erythermalgia) Factitial lymphedema (hysterical edema) Fibrinolysis syndrome (defibrinating syndrome, hypofibrinogenemia) Food-induced purpura Generalized essential telangiectasia (general essential telangiectasia) Giant-cell arteritis Gougerot–Blum syndrome (pigmented purpuric lichenoid dermatitis, pigmented purpuric lichenoid dermatitis of Gougerot and Blum) Granulomatosis with polyangiitis Harlequin color change Hematopoietic ulcer Hennekam syndrome (Hennekam lymphangiectasia-lymphedema syndrome, intestinal lymphagiectasia-lymphedema-mental retardation syndrome) Henoch–Schönlein purpura (anaphylactoid purpura, purpura rheumatica, Schönlein–Henoch purpura) Hereditary hemorrhagic telangiectasia (Oslers disease, Osler–Weber–Rendu disease) Idiopathic thrombocytopenic purpura (autoimmune thrombocytopenic purpura, Werlhofs disease) IgA vasculitis Kawasakis disease (mucocutaneous lymph node syndrome) Levamisole-induced vasculitis Lichen aureus (lichen purpuricus) Livedo racemosa Livedo reticularis Livedoid dermatitis (embolia cutis medicamentosa, Nicolau syndrome) Livedoid vasculopathy (atrophie blanche, livedo reticularis with summer ulceration, livedoid vasculitis, PURPLE syndrome, segmental hyalinizing vasculitis) Lymphedema praecox Lymphedema–distichiasis syndrome Maffucci syndrome Majocchis disease (purpura annularis telangiectodes, purpura annularis telangiectodes of Majocchi) Malignant atrophic papulosis (Degos disease) Marshall–White syndrome Meige lymphedema Microscopic polyangiitis (microscopic polyarteritis, microscopic polyarteritis nodosa) Mondors disease (Mondors syndrome of superficial thrombophlebitis) Neuropathic ulcer (mal perforans) Njolstad syndrome Nonne–Milroy–Meige syndrome (hereditary lymphedema, Milroy disease) Obstructive purpura Orthostatic purpura (stasis purpura) Painful bruising syndrome (autoerythrocyte sensitization, Gardner–Diamond syndrome, psychogenic purpura) Parkes Weber syndrome Paroxysmal hand hematoma (Achenbach syndrome) Paroxysmal nocturnal hemoglobinuria Polyarteritis nodosa (panarteritis nodosa, periarteritis nodosa) Postcardiotomy syndrome Perinatal gangrene of the buttock Pigmentary purpuric eruptions (progressive pigmentary dermatosis, progressive pigmenting purpura, purpura pigmentosa chronica) Postinflammatory lymphedema Postmastectomy lymphangiosarcoma (Stewart–Treves syndrome) Purpura fulminans (purpura gangrenosa) Purpura secondary to clotting disorders Purpuric agave dermatitis Raynaud phenomenon Raynauds disease (primary Raynauds phenomenon) Reactive angioendotheliomatosis Schambergs disease (progressive pigmentary dermatosis of Schamberg, purpura pigmentosa progressiva, Schambergs purpura) Secondary lymphedema Septic thrombophlebitis Sinusoidal hemangioma Sneddons syndrome (idiopathic livedo reticularis with cerebrovascular accidents) Solar purpura (actinic purpura, senile purpura) Stasis dermatitis (congestion eczema, gravitational dermatitis, gravitational eczema, stasis eczema, varicose eczema) Superficial thrombophlebitis Takayasu arteritis (aortic arch syndrome, pulseless disease) Temporal arteritis (cranial arteritis, Hortons disease) Thromboangiitis obliterans (Buergers disease) Thrombotic thrombocytopenic purpura (Moschcowitz syndrome) Traumatic purpura Trousseaus syndrome Unilateral nevoid telangiectasia (nevoid telangiectasia) Urticarial vasculitis (chronic urticaria as a manifestation of venulitis, hypocomplementemic urticarial vasculitis syndrome, hypocomplementemic vasculitis, unusual lupus-like syndrome) Venous insufficiency ulceration Waldenström hyperglobulinemic purpura (purpura hyperglobulinemica) Waldenström macroglobulinemia Yellow nail syndrome (primary lymphedema associated with yellow nails and pleural effusion) See also Category:Cutaneous conditions Dermatology List of conditions associated with café au lait macules List of contact allergens List of cutaneous conditions associated with increased risk of nonmelanoma skin cancer List of cutaneous conditions associated with internal malignancy List of cutaneous conditions caused by mutations in keratins List of cutaneous neoplasms associated with systemic syndromes List of cutaneous conditions caused by problems with junctional proteins List of dental abnormalities associated with cutaneous conditions List of genes mutated in cutaneous conditions List of genes mutated in pigmented cutaneous lesions List of histologic stains that aid in diagnosis of cutaneous conditions List of human leukocyte antigen alleles associated with cutaneous conditions List of immunofluorescence findings for autoimmune bullous conditions List of inclusion bodies that aid in diagnosis of cutaneous conditions List of keratins expressed in the human integumentary system List of migrating cutaneous conditions List of mites associated with cutaneous reactions List of radiographic findings associated with cutaneous conditions List of specialized glands within the human integumentary system List of spiders associated with cutaneous reactions List of target antigens in pemphigoid List of target antigens in pemphigus List of verrucous carcinoma subtypes List of xanthoma variants associated with hyperlipoproteinemia subtypes Footnotes References Further reading External links Skin Disorders at Curlie All the Internet - Directory - Main/Health/Conditions_and_Diseases/Skin_Disorders Archived 18 June 2019 at the Wayback Machine Images in Clinical Dermatology at the New England Journal of Medicine

Pruritus of genital organs

Pruritus of genital organs may refer to: Pruritus scroti Pruritus vulvae

Gulf War syndrome

Gulf War syndrome or Gulf War illness is a chronic and multi-symptomatic disorder affecting military veterans of both sides of the 1990–1991 Persian Gulf War. A wide range of acute and chronic symptoms have been linked to it, including fatigue, muscle pain, cognitive problems, insomnia, rashes and diarrhea. Approximately 250,000 of the 697,000 U.S. veterans who served in the 1991 Gulf War have enduring chronic multi-symptom illness, a condition with serious consequences.The Royal British Legion said research suggested up to 33,000 UK Gulf War veterans could be living with the syndrome, with 1,300 claiming a war pension for conditions connected to their service. In 2007 the Royal British Legion produced a comprehensive report entitled Legacy of Suspicion, which made recommendations about necessary research and compensation. The Royal British Legion is still campaigning for the UK government to properly address symptoms experienced by veterans of the Gulf War.From 1995 to 2005, the health of combat veterans worsened in comparison with nondeployed veterans, with the onset of more new chronic diseases, functional impairment, repeated clinic visits and hospitalizations, chronic fatigue syndrome-like illness, post-traumatic stress disorder, and greater persistence of adverse health incidents.Exposure to pesticides and exposure to pills containing pyridostigmine bromide (used as a pretreatment to protect against nerve agent effects) has been found to be associated with the neurological effects seen in Gulf War syndrome. Other causes that have been investigated are sarin, cyclosarin, and emissions from oil well fires, but their relationship to the illness is not as clear.Studies have consistently indicated that Gulf War syndrome is not the result of combat or other stressors and that Gulf War veterans have lower rates of post-traumatic stress disorder (PTSD) than veterans of other wars.According to a 2013 report by the Iraq and Afghanistan Veterans of America, veterans of the U.S. wars in Iraq and Afghanistan may also have Gulf War syndrome, though later findings identified causes that would not have been present in those wars.In 2022, researchers led by Robert Haley, MD at University of Texas Southwestern Medical Center found that exposure to sarin nerve gas in soldiers who had a particular genetic mutation that prevented them from breaking down the nerve gas is likely to be responsible for the syndrome. The findings and an editorial by two leading epidemiologists were published in Environmental Health Perspectives. Signs and symptoms According to an April 2010 U.S. Department of Veterans Affairs (VA) sponsored study conducted by the Institute of Medicine (IOM), part of the U.S. National Academy of Sciences, 250,000 of the 696,842 U.S. servicemen and women in the 1991 Gulf War continue to be affected by chronic multi-symptom illness, which the IOM now refers to as Gulf War illness. The IOM found that it continued to affect these veterans nearly 20 years after the war. According to the IOM, "It is clear that a significant portion of the soldiers deployed to the Gulf War have experienced troubling constellations of symptoms that are difficult to categorize," said committee chair Stephen L. Hauser, professor and chair, department of neurology, University of California, San Francisco (UCSF). Unfortunately, symptoms that cannot be easily quantified are sometimes incorrectly dismissed as insignificant and receive inadequate attention and funding by the medical and scientific establishment. Veterans who continue to suffer from these symptoms deserve the very best that modern science and medicine can offer to speed the development of effective treatments, cures, and—we hope—prevention. Our report suggests a path forward to accomplish this goal, and we believe that through a concerted national effort and rigorous scientific input, answers can be found. Questions still exist regarding why certain veterans showed, and still show, medically unexplained symptoms while others did not, why symptoms are diverse in some and specific in others, and why combat exposure is not consistently linked to having or not having symptoms. The lack of data on veterans pre-deployment and immediate post-deployment health status and lack of measurement and monitoring of the various substances to which veterans may have been exposed make it difficult—and in many cases impossible—to reconstruct what happened to service members during their deployments nearly 20 years after the fact, the committee noted. The report called for a substantial commitment to improving identification and treatment of multisymptom illness in Gulf War veterans focussing on continued monitoring of Gulf War veterans, improved medical care, examination of genetic differences between symptomatic and asymptomatic groups and studies of environment-gene interactions.A variety of signs and symptoms have been associated with GWI: * This table applies only to coalition forces involved in combat.Birth defects have been suggested as a consequence of Gulf War deployment. However, a 2006 review of several studies of international coalition veterans children found no strong or consistent evidence of an increase in birth defects, finding a modest increase in birth defects that was within the range of the general population, in addition to being unable to exclude recall bias as an explanation for the results. A 2008 report stated that "it is difficult to draw firm conclusions related to birth defects and pregnancy outcomes in Gulf War veterans", observing that while there have been "significant, but modest, excess rates of birth defects in children of Gulf War veterans", the "overall rates are still within the normal range found in the general population". The same report called for more research on the issue. Comorbid illnesses Gulf War veterans have been identified to have an increased risk of multiple sclerosis.A 2017 study by the U.S. Department of Veterans Affairs found that veterans possibly exposed to chemical warfare agents at Khamisiyah experienced different patterns of brain cancer mortality risk compared to the other groups, with veterans possibly exposed having a higher risk of brain cancer in the time period immediately following the Gulf War. Iraqi veterans Although an understudied group, opposing Iraqi veterans of the Iraqi Army in the Gulf War also experienced acute and chronic symptoms associated with Gulf War syndrome. A 2011 study in the U.S Army Medical Department Journal reported Iraqi veterans of the Gulf War had a higher prevalence of somatic disorders as compared to Iraqi civilians, with risk greater in troops stationed in Kuwait.In comparison to Allied troops, health symptoms were similar amongst Iraqi veterans: * Zone 1 = In Kuwait, Zone 3 = 360 km from Kuwait. Causes The United States Congress mandated the U.S. Department of Veterans Affairs contract with the National Academy of Sciences (NAS) to provide reports on Gulf War illnesses. Since 1998, the NASs Institute of Medicine (IOM) has authored ten such reports. In addition to the many physical and psychological issues involved in any war zone deployment, Gulf War veterans were exposed to a unique mix of hazards not previously experienced during wartime. These included pyridostigmine bromide pills (given to protect troops from the effects of nerve agents), depleted uranium munitions, and multiple simultaneous vaccinations including anthrax and botulinum toxin vaccines. The oil and smoke that spewed for months from hundreds of burning oil wells presented another exposure hazard not previously encountered in a war zone. Military personnel also had to cope with swarms of insects, requiring the widespread use of pesticides. High-powered microwaves were used to disrupt Iraqi communications, and though it is unknown whether this might have contributed to the syndrome, research has suggested that safety limits for electromagnetic radiation are too lenient.The Research Advisory Committee on Gulf War Veterans Illnesses (RAC), a VA federal advisory committee mandated by Congress in legislation enacted in 1998, found that pre-2005 studies suggested the veterans illnesses are neurological and apparently are linked to exposure to neurotoxins, such as the nerve gas sarin, the anti-nerve gas drug pyridostigmine bromide, and pesticides that affect the nervous system. The RAC concluded in 2004 that, "research studies conducted since the war have consistently indicated that psychiatric illness, combat experience or other deployment-related stressors do not explain Gulf War veterans illnesses in the large majority of ill veterans."The RAC concluded that "exposure to pesticides and/or to PB [pyridostigmine bromide nerve agent protective pills] are causally associated with GWI and the neurological dysfunction in GW veterans. Exposure to sarin and cyclosarin and to oil well fire emissions are also associated with neurologically based health effects, though their contribution to development of the disorder known as GWI is less clear. Gene-environment interactions are likely to have contributed to development of GWI in deployed veterans. The health consequences of chemical exposures in the GW and other conflicts have been called "toxic wounds" by veterans. This type of injury requires further study and concentrated treatment research efforts that may also benefit other occupational groups with similar exposure-related illnesses." Earlier considered potential causes Depleted uranium Depleted uranium (DU) was widely used in tank kinetic energy penetrator and autocannon rounds for the first time ever during the Gulf War and has been suggested as a possible cause of Gulf War syndrome. A 2008 review by the U.S. Department of Veterans Affairs found no association between DU exposure and multisymptom illness, concluding that "exposure to DU munitions is not likely a primary cause of Gulf War illness". However, there are suggestions that long-term exposure to high doses of DU may cause other health problems unrelated to GWI.More recent medical literature reviews disagree, stating for example that, "the number of Gulf War veterans who developed the Gulf War syndrome following exposure to high quantities of DU has risen to about one-third of the 800,000 U.S. forces deployed," with 25,000 of those having had a premature death. Since 2011, US combat veterans may claim disability compensation for health problems related to exposure to depleted uranium. The Veterans Administration decides these claims on a case-by-case basis. A team at the University of Portsmouth led by Professor Randall Parrish tested urine samples of 154 US veterans in 2021, reporting that no soldiers with the syndrome were exposed to significant amounts of depleted uranium and that it "is not and never was in the bodies of those who are ill at sufficient quantities to cause disease". Pyridostigmine bromide nerve gas antidote The US military issued pyridostigmine bromide (PB) pills to protect against exposure to nerve gas agents such as sarin and soman. PB was used as a prophylactic against nerve agents; it is not a vaccine. Taken before exposure to nerve agents, PB was thought to increase the efficiency of nerve agent antidotes. PB had been used since 1955 for patients who have myasthenia gravis with doses up to 1,500 mg a day, far in excess of the 90 mg given to soldiers, and was considered safe by the FDA at either level for indefinite use and its use to pre-treat nerve agent exposure had recently been approved.Given both the large body of epidemiological data on myasthenia gravis patients and follow-up studies done on veterans it was concluded that while it was unlikely that health effects reported today by Gulf War veterans are the result of exposure solely to PB, use of PB was causally associated with illness. However, a later review by the Institute of Medicine concluded that the evidence was not strong enough to establish a causal relationship. Organophosphates Organophosphate-induced delayed neuropathy (OPIDN, aka organophosphate-induced delayed polyneuropathy) may contribute to the unexplained illnesses of the Gulf War veterans. Organophosphate pesticides The use of organophosphate pesticides and insect repellents during the first Gulf War is credited with keeping rates of pest-borne diseases low. Pesticide use is one of only two exposures consistently identified by Gulf War epidemiologic studies to be significantly associated with Gulf War illness. Multisymptom illness profiles similar to Gulf War illness have been associated with low-level pesticide exposures in other human populations. In addition, Gulf War studies have identified dose-response effects, indicating that greater pesticide use is more strongly associated with Gulf War illness than more limited use. Pesticide use during the Gulf War has also been associated with neurocognitive deficits and neuroendocrine alterations in Gulf War veterans in clinical studies conducted following the end of the war. The 2008 report concluded that "all available sources of evidence combine to support a consistent and compelling case that pesticide use during the Gulf War is causally associated with Gulf War illness." Sarin nerve agent Many of the symptoms of Gulf War illness are similar to the symptoms of organophosphate, mustard gas, and nerve gas poisoning. Gulf War veterans were exposed to a number of sources of these compounds, including nerve gas and pesticides.Chemical detection units from Czechoslovakia, France, and Britain confirmed chemical agents. French detection units detected chemical agents. Both Czech and French forces reported detections immediately to U.S. forces. U.S. forces detected, confirmed, and reported chemical agents; and U.S. soldiers were awarded medals for detecting chemical agents. The Riegle Report said that chemical alarms went off 18,000 times during the Gulf War. After the air war started on January 16, 1991, coalition forces were chronically exposed to low but nonlethal levels of chemical and biological agents released primarily by direct Iraqi attack via missiles, rockets, artillery, or aircraft munitions and by fallout from allied bombings of Iraqi chemical warfare munitions facilities.In 1997, the US Government released an unclassified report that stated: "The US Intelligence Community (IC) has assessed that Iraq did not use chemical weapons during the Gulf war. However, based on a comprehensive review of intelligence information and relevant information made available by the United Nations Special Commission (UNSCOM), we conclude that chemical warfare (CW) agent was released as a result of US postwar demolition of rockets with chemical warheads in a bunker (called Bunker 73 by Iraq) and a pit in an area known as Khamisiyah."Over 125,000 U.S. troops and 9,000 U.K. troops were exposed to nerve gas and mustard gas when the Iraqi depot in Khamisiyah was destroyed.Recent studies have confirmed earlier suspicions that exposure to sarin, in combination with other contaminants such as pesticides and PB were related to reports of veteran illness. Estimates range from 100,000 to 300,000 individuals exposed to nerve agents.While low-level exposure to nerve agents has been suggested as the cause of GWI, the 2008 report by the U.S. Department of Veterans Affairs (VA) Research Advisory Committee on Gulf War illnesses (RAC) stated that "evidence is inconsistent or limited in important ways." The VAs 2014 RAC report concluded that, "exposure to the nerve gas agents sarin/cyclosarin has been linked in two more studies to changes in structural magnetic resonance imaging findings that are associated with cognitive decrements, further supporting the conclusion from evidence reviewed in the 2008 report that exposure to these agents is etiologically important to the central nervous system dysfunction that occurs in some subsets of Gulf War veterans."A 2022 study by Dr. Robert W. Haley of the University of Texas Southwestern Medical Center, et al., of 1,016 U.S. Gulf War veterans found evidence of a causal link between GWI and exposure to low levels of sarin, which was released into the air by coalition bombing of Iraqi chemical weapons facilities. Significantly, the study found an increased incidence of GWI not only among veterans who recounted hearing nerve agent alarms, but also among veterans with the RR or QR (as opposed to the QQ) forms of the PON1 gene, which produces an enzyme that deactivates organophosphates (including sarin) through hydrolysis. By contrast, GWI was inversely associated with higher levels of the type Q isozyme, which is more efficient at breaking down sarin than its type R counterpart. The authors "found that the PON1 genotype and hearing nerve agent alarms were independent and the findings robust to both measured and unmeasured confounding, supporting a mechanistic [gene–environment] interaction. ... Moreover, the change in the combined effect from one category to the next was significantly greater than the sum of the independent effects of the environmental exposure and the genotype". Although organophosphate pesticides could have triggered the nerve agent alarms in use at the time and contributed to neurotoxic symptoms similar to GWI, Haley et al. ruled out pesticides as a primary cause of GWI, citing that pesticide use was "ubiquitous long before the approximately 10,000 alarms began sounding at the start of the air campaign when Coalition bombing of Iraqi chemical weapon facilities released the fallout cloud that reached U.S. troop concentrations just as sarin was detected at multiple sites," while "the PON1 R isoenzyme is the more efficient detoxifier of most pesticides." Less likely causes According to the VAs 2008 RAC report, "For several Gulf War exposures, an association with Gulf War illness cannot be ruled out. These include low-level exposure to nerve agents, close proximity to oil well fires, receipt of multiple vaccines, and effects of combinations of Gulf War exposures." However, several potential causes of GWI were deemed, "not likely to have caused Gulf War illness for the majority of ill veterans," including "depleted uranium, anthrax vaccine, fuels, solvents, sand and particulates, infectious diseases, and chemical agent resistant coating (CARC)," for which "there is little evidence supporting an association with Gulf War illness or a major role is unlikely based on what is known about exposure patterns during the Gulf War and more recent deployments."The VAs 2014 RAC report reinforced its 2008 report findings: "The research reviewed in this report supports and reinforces the conclusion in the 2008 RACGWVI report that exposures to pesticides and pyridostigmine bromide are causally associated with Gulf War illness. Evidence also continues to demonstrate that Gulf War illness is not the result of psychological stressors during the war." It also found additional evidence since the 2008 report for the role of sarin in GWI, but inadequate evidence regarding exposures to oil well fires, vaccines, and depleted uranium to make new conclusions about them. Oil well fires During the war, many oil wells were set on fire in Kuwait by the retreating Iraqi army, and the smoke from those fires was inhaled by large numbers of soldiers, many of whom had acute pulmonary and other chronic effects, including asthma and bronchitis. However, firefighters who were assigned to the oil well fires and encountered the smoke, but who did not take part in combat, have not had GWI symptoms.: 148, 154, 156  The 2008 RAC report states that "evidence [linking oil well fires to GWI] is inconsistent or limited in important ways." Anthrax vaccine Iraq had loaded anthrax, botulinum toxin, and aflatoxin into missiles and artillery shells in preparing for the Gulf War and these munitions were deployed to four locations in Iraq. During Operation Desert Storm, 41% of U.S. combat soldiers and 75% of UK combat soldiers were vaccinated against anthrax.: 73  Reactions included local skin irritation, some lasting for weeks or months. While the Food and Drug Administration (FDA) approved the vaccine, it never went through large-scale clinical trials.While recent studies have demonstrated the vaccine is highly reactogenic, there is no clear evidence or epidemiological studies on Gulf War veterans linking the vaccine to Gulf War illness. Combining this with the lack of symptoms from current deployments of individuals who have received the vaccine led the Committee on Gulf War Veterans Illnesses to conclude that the vaccine is not a likely cause of Gulf War illness for most ill veterans. However, the committee report does point out that veterans who received a larger number of various vaccines in advance of deployment have shown higher rates of persistent symptoms since the war.However, research was done by PB Asa, Y Cao, and RF Garry on serum antibodies to squalene in Gulf War Syndrome patients. The results showed "the substantial majority (95%) of overtly ill deployed GWS patients had antibodies to squalene. All (100%) GWS patients immunized for service in Desert Shield/Desert Storm who did not deploy, but had the same signs and symptoms as those who did deploy, had antibodies to squalene. In contrast, none (0%) of the deployed Persian Gulf veterans not showing signs and symptoms of GWS have antibodies to squalene. Neither patients with idiopathic autoimmune disease nor healthy controls had detectable serum antibodies to squalene." Their work of the researchers was profiled by Gary Matsumoto in "Vaccine A". Combat stress Research studies conducted since the war have consistently indicated that psychiatric illness, combat experience or other deployment-related stressors do not explain Gulf War veterans illnesses in the large majority of ill veterans, according to a U.S. Department of Veterans Affairs (VA) review committee.An April 2010 Institute of Medicine review found, "the excess of unexplained medical symptoms reported by deployed [1991] Gulf war veterans cannot be reliably ascribed to any known psychiatric disorder", although they also concluded that "the constellation of unexplained symptoms associated with the Gulf War illness complex could result from interplay between both biological and psychological factors." Pathobiology Chronic inflammation The 2008 VA report on Gulf War illness and the Health of Gulf War Veterans suggested a possible link between GWI and chronic, nonspecific inflammation of the central nervous system that cause pain, fatigue and memory issues, possibly due to pathologically persistent increases in cytokines and suggested further research be conducted on this issue. Diagnosis Clinical diagnosis of Gulf War illness has been complicated by multiple case definitions. In 2014, the National Academy of Sciences Institute of Medicine (IOM)—contracted by the U.S. Department of Veterans Affairs for the task—released a report concluding that the creation of a new case definition for chronic multisymptom illness in Gulf War veterans was not possible because of insufficient evidence in published studies regarding its onset, duration, severity, frequency of symptoms, exclusionary criteria, and laboratory findings. Instead, the report recommended the use of two case definitions, the "Kansas" definition and the "Centers for Disease Control and Prevention (CDC)" definition, noting: "There is a set of symptoms (fatigue, pain, neurocognitive) that are reported in all the studies that have been reviewed. The CDC definition captures those three symptoms; the Kansas definition also captures them, but it also includes the symptoms reported most frequently by Gulf War veterans."The Kansas case definition is more specific and may be more applicable for research settings, while the CDC case definition is more broad and may be more applicable for clinical settings. Classification Medical ailments associated with service in the 1990–1991 Gulf War have been recognized by both the U.S. Department of Defense and the U.S. Department of Veterans Affairs.Before 1998, the terms Gulf War syndrome, Gulf War veterans illness, unexplained illness, and undiagnosed illness were used interchangeably to describe chronic unexplained symptoms in veterans of the 1991 Gulf War. The term chronic multisymptom illness (CMI) was first used following publication of a 1998 study describing chronic unexplained symptoms in Air Force veterans of the 1991 Gulf War.In a 2014 report contracted by the U.S. Department of Veterans Affairs, the National Academy of Sciences Institute of Medicine recommended the use the term Gulf War illness rather than chronic multisymptom illness. Since that time, relevant publications by the National Academy of Science and the U.S. Department of Defense have used only the term Gulf War illness (GWI).The U.S. Department of Veterans Affairs (VA) confusingly still uses an array of both old and new terminology for Gulf War illness. VAs specialty clinical evaluation War Related Illness and Injury Study Centers (WRIISCs) use the recommended term Gulf War illness, as do VAs Office of Research and Development (VA-ORD) and many recent VA research publications. However, VAs Public Health website still uses Gulf War veterans medically unexplained illnesses, chronic multi-symptom illness (CMI), and undiagnosed illnesses, but explains that VA doesnt use the term Gulf War syndrome because of varying symptoms.The Veterans Health Administration (VHA) originally classified individuals with related ailments believed to be connected to their service in the Persian Gulf a special non-ICD-9 code DX111, as well as ICD-9 code V65.5. Kansas definition In 1998, the State of Kansas Persian Gulf Veterans Health Initiative sponsored an epidemiological survey led by Dr. Lea Steele of deployment-related symptoms in 2,030 Gulf War veterans. The result was a "clinically based descriptive definition using correlated symptoms" in six symptom groups: fatigue and sleep problems, pain, neurologic and mood, gastrointestinal, respiratory symptoms, and skin (dermatologic) symptoms.To meet the "Kansas" case definition, a veteran of the 1990–91 Gulf War must have symptoms in at least three of the six symptom domains, which during the survey were scored based on severity ("severity"). Symptom onset must have developed during or after deploying to the 1990–91 Gulf War theatre of operations ("onset") and must have been present in the year before interview ("duration"). Participants were excluded if they had a diagnosis of or were being treated for any of several conditions that might otherwise explain their symptoms ("exclusionary criteria"), including cancer, diabetes, heart disease, chronic infectious disease, lupus, multiple sclerosis, stroke, or any serious psychiatric condition.Applying the Kansas case definition to the original Kansas study cohort resulted in a prevalence of Gulf War illness of 34.2% in Gulf War veterans and 8.3% in nondeployed Gulf War era veterans, or an excess rate of GWI of 26.3% in Gulf War veterans. CDC definition Also in 1998, a study published by Dr. Keiji Fukuda under the auspices of the U.S. Centers for Disease Control and Prevention (CDC) examined chronic multisymptom illness through a cross-sectional survey of 3,675 ill and healthy U.S. Air Force veterans of the 1990–91 Gulf War, including from a Pennsylvania-based Air National Guard unit and three comparison Air Force units. The CDC case definition was derived from clinical data and statistical analyses.The result was a symptom-category approach to a case definition, with three symptom categories: fatigue, mood–cognition, and musculoskeletal. To meet the case definition, the veteran of the 1990–91 Gulf War must have symptoms in two of the three categories and have experienced the illness for six months or longer ("duration").The original study also including a determination of severity of symptoms ("severity"). "Severe cases were identified if at least one symptom in each of the required categories was rated as severe. Of 1,155 participating Gulf War veterans, 6% had severe CMI, and 39% had mild to moderate CMI; of the 2,520 nondeployed era veterans Of 1,155 participating Gulf War veterans, 6% had severe CMI, and 39% had mild to moderate CMI; of the 2,520 nondeployed era veterans, 0.7% had severe and 14% had mild to moderate CMI." Treatment A 2013 report by the Institute of Medicine reviewed the peer-reviewed published medical literature for evidence regarding treatments for symptoms associated with chronic multisymptom illness (CMI) in 1990–91 Gulf War veterans, and in other chronic multisymptom conditions. For the studies the report reviewed that were specifically regarding CMI in 1990–91 Gulf War veterans (Gulf War illness), the report made the following conclusions: Doxycycline: "Although the study of doxycycline was found to have high strength of evidence and was conducted in a group of 1991 Gulf War veterans who had CMI, it did not demonstrate efficacy; that is, doxycycline did not reduce or eliminate the symptoms of CMI in the study population." Cognitive Behavioral Therapy (CBT) and Exercise: "These studies evaluated the effects of exercise and CBT in combination and individually. The therapeutic benefit of exercise was unclear in those studies. Group CBT rather than exercise may confer the main therapeutic benefit with respect to physical symptoms."The report concluded: "On the basis of the evidence reviewed, the committee cannot recommend any specific therapy as a set treatment for [Gulf War] veterans who have CMI. The committee believes that a one-size-fits-all approach is not effective for managing [Gulf War] veterans who have CMI and that individualized health care management plans are necessary."By contrast, the U.S. Department of Defense (DoD) noted in a May 2018 publication that the primary focus of its Gulf War illness Research Program (GWIRP) "has been to fund research studies to identify treatment targets and test interventional approaches to alleviate symptoms. While most of these studies remain in progress, several have already shown varying levels of promise as GWI treatments." According to the May 2018 DoD publication: Published Results on Treatments The earliest federally funded multi-center clinical trials were VA- and DoD-funded trials that focused on antibiotic treatment (doxycycline) (Donta, 2004) and cognitive behavioral therapy with exercise (Donta, 2003). Neither intervention provided long-lasting improvement for a substantial number of Veterans. Preliminary analysis from a placebo-controlled trial showed that 100 mg of Coenzyme Q10 (known as CoQ10 or Ubiquinone) significantly improved general self-reported health and physical functioning, including among 20 symptoms, each of which was present in at least half of the study participants, with the exception of sleep. These improvements included reducing commonly reported symptoms of fatigue, dysphoric mood, and pain (Golomb, 2014). These results are currently being expanded in a GWIRP-funded trial of a "mitochondrial cocktail" for GWI of CoQ10 plus a number of nutrients chosen to support cellular energy production and defend against oxidative stress. The treatment is also being investigated in a larger, VA- sponsored Phase III trial of Ubiquinol, the reduced form of CoQ10. In a randomized, sham-controlled VA-funded trial of a nasal CPAP mask (Amin, 2011-b), symptomatic GW Veterans with sleep-disordered breathing receiving the CPAP therapy showed significant improvements in fatigue scores, cognitive function, sleep quality, and measures of physical and mental health (Amin, 2011a). Preliminary data from a GWIRP-funded acupuncture treatment study showed that Veterans reported significant reductions in pain and both primary and secondary health complaints, with results being more positive in the bi-weekly versus weekly treatment group (Conboy, 2012). Current studies funded by the GWIRP and the VA are also investigating yoga as a treatment for GWI. An amino acid supplement containing L-carnosine was found to reduce irritable bowel syndrome-associated diarrhea in a randomized, controlled GWIRP-funded trial in GW Veterans (Baraniuk, 2013). Veterans receiving L-carnosine showed a significant improvement in performance in a cognitive task, but no improvement in fatigue, pain, hyperalgesia, or activity levels. Results from a 26 week GWIRP-funded trial comparing standard care to nasal irrigation with either saline or a xylitol solution revealed that both irrigation protocols reduced GWI respiratory (chronic rhinosinusitis) and fatigue symptoms (Hayer, 2015). Administration of the glucocorticoid receptor antagonist mifepristone to GW Veterans in a GWIRP-funded randomized trial resulted in an improvement in verbal learning, but no improvement in self-reported physical health or other self-reported measures of mental health (Golier, 2016).Ongoing Intervention Studies The GWIRP is currently funding many early-phase clinical trials aimed at GWI. Interventions include direct electrical nerve stimulation, repurposing FDA-approved pharmaceuticals, and dietary protocols and/or nutraceuticals. Both ongoing and closed GWIRP-supported clinical treatment trials and pilot studies can be found at [1]. A Clinical Consortium Award was offered [in FY2017] to support a group of institutions, coordinated through an Operations Center that will conceive, design, develop, and conduct collaborative Phase I and II clinical evaluations of promising therapeutic agents for the management or treatment of GWI. These mechanisms were designed to build on the achievements of the previously established consortia and to further promote collaboration and resource sharing. The U.S Congress has made significant and continuing investment in DoDs Gulf War illness treatment research, with $129 million appropriated for the GWIRP between federal fiscal years (FY) 2006 and 2016. The funding has risen from $5 million in FY2006, to $20 million each year from FY2013 through FY2017, and to $21 million for FY2018. Prognosis According to the May 2018 DoD publication cited above, "Research suggests that the GWI symptomology experienced by Veterans has not improved over the last 25 years, with few experiencing improvement or recovery ... . Many [Gulf War] Veterans will soon begin to experience the common co-morbidities associated with aging. The effect that aging will have on this unique and vulnerable population remains a matter of significant concern, and population-based research to obtain a better understanding of mortality, morbidity, and symptomology over time is needed." Prevalence The 2008 and 2014 VA (RAC) reports and the 2010 IOM report found that the chronic multisymptom illness in Gulf War veterans—Gulf War illness—is more prevalent in Gulf War veterans than their non-deployed counterparts or veterans of previous conflicts. While a 2009 study found the pattern of comorbidities similar for actively deployed and nondeployed Australian military personnel, the large body of U.S. research reviewed in the VA and IOM reports showed the opposite in U.S. troops. The VAs 2014 RAC report found Gulf War illness in "an excess of 26–32 percent of Gulf War veterans compared to nondeployed era veterans" in pre-2008 studies, and "an overall multisymptom illness prevalence of 37 percent in Gulf War veterans and an excess prevalence of 25 percent" in a later, larger VA study.According to a May 2018 report by the U.S. Department of Defense, "GWI is estimated to have affected 175,000 to 250,000 of the nearly 700,000 troops deployed to the 1990–1991 GW theater of operations. Twenty-seven of the 28 Coalition members participating in the GW conflict have reported GWI in their troops. Epidemiologic studies indicate that rates of GWI vary in different subgroups of GW Veterans. GWI affects Veterans who served in the U.S. Army and Marines Corps at higher rates than those who served in the Navy and Air Force, and U.S. enlisted personnel are affected more than officers. Studies also indicate that GWI rates differ according to where Veterans were located during deployment, with the highest rates among troops who served in forward areas." Research Epidemiologic studies have looked at many suspected causal factors for Gulf War illness as seen in veteran populations. Below is a summary of epidemiologic studies of veterans displaying multisymptom illness and their exposure to suspect conditions from the 2008 U.S. Department of Veterans Affairs report.A fuller understanding of immune function in ill Gulf War veterans is needed, particularly in veteran subgroups with different clinical characteristics and exposure histories. It is also important to determine the extent to which identified immune perturbations may be associated with altered neurological and endocrine processes that are associated with immune regulation. Very limited cancer data have been reported for U.S. Gulf War veterans in general, and no published research on cases occurring after 1999. Because of the extended latency periods associated with most cancers, it is important that cancer information is brought up to date and that cancer rates be assessed in Gulf War veterans on an ongoing basis. In addition, cancer rates should be evaluated in relation to identifiable exposure and location subgroups. Controversies An early argument in the years following the Gulf War was that similar syndromes have been seen as an after effect of other conflicts — for example, "shell shock" after World War I, and post-traumatic stress disorder (PTSD) after the Vietnam War. Cited as evidence for this argument was a review of the medical records of 15,000 American Civil War soldiers showing that "those who lost at least 5% of their company had a 51% increased risk of later development of cardiac, gastrointestinal, or nervous disease."Early Gulf War research also failed to accurately account for the prevalence, duration, and health impact of Gulf War illness. For example, a November 1996 article in the New England Journal of Medicine found no difference in death rates, hospitalization rates, or self-reported symptoms between Persian Gulf veterans and non-Persian Gulf veterans. This article was a compilation of dozens of individual studies involving tens of thousands of veterans. The study did find a statistically significant elevation in the number of traffic accidents Gulf War veterans had. An April 1998 article in Emerging Infectious Diseases similarly found no increased rate of hospitalization and better health on average for veterans of the Persian Gulf War in comparison to those who stayed home.In contrast to those early studies, in January 2006, a study led by Melvin Blanchard published in the Journal of Epidemiology, part of the "National Health Survey of Gulf War-Era Veterans and Their Families", found that veterans deployed in the Persian Gulf War had nearly twice the prevalence of chronic multisymptom illness, a cluster of symptoms similar to a set of conditions often at that time called Gulf War Syndrome. On November 17, 2008, the Department of Veterans Affairs (VA) Research Advisory Committee on Gulf War Veterans Illnesses (RAC), a Congressionally mandated federal advisory committee composed of VA-appointed clinicians, researchers, and representative Gulf War veterans, issued a major report announcing scientific findings, in part, that "Gulf War illness is real", that GWI is a distinct physical condition, and that it is not psychological in nature. The 454 page report reviewed 1,840 published studies to form its conclusions identifying the high prevalence of Gulf War illness, suggesting likely causes rooted in toxic exposures while ruling out combat stress as a cause, and opining that treatments likely could be found. It recommended that Congress increase funding for treatment-focused Gulf War illness research to at least $60 million per year.In March 2013, a hearing was held before the Subcommittee on Oversight and Investigations of the Committee on Veterans Affairs, U.S. House of Representatives, to determine not whether Gulf War illness exists, but rather how it is identified, diagnosed and treated, and how the tools put in place to aid these efforts have been used.By 2016, the National Academy of Sciences, Engineering, and Medicine (NASEM) concluded there was sufficient evidence of a positive association between deployment to the 1990–1991 Gulf War and Gulf War illness. Jones controversy Louis Jones Jr., the perpetrator of the 1995 murder of Tracie McBride, stated that the Gulf War syndrome caused him to commit the crime and he sought clemency, hoping to avoid the death penalty given to him by a federal court. Jones was executed in 2003. Related legislation On March 14, 2014, Representative Mike Coffman introduced the Gulf War Health Research Reform Act of 2014 (H.R. 4261; 113th Congress) into the United States House of Representatives, where it passed the House by unanimous consent but then died in Congress when the Senate failed to take action on it. The bill would have altered the relationship between the Research Advisory Committee on Gulf War Veterans Illnesses (RAC) and the United States Department of Veterans Affairs (VA) under which the RAC is constituted. The bill would have made the RAC an independent organization within the VA, require that a majority of the RACs members be appointed by Congress instead of the VA, and authorized the RAC to release its reports without needing prior approval from the VA Secretary. The RAC is responsible for investigating Gulf War illness, a chronic multisymptom disorder affecting returning military veterans of the 1990–91 Gulf War.In the year prior to the consideration of this bill, the VA and the RAC were at odds with one another. The VA replaced all but one of the members of the RAC, removed some of their supervisory tasks, tried to influence the board to decide that stress, rather than biology was the cause of Gulf War illness, and told the RAC that it could not publish reports without permission. The RAC was created after Congress decided that the VAs research into the issue was flawed, and focused on psychological causes, while mostly ignoring biological ones.The RAC was first authorized under the Veterans Programs Enhancement Act of 1998 (Section 104 of Public Law 105–368, enacted November 11, 1998, and now codified as 38 U.S.C. § 527 note). While the law directing its creation mandated that it be established not later than January 1, 1999, the RACs first charter was not issued until January 23, 2002, by VA Secretary Anthony Principi. The RAC convened for its first meetings on April 11–12, 2002. See also Organophosphate-induced delayed neuropathy Environmental issues with war Michael Donnelly, an activist for those affected by Gulf War illness Post-traumatic stress disorder Burn pits References External links Gulf War syndrome at Curlie

Hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH), also known as haemophagocytic lymphohistiocytosis (British spelling), and hemophagocytic or haemophagocytic syndrome, is an uncommon hematologic disorder seen more often in children than in adults. It is a life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages, characterised by proliferation of morphologically benign lymphocytes and macrophages that secrete high amounts of inflammatory cytokines. It is classified as one of the cytokine storm syndromes. There are inherited and non-inherited (acquired) causes of hemophagocytic lymphohistiocytosis (HLH). Signs and symptoms The onset of HLH occurs before the age of one year in approximately 70 percent of cases. Familial HLH should be suspected if siblings are diagnosed with HLH or if symptoms recur when therapy has been stopped. Familial HLH is an autosomal recessive disease, hence each sibling of a child with familial HLH has a twenty-five–percent chance of developing the disease, a fifty-percent chance of carrying the defective gene (which is very rarely associated with any risk of disease), and a twenty-five–percent chance of not being affected and not carrying the gene defect.Patients with HLH, especially when untreated, may need intensive therapy. Therefore, HLH should be included in the differential diagnosis of intensive care unit patients with cytopenia and hyperferritinemia. Patients in the earlier stages of HLH are frequently hospitalized at internal medicine wards.HLH clinically manifests with fever, enlargement of the liver and spleen, enlarged lymph nodes, yellow discoloration of the skin and eyes, and a rash. Laboratory findings may include elevated triglyceride levels, low fibrinogen levels, transaminitis, and elevated ferritin levels (among others). Causes Primary HLH is caused by loss of function, (i.e. inactivating) mutations in genes that code for proteins cytotoxic T cells and NK cells use to kill targeted cells, such as those infected with pathogens like the Epstein-Barr virus (EBV) or the Dengue virus. These mutations include those in the following genes: UNC13D, STX11, RAB27A, STXBP2, LYST, PRF1 1, SH2D1A, BIRC4, ITK, CD27, and MAGT1.Secondary HLH (sHLH) is associated with, and thought to be promoted by, malignant and non-malignant diseases that likewise weaken the ability of the immune system to attack EBV-infected cells. Malignant disorders associated with secondary HLH include T-cell lymphoma, B-cell lymphoma, acute lymphocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome. Non-malignant disorders associated with secondary HLH include: autoimmune disorders such as juvenile idiopathic arthritis, juvenile Kawasaki disease, systemic lupus erythematosus, the juvenile onset and adult onset forms of Stills disease, and rheumatoid arthritis; immunodeficiency disorders such as severe combined immunodeficiency, DiGeorge syndrome, Wiskott–Aldrich syndrome, ataxia–telangiectasia, and dyskeratosis congenita); and infections caused by EBV, cytomegalovirus, HIV/AIDS, bacteria, protozoa, fungi and SARS-CoV-2. Secondary HLH may also result from iatrogenic causes such as bone marrow or other organ transplantations; chemotherapy; or therapy with immunosuppressing agents;About 33% of all HLH cases, ~75% of Asian HLH cases, and nearly 100% of HLH cases caused by mutations in SH2D1A (see X-linked lymphoproliferative disease type 1) are associated with, and thought triggered or promoted by, EBV infection. These cases of HLH are classified as belonging to the class of Epstein–Barr_virus–associated_lymphoproliferative_diseases and termed EBV+ HLH. Genetics Five genetic subtypes (FHL1, FHL2, FHL3, FHL4, and FHL5) are described, with an estimated overall prevalence of one in 50,000 and equal gender distribution. Molecular genetic testing for four of the causative genes, PRF1 (FHL2), UNC13D (FHL3), STX11 (FHL4), and STXBP2 (FHL5), is available on a clinical basis. Symptoms of FHL are usually evident within the first few months of life and may even develop in utero. However, symptomatic presentation throughout childhood and even into young adulthood has been observed in some cases.The five subtypes of FHL are each associated with a specific gene: FHL1: HPLH1 FHL2: PRF1 (Perforin) FHL3: UNC13D (Munc13-4) FHL4: STX11 (Syntaxin 11) FHL5: STXBP2 (Syntaxin binding protein 2)/UNC18-2Nearly half of the cases of type 2 familial hemophagocytic lymphohistiocytosis are due to bi-allelic PRF1 mutations. Pathophysiology The underlying causes, either inherited or acquired, lead to an unchecked immune response when exposed to triggers. Impaired NK-cell cytotoxicity is the hallmark of HLH. All genetic defects for familial HLH are related to granule-dependent cytotoxicity. This inability to remove infected and antigen-presenting cells and terminate the immune response leads to uncontrolled proliferation and activation of the immune system with release of excessive cytokines. These cells then infiltrate organs, releasing more cytokines, which gives the clinical picture. The fever is caused by IL-1, IL-6 and TNF-alpha; the cytopenia is due to the suppressive effect on hematopoiesis by TNF-alpha and TNF-gamma. TNF-alpha and TNF-gamma may also lead to inhibition of lipoprotein lipase or stimulate triglyceride synthesis. Activated macrophages secrete ferritin and plasminogen activator leading to hyperfibrinolysis. Diagnosis The blood count typically shows decreased numbers of blood cells—including a decreased number of circulating red blood cells, white blood cells, and platelets. The bone marrow may show hemophagocytosis. The liver function tests are usually elevated. A low level of the protein albumin in the blood is common.The serum C reactive protein, erythrocyte sedimentation rate, and ferritin level are markedly elevated. In children, a ferritin above 10000 is very sensitive and specific for the diagnosis of HLH, however, the diagnostic utility for ferritin is less for adult HLH patients.The serum fibrinogen level is usually low and the D-dimer level is elevated. The sphingomyelinase is elevated.Bone marrow biopsy shows histiocytosis. Classification Primary HLH, also known as familial haemophagocytic lymphohistiocytosis (FHL) or familial erythrophagocytic lymphohistiocytosis, is a heterogeneous autosomal recessive disorder found to be more prevalent with parental consanguinity.Secondary haemophagocytic lymphohistiocytosis (acquired haemophagocytic lymphohistiocytosis) occurs after strong immunologic activation, such as that which can occur with systemic infection, immunodeficiency, or underlying malignancy.Both forms are characterized by the overwhelming activation of normal T lymphocytes and macrophages, invariably leading to clinical and haematologic alterations and death in the absence of treatment.A subtype of primary HLH where the inflammation is limited to the central nervous system has been described. Diagnostic criteria The current (2008) diagnostic criteria for HLH are1. A molecular diagnosis consistent with HLH. These include the identification of pathologic mutations of PRF1, UNC13D, or STX11. OR 2. Fulfillment of five out of the eight criteria below: Fever (defined as a temperature >100.3 °F, >38 °C) Enlargement of the spleen Decreased blood cell counts affecting at least two of three lineages in the peripheral blood: Haemoglobin <9 g/100 ml (in infants <4 weeks: haemoglobin <10 g/100 ml) (anemia) Platelets <100×109/L (thrombocytopenia) Neutrophils <1×109/L (neutropenia) High blood levels of triglycerides (fasting, greater than or equal to 265 mg/100 ml) and/or decreased amounts of fibrinogen in the blood (≤ 150 mg/100 ml) Ferritin ≥ 500 ng/ml Haemophagocytosis in the bone marrow, spleen or lymph nodes Low or absent natural killer cell activity Soluble CD25 (soluble IL-2 receptor) >2400 U/ml (or per local reference laboratory)In addition, in the case of familial HLH, no evidence of malignancy should be apparent. Not all five out of eight criteria are required for diagnosis of HLH in adults, and a high index of suspicion is required for diagnosis as delay results in increased mortality. The diagnostic criteria were developed in pediatric populations and have not been validated for adult HLH patients. Attempts to improve diagnosis of HLH have included use of the HScore, which can be used to estimate an individuals risk of HLH. In adults, soluble IL-2 receptor has been found to be a very sensitive marker for HLH, demonstrating 100% sensitivity for ruling out HLH below a cutoff of 2400 U/mL and optimal cutoff for ruling in at 2515 U/mL (sensitivity, 100%; specificity, 72.5%), with 93% specificity at >10 000 U/mL. Differential diagnosis The differential diagnosis of HLH includes secondary HLH and macrophage-activation syndrome or other primary immunodeficiencies that present with hemophagocytic lymphohistiocytosis, such as X-linked lymphoproliferative disease.Other conditions that may be confused with this condition include autoimmune lymphoproliferative syndrome. As a syndrome of intense inflammation it needs to be differentiated from sepsis, which may be extremely challenging.The diagnosis of acquired, or secondary, HLH is usually made in association with infection by viruses, bacteria, fungi, or parasites or in association with lymphoma, autoimmune disease, or metabolic disease. Acquired HLH may have decreased, normal, or increased NK cell activity. Griscelli syndrome A major differential diagnosis of HLH is Griscelli syndrome (type 2). This is a rare autosomal recessive disorder characterized by partial albinism, hepatosplenomegaly, pancytopenia, hepatitis, immunologic abnormalities, and lymphohistiocytosis. Most cases have been diagnosed between 4 months and 7 years of age, with a mean age of about 17 months.Three types of Griscelli syndrome are recognised: type 1 has neurologic symptoms and mutations in MYO5A. Prognosis depends on the severity of neurologic manifestations. Type 2 has mutations in RAB27A and haemophagocytic syndrome, with abnormal T-cell and macrophage activation. This type has a grave prognosis if untreated. Type 3 has mutations in melanophilin and is characterized by partial albinism. This type does not pose a threat to those so affected. Treatment In secondary cases, treatment of the cause, where possible, is indicated. Additionally, treatment for HLH itself is usually required.While optimal treatment of HLH is still being debated, current treatment regimes usually involve high dose corticosteroids, etoposide and cyclosporin. Intravenous immunoglobulin is also used. Methotrexate and vincristine have also been used. Other medications include cytokine targeted therapy.On 20 November 2018, the FDA approved the anti-IFN-gamma monoclonal antibody emapalumab (proprietary name Gamifant) for the treatment of pediatric and adult primary HLH.In October 2021 NHS England published Clinical Commissioning Policy: Anakinra for Haemophagocytic Lymphohistiocytosis (HLH) for adults and children in all ages, allowing Anakinra (a modified recombinant interleukin 1 receptor antagonist) to be used in the treatment of HLH. Prognosis The prognosis is guarded with an overall mortality of 50%. Poor prognostic factors included HLH associated with malignancy, with half the patients dying by 1.4 months compared to 22.8 months for non-tumour associated HLH patients.Secondary HLH in some individuals may be self-limited because patients are able to fully recover after having received only supportive medical treatment (i.e., IV immunoglobulin only). However, long-term remission without the use of cytotoxic and immune-suppressive therapies is unlikely in the majority of adults with HLH and in those with involvement of the central nervous system (brain and/or spinal cord). History The first case report of HLH was published in 1939 under the term HISTIOCYTIC MEDULLARY RETICULOSIS. A second report would come out in 1952 that would rename the disorder in 1952. Research A systematic review recently reported the pooled proportion are fever 97.2%, hepatomegaly 70.2%, splenomegaly 78.4%, thrombocytopenia 90.1%, anemia 76.0%, and serum ferritin ≥500 μg/L 97.1%. The case fatality rate is 14.6% among dengue hemophagocytic lymphohistiocytosis patients. See also Emperipolesis X-linked lymphoproliferative disease#XLP2 References == External links ==

Carnitine palmitoyltransferase I deficiency

Carnitine palmitoyltransferase I deficiency is a rare metabolic disorder that prevents the body from converting certain fats called long-chain fatty acids into energy, particularly during periods without food. It is caused by a mutation in CPT1A on chromosome 11.Carnitine, a natural substance acquired mostly through the diet, is used by cells to process fats and produce energy. People with this disorder have a faulty enzyme, carnitine palmitoyltransferase I, that prevents these long-chain fatty acids from being transported into the mitochondria to be broken down. Symptoms and signs Signs and symptoms of this disorder include low levels of ketones (hypoketosis) and low blood sugar (hypoglycemia). Together these signs are called hypoketotic hypoglycemia. People with this disorder typically also have an enlarged liver (hepatomegaly), muscle weakness, and elevated levels of carnitine in the blood. Genetics Mutations in the CPT1A gene cause carnitine palmitoyltransferase I deficiency by producing a defective version of an enzyme called carnitine palmitoyltransferase I. Without this enzyme, long-chain fatty acids from food and fats stored in the body cannot be transported into mitochondria to be broken down and processed. As a result, excessive levels of long-chain fatty acids may more rapidly build up in tissues, damaging the liver, heart and/or brain. This condition has an autosomal recessive inheritance pattern, which means the defective gene must be inherited from both parents. The parents of a child with an autosomal recessive disorder are carriers of one copy of the defective gene, but are usually not affected by the disorder.The prevalence of mutations associated with this condition reach 68% to 81% in certain arctic coastal populations, suggesting that the condition had some adaptive value in those habitats at some time. Fewer than 50 people have been identified with this condition. Diagnosis Genetic testing is necessary for diagnosis. Differential diagnosis This condition is sometimes mistaken for fatty acid and ketogenesis disorders such as Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCAD), other long-chain fatty acid oxidation disorders such as Carnitine palmitoyltransferase II deficiency (CPT-II) and Reye syndrome. Treatment Treatment for this condition is supportive. There is no cure. Affected people should eat a high-carbohydrate, low-fat diet and avoid fasting. See also Primary carnitine deficiency Carnitine palmitoyltransferase II deficiency References External links This article incorporates public domain text from The U.S. National Library of Medicine

Osteoclast

An osteoclast (from Ancient Greek ὀστέον (osteon) bone, and κλαστός (clastos) broken) is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated protein and mineral at a molecular level by secreting acid and a collagenase, a process known as bone resorption. This process also helps regulate the level of blood calcium. Osteoclasts are found on those surfaces of bone which are undergoing resorption. On such surfaces, the osteoclasts are seen to be located in shallow depressions called resorption bays (Howships lacunae). The resorption bays are created by erosive action of osteoclasts on the underlying bone. The border of the lower part of an osteoclast exhibits finger-like processes due to presence of deep infoldings of the cell membrane; this border is called ruffled border. The ruffled border lies in contact with the bone surface within a resorption bay. The periphery of the ruffled border is surrounded by a ring-like zone of cytoplasm which is devoid of cell organelles but is rich in actin filaments. This zone is called clear zone or sealing zone. The actin filaments enable the cell membrane surrounding the sealing zone to be anchored firmly to the bony wall of Howships lacunae. In this way, a closed subosteoclastic compartment is created between the ruffled border and the bone that is undergoing resorption. The osteoclasts secrete hydrogen ions, collagenase, cathepsin K and hydrolytic enzymes into this compartment. Resorption of bone matrix by the osteoclasts involves two steps: (1) dissolution of inorganic components (minerals), and (2) digestion of organic component of the bone matrix. The osteoclasts pump hydrogen ions into subosteoclastic compartment and thus create an acidic microenvironment, which increases solubility of bone mineral, resulting in the release and re-entry of bone minerals into the cytoplasm of osteoclasts to be delivered to nearby capillaries. After the removal of minerals, collagenase and gelatinase are secreted into the subosteoclastic compartment. These enzymes digest and degrade collagen and other organic components of decalcified bone matrix. The degradation products are phagocytosed by osteoclasts at the ruffled border. Because of their phagocytic properties, osteoclasts are considered to be a component of the mononuclear phagocyte system (MPS). The activity of osteoclasts is controlled by hormones and cytokines. Calcitonin, a hormone of thyroid gland, suppresses the osteoclastic activity. The osteoclasts do not have receptors for parathyroid hormone (PTH). However, PTH stimulates the osteoblasts to secrete the cytokine called osteoclast-stimulating factor, which is a potent stimulator of the osteoclastic activity.An odontoclast (/odon·to·clast/; o-don´to-klast) is an osteoclast associated with absorption of the roots of deciduous teeth. Structure An osteoclast is a large multinucleated cell and human osteoclasts on bone typically have five nuclei and are 150–200 µm in diameter. When osteoclast-inducing cytokines are used to convert macrophages to osteoclasts, very large cells that may reach 100 µm in diameter occur. These may have dozens of nuclei, and typically express major osteoclast proteins but have significant differences from cells in living bone because of the not-natural substrate. The size of the multinucleated assembled osteoclast allows it to focus the ion transport, protein secretory and vesicular transport capabilities of many macrophages on a localized area of bone. Location In bone, osteoclasts are found in pits in the bone surface which are called resorption bays, or Howships lacunae. Osteoclasts are characterized by a cytoplasm with a homogeneous, "foamy" appearance. This appearance is due to a high concentration of vesicles and vacuoles. These vacuoles include lysosomes filled with acid phosphatase. This permits characterization of osteoclasts by their staining for high expression of tartrate resistant acid phosphatase (TRAP) and cathepsin K. Osteoclast rough endoplasmic reticulum is sparse, and the Golgi complex is extensive.At a site of active bone resorption, the osteoclast forms a specialized cell membrane, the "ruffled border", that opposes the surface of the bone tissue. This extensively folded or ruffled border facilitates bone removal by dramatically increasing the cell surface for secretion and uptake of the resorption compartment contents and is a morphologic characteristic of an osteoclast that is actively resorbing bone. Development Since their discovery in 1873 there has been considerable debate about their origin. Three theories were dominant: from 1949 to 1970 the connective tissue origin was popular, which stated that osteoclasts and osteoblasts are of the same lineage, and osteoblasts fuse together to form osteoclasts. After years of controversy it is now clear that these cells develop from the self fusion of macrophages. It was in the beginning of 1980 that the monocyte phagocytic system was recognized as precursor of osteoclasts. Osteoclast formation requires the presence of RANKL (receptor activator of nuclear factor κβ ligand) and M-CSF (Macrophage colony-stimulating factor). These membrane-bound proteins are produced by neighbouring stromal cells and osteoblasts, thus requiring direct contact between these cells and osteoclast precursors. M-CSF acts through its receptor on the osteoclast, c-fms (colony-stimulating factor 1 receptor), a transmembrane tyrosine kinase-receptor, leading to secondary messenger activation of tyrosine kinase Src. Both of these molecules are necessary for osteoclastogenesis and are widely involved in the differentiation of monocyte/macrophage derived cells. RANKL is a member of the tumour necrosis family (TNF), and is essential in osteoclastogenesis. RANKL knockout mice exhibit a phenotype of osteopetrosis and defects of tooth eruption, along with an absence or deficiency of osteoclasts. RANKL activates NF-κβ (nuclear factor-κβ) and NFATc1 (nuclear factor of activated t cells, cytoplasmic, calcineurin-dependent 1) through RANK. NF-κβ activation is stimulated almost immediately after RANKL-RANK interaction occurs and is not upregulated. NFATc1 stimulation, however, begins ~24–48 hours after binding occurs and its expression has been shown to be RANKL dependent. Osteoclast differentiation is inhibited by osteoprotegerin (OPG), which is produced by osteoblasts and binds to RANKL thereby preventing interaction with RANK. It may be important to note that while osteoclasts are derived from the hematopoietic lineage, osteoblasts are derived from mesenchymal stem cells. Function Once activated, osteoclasts move to areas of microfracture in the bone by chemotaxis. Osteoclasts lie in small cavities called Howships lacunae, formed from the digestion of the underlying bone. The sealing zone is the attachment of the osteoclasts plasma membrane to the underlying bone. Sealing zones are bounded by belts of specialized adhesion structures called podosomes. Attachment to the bone matrix is facilitated by integrin receptors, such as αvβ3, via the specific amino acid motif Arg-Gly-Asp in bone matrix proteins, such as osteopontin. The osteoclast releases hydrogen ions through the action of carbonic anhydrase (H2O + CO2 → HCO3− + H+) through the ruffled border into the resorptive cavity, acidifying and aiding dissolution of the mineralized bone matrix into Ca2+, H3PO4, H2CO3, water and other substances. Dysfunction of the carbonic anhydrase has been documented to cause some forms of osteopetrosis. Hydrogen ions are pumped against a high concentration gradient by proton pumps, specifically a unique vacuolar-ATPase. This enzyme has been targeted in the prevention of osteoporosis. In addition, several hydrolytic enzymes, such as members of the cathepsin and matrix metalloprotease (MMP) groups, are released to digest the organic components of the matrix. These enzymes are released into the compartment by lysosomes. Of these hydrolytic enzymes, cathepsin K is of most importance. Cathepsin K and other cathepsins Cathepsin K is a collagenolytic papain-like cysteine protease that is mainly expressed in osteoclasts, and is secreted into the resorptive pit. Cathepsin K is the major protease involved in the degradation of type I collagen and other noncollagenous proteins. Mutations in the cathepsin K gene are associated with pycnodysostosis, a hereditary osteopetrotic disease, characterised by a lack of functional cathepsin K expression. Knockout studies of cathepsin K in mice lead to an osteopetrotic phenotype, which, is partially compensated by increased expression of proteases other that cathepsin K and enhanced osteoclastogenesis. Cathepsin K has an optimal enzymatic activity in acidic conditions. It is synthesized as a proenzyme with a molecular weight of 37kDa, and upon activation by autocatalytic cleavage, is transformed into the mature, active form with a molecular weight of ~27kDa. Upon polarization of the osteoclast over the site of resorption, cathepsin K is secreted from the ruffled border into the resorptive pit. Cathepsin K transmigrates across the ruffled border by intercellular vesicles and is then released by the functional secretory domain. Within these intercellular vesicles, cathepsin K, along with reactive oxygen species generated by TRAP, further degrades the bone extracellular matrix. Several other cathepsins are expressed in osteoclasts including cathepsins B, C, D, E, G, and L. The function of these cysteine and aspartic proteases is generally unknown within bone, and they are expressed at much lower levels than cathepsin K. Studies on cathepsin L knockout mice have been mixed, with a report of reduced trabecular bone in homozygous and heterozygous cathepsin L knockout mice compared to wild-type and another report finding no skeletal abnormalities. Matrix metalloproteinases The matrix metalloproteinases (MMPs) comprise a family of more than 20 zinc-dependent endopeptidases. The role of matrix metalloproteinases (MMPs) in osteoclast biology is ill-defined, but in other tissue they have been linked with tumor promoting activities, such as activation of growth factors and are required for tumor metastasis and angiogenesis. MMP9 is associated with the bone microenvironment. It is expressed by osteoclasts, and is known to be required for osteoclast migration and is a powerful gelatinase. Transgenic mice lacking MMP-9 develop defects in bone development, intraosseous angiogenesis, and fracture repair. MMP-13 is believed to be involved in bone resorption and in osteoclast differentiation, as knockout mice revealed decreased osteoclast numbers, osteopetrosis, and decreased bone resorption. MMPs expressed by the osteoclast include MMP-9, -10, -12, and -14. apart from MMP-9, little is known about their relevance to the osteoclast, however, high levels of MMP-14 are found at the sealing zone. Osteoclast physiology In the 1980s and 90s the physiology of typical osteoclasts was studied in detail. With the isolation of the ruffled border, ion transport across it was studied directly in biochemical detail. Energy-dependent acid transport was verified and the postulated proton pump purified. With the successful culture of osteoclasts, it became apparent that they are organized to support the massive transport of protons for acidification of the resorption compartment and solubilization of the bone mineral. This includes ruffled border Cl− permeability to control membrane potential and basolateral Cl−/HCO3− exchange to maintain cytosolic pH in physiologically acceptable ranges.The effectiveness of its ion secretion depends upon the osteoclast forming an effective seal around the resorption compartment. The positioning of this "sealing zone" appears to be mediated by integrins expressed on the osteoclast surface. With the sealing zone in place, the multinucleated osteoclast reorganizes itself. Developing the highly invaginated ruffled membrane apposing the resorption compartment allows massive secretory activity. In addition, it permits the vesicular transcytosis of the mineral and degraded collagen from the ruffled border to the free membrane of the cell, and its release into the extracellular compartment. This activity completes the bone resorption, and both the mineral components and collagen fragments are released to the general circulation. Regulation Osteoclasts are regulated by several hormones, including parathyroid hormone (PTH) from the parathyroid gland, calcitonin from the thyroid gland, and growth factor interleukin 6 (IL-6). This last hormone, IL-6, is one of the factors in the disease osteoporosis. Osteoporosis occurs when there is an imbalance between the bone resorption activities of osteoclasts and the bone formation activities of osteoblasts.Osteoclast activity is also mediated by the interaction of two molecules produced by osteoblasts, namely osteoprotegerin and RANK ligand. Note that these molecules also regulate differentiation of the osteoclast. Odontoclast An odontoclast (/odon·to·clast/; o-don´to-klast) is an osteoclast associated with absorption of the roots of deciduous teeth. Alternate use of term An osteoclast can also be an instrument used to fracture and reset bones (the origin is Greek osteon: bone and klastos: broken). To avoid confusion, the cell was originally termed osotoclast. When the surgical instrument went out of use, the cell became known by its present name. Clinical significance Giant osteoclasts can occur in some diseases, including Pagets disease of bone and bisphosphonate toxicity. In cats, abnormal odontoclast activity can cause feline odontoclastic resorptive lesions, necessitating extraction of the affected teeth. History Osteoclasts were discovered by Kolliker in 1873. See also List of human cell types derived from the germ layers References External links MedicineNet Osteoclasts at the US National Library of Medicine Medical Subject Headings (MeSH) The Life of Osteoclast Random42: Animation by Random42 Scientific Communication on the role of osteoclasts in bone remodeling

Gallstone

A gallstone is a stone formed within the gallbladder from precipitated bile components. The term cholelithiasis may refer to the presence of gallstones or to any disease caused by gallstones, and choledocholithiasis refers to the presence of migrated gallstones within bile ducts. Most people with gallstones (about 80%) are asymptomatic. However, when a gallstone obstructs the bile duct and causes acute cholestasis, a reflexive smooth muscle spasm often occurs, resulting in an intense cramp-like visceral pain in the right upper part of the abdomen known as a biliary colic (or "gallbladder attack"). This happens in 1–4% of those with gallstones each year. Complications from gallstones may include inflammation of the gallbladder (cholecystitis), inflammation of the pancreas (pancreatitis), obstructive jaundice, and infection in bile ducts (cholangitis). Symptoms of these complications may include pain that lasts longer than five hours, fever, yellowish skin, vomiting, dark urine, and pale stools.Risk factors for gallstones include birth control pills, pregnancy, a family history of gallstones, obesity, diabetes, liver disease, or rapid weight loss. The bile components that form gallstones include cholesterol, bile salts, and bilirubin. Gallstones formed mainly from cholesterol are termed cholesterol stones, and those formed mainly from bilirubin are termed pigment stones. Gallstones may be suspected based on symptoms. Diagnosis is then typically confirmed by ultrasound. Complications may be detected using blood tests.The risk of gallstones may be decreased by maintaining a healthy weight with exercise and a healthy diet. If there are no symptoms, treatment is usually not needed. In those who are having gallbladder attacks, surgery to remove the gallbladder is typically recommended. This can be carried out either through several small incisions or through a single larger incision, usually under general anesthesia. In rare cases when surgery is not possible, medication can be used to dissolve the stones or lithotripsy can be used to break them down.In developed countries, 10–15% of adults experience gallstones. Gallbladder and biliary-related diseases occurred in about 104 million people (1.6% of people) in 2013 and resulted in 106,000 deaths. Gallstones are more common among women than men and occur more commonly after the age of 40. Gallstones occur more frequently among certain ethnic groups than others. For example, 48% of Native Americans experience gallstones, whereas gallstone rates in many parts of Africa are as low as 3%. Once the gallbladder is removed, outcomes are generally positive. Definition Gallstone disease refers to the condition where gallstones are either in the gallbladder or common bile duct. The presence of stones in the gallbladder is referred to as cholelithiasis, from the Greek chol- (bile) + lith- (stone) + -iasis (process). The presence of gallstones in the common bile duct is called choledocholithiasis, from the Greek chol- (bile) + docho- (duct) + lith- (stone) + iasis- (process). Choledocholithiasis is frequently associated with obstruction of the bile ducts, which can lead to cholangitis, from the Greek: chol- (bile) + ang- (vessel) + itis- (inflammation), a serious infection of the bile ducts. Gallstones within the ampulla of Vater can obstruct the exocrine system of the pancreas and can result in pancreatitis. Signs and symptoms Gallstones, regardless of size or number, are often asymptomatic. These "silent stones" do not require treatment and can remain asymptomatic even years after they form.A characteristic symptom of a gallstone attack is the presence of colic-like pain in the upper-right side of the abdomen, often accompanied by nausea and vomiting. Pain from symptomatic gallstones may range from mild to severe and can steadily increase over a period lasting from 30 minutes to several hours. Other symptoms may include fever, as well as referred pain between the shoulder blades or below the right shoulder. If one or more gallstones block the bile ducts and cause bilirubin to leak into the bloodstream and surrounding tissue, jaundice and itching may also occur. In this case, liver enzyme levels are likely to be raised.Often, gallbladder attacks occur after eating a heavy meal. Attacks are most common in the evening or at night. Other complications In rare cases, gallstones that cause severe inflammation can erode through the gallbladder into adherent bowel, potentially causing an obstruction termed gallstone ileus.Other complications can include ascending cholangitis, which occurs when a bacterial infection causes purulent inflammation in the biliary tree and liver, and acute pancreatitis caused by blockage of the bile ducts that prevents active enzymes from being secreted into the bowel, instead damaging the pancreas. Rarely, gallbladder cancer may occur as a complication. Risk factors Gallstone risk increases for females (especially before menopause) and for people near or above 40 years; the condition is more prevalent among both North and South Americans and people of European descent than among other ethnicities. A lack of melatonin could significantly contribute to gallbladder stones, as melatonin inhibits cholesterol secretion from the gallbladder, enhances the conversion of cholesterol to bile, and is an antioxidant, which is able to reduce oxidative stress to the gallbladder. Gilbert syndrome has been linked to an increased risk of gallstones. Researchers believe that gallstones may be caused by a combination of factors, including inherited body chemistry, body weight, gallbladder motility (movement), and low-calorie diet. The absence of such risk factors does not, however, preclude the formation of gallstones. Nutritional factors that may increase risk of gallstones include constipation; eating fewer meals per day; low intake of the nutrients folate, magnesium, calcium, and vitamin C; low fluid consumption; and, at least for men, a high intake of carbohydrate, a high glycemic load, and high glycemic index diet. Wine and whole-grained bread may decrease the risk of gallstones.Rapid weight loss increases risk of gallstones. The weight loss drug orlistat is known to increase the risk of gallstones.Cholecystokinin deficiency caused by celiac disease increases risk of gallstone formation, especially when diagnosis of celiac disease is delayed.Pigment gallstones are most commonly seen in the developing world. Risk factors for pigment stones include hemolytic anemias (such as from sickle-cell disease and hereditary spherocytosis), cirrhosis, and biliary tract infections. People with erythropoietic protoporphyria (EPP) are at increased risk to develop gallstones. Additionally, prolonged use of proton pump inhibitors has been shown to decrease gallbladder function, potentially leading to gallstone formation.Cholesterol modifying medications can affect gallstone formation. Statins inhibit cholesterol synthesis and there is evidence that their use may decrease the risk of getting gallstones. Fibrates increase cholesterol concentration in bile and their use has been associated with an increased risk of gallstones. Bile acid malabsorption may also be a risk. Pathophysiology Cholesterol gallstones develop when bile contains too much cholesterol and not enough bile salts. Besides a high concentration of cholesterol, two other factors are important in causing gallstones. The first is how often and how well the gallbladder contracts; incomplete and infrequent emptying of the gallbladder may cause the bile to become overconcentrated and contribute to gallstone formation. This can be caused by high resistance to the flow of bile out of the gallbladder due to the complicated internal geometry of the cystic duct. The second factor is the presence of proteins in the liver and bile that either promote or inhibit cholesterol crystallization into gallstones. In addition, increased levels of the hormone estrogen, as a result of pregnancy or hormone therapy, or the use of combined (estrogen-containing) forms of hormonal contraception, may increase cholesterol levels in bile and also decrease gallbladder motility, resulting in gallstone formation. Composition The composition of gallstones is affected by age, diet and ethnicity. On the basis of their composition, gallstones can be divided into the following types: cholesterol stones, pigment stones, and mixed stones. An ideal classification system is yet to be defined. Cholesterol stones Cholesterol stones vary from light yellow to dark green or brown or chalk white and are oval, usually solitary, between 2 and 3 cm long, each often having a tiny, dark, central spot. To be classified as such, they must be at least 80% cholesterol by weight (or 70%, according to the Japanese classification system). Between 35% and 90% of stones are cholesterol stones. Pigment stones Bilirubin ("pigment", "black pigment") stones are small, dark (often appearing black), and usually numerous. They are composed primarily of bilirubin (insoluble bilirubin pigment polymer) and calcium (calcium phosphate) salts that are found in bile. They contain less than 20% of cholesterol (or 30%, according to the Japanese classification system). Between 2% and 30% of stones are bilirubin stones. Mixed stones Mixed (brown pigment stones) typically contain 20–80% cholesterol (or 30–70%, according to the Japanese classification system). Other common constituents are calcium carbonate, palmitate phosphate, bilirubin and other bile pigments (calcium bilirubinate, calcium palmitate and calcium stearate). Because of their calcium content, they are often radiographically visible. They typically arise secondary to infection of the biliary tract which results in the release of β-glucuronidase (by injured hepatocytes and bacteria) which hydrolyzes bilirubin glucuronides and increases the amount of unconjugated bilirubin in bile. Between 4% and 20% of stones are mixed.Gallstones can vary in size and shape from as small as a grain of sand to as large as a golf ball. The gallbladder may contain a single large stone or many smaller ones. Pseudoliths, sometimes referred to as sludge, are thick secretions that may be present within the gallbladder, either alone or in conjunction with fully formed gallstones. Diagnosis Diagnosis is typically confirmed by abdominal ultrasound. Other imaging techniques used are ERCP and MRCP. Gallstone complications may be detected on blood tests.On abdominal ultrasound, sinking gallstones usually have posterior acoustic shadowing. In floating gallstones, reverberation echoes (or comet-tail artifact) is seen instead in a clinical condition called adenomyomatosis. Another sign is wall-echo-shadow (WES) triad (or double-arc shadow) which is also characteristic of gallstones.A positive Murphys sign is a common finding on physical examination during a gallbladder attack. Prevention Maintaining a healthy weight by getting sufficient exercise and eating a healthy diet that is high in fiber may help prevent gallstone formation.Ursodeoxycholic acid (UDCA) appears to prevent formation of gallstones during weight loss. A high fat diet during weight loss also appears to prevent gallstones. Treatment Lithotripsy Extracorporeal shock wave lithotripsy is a non-invasive method to manage gallstones that uses high-energy sound waves to disintegrate them first applied in January 1985. Side effects of extracorporeal shock wave lithotripsy include biliary pancreatitis and liver haematoma. Surgical Cholecystectomy (gallbladder removal) has a 99% chance of eliminating the recurrence of cholelithiasis. The lack of a gallbladder has no negative consequences in most people, however 10 to 15% of people develop postcholecystectomy syndrome, which may cause nausea, indigestion, diarrhea, and episodes of abdominal pain.There are two surgical options for cholecystectomy: Open cholecystectomy is performed via an abdominal incision (laparotomy) below the lower right ribs. Recovery typically requires 3–5 days of hospitalization, with a return to normal diet a week after release and to normal activity several weeks after release. Laparoscopic cholecystectomy, introduced in the 1980s, is performed via three to four small puncture holes for a camera and instruments. Post-operative care typically includes a same-day release or a one-night hospital stay, followed by a few days of home rest and pain medication. Perforation of the gall bladder is not uncommon—it has been reported in the range of 10% to 40%. Unretrieved gallstone spillage has been reported as 6% to 30%, but gallstones that are not retrieved rarely cause complications (0.08%–0.3%).Obstruction of the common bile duct with gallstones can sometimes be relieved by endoscopic retrograde sphincterotomy (ERS) following endoscopic retrograde cholangiopancreatography (ERCP). Medical The medications ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) have been used in treatment to dissolve gallstones. A 2013 meta-analysis concluded that UDCA or higher dietary fat content appeared to prevent formation of gallstones during weight loss. Medical therapy with oral bile acids has been used to treat small cholesterol stones, and for larger cholesterol gallstones when surgery is either not possible or unwanted. CDCA treatment can cause diarrhea, mild reversible hepatic injury, and a small increase in the plasma cholesterol level. UDCA may need to be taken for years. Use in traditional medicine Gallstones can be a valued by-product of animals butchered for meat because of their use as an antipyretic and antidote in the traditional medicine of some cultures, particularly traditional Chinese medicine. The most highly prized gallstones tend to be sourced from old dairy cows, termed calculus bovis or niu-huang (yellow thing of cattle) in Chinese. Some slaughterhouses carefully scrutinize workers for gallstone theft. See also Porcelain gallbladder Mirizzis syndrome References External links "Gallstones". MedlinePlus. U.S. National Library of Medicine.

Adenoiditis

Adenoiditis is the inflammation of the adenoid tissue usually caused by an infection. Adenoiditis is treated using medication (antibiotics and/or steroids) or surgical intervention. Adenoiditis may produce cold-like symptoms. However, adenoiditis symptoms often persist for ten or more days, and often include pus-like discharge from nose. The infection cause is usually viral. However, if the adenoiditis is caused by a bacterial infection, antibiotics may be prescribed for treatment. A steroidal nasal spray may also be prescribed in order to reduce nasal congestion. Severe or recurring adenoiditis may require surgical removal of the adenoids (adenotonsillectomy). Signs and symptoms Acute adenoiditis is characterized by fever, runny nose, nasal airway obstruction resulting in predominantly oral breathing, snoring and sleep apnea, Rhinorrhea with serous secretion in viral forms and mucous-purulent secretion in bacterial forms. In cases due to viral infection symptoms usually recede spontaneously after 48 hours, symptoms of bacterial adenoiditis typically persist up to a week. Adenoiditis is sometimes accompanied by tonsillitis. Repeated adenoiditis may lead to enlarged adenoids. Complications Complications of acute adenoiditis can occur due to extension of inflammation to the neighboring organs. Cause Viruses that may cause adenoiditis include adenovirus, rhinovirus and paramyxovirus. Bacterial causes include Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis and various species of Staphylococcus including Staphylococcus aureus. Pathophysiology It is currently believed that bacterial biofilms play an integral role in the harboring of chronic infection by tonsil and adenoid tissue so contributing to recurrent sinusitis and recurrent or persistent ear disease. Also, enlarged adenoids and tonsils may lead to the obstruction of the breathing patterns in children, causing apnea during sleep. The most common bacteria isolated are Haemophilus influenzae, group A beta-hemolytic Streptococcus, Staphylococcus aureus, Moraxella catarrhalis, and Streptococcus pneumoniae. Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae are the three most resistant pathogens of otitis and rhinosinusitis in children with these diseases. Diagnosis Optical fiber endoscopy can confirm the diagnosis in case of doubt, directly visualizing the inflamed adenoid. Treatment In cases of viral adenoiditis, treatment with analgesics or antipyretics is often sufficient. Bacterial adenoiditis may be treated with antibiotics, such as amoxicillin - clavulanic acid or a cephalosporin. In case of adenoid hypertrophy, adenoidectomy may be performed to remove the adenoid. Epidemiology Adenoiditis occurs mainly in childhood, often associated with acute tonsillitis. Incidence decreases with age, with adenoiditis being rare in children over 15 years due to physiological atrophy of the adenoid tissue. See also Tonsilitis == References ==

Keratosis pilaris

Keratosis pilaris (KP; also follicular keratosis, lichen pilaris, or colloquially chicken skin) is a common, autosomal-dominant, genetic condition of the skins hair follicles characterized by the appearance of possibly itchy, small, gooseflesh-like bumps, with varying degrees of reddening or inflammation. It most often appears on the outer sides of the upper arms (the forearms can also be affected), thighs, face, back, and buttocks; KP can also occur on the hands, and tops of legs, sides, or any body part except glabrous (hairless) skin (like the palms or soles of feet). Often the lesions can appear on the face, which may be mistaken for acne or folliculitis. The several types of KP have been associated with pregnancy, type 1 diabetes mellitus, obesity, dry skin, allergic diseases (e.g., atopic dermatitis), and rarely cancer. Many rarer types of the disorder are part of inherited genetic syndromes.The cause of KP is not completely understood. As of 2018, KP is thought to be due to abnormalities in the process of depositing the protein keratin in hair follicles, abnormalities in the hair shaft, or both. KP is usually diagnosed by a medical professional based on the appearance of the skin, but dermoscopy can be used, as well, if the diagnosis is unclear. Variants of the ABCA12 gene have been associated with KP.KP is the most common disorder of the hair follicle in children. How common KP is in adults is unclear, with estimates ranging from 0.75 to 34% of the population. No single approach has been found to completely cure KP, but treatments can improve the cosmetic appearance of the condition. Treatment includes the application of topical preparations of moisturizers and medications such as glycolic acid, lactic acid, salicylic acid, urea, or retinoids to the skin. Fractional carbon dioxide lasers and Nd:YAG laser therapies are also effective. Signs and symptoms KP results in small, rough bumps on the surface of the skin. They are skin-colored bumps the size of a grain of sand, many of which are surrounded by a slight pink color in light-skinned people and dark spots in dark-skinned people. Most people with KP do not have symptoms, but the bumps in the skin can occasionally be itchy. Irritation due to scratching KP bumps can result in redness and inflammation. Though people with KP experience the condition year-round, the problem can become exacerbated, with the bumps likely to look and feel more pronounced in color and texture, during the colder months, when moisture levels in the air are lower. The symptoms may also worsen during pregnancy or after childbirth. Increased sun exposure might mitigate the symptoms of KP. Pathophysiology KP occurs when the human body produces excess amounts of the skin protein keratin, resulting in the formation of small, raised bumps in the skin, often with surrounding redness. The excess keratin, which is the same color as the persons natural skin tone, surrounds and entraps the hair follicles in the pore. This causes the formation of hard plugs (a process known as hyperkeratinization). Many KP bumps contain an ingrown hair that has coiled. This is a result of the keratinized skins "capping off" the hair follicle, preventing the hair from exiting. The hair grows encapsulated inside the follicle. KP is more common in patients affected by atopic diseases such as allergic rhinitis and atopic dermatitis. KP subtypes are occasionally part of genetically inherited syndromes associated with intellectual disability, neuro-cardio-facial-cutaneous syndromes, RASopathies, ectodermal dysplasias, and certain myopathies. Diagnosis Physicians can often diagnose KP simply by examining the skin without specialized tests, but a dermatologist can use dermoscopy to confirm the diagnosis and assess if a person with KP is responding to treatment. Physicians often consider family history and the presence of symptoms when making the diagnosis. Those with this condition are generally encouraged to contact a physician if the bumps are bothersome and do not improve with over-the-counter lotions. Differential diagnosis Several medications that can cause a skin eruption similar to KP include cyclosporine, BRAF inhibitors, and tyrosine kinase inhibitors. Classification The several different types of KP include KP rubra (red, inflamed bumps, which can be on arms, head, legs), KP alba (rough, bumpy skin with no irritation), KP rubra faceii (reddish rash on the cheeks), KP atrophicans, keratosis follicularis spinulosa decalvans, atrophoderma vermiculatum, KP atrophicans faciei, erythromelanosis follicularis faciei et colli, and papular profuse precocious KP.KP is commonly described in association with other dry-skin conditions, such as ichthyosis vulgaris, dry skin, and atopic dermatitis, including those of asthma and allergies. KP does not bear any known, long-term health implications, nor is it associated with increased mortality or morbidity. It is not related to goose bumps, which result from muscle contractions, except that both occur in the area where the hair shaft exits the skin. Gallery Treatment KP is medically harmless, but many individuals may seek treatment, as the condition can cause emotional distress. Topical creams and lotions are currently the most commonly used treatment for KP, specifically those consisting of moisturizing or keratolytic treatments, including urea, lactic acid, glycolic acid, salicylic acid, vitamin D, fish oil, or topical retinoids such as tretinoin. Improvement of the skin often takes months, and the bumps are likely to return. Limiting time in the shower and using gentle exfoliation to unplug pores can help. Many products are available that apply abrasive materials, with alpha or beta hydroxy acids to assist with exfoliation. Some cases of KP have been successfully treated with laser therapy, which involves passing intense bursts of light into targeted areas of the skin. Depending on the bodys response to the treatment, multiple sessions over the course of a few months may be necessary. Epidemiology Worldwide, KP affects an estimated 30 to 50% of the adult population, and around 50 to 80% of all adolescents. It is more common in women than in men, and it is often present in otherwise healthy individuals. The skin condition is prevalent in persons of all ethnicities, and no particular ethnicity is at higher risk for developing KP. Although KP may manifest in persons of any age, it usually appears within the first decade of life and is more common in young children. In most cases, the condition gradually improves before age 30, but it can persist longer. See also Ichthyosis linearis circumflexa References External links The American Academy of Dermatology The American Osteopathic College of Dermatology - Article on keratosis pilaris

Piedraia hortae

Piedraia hortae is a superficial fungus that exists in the soils of tropical and subtropical environments and affects both sexes of all ages. The fungus grows very slowly, forming dark hyphae, which contain chlamydoconidia cells and black colonies when grown on agar. Piedraia hortae is a dermatophyte and causes a superficial fungal infection known as black piedra, which causes the formation of black nodules on the hair shaft and leads to progressive weakening of the hair. The infection usually infects hairs on the scalp and beard, but other varieties tend to grow on pubic hairs. The infection is usually treated with cutting or shaving of the hair and followed by the application of anti-fungal and topical agents. The fungus is used for cosmetic purposes to darken hair in some societies as a symbol of attractiveness. Morphology When grown on agar at 25 °C (77 °F) Piedraia hortae grows very slowly to form black-greenish, limited and pointed colonies. Piedraia hortae taken from infected hairs have dark brown nodules, which are made up of ascostroma. The nodules have a gritty feel, organized in a stromatic fashion and have a high concentration of chitin and melanoid pigments. The colonies produce a red pigment and remain smooth and covered with short aerial hyphae. Microscopically, P. hortae produces short, dark hyphae containing thick-walled resting cells. The ascomata consist of irregularly shaped pseudothecia that are black in colour. Each ascoma contains a single ascus containing eight ascospores. The ascospores are dark, curved and become very narrow at the ends forming whip-like appendages. Affected hairs develop stone-like black nodules affixed to the hair shaft that cause weakness of the hair. Infected hairs treated with potassium hydroxide fluoresce under ultraviolet light despite that the fungus itself does not normally fluoresce. Fluorescence of the piedra indicates secondary contamination by bacteria. Identification is easily achieved by microscopic examination of the hair nodules, and can be confirmed by sequence analysis of the nuclear ribosomal internal transcribed spacer region. Pathology Piedraia hortae causes the formation of nodules on the hair shaft, a clinical superficial disease commonly known as black piedra. Black piedra is usually seen in tropical regions and it usually targets humans of all ages and targets the scalp, moustache and occasionally pubic hair. The source of the infection is usually in soils, poor hygiene, long hair, cultural use of veils and the application of plant oils to wet hair favours the growth of the infection. Black piedra is a superficial fungal infection, which means that it is restricted to the stratum corneum and causes no inflammation. The infection of the hair shaft results in the formation of nodules on the scalp, moustache and pubic hair. The nodules are hard and gritty, which produce a metallic sound when the hair is combed. The nodules colonize the hair shaft, which causes progressive weakness of the hair and leads to breakage of the hair in severe cases, which can lead to hair loss and baldness. The fungus also has the potential to destroy the cuticular layers of the hair and move into the cortex. Piedraia hortae survives in the scalp is due to the slow rate of the keratin degradation near the cortex and the compact formation of the nodules and the hyphae are tightly packed in black piedra cases. The initial invasion of human hair by P. hortae is achieved by using an eroding hyphae, which force their way beneath or between the cuticular layer. The force applied between or beneath the hair cuticle arises from the growth of the fungus itself. The breakdown of keratin is mainly due to enzymatic processes and corresponds to the abundance of localized mitochondria. The breakdown of keratin begins with the cementing material and progresses to the cortex of the hair shaft. In the cortex two types of degradative patterns are produced which are either parallel or vertical to the axis hair shaft. The parallel pattern arises from hyphal separation of the external cortical layers. The vertical pattern is produced by direct hyphal penetration which creates channels that increase in size as the cortex degrades. Treatment The infection cannot easily be removed mechanically, although further proliferation of infection can be achieved by avoidance of moisture. Removal generally involves cutting or shaving of the hair, but chemical treatments may be similarly useful. For women some individuals use a fine comb to remove as much of the infection as possible and then they cut or shave their hair. This is then followed by the application of a sublimate solution in 60% alcohol solution to the scalp. Historical treatments have used alcoholic tinctures of heavy metals, such as mercury bichloride. The application of antifungal shampoos such as pyrithione zinc, formaldehyde and salicylic acid is effective against black piedra. Oral therapy with itraconazole or terbinafine also causes nodules to break down over time. Removal of affected hair and treatment with topical agents is also effective and results in very low recurrences rates. However, even in the absence of treatment, spontaneous remission may occur.Terbinafine has been used in the treatment. Cosmetic uses Black piedra is sometimes cultivated for cosmetic purposes due to social factors that favour a specific hair colour, which makes them more attractive in their society. Several Indian tribes located from Panama have been known to use several methods in order to darken the hair of albino individuals within their community. One of these methods is the cultivation of black piedra for an extensive period of time in the individuals hair. In Malaysia the nodules of black piedra are very attractive and women are encouraged to sleep with their hair buried in the soil to encourage growth of the black nodules. Similar taxa The genus Piedraia contains another species known as Piedraia quintanilhae, which is more common in chimpanzees than humans. It differs from P. hortae in terms of the ascospores do not have any attachments. Another species known as Trichosporon biegelii is commonly known to cause white piedra . White piedra is more common in temperate and semitropical climates, such as South America, Asia, Europe, Japan, and parts of the southern United States. Black piedra usually affects scalp hair, whereas white piedra is more commonly found in pubic hair, axillary hair, beards, moustaches, and eyelashes. White piedra affects horses and monkeys, in addition to humans and the nodules are white and brown in colour and can be easily detached from the hair shaft. White piedra is treated by using topical and antifungal agents, but a more effective approach is to use itraconazole therapy. Recent studies have shown that the black, lichen-colonizing fungus, Xanthoriicola physciae, is closely related to P. hortae. See also White piedra Piedra References == External links ==

Extravasation of urine

Extravasation of urine refers to the condition where an interruption of the urethra leads to a collection of urine in other cavities, such as the scrotum or the penis in males. It can be associated with a calculus. Mechanism An injury to the urethra leaving Bucks fascia intact results in a collection of urine (extravasation) limited to the penis, deep to Bucks fascia. However, if the injury to the bulb of the penis results in urethral injury accompanying a tear of the Bucks fascia, then extravasated blood and urine would accumulate in the superficial perineal space, passing into the penis (outer to Bucks fascia) as well as the scrotum and lower anterior abdominal wall. Extravasation of urine involving a compromised Bucks fascia can be appreciated clinically by blood collecting in the superficial pouch, resulting in a butterfly-shaped region around the penis. Urinoma Long term complications of renal trauma, ureteral obstruction, or kidney transplant can lead to the formation of an urinoma encapsulating extravasated urine. References == External links ==

Mannosidosis

Mannosidosis is a deficiency in mannosidase, an enzyme.There are two types: Alpha-mannosidosis Beta-mannosidosis See also Swainsonine == References ==

Partial androgen insensitivity syndrome

Partial androgen insensitivity syndrome (PAIS) is a condition that results in the partial inability of the cell to respond to androgens. It is an X linked recessive condition. The partial unresponsiveness of the cell to the presence of androgenic hormones impairs the masculinization of male genitalia in the developing fetus, as well as the development of male secondary sexual characteristics at puberty, but does not significantly impair female genital or sexual development. As such, the insensitivity to androgens is clinically significant only when it occurs in individuals with a Y chromosome (or more specifically, an SRY gene). Clinical features include ambiguous genitalia at birth and primary amenhorrhoea with clitoromegaly with inguinal masses. Mullerian structures are not present in the individual. PAIS is one of three types of androgen insensitivity syndrome, which is divided into three categories that are differentiated by the degree of genital masculinization: complete androgen insensitivity syndrome (CAIS) is indicated when the external genitalia is that of a typical female, mild androgen insensitivity syndrome (MAIS) is indicated when the external genitalia is that of a typical male, and partial androgen insensitivity syndrome (PAIS) is indicated when the external genitalia is partially, but not fully masculinized.Androgen insensitivity syndrome is the largest single entity that leads to 46,XY undermasculinization.There are differing opinions on whether treatment is necessary. Treatment may include irreversible and far reaching surgical operations such as gonadectomy, as well as hormone replacement therapy, or vaginoplasty if the patient has desire to engage in penetrative sex. Signs and symptoms A supplemental system of phenotypic grading that uses seven classes instead of the traditional three was proposed by pediatric endocrinologist Charmian A. Quigley et al. in 1995. The first six grades of the scale, grades 1 through 6, are differentiated by the degree of genital masculinization; grade 1 is indicated when the external genitalia is fully masculinized, grade 6 is indicated when the external genitalia is fully feminized, and grades 2 through 5 quantify four degrees of increasingly feminized genitalia that lie in the interim. Grade 7 is indistinguishable from grade 6 until puberty, and is thereafter differentiated by the presence of secondary terminal hair; grade 6 is indicated when secondary terminal hair is present, whereas grade 7 is indicated when it is absent. The Quigley scale can be used in conjunction with the traditional three classes of AIS to provide additional information regarding the degree of genital masculinization, and is particularly useful when the diagnosis is PAIS. Partial androgen insensitivity syndrome is diagnosed when the degree of androgen insensitivity in an individual with a 46,XY karyotype is great enough to partially prevent the masculinization of the genitalia, but is not great enough to completely prevent genital masculinization. This includes any phenotype resulting from androgen insensitivity where the genitalia is partially, but not completely masculinized. Genital ambiguities are frequently detected during clinical examination at birth, and consequently, a PAIS diagnosis can be made during infancy as part of a differential diagnostic workup.Pubertal undervirilization is common, including gynecomastia, decreased secondary terminal hair, and / or a high pitched voice. The phallic structure ranges from a penis with varying degrees of diminished size and hypospadias to a slightly enlarged clitoris. Wolffian structures (the epididymides, vasa deferentia, and seminal vesicles) are typically partially or fully developed. The prostate is typically small or impalpable. Müllerian remnants are rare, but have been reported.The gonads in individuals with PAIS are testes, regardless of phenotype; during the embryonic stage of development, testes form in an androgen-independent process that occurs due to the influence of the SRY gene on the Y chromosome. Cryptorchidism is common, and carries with it a 50% risk of germ cell malignancy. If the testes are located intrascrotally, there may still be significant risk of germ cell malignancy; studies have not yet been published to assess this risk.Predominantly male phenotypes vary in the degree of genital undermasculinization to include micropenis, chordee, bifid scrotum, and / or pseudovaginal perineoscrotal hypospadias. Impotence may be fairly common, depending on phenotypic features; in one study of 15 males with PAIS, 80% of those interviewed indicated that they had some degree of impotence. Anejaculation appears to occur somewhat independently of impotence; some men are still able to ejaculate despite impotence, and others without erectile difficulties cannot. Predominantly female phenotypes include a variable degree of labial fusion and clitoromegaly. Ambiguous phenotypic states include a phallic structure that is intermediate between a clitoris and a penis, and a single perineal orifice that connects to both the urethra and the vagina (i.e. urogenital sinus). At birth, it may not be possible to immediately differentiate the external genitalia of individuals with PAIS as being either male or female, although the majority of individuals with PAIS are raised male. Given the wide diversity of phenotypes associated with PAIS, the diagnosis is often further specified by assessing genital masculinization. Grades 2 through 5 of the Quigley scale quantify four degrees of increasingly feminized genitalia that correspond to PAIS.Grade 2, the mildest form of PAIS, presents with a predominantly male phenotype that presents with minor signs of undermasculinized genitalia, such as isolated hypospadias, which can be severe. Hypospadias may manifest with a partially formed channel from the urethral opening to the glans. Until recently, it was thought that isolated micropenis was not a manifestation of PAIS. However, in 2010, two cases of PAIS manifesting with isolated micropenis were documented. Grade 3, the most common phenotypic form of PAIS, features a predominantly male phenotype that is more severely undermasculinized, and typically presents with micropenis and pseudovaginal perineoscrotal hypospadias with bifid scrotum.Grade 4 presents with a gender ambiguous phenotype, including a phallic structure that is intermediate between a clitoris and a penis. The urethra typically opens into a common channel with the vagina (i.e. urogenital sinus).Grade 5, the form of PAIS with the greatest degree of androgen insensitivity, presents with a mostly female phenotype, including separate urethral and vaginal orifices, but also shows signs of slight masculinization including mild clitoromegaly and / or partial labial fusion.Previously, it was erroneously thought that individuals with PAIS were always infertile; at least one case report has been published that describes fertile men that fit the criteria for grade 2 PAIS (micropenis, penile hypospadias, and gynecomastia). Comorbidity All forms of androgen insensitivity are associated with infertility, though exceptions have been reported for both the mild and partial forms.PAIS is associated with a 50% risk of germ cell malignancy when the testes are undescended. If the testes are located intrascrotally, there may still be significant risk of germ cell malignancy; studies have not yet been published to assess this risk. Some men with PAIS may experience sexual dysfunction including impotence and anejaculation. A few AR mutations that cause PAIS are also associated with prostate and breast cancers. Vaginal hypoplasia, a relatively frequent finding in CAIS and some forms of PAIS, is associated with sexual difficulties including vaginal penetration difficulties and dyspareunia.There are indications that individuals with an intersex condition may be more prone to psychological difficulties, due at least in part to parental attitudes and behaviors, and concludes that preventative long-term psychological counseling for parents as well as for affected individuals should be initiated at the time of diagnosis. More recent research based on interviews of people with intersex variations indicate a need for more family protection from intervention and more family support. Lifespan is not thought to be affected by AIS. Diagnosis Unfortunately, the number of differentials to consider for PAIS is particularly large. Prompt diagnosis is particularly urgent when a child is born with ambiguous genitalia, as some causes are associated with potentially life-threatening adrenal crises. Determination of testosterone, testosterone precursors and dihydrotestosterone (DHT) at baseline and / or after human chorionic gonadotropin (hCG) stimulation can be used to exclude such defects in androgen biosynthesis.Approximately one half of all 46,XY individuals born with ambiguous genitalia will not receive a definitive diagnosis. Androgen receptor (AR) gene mutations cannot be found in 27% to 72% of individuals with PAIS. As a result, genetic analysis can be used to confirm a diagnosis of PAIS, but it cannot be used to rule out PAIS. Evidence of abnormal androgen binding in a genital skin fibroblast study has long been the gold standard for the diagnosis of PAIS, even when an AR mutation is not present. However, some cases of PAIS, including AR-mutant-positive cases, will show normal androgen binding. A family history consistent with X-linked inheritance is more commonly found in AR-mutant-positive cases than AR-mutant-negative cases.The use of dynamic endocrine tests is particularly helpful in isolating a diagnosis of PAIS. One such test is the human chorionic gonadotropin (hCG) stimulation test. If the gonads are testes, there will be an increase in the level of serum testosterone in response to the hCG, regardless of testicular descent. The magnitude of the testosterone increase can help differentiate between androgen resistance and gonadal dysgenesis, as does evidence of a uterus on ultrasound examination. Testicular function can also be assessed by measuring serum anti-Müllerian hormone levels, which in turn can further differentiate PAIS from gonadal dysgenesis and bilateral anorchia.Another useful dynamic test involves measuring the response to exogenous steroids; individuals with AIS show a decreased response in serum sex hormone binding globulin (SHBG) after a short term administration of anabolic steroids. Two studies indicate that measuring the response in SHBG after the administration of stanozolol could help to differentiate individuals with PAIS from those with other causes of ambiguous genitalia, although the response in individuals with predominantly male phenotypes overlaps somewhat with the response in normal males. Management Management of AIS is currently limited to symptomatic management; methods to correct a malfunctioning androgen receptor protein that result from an AR gene mutation are not currently available. Areas of management include sex assignment, genitoplasty, gonadectomy in relation to tumor risk, hormone replacement therapy, and genetic and psychological counseling. Non-consensual interventions are still often performed, although general awareness on the resulting psychological traumatization is rising. Sex assignment The decision of whether to raise an individual with PAIS as a boy or a girl may not be obvious; grades 3 and 4 in particular present with a phenotype that may be difficult to classify as primarily male or female, and some will be incapable of virilization at puberty. Parents of an affected newborn should seek immediate help at a center with an experienced multidisciplinary team, and should avoid gender assignment beforehand. Older guidelines from 2006 advised against waiting for the child to decide for themselves. According to them, key considerations involved in assigning gender include the appearance of the genitalia, the extent to which the child can virilize at puberty, surgical options and the postoperative sexual function of the genitalia, genitoplasty complexity, potential for fertility, and the projected gender identity of the child. The majority of individuals with PAIS are raised male. More recently, the interests of intersex people themselves are being taken into consideration by the medical community. Some parents have pushed their children with intersex variations to display gender normative roles and behaviours, or to engage in hormonal and surgical interventions to make their bodies appear more aesthetically normative. Research based on interviews of people with intersex variations indicate a need for more family protection from intervention and more family support. Virilization capacity can be assessed by measuring the response to a trial of exogenous androgens; some studies have measured the growth of the phallus in response to exogenous testosterone or dihydrotestosterone, while others have measured the change in sex hormone binding globulin (SHBG) in response to the artificial androgen stanozolol to assess androgen sensitivity. Some experts have cautioned that it remains to be proved that a good response to exogenous androgens in neonates is a good predictor of androgen response at puberty. If a mutation in the AR gene is found, it is important to determine whether the mutation is inherited or de novo (i.e. a somatic mutation); a certain amount of the wild-type androgen receptor will be present in cases of somatic mutation, which can induce virilization at puberty. A genital skin fibroblast study and a human chorionic gonadotropin (hCG) stimulation test may also provide information helpful in the assessment of virilization capacity. Psychosexual development is influenced by many factors, including the timing, amount, and type of androgen exposure, receptor functionality, and environment, and is thus difficult to predict. Gender identity begins to develop before 3 years of age, although the earliest age at which it can be reliably assessed has yet to be determined. Approximately 25% of individuals with PAIS are dissatisfied with their assigned gender, regardless of being raised as male or female. One study reports that 46,XY individuals born with micropenis and no hypospadias are better off being raised male, despite the success of some being raised female. Studies involving the more ambiguous phenotypic forms of PAIS are less decisive. Homosexuality with respect to assigned gender and atypical gender role behavior are known to occur more frequently in individual with PAIS, and may occur with or without gender dysphoria; neither should be interpreted as an indication of incorrect gender assignment. If an affected child does express feelings of gender dysphoria, the opportunity to explore such feelings with a psychologist experienced in treating intersex conditions should be accommodated. If feelings of gender dysphoria persist, gender reassignment should be initiated, possibly with the aid of a specialist in the field. Genitoplasty Genitoplasty, unlike gender assignment, can be irreversible, and there is no guarantee that adult gender identity will develop as assigned despite surgical intervention. Some aspects of genitoplasty are still being debated; a variety of different opinions have been presented by professionals, self-help groups, and patients over the last few decades. Points of consideration include what conditions justify genitoplasty, the extent and type of genitoplasty that should be employed, when genitoplasty should be performed, and what the goals of genitoplasty should be. Gender assignment itself does not predicate the need for immediate genitoplasty; in some cases, surgical intervention can be delayed to allow the affected child to reach an age and maturity sufficient to have a role in such decisions. Some studies suggest that early surgeries can still produce satisfactory outcomes, while others suggest it to be unlikely. Even surgeries that are planned as one-stage procedures often require further major surgery. Scarring and tissue loss that result from repeated surgical procedures are of particular concern, due to the presumed negative impact on sexual function.While it is thought that feminizing genitoplasty typically requires fewer surgeries to achieve an acceptable result and results in fewer urologic difficulties, there is no evidence that feminizing surgery results in a better psychosocial outcome. In one study, individuals with grade 3 PAIS who were raised male rated their body image and sexual function similarly to those who were raised female, even though they were more likely to have genitalia that were abnormal in size and appearance; more than half of the male participants had a stretched penile length that was below 2.5 standard deviations of the mean, while only 6% of female participants presented with a short vagina in adulthood, and participating physicians gave a lower cosmetic rating to the surgical results of the men than the women. Both male and female participants cited the appearance of their genitalia as being the greatest contributing factor to their dissatisfaction with their body image. In two larger studies, the common predictor of gender reassignment was stigmatization related to having an intersex condition. The outcome of masculinizing genitoplasty is dependent on the amount of erectile tissue and the extent of hypospadias. Procedures include correction of penile curvature and chordee, reconstruction of the urethra, hypospadias correction, orchidopexy, and Müllerian remnant removal to prevent infection and pseudo-incontinence. Erectile prosthesis may be inserted in cases of successful neophalloplasty in adulthood, although it has a high morbidity. Additional surgeries may be required to correct postsurgical complications such as stenosis of the anastomosis between the native urethra and the graft, urethral fistulas, and posterior displacement of the balanic meatus. Successful masculinizing genitoplasty performed on individuals with grade 3 PAIS often requires multiple surgeries. If feminizing genitoplasty is performed in infancy, the result will need to be refined at puberty through additional surgery. Procedures include clitoral reduction / recession, labiaplasty, repair of the common urogenital sinus, vaginoplasty, and vaginal dilation through non-surgical pressure methods. Clitoral reduction / recession surgery carries with it the risk of necrosis as well as the risk of impairing the sexual function of the genitalia, and thus should not be performed for less severe clitoromegaly. Clitoral surgery should be focused on function rather than appearance, with care being taken to spare the erectile function and innervation of the clitoris. If PAIS presents with a common urogenital sinus, the American Academy of Pediatrics currently recommends that surgery to separate the urethra from the vagina be performed at an early age. As is the case for CAIS, vaginal dilation using pressure dilation methods should be attempted before the surgical creation of a neovagina is considered, and neither should be performed before puberty. Complications of feminizing genitoplasty can include vaginal stenosis, meatal stenosis, vaginourethral fistula, female hypospadias, urinary tract injuries, and recurrent clitoromegaly. Successful feminizing genitoplasty performed on individuals with grade 3 PAIS often requires multiple surgeries, although more surgeries are typically required for successful masculinizing genitoplasty in this population.Many surgical procedures have been developed to create a neovagina, as none of them is ideal. Surgical intervention should be considered only after non-surgical pressure dilation methods have failed to produce a satisfactory result. Neovaginoplasty can be performed using skin grafts, a segment of bowel, ileum, peritoneum, Interceed, buccal mucosa, amnion, or dura mater. Success of such methods should be determined by sexual function, and not by vaginal length alone, as has been done in the past. Ileal or cecal segments may be problematic because of a shorter mesentery, which may produce tension on the neovagina, leading to stenosis. The sigmoid neovagina is thought to be self-lubricating, without the excess mucus production associated with segments of small bowel. Vaginoplasty may create scarring at the introitus (the vaginal opening), requiring additional surgery to correct. Vaginal dilators are required postoperatively to prevent vaginal stenosis from scarring. Other complications include bladder and bowel injuries. Yearly exams are required, as neovaginoplasty carries a risk of carcinoma, although carcinoma of the neovagina is uncommon. Neither neovaginoplasty nor vaginal dilation should be performed before puberty. Gonadectomy Gonadectomy at time of diagnosis is the current recommendation for PAIS if presenting with cryptorchidism. The risk of malignancy when testes are located intrascrotally is unknown; the current recommendation is to biopsy the testes at puberty, allowing investigation of at least 30 seminiferous tubules, with diagnosis preferably based on OCT3/4 immunohistochemistry, followed by regular examinations. Hormone replacement therapy is required after gonadectomy, and should be modulated over time to replicate the hormone levels naturally present in the body during the various stages of puberty. Artificially induced puberty results in the same, normal development of secondary sexual characteristics, growth spurt, and bone mineral accumulation. Women with PAIS may have a tendency towards bone mineralization deficiency, although this increase is thought to be less than is typically seen in CAIS, and is similarly managed. Hormonal replacement therapy Testosterone has been used to successfully treat undervirilization in some but not all men with PAIS, despite having supraphysiological levels of testosterone to start with. Treatment options include transdermal gels or patches, oral or injectable testosterone undecanoate, other injectable testosterone esters, testosterone pellets, or buccal testosterone systems. Supraphysiological doses may be required to achieve the desired physiological effect, which may be difficult to achieve using non-injectable testosterone preparations. Exogenous testosterone supplementation in unaffected men can produce various unwanted side effects, including prostatic hypertrophy, polycythemia, gynecomastia, hair loss, acne, and the suppression of the hypothalamic-pituitary-gonadal axis, resulting in the reduction of gonadotropins (i.e., luteinizing hormone and follicle-stimulating hormone) and spermatogenic defect. These effects may not manifest at all in men with AIS, or might only manifest at a much higher concentration of testosterone, depending on the degree of androgen insensitivity. Those undergoing high dose androgen therapy should be monitored for safety and efficacy of treatment, possibly including regular breast and prostate examinations. Some individuals with PAIS have a sufficiently high sperm count to father children; at least one case report has been published that describes fertile men who fit the criteria for grade 2 PAIS (micropenis, penile hypospadias, and gynecomastia). Several publications have indicated that testosterone treatment can correct low sperm counts in men with MAIS. At least one case report has been published that documents the efficacy of treating a low sperm-count with tamoxifen in an individual with PAIS. Counseling Depending on phenotypic features, impotence and other sexual problems such as anejaculation or sexual aversion may be fairly common among individuals with PAIS, but do not necessarily indicate low libido. Support groups for individuals with PAIS may help affected individuals discuss their concerns more comfortably. Some individuals with PAIS may try to avoid intimate relationships out of fear of rejection; individual therapy may help some to overcome social anxiety, and restore focus to interpersonal relationships instead of solely on sexual function and activity. Society and culture Adults with partial androgen insensitivity syndrome include Australian-Maltese advocate Tony Briffa, considered to be the worlds first openly intersex mayor and public office-bearer. Briffa served as Deputy Mayor of the City of Hobsons Bay, Victoria, between 2009 and 2011, and Mayor between 2011 and 2012.In history, the Roman sophist and philosopher Favorinus of Arelate has been described as having partial androgen insensitivity syndrome. Notable people with PAIS Tony Briffa Small Luk Eliana Rubashkyn Sean Saifa Wall Sogto Ochirov Sentencia SU 337/99, Colombia In Sentencia SU-337/99, of May 12, 1999, the Constitutional Court of Colombia determined that "qualified and persistent" informed consent is required for genital surgeries in children. The Court ruled in the case of XX, an 8-year old with ambiguous genitalia, androgen insensitivity and XY chromosomes, raised as a girl. Doctors recommended feminizing surgeries, including a gonadectomy, vaginoplasty and clitoroplasty before puberty, but the hospital would not proceed without the consent of the Colombian Institute of Family Welfare and the Office of the Public Advocate. The mother brought a case against Institute and Office of the Public Advocate, seeking to provide substitute consent. The mother argued that “the capacity to decide, it would be too late and would prevent normal psychological, physical, and social development”.The Court refused the mothers claim. It questioned the urgency of the case, argued by medical teams. Civil rights advocates and a minority of doctors favored deferring treatment due to lack of evidence and the irreversible nature of the proposed interventions. The Court observed that advocates of surgery were more numerous than opponents, alternatives to surgery were not entirely feasible, and surgeries had improved, “making it less likely that sexual sensitivity would be destroyed; and the medical community was improving communication with parents”.The Court determined that a constitutional protection of a right to free development of personality meant that a childs autonomy increases with age, including the development of a gender identity and bodily awareness. It determined that the best interests of the child were protected by allowing the child to determine their own gender identity. The Court determined that genital surgeries should not be conducted on children over the age of five, and that multidisciplinary teams should assess childrens needs on a case-by-case basis. References External links androgen at NIH/UW GeneTests

Perihepatitis

Perihepatitis is inflammation of the serous or peritoneal coating of the liver. Perihepatitis is often caused by one of the inflammatory disorders of the female upper genital tract, known collectively as pelvic inflammatory disease. Some patients have sharp right upper abdominal quadrant pain. One of the complications of perihepatitis is Fitz-Hugh–Curtis syndrome.Common bacterial causes for this disease are Chlamydia trachomatis and Neisseria gonorrhoeae. == References ==

Subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH) is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain. Symptoms may include a severe headache of rapid onset, vomiting, decreased level of consciousness, fever, and sometimes seizures. Neck stiffness or neck pain are also relatively common. In about a quarter of people a small bleed with resolving symptoms occurs within a month of a larger bleed.SAH may occur as a result of a head injury or spontaneously, usually from a ruptured cerebral aneurysm. Risk factors for spontaneous cases include high blood pressure, smoking, family history, alcoholism, and cocaine use. Generally, the diagnosis can be determined by a CT scan of the head if done within six hours of symptom onset. Occasionally, a lumbar puncture is also required. After confirmation further tests are usually performed to determine the underlying cause.Treatment is by prompt neurosurgery or endovascular coiling. Medications such as labetalol may be required to lower the blood pressure until repair can occur. Efforts to treat fevers are also recommended. Nimodipine, a calcium channel blocker, is frequently used to prevent vasospasm. The routine use of medications to prevent further seizures is of unclear benefit. Nearly half of people with a SAH due to an underlying aneurysm die within 30 days and about a third who survive have ongoing problems. Between ten and fifteen percent die before reaching a hospital.Spontaneous SAH occurs in about one per 10,000 people per year. Females are more commonly affected than males. While it becomes more common with age, about 50% of people present under 55 years old. It is a form of stroke and comprises about 5 percent of all strokes. Surgery for aneurysms was introduced in the 1930s. Since the 1990s many aneurysms are treated by a less invasive procedure called endovascular coiling, which is carried out through a large blood vessel. Signs and symptoms The classic symptom of subarachnoid hemorrhage is thunderclap headache (a headache described as "like being kicked in the head", or the "worst ever", developing over seconds to minutes). This headache often pulsates towards the occiput (the back of the head). About one-third of people have no symptoms apart from the characteristic headache, and about one in ten people who seek medical care with this symptom are later diagnosed with a subarachnoid hemorrhage. Vomiting may be present, and 1 in 14 have seizures. Confusion, decreased level of consciousness or coma may be present, as may neck stiffness and other signs of meningism.Neck stiffness usually presents six hours after initial onset of SAH. Isolated dilation of a pupil and loss of the pupillary light reflex may reflect brain herniation as a result of rising intracranial pressure (pressure inside the skull). Intraocular hemorrhage (bleeding into the eyeball) may occur in response to the raised pressure: subhyaloid hemorrhage (bleeding under the hyaloid membrane, which envelops the vitreous body of the eye) and vitreous hemorrhage may be visible on fundoscopy. This is known as Terson syndrome (occurring in 3–13 percent of cases) and is more common in more severe SAH.Oculomotor nerve abnormalities (affected eye looking downward and outward and inability to lift the eyelid on the same side) or palsy (loss of movement) may indicate bleeding from the posterior communicating artery. Seizures are more common if the hemorrhage is from an aneurysm; it is otherwise difficult to predict the site and origin of the hemorrhage from the symptoms. SAH in a person known to have seizures is often diagnostic of a cerebral arteriovenous malformation.The combination of intracerebral hemorrhage and raised intracranial pressure (if present) leads to a "sympathetic surge", i.e. over-activation of the sympathetic system. This is thought to occur through two mechanisms, a direct effect on the medulla that leads to activation of the descending sympathetic nervous system and a local release of inflammatory mediators that circulate to the peripheral circulation where they activate the sympathetic system. As a consequence of the sympathetic surge there is a sudden increase in blood pressure; mediated by increased contractility of the ventricle and increased vasoconstriction leading to increased systemic vascular resistance. The consequences of this sympathetic surge can be sudden, severe, and are frequently life-threatening. The high plasma concentrations of adrenaline also may cause cardiac arrhythmias (irregularities in the heart rate and rhythm), electrocardiographic changes (in 27 percent of cases) and cardiac arrest (in 3 percent of cases) may occur rapidly after the onset of hemorrhage. A further consequence of this process is neurogenic pulmonary edema where a process of increased pressure within the pulmonary circulation causes leaking of fluid from the pulmonary capillaries into the air spaces, the alveoli, of the lung.Subarachnoid hemorrhage may also occur in people who have had a head injury. Symptoms may include headache, decreased level of consciousness and hemiparesis (weakness of one side of the body). SAH is a frequent occurrence in traumatic brain injury, and carries a poor prognosis if it is associated with deterioration in the level of consciousness.While thunderclap headache is the characteristic symptom of subarachnoid hemorrhage, less than 10% of those with concerning symptoms have SAH on investigations. A number of other causes may need to be considered. Causes Most cases of SAH are due to trauma such as a blow to the head. Traumatic SAH usually occurs near the site of a skull fracture or intracerebral contusion. It often happens in the setting of other forms of traumatic brain injury. In these cases prognosis is poorer; however, it is unclear if this is a direct result of the SAH or whether the presence of subarachnoid blood is simply an indicator of a more severe head injury.In 85 percent of spontaneous cases the cause is a cerebral aneurysm—a weakness in the wall of one of the arteries in the brain that becomes enlarged. They tend to be located in the circle of Willis and its branches. While most cases are due to bleeding from small aneurysms, larger aneurysms (which are less common) are more likely to rupture. Aspirin also appears to increase the risk.In 15–20 percent of cases of spontaneous SAH, no aneurysm is detected on the first angiogram. About half of these are attributed to non-aneurysmal perimesencephalic hemorrhage, in which the blood is limited to the subarachnoid spaces around the midbrain (i.e. mesencephalon). In these, the origin of the blood is uncertain. The remainder are due to other disorders affecting the blood vessels (such as cerebral arteriovenous malformations), disorders of the blood vessels in the spinal cord, and bleeding into various tumors.Cocaine abuse and sickle cell anemia (usually in children) and, rarely, anticoagulant therapy, problems with blood clotting and pituitary apoplexy can also result in SAH. Dissection of the vertebral artery, usually caused by trauma, can lead to subarachnoid hemorrhage if the dissection involves the part of the vessel inside the skull. Pathophysiology Cerebral vasospasm is one of the complications caused by subarachnoid hemorrhage. It usually happens from the third day after the aneurysm event, and reaches its peak on 5th to 7th day. There are several mechanisms proposed for this complication. Blood products released from subarachnoid hemorrhage stimulates the tyrosine kinase pathway causing the release of calcium ions from intracellular storage, resulting in smooth muscle contraction of cerebral arteries. Oxyhaemoglobin in cerebrospinal fluid (CSF) causes vasoconstriction by increasing free radicals, endothelin-1, prostaglandin and reducing the level of nitric oxide and prostacyclin. Besides, the disturbances of autonomic nervous system innervating cerebral arteries is also thought to cause vasospasm. Diagnosis As only 10 percent of people admitted to the emergency department with a thunderclap headache are having an SAH, other possible causes are usually considered simultaneously, such as meningitis, migraine, and cerebral venous sinus thrombosis. Intracerebral hemorrhage, in which bleeding occurs within the brain itself, is twice as common as SAH and is often misdiagnosed as the latter. It is not unusual for SAH to be initially misdiagnosed as a migraine or tension headache, which can lead to a delay in obtaining a CT scan. In a 2004 study, this occurred in 12 percent of all cases and was more likely in people who had smaller hemorrhages and no impairment in their mental status. The delay in diagnosis led to a worse outcome. In some people, the headache resolves by itself, and no other symptoms are present. This type of headache is referred to as "sentinel headache", because it is presumed to result from a small leak (a "warning leak") from an aneurysm. A sentinel headache still warrants investigations with CT scan and lumbar puncture, as further bleeding may occur in the subsequent three weeks.The initial steps for evaluating a person with a suspected subarachnoid hemorrhage are obtaining a medical history and performing a physical examination. The diagnosis cannot be made on clinical grounds alone and in general medical imaging and possibly a lumbar puncture is required to confirm or exclude bleeding. Imaging The modality of choice is computed tomography (CT scan), without contrast, of the brain. This has a high sensitivity and will correctly identify 98.7% of cases within six hours of the onset of symptoms. A CT scan can rule out the diagnosis in someone with a normal neurological exam if done within six hours. Its efficacy declines thereafter, and magnetic resonance imaging (MRI) is more sensitive than CT after several days. Angiography After a subarachnoid hemorrhage is confirmed, its origin needs to be determined. If the bleeding is likely to have originated from an aneurysm (as determined by the CT scan appearance), the choice is between cerebral angiography (injecting radiocontrast through a catheter to the brain arteries) and CT angiography (visualizing blood vessels with radiocontrast on a CT scan) to identify aneurysms. Catheter angiography also offers the possibility of coiling an aneurysm (see below).In emergency department patients complaining of acute-onset headache without significant risk factors for SAH, evidence suggests that CT scanning of the head followed by CT angiography can reliably exclude SAH without the need for a lumbar puncture. The risk of missing an aneurysmal bleed as the cause of SAH with this approach is less than 1%. Lumbar puncture Lumbar puncture, in which cerebrospinal fluid (CSF) is removed from the subarachnoid space of the spinal canal using a hypodermic needle, shows evidence of bleeding in three percent of people in whom a non-contrast CT was found normal. A lumbar puncture or CT scan with contrast is therefore regarded as mandatory in people with suspected SAH when imaging is delayed to after six hours from the onset of symptoms and is negative. At least three tubes of CSF are collected. If an elevated number of red blood cells is present equally in all bottles, this indicates a subarachnoid hemorrhage. If the number of cells decreases per bottle, it is more likely that it is due to damage to a small blood vessel during the procedure (known as a "traumatic tap"). While there is no official cutoff for red blood cells in the CSF no documented cases have occurred at less than "a few hundred cells" per high-powered field.The CSF sample is also examined for xanthochromia—the yellow appearance of centrifugated fluid. This can be determined by spectrophotometry (measuring the absorption of particular wavelengths of light) or visual examination. It is unclear which method is superior. Xanthochromia remains a reliable ways to detect SAH several days after the onset of headache. An interval of at least 12 hours between the onset of the headache and lumbar puncture is required, as it takes several hours for the hemoglobin from the red blood cells to be metabolized into bilirubin. ECG Electrocardiographic changes are relatively common in subarachnoid hemorrhage, occurring in 40–70 percent of cases. They may include QT prolongation, Q waves, cardiac dysrhythmias, and ST elevation that mimics a heart attack.Also one of the characteristic ECG changes that could be found in patients with subarachnoid hemorrhage, is the J waves or Osborn waves, which are positive deflections that occur at the junction between QRS complexes and ST segments, where the S point, also known as the J point, has a myocardial infarction-like elevation. J waves or Osborn waves, which represent an early repolarization and delayed depolarization of the heart ventricles, are thought to be caused by the high catecholamines surge released in patients with subarachnoid hemorrhage or brain damage, the issue that might lead to ventricular fibrillation and cardiac arrest in unmanaged patients. Classification There are several grading scales available for SAH. The Glasgow Coma Scale (GCS) is ubiquitously used for assessing consciousness. Its three specialized scores are used to evaluate SAH; in each, a higher number is associated with a worse outcome. These scales have been derived by retrospectively matching characteristics of people with their outcomes. The first widely used scale for neurological condition following SAH was published by Botterell and Cannell in 1956 and referred to as the Botterell Grading Scale. This was modified by Hunt and Hess in 1968: The Fisher Grade classifies the appearance of subarachnoid hemorrhage on CT scan. This scale has been modified by Claassen and coworkers, reflecting the additive risk from SAH size and accompanying intraventricular hemorrhage (0 – none; 1 – minimal SAH w/o IVH; 2 – minimal SAH with IVH; 3 – thick SAH w/o IVH; 4 – thick SAH with IVH);.The World Federation of Neurosurgeons (WFNS) classification uses Glasgow coma score and focal neurological deficit to gauge severity of symptoms. A comprehensive classification scheme has been suggested by Ogilvy and Carter to predict outcome and gauge therapy. The system consists of five grades and it assigns one point for the presence or absence of each of five factors: age greater than 50; Hunt and Hess grade 4 or 5; Fisher scale 3 or 4; aneurysm size greater than 10 mm; and posterior circulation aneurysm 25 mm or more. Screening and prevention Screening for aneurysms is not performed on a population level; because they are relatively rare, it would not be cost-effective. However, if someone has two or more first-degree relatives who have had an aneurysmal subarachnoid hemorrhage, screening may be worthwhile.Autosomal dominant polycystic kidney disease (ADPKD), a hereditary kidney condition, is known to be associated with cerebral aneurysms in 8 percent of cases, but most such aneurysms are small and therefore unlikely to rupture. As a result, screening is only recommended in families with ADPKD where one family member has had a ruptured aneurysm.An aneurysm may be detected incidentally on brain imaging; this presents a conundrum, as all treatments for cerebral aneurysms are associated with potential complications. The International Study of Unruptured Intracranial Aneurysms (ISUIA) provided prognostic data both in people having previously had a subarachnoid hemorrhage and people who had aneurysms detected by other means. Those having previously had a SAH were more likely to bleed from other aneurysms. In contrast, those having never bled and had small aneurysms (smaller than 10 mm) were very unlikely to have a SAH and were likely to sustain harm from attempts to repair these aneurysms. On the basis of the ISUIA and other studies, it is now recommended that people are considered for preventive treatment only if they have a reasonable life expectancy and have aneurysms that are highly likely to rupture. Moreover, there is only limited evidence that endovascular treatment of unruptured aneurysms is actually beneficial. Treatment Management involves general measures to stabilize the person while also using specific investigations and treatments. These include the prevention of rebleeding by obliterating the bleeding source, prevention of a phenomenon known as vasospasm, and prevention and treatment of complications.Stabilizing the person is the first priority. Those with a depressed level of consciousness may need to be intubated and mechanically ventilated. Blood pressure, pulse, respiratory rate, and Glasgow Coma Scale are monitored frequently. Once the diagnosis is confirmed, admission to an intensive care unit may be preferable, especially since 15 percent may have further bleeding soon after admission. Nutrition is an early priority, mouth or nasogastric tube feeding being preferable over parenteral routes. In general, pain control is restricted to less-sedating agents such as codeine, as sedation may impact on the mental status and thus interfere with the ability to monitor the level of consciousness. Deep vein thrombosis is prevented with compression stockings, intermittent pneumatic compression of the calves, or both. A bladder catheter is usually inserted to monitor fluid balance. Benzodiazepines may be administered to help relieve distress. Antiemetic drugs should be given to awake persons.People with poor clinical grade on admission, acute neurologic deterioration, or progressive enlargement of ventricles on CT scan are, in general, indications for the placement of an external ventricular drain by a neurosurgeon. The external ventricular drain may be inserted at the bedside or in the operating room. In either case, strict aseptic technique must be maintained during insertion. In people with aneurysmal subarachnoid hemorrhage the EVD is used to remove cerebrospinal fluid, blood, and blood byproducts that increase intracranial pressure and may increase the risk for cerebral vasospasm. Preventing rebleeding Efforts to keep a persons systolic blood pressure somewhere between 140 and 160 mmHg is generally recommended. Medications to achieve this may include labetalol or nicardipine.People whose CT scan shows a large hematoma, depressed level of consciousness, or focal neurologic signs may benefit from urgent surgical removal of the blood or occlusion of the bleeding site. The remainder are stabilized more extensively and undergo a transfemoral angiogram or CT angiogram later. It is hard to predict who will have a rebleed, yet it may happen at any time and carries a dismal prognosis. After the first 24 hours have passed, rebleeding risk remains around 40 percent over the subsequent four weeks, suggesting that interventions should be aimed at reducing this risk as soon as possible. Some predictors of early rebleeding are high systolic blood pressure, the presence of a hematoma in the brain or ventricles, poor Hunt-Hess grade (III-IV), aneurysms in the posterior circulation, and an aneurysm >10 mm in size.If a cerebral aneurysm is identified on angiography, two measures are available to reduce the risk of further bleeding from the same aneurysm: clipping and coiling. Clipping requires a craniotomy (opening of the skull) to locate the aneurysm, followed by the placement of clips around the neck of the aneurysm. Coiling is performed through the large blood vessels (endovascularly): a catheter is inserted into the femoral artery in the groin and advanced through the aorta to the arteries (both carotid arteries and both vertebral arteries) that supply the brain. When the aneurysm has been located, platinum coils are deployed that cause a blood clot to form in the aneurysm, obliterating it. The decision as to which treatment is undertaken is typically made by a multidisciplinary team consisting of a neurosurgeon, neuroradiologist, and often other health professionals.In general, the decision between clipping and coiling is made on the basis of the location of the aneurysm, its size and the condition of the person. Aneurysms of the middle cerebral artery and its related vessels are hard to reach with angiography and tend to be amenable to clipping. Those of the basilar artery and posterior cerebral artery are hard to reach surgically and are more accessible for endovascular management. These approaches are based on general experience, and the only randomized controlled trial directly comparing the different modalities was performed in relatively well people with small (less than 10 mm) aneurysms of the anterior cerebral artery and anterior communicating artery (together the "anterior circulation"), who constitute about 20 percent of all people with aneurysmal SAH. This trial, the International Subarachnoid Aneurysm Trial (ISAT), showed that in this group the likelihood of death or being dependent on others for activities of daily living was reduced (7.4 percent absolute risk reduction, 23.5 percent relative risk reduction) if endovascular coiling was used as opposed to surgery. The main drawback of coiling is the possibility that the aneurysm will recur; this risk is extremely small in the surgical approach. In ISAT, 8.3 percent needed further treatment in the longer term. Hence, people who have undergone coiling are typically followed up for many years afterwards with angiography or other measures to ensure recurrence of aneurysms is identified early. Other trials have also found a higher rate of recurrence necessitating further treatments. Vasospasm Vasospasm, in which the blood vessels constrict and thus restrict blood flow, is a serious complication of SAH. It can cause ischemic brain injury (referred to as "delayed ischemia") and permanent brain damage due to lack of oxygen in parts of the brain. It can be fatal if severe. Delayed ischemia is characterized by new neurological symptoms, and can be confirmed by transcranial doppler or cerebral angiography. About one third of people admitted with subarachnoid hemorrhage will have delayed ischemia, and half of those have permanent damage as a result. It is possible to screen for the development of vasospasm with transcranial Doppler every 24–48 hours. A blood flow velocity of more than 120 centimeters per second is suggestive of vasospasm.The pathogenesis of cerebral vasospasm following subarachnoid hemorrhage is attributed to the higher levels of endothelin 1, a potent vasoconstrictor, and the lower levels of endothelial NOS (eNOS), a potent vasodilator. Both of which are produced from a series of events that begin from the inflammatory reaction caused by the products released from erythrocytes degradation. Following subarachnoid hemorrhage, different clotting factors and blood products are released into the surrounding perivascular spaces known as (Virchow-Robin spaces). The released clotting factors like; fibrinopeptides, thromboxane A2 and others lead to microthrombosis around near vessels that leads to extrinsic vasoconstriction of these vessels. Besides that extrinsic vasoconstriction, the erythrocytes degradation products like; bilirubin and oxyhemoglobin lead to neuroinflammation that in turn increases the production of reactive oxygen species (ROS) which increases and decreases the production of endothelin 1 and endothelial NOS, respectively, the issue that yields in intrinsic vasoconstriction of the neighboring blood vessels and results in cerebral ischemia if left untreated.The use of calcium channel blockers, thought to be able to prevent the spasm of blood vessels by preventing calcium from entering smooth muscle cells, has been proposed for prevention. The calcium channel blocker nimodipine when taken by mouth improves outcome if given between the fourth and twenty-first day after the bleeding, even if it does not reduce the amount of vasospasm detected on angiography. It is the only Food and Drug Administration (FDA)-approved drug for treating cerebral vasospasm. In traumatic subarachnoid hemorrhage, nimodipine does not affect long-term outcome, and is not recommended. Other calcium channel blockers and magnesium sulfate have been studied, but are not presently recommended; neither is there any evidence that shows benefit if nimodipine is given intravenously.Nimodipine is readily authorized in the form of tablets and solution for infusion for the prevention and treatment of complications due to vasospasm following subarachnoid hemorrhage. Another sustained formulation of nimodipine administered via an external ventricular drain (EVD), called EG-1962, is also available. In contrast to the tablets and solution formulations of Nimodipine which require an administration every 4hrs for a total of 21 days, the sustained formulation, EG-1962, needs to be administered once directly into the ventricles. The CSF concentrations from EG-1962, however, were at least 2 orders of magnitude higher than those with oral nimodipine. These results supported a phase 3 study that demonstrated a favorable safety profile for EG-1962 but yielded inconclusive efficacy results due to notable differences in clinical outcome based on baseline disease severity.Some older studies have suggested that statin therapy might reduce vasospasm, but a subsequent meta-analysis including further trials did not demonstrate benefit on either vasospasm or outcomes. While corticosteroids with mineralocorticoid activity may help prevent vasospasm their use does not appear to change outcomes. A protocol referred to as "triple H" is often used as a measure to treat vasospasm when it causes symptoms; this is the use of intravenous fluids to achieve a state of hypertension (high blood pressure), hypervolemia (excess fluid in the circulation), and hemodilution (mild dilution of the blood). Evidence for this approach is inconclusive; no randomized controlled trials have been undertaken to demonstrate its effect.If the symptoms of delayed ischemia do not improve with medical treatment, angiography may be attempted to identify the sites of vasospasms and administer vasodilator medication (drugs that relax the blood vessel wall) directly into the artery. Angioplasty (opening the constricted area with a balloon) may also be performed. Other complications Hydrocephalus (obstruction of the flow of cerebrospinal fluid) may complicate SAH in both the short and long term. It is detected on CT scanning, on which there is enlargement of the lateral ventricles. If the level of consciousness is decreased, drainage of the excess fluid is performed by therapeutic lumbar puncture, extraventricular drain (a temporary device inserted into one of the ventricles), or occasionally a permanent shunt. Relief of hydrocephalus can lead to an enormous improvement in a persons condition. Fluctuations in blood pressure and electrolyte imbalance, as well as pneumonia and cardiac decompensation occur in about half the hospitalized persons with SAH and may worsen prognosis. Seizures occur during the hospital stay in about a third of cases.People have often been treated with preventative antiepileptic medications. This is controversial and not based on good evidence. In some studies, use of these medications was associated with a worse prognosis; although it is unclear whether this might be because the drugs themselves actually cause harm, or because they are used more often in persons with a poorer prognosis. There is a possibility of a gastric hemorrhage due to stress ulcers. Prognosis Short-term outcomes SAH is often associated with a poor outcome. The death rate (mortality) for SAH is between 40 and 50 percent, but trends for survival are improving. Of those that survive hospitalization, more than a quarter have significant restrictions in their lifestyle, and less than a fifth have no residual symptoms whatsoever. Delay in diagnosis of minor SAH (mistaking the sudden headache for migraine) contributes to poor outcome. Factors found on admission that are associated with poorer outcome include poorer neurological grade; systolic hypertension; a previous diagnosis of heart attack or SAH; liver disease; more blood and larger aneurysm on the initial CT scan; location of an aneurysm in the posterior circulation; and higher age. Factors that carry a worse prognosis during the hospital stay include occurrence of delayed ischemia resulting from vasospasm, development of intracerebral hematoma, or intraventricular hemorrhage (bleeding into the ventricles of the brain) and presence of fever on the eighth day of admission.So-called "angiogram-negative subarachnoid hemorrhage", SAH that does not show an aneurysm with four-vessel angiography, carries a better prognosis than SAH with aneurysm, but it is still associated with a risk of ischemia, rebleeding, and hydrocephalus. Perimesencephalic SAH (bleeding around the mesencephalon in the brain), however, has a very low rate of rebleeding or delayed ischemia, and the prognosis of this subtype is excellent.The prognosis of head trauma is thought to be influenced in part by the location and amount of subarachnoid bleeding. It is difficult to isolate the effects of SAH from those of other aspects of traumatic brain injury; it is unknown whether the presence of subarachnoid blood actually worsens the prognosis or whether it is merely a sign that a significant trauma has occurred. People with moderate and severe traumatic brain injury who have SAH when admitted to a hospital have as much as twice the risk of dying as those who do not. They also have a higher risk of severe disability and persistent vegetative state, and traumatic SAH has been correlated with other markers of poor outcome such as post traumatic epilepsy, hydrocephalus, and longer stays in the intensive care unit. More than 90 percent of people with traumatic subarachnoid bleeding and a Glasgow Coma Score over 12 have a good outcome.There is also modest evidence that genetic factors influence the prognosis in SAH. For example, having two copies of ApoE4 (a variant of the gene encoding apolipoprotein E that also plays a role in Alzheimers disease) seems to increase risk for delayed ischemia and a worse outcome. The occurrence of hyperglycemia (high blood sugars) after an episode of SAH confers a higher risk of poor outcome. Long-term outcomes Neurocognitive symptoms, such as fatigue, mood disturbances, and other related symptoms, are common sequelae. Even in those who have made good neurological recovery, anxiety, depression, posttraumatic stress disorder, and cognitive impairment are common; 46 percent of people who have had a subarachnoid hemorrhage have cognitive impairment that affects their quality of life. Over 60 percent report frequent headaches. Aneurysmal subarachnoid hemorrhage may lead to damage of the hypothalamus and the pituitary gland, two areas of the brain that play a central role in hormonal regulation and production. More than a quarter of people with a previous SAH may develop hypopituitarism (deficiencies in one or more of the hypothalamic–pituitary hormones such as growth hormone, luteinizing hormone, or follicle-stimulating hormone). SAH is also associated with SIADH and cerebral salt wasting, and is the most common cause of the latter. Epidemiology According to a review of 51 studies from 21 countries, the average incidence of subarachnoid hemorrhage is 9.1 per 100,000 annually. Studies from Japan and Finland show higher rates in those countries (22.7 and 19.7, respectively), for reasons that are not entirely understood. South and Central America, in contrast, have a rate of 4.2 per 100,000 on average.Although the group of people at risk for SAH is younger than the population usually affected by stroke, the risk still increases with age. Young people are much less likely than middle-age people (risk ratio 0.1, or 10 percent) to have a subarachnoid hemorrhage. The risk continues to rise with age and is 60 percent higher in the very elderly (over 85) than in those between 45 and 55. Risk of SAH is about 25 percent higher in women over 55 compared to men the same age, probably reflecting the hormonal changes that result from the menopause, such as a decrease in estrogen levels.Genetics may play a role in a persons disposition to SAH; risk is increased three- to fivefold in first-degree relatives of people having had a subarachnoid hemorrhage. But lifestyle factors are more important in determining overall risk. These risk factors are smoking, hypertension (high blood pressure), and excessive alcohol consumption. Having smoked in the past confers a doubled risk of SAH compared to those who have never smoked. Some protection of uncertain significance is conferred by caucasian ethnicity, hormone replacement therapy, and diabetes mellitus. There is likely an inverse relationship between total serum cholesterol and the risk of non-traumatic SAH, though confirmation of this association is hindered by a lack of studies. Approximately 4 percent of aneurysmal bleeds occur after sexual intercourse and 10 percent of people with SAH are bending over or lifting heavy objects at the onset of their symptoms.Overall, about 1 percent of all people have one or more cerebral aneurysms. Most of these are small and unlikely to rupture. History While the clinical picture of subarachnoid hemorrhage may have been recognized by Hippocrates, the existence of cerebral aneurysms and the fact that they could rupture was not established until the 18th century. The associated symptoms were described in more detail in 1886 by Edinburgh physician Dr Byrom Bramwell. In 1924, London neurologist Sir Charles P. Symonds (1890–1978) gave a complete account of all major symptoms of subarachnoid hemorrhage, and he coined the term "spontaneous subarachnoid hemorrhage". Symonds also described the use of lumbar puncture and xanthochromia in diagnosis.The first surgical intervention was performed by Norman Dott, who was a pupil of Harvey Cushing then working in Edinburgh. He introduced the wrapping of aneurysms in the 1930s, and was an early pioneer in the use of angiograms. American neurosurgeon Dr Walter Dandy, working in Baltimore, was the first to introduce clips in 1938. Microsurgery was applied to aneurysm treatment in 1972 in order to further improve outcomes. The 1980s saw the introduction of triple H therapy as a treatment for delayed ischemia due to vasospasm, and trials with nimodipine in an attempt to prevent this complication. In 1983, the Russian neurosurgeon Zubkov and colleagues reported the first use of transluminal balloon angioplasty for vasospasm after aneurysmal SAH. The Italian neurosurgeon Dr Guido Guglielmi introduced his endovascular coil treatment in 1991. References == External links ==

Dysequilibrium syndrome

Dysequilibrium syndrome may refer to: Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 1 (CAMRQ1), an autosomal recessive cerebellar ataxia associated with the VLDLR gene Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2 (CAMRQ2), an autosomal recessive cerebellar ataxia associated with the WDR81 gene Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 3 (CAMRQ3), an autosomal recessive cerebellar ataxia associated with the CA8 gene Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 (CAMRQ4), an autosomal recessive cerebellar ataxia associated with the ATP8A2 gene

Gingival and periodontal pocket

Gingival and periodontal pockets (also informally referred to as gum pockets) are dental terms indicating the presence of an abnormal depth of the gingival sulcus near the point at which the gingival tissue contacts the tooth. Tooth gingival interface The interface between a tooth and the surrounding gingival tissue is a dynamic structure. The gingival tissue forms a crevice surrounding the tooth, similar to a miniature, fluid-filled moat, wherein food debris, endogenous and exogenous cells, and chemicals float. The depth of this crevice, known as a sulcus, is in a constant state of flux due to microbial invasion and subsequent immune response. Located at the depth of the sulcus is the epithelial attachment, consisting of approximately 1 mm of junctional epithelium and another 1 mm of gingival fiber attachment, comprising the 2 mm of biologic width naturally found in the oral cavity. The sulcus is literally the area of separation between the surrounding epithelium and the surface of the encompassed tooth. Gingival pocket A gingival pocket presents when the marginal gingiva experiences an edematous reaction, whether due to localized irritation and subsequent inflammation, systemic issues, or drug induced gingival hyperplasia. Regardless of the etiology, when gingival hyperplasia occurs, greater than normal (the measurement in a pre-pathological state) periodontal probing measurements can be read, creating the illusion that periodontal pockets have developed. This phenomenon is also referred to as a false pocket or pseudopocket. The epithelial attachment does not migrate, it simply remains at the same attachment level found in pre-pathological health. The only anatomical landmark experiencing migration is the gingival margin in a coronal direction. In a gingival pocket, no destruction of the connective tissue fibers (gingival fibers) or alveolar bone occurs. This early sign of disease in the mouth is completely reversible when the etiology of the edematous reaction is eliminated and frequently occurs without dental surgical therapy. However, in certain situations, a gingivectomy is necessary to reduce the gingival pocket depths to a healthy 1–3 mm. Periodontal pocket As the original sulcular depth increases and the apical migration of the junctional epithelium has simultaneously occurred, the pocket is now lined by pocket epithelium (PE) instead of junctional epithelium (JE). To have a true periodontal pocket, a probing measurement of 4 mm or more must be clinically evidenced. In this state, much of the gingival fibers that initially attached the gingival tissue to the tooth have been irreversibly destroyed. The depth of the periodontal pockets must be recorded in the patient record for proper monitoring of periodontal disease. Unlike in clinically healthy situations, parts of the sulcular epithelium can sometimes be seen in periodontally involved gingival tissue if air is blown into the periodontal pocket, exposing the newly denuded roots of the tooth. A periodontal pocket can become an infected space and may result in an abscess formation with a papule on the gingival surface. Incision and drainage of the abscess may be necessary, as well as systemic antibiotics; placement of local antimicrobial delivery systems within the periodontal pocket to reduce localized infections may also be considered. It is classified as supra bony and infra bony based on its depth in relation to alveolar bone. Mucogingival defect If the destruction continues unabated apically and reaches the junction of the attached gingiva and alveolar mucosa, the pocket would thus be in violation of the mucogingival junction and would be termed a mucogingival defect. Pocket formation For the periodontal pocket to form, several elements need to be present. It all starts with the dental plaque . The invasion of the bacteria from the plaque eventually triggers inflammatory response. This in turn results in the gradual destruction of the tissues surrounding the teeth, known as the periodontium. Plaque that has been present long enough to harden and calcify will welcome additional bacteria to the pocket and make it virtually impossible to clean by means of a traditional toothbrush. Continuous destruction of surrounding tissues due to inflammation will lead to degradation of attachment and bone, eventually causing tooth loss. Certain circumstances can worsen the condition and are known as risk factors. These can either be systemic (like diabetes or smoking) or local (like overhanging dental restorative materials causing food trap). It is, therefore, important to manage plaque levels by appropriate oral hygiene measures. The importance of using interdental brushes along with standard or electric toothbrushing should be stressed early on. Early detection of high plaque levels at routine dental visits are found to be beneficial to avoid progression of the pocket formation. External links Scapoli, L; Girardi, A; Palmieri, A; Testori, T; Zuffetti, F; Monguzzi, R; Lauritano, D; Carinci, F (2012). "Microflora and periodontal disease". Dental Research Journal. 9 (Suppl 2): S202–6. doi:10.4103/1735-3327.109755 (inactive 31 July 2022). PMC 3692174. PMID 23814584.{{cite journal}}: CS1 maint: DOI inactive as of July 2022 (link) == References ==

Torus

In geometry, a torus (plural tori, colloquially donut or doughnut) is a surface of revolution generated by revolving a circle in three-dimensional space about an axis that is coplanar with the circle. If the axis of revolution does not touch the circle, the surface has a ring shape and is called a torus of revolution. If the axis of revolution is tangent to the circle, the surface is a horn torus. If the axis of revolution passes twice through the circle, the surface is a spindle torus. If the axis of revolution passes through the center of the circle, the surface is a degenerate torus, a double-covered sphere. If the revolved curve is not a circle, the surface is a related shape, a toroid. Real-world objects that approximate a torus of revolution include swim rings, inner tubes and ringette rings. Eyeglass lenses that combine spherical and cylindrical correction are toric lenses.A torus should not be confused with a solid torus, which is formed by rotating a disk, rather than a circle, around an axis. A solid torus is a torus plus the volume inside the torus. Real-world objects that approximate a solid torus include O-rings, non-inflatable lifebuoys, ring doughnuts, and bagels. In topology, a ring torus is homeomorphic to the Cartesian product of two circles: S1 × S1, and the latter is taken to be the definition in that context. It is a compact 2-manifold of genus 1. The ring torus is one way to embed this space into Euclidean space, but another way to do this is the Cartesian product of the embedding of S1 in the plane with itself. This produces a geometric object called the Clifford torus, a surface in 4-space. In the field of topology, a torus is any topological space that is homeomorphic to a torus. The surface of a coffee cup and a doughnut are both topological tori with genus one. An example of a torus can be constructed by taking a rectangular strip of flexible material, for example, a rubber sheet, and joining the top edge to the bottom edge, and the left edge to the right edge, without any half-twists (compare Möbius strip). Geometry A torus can be defined parametrically by: where θ, φ are angles which make a full circle, so their values start and end at the same point, R is the distance from the center of the tube to the center of the torus, r is the radius of the tube.Angle θ represents rotation around the tube, whereas φ represents rotation around the torus axis of revolution. R is known as the "major radius" and r is known as the "minor radius". The ratio R divided by r is known as the "aspect ratio". The typical doughnut confectionery has an aspect ratio of about 3 to 2. An implicit equation in Cartesian coordinates for a torus radially symmetric about the z-axis is or the solution of f(x, y, z) = 0, where Algebraically eliminating the square root gives a quartic equation, The three classes of standard tori correspond to the three possible aspect ratios between R and r: When R > r, the surface will be the familiar ring torus or anchor ring. R = r corresponds to the horn torus, which in effect is a torus with no "hole". R < r describes the self-intersecting spindle torus; its inner shell is a lemon and its outer shell is an apple When R = 0, the torus degenerates to the sphere.When R ≥ r, the interior of this torus is diffeomorphic (and, hence, homeomorphic) to a product of a Euclidean open disk and a circle. The volume of this solid torus and the surface area of its torus are easily computed using Pappuss centroid theorem, giving: These formulas are the same as for a cylinder of length 2πR and radius r, obtained from cutting the tube along the plane of a small circle, and unrolling it by straightening out (rectifying) the line running around the center of the tube. The losses in surface area and volume on the inner side of the tube exactly cancel out the gains on the outer side. Expressing the surface area and the volume by the distance p of an outermost point on the surface of the torus to the center, and the distance q of an innermost point to the center (so that R = p + q/2 and r = p − q/2), yields As a torus is the product of two circles, a modified version of the spherical coordinate system is sometimes used. In traditional spherical coordinates there are three measures, R, the distance from the center of the coordinate system, and θ and φ, angles measured from the center point. As a torus has, effectively, two center points, the centerpoints of the angles are moved; φ measures the same angle as it does in the spherical system, but is known as the "toroidal" direction. The center point of θ is moved to the center of r, and is known as the "poloidal" direction. These terms were first used in a discussion of the Earths magnetic field, where "poloidal" was used to denote "the direction toward the poles".In modern use, toroidal and poloidal are more commonly used to discuss magnetic confinement fusion devices. Topology Topologically, a torus is a closed surface defined as the product of two circles: S1 × S1. This can be viewed as lying in C2 and is a subset of the 3-sphere S3 of radius √2. This topological torus is also often called the Clifford torus. In fact, S3 is filled out by a family of nested tori in this manner (with two degenerate circles), a fact which is important in the study of S3 as a fiber bundle over S2 (the Hopf bundle). The surface described above, given the relative topology from R3, is homeomorphic to a topological torus as long as it does not intersect its own axis. A particular homeomorphism is given by stereographically projecting the topological torus into R3 from the north pole of S3. The torus can also be described as a quotient of the Cartesian plane under the identifications ( x , y ) ∼ ( x + 1 , y ) ∼ ( x , y + 1 ) , {\displaystyle (x,y)\sim (x+1,y)\sim (x,y+1),\,} or, equivalently, as the quotient of the unit square by pasting the opposite edges together, described as a fundamental polygon ABA−1B−1. The fundamental group of the torus is just the direct product of the fundamental group of the circle with itself: π 1 ( T 2 ) = π 1 ( S 1 ) × π 1 ( S 1 ) ≅ Z × Z . {\displaystyle \pi _{1}(\mathbf {T} ^{2})=\pi _{1}(S^{1})\times \pi _{1}(S^{1})\cong \mathbf {Z} \times \mathbf {Z} .} Intuitively speaking, this means that a closed path that circles the torus "hole" (say, a circle that traces out a particular latitude) and then circles the torus "body" (say, a circle that traces out a particular longitude) can be deformed to a path that circles the body and then the hole. So, strictly latitudinal and strictly longitudinal paths commute. An equivalent statement may be imagined as two shoelaces passing through each other, then unwinding, then rewinding. If a torus is punctured and turned inside out then another torus results, with lines of latitude and longitude interchanged. This is equivalent to building a torus from a cylinder, by joining the circular ends together, in two ways: around the outside like joining two ends of a garden hose, or through the inside like rolling a sock (with the toe cut off). Additionally, if the cylinder was made by gluing two opposite sides of a rectangle together, choosing the other two sides instead will cause the same reversal of orientation. The first homology group of the torus is isomorphic to the fundamental group (this follows from Hurewicz theorem since the fundamental group is abelian). Two-sheeted cover The 2-torus double-covers the 2-sphere, with four ramification points. Every conformal structure on the 2-torus can be represented as a two-sheeted cover of the 2-sphere. The points on the torus corresponding to the ramification points are the Weierstrass points. In fact, the conformal type of the torus is determined by the cross-ratio of the four points. n-dimensional torus The torus has a generalization to higher dimensions, the n-dimensional torus, often called the n-torus or hypertorus for short. (This is the more typical meaning of the term "n-torus", the other referring to n holes or of genus n.) Recalling that the torus is the product space of two circles, the n-dimensional torus is the product of n circles. That is: T n = S 1 × ⋯ × S 1 ⏟ n . {\displaystyle \mathbf {T} ^{n}=\underbrace {S^{1}\times \cdots \times S^{1}} _{n}.} The 1-torus is just the circle: T1 = S1. The torus discussed above is the 2-torus, T2. And similar to the 2-torus, the n-torus, Tn can be described as a quotient of Rn under integral shifts in any coordinate. That is, the n-torus is Rn modulo the action of the integer lattice Zn (with the action being taken as vector addition). Equivalently, the n-torus is obtained from the n-dimensional hypercube by gluing the opposite faces together. An n-torus in this sense is an example of an n-dimensional compact manifold. It is also an example of a compact abelian Lie group. This follows from the fact that the unit circle is a compact abelian Lie group (when identified with the unit complex numbers with multiplication). Group multiplication on the torus is then defined by coordinate-wise multiplication. Toroidal groups play an important part in the theory of compact Lie groups. This is due in part to the fact that in any compact Lie group G one can always find a maximal torus; that is, a closed subgroup which is a torus of the largest possible dimension. Such maximal tori T have a controlling role to play in theory of connected G. Toroidal groups are examples of protori, which (like tori) are compact connected abelian groups, which are not required to be manifolds. Automorphisms of T are easily constructed from automorphisms of the lattice Zn, which are classified by invertible integral matrices of size n with an integral inverse; these are just the integral matrices with determinant ±1. Making them act on Rn in the usual way, one has the typical toral automorphism on the quotient. The fundamental group of an n-torus is a free abelian group of rank n. The k-th homology group of an n-torus is a free abelian group of rank n choose k. It follows that the Euler characteristic of the n-torus is 0 for all n. The cohomology ring H•(Tn, Z) can be identified with the exterior algebra over the Z-module Zn whose generators are the duals of the n nontrivial cycles. Configuration space As the n-torus is the n-fold product of the circle, the n-torus is the configuration space of n ordered, not necessarily distinct points on the circle. Symbolically, Tn = (S1)n. The configuration space of unordered, not necessarily distinct points is accordingly the orbifold Tn/Sn, which is the quotient of the torus by the symmetric group on n letters (by permuting the coordinates). For n = 2, the quotient is the Möbius strip, the edge corresponding to the orbifold points where the two coordinates coincide. For n = 3 this quotient may be described as a solid torus with cross-section an equilateral triangle, with a twist; equivalently, as a triangular prism whose top and bottom faces are connected with a 1/3 twist (120°): the 3-dimensional interior corresponds to the points on the 3-torus where all 3 coordinates are distinct, the 2-dimensional face corresponds to points with 2 coordinates equal and the 3rd different, while the 1-dimensional edge corresponds to points with all 3 coordinates identical. These orbifolds have found significant applications to music theory in the work of Dmitri Tymoczko and collaborators (Felipe Posada, Michael Kolinas, et al.), being used to model musical triads. Flat torus A flat torus is a torus with the metric inherited from its representation as the quotient, R2/L, where L is a discrete subgroup of R2 isomorphic to Z2. This gives the quotient the structure of a Riemannian manifold. Perhaps the simplest example of this is when L = Z2: R2/Z2, which can also be described as the Cartesian plane under the identifications (x, y) ~ (x + 1, y) ~ (x, y + 1). This particular flat torus (and any uniformly scaled version of it) is known as the "square" flat torus. This metric of the square flat torus can also be realised by specific embeddings of the familiar 2-torus into Euclidean 4-space or higher dimensions. Its surface has zero Gaussian curvature everywhere. Its surface is flat in the same sense that the surface of a cylinder is flat. In 3 dimensions, one can bend a flat sheet of paper into a cylinder without stretching the paper, but this cylinder cannot be bent into a torus without stretching the paper (unless some regularity and differentiability conditions are given up, see below). A simple 4-dimensional Euclidean embedding of a rectangular flat torus (more general than the square one) is as follows: ( x , y , z , w ) = ( R cos ⁡ u , R sin ⁡ u , P cos ⁡ v , P sin ⁡ v ) {\displaystyle (x,y,z,w)=(R\cos u,R\sin u,P\cos v,P\sin v)} where R and P are positive constants determining the aspect ratio. It is diffeomorphic to a regular torus but not isometric. It can not be analytically embedded (smooth of class Ck, 2 ≤ k ≤ ∞) into Euclidean 3-space. Mapping it into 3-space requires one to stretch it, in which case it looks like a regular torus. For example, in the following map: ( x , y , z ) = ( ( R + P sin ⁡ v ) cos ⁡ u , ( R + P sin ⁡ v ) sin ⁡ u , P cos ⁡ v ) . {\displaystyle (x,y,z)=((R+P\sin v)\cos u,(R+P\sin v)\sin u,P\cos v).} If R and P in the above flat torus parametrization form a unit vector (R, P) = (cos(η), sin(η)) then u, v, and 0 < η < π/2 parameterize the unit 3-sphere as Hopf coordinates. In particular, for certain very specific choices of a square flat torus in the 3-sphere S3, where η = π/4 above, the torus will partition the 3-sphere into two congruent solid tori subsets with the aforesaid flat torus surface as their common boundary. One example is the torus T defined by T = { ( x , y , z , w ) ∈ S 3 ∣ x 2 + y 2 = 1 2 , z 2 + w 2 = 1 2 } . {\displaystyle T=\left\{(x,y,z,w)\in \mathbf {S} ^{3}\mid x^{2}+y^{2}={\frac {1}{2}},\ z^{2}+w^{2}={\frac {1}{2}}\right\}.} Other tori in S3 having this partitioning property include the square tori of the form Q⋅T, where Q is a rotation of 4-dimensional space R4, or in other words Q is a member of the Lie group SO(4). It is known that there exists no C2 (twice continuously differentiable) embedding of a flat torus into 3-space. (The idea of the proof is to take a large sphere containing such a flat torus in its interior, and shrink the radius of the sphere until it just touches the torus for the first time. Such a point of contact must be a tangency. But that would imply that part of the torus, since it has zero curvature everywhere, must lie strictly outside the sphere, which is a contradiction.) On the other hand, according to the Nash-Kuiper theorem, which was proven in the 1950s, an isometric C1 embedding exists. This is solely an existence proof and does not provide explicit equations for such an embedding. In April 2012, an explicit C1 (continuously differentiable) embedding of a flat torus into 3-dimensional Euclidean space R3 was found. It is similar in structure to a fractal as it is constructed by repeatedly corrugating an ordinary torus. Like fractals, it has no defined Gaussian curvature. However, unlike fractals, it does have defined surface normals. It is a flat torus in the sense that as metric spaces, it is isometric to a flat square torus. (These infinitely recursive corrugations are used only for embedding into three dimensions; they are not an intrinsic feature of the flat torus.) This is the first time that any such embedding was defined by explicit equations or depicted by computer graphics. Genus g surface In the theory of surfaces there is another object, the "genus" g surface. Instead of the product of n circles, a genus g surface is the connected sum of g two-tori. To form a connected sum of two surfaces, remove from each the interior of a disk and "glue" the surfaces together along the boundary circles. To form the connected sum of more than two surfaces, sum two of them at a time until they are all connected. In this sense, a genus g surface resembles the surface of g doughnuts stuck together side by side, or a 2-sphere with g handles attached. As examples, a genus zero surface (without boundary) is the two-sphere while a genus one surface (without boundary) is the ordinary torus. The surfaces of higher genus are sometimes called n-holed tori (or, rarely, n-fold tori). The terms double torus and triple torus are also occasionally used. The classification theorem for surfaces states that every compact connected surface is topologically equivalent to either the sphere or the connect sum of some number of tori, disks, and real projective planes. Toroidal polyhedra Polyhedra with the topological type of a torus are called toroidal polyhedra, and have Euler characteristic V − E + F = 0. For any number of holes, the formula generalizes to V − E + F = 2 − 2N, where N is the number of holes. The term "toroidal polyhedron" is also used for higher-genus polyhedra and for immersions of toroidal polyhedra. Automorphisms The homeomorphism group (or the subgroup of diffeomorphisms) of the torus is studied in geometric topology. Its mapping class group ( the connected components of the homeomorphism group) is surjective onto the group GL(n, Z) of invertible integer matrices, which can be realized as linear maps on the universal covering space Rn that preserve the standard lattice Zn (this corresponds to integer coefficients) and thus descend to the quotient. At the level of homotopy and homology, the mapping class group can be identified as the action on the first homology (or equivalently, first cohomology, or on the fundamental group, as these are all naturally isomorphic; also the first cohomology group generates the cohomology algebra: MCG Ho ⁡ ( T n ) = Aut ⁡ ( π 1 ( X ) ) = Aut ⁡ ( Z n ) = GL ⁡ ( n , Z ) . {\displaystyle \operatorname {MCG} _{\operatorname {Ho} }(\mathbf {T} ^{n})=\operatorname {Aut} (\pi _{1}(X))=\operatorname {Aut} (\mathbf {Z} ^{n})=\operatorname {GL} (n,\mathbf {Z} ).} Since the torus is an Eilenberg–MacLane space K(G, 1), its homotopy equivalences, up to homotopy, can be identified with automorphisms of the fundamental group); all homotopy equivalences of the torus can be realized by homeomorphisms – every homotopy equivalence is homotopic to a homeomorphism. Thus the short exact sequence of the mapping class group splits (an identification of the torus as the quotient of Rn gives a splitting, via the linear maps, as above): 1 → Homeo 0 ⁡ ( T n ) → Homeo ⁡ ( T n ) → MCG TOP ⁡ ( T n ) → 1. {\displaystyle 1\to \operatorname {Homeo} _{0}(\mathbf {T} ^{n})\to \operatorname {Homeo} (\mathbf {T} ^{n})\to \operatorname {MCG} _{\operatorname {TOP} }(\mathbf {T} ^{n})\to 1.} The mapping class group of higher genus surfaces is much more complicated, and an area of active research. Coloring a torus The toruss chromatic number is seven, meaning every graph that can be embedded on the torus has a chromatic number of at most seven. (Since the complete graph K 7 {\displaystyle {\mathsf {K_{7}}}} can be embedded on the torus, and χ ( K 7 ) = 7 {\displaystyle \chi ({\mathsf {K_{7}}})=7} , the upper bound is tight.) Equivalently, in a torus divided into regions, it is always possible to color the regions using no more than seven colors so that no neighboring regions are the same color. (Contrast with the four color theorem for the plane.) de Bruijn torus In combinatorial mathematics, a de Bruijn torus is an array of symbols from an alphabet (often just 0 and 1) that contains every m-by-n matrix exactly once. It is a torus because the edges are considered wraparound for the purpose of finding matrices. Its name comes from the De Bruijn sequence, which can be considered a special case where n is 1 (one dimension). Cutting a torus A solid torus of revolution can be cut by n (> 0) planes into maximally ( n + 2 n − 1 ) + ( n n − 1 ) = 1 6 ( n 3 + 3 n 2 + 8 n ) {\displaystyle {\begin{pmatrix}n+2\\n-1\end{pmatrix}}+{\begin{pmatrix}n\\n-1\end{pmatrix}}={\tfrac {1}{6}}(n^{3}+3n^{2}+8n)} parts.The first 11 numbers of parts, for 0 ≤ n ≤ 10 (including the case of n = 0, not covered by the above formulas), are as follows: 1, 2, 6, 13, 24, 40, 62, 91, 128, 174, 230, ... (sequence A003600 in the OEIS). See also Notes Nociones de Geometría Analítica y Álgebra Lineal, ISBN 978-970-10-6596-9, Author: Kozak Ana Maria, Pompeya Pastorelli Sonia, Verdanega Pedro Emilio, Editorial: McGraw-Hill, Edition 2007, 744 pages, language: Spanish Allen Hatcher. Algebraic Topology. Cambridge University Press, 2002. ISBN 0-521-79540-0. V. V. Nikulin, I. R. Shafarevich. Geometries and Groups. Springer, 1987. ISBN 3-540-15281-4, ISBN 978-3-540-15281-1. "Tore (notion géométrique)" at Encyclopédie des Formes Mathématiques Remarquables References External links Creation of a torus at cut-the-knot "4D torus" Fly-through cross-sections of a four-dimensional torus "Relational Perspective Map" Visualizing high dimensional data with flat torus Polydoes, doughnut-shaped polygons Archived at Ghostarchive and the Wayback Machine: Séquin, Carlo H (27 January 2014). "Topology of a Twisted Torus – Numberphile" (video). Brady Haran. Anders Sandberg (4 February 2014). "Torus Earth". Retrieved 24 July 2019.

Paronychia

Paronychia is an inflammation of the skin around the nail, which can occur suddenly, when it is usually due to the bacterium Staphylococcus aureus, or gradually when it is commonly caused by the fungus Candida albicans. The term is from Greek: παρωνυχία from para around, onyx nail, and the abstract noun suffix -ia.Risk factors include repeatedly washing hands and trauma to the cuticle such as may occur from repeated nail biting or hangnails. Treatment includes antibiotics and antifungals, and if pus is present, the consideration of incision and drainage.Paronychia is commonly misapplied as a synonym for herpetic whitlow or felon. Definition and etymology Paronychia is an inflammation of the skin around the nail, which can occur suddenly (acute), when it is usually due to the bacterium Staphylococcus aureus, or gradually (chronic) when it is commonly caused by Candida albicans.The term is from Greek: παρωνυχία from para, "around", onyx, "nail" and the noun suffix -ia. Signs and symptoms The index and middle fingers are most commonly affected and may present with redness, swelling and pain. Pus or discharge may be present. Causes Acute paronychia is usually caused by bacteria. It is often treated with antibiotics, either topical (applied to the skin) or oral (taken by mouth), or both. Chronic paronychia is most often caused by a yeast infection of the soft tissues around the nail, but can also be traced to a bacterial infection. If the infection is continuous, the cause is often fungal and needs antifungal cream or paint to be treated.Risk factors include repeatedly washing hands and trauma to the cuticle such as may occur from repeated nail biting. or hangnails. In the context of bartending, it is known as "bar rot".Prosectors paronychia is a primary inoculation of tuberculosis of the skin and nails, named after its association with prosectors, who prepare specimens for dissection. Paronychia around the entire nail is sometimes referred to as "runaround paronychia".Painful paronychia in association with a scaly, erythematous, keratotic rash (papules and plaques) of the ears, nose, fingers, and toes may be indicative of acrokeratosis paraneoplastica, which is associated with squamous-cell carcinoma of the larynx.Paronychia can occur with diabetes, drug-induced immunosuppression, or systemic diseases such as pemphigus. Diagnosis Types Paronychia may be divided as occurring suddenly, acute, or gradually, chronic. Acute Acute paronychia is an infection of the folds of tissue surrounding the nail of a finger or, less commonly, a toe, lasting less than six weeks. The infection generally starts in the paronychium at the side of the nail, with local redness, swelling, and pain.: 660  Acute paronychia is usually caused by direct or indirect trauma to the cuticle or nail fold, and may be from relatively minor events, such as dishwashing, an injury from a splinter or thorn, nail biting, biting or picking at a hangnail, finger sucking, an ingrown nail, or manicure procedures.: 339 Chronic Chronic paronychia is an infection of the folds of tissue surrounding the nail of a finger or, less commonly, a toe, lasting more than six weeks. It is a nail disease prevalent in individuals whose hands or feet are subject to moist local environments, and is often due to contact dermatitis.: 660  In chronic paronychia, the cuticle separates from the nail plate, leaving the region between the proximal nail fold and the nail plate vulnerable to infection.: 343  It can be the result of dish washing, finger sucking, aggressively trimming the cuticles, or frequent contact with chemicals (mild alkalis, acids, etc.). Alternatively, paronychia may be divided as follows: Candidal paronychia is an inflammation of the nail fold produced by C. albicans.: 310  Pyogenic paronychia is an inflammation of the folds of skin surrounding the nail caused by bacteria.: 254  Generally, acute paronychia is pyogenic, as it is usually caused by a bacterial infection. Differential Differential diagnosis of paronychia includes: Cellulitis is a superficial infection and presents as erythema and swelling to the affected portion of the body with no area of fluctuance. Treatment is with oral antibiotics. Whitlow or felon is a subcutaneous infection of the digital pulp space. The area becomes warm, red, tense, and very painful due to the confinement of the infection, creating pressure in the individual compartments created by the septa of the finger pad. These require excision and drainage, usually with a longitudinal incision and blunt dissection to ensure adequate drainage. Herpetic whitlow is a viral infection of the distal finger caused by HSV. Patients usually develop a burning, pruritic sensation before the infection erupts. A physical exam shows vesicles and vesicopustules, along with pain and erythema. It is important to not confuse this with a felon or a paronychia as incision and drainage of herpetic whitlow could result in a secondary bacterial infection and failure to heal. Onychomycosis is a fungal infection of the nail that causes whitish-yellowish discoloration. Sometimes, it is difficult to treat and requires oral antibiotics instead of topical. Nail psoriasis can affect the fingernails and toenails. It may cause thickening of the nails with areas of pitting, ridges, irregular contour, and even raising of the nail from the nail bed. Squamous-cell carcinoma is mainly cancer of the skin, but can also affect the nail bed. It is a rare malignant subungual tumor subject to misdiagnosis as chronic paronychia. Treatment When no pus is present, warm soaks for acute paronychia are reasonable, though evidence to support its use is lacking.Chronic paronychia is treated by avoiding whatever is causing it, a topical antifungal, and a topical steroid. In those who do not improve following these measures, oral antifungals and steroids may be used or the nail fold may be removed surgically. Antibiotics No strong evidence has been found to recommend topical vs. oral antibiotics, and this may be physician-dependent based on experience. Antibiotics used should have S. aureus coverage. Topical antibiotics used may be a triple antibiotic ointment, bacitracin, or mupirocin. In patients failing topical treatment or more severe cases, oral antibiotics are an option; dicloxacillin or cephalexin can be used. Indications for antibiotics with anaerobic coverage include patients where a concern exists for oral inoculation; this would require the addition of clindamycin or amoxicillin-clavulanate. Antibiotics such as clindamycin or cephalexin are also often used, the first being more effective in areas where MRSA is common. If signs of an abscess (the presence of pus) are seen, drainage is recommended. Epidemiology Paronychia is more common in women than in men, by a ratio of three to one. Usually, they affect manual-labor workers or people in occupations that require them to have their hands or feet submerged in water for prolonged periods (e.g., dishwashers). Middle-aged females are at the highest risk of infection. References External links "Paronychia Nail Infection". Dermatologic Disease Database. American Osteopathic College of Dermatology. Archived from the original on 2013-03-30. Retrieved 2006-07-12.

Acephaly

Acephaly (in Greek: a = without / képhalê = head) is a term used to define: In medicine: in forensic medicine: a decapitated corpse whose head has not been found Twin reversed arterial perfusion an animal without a head. For example: Great scallop Maggot, the larva of the fly a relatively complete sculpture, the head of which has not been found. For example: Winged Victory of Samothrace Venus of Arles Commons:Category:Headless statues

Lung cavity

A lung cavity or pulmonary cavity is an abnormal, thick-walled, air-filled space within the lung. Cavities in the lung can be caused by infections, cancer, autoimmune conditions, trauma, congenital defects, or pulmonary embolism. The most common cause of a single lung cavity is lung cancer. Bacterial, mycobacterial, and fungal infections are common causes of lung cavities. Globally, tuberculosis is likely the most common infectious cause of lung cavities. Less commonly, parasitic infections can cause cavities. Viral infections almost never cause cavities. The terms cavity and cyst are frequently used interchangeably; however, a cavity is thick walled (at least 5 mm), while a cyst is thin walled (4 mm or less). The distinction is important because cystic lesions are unlikely to be cancer, while cavitary lesions are often caused by cancer.Diagnosis of a lung cavity is made with a chest X-ray or CT scan of the chest, which helps to exclude mimics like lung cysts, emphysema, bullae, and cystic bronchiectasis. Once an imaging diagnosis has been made, a person’s symptoms can be used to further narrow the differential diagnosis. For example, recent onset of fever and productive cough suggest an infection, while a chronic cough, fatigue, and unintentional weight loss suggest cancer or tuberculosis. Symptoms of a lung cavity due to infection can include fever, chills, and cough. Knowing how long someone has had symptoms for or how long a cavity has been present on imaging can also help to narrow down the diagnosis. If symptoms or imaging findings have been present for less than three months, the cause is most likely an acute infection; if they have been present for more than three months, the cause is most likely a chronic infection, cancer, or an autoimmune disease.The presence of lung cavities is associated with worse outcomes in lung cancer and tuberculosis; however, if a lung cancer develops cavitation after chemotherapy and radiofrequency ablation, that indicates a good response to treatment. Formal definition In the 2008 Fleischner Society "Glossary of Terms for Thoracic Imaging", a cavity is radiographically defined as “a gas-filled space, seen as a lucency or low-attenuation area, within [a] pulmonary consolidation, a mass, or a nodule”. Pathologically, a cavity is “usually produced by the expulsion or drainage of a necrotic part of the lesion via the bronchial tree.” Lung cavity mimics The first step in evaluating a suspected lung cavity lesion is to exclude other kinds of abnormal air-filled spaces in the lung, including lung cysts, emphysema, bullae, and cystic bronchiectasis. Lung cysts are the most common mimics of lung cavities. Cavities and cysts are similar in that they are both abnormal, air-containing spaces with clearly defined walls. The difference between cavities and cysts is that cavities are thick walled, while cysts are thin walled. Generally, cavities have walls that are at least 5 mm thick, while cysts have walls that are 4 mm or less, and often less than 2 mm.The distinction between cysts and cavities is important because the thicker the wall is, the more likely it is to be cancer. Thus, cystic lesions are unlikely to be cancer, while cavitary lesions are often caused by cancer. In a study from 1980 that used chest X-rays to evaluate 65 cases of solitary lung cavities, 0% percent of cavities with walls 1 mm or less were malignant (that is, cancerous), versus 8% of cavities with walls 4 mm or less, 49% of cavities with walls 5 to 15 mm, and 95% of cavities with walls 15 mm or greater. However, a 2007 study that used CT to evaluate lung cavities showed no relationship between wall thickness and the likelihood of malignancy. It did show that malignant cavities are more likely than benign cavities to have an irregular internal wall (49% vs 26%) and have an indentation of the outer wall of the cavity (54% vs 29%).Areas of emphysema are abnormal, air-filled spaces that usually do not have visible walls, and bullae are very thin walled (<1 mm). Cystic bronchiectasis is irreversible bronchial dilation, which is permanent widening of the bronchioles (small airways) in the lung. It can be distinguished on imaging by a lack of bronchial tapering, meaning that the bronchioles do not get narrower as they travel further into the lung. Cystic bronchiectasis is also associated with an increased bronchoarterial ratio, meaning that the bronchioles are larger than the blood vessels that run alongside them. Infectious causes Bacterial, mycobacterial, and fungal infections are common causes of lung cavities. Globally, tuberculosis is likely the most common infectious cause of lung cavities. Less commonly, parasitic infections can cause cavities. Viral infections almost never cause lung cavities; in a small study of immunocompromised patients with a lung infection, the presence of a cavity on CT scan essentially ruled out viral infection. In the same study, about one-third of the cavities were caused by a bacterial infection, another third were caused by a mycobacterial infection, and another third were caused by a fungal infection. Bacterial Bacteria can cause lung cavities in one of two ways; they can either enter the lung through the trachea (windpipe), or they can enter through the bloodstream as septic pulmonary emboli (infected blood clots). Community-acquired pneumonia is an uncommon cause of lung cavities, but cavitary pneumonia is occasionally seen with Streptococcus pneumoniae or Haemophilus influenzae infection. However, since these two species of bacteria are such common causes of pneumonia, they may cause a significant fraction of all cavitary pneumonias. The most common bacterial causes of lung cavities are Streptococcus species and Klebsiella pneumoniae. Less commonly, the bacteria Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter, Escherichia coli, and Legionella can cause cavitation. Nocardia is a bacterium that can cause pulmonary nocardiosis and lung cavities in people who are immunocompromised (have weak immune systems), including organ transplant recipients who are on immunosuppressants, and those with AIDS, lymphoma, or leukemia. Melioidosis, caused by the bacteria Burkholderia pseudomallei, is common in tropical areas, especially Southeast Asia, and is frequently associated with lung cavities.Pneumonia can lead to the development of a lung abscess, which is a pus-containing necrotic lesion of the lung parenchyma (lung tissue). On CT scan of the chest, a lung abscess appears as an intermediate- or thick-walled cavity with or without an air-fluid level (a flat line separating the air in the cavity from the fluid). An abscess can occur anywhere in the lung. Risk factors for polymicrobial lung abscesses (abscesses caused by multiple species of bacteria) include alcoholism, a history of aspiration (food or water accidentally going down the trachea), poor dentition (bad teeth), older age, diabetes mellitus, drug abuse, and artificial ventilation. Polymicrobial lung abscesses are usually due to aspiration and are located in the posterior segments of the upper lobes or superior segments of the lower lobes. Klebsiella pneumoniae is a common cause of lung abscesses and is usually monomicrobial (caused by a single species of bacteria). Risk factors include diabetes and chronic lung disease. A lung abscess due to Klebsiella can progress to massive pulmonary gangrene, a rare condition in which an entire section of the lung is completely destroyed. Half of all cases of pulmonary gangrene are caused by Klebsiella. Imaging in pulmonary gangrene shows multiple small cavities joining together to form a large cavity. Mycobacterial Mycobacteria that can cause cavitations include Mycobacterium tuberculosis and nontuberculous mycobacteria, most commonly Mycobacterium avium complex. Primary tuberculosis is caused by the initial infection with Mycobacterium tuberculosis and rarely results in the formation of lung cavities. 90% of people with primary tuberculosis are able to contain the infection and enter a latent phase. Reactivation tuberculosis, which is caused by the reactivation of latent tuberculosis, results in lung cavities visible on X-ray 30 to 50% of the time. There are frequently multiple cavities, and they most commonly occur in the apical and posterior segments of the upper lobes or the superior segment of the lower lobes. Cavitary tuberculosis is associated with worse outcomes, a higher rate of treatment failure, more frequent relapse after treatment, and a higher risk of transmitting the disease to others. Even after successful treatment with anti-tuberculosis drugs, 20-50% of patients with cavitary tuberculosis have persistent cavities, which results in decreased lung function and increased risk of opportunistic infections by Aspergillus fumigatus and other fungal pathogens.Nontuberculous mycobacteria (NTM) are all mycobacterial species other than Mycobacteria tuberculosis (which causes tuberculosis) and Mycobacterium leprae (which causes leprosy). NTM are found everywhere in the environment but are most commonly found in soil and water. Lung disease is caused by inhaling or ingesting nontuberculous mycobacteria. Unlike tuberculosis, NTM infection is not transmitted from person to person. Although NTM lung infections can cause lung cavities, the most common finding on imaging is bronchiectasis, which may occur with or without cavities. Mycobacterium avium complex (MAC) is the most common cause of NTM lung disease in most countries, including the United States. Classically, MAC infection results in either upper lobe cavities in male smokers with COPD or bronchiectasis in thin, older women; however, it is possible to have both cavities and bronchiectasis in the same patient. Similar to tuberculosis, the presence of cavities in MAC infection is associated with worse outcomes. Mycobacterium kansasii, Mycobacterium xenopi, and the rapidly-growing Mycobacterium abscessus have also been associated with lung cavities. Fungal Fungal infections that can cause cavitations include histoplasmosis, coccidiomycosis, cryptococcosis, and aspergillosis. Aspergillosis, most commonly caused by Aspergillus fumigatus, can present in four different ways (listed in order of increasing severity): aspergilloma, allergic bronchopulmonary aspergillosis (ABPA), chronic necrotizing aspergillosis, and invasive aspergillosis. All of these are associated with lung cavities except for ABPA, which is a hypersensitivity response associated with bronchiectasis on imaging. An aspergilloma is an infection of a pre-existing lung cavity by Aspergillus species without tissue invasion and results in the formation of a fungal ball. Historically, tuberculosis was the most common cause of the lung cavity (and still is in areas where tuberculosis is endemic); however, the cavity can also be caused by sarcoidosis, bullae, bronchiectasis, or cystic lung disease. Chronic necrotizing aspergillosis and invasive aspergillosis are usually seen in immunocompromised people. Risk factors for chronic necrotizing aspergillosis include advanced age, alcoholism, diabetes, and mild immunosuppression. Invasive pulmonary aspergillosis is mainly seen in severely immunocompromised people, especially those with hematological malignancies (cancers of the blood), bone marrow transplant recipients, and people on long-term corticosteroid therapy, such as prednisone. Allogeneic bone marrow transplant recipients have the highest risk of getting invasive aspergillosis. Lung transplant recipients are also at high risk. Parasitic Parasitic infections associated with cavitations include echinococcosis and paragonimiasis. Echinococcus is a tapeworm that most commonly infects dogs; people become infected by ingesting food or water that contains Echinococcus eggs. This results in cysts forming in the body, most commonly in the liver, but lung involvement is seen in 10-30% of cases. The cysts in the lung sometimes look like cavities on imaging. Paragonimus westermani, also called the lung fluke, is a flatworm which is transmitted by eating freshwater crabs or crayfish containing metacercaria (the infective form of the tapeworm). They mature into adult lung flukes in the lung, where cavitations may be seen in 15-59% of cases. Paragonimiasis is common in East Asia and Southeast Asia. Noninfectious causes Lung cancer The most common cause of a single lung cavity is lung cancer. Usually, the cavity forms because the cancer grows more rapidly then its blood supply, resulting in necrosis (cell death) in the central part of the cancer. 81% of lung cancers that develop cavities over-express epidermal growth factor receptor (EGFR), which could be related to rapid growth, central necrosis, and cavity formation. 11% of primary lung cancers (cancers that start in the lung) have cavities that can be seen on chest X-ray; 22% of primary lung cancers will have cavities on CT, which is more sensitive. Squamous-cell carcinoma of the lung is more likely to develop cavitations than lung adenocarcinoma or large-cell lung carcinoma. Other primary cancers of the lung, such as lymphoma and Kaposi’s sarcoma, can also cavitate, especially in people with AIDS. Lung cancers that develop cavities are associated with a poor prognosis (worse outcomes). Cancers that metastasize (spread) to the lung can also develop cavitations, but this is only seen about 4% of the time on X-ray. Metastatic cancers of squamous cell origin are also more likely to cavitate than cancers of other origins. Both chemotherapy (drugs to treat cancer) and radiofrequency ablation (destroying cancer with radio waves) can cause lung cancers to develop cavities, which is a sign of a good response to treatment. It is possible to have both an infection and lung cancer in the same cavity; the most common combination is primary lung cancer and tuberculosis. Autoimmune Autoimmune causes of lung cavities include granulomatosis with polyangiitis, rheumatoid arthritis, and rarely necrotizing sarcoidosis (less than 1% of people with sarcoidosis develop lung cavities). Ankylosing spondylitis, eosinophilic granulomatosis with polyangiitis, and systemic lupus erythematous rarely cause lung cavities. Pulmonary embolism and septic emboli Pulmonary embolism (a blood clot in the lung) causes pulmonary infarction (the death of lung tissue) less than 15% of the time, and only about 5% of pulmonary infarctions result in lung cavities. Septic pulmonary emboli (infected blood clots) are collections of infectious organisms, fibrin, and platelets that travel through the blood to the lung and cause small areas of pulmonary infarction by blocking off blood flow. This results in multiple small cavities 85% of the time. Symptoms can include cough, dyspnea (shortness of breath), chest pain, hemoptysis (coughing up blood) and sinus tachycardia (a fast heart rate). Risk factors for septic pulmonary emboli include IV drug use, implanted prosthetic devices (like central lines, pacemakers, and right-sided heart valves), and septic thrombophlebitis (a blood clot in a vein due to infection). Two forms of septic thrombophlebitis include pelvic thrombophlebitis and Lemierres syndrome (septic thrombophlebitis of the internal jugular vein). Trauma Pulmonary contusion (lung bruise) from blunt chest trauma causes bleeding into the alveoli (air sacs) and can cause small cavities to form that are called traumatic pulmonary pseudocysts (TPP). This is rare, as less than 3% of lung injuries lead to TPP. It can occur at any age, but is more common in children and adults under the age of 30. Although it can occur anywhere in the lung, it is most common in the lower lobes. TPP usually resolves on its own within four weeks. Congenital Congenital lung cavities, or lung cavities present at birth, include bronchogenic cysts, congenital pulmonary airway malformation, and pulmonary sequestration. These congenital lesions are the most common cause of lung cavities in infants, children, and young adults. Bronchogenic cysts are due to abnormal budding of the bronchial tree. About 70% are found in the mediastinum, which is the central part of the chest where the heart is. Another 15 to 20% are intrapulmonary (within the lung), usually in the lower lobes. Congenital pulmonary airway malformation, formerly called congenital cystic adenomatoid malformation, is a benign tumor the results in the formation of single or multiple cysts. Pulmonary sequestration refers to abnormal lung tissue that gets its blood supply from the systemic circulation instead of the pulmonary circulation, like the rest of the lung. This lung tissue is also not connected to the trachea. See also Focal lung pneumatosis, article comparing lung blebs, bullae, cysts, and cavities == References ==

Elective mutism

Elective mutism is a now outdated term which was defined as a refusal to speak in almost all social situations (despite normal ability to do so), while selective mutism was considered to be a failure to speak in specific situations and is strongly associated with social anxiety disorder. In contrast to selective mutism, it was thought someone who was electively mute may not speak in any situation, as is usually shown in books and films. Elective mutism was often attributed to defiance or the effect of trauma. Those who are able to speak freely in some situations but not in others are now better described by selective mutism. History In 1877, a German physician named the disorder aphasia voluntaria to describe children who were able to speak normally but often "refused" to.In 1980, a study by Torey Hayden identified four "subtypes" of Elective Mutism: Symbiotic mutism: the most common of the forms, caused by a vocal and dominating mother and absent father (very rarely the other way around) and characterized by the use of mutism as controlling behavior around other adults. Speech phobic mutism: the least common, in which the child showed distinct fear at hearing a recording of their voice. This also involved ritualistic behaviors, which may reflect OCD, and was thought to be caused by the child having been told to keep a family secret. Reactive mutism: a reaction to trauma and/or abuse, with all children showing symptoms of depression and being notably withdrawn, usually showing no facial expressions. Notably, Hayden admits that some children put in this category had no apparent incident to react to, but they were included because of their symptoms. Passive-aggressive mutism: silence is used as a display of hostility, connected to antisocial behavior. Some of the children in her study had reportedly not been mute until age 9–12.The Diagnostic and Statistical Manual of Mental Disorders (DSM), first published in 1952, first included Elective Mutism in its third edition, published in 1980. Elective mutism was described as "a continuous refusal to speak in almost all social situations" despite normal ability to speak. While "excessive shyness" and other anxiety-related traits were listed as associated features, predisposing factors included "maternal overprotection", intellectual disability, and trauma. Elective mutism in the third edition revised (DSM III-R) is described similarly as in the third edition except for specifying that the disorder is not related to social anxiety disorder. In 1994, the fourth edition of the DSM reflected the name change to selective mutism and redefined the disorder. Cultural references Though elective mutism is no longer recognized by most psychiatrists, it is a popular character element or plot point in stories and movies. Many characters choose to stop speaking, for various reasons. Even more commonly, there are also characters who stop speaking after a traumatic incident. In both these cases, often, and almost always in the second, the character is silent in all situations. This is therefore not selective mutism, and anxiety is very rarely involved. Selective mutism itself is almost nonexistent in pop culture. The following are a few references to stories including a character who does not speak despite being physically able to. In the book Cut by Patricia McCormick, the main character, Callie, is an elective mute. In The House of the Spirits by Isabel Allende, Clara Trueba is mute after witnessing her sisters molestation and autopsy. "She could not move until the first lights of dawn appeared. Only then did she slip back into her bed, feeling within her the silence of the entire world. Silence filled her utterly." In Hannibal Rising by Thomas Harris, Hannibal Lecter is mute after witnessing his sister killed and eaten. In the book Flying Solo, the character Rachel is mute for six months after a classmate dies. In The Piano, Ada is an elective mute. She chooses to learn to speak at the end of the film. In the 1993 movie, House of Cards, Sally Matthews chooses not to speak after her father dies. In the book Halo: Ghosts of Onyx, Lucy-B091 is mute after she is one of only two survivors from her unit of 300. In the movie The Prophet Kamilas daughter, Elmitra, is depicted as mute after the death of her father. In the 2014 video game Watch Dogs, Aiden Pearces nephew, Jackson, is electively mute after the death of his sister. In the book Fifty Shades of Grey, Christian Grey is depicted as having been an elective mute from age 4, when he witnessed his birth mothers drug overdose and death and was with her body for days before being discovered, until he was 6 years old and he spoke his newly adopted baby sisters name. In John Greens narrative YouTube series Swindon Town Swoodilypoopers, midfielder Maric Maric is selectively mute. In A Good Woman Is Hard to Find, Ben Collins stops speaking after witnessing his father being knifed to death. In the season 7 episode of Little House on the Prairie "The Silent Cry", one of the two brothers is depicted as an elective mute, much of the story revolving around the issues with adopting him due to not speaking. == References ==

Hypermethioninemia

Hypermethioninemia is an excess of the amino acid methionine, in the blood. This condition can occur when methionine is not broken down properly in the body. Presentation Genetics Hypermethioninemia can have different inheritance patterns. This condition is usually inherited in an autosomal recessive pattern, which means two copies of the gene 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.Hypermethioninemia is occasionally inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In these cases, an affected person usually has one parent with the condition. Pathophysiology Inherited hypermethioninemia that is not associated with other metabolic disorders can be caused by shortages in the enzymes that break down methionine. These enzymes are produced from the MAT1A, GNMT and AHCY genes. The reactions involved in metabolizing methionine help supply some of the amino acids needed for protein production. These reactions are also involved in transferring methyl groups, consisting of a carbon atom and three hydrogen atoms, from one molecule to another (transmethylation), which is important in many cellular processes. The MAT1A gene provides instructions for producing the enzyme methionine adenosyltransferase. This enzyme converts methionine into a compound called S-adenosylmethionine. The GNMT gene provides instructions for making the enzyme glycine N-methyltransferase. This enzyme starts the next step in the process, converting S-adenosylmethionine to a compound called S-adenosyl homocysteine. The AHCY gene provides instructions for producing the enzyme S-adenosylhomocysteine hydrolase. This enzyme converts the S-adenosyl homocysteine into the compound homocysteine. Homocysteine may be converted back to methionine or into another amino acid, cysteine.A deficiency of any of these enzymes results in a buildup of methionine in the body, and may cause signs and symptoms related to hypermethioninemia. Diagnosis People with hypermethioninemia often do not show any symptoms. Some individuals with hypermethioninemia exhibit learning disabilities, mental retardation, and other neurological problems; delays in motor skills such as standing or walking; sluggishness; muscle weakness; liver problems; unusual facial features; and their breath, sweat, or urine may have a smell resembling boiled cabbage.Hypermethioninemia can occur with other metabolic disorders, such as homocystinuria, tyrosinemia and galactosemia, which also involve the faulty breakdown of particular molecules. It can also result from liver disease or excessive dietary intake of methionine from consuming large amounts of protein or a methionine-enriched infant formula. Treatment See also List of amino acid metabolism disorders References == External links ==

Sideroblastic anemia

Sideroblastic anemia, or sideroachrestic anemia, is a form of anemia in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells (erythrocytes). In sideroblastic anemia, the body has iron available but cannot incorporate it into hemoglobin, which red blood cells need in order to transport oxygen efficiently. The disorder may be caused either by a genetic disorder or indirectly as part of myelodysplastic syndrome, which can develop into hematological malignancies (especially acute myeloid leukemia). Sideroblasts (sidero- + -blast) are nucleated erythroblasts (precursors to mature red blood cells) with granules of iron accumulated in the mitochondria surrounding the nucleus. Normally, sideroblasts are present in the bone marrow, and enter the circulation after maturing into a normal erythrocyte. The presence of sideroblasts per se does not define sideroblastic anemia. Only the finding of ring (or ringed) sideroblasts characterizes sideroblastic anemia. Ring sideroblasts are named so because iron-laden mitochondria form a ring around the nucleus. It is a subtype of basophilic granules of the erythrocyte, but which can only be seen in bone marrow. To count a cell as a ring sideroblast, the ring must encircle a third or more of the nucleus and contain five or more iron granules, according to the 2008 WHO classification of the tumors of the hematopoietic and lymphoid tissues. Types The WHO International Working Group on Morphology of MDS (IWGM-MDS) defined three types of sideroblasts: Type 1 sideroblasts: fewer than 5 siderotic granules in the cytoplasm Type 2 sideroblasts: 5 or more siderotic granules, but not in a perinuclear distribution Type 3 or ring sideroblasts: 5 or more granules in a perinuclear position, surrounding the nucleus or encompassing at least one third of the nuclear circumference.Type 1 and type 2 are found in non-sideroblastic anemias. Type 3 is found only in sideroblastic anemia. Symptoms and signs Symptoms of sideroblastic anemia include skin paleness, fatigue, dizziness, and enlarged spleen and liver. Heart disease, liver damage, and kidney failure can result from iron buildup in these organs. Causes Causes of sideroblastic anemia can be categorized into three groups: congenital sideroblastic anemia, acquired clonal sideroblastic anemia, and acquired reversible sideroblastic anemia. All cases involve dysfunctional heme synthesis or processing. This leads to granular deposition of iron in the mitochondria that form a ring around the nucleus of the developing red blood cell. Congenital forms often present with normocytic or microcytic anemia while acquired forms of sideroblastic anemia are often normocytic or macrocytic. Congenital sideroblastic anemia X-linked sideroblastic anemia: This is the most common congenital cause of sideroblastic anemia and involves a defect in ALAS2, which is involved in the first step of heme synthesis. Although X-linked, approximately one third of patients are women due to skewed X-inactivation (lyonizations). Autosomal recessive sideroblastic anemia involves mutations in the SLC25A38 gene. The function of this protein is not fully understood, but it is involved in mitochondrial transport of glycine. Glycine is a substrate for ALAS2 and necessary for heme synthesis. The autosomal recessive form is typically severe in presentation. Genetic syndromes: Rarely, sideroblastic anemia may be part of a congenital syndrome and present with associated findings, such as ataxia, myopathy, and pancreatic insufficiency. Acquired clonal sideroblastic anemia Clonal sideroblastic anemias fall under the broader category of myelodysplastic syndromes (MDS). Three forms exist and include refractory anemia with ringed sideroblasts (RARS), refractory anemia with ringed sideroblasts and thrombocytosis (RARS-T), and refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS). These anemias are associated with increased risk for leukemic evolution. Acquired reversible sideroblastic anemia Causes include excessive alcohol use (the most common cause of sideroblastic anemia), pyridoxine deficiency (vitamin B6 is the cofactor in the first step of heme synthesis), lead poisoning and copper deficiency. Excess zinc can indirectly cause sideroblastic anemia by decreasing absorption and increasing excretion of copper. Antimicrobials that may lead to sideroblastic anemia include isoniazid (which interferes with pyridoxine metabolism), chloramphenicol (which, by inhibiting the synthesis of mitochondrial membrane protein, impairs mitochondrial respiration), cycloserine, and linezolid. Diagnosis Ringed sideroblasts are seen in the bone marrow. On the peripheral blood smear can be found erythrocytes with basophilic stippling (cytoplasmic granules of RNA precipitates) and Pappenheimer bodies (cytoplasmic granules of iron).The anemia is moderate to severe and dimorphic. Microscopic viewing of the red blood cells will reveal marked unequal cell size and abnormal cell shape. Basophilic stippling is marked and target cells are common. The mean cell volume is commonly decreased (i.e., a microcytic anemia), but it may also be normal or even high. The RDW is increased with the red blood cell histogram shifted to the left. Leukocytes and platelets are normal. Bone marrow shows erythroid hyperplasia with a maturation arrest.In excess of 40% of the developing erythrocytes are ringed sideroblasts. Serum iron, percentage saturation and ferritin are increased. The total iron-binding capacity of the cells is normal to decreased. Stainable marrow hemosiderin is increased. Classification Sideroblastic anemia is typically divided into subtypes based on its cause. Hereditary or congenital sideroblastic anemia may be X-linked or autosomal.GLRX5 has also been implicated. Acquired, or secondary, sideroblastic anemia develops after birth and is divided according to its cause. Laboratory findings Serum Iron: high increased ferritin levels decreased total iron-binding capacity high transferrin saturation Hematocrit of about 20-30% The mean corpuscular volume or MCV is usually normal or low for congenital causes of sideroblastic anemia but normal or high for acquired forms. With lead poisoning, see coarse basophilic stippling of red blood cells on peripheral blood smear Specific test: Prussian blue stain of RBC in marrow shows ringed sideroblasts. Prussian blue staining involves a non-enzymatic reaction of ferrous iron with ferrocyanide forming ferric-ferrocyanide, which is blue in color. A counterstain may be used to provide better visualization. Treatment Occasionally, the anemia is so severe that support with transfusion is required. These patients usually do not respond to erythropoietin therapy. Some cases have been reported that the anemia is reversed or heme level is improved through use of moderate to high doses of pyridoxine (vitamin B6). In severe cases of SBA, bone marrow transplant is also an option with limited information about the success rate. Some cases are listed on MedLine and various other medical sites. In the case of isoniazid-induced sideroblastic anemia, the addition of B6 is sufficient to correct the anemia. Deferoxamine, a chelating agent, is used to treat iron overload from transfusions. Therapeutic phlebotomy can be used to manage iron overload. Prognosis Sideroblastic anemias are often described as responsive or non-responsive in terms of increased hemoglobin levels to pharmacological doses of vitamin B6.1- Congenital: 80% are responsive, though the anemia does not completely resolve. 2- Acquired clonal: 40% are responsive, but the response may be minimal. 3- Acquired reversible: 60% are responsive, but course depends on treatment of the underlying cause. Severe refractory sideroblastic anemias requiring regular transfusions and/or that undergo leukemic transformation (5–10%) significantly reduce life expectancy. See also Anemia Siderosis List of hematologic conditions Hematopoietic stem cell transplantation References External links GeneReviews/NCBI/NIH/UW entry on X-Linked Sideroblastic Anemia and Ataxia

Melanocytic nevus

A melanocytic nevus (also known as nevocytic nevus, nevus-cell nevus and commonly as a mole) is a type of melanocytic tumor that contains nevus cells. Some sources equate the term mole with "melanocytic nevus", but there are also sources that equate the term mole with any nevus form.The majority of moles appear during the first two decades of a persons life, with about one in every 100 babies being born with moles. Acquired moles are a form of benign neoplasm, while congenital moles, or congenital nevi, are considered a minor malformation or hamartoma and may be at a higher risk for melanoma. A mole can be either subdermal (under the skin) or a pigmented growth on the skin, formed mostly of a type of cell known as a melanocyte. The high concentration of the bodys pigmenting agent, melanin, is responsible for their dark color. Moles are a member of the family of skin lesions known as nevi and can occur in all mammalian species, but have been documented most extensively in humans, dogs, and horses. Signs and symptoms According to the American Academy of Dermatology, the most common types of moles are skin tags, raised moles and flat moles. Benign moles are usually brown, tan, pink or black (especially on dark-colored skin). They are circular or oval and are usually small (commonly between 1–3 mm), though some can be larger than the size of a typical pencil eraser (>5 mm). Some moles produce dark, coarse hair. Common mole hair removal procedures include plucking, cosmetic waxing, electrolysis, threading and cauterization. Aging Moles tend to appear during early childhood and during the first 30 years of life. They may change slowly, becoming raised, changing color or gradually fading. Most people have between 30 and 40 moles, but some have as many as 600.The number of moles a person has was found to have a correlation with telomere length. However, the relation between telomeres and aging remains uncertain. Complications The American Academy of Dermatology says that the vast majority of moles are benign. Data on the chances of transformation from melanocytic nevus to melanoma is controversial, but it appears that about 10% of malignant melanomas have a precursor lesion, of which about 10% are melanocytic nevi. Therefore, it appears that malignant melanoma quite seldom (1% of cases) has a melanocytic nevus as a precursor. Cause The cause is not clearly understood, but is thought to be caused by a defect in embryologic development. This is in the first twelve weeks of pregnancy. The defect is thought to cause a proliferation of melanocytes. This means melanocytes, the cells in the body in charge of normal skin color, are being produced at an extremely fast rate, thus causing the melanocytes to form in clusters instead of spread out, causing abnormal skin pigmentation in some areas of the body. Genetics Genes can have an influence on a persons moles. Dysplastic nevus syndrome is a largely hereditary condition which causes a person to have a large quantity of moles (often 100 or more) with some larger than normal or atypical. This often leads to a higher risk of melanoma, a serious skin cancer. Dysplastic nevi are more likely than ordinary moles to become cancerous. Dysplastic nevi are common, and many people have a few of these abnormal moles. Having more than 50 ordinary moles increases the risk of developing melanoma.In the overall population, a slight majority of melanomas do not form in an existing mole, but rather create a new growth on the skin. Somewhat surprisingly, this also applies to those with dysplastic nevi. They are at a higher risk of melanoma occurring not only where there is an existing mole, but also where there are none. Such persons need to be checked regularly for any changes in their moles and to note any new ones. Sunlight Ultraviolet light from the sun causes premature aging of the skin and skin damage that can lead to melanoma. Some scientists hypothesize that overexposure to UV, including excessive sunlight, may play a role in the formation of acquired moles. However, more research is needed to determine the complex interaction between genetic makeup and overall exposure to ultraviolet light. Some strong indications that this is so (but falling short of proof), are: The relative lack of moles on the buttocks of people with dysplastic nevi. Freckles (spots of melanin on the skin, and distinct from moles) are known to be influenced by sunlight.Studies have found that sunburns and too much time in the sun can increase the risk factors for melanoma. This is in addition to those who have dysplastic nevi being at higher risk of this cancer (the uncertainty is in regard to acquiring benign moles). To prevent and reduce the risk of melanoma caused by UV radiation, the American Academy of Dermatology and the National Cancer Institute recommends staying out of the sun between 10 a.m. and 4 p.m. standard time (or whenever ones shadow is shorter than ones height). The National Cancer Institute also recommends wearing long sleeves and trousers, hats with a wide brim, sunscreens, and sunglasses that have UV-deflecting lenses. Diagnosis Clinical diagnosis can be made with the naked eye using the ABCD guideline or by using dermatoscopy. An online-screening test is also available to help screen out benign moles. Classification Melanocytic nevi can mainly be classified by depth, being congenital versus acquired, and/or specific dermatoscopy or histopathology patterns: Depth Congenital versus acquired Congenital nevus: Small to large nevus present at or near time of birth. Small ones have low potential for forming melanomas, however the risk increases with size, as in the giant pigmented nevus. Acquired nevus: Any melanocytic nevus that is not a congenital nevus or not present at birth or near birth.Specific dermatoscopy or histopathology patterns Recurrence Recurrent nevus: Any incompletely removed nevus with residual melanocytes left in the surgical wound. It creates a dilemma for the patient and physician, as these scars cannot be distinguished from a melanoma. Differentiation from melanoma It often requires a dermatologist to fully evaluate moles. For instance, a small blue or bluish-black spot, often called a blue nevus, is usually benign but often mistaken for melanoma. Conversely, a junctional nevus, which develops at the junction of the dermis and epidermis, is potentially cancerous.A basic reference chart used for consumers to spot suspicious moles is found in the mnemonic A-B-C-D, used by institutions such as the American Academy of Dermatology and the National Cancer Institute. The letters stand for asymmetry, border, color, and diameter. Sometimes, the letter E (for elevation or evolving) is added. According to the American Academy of Dermatology, if a mole starts changing in size, color, shape or, especially, if the border of a mole develops ragged edges or becomes larger than a pencil eraser, it would be an appropriate time to consult with a physician. Other warning signs include a mole, even if smaller than a pencil eraser, that is different from the others and begins to crust over, bleed, itch, or become inflamed. The changes may indicate developing melanomas. The matter can become clinically complicated because mole removal depends on which types of cancer, if any, come into suspicion. A recent and novel method of melanoma detection is the "ugly duckling sign" It is simple, easy to teach, and highly effective in detecting melanoma. Simply, correlation of common characteristics of a persons skin lesion is made. Lesions which greatly deviate from the common characteristics are labeled as an "ugly duckling", and further professional exam is required. The "little red riding hood sign", suggests that individuals with fair skin and light colored hair might have difficult-to-diagnose melanomas. Extra care and caution should be rendered when examining such individuals as they might have multiple melanomas and severely dysplastic nevi. A dermatoscope must be used to detect "ugly ducklings", as many melanomas in these individuals resemble non-melanomas or are considered to be "wolves in sheep clothing". These fair skinned individuals often have lightly pigmented or amelanotic melanomas which will not present easy-to-observe color changes and variation in colors. The borders of these amelanotic melanomas are often indistinct, making visual identification without a dermatoscope very difficult. People with a personal or family history of skin cancer or of dysplastic nevus syndrome (multiple atypical moles) should see a dermatologist at least once a year to be sure they are not developing melanoma. Management First, a diagnosis must be made. If the lesion is a seborrheic keratosis, then shave excision, electrodesiccation or cryosurgery may be performed, usually leaving very little if any scarring. If the lesion is suspected to be a skin cancer, a skin biopsy must be done first, before considering removal. This is unless an excisional biopsy is warranted. If the lesion is a melanocytic nevus, one has to decide if it is medically indicated or not. If a melanocytic nevus is suspected of being a melanoma, it needs to be sampled or removed and sent for microscopic evaluation by a pathologist by a method called skin biopsy. One can do a complete excisional skin biopsy or a punch skin biopsy, depending on the size and location of the original nevus. Other reasons for removal may be cosmetic, or because a raised mole interferes with daily life (e.g., shaving). Removal can be by excisional biopsy or by shaving. A shaved site leaves a red mark on the site which returns to the patients usual skin color in about two weeks. However, there might still be a risk of spread of the melanoma, so the methods of Melanoma diagnosis, including excisional biopsy, are still recommended even in these instances. Additionally, moles can be removed by laser, surgery or electrocautery. In properly trained hands, some medical lasers are used to remove flat moles level with the surface of the skin, as well as some raised moles. While laser treatment is commonly offered and may require several appointments, other dermatologists think lasers are not the best method for removing moles because the laser only cauterizes or, in certain cases, removes very superficial levels of skin. Moles tend to go deeper into the skin than non-invasive lasers can penetrate. After a laser treatment a scab is formed, which falls off about seven days later, in contrast to surgery, where the wound has to be sutured. A second concern about the laser treatment is that if the lesion is a melanoma, and was misdiagnosed as a benign mole, the procedure might delay diagnosis. If the mole is incompletely removed by the laser, and the pigmented lesion regrows, it might form a recurrent nevus. Electrocautery is available as an alternative to laser cautery. Electrocautery is a procedure that uses a light electrical current to burn moles, skin tags, and warts off the skin. Electric currents are set to a level such that they only reach the outermost layers of the skin, thus reducing the problem of scarring. Approximately 1–3 treatments may be needed to completely remove a mole. Typically, a local anesthetic is applied to the treated skin area before beginning the mole removal procedure.For surgery, many dermatologic and plastic surgeons first use a freezing solution, usually liquid nitrogen, on a raised mole and then shave it away with a scalpel. If the surgeon opts for the shaving method, he or she usually also cauterizes the stump. Because a circle is difficult to close with stitches, the incision is usually elliptical or eye-shaped. However, freezing should not be done to a nevus suspected to be a melanoma, as the ice crystals can cause pathological changes called "freezing artifacts" which might interfere with the diagnosis of the melanoma. Mole removal risks Mole removal risks mainly depend on the type of mole removal method the patient undergoes. First, mole removal may be followed by some discomfort that can be relieved with pain medication. Second, there is a risk that a scab will form or that redness will occur. However, such scabs and redness usually heal within one or two weeks. Third, as in other surgeries, there is also risk of infection or an anesthetic allergy or even nerve damage. Lastly, the mole removal may imply an uncomfortable scar depending on the mole size. Society and culture Throughout human history, individuals who have possessed facial moles have been subject to ridicule and attack based on superstition. Throughout most of history, facial moles were not considered objects of beauty on lovely faces. Rather most moles were considered hideous growths that appeared mostly on the noses, cheeks, and chins of witches, frogs and other low creatures. Both folklore and modern popular culture use physical traits to denote a characters either good or evil tendencies. In contrast to the fine features and smooth skin of its heroes and heroines, characters who possess negative or evil characteristics have also been known to possess more rugged features and skin blemishes, including facial moles.During the Salem witch trials, warts and other dermatological lesions such as moles, scars, and other blemishes, when found on accused women were considered evidence of a pact with the devil. Face mole reading In traditional Chinese culture, facial moles are respected and they are used in moleomancy, or face mole reading. The moles meaning varies according to which of the nine "wealth spots" of the face they are located in. Depending on their position and color, a persons facial moles may render their face "lucky" or "unlucky."Moles that can be easily seen may be considered warnings or reminders, while hidden moles may symbolize good luck and fortune. Furthermore, traditional Chinese culture holds that each facial mole indicates the presence of a corresponding mole on another part of the body. For instance, if a mole is present around the mouth, a corresponding mole should be found in the pubic region. See also Mole map Beauty mark References External links Media related to Melanocytic nevus at Wikimedia Commons Common Moles, Dysplastic Nevi, and Risk of Melanoma - National Cancer Institute.

Acute disseminated encephalomyelitis

Acute disseminated encephalomyelitis (ADEM), or acute demyelinating encephalomyelitis, is a rare autoimmune disease marked by a sudden, widespread attack of inflammation in the brain and spinal cord. As well as causing the brain and spinal cord to become inflamed, ADEM also attacks the nerves of the central nervous system and damages their myelin insulation, which, as a result, destroys the white matter. It is often triggered by a viral infection or (very rarely) vaccinations.ADEMs symptoms resemble the symptoms of multiple sclerosis (MS), so the disease itself is sorted into the classification of the multiple sclerosis borderline diseases. However, ADEM has several features that distinguish it from MS. Unlike MS, ADEM occurs usually in children and is marked with rapid fever, although adolescents and adults can get the disease too. ADEM consists of a single flare-up whereas MS is marked with several flare-ups (or relapses), over a long period of time. Relapses following ADEM are reported in up to a quarter of patients, but the majority of these multiphasic presentations following ADEM likely represent MS. ADEM is also distinguished by a loss of consciousness, coma and death, which is very rare in MS, except in severe cases. It affects about 8 per 1,000,000 people per year. Although it occurs in all ages, most reported cases are in children and adolescents, with the average age around 5 to 8 years old. The disease affects males and females almost equally. ADEM shows seasonal variation with higher incidence in winter and spring months which may coincide with higher viral infections during these months. The mortality rate may be as high as 5%; however, full recovery is seen in 50 to 75% of cases with increase in survival rates up to 70 to 90% with figures including minor residual disability as well. The average time to recover from ADEM flare-ups is one to six months. ADEM produces multiple inflammatory lesions in the brain and spinal cord, particularly in the white matter. Usually these are found in the subcortical and central white matter and cortical gray-white junction of both cerebral hemispheres, cerebellum, brainstem, and spinal cord, but periventricular white matter and gray matter of the cortex, thalami and basal ganglia may also be involved. When a person has more than one demyelinating episode of ADEM, the disease is then called recurrent disseminated encephalomyelitis or multiphasic disseminated encephalomyelitis (MDEM). Also, a fulminant course in adults has been described. Signs and symptoms ADEM has an abrupt onset and a monophasic course. Symptoms usually begin 1–3 weeks after infection. Major symptoms include fever, headache, nausea and vomiting, confusion, vision impairment, drowsiness, seizures and coma. Although initially the symptoms are usually mild, they worsen rapidly over the course of hours to days, with the average time to maximum severity being about four and a half days. Additional symptoms include hemiparesis, paraparesis, and cranial nerve palsies. ADEM in COVID-19 Neurological symptoms were the main presentation of COVID-19, which did not correlate with the severity of respiratory symptoms. The high incidence of ADEM with hemorrhage is striking. Brain inflammation is likely caused by an immune response to the disease rather than neurotropism. CSF analysis was not indicative of an infectious process, neurological impairment was not present in the acute phase of the infection, and neuroimaging findings were not typical of classical toxic and metabolic disorders. The finding of bilateral periventricular relatively asymmetrical lesions allied with deep white matter involvement, that may also be present in cortical gray-white matter junction, thalami, basal ganglia, cerebellum, and brainstem suggests an acute demyelination process. Additionally, hemorrhagic white matter lesions, clusters of macrophages related to axonal injury and ADEM-like appearance were also found in subcortical white matter. Causes Since the discovery of the anti-MOG specificity against multiple sclerosis diagnosis it is considered that ADEM is one of the possible clinical causes of anti-MOG associated encephalomyelitisAbout how the anti-MOG antibodies appear in the patients serum there are several theories: A preceding antigenic challenge can be identified in approximately two-thirds of people. Some viral infections thought to induce ADEM include influenza virus, dengue, enterovirus, measles, mumps, rubella, varicella zoster, Epstein–Barr virus, cytomegalovirus, herpes simplex virus, hepatitis A, coxsackievirus and COVID-19. Bacterial infections include Mycoplasma pneumoniae, Borrelia burgdorferi, Leptospira, and beta-hemolytic Streptococci. Exposure to vaccines: The only vaccine proven related to ADEM is the Semple form of the rabies vaccine, but hepatitis B, pertussis, diphtheria, measles, mumps, rubella, pneumococcus, varicella, influenza, Japanese encephalitis, and polio vaccines have all been implicated. The majority of the studies that correlate vaccination with ADEM onset use small samples or case studies. Large scale epidemiological studies (e.g., of MMR vaccine or smallpox vaccine) do not show increased risk of ADEM following vaccination. An upper bound for the risk of ADEM from measles vaccination, if it exists, can be estimated to be 10 per million, which is far lower than the risk of developing ADEM from an actual measles infection, which is about 1 per 1,000 cases. For a rubella infection, the risk is 1 per 5,000 cases. Some early vaccines, later shown to have been contaminated with host animal CNS tissue, had ADEM incident rates as high as 1 in 600. In rare cases, ADEM seems to follow from organ transplantation. Diagnosis ADEM term has been inconsistently used at different times. Currently, the commonly accepted international standard for the clinical case definition is the one published by the International Pediatric MS Study Group, revision 2007.Given that the definition is clinical, it is currently unknown if all the cases with ADEM are positive for anti-MOG autoantibody, but in any case, it seems strongly related to ADEM diagnosis. Differential diagnosis Multiple sclerosis While ADEM and MS both involve autoimmune demyelination, they differ in many clinical, genetic, imaging, and histopathological aspects. Some authors consider MS and its borderline forms to constitute a spectrum, differing only in chronicity, severity, and clinical course, while others consider them discretely different diseases.Typically, ADEM appears in children following an antigenic challenge and remains monophasic. Nevertheless, ADEM does occur in adults, and can also be clinically multiphasic.Problems for differential diagnosis increase due to the lack of agreement for a definition of multiple sclerosis. If MS were defined just by the separation in time and space of the demyelinating lesions as McDonald did, it would not be enough to make a difference, as some cases of ADEM satisfy these conditions. Therefore, some authors propose to establish the separation line in the shape of the lesions around the veins, being therefore "perivenous vs. confluent demyelination". The pathology of ADEM is very similar to that of MS with some differences. The pathological hallmark of ADEM is perivenular inflammation with limited "sleeves of demyelination". Nevertheless, MS-like plaques (confluent demyelination) can appearPlaques in the white matter in MS are sharply delineated, while the glial scar in ADEM is smooth. Axons are better preserved in ADEM lesions. Inflammation in ADEM is widely disseminated and ill-defined, and finally, lesions are strictly perivenous, while in MS they are disposed around veins, but not so sharply.Nevertheless, the co-occurrence of perivenous and confluent demyelination in some individuals suggests pathogenic overlap between acute disseminated encephalomyelitis and multiple sclerosis and misclassification even with biopsy or even postmortem ADEM in adults can progress to MS Multiphasic disseminated encephalomyelitis When the person has more than one demyelinating episode of ADEM, the disease is then called recurrent disseminated encephalomyelitis or multiphasic disseminated encephalomyelitis (MDEM). It has been found that anti-MOG auto-antibodies are related to this kind of ADEMAnother variant of ADEM in adults has been described, also related to anti-MOG auto-antibodies, has been named fulminant disseminated encephalomyelitis, and it has been reported to be clinically ADEM, but showing MS-like lesions on autopsy. It has been classified inside the anti-MOG associated inflammatory demyelinating diseases. Acute hemorrhagic leukoencephalitis Acute hemorrhagic leukoencephalitis (AHL, or AHLE), acute hemorrhagic encephalomyelitis (AHEM), acute necrotizing hemorrhagic leukoencephalitis (ANHLE), Weston-Hurst syndrome, or Hursts disease, is a hyperacute and frequently fatal form of ADEM. AHL is relatively rare (less than 100 cases have been reported in the medical literature as of 2006), it is seen in about 2% of ADEM cases, and is characterized by necrotizing vasculitis of venules and hemorrhage, and edema. Death is common in the first week and overall mortality is about 70%, but increasing evidence points to favorable outcomes after aggressive treatment with corticosteroids, immunoglobulins, cyclophosphamide, and plasma exchange. About 70% of survivors show residual neurological deficits, but some survivors have shown surprisingly little deficit considering the magnitude of the white matter affected.This disease has been occasionally associated with ulcerative colitis and Crohns disease, malaria, sepsis associated with immune complex deposition, methanol poisoning, and other underlying conditions. Also anecdotal association with MS has been reportedLaboratory studies that support diagnosis of AHL are: peripheral leukocytosis, cerebrospinal fluid (CSF) pleocytosis associated with normal glucose and increased protein. On magnetic resonance imaging (MRI), lesions of AHL typically show extensive T2-weighted and fluid-attenuated inversion recovery (FLAIR) white matter hyperintensities with areas of hemorrhages, significant edema, and mass effect. Treatment No controlled clinical trials have been conducted on ADEM treatment, but aggressive treatment aimed at rapidly reducing inflammation of the CNS is standard. The widely accepted first-line treatment is high doses of intravenous corticosteroids, such as methylprednisolone or dexamethasone, followed by 3–6 weeks of gradually lower oral doses of prednisolone. Patients treated with methylprednisolone have shown better outcomes than those treated with dexamethasone. Oral tapers of less than three weeks duration show a higher chance of relapsing, and tend to show poorer outcomes. Other anti-inflammatory and immunosuppressive therapies have been reported to show beneficial effect, such as plasmapheresis, high doses of intravenous immunoglobulin (IVIg), mitoxantrone and cyclophosphamide. These are considered alternative therapies, used when corticosteroids cannot be used or fail to show an effect.There is some evidence to suggest that patients may respond to a combination of methylprednisolone and immunoglobulins if they fail to respond to either separately In a study of 16 children with ADEM, 10 recovered completely after high-dose methylprednisolone, one severe case that failed to respond to steroids recovered completely after IV Ig; the five most severe cases – with ADAM and severe peripheral neuropathy – were treated with combined high-dose methylprednisolone and immunoglobulin, two remained paraplegic, one had motor and cognitive handicaps, and two recovered. A recent review of IVIg treatment of ADEM (of which the previous study formed the bulk of the cases) found that 70% of children showed complete recovery after treatment with IVIg, or IVIg plus corticosteroids. A study of IVIg treatment in adults with ADEM showed that IVIg seems more effective in treating sensory and motor disturbances, while steroids seem more effective in treating impairments of cognition, consciousness and rigor. This same study found one subject, a 71-year-old man who had not responded to steroids, that responded to an IVIg treatment 58 days after disease onset. Prognosis Full recovery is seen in 50 to 70% of cases, ranging to 70 to 90% recovery with some minor residual disability (typically assessed using measures such as mRS or EDSS), average time to recover is one to six months. The mortality rate may be as high as 5–10%. Poorer outcomes are associated with unresponsiveness to steroid therapy, unusually severe neurological symptoms, or sudden onset. Children tend to have more favorable outcomes than adults, and cases presenting without fevers tend to have poorer outcomes. The latter effect may be due to either protective effects of fever, or that diagnosis and treatment is sought more rapidly when fever is present. ADEM can progress to MS. It will be considered MS if some lesions appear in different times and brain areas Motor deficits Residual motor deficits are estimated to remain in about 8 to 30% of cases, the range in severity from mild clumsiness to ataxia and hemiparesis. Neurocognitive Patients with demyelinating illnesses, such as MS, have shown cognitive deficits even when there is minimal physical disability. Research suggests that similar effects are seen after ADEM, but that the deficits are less severe than those seen in MS. A study of six children with ADEM (mean age at presentation 7.7 years) were tested for a range of neurocognitive tests after an average of 3.5 years of recovery. All six children performed in the normal range on most tests, including verbal IQ and performance IQ, but performed at least one standard deviation below age norms in at least one cognitive domain, such as complex attention (one child), short-term memory (one child) and internalizing behaviour/affect (two children). Group means for each cognitive domain were all within one standard deviation of age norms, demonstrating that, as a group, they were normal. These deficits were less severe than those seen in similar aged children with a diagnosis of MS.Another study compared nineteen children with a history of ADEM, of which 10 were five years of age or younger at the time (average age 3.8 years old, tested an average of 3.9 years later) and nine were older (mean age 7.7y at time of ADEM, tested an average of 2.2 years later) to nineteen matched controls. Scores on IQ tests and educational achievement were lower for the young onset ADEM group (average IQ 90) compared to the late onset (average IQ 100) and control groups (average IQ 106), while the late onset ADEM children scored lower on verbal processing speed. Again, all groups means were within one standard deviation of the controls, meaning that while effects were statistically reliable, the children were as a whole, still within the normal range. There were also more behavioural problems in the early onset group, although there is some suggestion that this may be due, at least in part, to the stress of hospitalization at a young age. Research The relationship between ADEM and anti-MOG associated encephalomyelitis is currently under research. A new entity called MOGDEM has been proposed.About animal models, the main animal model for MS, experimental autoimmune encephalomyelitis (EAE) is also an animal model for ADEM. Being an acute monophasic illness, EAE is far more similar to ADEM than MS. See also Optic neuritis Transverse myelitis Victoria Arlen References External links Acute disseminated encephalomyelitis at NIHs Office of Rare Diseases Acute Disseminated Encephalomyelitis Information Page at NINDS Information for parents about Acute disseminated encephalomyelitis

Hereditary sclerosing poikiloderma

Hereditary sclerosing poikiloderma is an autosomal dominant conditions with skin changes consisting of generalized poikiloderma appearing in childhood.: 576 See also Mandibuloacral dysplasia Poikiloderma Skin lesion References == External links ==

Schilders disease

Schilders disease may refer to two different diseases described by Paul Schilder: Adrenoleukodystrophy Diffuse myelinoclastic sclerosis

Central serous chorioretinopathy

Central serous chorioretinopathy (CSC or CSCR), also known as central serous retinopathy (CSR), is an eye disease that causes visual impairment, often temporary, usually in one eye. When the disorder is active it is characterized by leakage of fluid under the retina that has a propensity to accumulate under the central macula. This results in blurred or distorted vision (metamorphopsia). A blurred or gray spot in the central visual field is common when the retina is detached. Reduced visual acuity may persist after the fluid has disappeared.The disease is considered of unknown cause. It mostly affects white males in the age group 20 to 50 (male:female ratio 6:1) and occasionally other groups. The condition is believed to be exacerbated by stress or corticosteroid use. Pathophysiology Recently, central serous chorioretinopathy has been understood to be part of the pachychoroid spectrum. In pachychoroid spectrum disorders, of which CSR represents stage II, the choroid, the highly vascularized layer below the retina, is thickened and congested with increased blood vessel diameter, especially in the deep choroid (the so-called Hallers layer). This results in increased pressure from the deep choroid against the superficial choroid close to the retina, damaging the fine blood vessels (capillaries) needed to supply oxygen and nutrients to the retinal pigment epithelium and retina. Additionally, fluid can leak from these damaged vessels and accumulate under the retina. Different stages of the pachychoroid are defined depending on the amount of cumulative damage. If there are defects in the retinal pigment epithelium without accumulation of fluid below the retina, a pachychoroid pigmentepitheliopathy (PPE) is present. Accumulation of fluid results in central serous chorioretinopathy (CSR). The development of secondary blood vessels, so-called choroidal neovascularization (CNV) leads to pachychoroid neovasculopathy (PNV). If parts of these new vessels bulge outward, so-called aneurysms develop within this CNV, defining pachychoroid aneurysmal type 1 CNV (or, still widely used, polypoidal choroidal vasculopathy (PCV)). Since the individual stages develop one after the other from the respective preliminary stage, pachychoroidal diseases of the macula are divided into 4 stages according to Siedlecki, Schworm and Priglinger: Risk factors CSR is sometimes called idiopathic CSR which means that its cause is unknown. Nevertheless, stress appears to play an important role. An oft-cited but potentially inaccurate conclusion is that persons in stressful occupations, such as airplane pilots, have a higher incidence of CSR. CSR has also been associated with cortisol and corticosteroids. Persons with CSR have higher levels of cortisol. Cortisol is a hormone secreted by the adrenal cortex which allows the body to deal with stress, which may explain the CSR-stress association. There is extensive evidence to the effect that corticosteroids (e.g. cortisone), commonly used to treat inflammations, allergies, skin conditions and even certain eye conditions, can trigger CSR, aggravate it and cause relapses. In a case report, a young male was using Prednisolone and began to display subretinal fluid indicative of CSR. With the discontinuation of the steroid drop the subretinal fluid resolved and did not show any sign of recurrence. Thus indicating the steroid was the probable cause of the CSR. A study of 60 persons with Cushings syndrome found CSR in 3 (5%). Cushings syndrome is characterized by very high cortisol levels. Certain sympathomimetic drugs have also been associated with causing the disease.Evidence has also implicated helicobacter pylori (see gastritis) as playing a role. It would appear that the presence of the bacteria is well correlated with visual acuity and other retinal findings following an attack. Evidence also shows that people with MPGN type II kidney disease can develop retinal abnormalities including CSR caused by deposits of the same material that originally damaged the glomerular basement membrane in the kidneys. Diagnosis The diagnosis usually starts with a dilated examination of the retina, followed with confirmation by optical coherence tomography and fluorescein angiography. The angiography test will usually show one or more fluorescent spots with fluid leakage. In 10%-15% of the cases these will appear in a "classic" smokestack shape. Differential diagnosis should be immediately performed to rule out retinal detachment, which is a medical emergency. A clinical record should be taken to keep a timeline of the detachment. The affected eye will sometimes exhibit a refractive spectacle prescription that is more far-sighted than the fellow eye due to the decreased focal length caused by the raising of the retina. Indocyanine green angiography or laser Doppler imaging can be used to reveal the underlying swollen choroidal vessels under the retinal pigment epithelium and assess the health of the retina in the affected area which can be useful in making a treatment decision. Treatment Any ongoing corticosteroid treatment should be tapered and stopped, where possible. It is important to check current medication, including nasal sprays and creams, for ingredients of corticosteroids, if found seek advice from a medical practitioner for an alternative. Most eyes with CSR undergo spontaneous resorption of subretinal fluid within 3–4 months. Recovery of visual acuity usually follows. Treatment should be considered if resorption does not occur within 3–4 months, spontaneously or as the result of counselling. The available evidence suggests that half-dose (or half-fluence) photodynamic therapy is the treatment of choice for CSR with subretinalfluid for longer than 3–4 months.Due to the natural disease course of CSR - in which spontaneous resolution of subretinal fluid may occur - retrospective studies may erroneously report positive treatment outcomes and should, therefore, be evaluated with caution. Laser treatments Full-dose photodynamic therapy (PDT) with verteporfin was first described in CSR in 2003. Later, reduced-settings PDT (half-dose, half-fluence, and half-time) was found to have the same efficacy and a lower chance of complications. Follow-up studies have confirmed the treatments long-term effectiveness including its effectiveness for the chronic variant of the disease. In the PLACE trial, half-dose photodynamic therapy was found to be superior compared to high-density subthreshold micropulse laser, both with regard to anatomical and functional outcomes. Indocyanine green angiography can be used to predict how the patient will respond to PDT.Laser photocoagulation, which effectively burns the leak area shut, may be considered in cases where there is little improvement in a 3- to 4-month duration, and the leakage is confined to a single or a few sources of leakage at a safe distance from the fovea. Laser photocoagulation is not indicated for cases where the leak is very near the central macula or for cases where the leakage is widespread and its source is difficult to identify. Laser photocoagulation can permanently damage vision where applied. Carefully tuned lasers can limit this damage. Even so, laser photocoagulation is not a preferred treatment for leaks in the central vision and is considered an outdated treatment by some doctors. Foveal attenuation has been associated with more than 4 months duration of symptoms, however a better long-term outcome has not been demonstrated with laser photocoagulation than without photocoagulation.In chronic cases, transpupillary thermotherapy has been suggested as an alternative to laser photocoagulation where the leak is in the central macula.Yellow micropulse laser has shown promise in very limited retrospective trials. Oral medications Spironolactone is a mineralocorticoid receptor antagonist that may help reduce the fluid associated with CSR. In a retrospective study noted by Acta Ophthalmologica, spironolactone improved visual acuity in CSR patients over the course of 8 weeks.Eplerenone is another mineralocorticoid receptor antagonist that has been thought to reduce the subretinal fluid that is present with CSR. In a study noted in International Journal of Ophthalmology, results showed Epleronone decreased the subretinal fluid both horizontally and vertically over time. However, the most recent and largest randomized controlled trial showed that eplerenone has no significant effect on chronic CSR.Low dosage ibuprofen has been shown to quicken recovery in some cases. Topical treatment Though no topical treatment has been proven to be effective in the treatment of CSR. Some doctors have attempted to use nonsteroidal topical medications to reduce the subretinal fluid associated with CSR. The nonsteroidal topical medications that are sometimes used to treat CSR are, Ketorolac, Diclofenac, or Bromfenac. Lifestyle changes People who have irregular sleep patterns, type A personalities, sleep apnea, or systemic hypertension are more susceptible to CSR, as stated in Medscape. "The pathogenesis here is thought to be elevated circulating cortisol and epinephrine, which affect the autoregulation of the choroidal circulation." With management of these lifestyle patterns and associated cortisol and epinephrine levels, it has been shown that the fluid associated with CSR can spontaneously resolve. Melatonin has been shown to help regulate sleep in people who have irregular sleep patterns (such as 3rd shift workers, or overnight employees), in turn, better regulating cortisol and epinephrine levels to manage CSR. A Cochrane review seeking to compare the effectiveness of various treatment for CSR found low quality evidence that half-dose PDT treatment resulted in improved visual acuity and less recurrence of CSR in patients with acute CSR, compared to patients in the control group. The review also found benefits in micropulse laser treatments, where patients with acute and chronic CSR had improved visual acuity compared to control patients. Prognosis The prognosis for CSR is generally excellent. While immediate vision loss may be as poor as 20/200 in the affected eye, clinically, over 90% of patients regain 20/25 vision or better within 45 days. Once the fluid has resolved, either spontaneously or through treatment, distortion is reduced and visual acuity improves as the eye heals. However, some visual abnormalities can remain even where visual acuity is measured at 20/20. This includes localized reductions in light sensitivity as assessed by visual field testing (microperimetry). Lasting problems include decreased night vision, reduced color discrimination, and localized distortion caused by scarring of the sub-retinal layers.Complications include subretinal neovascularization and pigment epithelial detachment.The disease can re-occur causing progressive vision loss. There is also a chronic form, titled as type II central serous retinopathy, which occurs in approximately 5% of cases. This exhibits diffuse rather than localized abnormality of the pigment epithelium, producing a persistent subretinal fluid. The serous fluid in these cases tends to be shallow rather than dome shaped. The prognosis for this condition is less favorable and continued clinical consultation is advised. See also Diabetic retinopathy Hypertensive retinopathy Macular degeneration Posterior vitreous detachment References == External links ==

Streptococcal pharyngitis

Streptococcal pharyngitis, also known as strep throat, or bacterial tonsillitis is an infection of the back of the throat including the tonsils caused by group A streptococcus (GAS). Common symptoms include fever, sore throat, red tonsils (tonsilitis), and enlarged lymph nodes in the neck. A headache and nausea or vomiting may also occur. Some develop a sandpaper-like rash which is known as scarlet fever. Symptoms typically begin one to three days after exposure and last seven to ten days.Strep throat is spread by respiratory droplets from an infected person. It may be spread directly or by touching something that has droplets on it and then touching the mouth, nose, or eyes. Some people may carry the bacteria without symptoms. It may also be spread by skin infected with group A strep. The diagnosis is made based on the results of a rapid antigen detection test or throat culture in those who have symptoms.Prevention is by washing hands and not sharing eating utensils. There is no vaccine for the disease. Treatment with antibiotics is only recommended in those with a confirmed diagnosis. Those infected should stay away from other people until fever is gone and for at least 12 hours after starting treatment. Pain can be treated with paracetamol (acetaminophen) and nonsteroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen.Strep throat is a common bacterial infection in children. It is the cause of 15–40% of sore throats among children and 5–15% among adults. Cases are more common in late winter and early spring. Potential complications include rheumatic fever and peritonsillar abscess. Signs and symptoms The typical signs and symptoms of streptococcal pharyngitis are a sore throat, fever of greater than 38 °C (100 °F), tonsillar exudates (pus on the tonsils), and large cervical lymph nodes.Other symptoms include: headache, nausea and vomiting, abdominal pain, muscle pain, or a scarlatiniform rash or palatal petechiae, the latter being an uncommon but highly specific finding.Symptoms typically begin one to three days after exposure and last seven to ten days.Strep throat is unlikely when any of the symptoms of red eyes, hoarseness, runny nose, or mouth ulcers are present. It is also unlikely when there is no fever. Cause Strep throat is caused by group A β-hemolytic Streptococcus (GAS or S. pyogenes). Humans are the primary natural reservoir for group A streptococcus. Other bacteria such as non–group A β-hemolytic streptococci and fusobacterium may also cause pharyngitis. It is spread by direct, close contact with an infected person; thus crowding, as may be found in the military and schools, increases the rate of transmission. Dried bacteria in dust are not infectious, although moist bacteria on toothbrushes or similar items can persist for up to fifteen days. Contaminated food can result in outbreaks, but this is rare. Of children with no signs or symptoms, 12% carry GAS in their pharynx, and, after treatment, approximately 15% of those remain positive, and are true "carriers". Diagnosis A number of scoring systems exist to help with diagnosis; however, their use is controversial due to insufficient accuracy. The modified Centor criteria are a set of five criteria; the total score indicates the probability of a streptococcal infection.One point is given for each of the criteria: Absence of a cough Swollen and tender cervical lymph nodes Temperature >38.0 °C (100.4 °F) Tonsillar exudate or swelling Age less than 15 (a point is subtracted if age >44)A score of one may indicate no treatment or culture is needed or it may indicate the need to perform further testing if other high risk factors exist, such as a family member having the disease.The Infectious Disease Society of America recommends against routine antibiotic treatment and considers antibiotics only appropriate when given after a positive test. Testing is not needed in children under three as both group A strep and rheumatic fever are rare, unless a child has a sibling with the disease. Laboratory testing A throat culture is the gold standard for the diagnosis of streptococcal pharyngitis, with a sensitivity of 90–95%. A rapid strep test (also called rapid antigen detection testing or RADT) may also be used. While the rapid strep test is quicker, it has a lower sensitivity (70%) and statistically equal specificity (98%) as a throat culture. In areas of the world where rheumatic fever is uncommon, a negative rapid strep test is sufficient to rule out the disease.A positive throat culture or RADT in association with symptoms establishes a positive diagnosis in those in which the diagnosis is in doubt. In adults, a negative RADT is sufficient to rule out the diagnosis. However, in children a throat culture is recommended to confirm the result. Asymptomatic individuals should not be routinely tested with a throat culture or RADT because a certain percentage of the population persistently "carries" the streptococcal bacteria in their throat without any harmful results. Differential diagnosis As the symptoms of streptococcal pharyngitis overlap with other conditions, it can be difficult to make the diagnosis clinically. Coughing, nasal discharge, diarrhea, and red, irritated eyes in addition to fever and sore throat are more indicative of a viral sore throat than of strep throat. The presence of marked lymph node enlargement along with sore throat, fever, and tonsillar enlargement may also occur in infectious mononucleosis. Other conditions that may present similarly include epiglottitis, Kawasaki disease, acute retroviral syndrome, Lemierres syndrome, Ludwigs angina, peritonsillar abscess, and retropharyngeal abscess. Prevention Tonsillectomy may be a reasonable preventive measure in those with frequent throat infections (more than three a year). However, the benefits are small and episodes typically lessen in time regardless of measures taken. Recurrent episodes of pharyngitis which test positive for GAS may also represent a person who is a chronic carrier of GAS who is getting recurrent viral infections. Treating people who have been exposed but who are without symptoms is not recommended. Treating people who are carriers of GAS is not recommended as the risk of spread and complications is low. Treatment Untreated streptococcal pharyngitis usually resolves within a few days. Treatment with antibiotics shortens the duration of the acute illness by about 16 hours. The primary reason for treatment with antibiotics is to reduce the risk of complications such as rheumatic fever and retropharyngeal abscesses. Antibiotics prevent acute rheumatic fever if given within 9 days of the onset of symptoms. Pain medication Pain medication such as NSAIDs and paracetamol (acetaminophen) helps in the management of pain associated with strep throat. Viscous lidocaine may also be useful. While steroids may help with the pain, they are not routinely recommended. Aspirin may be used in adults but is not recommended in children due to the risk of Reye syndrome. Antibiotics The antibiotic of choice in the United States for streptococcal pharyngitis is penicillin V, due to safety, cost, and effectiveness. Amoxicillin is preferred in Europe. In India, where the risk of rheumatic fever is higher, intramuscular benzathine penicillin G is the first choice for treatment.Appropriate antibiotics decrease the average 3–5 day duration of symptoms by about one day, and also reduce contagiousness. They are primarily prescribed to reduce rare complications such as rheumatic fever and peritonsillar abscess. The arguments in favor of antibiotic treatment should be balanced by the consideration of possible side effects, and it is reasonable to suggest that no antimicrobial treatment be given to healthy adults who have adverse reactions to medication or those at low risk of complications. Antibiotics are prescribed for strep throat at a higher rate than would be expected from how common it is.Erythromycin and other macrolides or clindamycin are recommended for people with severe penicillin allergies. First-generation cephalosporins may be used in those with less severe allergies and some low certainty evidence suggest cephalosporins are superior to penicillin. These late-generation antibiotics show a similar effect when prescribed for 3–7 days in comparison to the standard 10-days of penicillin when used in areas of low rheumatic heart disease. Streptococcal infections may also lead to acute glomerulonephritis; however, the incidence of this side effect is not reduced by the use of antibiotics. Prognosis The symptoms of strep throat usually improve within three to five days, irrespective of treatment. Treatment with antibiotics reduces the risk of complications and transmission; children may return to school 24 hours after antibiotics are administered. The risk of complications in adults is low. In children, acute rheumatic fever is rare in most of the developed world. It is, however, the leading cause of acquired heart disease in India, sub-Saharan Africa, and some parts of Australia. Complications Complications arising from streptococcal throat infections include: The economic cost of the disease in the United States in children is approximately $350 million annually. Epidemiology Pharyngitis, the broader category into which Streptococcal pharyngitis falls, is diagnosed in 11 million people annually in the United States. It is the cause of 15–40% of sore throats among children and 5–15% in adults. Cases usually occur in late winter and early spring. References == External links ==

Lipodermatosclerosis

Lipodermatosclerosis is a skin and connective tissue disease. It is a form of lower extremity panniculitis, an inflammation of the layer of fat under the epidermis. Signs and symptoms Pain may be the first noticed symptom. People with lipodermatosclerosis have tapering of their legs above the ankles, forming a constricting band resembling an inverted champagne bottle. In addition, there may be brownish-red pigmentation and induration. Causes The exact cause of lipodermatosclerosis is unknown. Venous disease, such as venous incompetence, venous hypertension, and body mass (obesity) may be relevant to the underlying pathogenesis.Increased blood pressure in the veins (venous hypertension) can cause diffusion of substances, including fibrin, out of capillaries. Fibrotic tissue may predispose the tissue to ulceration. Recurrent ulceration and fat necrosis is associated with lipodermatosclerosis. In advanced lipodermatosclerosis the proximal leg swells from chronic venous obstruction and the lower leg shrinks from chronic ulceration and fat necrosis resulting in the inverted coke bottle appearance of the lower leg.Lipodermatosclerosis is most commonly diagnosed in middle-aged women.The origin of lipodermatosclerosis is probably multifactorial, involving tissue hypoxia, leakage of proteins into the interstitium, and leukocyte activation. Studies of patients with lipodermatosclerosis have demonstrated significantly decreased concentrations of cutaneous oxygen associated with decreased capillary density. Capillaries are virtually absent in areas of fibrotic scars, leading to a condition known as atrophie blanche or livedoid vasculopathy. Diagnosis Diagnosis is clinical, based on observation. Biopsy is rarely required. Treatment The management of lipodermatosclerosis may include treating venous insufficiency with leg elevation and elastic compression stockings; in some difficult cases, the condition may be improved with the additional use of the fibrinolytic agent, stanozol. Fibrinolytic agents use an enzymatic action to help dissolve blood clots. Stanozol is injected directly into the affected area, Venous Ablation has also been known to help circulation in patients. See also Panniculitis List of cutaneous conditions Notes Note: This article contains material adapted from the public domain source "Lipodermatosclerosis: Questions and Answers", by the U.S federal governments Genetic and Rare Diseases Information Center External links "Lipodermatosclerosis: Questions and Answers". Genetic and Rare Diseases Information Center.

Bee sting

A bee sting is the wound and pain caused by the stinger of a female bee puncturing skin. Bee stings differ from insect bites, with the venom of stinging insects having considerable chemical variation. The reaction of a person to a bee sting may vary according to the bee species. While bee stinger venom is slightly acidic and causes only mild pain in most people, allergic reactions may occur in people with allergies to venom components. Honey bee stings A honey bee that is away from the hive foraging for nectar or pollen will rarely sting, except when stepped on or roughly handled. Honey bees will actively seek out and sting when they perceive the hive to be threatened, often being alerted to this by the release of attack pheromones (below). Although it is widely believed that a worker honey bee can sting only once, this is a partial misconception: although the stinger is in fact barbed so that it lodges in the victims skin, tearing loose from the bees abdomen and leading to its death in minutes, this only happens if the skin of the victim is sufficiently thick, such as a mammals. Honey bees are the only hymenoptera with a strongly barbed sting, though yellow jackets and some other wasps have small barbs. The venom of the honeybee contains histamine, mast cell degranulating peptide, melittin, phospholipase A2, hyaluronidase and acid phosphatase. The three proteins in honeybee venom which are important allergens are phospholipase A2, hyaluronidase and acid phosphatase. In addition, the polypeptide melittin is also antigenic. Bumblebee venom appears to be chemically and antigenically related to honeybee venom.Bees with barbed stingers can often sting other insects without harming themselves. Queen honeybees and bees of many other species, including bumblebees and many solitary bees, have smoother stingers with smaller barbs, and can sting mammals repeatedly.The stings injection of apitoxin into the victim is accompanied by the release of alarm pheromones, a process which is accelerated if the bee is fatally injured. The release of alarm pheromones near a hive may attract other bees to the location, where they will likewise exhibit defensive behaviors until there is no longer a threat, typically because the victim has either fled or been killed. (Note: A bee swarm, seen as a mass of bees flying or clumped together, is generally not hostile; it has deserted its hive and has no comb or young to defend.) These pheromones do not dissipate or wash off quickly, and if their target enters water, bees will resume their attack as soon as it leaves the water. The alarm pheromone emitted when a bee stings another animal smells like a banana.Drone bees, the males, are larger and do not have stingers. The female bees (worker bees and queens) are the only ones that can sting, and their stinger is a modified ovipositor. The queen bee has a barbed but smoother stinger and can, if need be, sting skin-bearing creatures multiple times, but the queen does not leave the hive under normal conditions. Her sting is not for defense of the hive; she only uses it for dispatching rival queens, ideally before they can emerge from their cells. Queen breeders who handle multiple queens and have the queen odor on their hands are sometimes stung by a queen. The stinger consists of three parts: a stylus and two barbed slides (or lancets), one on either side of the stylus. The bee does not push the stinger in but it is drawn in by the barbed slides. The slides move alternately up and down the stylus so when the barb of one slide has caught and retracts, it pulls the stylus and the other barbed slide into the wound. When the other barb has caught, it also retracts up the stylus pulling the sting further in. This process is repeated until the sting is fully in and even continues after the sting and its mechanism is detached from the bees abdomen. When a female honey bee stings a person, it cannot pull the barbed stinger back out, but rather leaves behind not only the stinger, but also part of its abdomen and digestive tract, plus muscles and nerves. This massive abdominal rupture kills the honey bee. Honey bees are the only bees to die after stinging. Venom and apitherapy The main component of bee venom responsible for pain in vertebrates is the toxin melittin; histamine and other biogenic amines may also contribute to pain and itching. In one of the alternative medical uses of honey bee products, apitherapy, bee venom has been used to treat arthritis and other painful conditions. All currently available evidence supporting this practice is either anecdotal, animal studies, or preliminary evidence, most of which has poor methodology. Apitherapy is not currently accepted as a viable medical treatment for any condition or disease; the risk of allergic reaction and anaphylaxis outweighs any benefits. According to the American Cancer Society, there is no scientific evidence that apitherapy or bee venom therapy can treat or change the course of cancer or any other disease. Clinical trials have shown that apitherapy is ineffective in treating multiple sclerosis or any other disease, and can exacerbate multiple sclerosis symptoms. Treatment The first step in treatment following a honey bee sting is removal of the stinger itself. The stinger should be removed as quickly as possible without regard to method: a study has shown the amount of venom delivered does not differ whether the sting is pinched or scraped off and even a delay of a few seconds leads to more venom being injected. Once the stinger is removed, pain and swelling should be reduced with a cold compress. A topical anesthetic containing benzocaine will relieve pain quickly and menthol is an effective anti-itch treatment. Itching can also be relieved by antihistamine or by a topical steroid cream.Many traditional remedies have been suggested for bee stings. No interventions have been proven to be effective in scientific studies and a randomized trial of aspirin paste and topical ice packs showed that aspirin was not effective in reducing the duration of swelling or pain in bee and wasp stings, and significantly increased the duration of redness. The study concluded that ice alone is a better treatment for bee and wasp stings than aspirin.For about 2 percent of people, a hypersensitivity can develop after being stung, creating a more severe reaction. This sensitisation may happen after a single sting, or after a series of stings. An allergic person may suffer anaphylactic shock from certain proteins in the venom, which can be life-threatening and requires emergency treatment. People known to be highly allergic may carry around epinephrine (adrenaline) in the form of a self-injectable EpiPen for the treatment of an anaphylactic shock. For people who experience severe or life-threatening reactions to insect stings, allergy injections composed of increasing concentrations of naturally occurring venom may provide protection against future insect stings. See also Apitoxin Bee venom therapy Characteristics of common wasps and bees Hornet stings Schmidt sting pain index Topical tobacco paste References == External links ==

Nicotine withdrawal

Nicotine withdrawal is a group of symptoms that occur in the first few weeks after stopping or decreasing use of nicotine. Symptoms include intense cravings for nicotine, anger or irritability, anxiety, depression, impatience, trouble sleeping, restlessness, hunger or weight gain, and difficulty concentrating. Withdrawal symptoms make it harder to quit nicotine products, and most methods for quitting smoking involve reducing nicotine withdrawal. Quit smoking programs can make it easier to quit. Nicotine withdrawal is recognized in both the American Psychiatric Association Diagnostic and Statistical Manual and the WHO International Classification of Diseases. Signs and symptoms The most documented symptoms of nicotine withdrawal are cravings for nicotine, anger or irritability, anxiety, depression, impatience, trouble sleeping, restlessness (psychomotor agitation, including indeliberate movement), hunger or weight gain, and difficulty concentrating. Symptoms are usually strongest for the first few days and then dissipate over 2–4 weeks. The most common symptoms are irritability, anxiety, and difficulty concentrating. Depression and insomnia are the least common. Other withdrawal symptoms may include anhedonia, constipation, cough, decreased positive affect, dizziness, drowsiness, headache, impulsivity, fatigue, flu symptoms, mood swings, mouth ulcers, and increased dreaming. Cessation of nicotine can also require changes in levels of various medications. Definition Nicotine withdrawal refers to the effects that nicotine-dependent individuals experience after they discontinue or decrease nicotine use. Nicotine is an addictive substance found most commonly in tobacco and tobacco products including cigarettes, cigars, chewing tobacco, e-cigarette liquid, pipe tobacco, snus, snuff, and nicotine medications such as nicotine gum. Withdrawal is the body’s reaction to not having the nicotine it had become accustomed to. Withdrawal is most common and intense in cigarette smokers and intermediate in smokeless and e-cigarette users. The symptoms of nicotine withdrawal usually appear 2–3 hours after last intake of nicotine and peak in 2–3 days. In a minority of smokers, cravings may last for years. Nicotine withdrawal causes few physical signs and is not life-threatening but associated cravings can be as severe as withdrawal from other drugs. After the initial withdrawal period, anxiety, depression, and quality of life generally improve such that former smokers are better off than continuing smoking. Causes Various causes have been proposed to explain the causes of nicotine withdrawal. Nicotine binds to nicotinic receptors in the brain that, in turn, cause an increase in dopamine. Dopamine is the major chemical that stimulates reward centers in the brain. The brain recruits an opposing force to dampen the effects of nicotine and this causes tolerance (the reduction in the effect of nicotine). The onset of this opposing force and the fact that the brain becomes used to and dependent on nicotine to function normally is known as physical dependence. When nicotine intake is decreased, the brains opposing force is now unopposed and this causes withdrawal symptoms. It also appears that opiate, serotonergic, glutamic, cannabinoid, and corticotrophin receptors may play a role in nicotine withdrawal. In addition, smoking becomes conditioned to environmental cues that can then prompt withdrawal symptoms. In the brain, the dorsal striatum may be associated with physical (motor) but not affective withdrawal sign. Treatment Gradually reducing nicotine intake causes less withdrawal than abruptly stopping. Another way to reduce nicotine withdrawal symptoms is to provide the body with an alternative source of nicotine (nicotine replacement therapy) for a temporary period and then taper this new nicotine intake. Other medication used for quitting smoking include bupropion, varenicline, cytisine, nortriptyline, and clonidine. Treatments other than medication, such as increased exercise, can also reduce nicotine withdrawal. Many behavior changes such as avoiding situations where one usually smoked, planning ahead to deal with temptations, and seeking the support of friends and family are effective in helping people quit smoking, but whether this is due to reduced withdrawal is unclear. Epidemiology Most nicotine users have at least one of the above withdrawal symptoms when they try to stop. These effects are much milder to those who use isolated nicotine over tobacco. Withdrawal can occur in less frequent users, but heavier users and those with a past or current psychiatric disorder tend to have more severe withdrawal. Genetics also influence the severity of withdrawal. See also Withdrawal Smoking cessation Nicotine dependence References == External links ==

Menopause

Menopause, also known as the climacteric, is the time in womens lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often define menopause as having occurred when a woman has not had any menstrual bleeding for a year. It may also be defined by a decrease in hormone production by the ovaries. In those who have had surgery to remove their uterus but still have functioning ovaries, menopause is not considered to have yet occurred. Following the removal of the uterus, symptoms typically occur earlier.In the years before menopause, a womans periods typically become irregular, which means that periods may be longer or shorter in duration or be lighter or heavier in the amount of flow. During this time, women often experience hot flashes; these typically last from 30 seconds to ten minutes and may be associated with shivering, sweating, and reddening of the skin. Hot flashes can last from four to five years. Other symptoms may include vaginal dryness, trouble sleeping, and mood changes. The severity of symptoms varies between women. Menopause before the age of 45 years is considered to be "early menopause" and when ovarian failure/surgical removal of the ovaries occurs before the age of 40 years this is termed "premature ovarian insufficiency".In addition symptoms (hot flushes/flashes, night sweats, mood changes, arthralgia and vaginal dryness) the physical consequences of menopause include bone loss, increased central abdominal fat, and adverse changes in a womans cholesterol profile and vascular function. These changes predispose postmenopausal women to increased risks of osteoporosis and fracture and cardio-metabolic disease (diabetes and cardiovascular disease).Menopause is usually a natural change. It can occur earlier in those who smoke tobacco. Other causes include surgery that removes both ovaries or some types of chemotherapy. At the physiological level, menopause happens because of a decrease in the ovaries production of the hormones estrogen and progesterone. While typically not needed, a diagnosis of menopause can be confirmed by measuring hormone levels in the blood or urine. Menopause is the opposite of menarche, the time when a girls periods start.The primary indications for treatment of menopause are symptoms and prevention of bone loss. Mild symptoms, however, may be improved with treatment. With respect to hot flashes, avoiding smoking, caffeine, and alcohol is often recommended. Sleeping in a cool room and using a fan may help. The most effective treatment for menopausal symptoms is menopausal hormone therapy (MHT). Non hormonal therapies for hot flushes/flashes include clonidine, gabapentin, or selective serotonin reuptake inhibitors. These will not improve symptoms such as joint pain or vaginal dryness which affects over 55% of women. Exercise may help with sleeping problems. While Many of the concerns about the use of MHT raised by older studies are no longer considered barriers to MHT in healthy women. High-quality evidence for the effectiveness of alternative medicine has not been found. There is tentative evidence for phytoestrogens. Signs and symptoms During early menopause transition, the menstrual cycles remain regular but the interval between cycles begins to lengthen. Hormone levels begin to fluctuate. Ovulation may not occur with each cycle.The term menopause refers to a point in time that follows one year after the last menstruation. During the menopausal transition and after menopause, women can experience a wide range of symptoms. However, for women who enter the menopause transition without having regular menstrual cycles due to prior surgery, other medical conditions or ongoing hormonal contraception the menopause cannot be identified by bleeding patterns and is defined as the permanent loss of ovarian function. Vagina and uterus During the transition to menopause, menstrual patterns can show shorter cycling (by 2–7 days); longer cycles remain possible. There may be irregular bleeding (lighter, heavier, spotting). Dysfunctional uterine bleeding is often experienced by women approaching menopause due to the hormonal changes that accompany the menopause transition. Spotting or bleeding may simply be related to vaginal atrophy, a benign sore (polyp or lesion), or may be a functional endometrial response. The European Menopause and Andropause Society has released guidelines for assessment of the endometrium, which is usually the main source of spotting or bleeding.In post-menopausal women, however, any unscheduled vaginal bleeding is of concern and requires an appropriate investigation to rule out the possibility of malignant diseases. Urogenital symptoms that may appear during menopause and continue through postmenopause include: painful intercourse vaginal dryness atrophic vaginitis – thinning of the membranes of the vulva, the vagina, the cervix, and the outer urinary tract, along with considerable shrinking and loss in elasticity of all of the outer and inner genital areas. Urinary urgency and burning Other physical Other physical symptoms of menopause include lack of energy, joint soreness, stiffness, back pain, breast enlargement, breast pain, heart palpitations, headache, dizziness, dry, itchy skin, thinning, tingling skin, rosacea, weight gain, urinary incontinence,urinary urgency, interrupted sleeping patterns, heavy night sweats, and hot flashes. Mood and memory effects Psychological symptoms include anxiety, poor memory, inability to concentrate, depressive mood, irritability, mood swings, and less interest in sexual activity.Menopause-related cognitive impairment can be confused with the mild cognitive impairment that precedes dementia. Tentative evidence has found that forgetfulness affects about half of menopausal women and is probably caused by the effects of declining estrogen levels on the brain, or perhaps by reduced blood flow to the brain during hot flashes. Long-term effects Cardiovascular health Exposure to endogenous estrogen during reproductive years provides women with protection against cardiovascular disease, which is lost around 10 years after the onset of menopause. The menopausal transition is associated with an increase in fat mass (predominantly in visceral fat), an increase in insulin resistance, dyslipidaemia, and endothelial dysfunction. Women with vasomotor symptoms during menopause seem to have an especially unfavorable cardiometabolic profile, as well as women with premature onset of menopause (before 45 years of age). These risks can be reduced by managing risk factors, such as tobacco smoking, hypertension, increased blood lipids and body weight. Bone health The annual rates of bone mineral density loss are highest during one year before through two years after the final menstrual period. Thus, post menopausal women are at increased risk of osteopenia, osteoporosis and fractures. Causes Menopause can be induced or occur naturally. Induced menopause occurs as a result of medical treatment such as chemotherapy, radiotherapy, oophorectomy, or complications of tubal ligation, hysterectomy, unilateral or bilateral salpingo-oophorectomy or leuprorelin usage. Age Menopause typically occurs between 47 and 54 years of age. According to various data, more than 85% of women have their last period between the ages of 47–54 (median 49–50). 2% of women under the age of 40, 5% between the ages of 40–45 and the same number between the ages of 55–58 have their last bleeding. The average age of the last period in the United States is 51 years, in Russia is 50 years, in Greece is 49 years, in Turkey is 47 years, in Egypt is 47 years and in India is 46 years. The menopausal transition or perimenopause leading up to menopause usually lasts 3–4 years (sometimes as long as 5–14 years).In rare cases, a womans ovaries stop working at a very early age, ranging anywhere from the age of puberty to age 40. This is known as premature ovarian failure and affects 1 to 2% of women by age 40.Undiagnosed and untreated coeliac disease is a risk factor for early menopause. Coeliac disease can present with several non-gastrointestinal symptoms, in the absence of gastrointestinal symptoms, and most cases escape timely recognition and go undiagnosed, leading to a risk of long-term complications. A strict gluten-free diet reduces the risk. Women with early diagnosis and treatment of coeliac disease present a normal duration of fertile life span.Women who have undergone hysterectomy with ovary conservation go through menopause on average 1.5 years earlier than the expected age. Other factors that can promote an earlier onset of menopause (usually 1 to 3 years early) are smoking cigarettes. Premature ovarian insufficiency Premature ovarian insufficiency (POI) is when the ovaries stop functioning before the age of 40 years. It is diagnosed or confirmed by high blood levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) on at least three occasions at least four weeks apart.Premature ovarian insufficiency may be auto immune and therefore co occur with other autoimmune disorders such as thyroid disease, [adrenal insufficiency], and diabetes mellitus. Other causes include chemotherapy, being a carrier of the fragile X syndrome gene, and radiotherapy. However, in about 50–80% of cases of premature ovarian insufficiency, the cause is unknown, i.e., it is generally idiopathic.An early menopause can be related to cigarette smoking, higher body mass index, racial and ethnic factors, illnesses, and the removal of the uterus.Rates of premature menopause have been found to be significantly higher in fraternal and identical twins; approximately 5% of twins reach menopause before the age of 40. The reasons for this are not completely understood. Transplants of ovarian tissue between identical twins have been successful in restoring fertility. Surgical menopause Menopause can be surgically induced by bilateral oophorectomy (removal of ovaries), which is often, but not always, done in conjunction with removal of the Fallopian tubes (salpingo-oophorectomy) and uterus (hysterectomy). Cessation of menses as a result of removal of the ovaries is called "surgical menopause". Surgical treatments, such as the removal of ovaries, might cause periods to stop altogether. The sudden and complete drop in hormone levels may produce extreme withdrawal symptoms such as hot flashes, etc. The symptoms of early menopause may be more severe.Removal of the uterus without removal of the ovaries does not directly cause menopause, although pelvic surgery of this type can often precipitate a somewhat earlier menopause, perhaps because of a compromised blood supply to the ovaries. The time between surgery and possible early menopause is due to the fact that ovaries are still producing hormones. Mechanism The menopausal transition, and postmenopause itself, is a natural change, not usually a disease state or a disorder. The main cause of this transition is the natural depletion and aging of the finite amount of oocytes (ovarian reserve). This process is sometimes accelerated by other conditions and is known to occur earlier after a wide range of gynecologic procedures such as hysterectomy (with and without ovariectomy), endometrial ablation and uterine artery embolisation. The depletion of the ovarian reserve causes an increase in circulating follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels because there are fewer oocytes and follicles responding to these hormones and producing estrogen. The transition has a variable degree of effects.The stages of the menopause transition have been classified according to a womans reported bleeding pattern, supported by changes in the pituitary follicle-stimulating hormone (FSH) levels.In younger women, during a normal menstrual cycle the ovaries produce estradiol, testosterone and progesterone in a cyclical pattern under the control of FSH and luteinizing hormone (LH), which are both produced by the pituitary gland. During perimenopause (approaching menopause), estradiol levels and patterns of production remain relatively unchanged or may increase compared to young women, but the cycles become frequently shorter or irregular. The often observed increase in estrogen is presumed to be in response to elevated FSH levels that, in turn, is hypothesized to be caused by decreased feedback by inhibin. Similarly, decreased inhibin feedback after hysterectomy is hypothesized to contribute to increased ovarian stimulation and earlier menopause.The menopausal transition is characterized by marked, and often dramatic, variations in FSH and estradiol levels. Because of this, measurements of these hormones are not considered to be reliable guides to a womans exact menopausal status.Menopause occurs because of the sharp decrease of estradiol and progesterone production by the ovaries. After menopause, estrogen continues to be produced mostly by aromatase in fat tissues and is produced in small amounts in many other tissues such as ovaries, bone, blood vessels, and the brain where it acts locally. The substantial fall in circulating estradiol levels at menopause impacts many tissues, from brain to skin. In contrast to the sudden fall in estradiol during menopause, the levels of total and free testosterone, as well as dehydroepiandrosterone sulfate (DHEAS) and androstenedione appear to decline more or less steadily with age. An effect of natural menopause on circulating androgen levels has not been observed. Thus specific tissue effects of natural menopause cannot be attributed to loss of androgenic hormone production.Hot flashes and other vasomotor and body symptoms accompanying the menopausal transition are associated with estrogen insufficiency and changes that occur in the brain, primarily the hypothalamus and involve complex interplay between the neurotransmitters kisspeptin, neurokinin 3B (NK3B) and dynorphin, which are found in ‘KNDy’ neurons in the infundibular nucleus.Long-term effects of menopause may include osteoporosis, vaginal atrophy as well as changed metabolic profile resulting in increased cardiac and metabolic disease (diabetes) risks. Ovarian aging Decreased inhibin feedback after hysterectomy is hypothesized to contribute to increased ovarian stimulation and earlier menopause. Hastened ovarian aging has been observed after endometrial ablation. While it is difficult to prove that these surgeries are causative, it has been hypothesized that the endometrium may be producing endocrine factors contributing to the endocrine feedback and regulation of the ovarian stimulation. Elimination of these factors contributes to faster depletion of the ovarian reserve. Reduced blood supply to the ovaries that may occur as a consequence of hysterectomy and uterine artery embolisation has been hypothesized to contribute to this effect.Impaired DNA repair mechanisms may contribute to earlier depletion of the ovarian reserve during aging. As women age, double-strand breaks accumulate in the DNA of their primordial follicles. Primordial follicles are immature primary oocytes surrounded by a single layer of granulosa cells. An enzyme system is present in oocytes that ordinarily accurately repairs DNA double-strand breaks. This repair system is called "homologous recombinational repair", and it is especially effective during meiosis. Meiosis is the general process by which germ cells are formed in all sexual eukaryotes; it appears to be an adaptation for efficiently removing damages in germ line DNA.Human primary oocytes are present at an intermediate stage of meiosis, termed prophase I (see Oogenesis). Expression of four key DNA repair genes that are necessary for homologous recombinational repair during meiosis (BRCA1, MRE11, Rad51, and ATM) decline with age in oocytes. This age-related decline in ability to repair DNA double-strand damages can account for the accumulation of these damages, that then likely contributes to the depletion of the ovarian reserve. Diagnosis Ways of assessing the impact on women of some of these menopause effects, include the Greene climacteric scale questionnaire, the Cervantes scale and the Menopause rating scale. Premenopause Premenopause is a term used to mean the years leading up to the last period, when the levels of reproductive hormones are becoming more variable and lower, and the effects of hormone withdrawal are present. Premenopause starts some time before the monthly cycles become noticeably irregular in timing. Perimenopause The term "perimenopause", which literally means "around the menopause", refers to the menopause transition years before the date of the final episode of flow. According to the North American Menopause Society, this transition can last for four to eight years. The Centre for Menstrual Cycle and Ovulation Research describes it as a six- to ten-year phase ending 12 months after the last menstrual period.During perimenopause, estrogen levels average about 20–30% higher than during premenopause, often with wide fluctuations. These fluctuations cause many of the physical changes during perimenopause as well as menopause, especially during the last 1–2 years of perimenopause (before menopause). Some of these changes are hot flashes, night sweats, difficulty sleeping, mood swings, vaginal dryness or atrophy, incontinence, osteoporosis, and heart disease. Perimenopause is also associated with a higher likelihood of depression (affecting from 45 percent to 68 percent of perimenopausal women), which is twice as likely to affect those with a history of depression.During this period, fertility diminishes but is not considered to reach zero until the official date of menopause. The official date is determined retroactively, once 12 months have passed after the last appearance of menstrual blood. The menopause transition typically begins between 40 and 50 years of age (average 47.5). The duration of perimenopause may be for up to eight years. Women will often, but not always, start these transitions (perimenopause and menopause) about the same time as their mother did.In some women, menopause may bring about a sense of loss related to the end of fertility. In addition, this change often occurs when other stressors may be present in a womans life: Caring for, and/or the death of, elderly parents Empty nest syndrome when children leave home The birth of grandchildren, which places people of "middle age" into a new category of "older people" (especially in cultures where being older is a state that is looked down on)Some research appears to show that melatonin supplementation in perimenopausal women can improve thyroid function and gonadotropin levels, as well as restoring fertility and menstruation and preventing depression associated with menopause. Postmenopause The term "postmenopausal" describes women who have not experienced any menstrual flow for a minimum of 12 months, assuming that they have a uterus and are not pregnant or lactating. In women without a uterus, menopause or postmenopause can be identified by a blood test showing a very high FSH level. Thus postmenopause is the time in a womans life that takes place after her last period or, more accurately, after the point when her ovaries become inactive. The reason for this delay in declaring postmenopause is that periods are usually erratic at this time of life. Therefore, a reasonably long stretch of time is necessary to be sure that the cycling has ceased. At this point a woman is considered infertile; however, the possibility of becoming pregnant has usually been very low (but not quite zero) for a number of years before this point is reached. A womans reproductive hormone levels continue to drop and fluctuate for some time into post-menopause, so hormone withdrawal effects such as hot flashes may take several years to disappear. A period-like flow during postmenopause, even spotting, may be a sign of endometrial cancer. Management Perimenopause is a natural stage of life. It is not a disease or a disorder. Therefore, it does not automatically require any kind of medical treatment. However, in those cases where the physical, mental, and emotional effects of perimenopause are strong enough that they significantly disrupt the life of the woman experiencing them, palliative medical therapy may sometimes be appropriate. Menopausal Hormone therapy In the context of the menopause, Menopausal hormone therapy (MHT) is the use of estrogen in women without a uterus and estrogen plus progestogen in women who have an intact uterus.MHT may be reasonable for the treatment of menopausal symptoms, such as hot flashes. It is the most effective treatment option, especially when delivered as a skin patch. Its use, however, appears to increase the risk of strokes and blood clots. When used for menopausal symptoms the global recommendation is MHT should be prescribed for a long as there are defined treatment effects and goals for the individual woman.MHT is also effective for preventing bone loss and osteoporotic fracture, but it is generally recommended only for women at significant risk for whom other therapies are unsuitable.MHT may be unsuitable for some women, including those at increased risk of cardiovascular disease, increased risk of thromboembolic disease (such as those with obesity or a history of venous thrombosis) or increased risk of some types of cancer. There is some concern that this treatment increases the risk of breast cancer. Women at increased risk of cardiometabolic disease and VTE may be able to use transdermal estradiol which does not appear to increase risks in low to moderate doses.Adding testosterone to hormone therapy has a positive effect on sexual function in postmenopausal women, although it may be accompanied by hair growth, acne if used in excess. Transdermal testosterone therapy in appropriate dosing is generally safe Selective estrogen receptor modulators SERMs are a category of drugs, either synthetically produced or derived from a botanical source, that act selectively as agonists or antagonists on the estrogen receptors throughout the body. The most commonly prescribed SERMs are raloxifene and tamoxifen. Raloxifene exhibits oestrogen agonist activity on bone and lipids, and antagonist activity on breast and the endometrium. Tamoxifen is in widespread use for treatment of hormone sensitive breast cancer. Raloxifene prevents vertebral fractures in postmenopausal, osteoporotic women and reduces the risk of invasive breast cancer. Other medications Some of the SSRIs and SNRIs appear to provide some relief from vasomotor symptoms. Low dose paroxetine is the only non-hormonal medication that was FDA-approved to treat moderate-to-severe vasomotor symptoms associated with menopause as of 2016. They may, however, be associated with appetite and sleeping problems, constipation and nausea.Gabapentin or clonidine may help but do not work as well as hormone therapy. Gabapentin can decrease the amount of hot flashes. Side effects associated with its use include drowsiness and headaches. Clonidine is used to improve vasomotor symptoms and may be associated with constipation, dizziness, nausea and sleeping problems. Therapy One review found mindfulness and cognitive behavioural therapy decreases the amount women are affected by hot flashes. Another review found not enough evidence to make a conclusion. A 2018 study found that 85% of study participants reported reduced hot flashes and night sweats when using a climate control system in their beds. Exercise Exercise has been thought to reduce postmenopausal symptoms through the increase of endorphin levels, which decrease as estrogen production decreases. Additionally, high BMI is a risk factor for vasomotor symptoms in particular. However, there is insufficient evidence to support the benefits of weight loss for symptom management. There are mixed perspectives on the benefits of physical exercise. While one review found that there was a lack of quality evidence supporting a benefit of exercise, another review recommended regular healthy exercise to reduce comorbidities, improve mood and anxiety symptoms, enhance cognition, and decrease the risk of fractures. Yoga may help with postmenopausal symptoms similar to other exercise. There is insufficient evidence to suggest that relaxation techniques reduce menopausal symptoms. Alternative medicine There is no evidence of consistent benefit of alternative therapies for menopausal symptoms despite their popularity.The effect of soy isoflavones on menopausal symptoms is promising for reduction of hot flashes and vaginal dryness. Evidence does not support a benefit from phytoestrogens such as coumestrol, femarelle, or the non-phytoestrogen black cohosh. As of 2011 there is no support for herbal or dietary supplements in the prevention or treatment of the mental changes that occur around menopause.Hypnosis may reduce the severity of hot flashes. In addition, relaxation training with at-home relaxation audiotapes such as deep breathing, paced respiration, and guided imagery may have positive effects on relaxing muscles and reducing stress.There is no evidence to support the efficacy of acupuncture as a management for menopausal symptoms. A 2016 Cochrane review found not enough evidence to show a difference between Chinese herbal medicine and placebo for the vasomotor symptoms. Other efforts Lack of lubrication is a common problem during and after perimenopause. Vaginal moisturizers can help women with overall dryness, and lubricants can help with lubrication difficulties that may be present during intercourse. It is worth pointing out that moisturizers and lubricants are different products for different issues: some women complain that their genitalia are uncomfortably dry all the time, and they may do better with moisturizers. Those who need only lubricants do well using them only during intercourse. Low-dose prescription vaginal estrogen products such as estrogen creams are generally a safe way to use estrogen topically, to help vaginal thinning and dryness problems (see vaginal atrophy) while only minimally increasing the levels of estrogen in the bloodstream. In terms of managing hot flashes, lifestyle measures such as drinking cold liquids, staying in cool rooms, using fans, removing excess clothing, and avoiding hot flash triggers such as hot drinks, spicy foods, etc., may partially supplement (or even obviate) the use of medications for some women. Individual counseling or support groups can sometimes be helpful to handle sad, depressed, anxious or confused feelings women may be having as they pass through what can be for some a very challenging transition time. Osteoporosis can be minimized by smoking cessation, adequate vitamin D intake and regular weight-bearing exercise. The bisphosphonate drug alendronate may decrease the risk of a fracture, in women that have both bone loss and a previous fracture and less so for those with just osteoporosis. A surgical procedure where a part of one of the ovaries is removed earlier in life and frozen and then over time thawed and returned to the body has been tried. While at least 11 women have undergone the procedure and paid over £6,000, there is no evidence it is safe or effective. Society and culture The cultural context within which a woman lives can have a significant impact on the way she experiences the menopausal transition. Menopause has been described as a subjective experience, with social and cultural factors playing a prominent role in the way menopause is experienced and perceived. The word menopause was invented by French doctors at the beginning of the nineteenth century. Some of them noted that peasant women had no complaints about the end of menses, while urban middle-class women had many troubling symptoms. Doctors at this time considered the symptoms to be the result of urban lifestyles of sedentary behaviour, alcohol consumption, too much time indoors, and over-eating, with a lack of fresh fruit and vegetables. Within the United States, social location affects the way women perceive menopause and its related biological effects. Research indicates that whether a woman views menopause as a medical issue or an expected life change is correlated with her socio-economic status. The paradigm within which a woman considers menopause influences the way she views it: Women who understand menopause as a medical condition rate it significantly more negatively than those who view it as a life transition or a symbol of aging.Ethnicity and geography play roles in the experience of menopause. American women of different ethnicities report significantly different types of menopausal effects. One major study found Caucasian women most likely to report what are sometimes described as psychosomatic symptoms, while African-American women were more likely to report vasomotor symptoms.It seems that Japanese women experience menopause effects, or konenki, in a different way from American women. Japanese women report lower rates of hot flashes and night sweats; this can be attributed to a variety of factors, both biological and social. Historically, konenki was associated with wealthy middle-class housewives in Japan, i.e., it was a "luxury disease" that women from traditional, inter-generational rural households did not report. Menopause in Japan was viewed as a symptom of the inevitable process of aging, rather than a "revolutionary transition", or a "deficiency disease" in need of management.In Japanese culture, reporting of vasomotor symptoms has been on the increase, with research conducted in 2005 finding that of 140 Japanese participants, hot flashes were prevalent in 22.1%. This was almost double that of 20 years prior. Whilst the exact cause for this is unknown, possible contributing factors include significant dietary changes, increased medicalisation of middle-aged women and increased media attention on the subject. However, reporting of vasomotor symptoms is still significantly lower than North America.Additionally, while most women in the United States apparently have a negative view of menopause as a time of deterioration or decline, some studies seem to indicate that women from some Asian cultures have an understanding of menopause that focuses on a sense of liberation and celebrates the freedom from the risk of pregnancy. Diverging from these conclusions, one study appeared to show that many American women "experience this time as one of liberation and self-actualization". Etymology Menopause literally means the "end of monthly cycles" (the end of monthly periods or menstruation), from the Greek word pausis ("pause") and mēn ("month"). This is a medical coinage; the Greek word for menses is actually different. In Ancient Greek, the menses were described in the plural, ta emmēnia, ("the monthlies"), and its modern descendant has been clipped to ta emmēna. The Modern Greek medical term is emmenopausis in Katharevousa or emmenopausi in Demotic Greek. The word "menopause" was coined specifically for human females, where the end of fertility is traditionally indicated by the permanent stopping of monthly menstruations. However, menopause exists in some other animals, many of which do not have monthly menstruation; in this case, the term means a natural end to fertility that occurs before the end of the natural lifespan. Menopause in popular culture In recent years celebrities have spoken out about their experiences of the menopause which has led to it becoming less of a taboo as it has boosted awareness of the debilitating symptoms. This has led to TV shows running features on the menopause to help women experiencing symptoms. In the UK Lorraine Kelly has been an advocate for getting women to speak about their experiences including sharing her own. This has led to an increase in women seeking treatment such as HRT Evolutionary rationale Few animals have a menopause: humans are joined by just four other species in which females live substantially longer than their ability to reproduce. The others are all cetaceans: beluga whales, narwhals, orcas and short-finned pilot whales. Various theories have been suggested that attempt to suggest evolutionary benefits to the human species stemming from the cessation of womens reproductive capability before the end of their natural lifespan. Explanations can be categorized as adaptive and non-adaptive: Non-adaptive hypotheses The high cost of female investment in offspring may lead to physiological deteriorations that amplify susceptibility to becoming infertile. This hypothesis suggests the reproductive lifespan in humans has been optimized, but it has proven more difficult in females and thus their reproductive span is shorter. If this hypothesis were true, however, age at menopause should be negatively correlated with the amount of energy expended to maintain the reproductive organs, and the available data does not support this.A recent increase in female longevity due to improvements in the standard of living and social care has also been suggested. It is difficult for selection, however, to favor aid to offspring from parents and grandparents. Irrespective of living standards, adaptive responses are limited by physiological mechanisms. In other words, senescence is programmed and regulated by specific genes. Early human selection shadow While it is fairly common for extant hunter-gatherers to live past age 50 provided that they survive childhood, fossil evidence shows that mortality in adults has decreased over the last 30,000 to 50,000 years and that it was extremely unusual for early Homo sapiens to live to age 50. This discovery has led some biologists to argue that there was no selection for or against menopause at the time at which the ancestor of all modern humans lived in Africa, suggesting that menopause is instead a random evolutionary effect of a selection shadow regarding aging in early Homo sapiens. It is also argued that since the population fraction of post-menopausal women in early Homo sapiens was so low, menopause had no evolutionary effect on mate selection or social behaviors related to mate selection. Adaptive hypotheses "Survival of the fittest" hypothesis This hypothesis suggests that younger mothers and offspring under their care will fare better in a difficult and predatory environment because a younger mother will be stronger and more agile in providing protection and sustenance for herself and a nursing baby. The various biological factors associated with menopause had the effect of male members of the species investing their effort with the most viable of potential female mates.A problem with this hypothesis is that, if true, we would expect to see menopause exhibited among many species in the animal kingdom, and another problem is that in the case of extended child development, even a female who was relatively young, still agile, and attractive when producing a child would lose future support from her male partner due to him seeking out fertile mates when she reaches menopause, while the child is still not independent. This would be counterproductive to the supposed adaptation of getting male support, as it would significantly decrease the survival for children produced over much of the females fertile and agile life, unless children were raised in ways that did not rely on support from a male partner, which would eliminate the supposed evolutionary benefit anyway. Young female preference hypothesis The young female preference hypothesis proposes that changes in male preferences for younger mates allowed late-age acting fertility mutations to accumulate in females without any evolutionary penalty, giving rise to menopause. A computer model was constructed to test this hypothesis, and showed that it was feasible. However, in order for deleterious mutations that affect fertility past roughly age fifty to accumulate, human maximum lifespan had to first be extended to about its present value. As of 2016 it was unclear if there has been sufficient time since that happened for such an evolutionary process to occur. Male-biased philopatry hypothesis The male-biased philopatry theory proposes that if human social groups were originally based around men leaving their birth communities more frequently than women, then this leads to increased relatedness to the group in relation to female age, making inclusive fitness benefits older females receive from helping the group greater than what they would receive from continued reproduction, which in turn eventually led to the evolution of menopause. In a pattern of male-biased dispersal and local mating, the relatedness of the individuals in the group decreases with female age, leading to a decrease in kin selection with female age. This occurs because a female will stay with her father in her birth community throughout life, initially being closely related to the males and females. Females are born and stay in the group, so relatedness to the females stays about the same. However, throughout time, the older male relatives will die and any sons she gives birth to will disperse, so that local relatedness to males, and therefore the whole group, declines. The situation is reversed in species where males are philopatric and either females disperse, or mating is non-local. Under these conditions, a females reproductive life begins away from her father and paternal relatives because she was either born into a new group from non-local mating or because she dispersed. In the case of female-biased dispersal, the female is initially equally unrelated with every individual in the group, and with non-local mating, the female is closely related to the females of the group, but not the males since her paternal relatives are in another group. As she gives birth, her sons will stay with her, increasing her relatedness to males in the group over time and thus her relatedness with the overall group. The common feature that connects these two otherwise different behaviors is male-biased philopatry, which leads to an increase in kin selection with female age. While not conclusive, evidence does exist to support the idea that female-biased dispersal existed in pre-modern humans. The closest living relatives to humans, chimpanzees, bonobos, and both mountain gorillas and western lowland gorillas, are female-biased dispersers. Analysis of sex specific genetic material, the non-recombining portions of the Y chromosome and mitochondrial DNA, show evidence of a prevalence of female-biased dispersal as well; however, these results could also be affected by the effective breeding numbers of males and females in local populations. Evidence of female-biased dispersion in hunter-gatherers is not definitive, with some studies supporting the idea, and others suggesting there is no strong bias towards either sex. In orcas, both sexes mate non-locally with members of a different pod but return to the pod after copulation. Demographic data shows that a females mean relatedness to the group does increase over time due to increasing relatedness to males. While less well-studied, there is evidence that short-finned pilot whales, another menopausal species, also display this behavior. However, mating behavior that increases local relatedness with female age is prevalent in non-menopausal species, making it unlikely that it is the only factor that determines if menopause will evolve in a species. Mother hypothesis The mother hypothesis suggests that menopause was selected for humans because of the extended development period of human offspring and high costs of reproduction so that mothers gain an advantage in reproductive fitness by redirecting their effort from new offspring with a low survival chance to existing children with a higher survival chance. Grandmother hypothesis The grandmother hypothesis suggests that menopause was selected for humans because it promotes the survival of grandchildren. According to this hypothesis, post-reproductive women feed and care for children, adult nursing daughters, and grandchildren whose mothers have weaned them. Human babies require large and steady supplies of glucose to feed the growing brain. In infants in the first year of life, the brain consumes 60% of all calories, so both babies and their mothers require a dependable food supply. Some evidence suggests that hunters contribute less than half the total food budget of most hunter-gatherer societies, and often much less than half, so that foraging grandmothers can contribute substantially to the survival of grandchildren at times when mothers and fathers are unable to gather enough food for all of their children. In general, selection operates most powerfully during times of famine or other privation. So although grandmothers might not be necessary during good times, many grandchildren cannot survive without them during times of famine. Post-reproductive female orcas tend to lead their pods, especially during years of food scarcity. Furthermore, the increased mortality risk of an orca due to losing a grandmother is stronger in years of food scarcityAnalysis of historical data found that the length of a females post-reproductive lifespan was reflected in the reproductive success of her offspring and the survival of her grandchildren. Another study found comparative effects but only in the maternal grandmother—paternal grandmothers had a detrimental effect on infant mortality (probably due to paternity uncertainty). Differing assistance strategies for maternal and paternal grandmothers have also been demonstrated. Maternal grandmothers concentrate on offspring survival, whereas paternal grandmothers increase birth rates.Some believe variations on the mother, or grandmother effect fail to explain longevity with continued spermatogenesis in males (oldest verified paternity is 94 years, 35 years beyond the oldest documented birth attributed to females). Notably, the survival time past menopause is roughly the same as the maturation time for a human child. That a mothers presence could aid in the survival of a developing child, while an unidentified fathers absence might not have affected survival, could explain the paternal fertility near the end of the fathers lifespan. A man with no certainty of which children are his may merely attempt to father additional children, with support of existing children present but small. Note the existence of partible paternity supporting this. Some argue that the mother and grandmother hypotheses fail to explain the detrimental effects of losing ovarian follicular activity, such as osteoporosis, osteoarthritis, Alzheimers disease and coronary artery disease.The theories discussed above assume that evolution directly selected for menopause. Another theory states that menopause is the byproduct of the evolutionary selection for follicular atresia, a factor that causes menopause. Menopause results from having too few ovarian follicles to produce enough estrogen to maintain the ovarian-pituitary-hypothalamic loop, which results in the cessation of menses and the beginning of menopause. Human females are born with approximately a million oocytes, and approximately 400 oocytes are lost to ovulation throughout life. Reproductive conflict hypothesis In social vertebrates, the sharing of resources among the group places limits on how many offspring can be produced and supported by members of the group. This creates a situation in which each female must compete with others of the group to ensure they are the one that reproduces. The reproductive conflict hypothesis proposes that this female reproductive conflict favors the cessation of female reproductive potential in older age to avoid reproductive conflict, increasing the older females fitness through inclusive benefits. Female-biased dispersal or non-local mating leads to an increase in relatedness to the social group with female age. In the human case of female-biased dispersal, when a young female enters a new group, she is not related to any individual and she reproduces to produce an offspring with a relatedness of 0.5. An older female could also choose to reproduce, producing an offspring with a relatedness of 0.5, or she could refrain from reproducing and allow another pair to reproduce. Because her relatedness to males in the group is high, there is a fair probability that the offspring will be her grandchild with a relatedness of 0.25. The younger female experiences no cost to her inclusive fitness from using the resources necessary to successfully rear offspring since she is not related to members of the group, but there is a cost for the older female. As a result, the younger female has the advantage in reproductive competition. Although a female orca born into a social group is related to some members of the group, the whale case of non-local mating leads to similar outcomes because the younger female relatedness to the group as a whole is less than the relatedness of the older female. This behavior makes more likely the cessation of reproduction late in life to avoid reproductive conflict with younger females. Research using both human and orca demographic data has been published that supports the role of reproductive conflict in the evolution of menopause. Analysis of demographic data from pre-industrial Finnish populations found significant reductions in offspring survivorship when mothers-in-laws and daughters-in-laws had overlapping births, supporting the idea that avoiding reproductive conflict is beneficial to offspring survivorship. Humans, more so than other primates, rely on food sharing for survival, so the large survivorship reduction values could be caused by a straining of community resources. Avoiding such straining is a possible explanation for why the reproductive overlap seen in humans is much lower than other primates. Food sharing is also prevalent among another menopausal species, orcas. Reproductive conflict has also been observed in orcas, with increased calf mortality seen when reproductive overlap between a younger and older generational female occurred. Other animals Menopause in the animal kingdom appears to be uncommon, but the presence of this phenomenon in different species has not been thoroughly researched. Life histories show a varying degree of senescence; rapid senescing organisms (e.g., Pacific salmon and annual plants) do not have a post-reproductive life-stage. Gradual senescence is exhibited by all placental mammalian life histories. Menopause has been observed in several species of nonhuman primates, including rhesus monkeys and chimpanzees. Some research suggests that wild chimpanzees do not experience menopause, as their fertility declines are associated with declines in overall health. Menopause also has been reported in a variety of other vertebrate species including elephants, short-finned pilot whales, orcas, narwhals, beluga whales, and the guppy. However, with the exception of the short-finned pilot whale, killer whale, narwhals, and beluga whales, such examples tend to be from captive individuals, and thus they are not necessarily representative of what happens in natural populations in the wild. Dogs do not experience menopause; the canine estrus cycle simply becomes irregular and infrequent. Although older female dogs are not considered good candidates for breeding, offspring have been produced by older animals. Similar observations have been made in cats. See also European Menopause and Andropause Society Menopause in the workplace Menopause in incarceration Pregnancy over age 50 References External links Menopause: MedlinePlus Menopause and Menopause Treatments

Trisomy 9

Full trisomy 9 is a lethal chromosomal disorder caused by having three copies (trisomy) of chromosome number 9. It can be a viable condition if trisomy affects only part of the cells of the body (mosaicism) or in cases of partial trisomy (trisomy 9p) in which cells have a normal set of two entire chromosomes 9 plus part of a third copy, usually of the short arm of the chromosome (arm p). Presentation Symptoms vary, but usually result in dysmorphisms in the skull, nervous system problems, and developmental delay. Dysmorphisms in the heart, kidneys, and musculoskeletal system may also occur. An infant with complete trisomy 9 surviving 20 days after birth showed clinical features including a small face, wide fontanelle, prominent occiput, micrognathia, low set ears, upslanting palpebral fissures, high-arched palate, short sternum, overlapping fingers, limited hip abduction, rocker bottom feet, heart murmurs and a webbed neck.Trisomy 9p is one of the most frequent autosomal anomalies compatible with long survival rate. A study of five cases showed an association with Coffin–Siris syndrome, as well as a wide gap between the first and second toes in all five, while three had brain malformations including dilated ventricles with hypogenesis of the corpus callosum and Dandy-Walker malformation. Diagnosis Trisomy 9 can be detected prenatally with chorionic villus sampling and cordocentesis, and can be suggested by obstetric ultrasonography.Because trisomy 9 may appear with mosaicism, it is suggested that doctors take samples from multiple tissues when karyotyping for diagnosis. References External links NORD - National Organization for Rare Disorders, Inc. Chromosome 9, Trisomy 9p (Multiple Variants) NORD - National Organization for Rare Disorders, Inc. Chromosome 9, Trisomy Mosaic

Nuchal cord

A nuchal cord is when the umbilical cord becomes wrapped around the fetuss neck. Symptoms present in the baby shortly after birth from a prior nuchal cord may include duskiness of face, facial petechia, and bleeding in the whites of the eye. Complications can include meconium, respiratory distress, anemia, and stillbirth. Multiple wraps are associated with greater risk.The diagnosis may be suspected if there is a decrease in the babys heart rate during delivery. Nuchal cords are typically checked for by running the finger over the babys neck once the head has delivered. Ultrasound may pick up the condition before labor.If detected during delivery, management includes trying to unwrap the cord or if this is not possible clamping and cutting the cord. Delivery can typically take place as normal and outcomes are generally good. Rarely long term brain damage or cerebral palsy may occur. Nuchal cords occur in about a quarter of deliveries. The condition has been described at least as early as 300 BC by Hippocrates. Signs and symptoms Symptoms of a prior nuchal cord shortly after birth in the baby may include duskiness of face, facial petechia, and bleeding in the whites of the eye. Complications can include meconium, respiratory disease, anemia, and still birth. Diagnosis In 1962, J. Selwyn Crawford MD from the British Research Council defined a nuchal cord as one that is wrapped 360 degrees around the fetal neck. Crawford commented "It is all the more remarkable, therefore, that little work has been done. to analyze its effects during labor and delivery". To date, there is no prospective case control double-blind study looking at nuchal cords and observational studies vary in opinion as to the degree of poor outcomes. Also not included in these studies is which umbilical cord form (of the 8 different possible structures) was considered a nuchal cord.Ultrasound diagnosis of a cord around the neck was first described in 1982. “Coils occur in about 25% of cases and ordinarily do no harm, but occasionally they may be so tight that constriction of the umbilical vessels and consequent hypoxia result.” Williams Obstetrics 16th Edition, has only one single sentence in the entire textbook regarding cords around the neck. By contrast, the First Edition of the Encyclopædia Britannica from 1770 had 20 pages of information about Umbilical Cord Pathology with drawings of Umbilical Cord Entanglement. The Royal College of Obstetricians and Gynaecologists has these images on its brochure. There are currently three recent texts on ultrasonography which demonstrate the ability of ultrasound to identify umbilical cord issues with reliability as of 2009.A study published in 2004 was done to establish the sensitivity of ultrasound in the diagnosis of a nuchal cord. Each of 289 women, induced the same day, underwent a transabdominal ultrasound scan with an Aloka 1700 ultrasound machine with a 3.5 MHz abdominal probe, using gray-scale and color Doppler imaging immediately prior to induction of labor. Presence of the cord was sought in the transverse and sagittal plane of the neck. A nuchal cord was diagnosed if the cord was visualized lying around at least 3 of the 4 sides of the neck. A cord was actually present at delivery in 52 of the 289 women. Only 18 of the 52 cords or 35% of the nuchal cords were detected on ultrasound done immediately before delivery, and 65% of nuchal cords were not detected. Of the 237 cases where there was no cord at delivery, ultrasound had false positive results, i.e. diagnosed a cord in 44 of the 237 cases (19%) in which there was no cord present at all. In this study, ultrasound was only 35% accurate at finding a single loop, and only 60% accurate at detecting a nuchal cord wrapped multiple times around the neck.In no study was it possible by ultrasound to distinguish between a loose or a tight cord, although at least 3 attempted to do so. Peregrine concludes that ultrasound diagnosis of nuchal cords will only be useful if doctors are able to do so reliably and predict which of those fetuses are likely to have a problem., However, perinatologists routinely look for umbilical cord issues in monoamniotic twins. Studies have shown an improvement in outcomes where cord entanglement was prenatally identified in these cases. Ultrasound measurement of the velocity of flow in the cord may be useful in the management of twins and chronically growth-retarded fetuses. Of course this depends on the training of the sonographer. To date there are no ultrasound courses which teach the identification of nuchal cord to physicians or technicians. A recent review by Wilson of the American Academy of Ultrasonography Technicians recommends the documentation of umbilical cord issues. Classification A "Type A" nuchal cord is wrapped around the neck but is free sliding A "Type B" pattern is described as a hitch which cannot be undone and ends up as a true knot. Treatment Management of a presenting nuchal cord should be tailored to prevent umbilical cord compression whenever possible. Techniques to preserve an intact nuchal cord depend on how tightly the cord is wrapped around the infant’s neck. If the cord is loose, it can easily be slipped over the infant’s head. The infant can be delivered normally and placed on maternal abdomen as desired. If the cord is too tight to go over the infant’s head, the provider may be able to slip it over the infant’s shoulders and deliver the body through the cord. The cord can then be unwrapped from around the baby after birth. Finally, if the cord is too tight to slip back over the shoulders, one may use the somersault maneuver to allow the body to be delivered. The birth attendant may also choose to clamp and cut the umbilical cord to allow for vaginal delivery if other methods of nuchal cord management are not feasible. Prognosis Retrospective data of over 182,000 births, with the statistical power to determine even mild associations, suggest that a single or multiple nuchal cords at the time of delivery is not associated with adverse perinatal outcomes, is associated with higher birthweights and fewer caesarean sections in births. Although some studies have found that a tight nuchal cord is associated with short term morbidity, it is unclear whether such outcomes are actually a result of the presence of the nuchal cord itself, or as a result of clamping and cutting the cord References == External links ==

Mosquito

Mosquitoes (or mosquitos) are members of a group of almost 3,600 species of small flies within the family Culicidae (from the Latin culex meaning "gnat"). The word "mosquito" (formed by mosca and diminutive -ito) is Spanish and Portuguese for "little fly". Mosquitoes have a slender segmented body, one pair of wings, one pair of halteres, three pairs of long hair-like legs, and elongated mouthparts. The mosquito life cycle consists of egg, larva, pupa, and adult stages. Eggs are laid on the water surface; they hatch into motile larvae that feed on aquatic algae and organic material. These larvae are important food sources for many freshwater animals, such as dragonfly nymphs, many fish, and some birds such as ducks. The adult females of most species have tube-like mouthparts (called a proboscis) that can pierce the skin of a host and feed on blood, which contains protein and iron needed to produce eggs. Thousands of mosquito species feed on the blood of various hosts ⁠— vertebrates, including mammals, birds, reptiles, amphibians, and some fish; along with some invertebrates, primarily other arthropods. The mosquitos saliva is transferred to the host during the bite, and can cause an itchy rash. In addition, many species can ingest pathogens while biting, and transmit them to future hosts. In this way, mosquitoes are important vectors of parasitic diseases such as malaria and filariasis, and arboviral diseases such as yellow fever, Chikungunya, West Nile, dengue fever, and Zika. By transmitting diseases, mosquitoes cause the deaths of more people than any other animal taxon: over 700,000 each year. It has been claimed that almost half of the people who have ever lived have died of mosquito-vectored disease, but this claim is disputed, with more conservative estimates placing the death toll closer to 5% of all humans. Mosquitoes cannot live or function properly when the air temperature is below 10 degrees Celsius (50 degrees Fahrenheit). They are mostly active at 15–25 degrees Celsius (60–80 degrees Fahrenheit). Fossil record and evolutionary history The oldest known mosquitoes are known from amber dating to the Late Cretaceous. Three species of Cretaceous mosquito are currently known, Burmaculex antiquus and Priscoculex burmanicus are known from Burmese amber from Myanmar, which dates to the earliest part of the Cenomanian stage of the Late Cretaceous, around 99 million years ago. Paleoculicis minutus, is known from Canadian amber from Alberta, Canada, which dates to the Campanian stage of the Late Cretaceous, around 79 million years ago. Priscoculex burmanicus can be definitively assigned to Anophelinae, one of the two subfamilies of mosquitoes alongside Culicinae, indicating the split between these two subfamilies occurred over 99 million years ago. Molecular estimates suggest that the split between the two subfamilies occurred 197.5 million years ago, during the Early Jurassic, but that major diversification did not take place until the Cretaceous.The mosquito Anopheles gambiae is currently undergoing speciation into the M(opti) and S(avanah) molecular forms. Consequently, some pesticides that work on the M form no longer work on the S form. Over 3,500 species of the Culicidae have already been described. They are generally divided into two subfamilies which in turn comprise some 43 genera. These figures are subject to continual change, as more species are discovered, and as DNA studies compel rearrangement of the taxonomy of the family. The two main subfamilies are the Anophelinae and Culicinae, with their genera as shown in the subsection below. The distinction is of great practical importance because the two subfamilies tend to differ in their significance as vectors of different classes of diseases. Roughly speaking, arboviral diseases such as yellow fever and dengue fever tend to be transmitted by Culicine species, not necessarily in the genus Culex. Some transmit various species of avian malaria, but it is not clear that they ever transmit any form of human malaria. Some species transmit various forms of filariasis, much as many Simuliidae do. Taxonomy Family Mosquitoes are members of a family of nematoceran flies: the Culicidae (from the Latin culex, genitive culicis, meaning "midge" or "gnat"). Superficially, mosquitoes resemble crane flies (family Tipulidae) and chironomid flies (family Chironomidae). Subfamilies Anophelinae Culicinae Genera Mosquitoes have been classified into 112 genera, some of the more common of which appear below. Species Over 3,500 species of mosquitoes have thus far been described in the scientific literature. Genomics An analysis by Matthews et al 2018 suggests mosquito species all carry a large and diverse number of transposable elements. Morphology As true flies, mosquitoes have one pair of wings, with distinct scales on the surface. Their wings are long and narrow, as are their long, thin legs. They have slender and dainty bodies of length typically 3–6 mm, with dark grey to black coloring. Some species harbor specific morphological patterns. When at rest they tend to hold their first pair of legs outward. They are similar in appearance to midges (Chironomidae), another ancient family of flies. Tokunagayusurika akamusi, for example, is a midge fly that looks very much like mosquitoes in that they also have slender and dainty bodies of similar colors, though larger in size. They also have only one pair of wings, but without scales on the surface. Another distinct feature to tell the two families of flies apart is the way they hold their first pair of legs – mosquitoes hold them outward, while midges hold them forward. Life cycle Overview Like all flies, mosquitoes go through four stages in their life cycles: egg, larva, pupa, and adult or imago. The first three stages—egg, larva, and pupa—are largely aquatic. Each of the stages typically lasts 5 to 14 days, depending on the species and the ambient temperature, but there are important exceptions. Mosquitoes living in regions where some seasons are freezing or waterless spend part of the year in diapause; they delay their development, typically for months, and carry on with life only when there is enough water or warmth for their needs. For instance, Wyeomyia larvae typically get frozen into solid lumps of ice during winter and only complete their development in spring. The eggs of some species of Aedes remain unharmed in diapause if they dry out, and hatch later when they are covered by water. Eggs hatch to become larvae, which grow until they are able to change into pupae. The adult mosquito emerges from the mature pupa as it floats at the water surface. Bloodsucking mosquitoes, depending on species, sex, and weather conditions, have potential adult lifespans ranging from as short as a week to as long as several months. Some species can overwinter as adults in diapause. Breeding In most species, adult females lay their eggs in stagnant water: some lay near the waters edge while others attach their eggs to aquatic plants. Each species selects the situation of the water into which it lays its eggs and does so according to its own ecological adaptations. Some breed in lakes, some in temporary puddles. Some breed in marshes, some in salt-marshes. Among those that breed in salt water (such as Opifex fuscus), some are equally at home in fresh and salt water up to about one-third the concentration of seawater, whereas others must acclimatize themselves to the salinity. Such differences are important because certain ecological preferences keep mosquitoes away from most humans, whereas other preferences bring them right into houses at night. Some species of mosquitoes prefer to breed in phytotelmata (natural reservoirs on plants), such as rainwater accumulated in holes in tree trunks, or in the leaf-axils of bromeliads. Some specialize in the liquid in pitchers of particular species of pitcher plants, their larvae feeding on decaying insects that had drowned there or on the associated bacteria; the genus Wyeomyia provides such examples — the harmless Wyeomyia smithii breeds only in the pitchers of Sarracenia purpurea.Some of the species of mosquitoes that are adapted to breeding in phytotelmata are dangerous disease vectors. In nature, they might occupy anything from a hollow tree trunk to a cupped leaf. Such species typically take readily to breeding in artificial water containers. Such casual puddles are important breeding places for some of the most serious disease vectors, such as species of Aedes that transmit dengue and yellow fever. Some with such breeding habits are disproportionately important vectors because they are well-placed to pick up pathogens from humans and pass them on. In contrast, no matter how voracious, mosquitoes that breed and feed mainly in remote wetlands and salt marshes may well remain uninfected, and if they do happen to become infected with a relevant pathogen, might seldom encounter humans to infect, in turn. Eggs and oviposition Mosquito habits of oviposition, the ways in which they lay their eggs, vary considerably between species, and the morphologies of the eggs vary accordingly. The simplest procedure is that followed by many species of Anopheles; like many other gracile species of aquatic insects, females just fly over the water, bobbing up and down to the water surface and dropping eggs more or less singly. The bobbing behavior occurs among some other aquatic insects as well, for example mayflies and dragonflies; it is sometimes called "dapping". The eggs of Anopheles species are roughly cigar-shaped and have floats down their sides. Females of many common species can lay 100–200 eggs during the course of the adult phase of their life cycles. Even with high egg and intergenerational mortality, over a period of several weeks, a single successful breeding pair can create a population of thousands. Some other species, for example members of the genus Mansonia, lay their eggs in arrays, attached usually to the under-surfaces of waterlily pads. Their close relatives, the genus Coquillettidia, lay their eggs similarly, but not attached to plants. Instead, the eggs form layers called "rafts" that float on the water. This is a common mode of oviposition, and most species of Culex are known for the habit, which also occurs in some other genera, such as Culiseta and Uranotaenia. Anopheles eggs may on occasion cluster together on the water, too, but the clusters do not generally look much like compactly glued rafts of eggs. In species that lay their eggs in rafts, rafts do not form adventitiously; the female Culex settles carefully on still water with its hind legs crossed, and as it lays the eggs one by one, it twitches to arrange them into a head-down array that sticks together to form the raft.Aedes females generally drop their eggs singly, much as Anopheles do, but not as a rule into water. Instead, they lay their eggs on damp mud or other surfaces near the waters edge. Such an oviposition site commonly is the wall of a cavity such as a hollow stump or a container such as a bucket or a discarded vehicle tire. The eggs generally do not hatch until they are flooded, and they may have to withstand considerable desiccation before that happens. They are not resistant to desiccation straight after oviposition, but must develop to a suitable degree first. After that, they can enter diapause for several months if they dry out. Clutches of eggs of the majority of mosquito species hatch as soon as possible, and all the eggs in the clutch hatch at much the same time. In contrast, a batch of Aedes eggs in diapause tends to hatch irregularly over an extended period of time. This makes it much more difficult to control such species than those mosquitoes whose larvae can be killed all together as they hatch. Some Anopheles species do also behave in such a manner, though not to the same degree of sophistication. Larva The mosquito larva has a well-developed head with mouth brushes used for feeding, a large thorax with no legs, and a segmented abdomen. Larvae breathe through spiracles located on their eighth abdominal segments, or through a siphon, so must come to the surface frequently. The larvae spend most of their time feeding on algae, bacteria, and other microbes in the surface microlayer. Mosquito larvae have been investigated as prey of other Dipteran flies. Species such as Bezzia nobilis within the family Ceratopogonidae have been observed in experiments to prey upon mosquito larvae.They dive below the surface when disturbed. Larvae swim either through propulsion with their mouth brushes, or by jerky movements of their entire bodies, giving them the common name of "wigglers" or "wrigglers". Larvae develop through four stages, or instars, after which they metamorphose into pupae. At the end of each instar, the larvae molt, shedding their skins to allow for further growth. Pupa As seen in its lateral aspect, the mosquito pupa is comma-shaped. The head and thorax are merged into a cephalothorax, with the abdomen curving around underneath. The pupa can swim actively by flipping its abdomen, and it is commonly called a "tumbler" because of its swimming action. As with the larva, the pupa of most species must come to the surface frequently to breathe, which they do through a pair of respiratory trumpets on their cephalothoraxes. They do not feed during this stage; typically they pass their time hanging from the surface of the water by their respiratory trumpets. If alarmed, say by a passing shadow, they nimbly swim downwards by flipping their abdomens in much the same way as the larvae do. If undisturbed, they soon float up again. After a few days or longer, depending on the temperature and other circumstances, the dorsal surface of its cephalothorax splits, and the adult mosquito emerges. The pupa is less active than the larva because it does not feed, whereas the larva feeds constantly. Adult The period of development from egg to adult varies among species and is strongly influenced by ambient temperature. Some species of mosquitoes can develop from egg to adult in as few as five days, but a more typical period of development in tropical conditions would be some 40 days or more for most species. The variation of the body size in adult mosquitoes depends on the density of the larval population and food supply within the breeding water. Adult mosquitoes usually mate within a few days after emerging from the pupal stage. In most species, the males form large swarms, usually around dusk, and the females fly into the swarms to mate. Males typically live for about 5–7 days, feeding on nectar and other sources of sugar. After obtaining a full blood meal, the female will rest for a few days while the blood is digested and eggs are developed. This process depends on the temperature, but usually takes two to three days in tropical conditions. Once the eggs are fully developed, the female lays them and resumes host-seeking. The cycle repeats itself until the female dies. While females can live longer than a month in captivity, most do not live longer than one to two weeks in nature. Their lifespans depend on temperature, humidity, and their ability to successfully obtain a blood meal while avoiding host defenses and predators. The length of the adult is typically between 3 mm and 6 mm. The smallest known mosquitoes are around 2 mm (0.1 in), and the largest around 19 mm (0.7 in). Mosquitoes typically weigh around 5 mg. All mosquitoes have slender bodies with three segments: a head, a thorax and an abdomen. The head is specialized for receiving sensory information and for feeding. It has eyes and a pair of long, many-segmented antennae. The antennae are important for detecting host odors, as well as odors of breeding sites where females lay eggs. In all mosquito species, the antennae of the males in comparison to the females are noticeably bushier and contain auditory receptors to detect the characteristic whine of the females. The compound eyes are distinctly separated from one another. Their larvae only possess a pit-eye ocellus. The compound eyes of adults develop in a separate region of the head. New ommatidia are added in semicircular rows at the rear of the eye. During the first phase of growth, this leads to individual ommatidia being square, but later in development they become hexagonal. The hexagonal pattern will only become visible when the carapace of the stage with square eyes is molted.The head also has an elongated, forward-projecting, stinger-like proboscis used for feeding, and two sensory palps. The maxillary palps of the males are longer than their proboscises, whereas the females’ maxillary palps are much shorter. In typical bloodsucking species, the female has an elongated proboscis. The thorax is specialized for locomotion. Three pairs of legs and a pair of wings are attached to the thorax. The insect wing is an outgrowth of the exoskeleton. The Anopheles mosquito can fly for up to four hours continuously at 1 to 2 km/h (0.6–1 mph), traveling up to 12 km (7.5 mi) in a night. Males beat their wings between 450 and 600 times per second.The abdomen is specialized for food digestion and egg development; the abdomen of a mosquito can hold three times its own weight in blood. This segment expands considerably when a female takes a blood meal. The blood is digested over time, serving as a source of protein for the production of eggs, which gradually fill the abdomen. Feeding by adults Typically, both male and female mosquitoes feed on nectar, aphid honeydew, and plant juices, but in many species the mouthparts of the females are adapted for piercing the skin of animal hosts and sucking their blood as ectoparasites. In many species, the female needs to obtain nutrients from a blood meal before it can produce eggs, whereas in many other species, obtaining nutrients from a blood meal enables the mosquito to lay more eggs. A mosquito has a variety of ways of finding nectar or its prey, including chemical, visual, and heat sensors. Both plant materials and blood are useful sources of energy in the form of sugars, and blood also supplies more concentrated nutrients, such as lipids, but the most important function of blood meals is to obtain proteins as materials for egg production.When a female reproduces without such parasitic meals, it is said to practice autogenous reproduction, as in Toxorhynchites; otherwise, the reproduction may be termed anautogenous, as occurs in mosquito species that serve as disease vectors, particularly Anopheles and some of the most important disease vectors in the genus Aedes. In contrast, some mosquitoes, for example, many Culex, are partially anautogenous: they do not need a blood meal for their first cycle of egg production, which they produce autogenously; subsequent clutches of eggs are produced anautogenously, at which point their disease vectoring activity becomes operative.Among humans, the feeding preferences of mosquitoes typically include: those with type O blood, heavy breathers, an abundance of skin bacteria, high body heat, and pregnant women. Individuals attractiveness to mosquitoes also has a heritable, genetically-controlled component.Female mosquitoes hunt their blood host by detecting organic substances such as carbon dioxide (CO2) and 1-octen-3-ol (mushroom alcohol, found in exhaled breath) produced from the host, and through visual recognition. Mosquitoes prefer some people over others. The preferred victims sweat smells more attractive than others because of the proportions of the carbon dioxide, octenol, and other compounds that make up body odor. The most powerful semiochemical that triggers the keen sense of smell of Culex quinquefasciatus is nonanal. Another compound identified in human blood that attracts mosquitoes is sulcatone or 6-methyl-5-hepten-2-one, especially for Aedes aegypti mosquitoes with the odor receptor gene Or4. A large part of the mosquitos sense of smell, or olfactory system, is devoted to sniffing out blood sources. Of 72 types of odor receptors on its antennae, at least 27 are tuned to detect chemicals found in perspiration. In Aedes, the search for a host takes place in two phases. First, the mosquito exhibits a nonspecific searching behavior until the perception of a hosts stimulants, then it follows a targeted approach.Most mosquito species are crepuscular (dawn or dusk) feeders. During the heat of the day, most mosquitoes rest in a cool place and wait for the evenings, although they may still bite if disturbed. Some species, such as the Asian tiger mosquito, are known to fly and feed during daytime.Prior to and during blood feeding, blood-sucking mosquitoes inject saliva into the bodies of their source(s) of blood. This saliva serves as an anticoagulant; without it the female mosquitos proboscis might become clogged with blood clots. The saliva also is the main route by which mosquito physiology offers passenger pathogens access to the hosts bloodstream. The salivary glands are a major target to most pathogens, whence they find their way into the host via the saliva. A mosquito bite often leaves an itchy weal, a raised bump, on the victims skin, which is caused by histamines trying to fight off the protein left by the attacking insect.Mosquitoes of the genus Toxorhynchites never drink blood. This genus includes the largest extant mosquitoes, the larvae of which prey on the larvae of other mosquitoes. These mosquito eaters have been used in the past as mosquito control agents, with varying success. Host animals Many, if not all, blood-sucking species of mosquitoes are fairly selective feeders that specialise in particular host species, though they often relax their selectivity when they experience severe competition for food, defensive activity on the part of the hosts, or starvation. Some species feed selectively on monkeys, while others prefer particular kinds of birds, but they become less selective as conditions become more difficult. For example, Culiseta melanura sucks the blood of passerine birds for preference, and such birds are typically the main reservoir of the Eastern equine encephalitis virus in North America. Early in the season while mosquito numbers are low, they concentrate on passerine hosts, but as mosquito numbers rise and the birds are forced to defend themselves more vigorously, the mosquitoes become less selective of hosts. Soon the mosquitoes begin attacking mammals more readily, thereby becoming the major vector of the virus, and causing epidemics of the disease, most conspicuously in humans and horses. Multiple mosquitoes withdrawal of blood from a host can add up to a large volume. In rare cases, heavy mosquito densities have directly killed livestock as large as cattle and horses.Even more dramatically, in most of its range in North America, the main vector for the Western equine encephalitis virus is Culex tarsalis, because it is known to feed variously on mammals, birds, reptiles, and amphibians. Even fish may be attacked by some mosquito species if they expose themselves above water level, as mudskippers do.In 1969 it was reported that some species of anautogenous mosquitoes would feed on the haemolymph of caterpillars although its nutritional value is questionable. Other observations include mosquitoes feeding on cicadas and mantids. In 2014, it was shown that malaria-transmitting mosquitoes actively seek out some species of caterpillars and feed on their haemolymph, and do so to the caterpillars apparent physical detriment. Mouthparts Mosquito mouthparts are very specialized, particularly those of the females, which in most species are adapted to piercing skin and then sucking blood. Apart from bloodsucking, the females generally also drink assorted fluids rich in dissolved sugar, such as nectar and honeydew, to obtain the energy they need. For this, their blood-sucking mouthparts are perfectly adequate. In contrast, male mosquitoes are not bloodsuckers; they only drink sugary fluids. Accordingly, their mouthparts do not require the same degree of specialization as those of females.Externally, the most obvious feeding structure of the mosquito is the proboscis. More specifically, the visible part of the proboscis is the labium, which forms the sheath enclosing the rest of the mouthparts. When the mosquito first lands on a potential host, its mouthparts are enclosed entirely in this sheath, and it will touch the tip of the labium to the skin in various places. Sometimes, it will begin to bite almost straight away, while other times, it will prod around, apparently looking for a suitable place. Occasionally, it will wander for a considerable time, and eventually fly away without biting. Presumably, this probing is a search for a place with easily accessible blood vessels, but the exact mechanism is not known. It is known that there are two taste receptors at the tip of the labium which may well play a role.The female mosquito does not insert its labium into the skin; it bends back into a bow when the mosquito begins to bite. The tip of the labium remains in contact with the skin of the host, acting as a guide for the other mouthparts. In total, there are six mouthparts besides the labium: two mandibles, two maxillae, the hypopharynx, and the labrum. The mandibles and the maxillae are used for piercing the skin. The mandibles are pointed, while the maxillae end in flat, toothed "blades". To force these into the skin, the mosquito moves its head backwards and forwards. On one movement, the maxillae are moved as far forward as possible. On the opposite movement, the mandibles are pushed deeper into the skin by levering against the maxillae. The maxillae do not slip back because the toothed blades grip the skin. The hypopharynx and the labrum are both hollow. Saliva with anticoagulant is pumped down the hypopharynx to prevent clotting, and blood is drawn up the labrum. To understand the mosquito mouthparts, it is helpful to draw a comparison with an insect that chews food, such as a dragonfly. A dragonfly has two mandibles, which are used for chewing, and two maxillae, which are used to hold the food in place as it is chewed. The labium forms the floor of the dragonflys mouth, the labrum forms the top, while the hypopharynx is inside the mouth and is used in swallowing. Conceptually, then, the mosquitos proboscis is an adaptation of the mouthparts that occur in other insects. The labium still lies beneath the other mouthparts, but also enfolds them, and it has been extended into a proboscis. The maxillae still "grip" the "food" while the mandibles "bite" it. The top of the mouth, the labrum, has developed into a channeled blade the length of the proboscis, with a cross-section like an inverted "U". Finally, the hypopharynx has extended into a tube that can deliver saliva at the end of the proboscis. Its upper surface is somewhat flattened so, when the lower part of the hypopharynx is pressed against it, the labrum forms a closed tube for conveying blood from the host. Saliva For the mosquito to obtain a blood meal, it must circumvent the vertebrates physiological responses. The mosquito, as with all blood-feeding arthropods, has mechanisms to effectively block the hemostasis system with their saliva, which contains a mixture of secreted proteins. Saglin is a protein produced by the salivary glands of mosquitoes. Mosquito saliva acts to reduce vascular constriction, blood clotting, platelet aggregation, angiogenesis and immunity, and creates inflammation. Universally, hematophagous arthropod saliva contains at least one anti-clotting, one anti-platelet, and one vasodilatory substance. Mosquito saliva also contains enzymes that aid in sugar feeding, and antimicrobial agents to control bacterial growth in the sugar meal. The composition of mosquito saliva is relatively simple, as it usually contains fewer than 20 dominant proteins. As of the early 2000s, scientists still were unable to ascribe functions to more than half of the molecules found in arthropod saliva. One promising application of components of mosquito saliva is the development of anti-clotting drugs, such as clotting inhibitors and capillary dilators, that could be useful for managing cardiovascular disease. It is now well recognized that feeding ticks, sandflies, and, more recently, mosquitoes, have an ability to modulate the immune response of the animals (hosts) on which they feed. The presence of this activity in vector saliva is a reflection of the inherent overlapping and interconnected nature of the host hemostatic and inflammatory/immunological responses and the intrinsic need to prevent these host defenses from disrupting successful feeding. The mechanism for mosquito saliva-induced alteration of the host immune response is unclear, but the data have become increasingly convincing that such an effect occurs. Early work described a factor in saliva that directly suppresses TNF-α release, but not antigen-induced histamine secretion, from activated mast cells. Experiments by Cross et al. (1994) demonstrated that the inclusion of Ae. aegypti mosquito saliva into naïve cultures led to a suppression of interleukin (IL)-2 and IFN-γ production, while the cytokines IL-4 and IL-5 are unaffected. Cellular proliferation in response to IL-2 is clearly reduced by prior treatment of cells with mosquito salivary gland extract. Correspondingly, activated splenocytes isolated from mice fed upon by either Ae. aegypti or Cx. pipiens mosquitoes produce markedly higher levels of IL-4 and IL-10 concurrent with suppressed IFN-γ production. Unexpectedly, this shift in cytokine expression is observed in splenocytes up to 10 days after mosquito exposure, suggesting natural feeding of mosquitoes can have a profound, enduring, and systemic effect on the immune response.T cell populations are decidedly susceptible to the suppressive effect of mosquito saliva, showing increased mortality and decreased division rates. Parallel work by Wasserman et al. (2004) demonstrated that T and B cell proliferation was inhibited in a dose dependent manner with concentrations as low as 1/7 of the saliva in a single mosquito. Depinay et al. (2005) observed a suppression of antibody-specific T cell responses mediated by mosquito saliva and dependent on mast cells and IL-10 expression.A 2006 study suggests mosquito saliva can also decrease expression of interferon−α/β during early mosquito-borne virus infection. The contribution of type I interferons (IFN) in recovery from infection with viruses has been demonstrated in vivo by the therapeutic and prophylactic effects of administration of IFN inducers or IFN itself, and different research suggests mosquito saliva exacerbates West Nile virus infection, as well as other mosquito-transmitted viruses.Studies in humanized mice bearing a reconstituted human immune system have suggested potential impact of mosquito saliva in humans. Work published in 2018 from the Baylor College of Medicine using such humanized mice came to several conclusions, among them being that mosquito saliva led to an increase in natural killer T cells in peripheral blood; to an overall decrease in ex vivo cytokine production by peripheral blood mononuclear cells (PBMCs); changes to proportions of subsets of PBMCs; changes in the prevalence of T cell subtypes across organs; and changes to circulating levels of cytokines. Egg development and blood digestion Most species of mosquito require a blood meal to begin the process of egg development. Females with poor larval nutrition may need to ingest sugar or a preliminary blood meal before their ovarian follicles can reach their resting stage. Once the follicles have reached the resting stage, digestion of a sufficiently large blood meal triggers a hormonal cascade that leads to egg development. Upon completion of feeding, the mosquito withdraws her proboscis, and as the gut fills up, the stomach lining secretes a peritrophic membrane that surrounds the blood. This membrane keeps the blood separate from anything else in the stomach. Like many Hemiptera and other insects that survive on dilute liquid diets, many adult mosquitoes must excrete unwanted aqueous fractions even as they feed. (See the photograph of a feeding Anopheles stephensi: Note that the excreted droplet patently is not whole blood, being far more dilute). As long as they are not disturbed, this permits mosquitoes to continue feeding until they have accumulated a full meal of nutrient solids. As a result, a mosquito replete with blood can continue to absorb sugar, even as the blood meal is slowly digested over a period of several days. Once blood is in the stomach, the midgut of the female synthesizes proteolytic enzymes that hydrolyze the blood proteins into free amino acids. These are used as building blocks for the synthesis of vitellogenin, which are the precursors for egg yolk protein.In the mosquito Anopheles stephensi, trypsin activity is restricted entirely to the posterior midgut lumen. No trypsin activity occurs before the blood meal, but activity increases continuously up to 30 hours after feeding, and subsequently returns to baseline levels by 60 hours. Aminopeptidase is active in the anterior and posterior midgut regions before and after feeding. In the whole midgut, activity rises from a baseline of approximately three enzyme units (EU) per midgut to a maximum of 12 EU at 30 hours after the blood meal, subsequently falling to baseline levels by 60 hours. A similar cycle of activity occurs in the posterior midgut and posterior midgut lumen, whereas aminopeptidase in the posterior midgut epithelium decreases in activity during digestion. Aminopeptidase in the anterior midgut is maintained at a constant, low level, showing no significant variation with time after feeding. Alpha-glucosidase is active in anterior and posterior midguts before and at all times after feeding. In whole midgut homogenates, alpha-glucosidase activity increases slowly up to 18 hours after the blood meal, then rises rapidly to a maximum at 30 hours after the blood meal, whereas the subsequent decline in activity is less predictable. All posterior midgut activity is restricted to the posterior midgut lumen. Depending on the time after feeding, greater than 25% of the total midgut activity of alpha-glucosidase is located in the anterior midgut. After blood meal ingestion, proteases are active only in the posterior midgut. Trypsin is the major primary hydrolytic protease and is secreted into the posterior midgut lumen without activation in the posterior midgut epithelium. Aminopeptidase activity is also luminal in the posterior midgut, but cellular aminopeptidases are required for peptide processing in both anterior and posterior midguts. Alpha-glucosidase activity is elevated in the posterior midgut after feeding in response to the blood meal, whereas activity in the anterior midgut is consistent with a nectar-processing role for this midgut region. Ecology Distribution Mosquitoes are cosmopolitan (world-wide): they are in every land region except Antarctica and a few islands with polar or subpolar climates. Iceland is such an island, being essentially free of mosquitoes.The absence of mosquitoes in Iceland and similar regions is probably because of quirks of their climate, which differs in some respects from mainland regions. At the start of the uninterrupted continental winter of Greenland and the northern regions of Eurasia and America, the pupa enters diapause under the ice that covers sufficiently deep water. The imago emerges only after the ice breaks in late spring. In Iceland, the weather is less predictable. In mid-winter it frequently warms up suddenly, causing the ice to break, but then to freeze again after a few days. By that time the mosquitoes will have emerged from their pupae, but the new freeze sets in before they can complete their life cycle. Any anautogenous adult mosquito would need a host to supply a blood meal before it could lay viable eggs; it would need time to mate, mature the eggs and oviposit in suitable wetlands. These requirements would not be realistic in Iceland and in fact the absence of mosquitoes from such subpolar islands is in line with the islands low insect biodiversity; Iceland has fewer than 1,500 described species of insects, many of them probably accidentally introduced by human agency. In Iceland most ectoparasitic insects live in sheltered conditions or actually on mammals; examples include lice, fleas and bedbugs, in whose living conditions freezing is no concern, and most of which were introduced inadvertently by humans.Some other aquatic Diptera, such as Simuliidae, do survive in Iceland, but their habits and adaptations differ from those of mosquitoes; Simuliidae for example, though they, like mosquitoes, are bloodsuckers, generally inhabit stones under running water that does not readily freeze and which is totally unsuited to mosquitoes; mosquitoes are generally not adapted to running water.Eggs of species of mosquitoes from the temperate zones are more tolerant of cold than the eggs of species indigenous to warmer regions. Many even tolerate subzero temperatures. In addition, adults of some species can survive the winter by taking shelter in suitable microhabitats such as buildings or hollow trees. Pollination Several flowers are pollinated by mosquitoes, including some members of the Asteraceae, Roseaceae and Orchidaceae. Activity In warm and humid tropical regions, some mosquito species are active for the entire year, but in temperate and cold regions they hibernate or enter diapause. Arctic or subarctic mosquitoes, like some other arctic midges in families such as Simuliidae and Ceratopogonidae may be active for only a few weeks annually as melt-water pools form on the permafrost. During that time, though, they emerge in huge numbers in some regions and may take up to 300 ml of blood per day from each animal in a caribou herd. Means of dispersal Worldwide introduction of various mosquito species over large distances into regions where they are not indigenous has occurred through human agencies, primarily on sea routes, in which the eggs, larvae, and pupae inhabiting water-filled used tires and cut flowers are transported. They have also been carried by personal vehicles, delivery trucks, trains, and aircraft. Man-made areas such as storm water retention basins, or storm drains also provide sprawling sanctuaries. Sufficient quarantine measures have proven difficult to implement. In addition, outdoor pool areas make a perfect place for them to grow. Climate and global distribution Seasonality In order for a mosquito to transmit a disease to the host there must be favorable conditions, referred to as transmission seasonality. Seasonal factors that impact the prevalence of mosquitoes and mosquito-borne diseases are primarily humidity, temperature, and precipitation. A positive correlation between malaria outbreaks and these climatic variables has been demonstrated in China; and El Niño has been shown to impact the location and number of outbreaks of mosquito-borne diseases observed in East Africa, Latin America, Southeast Asia and India. Climate change impacts each of these seasonal factors and in turn impacts the dispersal of mosquitoes. Past and future patterns Climatology and the study of mosquito-borne disease have been developed only over the past 100 years. Historical records of weather patterns and distinct symptoms associated with mosquito-borne diseases can be utilized to trace the prevalence of these diseases in relation to the climate over longer time periods. Further, statistical models are being created to predict the impact of climate change on vector-borne diseases using these past records, and these models can be utilized in the field of public health in order to create interventions to reduce the impact of these predicted outcomes. Two types of models are used to predict mosquito-borne disease spread in relation to climate: correlative models and mechanistic models. Correlative models focus primarily on vector distribution, and generally function in 3 steps. First, data is collected regarding geographical location of a target mosquito species. Next, a multivariate regression model establishes the conditions under which the target species can survive. Finally, the model determines the likelihood of the mosquito species to become established in a new location based on similar living conditions. The model can further predict future distributions based on environmental emissions data. Mechanistic models tend to be broader and include the pathogens and hosts in the analysis. These models have been used to recreate past outbreaks as well as predict the potential risk of a vector-borne disease based on an areas forecasted climate.Mosquito-borne diseases are currently most prevalent in East Africa, Latin America, Southeast Asia, and India. An emergence in Europe was recently observed. A weighted risk analysis demonstrated associations to climate for 49% of infectious diseases in Europe including all transmission routes. One statistical model predicts by 2030, the climate of southern Great Britain will be climatically suitable for malaria transmission Plasmodium vivax for 2 months of the year. By 2080 it is predicted that the same will be true for southern Scotland. Vectors of disease Mosquitoes can act as vectors for many disease-causing viruses and parasites. Infected mosquitoes carry these organisms from person to person without exhibiting symptoms themselves. Mosquito-borne diseases include: Viral diseases, such as yellow fever, dengue fever, and chikungunya, transmitted mostly by Aedes aegypti. Dengue fever is the most common cause of fever in travelers returning from the Caribbean, Central America, South America, and South Central Asia. This disease is spread through the bites of infected mosquitoes and cannot be spread person to person. Severe dengue can be fatal, but with good treatment, fewer than 1% of patients die from dengue. Work published in 2012 from Baylor College of Medicine suggested that for some diseases, such as dengue fever, which can be transmitted via mosquitoes and by other means, the severity of the mosquito-transmitted disease could be greater. The parasitic diseases collectively called malaria, caused by various species of Plasmodium, carried by female mosquitoes of the genus Anopheles. Lymphatic filariasis (the main cause of elephantiasis) which can be spread by a wide variety of mosquito species. West Nile virus is a significant concern in the United States but there are no reliable statistics on worldwide cases. Dengue viruses are a significant health risk globally. Severe cases of dengue often require hospitalization and can be life-threatening shortly after infection. Symptoms include a high fever, aches and pains, vomiting, and rashes. Warning signs of severe dengue infection include vomiting blood, bleeding from the gums or nose, and stomach tenderness/pain. Equine encephalitis viruses, such as Eastern equine encephalitis virus, Western equine encephalitis virus, and Venezuelan equine encephalitis virus, can be spread by mosquito vectors such as Aedes taeniorhynchus. Tularemia, a bacterial disease caused by Francisella tularensis, is variously transmitted, including by biting flies. Culex and Culiseta are vectors of tularemia, as well as arbovirus infections such as West Nile virus. Zika, recently notorious, though rarely deadly, causes fever, joint pain, rashes and conjunctivitis. The most serious consequence appears when the infected person is a pregnant woman, since during pregnancy this virus can originate a birth defect called microcephaly. St. Louis Encephalitis, a mosquito-borne disease that is characterized by fever and headaches upon initial onset of infection, arises from mosquitoes who feed on birds who are infected with the illness, and can result in death. The most common vector of this disease is Culex pipiens, also known as the common house mosquito. Heartworm disease, a parasitic roundworm infection that affects dogs and other canids. Mosquitoes transmit larvae to the definitive host through bites. Adult heart worms infest the right heart and pulmonary artery, where they can cause serious complications including congestive heart failure.Potential transmission of HIV was originally a public health concern, but practical considerations and detailed studies of epidemiological patterns suggest that any transmission of the HIV virus by mosquitoes is at worst extremely unlikely.Various species of mosquitoes are estimated to transmit various types of disease to more than 700 million people annually in Africa, South America, Central America, Mexico, Russia, and much of Asia, with millions of resultant deaths. At least two million people annually die of these diseases, and the morbidity rates are many times higher still. Methods used to prevent the spread of disease, or to protect individuals in areas where disease is endemic, include: Vector control aimed at mosquito control or eradication Disease prevention, using prophylactic drugs and developing vaccines Prevention of mosquito bites, with insecticides, nets, and repellentsSince most such diseases are carried by "elderly" female mosquitoes, some scientists have suggested focusing on these to avoid the evolution of resistance. Control Many measures have been tried for mosquito control, including the elimination of breeding places, exclusion via window screens and mosquito nets, biological control with parasites such as fungi and nematodes, or predators such as fish, copepods, dragonfly nymphs and adults, and some species of lizard and gecko. Another approach is to introduce large numbers of sterile males. Genetic modification methods including cytoplasmic incompatibility, chromosomal translocations, sex distortion and gene replacement, solutions seen as inexpensive and not subject to vector resistance, have been explored.According to an article in Nature discussing the idea of totally eradicating mosquitoes, "Ultimately, there seem to be few things that mosquitoes do that other organisms can’t do just as well—except perhaps for one. They are lethally efficient at sucking blood from one individual and mainlining it into another, providing an ideal route for the spread of pathogenic microbes." The control of disease-carrying mosquitoes may in the future be possible using gene drives. Repellents Insect repellents are applied on skin and give short-term protection against mosquito bites. The chemical DEET repels some mosquitoes and other insects. Some CDC-recommended repellents are picaridin, eucalyptus oil (PMD), and ethyl butylacetylaminopropionate (IR3535). Pyrethrum (from Chrysanthemum species, particularly C. cinerariifolium and C. coccineum) has been reviewed favorably in research published in 2021. Others are indalone, dimethyl phthalate, dimethyl carbate, and ethyl hexanediol. Electronic insect repellent devices that produce ultrasounds intended to keep away insects (and mosquitoes) are marketed. No EPA or university study has shown that these devices prevent a human from being bitten by a mosquito. Bites Mosquito bites lead to a variety of mild, occasionally serious, and, rarely, life-threatening allergic reactions. These include ordinary wheal and flare reactions and mosquito bite allergies (MBA). The MBA, also termed hypersensitivity to mosquito bites (HMB), are excessive reactions to mosquito bites that are not caused by any toxin or pathogen in the saliva injected by a mosquito at the time it takes its blood-meal. Rather, they are allergic hypersensitivity reactions caused by the non-toxic allergenic proteins contained in the mosquitos saliva. Studies have shown or suggest that numerous species of mosquitoes can trigger ordinary reactions as well as MBA. These include Aedes aegypti, Aedes vexans, Aedes albopictus, Anopheles sinensis, Culex pipiens, Aedes communis, Anopheles stephensi, Culex quinquefasciatus, Ochlerotatus triseriatus, and Culex tritaeniorhynchus. Furthermore, there is considerable cross-reactivity between the salivary proteins of mosquitoes in the same family and, to a lesser extent, different families. It is therefore assumed that these allergic responses may be caused by virtually any mosquito species (or other biting insect). The mosquito bite allergies are informally classified as 1) the Skeeter syndrome, i.e. severe local skin reactions sometimes associated with low-grade fever; 2) systemic reactions that range from high-grade fever, lymphadenopathy, abdominal pain, and/or diarrhea to, very rarely, life-threatening symptoms of anaphylaxis; and 3) severe and often systemic reactions occurring in individuals that have an Epstein-Barr virus-associated lymphoproliferative disease, Epstein-Barr virus-negative lymphoid malignancy, or another predisposing condition such as Eosinophilic cellulitis or chronic lymphocytic leukemia. Mechanism Visible, irritating bites are due to an immune response from the binding of IgG and IgE antibodies to antigens in the mosquitos saliva. Some of the sensitizing antigens are common to all mosquito species, whereas others are specific to certain species. There are both immediate hypersensitivity reactions (types I and III) and delayed hypersensitivity reactions (type IV) to mosquito bites. Both reactions result in itching, redness and swelling. Immediate reactions develop within a few minutes of the bite and last for a few hours. Delayed reactions take around a day to develop, and last for up to a week. Treatment Several anti-itch medications are commercially available, including those taken orally, such as diphenhydramine, or topically applied antihistamines and, for more severe cases, corticosteroids, such as hydrocortisone and triamcinolone. Aqueous ammonia (3.6%) has also been shown to provide relief.Both topical heat and cool may be useful to treat mosquito bites. In human culture Greek mythology Ancient Greek beast fables including "The Elephant and the Mosquito" and "The Bull and the Mosquito", with the general moral that the large beast does not even notice the small one, derive ultimately from Mesopotamia. Origin myths The peoples of Siberia have origin myths surrounding the mosquito. One Ostiak myth tells of a man-eating giant, Punegusse, who is killed by a hero but will not stay dead. The hero eventually burns the giant, but the ashes of the fire become mosquitoes that continue to plague mankind. Other myths from the Yakuts, Goldes (Nanai people), and Samoyed have the insect arising from the ashes or fragments of some giant creature or demon. Similar tales found in Native North American myth, with the mosquito arising from the ashes of a man-eater, suggest a common origin. The Tatars of the Altai had a similar myth, thought to be of Native North American origin, involving the fragments of the dead giant, Andalma-Muus, becoming mosquitoes and other insects. Modern era Winsor McCays 1912 film How a Mosquito Operates was one of the earliest works of animation, which has been described as far ahead of its time in technical quality. It depicts a giant mosquito tormenting a sleeping man.The de Havilland Mosquito was a high-speed aircraft manufactured between 1940 and 1950, and used in many roles. References Further reading External links Mosquito at Curlie Mosquito Information Website Mosquitoes chapter in United States Environmental Protection Agency National Public Health Pesticide Applicator Training Manual A film clip describing The Life Cycle of the Mosquito is available at the Internet Archive "Mosquitoes: The Worst". Stuff You Should Know (Podcast). Retrieved 2015-06-30. Parasitic Insects, Mites and Ticks: Genera of Medical and Veterinary Importance Wikibooks

Chromoblastomycosis

Chromoblastomycosis is a long-term fungal infection of the skin and subcutaneous tissue (a chronic subcutaneous mycosis).It can be caused by many different types of fungi which become implanted under the skin, often by thorns or splinters. Chromoblastomycosis spreads very slowly.It is rarely fatal and usually has a good prognosis, but it can be very difficult to cure. The several treatment options include medication and surgery.The infection occurs most commonly in tropical or subtropical climates, often in rural areas. Symptoms and signs The initial trauma causing the infection is often forgotten or not noticed. The infection builds at the site over a period of years, and a small red papule (skin elevation) appears. The lesion is usually not painful, with few, if any symptoms. Patients rarely seek medical care at this point.Several complications may occur. Usually, the infection slowly spreads to the surrounding tissue while still remaining localized to the area around the original wound. However, sometimes the fungi may spread through the blood vessels or lymph vessels, producing metastatic lesions at distant sites. Another possibility is secondary infection with bacteria. This may lead to lymph stasis (obstruction of the lymph vessels) and elephantiasis. The nodules may become ulcerated, or multiple nodules may grow and coalesce, affecting a large area of a limb. Cause Chromoblastomycosis is believed to originate in minor trauma to the skin, usually from vegetative material such as thorns or splinters; this trauma implants fungi in the subcutaneous tissue. In many cases, the patient will not notice or remember the initial trauma, as symptoms often do not appear for years. The fungi most commonly observed to cause chromoblastomycosis are: Fonsecaea pedrosoi Cladophialophora bantiana causes both cutaneous chromoblastomycosis and systemic phaeohyphomycosis Phialophora verrucosa Cladophialophora carrionii Fonsecaea compacta Mechanism Over months to years, an erythematous papule appears at the site of inoculation. Although the mycosis slowly spreads, it usually remains localized to the skin and subcutaneous tissue. Hematogenous and/or lymphatic spread may occur. Multiple nodules may appear on the same limb, sometimes coalescing into a large plaque. Secondary bacterial infection may occur, sometimes inducing lymphatic obstruction. The central portion of the lesion may heal, producing a scar, or it may ulcerate. Diagnosis The most informative test is to scrape the lesion and add potassium hydroxide (KOH), then examine under a microscope. (KOH scrapings are commonly used to examine fungal infections.) The pathognomonic finding is observing medlar bodies (also called muriform bodies or sclerotic cells). Scrapings from the lesion can also be cultured to identify the organism involved. Blood tests and imaging studies are not commonly used.On histology, chromoblastomycosis manifests as pigmented yeasts resembling "copper pennies". Special stains, such as periodic acid schiff and Gömöri methenamine silver, can be used to demonstrate the fungal organisms if needed. Prevention No preventive measure is known aside from avoiding the traumatic inoculation of fungi. At least one study found a correlation between walking barefoot in endemic areas and occurrence of chromoblastomycosis on the foot. Treatment Chromoblastomycosis is very difficult to cure. The primary treatments of choice are: Itraconazole, an antifungal azole, is given orally, with or without flucytosine. Alternatively, cryosurgery with liquid nitrogen has also been shown to be effective.Other treatment options are the antifungal drug terbinafine, another antifungal azole posaconazole, and heat therapy. Antibiotics may be used to treat bacterial superinfections.Amphotericin B has also been used.Photodynamic therapy is a newer type of therapy used to treat Chromblastomycosis. Prognosis The prognosis for chromoblastomycosis is very good for small lesions. Severe cases are difficult to cure, although the prognosis is still quite good. The primary complications are ulceration, lymphedema, and secondary bacterial infection. A few cases of malignant transformation to squamous cell carcinoma have been reported. Chromoblastomycosis is very rarely fatal. Epidemiology Chromoblastomycosis occurs around the world, most commonly in rural areas in tropical or subtropical climates.It is most common in rural areas between approximately 30°N and 30°S latitude. Over two-thirds of patients are male, and usually between the ages of 30 and 50. A correlation with HLA-A29 suggests genetic factors may play a role, as well. Social and cultural Chromoblastomycosis is considered a neglected tropical disease, affects mainly people living in poverty, and causes considerable morbidity, stigma and discrimination. See also List of cutaneous conditions References == External links ==

Gastric atresia

Gastric atresia is a congenital defect with complete occlusion of the pyloric outlet of the stomach. Cause Gastric atresia is a birth defect. It can be genetic, inherited in an autosomal recessive manner, and associated with conditions like Down syndrome and junctional epidermolysis bullosa (medicine). In about 60% of cases, the outlet of the stomach is covered by a membrane. In around 35% of cases, solid tissue blocks the outlet. In the remaining cases (less than 10%), there is a complete separation of the stomach and the small intestine. Diagnosis Polyhydramnios is often seen during pregnancy, and prenatal diagnosis is common. Infants with gastric atresia will exhibit forceful vomiting upon the first feeding. Imaging is required for diagnosis. Treatment Treatment is surgical and involves removing or bypassing the obstruction. Epidemiology It is seen in approximately 1 in 100,000 live births. == References ==

Antenatal depression

Antenatal depression, also known as prenatal or perinatal depression, is a form of clinical depression that can affect a woman during pregnancy, and can be a precursor to postpartum depression if not properly treated. It is estimated that 7% to 20% of pregnant women are affected by this condition. Any form of prenatal stress felt by the mother can have negative effects on various aspects of fetal development, which can cause harm to the mother and child. Even after birth, a child born from a depressed or stressed mother feels the affects. The child is less active and can also experience emotional distress. Antenatal depression can be caused by the stress and worry that pregnancy can bring, but at a more severe level. Other triggers include unplanned pregnancy, difficulty becoming pregnant, history of abuse, and economic or family situations.Commonly, symptoms involve how the patient views herself, how she feels about going through such a life changing event, the restrictions on the mothers lifestyle that motherhood will place, or how the partner or family feel about the baby. Pregnancy places significant strain on a womans body, so stress, mood swings, sadness, irritability, pain, and memory changes are to be expected. Left untreated, antenatal depression can be extremely dangerous for the health of the mother and the baby. It is highly recommended that mothers who feel they are experiencing antenatal depression have a discussion about it with their health care provider. Mothers with a history of mental health issues should also talk to their doctor about it early in the pregnancy to help with possible depressive symptoms. Signs and symptoms Antenatal depression is classified based on a womans symptoms. During pregnancy, a lot of changes to mood, memory, eating habits, and sleep are common. When these common traits become severe, and begin to alter ones day-to-day life, that is when it is considered to be antenatal depression. Symptoms of antenatal depression are: Inability to concentrate. Overwhelming anxiety and fear. Difficulty remembering. Feeling emotionally numb. Extreme irritability. Sleeping too much or not enough, or restless sleep. Extreme or unending fatigue. Desire to over eat, or not eat at all. Weight loss/gain unrelated to pregnancy. Loss of interest in sex. A sense of dread about everything, including the pregnancy. Feelings of failure, or guilt. Persistent sadness. Thoughts of suicide, or death.Other symptoms can include the inability to get excited about the pregnancy, and/or baby, a feeling of disconnection with the baby, and an inability to form/feel a bond with the developing baby. This can drastically affect the relationship between the mother and the baby, and can drastically affect the mothers capacity for self-care. Such inadequacies can lead to even greater risk factors for the mother. Antenatal depression can be triggered by various causes, including relationship problems, family or personal history of depression, infertility, previous pregnancy loss, complications in pregnancy, and a history of abuse or trauma. Onset and duration of symptoms Antenatal depression can be caused by many factors. Often it is associated with the fear and stress of the pregnancy. Other factors include unintended pregnancy, hyperemesis gravidarum, financial issues, living arrangements and relationships with the father and family. Typically, depression symptoms associated with pregnancy are categorized as postnatal depression, due to the onset of symptoms occurring after childbirth has occurred. The following is a breakdown of when a group of various women began to feel the onset of symptoms associated with depression: 11.8 percent at 18 weeks 13.5 percent at 32 weeks 9.1 percent 8 weeks after the birth 8.1 percent 8 months after the birthIn a recent article posted by The BabyCenter, the authors stated that "For years, experts mistakenly believed that pregnancy hormones protected against depression, leaving women more vulnerable to the illness only after the baby was born and their hormone levels plunged." This is a possible explanation as to why antenatal depression has just recently been identified. Prevalence and causes The prevalence of antenatal depression differs slightly by region of world. In the United States, antenatal depression is experienced in as many as 16% of pregnant women, while in South Asia it is experienced in as many as 24% of pregnant women. Its becoming more prevalent as more medical studies are being done. Antenatal depression was once thought to simply be the normal stress associated with any pregnancy, and was waved off as a common ailment. It can be caused by many factors, usually though involving aspects of the mothers personal life, such as family, economic standing, relationship status, etc. It can also be caused by hormonal and physical changes that are associated with pregnancy. Additional risk factors include lack of social support, marital dissatisfaction, discriminatory work environments, history of domestic abuse, and unplanned or unwanted pregnancy. Studies have determined that there may be a connection between antenatal and postpartum depression in women with lower vitamin D levels. There is a higher risk of antenatal depression in woman living in low-income countries who deal with less access to quality healthcare, have economic issues, and dont have a good support system. Screening Perinatal mental health screenings are important in detecting and diagnosing antenatal and postpartum depression early. The American College of Obstetricians and Gynecologists is one of the many maternal health organizations that strongly encourage universal screening for expectant and postpartum women for depression as part of routine obstetric care. In fact, many states, including California have already legislated laws that require providers to screen patients during visits because they recognize that early screenings can expedite the process in receiving effective treatment. The Patient Health Questionnaire 9 (PHQ-9) is a screening tool typically used to detect depression. Another tool, the Edinburgh Postnatal Depression Scale, was developed for the postnatal period, but has also been validated for use during pregnancy.PHQ-9 is a reliable depression severity scale that was formulated in accordance with DSM-IV criteria for depression, consisting of 9 items correlating to the 9 criteria listed in DSM-IV. It is a shortened version of the PHQ and has been assessed for comparable sensitivity and specificity. The screening test is self-administered to patients and are usually performed at the primary care clinic.However, it is not enough to just provide mental health screenings to at risk patients. Interventions such as referrals to treatment and mental health monitoring should be implemented in health care systems in order to ensure these women are helped consistently throughout their recovery journey.Studies suggest that obese woman tend to develop mental health issues more frequently and should discuss any symptoms with their doctor at the first prenatal appointment. Treatment Treatment for antenatal depression poses many challenges because the baby is also affected by any treatment given to the mother. There are both non-pharmacological and pharmacological treatment options which can be considered by women with antenatal depression. Non-pharmacological Therapy Psychotherapy Psychotherapy is recommended for any woman with antenatal depression, as it is an effective way for the mother to express her feelings in her own words. Specifically, Cognitive Behavioral Therapy effectively helps decrease symptoms of antenatal depression. In addition to psychotherapy, being seen by a psychiatrist is recommended as they can assess if medications will be beneficial and make specific medication recommendations, if warranted. Familial support may also play a role in helping with the emotional aspects of antenatal depression.While mental health specialists are trained in providing counseling interventions, results from a recent systematic review and meta-analysis of the literature found that nonspecialist providers, such as lay counselors, nurses, midwives, and teachers with no formal training in counseling interventions, often fill a gap in providing effective services related to depression and anxiety treatments. Exercise Therapy Studies suggest that forms of exercise can help with depressive symptoms both before and after birth, but not prevent it entirely.Exercise options that have been studied to help reduce symptoms: Yoga Walking Stretching Aerobic exercise Medications When discussing medication options for antenatal depression, it is important to ask the prescribing healthcare provider to share more details about all the risks and benefits of the available medications. During pregnancy, there are two main kinds of antidepressants used during pregnancy; tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). Once prescribed, anti-depressant medication has been found to be extremely effective in treating antenatal depression. Patients can expect to feel an improvement in mood in roughly 2 to 3 weeks on average, and can begin to feel themselves truly connect with their baby. Reported benefits of medication include returned appetite, increased mood, increased energy, and better concentration. Side effects are minor, though they are reported in some cases. Currently, no abnormalities of the baby have been associated with the use of antidepressants during pregnancy. It may be true that maternal SSRI use during pregnancy can lead to difficulty for their newborn adjusting to conditions outside of the womb immediately following birth. Some studies indicate that infants with exposure to SSRIs in the second and third trimester were more likely to be admitted to intensive care following their birth for respiratory, cardiac, low weight and other reasons, and that infants with prenatal SSRI exposure exhibited less motor control upon delivery than infants who were not exposed to SSRIs. Newborns who were exposed to SSRIs for five months or more prior to birth were at a greater risk for lower Apgar scores 1 and 5 minutes after delivery, indicating they were of lesser health than newborns who were not exposed to SSRIs before birth. However, prenatal SSRI exposure was not found to have a significant impact the long-term mental and physical health of the children. These results are not independent of any effects of prenatal depression on infants. Connection to postpartum depression and parenting stress Studies have found a strong link between antenatal depression and postpartum depression in women. In other words, women who have antenatal depression are very likely to also develop postpartum depression. The cause of this is based on the continuation of the antenatal depression into postpartum. In a logistical light, it makes sense that women who are depressed during their pregnancy will also be depressed following the birth of their child. This being said there are some factors that determine exclusively the presence of postpartum depression that are not necessarily linked with antenatal depression. These examples include variables like socioeconomic class, if a pregnancy was planned or not, and the parents relationship prior to conception and delivery of the child.In reference to a recent study by Coburn et al., the authors found that in addition to prenatal effects, higher maternal depressive symptoms during the postpartum period (12 weeks) were associated with more infant health concerns. This is consistent with other findings among low-SES Mexican-American women and their infants. Women with prenatal depressive symptoms are more likely to develop postpartum depression, which can also have negative consequences on children, such as emotional and behavior problems, attachment difficulties, cognitive deficits, physical growth and development, and feeding habits and attitudes. Related, maternal depression affects parenting behaviors, which in turn could affect child outcomes. Thus, womens mental health throughout the perinatal period should be a priority, not only to support women, but also to promote optimal functioning for their infants. Antenatal Depression and Infant Health Depression during pregnancy is associated with an increased risk of spontaneous abortion. In a review by Frazier et al., acute and chronic stress during pregnancy can diminish proper immunological activity crucial during pregnancy, and can possibly induce spontaneous abortion. There is still a debate on whether the miscarriage is due to the depressive disease state or the anti-depressant medication. A large study conducted in Denmark observed that there was a higher incidence of first trimester miscarriage in depressed women not exposed to SSRI compared to non-depressed women exposed to SSRI, indicating that the miscarriage may be associated with the psychological state of the mother rather than the anti-depressant. Depressive symptoms in pregnant women are linked with poor health outcomes in infants. The rates of hospitalization are found increased for infants who are born to women with high depression levels during pregnancy. Reduced breastfeeding, poor physical growth, lower birth weight, early gestational age and high rates of diarrheal infection are some of the reported outcomes of poor health among infants born to depressed pregnant women. In fact, positive antenatal screenings administered in the first or third trimester are found to be high risk factors for early cessation in breastfeeding. Studies also report that the environmental effects of maternal depression affect the developing fetus to such an extent that the impact can be seen during adulthood of the offspring. The effects are worse for women from low socio-economic backgrounds. In a recent study by Coburn et al., maternal prenatal depressive symptoms predicted significantly higher number of infant health concerns at 12-weeks (3 months) of age. The health concerns included rash, colic, cold, fever, cough, diarrhea, ear infections, and vomiting. Additional concerns for women in low-income backgrounds includes low birth rate and preterm births.An interesting and informative area of research has been done to see the role of confounding variables in relationship of maternal prenatal depression with infant health concerns. Age of mother, romantic partner, education, household income, immigrant status, and number of other children, breastfeeding, gestational age, birth weight are some of the mediating or moderating factors which are found correlated with infant health concerns. The studies of post-partum depressive symptoms are relatively more than those of prenatal depression and the studies should look into the role of various factors during pregnancy that may impact the health of infants, even continuing into adulthood. Male Perspective for Antenatal Depression Fathers can also experience depression during their partners pregnancy, commonly displayed as fatigue or changes in sleep and eating patterns. Men whose partners are women struggling with antenatal or postnatal depression often find themselves receiving less affection and intimacy from their partners. If symptoms of antenatal depression arise, it is recommended for fathers to provide encouragement for their partners to discuss their condition with a healthcare provider. It is also important for the father to also seek support for himself. In a research performed in Sweden observing 366,499 births, newly diagnosed paternal depression around the time of conception or during pregnancy was associated with an increased risk of preterm birth. However, a preexisting paternal depression did not show any correlation, which may be due to the mothers perception of the changes in her partners mood. See also Depression Gender disappointment Mood swings Postpartum depression Pregnancy Postpartum psychosis References Further reading Andrade C (2018). "Prenatal Depression and Infant Health: The Importance of Inadequately Measured, Unmeasured, and Unknown Confounds". Indian Journal of Psychological Medicine. 40 (4): 395–397. doi:10.4103/IJPSYM.IJPSYM_232_18. PMC 6065138. PMID 30093759.

Laryngo-onycho-cutaneous syndrome

Laryngo-onycho-cutaneous syndrome (also known as Shabbir syndrome) is a rare epithelial disorder inherited in an autosomal recessive fashion. It is characterized by abnormalities in the larynx, nails ("onycho-"), and skin ("cutaneous"). The disorder is only found in Punjabi Muslims and only a few cases have been reported.It was characterized by Pakistani dermatologist Syed Ghulam Shabbir (1923–2002) in 1986.It may be associated with LAMA3. See also Watson syndrome List of cutaneous conditions References External links Laryngo-onycho-cutaneous syndrome on MedlinePlus

Oral mucocele

Oral mucocele (also mucous extravasation cyst, mucous cyst of the oral mucosa, and mucous retention and extravasation phenomena.) is a condition caused by two related phenomena - mucus extravasation phenomenon and mucous retention cyst. Mucous extravasation phenomenon is a swelling of connective tissue consisting of a collection of fluid called mucus. This occurs because of a ruptured salivary gland duct usually caused by local trauma (damage) in the case of mucous extravasation phenomenon and an obstructed or ruptured salivary duct in the case of a mucus retention cyst. The mucocele has a bluish, translucent color, and is more commonly found in children and young adults. Although these lesions are often called cysts, mucoceles are not true cysts because they have no epithelial lining. Rather, they are polyps. Signs and symptoms The size of oral mucoceles vary from 1 mm to several centimeters and they usually are slightly transparent with a blue tinge. On palpation, mucoceles may appear fluctuant, but can also be firm. Their duration lasts from days to years, and may have recurrent swelling with occasional rupturing of its contents. Locations The most common location to find a mucocele is the inner surface of the lower lip. It can also be found on the inner side of the cheek (known as the buccal mucosa), on the anterior ventral tongue, and the floor of the mouth. When found on the floor of the mouth, the mucocele is referred to as a ranula. They are rarely found on the upper lip. As their name suggests, they are basically mucus-lined cysts and they can also occur in the paranasal sinuses, most commonly the frontal sinuses, the frontoethmoidal region, and the maxillary sinus. Sphenoid sinus involvement is extremely rare. When the lumen of the vermiform appendix of the intestine gets blocked due to any factor, a mucocele can also form there. Variations A variant of a mucocele is found on the palate, retromolar pad, and posterior buccal mucosa. Known as a "superficial mucocele", this type presents as single or multiple vesicles and bursts into an ulcer. Despite healing after a few days, superficial mucoceles recur often in the same location. Other causes of bumps inside lips are aphthous ulcer, lipoma, benign tumors of salivary glands, submucous abscesses, and haemangiomas. Diagnosis Microscopically, mucoceles appears as granulation tissue surrounding mucin. Since inflammation occurs concurrently, neutrophils and foamy histiocytes usually are present. On a CT scan, a mucocele is fairly homogenous, with an attenuation of about 10-18 Hounsfield units. Classification Both mucous retention and extravasation phenomena are classified as salivary gland disorders. Treatment Some mucoceles spontaneously resolve on their own after a short time. Others are chronic and require surgical removal. Recurrence is possible, thus the adjacent salivary gland may be excised as a preventive measure.Several types of procedures are available for the surgical removal of mucoceles. These include laser and minimally invasive techniques, which means recovery times are reduced drastically.Micromarsupialization is an alternative procedure to surgical removal. It uses silk sutures in the dome of a cyst to allow new epithelialized drainage pathways. It is simpler, less traumatic, and well tolerated by patients, especially children.A nonsurgical option that may be effective for a small or newly identified mucocele is to rinse the mouth thoroughly with salt water (one tablespoon of salt per cup) four to six times a day for a few days. This may draw out the fluid trapped underneath the skin without further damaging the surrounding tissue. If the mucocele persists, individuals should see a doctor to discuss further treatment. Smaller cysts may be removed by laser treatment, but larger cysts may have to be removed surgically. See also Sialocele Seroma References == External links ==

Fibrous hamartoma of infancy

Fibrous hamartoma of infancy (FHI) is a rare, typically painless, benign tumor that develops in the subcutaneous tissues of the axilla (i.e. armpit), arms, external genitalia, or, less commonly, various other areas. It is diagnosed in children who are usually less than 2 years old or, in up to 20% of cases, develops in utero and is diagnosed in an infant at birth.The cells involved in FHI include bland fibroblasts/myofibroblasts, mature fat cells, and primitive-appearing spindle-shaped and/or star-shaped cells. The tumor was first described by R.D. Reye in 1956 who termed the disorder "subdermal fibromatous tumor of infancy" and regarded it as a reactive lesion. In a 1964 study of 30 patients, F.M. Enzinger renamed the tumor hamartoma of infancy; he regarded it to be a hamartoma (i.e. a local malformation of various normal cell types due to a systemic genetic condition) rather than a reactive lesion. However, subsequent studies have found gene mutations in FHI tumor cells and conclude that it is a true neoplasm, i.e. a growth of cells which is uncoordinated with that of the normal surrounding tissue and persists in growing abnormally even if the original trigger is removed. In 2020, the World Health Organization classified FHI in the category of benign fibroblastic and myofibroblastic tumors.Fibrous hamartoma of infancy is generally a benign tumor but may be locally aggressive, locally infiltration, and in uncommon cases produce symptoms such as tenderness. Surgical excision is the treatment of choice for FHI tumors. Presentation The largest study to date examined 197 cases of FHI. In this study, most individuals presented with a slowly growing, symptomless, subcutaneous mass although rarely these masses were rapidly growing, and/or were tender, painful, warm, and/or were accompanied by skin changes, pigmentation, sweat gland enlargement, and/or increased hair overlaying the tumor. Sixty-eight percent of these cases were diagnosed in the first year of life, 23% were diagnoses at birth, and 9% were diagnosed in children 2–5 years old. The male-to female ratio was 2.4. The tumors were most common in the axilla (23% of cases), upper arm (12.5%), lower arm (10.5%), external genitalia area (9.5%), and inguinal region (7.5%); less common or rare sites for these tumors were the buttocks, back of the head, back of the neck, back of the torso, lower arm, leg, foot, chest, and anal area. Most cases presented as solitary masses but 3 cases presenting with 2 tumors and 1 case presenting with 5 tumors. Overall, the size of these tumors varied between 0.5 and 4.0 cm but in rare cases were as large as 20 cm. Two subsequent studies of 145 and 60 individuals agreed with all of these results but also did diagnose FHI in individuals as old as 8 and 14 years, respectively. Pathology On gross pathological examination, FHI tumors are soft, poorly demarcated, fibro-fatty masses located in subcutaneous tissues. These tumor masses tend to blend with the surrounding fat tissues, may be lobulated, and in rare cases, especially when large, extend into nearby muscles, nerves, and/or fibrous/connective tissue structures. Microscopic histopathological analyses of hematoxylin and eosin stained FHI tumor tissues consistently reveal three very different component zones in virtually all cases: 1) haphazardly arranged, intersecting bundles of bland fibroblast-like/myofibroblast-like cells; 2) mature adipose (i.e. fat) tissue; and 3) highly vascular, myxoid (i.e. connective tissue appearing more blue or purple than normal connective) nodules of primitive-appearing spindled-shaped to star-shaped cells. Chronic inflammatory cell (e.g. lymphocytes, macrophages, and plasma cells) aggregates are commonly present in these lesion. The relative proportion of fibroblast/myofibroblast, adipose tissue, and myxoid zones commonly vary from case to case.Earlier Immunohistochemical analyses of FHI tumor tissues in a small number of cases have given varying results. A more recent and larger study reported that 75% of tested cases showed variable expression of smooth muscle actin proteins by the cells located primarily in fibroblast/myofibroblast zones and occasionally by the cells located in myxoid zones; the S100 protein was expressed by the fat cells of the adipose tissue zone in all cases; CD34 protein was expressed by the cells in myxoid and fibroblast/myofibroblast zones in all cases; and cells expressing the desmin protein were not detected in any case. A smaller, more recent study also found that 8 of 13 FHI cases had tumor cells in the fibroblast/myofibrobalast zone that expressed smooth-muscle actin protein, 6 of 8 cases had tumor cells in the myxoid zone that expressed the CD34 protein, and 7 of 7 cases had tumor cells in the adipose tissue zone express the S100 protein. The expression pattern of one or more of these proteins has not yet been found to be of help in distinguishing FHI from other tumor types. Chromosome and gene abnormalities The EGFR gene which codes for the production of the epidermal growth factor receptor protein is located at band 11.2 on the short (or "p") arm of chromosome 7. Studies using next-generation sequencing targeted to the EGFR gene chromosomal area and confirmed by Sanger sequencing have detected insertion and/or deletion mutations in exon 20 of this gene in the tumor cells of 13 of 13 test FHI cases. While the activity of the normal EGFR protein is blocked by tyrosine kinase inhibitor drugs, most proteins coded by EGFR exon 20-mutated genes do not respond to these drugs due the structural configuration of their EGFR kinase domains; however, certain protein variants coded by these mutated EGFR genes may still be sensitive, and offer a potential treatment option, for a subset of FHI cases. In any event, the identification of these EGFR can help distinguish FHI from other pediatric spindle cell neoplasms with morphologies similar to FHI such as giant cell fibroblastoma.Genomic microarray analyses performed on the two FHI cases with tumors that had areas of sarcoma-like morphology found sarcoma-like cells hyperdiploid (i.e. cell with at least 2 more chromosomes than the normal 48), near tetraploid (i.e. four instead of the normal two chromosomes for some but not all chromosomes), single chromosome gains for several chromosomes, and loss of heterozygosity in the p arms of chromosomes 1 and 11 in the first case and in the second case a loss of the p arm in chromosome 10, lose of chromosome 14, and lose of a portion of the q arm of chromosome 22q. These two cases along with recurrent EGFR gene abnormalities strongly support the notation that FHI is as neoplastic tumor. Diagnosis The diagnosis of FHI is dependent on its presentation as a subcutaneous tumor that often occurs in individuals at birth or ages <1–2 years old; its highly characteristic histopathology consisting of fibroblast/myofibroblast, adipose tissue, and myxoid zones; and its content of tumor cells which have one of the EGFR gene mutations described in the previous section. The combination of these factors clearly distinguishes FHI from three recently defined tumors (i.e. fibroblastic connective tissue nevus, medallion-like dermal dendrocyte hamartoma, and plaque-like CD34-positive dermal fibroma) as well as various pediatric spindle-shaped cell neoplasms. Tumor imaging methods such as magnetic resonance imaging may also be helpful in suggesting that a tumor is an FHI. Treatment and prognosis FHI tumors, if left untreated, have been documented to grow for as long as ~5 years following their diagnosis. The treatment of choice for these tumors is complete surgical excision with clear margins (i.e. with removal of all tumor tissue). Recurrence rates at the site of excision in several studies have been ~15% although rates as low as 1% have been reported by specialized centers. These tumors do not metastasize (i.e. spread to distant tissues) and have an excellent long-term prognosis. See also List of cutaneous conditions Skin lesion Hamartoma == References ==

Sciatic nerve

The sciatic nerve, also called the ischiadic nerve, is a large nerve in humans and other vertebrate animals which is the largest branch of the sacral plexus and runs alongside the hip joint and down the lower limb. It is the longest and widest single nerve in the human body, going from the top of the leg to the foot on the posterior aspect. The sciatic nerve has no cutaneous branches for the thigh. This nerve provides the connection to the nervous system for the skin of the lateral leg and the whole foot, the muscles of the back of the thigh, and those of the leg and foot. It is derived from spinal nerves L4 to S3. It contains fibers from both the anterior and posterior divisions of the lumbosacral plexus. Structure In humans, the sciatic nerve is formed from the L4 to S3 segments of the sacral plexus, a collection of nerve fibres that emerge from the sacral part of the spinal cord. The lumbosacral trunk from the L4 and L5 roots descends between the sacral promontory and ala and the S1 to S3 roots emerge from the ventral sacral foramina. These nerve roots unite to form a single nerve in front of the piriformis muscle. The nerve passes beneath piriformis and through the greater sciatic foramen, quitting the pelvis.: 422–4  From here, it travels down the posterior thigh to the popliteal fossa. The nerve travels in the posterior compartment of the thigh behind (superficial to) the adductor magnus muscle, and is itself in front of (deep to) the long head of the biceps femoris muscle. At the popliteal fossa, the nerve divides into its two branches:: 532  The tibial nerve, which travels down the posterior compartment of the leg into the foot The common fibular nerve (also called the common peroneal nerve), which travels down the anterior and lateral compartments of the leg into the footThe sciatic nerve is the largest nerve in the human body.: 422–4 Development Function The sciatic nerve supplies sensation to the skin of the foot, as well as the entire lower leg (except for its inner side). Sensation to skin to the sole of the foot is provided by the tibial nerve, and the lower leg and upper surface of the foot via the common fibular nerve.: 422–4 The sciatic nerve also innervates muscles. In particular:: 422–4  Via the tibial nerve, the muscles in the posterior compartment of the leg and sole of the foot (plantar aspect). Via the common fibular nerve, the muscles in the anterior and lateral compartments of the leg. Clinical significance Sciatica Pain caused by a compression or irritation of the sciatic nerve by a problem in the lower back is called sciatica. Common causes of sciatica include the following lower back and hip conditions: spinal disc herniation, degenerative disc disease, lumbar spinal stenosis, spondylolisthesis, and piriformis syndrome. Other acute causes of sciatica include coughing, muscular hypertension, and sneezing. Injury Sciatic nerve injury occurs between 0.5% and 2.0% of the time during a hip replacement. Sciatic nerve palsy is a complication of total hip arthroplasty with an incidence of 0.2% to 2.8% of the time, or with an incidence of 1.7% to 7.6% following revision. Following the procedure, in rare cases, a screw, broken piece of trochanteric wire, fragment of methyl methacrylate bone cement, or of a Burch-Schneider antiprofusio cage can impinge on the nerve; this can cause sciatic nerve palsy which may resolve after the fragment is removed and the nerve freed. The nerve can be surrounded in oxidized regenerated cellulose to prevent further scarring. Sciatic nerve palsy can also result from severe spinal stenosis following the procedure, which can be addressed by spinal decompression surgery. It is unclear if inversion therapy is able to decompress the sacral vertebrae; it may only work on the lumbar aspects of the sciatic nerves. Sciatic nerve injury may also occur from improperly performed injections into the buttock, and may result in sensory loss.: 66 Other disease Bernese periacetabular osteotomy resulted in major nerve deficits in the sciatic or femoral nerves in 2.1% of 1760 patients, of whom approximately half experienced complete recovery within a mean of 5.5 months.Sciatic nerve exploration can be done by endoscopy in a minimally invasive procedure to assess lesions of the nerve. Endoscopic treatment for sciatic nerve entrapment has been investigated in deep gluteal syndrome. Patients were treated with sciatic nerve decompression by resection of fibrovascular scar bands, piriformis tendon release, obturator internus, or quadratus femoris or by hamstring tendon scarring. Anesthetic Signals from the sciatic nerve and its branches can be blocked, in order to interrupt transmission of pain signal from the innervation area, by performing a regional nerve blockade called a sciatic nerve block. Society and culture According to Jewish law, the sciatic nerve (Hebrew: Gid hanasheh) may not be eaten by Jews, to commemorate Jacobs injury in his struggle with an angel. Additional images See also Lesser sciatic notch Greater sciatic notch Notes References This article incorporates text in the public domain from page 960 of the 20th edition of Grays Anatomy (1918) External links Sciatic nerve at the Duke University Health Systems Orthopedics program MedlinePlus Image 19503 pelvis at The Anatomy Lesson by Wesley Norman (Georgetown University) (pelvicnerves) glutealregion at The Anatomy Lesson by Wesley Norman (Georgetown University) (glutealner) Sciatica and the Sciatic Nerve

Tufted angioma

A tufted angioma (also known as an "Acquired tufted angioma," "Angioblastoma," "Angioblastoma of Nakagawa," "Hypertrophic hemangioma," "Progressive capillary hemangioma," and "Tufted hemangioma") usually develops in infancy or early childhood on the neck and upper trunk, and is an ill-defined, dull red macule with a mottled appearance, varying from 2 to 5 cm in diameter.: 596 See also List of cutaneous conditions Skin lesion References == External links ==

Ablepharon macrostomia syndrome

Ablepharon macrostomia syndrome (AMS) is an extremely rare, autosomal dominant genetic disorder characterized by abnormal phenotypic appearances that primarily affect the head and face as well as the skull, skin, fingers and genitals. AMS generally results in abnormal ectoderm-derived structures. The most prominent abnormality is the underdevelopment (microblepharon) or absence of eyelids – signifying the ablepharon aspect of the disease – and a wide, fish-like mouth – macrostomia. Infants presenting with AMS may also have malformations of the abdominal wall and nipples. Children with AMS might also experience issues with learning development, language difficulties and intellectual disabilities. AMS is caused by mutations in the TWIST2 gene, among others. It is closely related to Barber–Say syndrome in terms of phenotypic abnormalities. Signs and symptoms AMS is generally characterized by abnormal appearances of the skin, eyes, fingers, genitals, head and face. Infants with AMS will have thin, redundantly wrinkled skin and excessive facial creases; wide-set eyes with absent or severely underdeveloped eyelids and down-turned lower eyelids; and a wide, fish-like mouth that may be fused together at the corners. Other appearances of the face and head include: broad nasal bridge, wide, flared nostrils and thick and flared alae nasi (edges of the nostrils).Abnormalities can also be seen in the hands and fingers, as infants with AMS will also have webbed fingers with limited ability to flex and extend the fingers. Infants with AMS will also display small, rudimentary ears that are atypically low-set on the skull. Absence of the zygomatic bone is also possible. Skin may be dry and coarse, excessively wrinkled around the face and loose around the hands yet tight around the finger joints, leading to diminished use of the fingers.Genital defects may include: ambiguous genitalia, a displaced and/or atypically small penis (micropenis), an absent scrotum around the testes and undescended testicles. Finally, alopecia and thin, sparse hair are also frequently observed. Causes Like Barber–Say syndrome, AMS is caused by mutations in the TWIST2 gene that affect a highly conserved residue of TWIST2 (twist-related protein 2). TWIST2 is a basic helix-loop-helix transcription factor that binds to E-box DNA motifs (5-CANNTG-3) as a heterodimer and inhibits transcriptional activation. Because TWIST2 mediates mesenchymal stem cell differentiation and prevents premature or ectopic osteoblast differentiation, mutations in TWIST2 that disrupt these functions by altering DNA-binding activity could explain many of the phenotypes of AMS. Current research points to the substitution of the wild-type amino acid for Lysine at TWIST2 residue 75 as a significant genetic cause of AMS.AMS is inherited in an autosomal dominant manner, in which an affected individual needs only one copy of the mutant allele in order to express the disease. Mechanism The mesenchyme is a mesodermal embryonic tissue that can develop into a multitude of different tissues depending on the needs of the developing embryo. The mesenchyme can develop into blood, cartilage, and membranes. In a normal patient, TWIST2 is highly expressed during embryonic development, specifically in the craniofacial development and chondrogenisis. TWIST2 works to prevent the premature maturation of chondrogenic cells and osteoblasts, the cells that will form cartilage and bone respectively. The dominant mutation in TWIST2 leads to the chondrogenic and osteoblastic cells becoming mature prematurely. This then leads to the primary craniofacial deformities seen in AMS patients. Diagnosis Ablepharon macrostomia syndrome can be diagnosed at birth by identification of characteristic physical findings, clinical evaluation, and specialized imaging techniques such as CT scans. CT scans can confirm the absence of the zygomatic arch and abnormalities in the cranial and mandibular bones. An ophthalmologist can diagnose abnormalities in the eyelids and confirm microblepharon or ablepharon. Teams of specialist will typically work together to confirm diagnosis and assess treatment options. Pediatricians, gastroenterologists, dermatologists, urologists, and other care providers can be expected to aid in the diagnosis and treatment. Treatment Primary treatment focuses on relief of immediate symptoms such as providing lubrication to the eyes to relieve pain and dryness; antibiotics may also be prescribed to prevent infections and inflammation. Surgical measures can be taken and a plastic surgeon can correct the lack of eyelids through reconstructive surgery. Surgery to correct malformations of the mouth, ears, genitals, fingers, and skin can also be performed as necessary. Macrostomia, the wide, fish-like mouth, can be corrected by a maxillofacial surgeon. The skin can be treated by means of creams to alleviate dryness and coarseness; in certain cases, botulinum toxin and skin grafts were used to improve the overall appearance. It is highly recommended that patients are able to seek the help of pediatric psychologists throughout the entire treatment process. Prognosis While there is no cure for AMS, treatment plans provided by doctors can help improve development, overall quality of life, and physical appearance. Physical appearance cannot be corrected to the "norm" but the life expectancy of patients diagnosed with AMS is normal. Research Current research into AMS focuses on both underlying causes of the disease and surgical methods for treatment. Currently, a study in Tokyo, Japan is focusing on the role of other TWIST genes in AMS development, specifically the role of TWIST1 and the amino acid substitution that must occur to mutate the gene. TWIST1 mutations are believed to lead to craniosynostosis and ablepharon.Clinical research focuses on the different surgical techniques used to treat the ablepharon aspect of AMS. The primary goal of such research is to determine which methods are most effective for the patient without being unnecessarily complex. According to a study conducted by the departments of ophthalmology in São Paulo and Lima, Peru, full thickness skin grafts have been shown to effectively treat microblepharon in patients with AMS without needing complicated surgeries. References == External links ==

Vitreomacular adhesion

Vitreomacular adhesion (VMA) is a human medical condition where the vitreous gel (or simply vitreous, AKA vitreous humour) of the human eye adheres to the retina in an abnormally strong manner. As the eye ages, it is common for the vitreous to separate from the retina. But if this separation is not complete, i.e. there is still an adhesion, this can create pulling forces on the retina that may result in subsequent loss or distortion of vision. The adhesion in of itself is not dangerous, but the resulting pathological vitreomacular traction (VMT) can cause severe ocular damage. The current standard of care for treating these adhesions is pars plana vitrectomy (PPV), which involves surgically removing the vitreous from the eye. A biological agent for non-invasive treatment of adhesions called ocriplasmin has been approved by the FDA on October 17, 2012. Symptom and signs Traction caused by VMA is the underlying pathology of an eye disease called symptomatic VMA. There is evidence that symptomatic VMA can contribute to the development of several well-known eye disorders, such as macular hole and macular pucker, that can cause visual impairment, including blindness. It may also be associated with age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion, and diabetic retinopathy (DR). Pathology Over time, it is common for the vitreous within the human eye to liquify and collapse in processes known as syneresis and synchisis respectively. This creates fluid-filled areas that can combine to form pockets of vitreous gel that are mostly liquid with very small concentrations of collagen. If these liquid pockets are close enough to the interface between the vitreous gel and the retina, they can cause complete separation of the vitreous from the retina in a normally occurring process in older humans called posterior vitreous detachment (PVD). PVD in of itself is not dangerous and a natural process.If the separation of the vitreous from the retina is not complete, areas of focal attachment or adhesions can occur, i.e. a VMA. The pulling forces or traction from this adhesion on the retinal surface can sometimes cause edema within the retina, damage to retinal blood vessels causing bleeding, or damage to the optic nerve causing disruption in the nerve signals sent to the brain for visual processing. It is important to note that while the VMA itself is not dangerous, the resultant pulling on the retina called vitreomacular traction (VMT) causes the above damage. The size and strength of the VMA determine the variety of resulting pathologies or symptoms.VMA can also lead to the development of VMT/traction-related complications such as macular puckers and macular holes leading to distorted vision or metamorphopsia; epiretinal membrane; tractional macular oedema; myopic macular retinoschisis; visual impairment; blindness. The incidence of VMA is reported as high as 84% for patients with macular hole, 100% for patients with vitreomacular traction syndrome, and 56% in idiopathic epimacular membrane. Diagnosis Careful eye examination by an ophthalmologist or optometrist is critical for diagnosing symptomatic VMA. Imaging technologies such as optical coherence tomography (OCT) have significantly improved the accuracy of diagnosing symptomatic VMA. Treatment A new FDA approved drug was released on the market late 2013. Jetrea (Brand name) or Ocriplasmin (Generic name) is the first drug of its kind used to treat vitreomacular adhesion.Mechanism of Action: Ocriplasmin is a truncated human plasmin with proteolytic activity against protein components of the vitreous body and vitreoretinal interface. It dissolves the protein matrix responsible for the vitreomacular adhesion. Adverse drug reactions: Decreased vision, potential for lens subluxation, dyschromatopsia (yellow vision), eye pain, floaters, blurred vision. New Drug comparison Rating gave Jetea a 5 indicating an important advance. Previously, no recommended treatment was available for the patient with mild symptomatic VMA. In symptomatic VMA patients with more significant vision loss, the standard of care is pars plana vitrectomy (PPV), which involves surgically removing the vitreous from the eye, thereby surgically releasing the symptomatic VMA. In other words, vitrectomy induces PVD to release the traction/adhesion on the retina. An estimated 850,000 vitrectomy procedures are performed globally on an annual basis with 250,000 in the United States alone. A standard PPV procedure can lead to serious complications including small-gauge PPV. Complications can include retinal detachment, retinal tears, endophthalmitis, and postoperative cataract formation. Additionally, PPV may result in incomplete separation, and it may potentially leave a nidus for vasoactive and vasoproliferative substances, or it may induce development of fibrovascular membranes. As with any invasive surgical procedure, PPV introduces trauma to the vitreous and surrounding tissue.There are data showing that nonsurgical induction of PVD using ocriplasmin (a recombinant protease with activity against fibronectin and laminin) can offer the benefits of successful PVD while eliminating the risks associated with a surgical procedure, i.e. vitrectomy. Pharmacologic vitreolysis is an improvement over invasive surgery as it induces complete separation, creates a more physiologic state of the vitreomacular interface, prevents the development of fibrovascular membranes, is less traumatic to the vitreous, and is potentially prophylactic. As of 2012, ThromboGenics is still developing the ocriplasmin biological agent. Ocriplasmin is approved recently under the name Jetrea for use in the United States by the FDA.view.An experimental test of injections of perfluoropropane (C3F8) on 15 symptomatic eyes of 14 patients showed that vitreomacular traction resolved in 6 eyes within 1 month and resolved in 3 more eyes within 6 months. A systematic review found high-certainty evidence that Ocriplasmin compared to no treatment increases the chance of resolution and improves vision in people with symptomatic VMA. Ocriplasmin probably reduces the need for surgery but there were more adverse events in eyes treated with ocriplasmin compared to control. References == External links ==

Dental plaque

Dental plaque is a biofilm of microorganisms (mostly bacteria, but also fungi) that grows on surfaces within the mouth. It is a sticky colorless deposit at first, but when it forms tartar, it is often brown or pale yellow. It is commonly found between the teeth, on the front of teeth, behind teeth, on chewing surfaces, along the gumline (supragingival), or below the gumline cervical margins (subgingival). Dental plaque is also known as microbial plaque, oral biofilm, dental biofilm, dental plaque biofilm or bacterial plaque biofilm. Bacterial plaque is one of the major causes for dental decay and gum disease.Progression and build-up of dental plaque can give rise to tooth decay – the localised destruction of the tissues of the tooth by acid produced from the bacterial degradation of fermentable sugar – and periodontal problems such as gingivitis and periodontitis; hence it is important to disrupt the mass of bacteria and remove it. Plaque control and removal can be achieved with correct daily or twice-daily tooth brushing and use of interdental aids such as dental floss and interdental brushes.Oral hygiene is important as dental biofilms may become acidic causing demineralization of the teeth (also known as dental caries) or harden into dental calculus (also known as tartar). Calculus cannot be removed through tooth brushing or with interdental aids, but only through professional cleaning. Plaque formation Dental plaque is a biofilm that attaches to tooth surfaces, restorations and prosthetic appliances (including dentures and bridges) if left undisturbed. Understanding the formation, composition and characteristics of plaque helps in its control. An acquired pellicle is a layer of saliva that is composed of mainly glycoproteins and forms shortly after cleaning of the teeth or exposure of new teeth. Bacteria then attach to the pellicle layer, form micro-colonies, and mature on the tooth, which can result in oral diseases. The following table provides a more detailed (six-step) explanation of biofilm formation: Components of plaque Different types of bacteria are normally present in the mouth. These bacteria, as well as leukocytes, neutrophils, macrophages, and lymphocytes, are part of the normal oral cavity and contribute to the individuals health. Approximately 80–90% of the weight of plaque is water. While 70% of the dry weight is bacteria, the remaining 30% consists of polysaccharides and glycoproteins. Bacteria The bulk of the microorganisms that form the biofilm are Streptococcus mutans and other anaerobes, though the precise composition varies by location in the mouth. Examples of such anaerobes include fusobacterium and actinobacteria. S. mutans and other anaerobes are the initial colonisers of the tooth surface, and play a major role in the establishment of the early biofilm community. Streptococcus mutans uses the enzyme glucansucrase to convert sucrose into a sticky, extracellular, dextran-based polysaccharide that allows the bacteria to cohere, forming plaque. (Sucrose is the only sugar that bacteria can use to form this sticky polysaccharide). These microorganisms all occur naturally in the oral cavity and are normally harmless. However, failure to remove plaque by regular tooth-brushing allows them to proliferate unchecked and thereby build up in a thick layer, which can by virtue of their ordinary metabolism cause any of various dental diseases for the host. Those microorganisms nearest the tooth surface typically obtain energy by fermenting dietary sucrose; during fermentation they begin to produce acids. The bacterial equilibrium position varies at different stages of formation. Below is a summary of the bacteria that may be present during the phases of plaque maturation: Early biofilm: primarily Gram-positive cocci Older biofilm (3–4 days): increased numbers of filaments and fusiforms 4–9 days undisturbed: more complex flora with rods, filamentous forms 7–14 days: Vibrio species, spirochetes, more Gram-negative organisms Dental plaque as a biofilm Dental plaque is considered a biofilm adhered to the tooth surface. It is a meticulously formed microbial community, that is organised to a particular structure and function. Plaque is rich in species, given the fact that about 1000 different bacterial species have been recognised using modern techniques.A clean tooth surface would immediately be colonised by salivary pellicles, which acts as an adhesive. This allows the first bacteria (early colonisers) to attach to the tooth, then colonise and grow. After some growth of early colonisers, the biofilm becomes more compliant to other species of bacteria, known as late colonisers. Early colonisers mainly Streptococcus species (60–90%) Eikenella spp. Haemophilus spp. Prevotella spp. Propionibacterium spp. Capnocytophaga spp. Veillonella spp. Late colonisers Aggregatibacter actinomycetemcomitans Prevotella intermedia Eubacterium spp. Treponema spp. Porphyromonas gingivalisFusobacterium nucleatum is found between the early and late colonisers, linking them together. Some salivary components are crucial for plaques ecosystem, such as salivary alpha-amylase which plays a role in binding and adhesion. Proline-rich proteins (PRP) and statherins are also involved in the formation of plaque. Supragingival biofilm Supragingival biofilm is dental plaque that forms above the gums, and is the first kind of plaque to form after the brushing of the teeth. It commonly forms in between the teeth, in the pits and grooves of the teeth and along the gums. It is made up of mostly aerobic bacteria, meaning these bacteria need oxygen to survive. If plaque remains on the tooth for a longer period of time, anaerobic bacteria begin to grow in this plaque. Subgingival biofilm Subgingival biofilm is plaque that is located under the gums. It occurs after the formation of the supragingival biofilm by a downward growth of the bacteria from above the gums to below. This plaque is mostly made up of anaerobic bacteria, meaning that these bacteria will only survive if there is no oxygen. As this plaque attaches in a pocket under the gums, they are not exposed to oxygen in the mouth and will therefore thrive if not removed.The extracellular matrix contains proteins, long-chain polysaccharides and lipids. The most common reasons for ecosystem disruption are the ecological factors discussed in the environment section. The bacteria that exhibit the most fit plasticity for the change in environment dominate the given environment. Often, this leads to opportunistic pathogens which may cause dental caries and periodontal disease. Pathogenic bacteria that have the potential to cause dental caries flourish in acidic environments; those that have the potential to cause periodontal disease flourish in a slightly alkaline environment.Antibodies to the oral pathogens Campylobacter rectus, Veillonella parvula, Prevotella melaninogenica were associated with hypertension. Environment Unlike other parts of the body, tooth surfaces are uniquely hard and non shedding. Therefore, the warm and moist environment of the mouth and the presence of teeth, makes a good environment for growth and development of dental plaque. The main ecological factors that contribute to plaque formation are pH, saliva, temperature and redox reactions. The normal pH range of saliva is between 6 and 7 and plaque biofilm is known to flourish in a pH between 6.7 and 8.3. This indicates that the natural environment of the mouth provided by saliva is ideal for the growth of bacteria in the dental plaque. Saliva acts as a buffer, which helps to maintain the pH in the mouth between 6 and 7. In addition to acting as a buffer, saliva and gingival crevicular fluid contain primary nutrients including amino acids, proteins and glycoproteins. This feeds the bacteria involved in plaque formation. The host diet plays only a minor role in providing nutrients for the resident microflora. The normal temperature of the mouth ranges between 35 and 36 °C, and a two-degree (°C) change has been shown to drastically shift the dominant species in the plaque. Redox reactions are carried out by aerobic bacteria. This keeps the oxygen levels in the mouth at a semi-stable homeostatic condition, which allows the bacteria to survive. Consequences of plaque build-up Gingivitis Gingivitis is an inflammatory lesion, mediated by host-parasite interactions that remains localised to the gingival tissue, it is a common result of plaque build-up around the gingival tissues. The bacteria found in the biofilm elicit a host response resulting in localized inflammation of the tissue. This is characterized by the cardinal signs of inflammation including a red, puffy appearance of the gums and bleeding due to brushing or flossing. Gingivitis due to plaque can be reversible by removal of the plaque. However, if left for an extended period of time, the inflammation may begin to affect the supporting tissues, in a progression referred to as periodontitis.: 96–97  The gingivitis response is a protective mechanism, averting periodontitis in many cases. Periodontitis Periodontitis is an infection of the gums which leads to bone destruction around the teeth in the jaw. Periodontitis occurs after gingivitis has been established, but not all individuals who have gingivitis will get periodontitis.: 111  Plaque accumulation is vital in the progression of periodontitis as the bacteria in plaque release enzymes which attack the bone and cause it to break down, and at the same time osteoclasts in the bone break down the bone as a way to prevent further infection. This can be treated with strict oral hygiene such as tooth brushing and cleaning in between the teeth as well as surgical debridement completed by a dental professional. Diseases linked to periodontitis Accumulated bacteria, due to the onset of periodontitis from dental plaque, may gain access to distant sites in the body through the circulatory and respiratory system, potentially contributing to various systematic diseases and conditions. Due to the infectious nature of bacteria hosted within the oral cavity, bacteria produced cavity can spread within the system of the human body and causes adverse health conditions. Bacteria access comes from the ulcerated epithelium of the periodontal pocket that results from accumulation of infection within the gingiva. Conditions and diseases can include: Atheromas Cardiovascular disease Respiratory disease Diabetes mellitus Caries Dental caries is an infectious disease caused primarily by Streptococcus mutans, characterized by acid demineralization of the enamel, which can progress to further breakdown of the more organic, inner dental tissue (dentin). The bacterial community would mainly consist of acidogenic and acid-tolerating species (e.g. Mutans streptococci and lactobacilli), while other species with relevant characteristics may also be involved. Everybody is susceptible to caries but the probability of development depends on the patient’s individual disease indicators, risk factors, and preventive factors. Factors that are considered high-risk for developing carious lesions on the teeth include: Low fluoride exposure Time, length, and frequency of sugar consumption Quality of tooth cleaning Fluctuations in salivary flow rates and composition Behavior of the individual Quality and composition of biofilmsOrganic acids released from dental plaque lead to demineralization of the adjacent tooth surface, and consequently to dental caries. Saliva is also unable to penetrate the build-up of plaque and thus cannot act to neutralize the acid produced by the bacteria and remineralize the tooth surface. Detection of plaque build-up There are two main methods of detecting dental plaque in the oral cavity: through the application of a disclosing gel or tablet, and/or visually through observation. Plaque detection is usually detected clinically by plaque disclosing agents. Disclosing agents contain dye which turns bright red to indicate plaque build-up.It is important for an individual to be aware of what to look for when doing a self-assessment for dental plaque. It is important to be aware that everyone has dental plaque, however, the severity of the build-up and the consequences of not removing the plaque can vary. Plaque disclosing gel Plaque disclosing products, also known as disclosants, make plaque clinically visible. Clean surfaces of the teeth do not absorb the disclosant, only rough surfaces. Plaque disclosing gels can be either completed at home or in the dental clinic. Before using these at home or in the dental clinic check with your general practitioners for any allergies to iodine, food colouring or any other ingredients that may be present in these products. These gels provide a visual aid in assessing plaque biofilm presence and can also show the maturity of the dental plaque. Disclosing tablets Disclosing tablets are similar to that of disclosing gels, except that they are placed in the mouth and chewed on for approximately one minute. The remaining tablet or saliva is then spit out. Disclosing gels will show the presence of the plaque, but will often not show the level of maturity of the plaque. Disclosing tablets are often prescribed or given to patients with orthodontic appliances for use before and after tooth brushing to ensure optimal cleaning. These are also helpful educational tools for young children or patients who are struggling to remove dental plaque in certain areas. Disclosing gels and tablets are useful for individuals of all ages in ensuring efficient dental plaque removal. Visual or tactile detection Dental biofilm begins to form on the tooth only minutes after brushing. It can be difficult to see dental plaque on the hard tissue surfaces, however it can be felt as a rough surface. It is often felt as a thick, fur-like deposit that may present as a yellow, tan or brown stain. These deposits are commonly found on teeth or dental appliances such as orthodontic brackets. The most common way dental plaque is assessed is through dental assessment in the dental clinic where dental instruments are able to scrape up some plaque. The most common areas where patients find plaque are between the teeth and along the cervical margins. Plaque in dogs and cats Dental plaque is also extremely common in domestic animals such as dogs and cats. However, the bacteria associated with canine and feline plaque appear to be different from those of humans. If untreated it can lead to more severe gum disease such as periodontitis; hence veterinarians often recommend oral healthcare products for affected pets. See also Flossing Gingiva Dental disease Oral hygiene Oral microbiology References External links A Biofilm Primer Archived 2018-07-16 at the Wayback Machine

Infantile systemic hyalinosis

Infantile systemic hyalinosis is an allelic autosomal-recessive condition characterized by multiple skin nodules, hyaline deposition, gingival hypertrophy, osteolytic bone lesions and joint contractures.: 606 Genetics This disease is caused by mutations in the CMG2 gene (ANTXR2). Diagnosis Management See also Skin lesion List of cutaneous conditions References External links GeneReview/NIH/UW entry on Hyalinosis, Inherited Systemic

Popliteal pterygium syndrome

Popliteal pterygium syndrome (PPS) is an inherited condition affecting the face, limbs, and genitalia. The syndrome goes by a number of names including the popliteal web syndrome and, more inclusively, the facio-genito-popliteal syndrome. The term PPS was coined by Gorlin et al. in 1968 on the basis of the most unusual anomaly, the popliteal pterygium (a web behind the knee). Symptoms and signs Clinical expressions of PPS are highly variable, but include the following: Limb findings: an extensive web running from behind the knee down to the heel (90%), malformed toenails, and webbed toes. Facial findings: cleft palate with or without cleft lip (75%), pits in the lower lip (40%), fibrous bands in the mouth known as syngnathia (25%), and tissue connecting the upper and lower eyelids Genital findings (50%): hypoplasia of the labia majora, malformation of the scrotum, and cryptorchidism. Genetics The genetic locus for PPS was localized to chromosome 1 in 1999. The disorder is inherited in an autosomal dominant manner and is due to mutation of the IRF6 gene. Most reported cases are sporadic; advanced parental age is found in a number of these cases, suggesting new mutations.The term PPS has also been used for two rare autosomal recessively inherited conditions: Lethal PPS and PPS with Ectodermal Dysplasia. Although both conditions feature a cleft lip/palate, syngnathia, and popliteal pterygium, they are clinically distinguishable from the autosomal dominant case. Lethal PPS is differentiated by microcephaly, corneal aplasia, ectropion, bony fusions, hypoplastic nose and absent thumbs, while PPS with Ectodermal Dysplasia is differentiated by woolly hair, brittle nails, ectodermal anomalies, and fissure of the sacral vertebrae. Relationship to Van der Woude syndrome Van der Woude syndrome (VDWS) and popliteal pterygium syndrome (PPS) are allelic variants of the same condition; that is, they are caused by different mutations of the same gene. PPS includes all the features of VDWS, plus popliteal pterygium, syngnathia, distinct toe/nail abnormality, syndactyly, and genito-urinary malformations. Diagnosis Treatment Epidemiology The diagnosis of PPS has been made in several ethnic groups, including Caucasian, Japanese, and sub-Saharan African. Males and females are equally likely to have the syndrome. Since the disorder is rare, its incidence rate is difficult to estimate, but is less than 1 in 300,000. See also List of cutaneous conditions Multiple pterygium syndrome References == External links ==

Perinatal asphyxia

Perinatal asphyxia (also known as neonatal asphyxia or birth asphyxia) is the medical condition resulting from deprivation of oxygen to a newborn infant that lasts long enough during the birth process to cause physical harm, usually to the brain. It is also the inability to establish and sustain adequate or spontaneous respiration upon delivery of the newborn. It remains a serious condition which causes significant mortality and morbidity. It is an emergency condition and requires adequate and quick resuscitation measures. Perinatal asphyxia is also an oxygen deficit from the 28th week of gestation to the first seven days following delivery. It is also an insult to the fetus or newborn due to lack of oxygen or lack of perfusion to various organs and may be associated with a lack of ventilation. In accordance with WHO, perinatal asphyxia is characterised by: profound metabolic acidosis, with a PH < 7.20 on umbilical cord arterial blood sample, persistence of an APGAR score of 3 at the 5th minute, clinical neurologic sequelae in the immediate neonatal period, or evidence of multiorgan system dysfunction in the immediate neonatal period. Hypoxic damage can occur to most of the infants organs (heart, lungs, liver, gut, kidneys), but brain damage is of most concern and perhaps the least likely to quickly or completely heal. In more pronounced cases, an infant will survive, but with damage to the brain manifested as either mental, such as developmental delay or intellectual disability, or physical, such as spasticity. It results most commonly from antepartum causes like a drop in maternal blood pressure or some other substantial interference with blood flow to the infants brain during delivery. This can occur due to inadequate circulation or perfusion, impaired respiratory effort, or inadequate ventilation. Perinatal asphyxia happens in 2 to 10 per 1000 newborns that are born at term, and more for those that are born prematurely. WHO estimates that 4 million neonatal deaths occur yearly due to birth asphyxia, representing 38% of deaths of children under 5 years of age.Perinatal asphyxia can be the cause of hypoxic ischemic encephalopathy or intraventricular hemorrhage, especially in preterm births. An infant with severe perinatal asphyxia usually has poor color (cyanosis), perfusion, responsiveness, muscle tone, and respiratory effort, as reflected in a low 5 minute Apgar score. Extreme degrees of asphyxia can cause cardiac arrest and death. If resuscitation is successful, the infant is usually transferred to a neonatal intensive care unit. There has long been a scientific debate over whether newborn infants with asphyxia should be resuscitated with 100% oxygen or normal air. It has been demonstrated that high concentrations of oxygen lead to generation of oxygen free radicals, which have a role in reperfusion injury after asphyxia. Research by Ola Didrik Saugstad and others led to new international guidelines on newborn resuscitation in 2010, recommending the use of normal air instead of 100% oxygen.There is considerable controversy over the diagnosis of birth asphyxia due to medicolegal reasons. Because of its lack of precision, the term is eschewed in modern obstetrics. Cause Basically, understanding of the etiology of perinatal asphyxia provides the platform on which to build on its pathophysiology. The general principles guiding the causes and the pathophysiology of perinatal asphyxia are grouped into antepartum causes and intra partum causes. As these are the various points to which insults can occur to the foetus. Antepartum causes Inadequate oxygenation of maternal blood due to hypoventilation during anesthesia, heart diseases, pneumonia, respiratory failure Low maternal blood pressure due to hypotension e.g. compression of vena cava and aorta, excess anaesthesia. Premature separation of placenta Placental insufficiency Intra partum causes Inadequate relaxation of uterus due to excess oxytocin Prolonged delivery Knotting of umbilical cord around the neck of infant Risk factors Elderly or young mothers Prolonged rupture of membranes Meconium-stained fluid Multiple births Lack of antenatal care Low birth weight infants Malpresentation Augmentation of labour with oxytocin Antepartum hemorrhage Severe eclampsia and pre-eclampsia Antepartum and intrapartum anemia Treatment A= Establish open airway: Suctioning, if necessary endotracheal intubation B= Breathing: Through tactile stimulation, PPV, bag and mask, or through endotracheal tube C= Circulation: Through chest compressions and medications if needed D= Drugs: Adrenaline .01 of .1 solution Hypothermia treatment to reduce the extent of brain injury Epinephrine 1:10000 (0.1-0.3ml/kg) IV Saline solution for hypovolemia Epidemiology A 2008 bulletin from the World Health Organization estimates that 900,000 total infants die each year from birth asphyxia, making it a leading cause of death for newborns.In the United States, intrauterine hypoxia and birth asphyxia was listed as the tenth leading cause of neonatal death. Medicolegal aspects There is current controversy regarding the medicolegal definitions and impacts of birth asphyxia. Plaintiffs attorneys often take the position that birth asphyxia is often preventable, and is often due to substandard care and human error. They have utilized some studies in their favor that have demonstrated that, "... although other potential causes exist, asphyxia and hypoxic-ihy affect a substantial number of babies, and they are preventable causes of cerebral palsy." The American Congress of Obstetricians and Gynecologists disputes that conditions such as cerebral palsy are usually attributable to preventable causes, instead associating them with circumstances arising prior to birth and delivery. References == External links ==

Teratospermia

Teratospermia or teratozoospermia is a condition characterized by the presence of sperm with abnormal morphology that affects fertility in males. Causes The causes of teratozoospermia are unknown in most cases. However, Hodgkins disease, coeliac disease, and Crohns disease may contribute in some instances. Lifestyle and habits (smoking, toxin exposure, etc.) can also cause poor morphology. Varicocele is another condition that is often associated with decreased normal forms (morphology). In cases of globozoospermia (sperm with round heads), the Golgi apparatus is not transformed into the acrosome that is needed for fertilization. Symptoms and treatment The presence of abnormally-shaped sperm can negatively affect fertility by preventing transport through the cervix and/or preventing sperm from adhering to the ovum. Achieving a pregnancy may be difficult.In testing for teratozoospermia, sperm are collected, stained and analyzed under a microscope to detect abnormalities. These abnormalities may include heads that are large, small, tapered, or pyriform or tails that are abnormally shaped.Antiestrogens have been shown to be effective in the treatment of teratozoospermia.Teratozoospermia (including the globozoospermia type), may be treated by intracytoplasmic sperm injection (ICSI), injecting sperm directly into the egg. Once the egg is fertilized, abnormal sperm morphology does not appear to influence blastocyst development or blastocyst morphology. Even with severe teratozoospermia, microscopy can still detect the few sperm cells that have a "normal" morphology, allowing for optimal success rate. See also Male infertility Semen quality References External links teratozoospermia.net

Bakers cyst

A Bakers cyst, also known as a popliteal cyst, is a type of fluid collection behind the knee. Often there are no symptoms. If symptoms do occur these may include swelling and pain behind the knee, or knee stiffness. If the cyst breaks open, pain may significantly increase with swelling of the calf. Rarely complications such as deep vein thrombosis, peripheral neuropathy, ischemia, or compartment syndrome may occur.Risk factors include other knee problems such as osteoarthritis, meniscal tears, or rheumatoid arthritis. The underlying mechanism involves the flow of synovial fluid from the knee joint to the gastrocnemio-semimembranosus bursa, resulting in its expansion. The diagnosis may be confirmed with ultrasound or magnetic resonance imaging (MRI).Treatment is initially with supportive care. If this is not effective aspiration and steroid injection or surgical removal may be carried out. Around 20% of people have a Bakers cyst. They occur most commonly in those 35 to 70 years old. It is named after the surgeon who first described it, William Morrant Baker (1838–1896). Signs and symptoms Symptoms may include swelling behind the knee, stiffness, and pain. If the cyst breaks open, pain may increase, and there may be swelling of the calf. Rupture of a Bakers cyst may also cause bruising below the medial malleolus of the ankle (Crescent sign). Cause In adults, Bakers cysts usually arise from almost any form of knee arthritis (e.g., rheumatoid arthritis) or cartilage (particularly a meniscus) tear. Bakers cysts in children do not point to underlying joint disease. Bakers cysts arise between the tendons of the medial head of the gastrocnemius and the semimembranosus muscles. They are posterior to the medial femoral condyle. The synovial sac of the knee joint can, under certain circumstances, produce a posterior bulge, into the popliteal space, the space behind the knee. When this bulge becomes large enough, it becomes palpable and cystic. Most Bakers cysts maintain this direct communication with the synovial cavity of the knee, but sometimes, the new cyst pinches off. A Bakers cyst can rupture and produce acute pain behind the knee and in the calf and swelling of the calf muscles. Diagnosis Diagnosis is by examination. A Bakers cyst is easier to see from behind with the patient standing with knees fully extended. It is most easily palpated (felt) with the knee partially flexed. Diagnosis is confirmed by ultrasonography, although if needed and there is no suspicion of a popliteal artery aneurysm then aspiration of synovial fluid from the cyst may be undertaken with care. An MRI image can reveal presence of a Bakers cyst. An infrequent but potentially life-threatening complication, which may need to be excluded by blood tests and ultrasonography, is a deep vein thrombosis (DVT). Quick assessment of the possibility of DVT may be required where a Bakers cyst has compressed vascular structures, causing leg edema, as this sets up conditions for a DVT to develop. A burst cyst commonly causes calf pain, swelling and redness that may mimic thrombophlebitis. Treatment Bakers cysts usually require no treatment unless they are symptomatic. It is very rare that the symptoms are actually coming from the cyst. In most cases, there is another disorder in the knee (arthritis, meniscal (cartilage) tear, etc.) that is causing the problem. Initial treatment should be directed at correcting the source of the increased fluid production. Often rest and leg elevation are all that is needed. If necessary, the cyst can be aspirated to reduce its size, then injected with a corticosteroid to reduce inflammation. Surgical excision is reserved for cysts that cause a great amount of discomfort to the patient. A ruptured cyst is treated with rest, leg elevation, and injection of a corticosteroid into the knee. Bakers cysts in children, unlike in older people, nearly always disappear with time, and rarely require excision.Ice pack therapy may sometimes be an effective way of controlling the pain related to Bakers cyst. Heat is also commonly used. A knee brace can offer support giving the feeling of stability in the joint. Exercise Many activities can put strain on the knee, and cause pain in the case of Bakers cyst. Avoiding activities such as squatting, kneeling, heavy lifting, climbing, and even running can help prevent pain. Despite this, some exercises can help relieve pain, and a physiotherapist may instruct on hamstring stretching to reduce pressure on the Bakers Cyst, and strengthening exercises for the quadriceps and/or the patellar ligament. References External links Media related to Bakers cyst at Wikimedia Commons

Reperfusion injury

Reperfusion injury, sometimes called ischemia-reperfusion injury (IRI) or reoxygenation injury, is the tissue damage caused when blood supply returns to tissue (re- + perfusion) after a period of ischemia or lack of oxygen (anoxia or hypoxia). The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and oxidative damage through the induction of oxidative stress rather than (or along with) restoration of normal function. Reperfusion injury is distinct from cerebral hyperperfusion syndrome (sometimes called "Reperfusion syndrome"), a state of abnormal cerebral vasodilation. Mechanisms Reperfusion of ischemic tissues is often associated with microvascular injury, particularly due to increased permeability of capillaries and arterioles that lead to an increase of diffusion and fluid filtration across the tissues. Activated endothelial cells produce more reactive oxygen species but less nitric oxide following reperfusion, and the imbalance results in a subsequent inflammatory response. The inflammatory response is partially responsible for the damage of reperfusion injury. White blood cells, carried to the area by the newly returning blood, release a host of inflammatory factors such as interleukins as well as free radicals in response to tissue damage. The restored blood flow reintroduces oxygen within cells that damages cellular proteins, DNA, and the plasma membrane. Damage to the cells membrane may in turn cause the release of more free radicals. Such reactive species may also act indirectly in redox signaling to turn on apoptosis. White blood cells may also bind to the endothelium of small capillaries, obstructing them and leading to more ischemia.Reperfusion injury plays a major part in the biochemistry of hypoxic brain injury in stroke. Similar failure processes are involved in brain failure following reversal of cardiac arrest; control of these processes is the subject of ongoing research. Repeated bouts of ischemia and reperfusion injury also are thought to be a factor leading to the formation and failure to heal of chronic wounds such as pressure sores and diabetic foot ulcer. Continuous pressure limits blood supply and causes ischemia, and the inflammation occurs during reperfusion. As this process is repeated, it eventually damages tissue enough to cause a wound.The main reason for the acute phase of ischemia-reperfusion injury is oxygen deprivation and, therefore, arrest of generation of ATP (cellular energy currency) by mitochondria oxidative phosphorylation. Tissue damage due to the general energy deficit during ischemia is followed by reperfusion (increase of oxygen level) when the injury is enhanced. Mitochondrial complex I is thought to be the most vulnerable enzyme to tissue ischemia/reperfusion but the mechanism of damage is different in different tissues. For example brain ischemia/reperfusion injury is mediated via complex I redox-dependent inactivation. It was found that lack of oxygen leads to conditions in which mitochondrial complex I loses its natural cofactor, flavin mononucleotide (FMN) and become inactive. When oxygen is present the enzyme catalyzes a physiological reaction of NADH oxidation by ubiquinone, supplying electrons downstream of the respiratory chain (complexes III and IV). Ischemia leads to dramatic increase of succinate level. In the presence of succinate mitochondria catalyze reverse electron transfer so that fraction of electrons from succinate is directed upstream to FMN of complex I. Reverse electron transfer results in a reduction of complex I FMN, increased generation of ROS, followed by a loss of the reduced cofactor (FMNH2) and impairment of mitochondria energy production. The FMN loss by complex I and I/R injury can be alleviated by the administration of FMN precursor, riboflavin.Reperfusion can cause hyperkalemia.Reperfusion injury is a primary concern in liver transplantation surgery. Treatment Therapeutic hypothermia However, the therapeutic effect of hypothermia does not confine itself to metabolism and membrane stability. Another school of thought focuses on hypothermias ability to prevent the injuries that occur after circulation returns to the brain, or what is termed reperfusion injuries. In fact an individual suffering from an ischemic insult continues suffering injuries well after circulation is restored. In rats it has been shown that neurons often die a full 24 hours after blood flow returns. Some theorize that this delayed reaction derives from the various inflammatory immune responses that occur during reperfusion. These inflammatory responses cause intracranial pressure, pressure which leads to cell injury and in some situations cell death. Hypothermia has been shown to help moderate intracranial pressure and therefore to minimize the harmful effect of a patients inflammatory immune responses during reperfusion. Beyond this, reperfusion also increases free radical production. Hypothermia too has been shown to minimize a patients production of deadly free radicals during reperfusion. Many now suspect it is because hypothermia reduces both intracranial pressure and free radical production that hypothermia improves patient outcome following a blockage of blood flow to the brain. Hydrogen sulfide treatment There are some preliminary studies in mice that seem to indicate that treatment with hydrogen sulfide (H2S) can have a protective effect against reperfusion injury. Cyclosporin In addition to its well-known immunosuppressive capabilities, the one-time administration of cyclosporin at the time of percutaneous coronary intervention (PCI) has been found to deliver a 40 percent reduction in infarct size in a small group proof of concept study of human patients with reperfusion injury published in The New England Journal of Medicine in 2008.Cyclosporin has been confirmed in studies to inhibit the actions of cyclophilin D, a protein which is induced by excessive intracellular calcium flow to interact with other pore components and help open the MPT pore. Inhibiting cyclophilin D has been shown to prevent the opening of the MPT pore and protect the mitochondria and cellular energy production from excessive calcium inflows.However, the studies CIRCUS and CYCLE (published in September 2015 and February 2016 respectively) looked at the use of cyclosporin as a one time IV dose given right before perfusion therapy (PCI). Both studies found there is no statistical difference in outcome with cyclosporin administration.Reperfusion leads to biochemical imbalances within the cell that lead to cell death and increased infarct size. More specifically, calcium overload and excessive production of reactive oxygen species in the first few minutes after reperfusion set off a cascade of biochemical changes that result in the opening of the so-called mitochondrial permeability transition pore (MPT pore) in the mitochondrial membrane of cardiac cells.The opening of the MPT pore leads to the inrush of water into the mitochondria, resulting in mitochondrial dysfunction and collapse. Upon collapse, the calcium is then released to overwhelm the next mitochondria in a cascading series of events that cause mitochondrial energy production supporting the cell to be reduced or stopped completely. The cessation of energy production results in cellular death. Protecting mitochondria is a viable cardioprotective strategy.In 2008, an editorial in the New England Journal of Medicine called for more studies to determine if cyclosporin can become a treatment to ameliorate reperfusion injury by protecting mitochondria. To that end, in 2011 the researchers involved in the original 2008 NEJM study initiated a phase III clinical study of reperfusion injury in 1000 myocardial infarction patients in centers throughout Europe. Results of that study were announced in 2015 and indicated that "intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year." This same process of mitochondrial destruction through the opening of the MPT pore is implicated in making traumatic brain injuries much worse. TRO40303 TRO40303 is a new cardioprotective compound that was shown to inhibit the MPT pore and reduce infarct size after ischemia-reperfusion. It was developed by Trophos company and currently is in Phase I clinical trial. Stem cell therapy Recent investigations suggest a possible beneficial effect of mesenchymal stem cells on heart and kidney reperfusion injury. Superoxide dismutase Superoxide dismutase is an effective anti-oxidant enzyme which converts superoxide anions to water and hydrogen peroxide. Recent researches have shown significant therapeutic effects on pre-clinical models of reperfusion injury after ischemic stroke. Metformin A series of 2009 studies published in the Journal of Cardiovascular Pharmacology suggest that Metformin may prevent cardiac reperfusion injury by inhibition of Mitochondrial Complex I and the opening of MPT pore and in rats. Riboflavin In neonatal in vivo model of brain ischemia/reperfusion, tissue injury can be alleviated by the administration of FMN precursor, riboflavin that prevents inactivation of mitochondrial complex I. Cannabinoids A study published in 2012 show that the synthetic analogue of the phytocannabinoid Tetrahydrocannabivarin (THCV), Δ8-Tetrahydrocannabivarin (Δ8-THCV) and its metabolite 11-OH-Δ8-THCV, prevent hepatic ischaemia/reperfusion injury by decreasing oxidative stress and inflammatory responses through cannabinoid CB2 receptors and thereby decrease tissue injury and inflammation with a protective effect against liver damage. Pretreatment with a CB2 receptor antagonist attenuated the protective effects of Δ8-THCV, while a CB1 antagonist tended to enhance it.An earlier study published in 2011 found, that Cannabidiol (CBD) also protects against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response of oxidative and nitrative stress, and thereby cell death and tissue injury, but independent from classical CB1 and CB2 receptors. Reperfusion protection in obligate hibernators Obligatory hibernators such as the ground squirrels show resistance to ischemia/reperfusion (I/R) injury in liver, heart, and small intestine during the hibernation season when there is a switch from carbohydrate metabolism to lipid metabolism for cellular energy supply. This metabolic switch limits anaerobic metabolism and the formation of lactate, a herald of poor prognosis and multi-organ failure (MOF) after I/R injury. In addition, the increase in lipid metabolism generates ketone bodies and activates peroxisome proliferating-activated receptors (PPARs), both of which have been shown to be protective against I/R injury. See also Crush syndrome Ischemic stroke Myocardial infarction — Reperfusion Therapeutic hypothermia Hypothermia therapy for neonatal encephalopathy Remote ischemic conditioning Ischemia-reperfusion injury of the appendicular musculoskeletal system References == External links ==

Rhinolith

A rhinolith is a stone present in the nasal cavity. The word is derived from the roots rhino- and -lith, literally meaning "nose stone". It is an uncommon medical phenomenon, not to be confused with dried nasal mucus. A rhinolith usually forms around the nucleus of a small exogenous foreign body, blood clot or secretion by slow deposition of calcium and magnesium carbonate and phosphate salts. Over a period of time, they grow into large irregular masses that fill the nasal cavity. They may cause pressure necrosis of the nasal septum or lateral wall of nose. Rhinoliths can cause nasal obstruction, epistaxis, headache, sinusitis and epiphora. They can be diagnosed from the history with unilateral foul-smelling blood-stained nasal discharge or by anterior rhinoscopy. On probing, the probe can be passed around all its corners. In both CT and MRI a rhinolith will appear like a radiopaque irregular material. Small rhinoliths can be removed by a foreign body hook. Whereas large rhinoliths can be removed either by crushing with Lucs forceps or by Moores lateral rhinotomy approach. Signs and symptoms Rhinoliths present as a unilateral nasal obstruction. Foul-smelling, blood-stained discharge is often present. Nosebleed and pain may occur due to the ulceration of surrounding mucosa. Management They are removed under general anaesthesia. Most can be removed through anterior nares. Large ones need to be broken into pieces before removal. Some particularly hard and irregular ones may require lateral rhinotomy. References == External links ==

Ectrodactyly

Ectrodactyly, split hand, or cleft hand (derived from Greek ektroma abortion and daktylos finger) involves the deficiency or absence of one or more central digits of the hand or foot and is also known as split hand/split foot malformation (SHFM). The hands and feet of people with ectrodactyly (ectrodactyls) are often described as "claw-like" and may include only the thumb and one finger (usually either the little finger, ring finger, or a syndactyly of the two) with similar abnormalities of the feet.It is a substantial rare form of a congenital disorder in which the development of the hand is disturbed. It is a type I failure of formation – longitudinal arrest. The central ray of the hand is affected and usually appears without proximal deficiencies of nerves, vessels, tendons, muscles and bones in contrast to the radial and ulnar deficiencies. The cleft hand appears as a V-shaped cleft situated in the centre of the hand. The digits at the borders of the cleft might be syndactilyzed, and one or more digits can be absent. In most types, the thumb, ring finger and little finger are the less affected parts of the hand. The incidence of cleft hand varies from 1 in 90,000 to 1 in 10,000 births depending on the used classification. Cleft hand can appear unilateral or bilateral, and can appear isolated or associated with a syndrome. Split hand/foot malformation (SHFM) is characterized by underdeveloped or absent central digital rays, clefts of hands and feet, and variable syndactyly of the remaining digits. SHFM is a heterogeneous condition caused by abnormalities at one of multiple loci, including SHFM1 (SHFM1 at 7q21-q22), SHFM2 (Xq26), SHFM3 (FBXW4/DACTYLIN at 10q24), SHFM4 (TP63 at 3q27), and SHFM5 (DLX1 and DLX 2 at 2q31). SHFM3 is unique in that it is caused by submicroscopic tandem chromosome duplications of FBXW4/DACTYLIN. SHFM3 is considered isolated ectrodactyly and does not show a mutation of the tp63 gene. Presentation Ectrodactyly can be caused by various changes to 7q. When 7q is altered by a deletion or a translocation, ectrodactyly can sometimes be associated with hearing loss. Ectrodactyly, or Split hand/split foot malformation (SHFM) type 1 is the only form of split hand/ malformation associated with sensorineural hearing loss. Genetics A large number of human gene defects can cause ectrodactyly. The most common mode of inheritance is autosomal dominant with reduced penetrance, while autosomal recessive and X-linked forms occur more rarely. Ectrodactyly can also be caused by a duplication on 10q24. Detailed studies of a number of mouse models for ectrodactyly have also revealed that a failure to maintain median apical ectodermal ridge (AER) signalling can be the main pathogenic mechanism in triggering this abnormality.A number of factors make the identification of the genetic defects underlying human ectrodactyly a complicated process: the limited number of families linked to each split hand/foot malformation (SHFM) locus, the large number of morphogens involved in limb development, the complex interactions between these morphogens, the involvement of modifier genes, and the presumed involvement of multiple gene or long-range regulatory elements in some cases of ectrodactyly. In the clinical setting these genetic characteristics can become problematic and making predictions of carrier status and severity of the disease impossible to predict.In 2011, a novel mutation in DLX5 was found to be involved in SHFM.Ectrodactyly is frequently seen with other congenital anomalies. Syndromes in which ectrodactyly is associated with other abnormalities can occur when two or more genes are affected by a chromosomal rearrangement. Disorders associated with ectrodactyly include Ectrodactyly-Ectodermal Dysplasia-Clefting (EEC) syndrome, which is closely correlated to the ADULT syndrome and Limb-mammary (LMS) syndrome, Ectrodactyly-Cleft Palate (ECP) syndrome, Ectrodactyly-Ectodermal Dysplasia-Macular Dystrophy syndrome, Ectrodactyly-Fibular Aplasia/Hypoplasia (EFA) syndrome, and Ectrodactyly-Polydactyly. More than 50 syndromes and associations involving ectrodactyly are distinguished in the London Dysmorphology Database. Pathophysiology The pathophysiology of cleft hand is thought to be a result of a wedge-shaped defect of the apical ectoderm of the limb bud (AER: apical ectodermal ridge). Polydactyly, syndactyly and cleft hand can occur within the same hand, therefore some investigators suggest that these entities occur from the same mechanism. This mechanism is not yet defined. Genetics The cause of cleft hand lies, for what is known, partly in genetics. The inheritance of cleft hand is autosomal dominant and has a variable penetrance of 70%. Cleft hand can be a spontaneous mutation during pregnancy (de novo mutation). The exact chromosomal defect in isolated cleft hand is not yet defined. However, the genetic causes of cleft hand related to syndromes have more clarity. The identified mutation for SHSF syndrome (split-hand/split-foot syndrome) a duplication on 10q24, and not a mutation of the tp63 gene as in families affected by EEC syndrome (ectrodactyly–ectodermal dysplasia–cleft syndrome). The p63 gene plays a critical role in the development of the apical ectodermal ridge (AER), this was found in mutant mice with dactylaplasia. Embryology Some studies have postulated that polydactyly, syndactyly and cleft hand have the same teratogenic mechanism. In vivo tests showed that limb anomalies were found alone or in combination with cleft hand when they were given Myleran. These anomalies take place in humans around day 41 of gestation. Diagnosis Classification There are several classifications for cleft hand, but the most used classification is described by Manske and Halikis see table 3. This classification is based on the first web space. The first web space is the space between the thumb and the index finger. Table 3: Classification for cleft hand described by Manske and Halikis Treatment The treatment of cleft hand is usually invasive and can differ each time because of the heterogeneity of the condition. The function of a cleft hand is mostly not restricted, yet improving the function is one of the goals when the thumb or first webspace is absent.The social and stigmatising aspects of a cleft hand require more attention. The hand is a part of the body which is usually shown during communication. When this hand is obviously different and deformed, stigmatisation or rejection can occur. Sometimes, in families with cleft hand with good function, operations for cosmetic aspects are considered marginal and the families choose not to have surgery. Indications Surgical treatment of the cleft hand is based on several indications: Improving function Absent thumb Deforming syndactyly (mostly between digits of unequal length like index and thumb) Transverse bones (this will progress the deformity; growth of these bones will widen the cleft) Narrowed first webspace The feetAesthetical aspects Reducing deformity Timing of surgical interventions The timing of surgical interventions is debatable. Parents have to decide about their child in a very vulnerable time of their parenthood. Indications for early treatment are progressive deformities, such as syndactyly between index and thumb or transverse bones between the digital rays. Other surgical interventions are less urgent and can wait for 1 or 2 years. Classification and treatment When surgery is indicated, the choice of treatment is based on the classification. Table 4 shows the treatment of cleft hand divided into the classification of Manske and Halikis. Techniques described by Ueba, Miura and Komada and the procedure of Snow-Littler are guidelines; since clinical and anatomical presentation within the types differ, the actual treatment is based on the individual abnormality.Table 4: Treatment based on the classification of Manske and Halikis Snow-Littler The goal of this procedure is to create a wide first web space and to minimise the cleft in the hand. The index digit will be transferred to the ulnar side of the cleft. Simultaneously a correction of index malrotation and deviation is performed. To minimise the cleft, it is necessary to fix together the metacarpals which used to border the cleft. Through repositioning flaps, the wound can be closed. Ueba Ueba described a less complicated surgery. Transverse flaps are used to resurface the palm, the dorsal side of the transposed digit and the ulnar part of the first web space. A tendon graft is used to connect the common extensor tendons of the border digits of the cleft to prevent digital separation during extension. The closure is simpler, but has cosmetic disadvantage because of the switch between palmar and dorsal skin. Miura and Komada The release of the first webspace has the same principle as the Snow-Littler procedure. The difference is the closure of the first webspace; this is done by simple closure or closure with Z-plasties. History Literature shows that cleft hand is described centuries ago. The first reference to what might be considered a cleft hand was by Ambroise Paré in 1575. Hartsink (1770) wrote the first report of true cleft hand. In 1896, the first operation of the cleft hand was performed by Doctor Charles N. Dowed of New York City. However, the first certain description of what we know as a cleft hand as we know it today was described at the end of the 19th century. Symbrachydactyly Historically, a U-type cleft hand was also known as atypical cleft hand. The classification in which typical and atypical cleft hand are described was mostly used for clinical aspects and is shown in table 1. Nowadays, this "atypical cleft hand" is referred to as symbrachydactyly and is not a subtype of cleft hand. Notable cases Bree Walker Once a popular television anchor woman in Los Angeles, she has appeared in the television drama Nip/Tuck as an inspirational character who battles her disease and counsels another family who have children with ectrodactyly Grady Stiles Sr. and Grady Stiles Jr.: known publicly as Lobster Boy and family, famous side show acts, featured on the AMC reality show, Freakshow. The Vadoma tribe in northern Zimbabwe Mikhail Tal, Soviet chess player, World Chess Champion 1960–61 Lee Hee-ah, a Korean pianist with only two fingers on each hand. Cédric Grégoire (better known as Lord Lokhraed) is the guitarist and lead vocalist of French black metal band Nocturnal Depression and has ectrodactyly on his fretting hand, which has only two fingers. Black Scorpion, freak show performer. Sam Schröder, 2020 US Open Quad Champion. Francesca Jones, British pro tennis player, former #149 in WTA rankings. Other animals Ectrodactyly is not only a genetic characteristic in humans, but can also occur in frogs and toads, mice, salamanders, cows, chickens, rabbits, marmosets, cats and dogs, and even West Indian manatees. The following examples are studies showing the natural occurrence of ectrodactyly in animals, without the disease being reproduced and tested in a laboratory. In all three examples we see how rare the actual occurrence of ectrodactyly is. Wood frog The Department of Biological Sciences at the University of Alberta in Edmonton, Alberta performed a study to estimate deformity levels in wood frogs in areas of relatively low disturbance. After roughly 22,733 individuals were examined during field studies, it was found that only 49 wood frogs had the ectrodactyly deformity. Salamanders In a study performed by the Department of Forestry and Natural Resources at Purdue University, approximately 2000 salamanders (687 adults and 1259 larvae) were captured from a large wetland complex and evaluated for malformations. Among the 687 adults, 54 (7.9%) were malformed. Of these 54 adults, 46 (85%) had missing (ectrodactyly), extra (polyphalangy) or dwarfed digits (brachydactyly). Among the 1259 larvae, 102 were malformed, with 94 (92%) of the malformations involving ectrodactyly, polyphalangy, and brachydactyly. Results showed few differences in the frequency of malformations among life-history changes, suggesting that malformed larvae do not have substantially higher mortality than their adult conspecifics. Cats and dogs Davis and Barry 1977 tested allele frequencies in domestic cats. Among the 265 cats observed, there were 101 males and 164 females. Only one cat was recorded to have the ectrodactyly abnormality, illustrating this rare disease. According to M.P. Ferreira, a case of ectrodactyly was found in a two-month-old male mixed Terrier dog. In another study, Carrig and co-workers also reported a series of 14 dogs with this abnormality proving that although ectrodactyly is an uncommon occurrence for dogs, it is not entirely unheard of. See also Oligodactyly Sonic hedgehog, a main gene responsible for body symmetry during development. References External links Media related to Ectrodactyly at Wikimedia Commons Online Mendelian Inheritance in Man (OMIM): 183600 Online Mendelian Inheritance in Man (OMIM): 183800

Trichorrhexis invaginata

Trichorrhexis invaginata is a distinctive hair shaft abnormality that may occur sporadically, either in normal hair or with other hair shaft abnormalities, or regularly as a marker for Nethertons syndrome.: 638 : 766–7  The primary defect appears to be abnormal keratinization of the hair shaft in the keratogenous zone, allowing for intussusception of the fully keratinized and hard distal shaft into the incompletely keratinized and soft proximal portion of the shaft.: 638 Genetics "Bamboo hair" is a rare autosomal recessive genodermatosis characterized by congenital ichthyosiform erythroderma, trichorrhexis invaginata, and atopic diathesis with failure to thrive. Chronic skin inflammation results in scaling and exfoliation, predisposing these patients to life-threatening infections, sepsis, and dehydration. The Netherton syndrome Mendelian Inheritance in Man is inherited as an autosomal recessive disorder due to mutations of both copies of the SPINK5 gene (localized to band 5q31-32), which encodes the serine protease inhibitor LEKTI (lymphoepithelial Kazal-type-related inhibitor). LEKTI is expressed in epithelial and mucosal surfaces and in the thymus. Each SPINK5 mutation leads to a different length of LEKTI protein, resulting in genotype/phenotype correlations in cutaneous severity, susceptibility to atopic dermatitis, growth retardation, skin infection, increased stratum corneum protease activities, and elevated kallikrein levels in the stratum corneum.Trichorrhexis invaginata, or bamboo hair, is a hair shaft abnormality that occurs as a result of an intermittent keratinizing defect of the hair cortex. Incomplete conversion of the sulfhydryl –SH group onto S-S disulfide bonds in the protein of the cortical fibers leads to cortical softness and subsequent invagination of the fully keratinized distal hair shaft into the softer, abnormally keratinized proximal hair shaft. Intussusception of the distal hair shaft into the proximal hair shaft results in a distinctive ball-and-socket hair shaft deformity. The affected hairs are brittle and breakage is common, resulting in short hairs.Migratory lesions of ichthyosis linearis circumflexa may be caused by a dermal influx of inflammatory cells that undergo phagocytosis and digestion by keratinocytes, resulting in disruption of keratinization.Increased transepidermal water loss resulting from the disturbance of corneocyte barrier function in erythroderma may cause profound metabolic abnormalities and hypernatremia, particularly in neonates. Epidemiology Approximately 200 cases of trichorrhexis invaginata (bamboo hair) have been reported in the literature, but the true incidence is not known. The incidence of trichorrhexis invaginata (bamboo hair) may be as high as 1 case in 50,000 population. Girls are affected more often by trichorrhexis invaginata (bamboo hair) than boys, but is present in all races. History In 1937, Touraine and Solente first noted the association between hair-shaft defects (bamboo node) and ichthyosiform erythroderma. Còme first coined the term ichthyosis linearis circumflexa in 1949, although Rille had previously recorded the distinctive features of ichthyosis linearis circumflexa by 1922. In 1958, Netherton described a young girl with generalized scaly dermatitis and fragile nodular hair-shaft deformities, which he termed trichorrhexis nodosa. Later, this was more appropriately renamed as trichorrhexis invaginata (bamboo hair) for a ball-and-socket–type hair-shaft deformity at the suggestion of Wilkinson et al. In 1974, Mevorah et al. established the clinical relationship between ichthyosis linearis circumflexa and Netherton syndrome, and an atopic diathesis was found to occur in approximately 75% of patients with Netherton syndrome. See also Trichomegaly List of cutaneous conditions References == External links ==

Muehrckes nails

Muehrckes nails or Muehrckes lines (apparent leukonychia striata) are changes in the fingernail that may be a sign of an underlying medical condition. The term refers to a set of one or more pale transverse bands extending all the way across the nail, parallel to the lunula. In contrast to Beaus lines, they are not grooved (no 3-dimensional deformity), and in contrast to Mees lines, the thumb is usually not involved.Muehrckes lines are a strong indicator of hypoalbuminemia, which can result from a variety of different causes.The lines are actually in the vascular bed underneath the nail plate. As such, they do not move with nail growth, and disappear when pressure is applied to the nail (blanching the underlying nail bed): this distinguishes them from "true leukonychia striata" such as Mees lines. As in Terrys and half-and-half nails, the pattern is thought to be formed by bands of localized edema exerting pressure on the surrounding capillaries. Physiology The appearance of Muehrckes lines is associated specifically with marked hypoalbuminemia (serum albumin ≤ 2.2 g/dL) indicating decreased protein synthesis, which may occur during periods of metabolic stress (e.g. systemic infection, trauma, AIDS, chemotherapy), or in hypoalbuminemic states such as the nephrotic syndrome or dietary protein deficiency. They are also seen in patients with end-stage kidney disease on hemodialysis, Hodgkins disease, pellagra, and sickle cell anaemia.The lines remain visible as long as protein intake is inadequate or synthesis is impaired, and they should disappear upon return to normal function.In extreme conditions, Muehrckes lines may also arise from physical changes in peripheral circulation: one case study reported appearance of the lines in a healthy subject following ascent to 8,848 meters (29,029 ft) on Mount Everest. History Muehrckes lines were described by American physician Robert C. Muehrcke (1921–2003) in 1956. In a study published in BMJ, he examined patients with known chronic hypoalbuminemia and healthy volunteers, finding that the appearance of multiple transverse white lines was a highly specific marker for low serum albumin (no subject with the sign had SA over 2.2 g/dL), was associated with severity of the underlying condition, and disappeared upon successful treatment (corticosteroids in nephrotic syndrome) or direct infusion of HSA. See also Mees lines – a similar appearance, except the lines are in the nail and move as the nail grows Half and half nails Terrys nails List of cutaneous conditions References Bibliography Fawcett, Robert S.; Sean Linford; Daniel L. Stulberg (March 15, 2004). "Nail Abnormalities: Clues to Systemic Disease". American Family Physician. 69 (6): 1417–24. PMID 15053406. James, William; Berger, Timothy; Elston, Dirk (2005). Andrews Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0. Muehrcke Lines of the Fingernails at eMedicine Muehrckes Lines of the Fingernails on WebMD

Oxygen toxicity

Oxygen toxicity is a condition resulting from the harmful effects of breathing molecular oxygen (O2) at increased partial pressures. Severe cases can result in cell damage and death, with effects most often seen in the central nervous system, lungs, and eyes. Historically, the central nervous system condition was called the Paul Bert effect, and the pulmonary condition the Lorrain Smith effect, after the researchers who pioneered the discoveries and descriptions in the late 19th century. Oxygen toxicity is a concern for underwater divers, those on high concentrations of supplemental oxygen (particularly premature babies), and those undergoing hyperbaric oxygen therapy. The result of breathing increased partial pressures of oxygen is hyperoxia, an excess of oxygen in body tissues. The body is affected in different ways depending on the type of exposure. Central nervous system toxicity is caused by short exposure to high partial pressures of oxygen at greater than atmospheric pressure. Pulmonary and ocular toxicity result from longer exposure to increased oxygen levels at normal pressure. Symptoms may include disorientation, breathing problems, and vision changes such as myopia. Prolonged exposure to above-normal oxygen partial pressures, or shorter exposures to very high partial pressures, can cause oxidative damage to cell membranes, collapse of the alveoli in the lungs, retinal detachment, and seizures. Oxygen toxicity is managed by reducing the exposure to increased oxygen levels. Studies show that, in the long term, a robust recovery from most types of oxygen toxicity is possible. Protocols for avoidance of the effects of hyperoxia exist in fields where oxygen is breathed at higher-than-normal partial pressures, including underwater diving using compressed breathing gases, hyperbaric medicine, neonatal care and human spaceflight. These protocols have resulted in the increasing rarity of seizures due to oxygen toxicity, with pulmonary and ocular damage being mainly confined to the problems of managing premature infants. In recent years, oxygen has become available for recreational use in oxygen bars. The US Food and Drug Administration has warned those who have conditions such as heart or lung disease not to use oxygen bars. Scuba divers use breathing gases containing up to 100% oxygen, and should have specific training in using such gases. Classification The effects of oxygen toxicity may be classified by the organs affected, producing three principal forms: Central nervous system, characterised by convulsions followed by unconsciousness, occurring under hyperbaric conditions; Pulmonary (lungs), characterised by difficulty in breathing and pain within the chest, occurring when breathing increased pressures of oxygen for extended periods; Ocular (retinopathic conditions), characterised by alterations to the eyes, occurring when breathing increased pressures of oxygen for extended periods.Central nervous system oxygen toxicity can cause seizures, brief periods of rigidity followed by convulsions and unconsciousness, and is of concern to divers who encounter greater than atmospheric pressures. Pulmonary oxygen toxicity results in damage to the lungs, causing pain and difficulty in breathing. Oxidative damage to the eye may lead to myopia or partial detachment of the retina. Pulmonary and ocular damage are most likely to occur when supplemental oxygen is administered as part of a treatment, particularly to newborn infants, but are also a concern during hyperbaric oxygen therapy. Oxidative damage may occur in any cell in the body but the effects on the three most susceptible organs will be the primary concern. It may also be implicated in damage to red blood cells (haemolysis), the liver, heart, endocrine glands (adrenal glands, gonads, and thyroid), or kidneys, and general damage to cells.In unusual circumstances, effects on other tissues may be observed: it is suspected that during spaceflight, high oxygen concentrations may contribute to bone damage. Hyperoxia can also indirectly cause carbon dioxide narcosis in patients with lung ailments such as chronic obstructive pulmonary disease or with central respiratory depression. Hyperventilation of atmospheric air at atmospheric pressures does not cause oxygen toxicity, because sea-level air has a partial pressure of oxygen of 0.21 bar (21 kPa) whereas toxicity does not occur below 0.3 bar (30 kPa). Signs and symptoms Central nervous system Central nervous system oxygen toxicity manifests as symptoms such as visual changes (especially tunnel vision), ringing in the ears (tinnitus), nausea, twitching (especially of the face), behavioural changes (irritability, anxiety, confusion), and dizziness. This may be followed by a tonic–clonic seizure consisting of two phases: intense muscle contraction occurs for several seconds (tonic phase); followed by rapid spasms of alternate muscle relaxation and contraction producing convulsive jerking (clonic phase). The seizure ends with a period of unconsciousness (the postictal state). The onset of seizure depends upon the partial pressure of oxygen in the breathing gas and exposure duration. However, exposure time before onset is unpredictable, as tests have shown a wide variation, both amongst individuals, and in the same individual from day to day. In addition, many external factors, such as underwater immersion, exposure to cold, and exercise will decrease the time to onset of central nervous system symptoms. Decrease of tolerance is closely linked to retention of carbon dioxide. Other factors, such as darkness and caffeine, increase tolerance in test animals, but these effects have not been proven in humans. Lungs Pulmonary toxicity symptoms result from an inflammation that starts in the airways leading to the lungs and then spreads into the lungs (tracheobronchial tree). The symptoms appear in the upper chest region (substernal and carinal regions). This begins as a mild tickle on inhalation and progresses to frequent coughing. If breathing increased partial pressures of oxygen continues, patients experience a mild burning on inhalation along with uncontrollable coughing and occasional shortness of breath (dyspnea). Physical findings related to pulmonary toxicity have included bubbling sounds heard through a stethoscope (bubbling rales), fever, and increased blood flow to the lining of the nose (hyperaemia of the nasal mucosa). X-rays of the lungs show little change in the short term, but extended exposure leads to increasing diffuse shadowing throughout both lungs. Pulmonary function measurements are reduced, as noted by a reduction in the amount of air that the lungs can hold (vital capacity) and changes in expiratory function and lung elasticity. Tests in animals have indicated a variation in tolerance similar to that found in central nervous system toxicity, as well as significant variations between species. When the exposure to oxygen above 0.5 bar (50 kPa) is intermittent, it permits the lungs to recover and delays the onset of toxicity. Eyes In premature babies, signs of damage to the eye (retinopathy of prematurity, or ROP) are observed via an ophthalmoscope as a demarcation between the vascularised and non-vascularised regions of an infants retina. The degree of this demarcation is used to designate four stages: (I) the demarcation is a line; (II) the demarcation becomes a ridge; (III) growth of new blood vessels occurs around the ridge; (IV) the retina begins to detach from the inner wall of the eye (choroid). Causes Oxygen toxicity is caused by exposure to oxygen at partial pressures greater than those to which the body is normally exposed. This occurs in three principal settings: underwater diving, hyperbaric oxygen therapy, and the provision of supplemental oxygen, particularly to premature infants. In each case, the risk factors are markedly different. Central nervous system toxicity Exposures, from minutes to a few hours, to partial pressures of oxygen above 1.6 bars (160 kPa)—about eight times normal atmospheric partial pressure—are usually associated with central nervous system oxygen toxicity and are most likely to occur among patients undergoing hyperbaric oxygen therapy and divers. Since sea level atmospheric pressure is about 1 bar (100 kPa), central nervous system toxicity can only occur under hyperbaric conditions, where ambient pressure is above normal. Divers breathing air at depths beyond 60 m (200 ft) face an increasing risk of an oxygen toxicity "hit" (seizure). Divers breathing a gas mixture enriched with oxygen, such as nitrox, can similarly have a seizure at shallower depths, should they descend below the maximum operating depth allowed for the mixture. Lung toxicity The lungs and the remainder of the respiratory tract are exposed to the highest concentration of oxygen in the human body and are therefore the first organs to show toxicity. Pulmonary toxicity occurs only with exposure to partial pressures of oxygen greater than 0.5 bar (50 kPa), corresponding to an oxygen fraction of 50% at normal atmospheric pressure. The earliest signs of pulmonary toxicity begin with evidence of tracheobronchitis, or inflammation of the upper airways, after an asymptomatic period between 4 and 22 hours at greater than 95% oxygen, with some studies suggesting symptoms usually begin after approximately 14 hours at this level of oxygen.At partial pressures of oxygen of 2 to 3 bar (200 to 300 kPa)—100% oxygen at 2 to 3 times atmospheric pressure—these symptoms may begin as early as 3 hours after exposure to oxygen. Experiments on rats breathing oxygen at pressures between 1 and 3 bars (100 and 300 kPa) suggest that pulmonary manifestations of oxygen toxicity may not be the same for normobaric conditions as they are for hyperbaric conditions. Evidence of decline in lung function as measured by pulmonary function testing can occur as quickly as 24 hours of continuous exposure to 100% oxygen, with evidence of diffuse alveolar damage and the onset of acute respiratory distress syndrome usually occurring after 48 hours on 100% oxygen. Breathing 100% oxygen also eventually leads to collapse of the alveoli (atelectasis), while—at the same partial pressure of oxygen—the presence of significant partial pressures of inert gases, typically nitrogen, will prevent this effect.Preterm newborns are known to be at higher risk for bronchopulmonary dysplasia with extended exposure to high concentrations of oxygen. Other groups at higher risk for oxygen toxicity are patients on mechanical ventilation with exposure to levels of oxygen greater than 50%, and patients exposed to chemicals that increase risk for oxygen toxicity such the chemotherapeutic agent bleomycin. Therefore, current guidelines for patients on mechanical ventilation in intensive care recommends keeping oxygen concentration less than 60%. Likewise, divers who undergo treatment of decompression sickness are at increased risk of oxygen toxicity as treatment entails exposure to long periods of oxygen breathing under hyperbaric conditions, in addition to any oxygen exposure during the dive. Ocular toxicity Prolonged exposure to high inspired fractions of oxygen causes damage to the retina. Damage to the developing eye of infants exposed to high oxygen fraction at normal pressure has a different mechanism and effect from the eye damage experienced by adult divers under hyperbaric conditions. Hyperoxia may be a contributing factor for the disorder called retrolental fibroplasia or retinopathy of prematurity (ROP) in infants. In preterm infants, the retina is often not fully vascularised. Retinopathy of prematurity occurs when the development of the retinal vasculature is arrested and then proceeds abnormally. Associated with the growth of these new vessels is fibrous tissue (scar tissue) that may contract to cause retinal detachment. Supplemental oxygen exposure, while a risk factor, is not the main risk factor for development of this disease. Restricting supplemental oxygen use does not necessarily reduce the rate of retinopathy of prematurity, and may raise the risk of hypoxia-related systemic complications.Hyperoxic myopia has occurred in closed circuit oxygen rebreather divers with prolonged exposures. It also occurs frequently in those undergoing repeated hyperbaric oxygen therapy. This is due to an increase in the refractive power of the lens, since axial length and keratometry readings do not reveal a corneal or length basis for a myopic shift. It is usually reversible with time.A possible side effect of hyperbaric oxygen therapy is the initial or further development of cataracts, which are a increase in opacity of the lens of the eye which reduces visual acuity, and can eventually result in blindness. This is a rare event, associated with lifetime exposure to raised oxygen concentration, and may be under-reported as it develops very slowly. The cause is not fully understood, but evidence suggests that raised oxygen levels may cause accelerated deterioration of the vitreous humour due to degradation of lens crystallins by cross-linking, forming aggregates capable of scattering light. This may be an end-state development of the more commonly observed myopic shift associated with hyperbaric treatment. Mechanism The biochemical basis for the toxicity of oxygen is the partial reduction of oxygen by one or two electrons to form reactive oxygen species, which are natural by-products of the normal metabolism of oxygen and have important roles in cell signalling. One species produced by the body, the superoxide anion (O−2), is possibly involved in iron acquisition. Higher than normal concentrations of oxygen lead to increased levels of reactive oxygen species. Oxygen is necessary for cell metabolism, and the blood supplies it to all parts of the body. When oxygen is breathed at high partial pressures, a hyperoxic condition will rapidly spread, with the most vascularised tissues being most vulnerable. During times of environmental stress, levels of reactive oxygen species can increase dramatically, which can damage cell structures and produce oxidative stress.While all the reaction mechanisms of these species within the body are not yet fully understood, one of the most reactive products of oxidative stress is the hydroxyl radical (·OH), which can initiate a damaging chain reaction of lipid peroxidation in the unsaturated lipids within cell membranes. High concentrations of oxygen also increase the formation of other free radicals, such as nitric oxide, peroxynitrite, and trioxidane, which harm DNA and other biomolecules. Although the body has many antioxidant systems such as glutathione that guard against oxidative stress, these systems are eventually overwhelmed at very high concentrations of free oxygen, and the rate of cell damage exceeds the capacity of the systems that prevent or repair it. Cell damage and cell death then result. Diagnosis Diagnosis of central nervous system oxygen toxicity in divers prior to seizure is difficult as the symptoms of visual disturbance, ear problems, dizziness, confusion and nausea can be due to many factors common to the underwater environment such as narcosis, congestion and coldness. However, these symptoms may be helpful in diagnosing the first stages of oxygen toxicity in patients undergoing hyperbaric oxygen therapy. In either case, unless there is a prior history of epilepsy or tests indicate hypoglycaemia, a seizure occurring in the setting of breathing oxygen at partial pressures greater than 1.4 bar (140 kPa) suggests a diagnosis of oxygen toxicity.Diagnosis of bronchopulmonary dysplasia in newborn infants with breathing difficulties is difficult in the first few weeks. However, if the infants breathing does not improve during this time, blood tests and x-rays may be used to confirm bronchopulmonary dysplasia. In addition, an echocardiogram can help to eliminate other possible causes such as congenital heart defects or pulmonary arterial hypertension.The diagnosis of retinopathy of prematurity in infants is typically suggested by the clinical setting. Prematurity, low birth weight, and a history of oxygen exposure are the principal indicators, while no hereditary factors have been shown to yield a pattern. Prevention The prevention of oxygen toxicity depends entirely on the setting. Both underwater and in space, proper precautions can eliminate the most pernicious effects. Premature infants commonly require supplemental oxygen to treat complications of preterm birth. In this case prevention of bronchopulmonary dysplasia and retinopathy of prematurity must be carried out without compromising a supply of oxygen adequate to preserve the infants life. Underwater Oxygen toxicity is a catastrophic hazard in scuba diving, because a seizure results in high risk of death by drowning. The seizure may occur suddenly and with no warning symptoms. The effects are sudden convulsions and unconsciousness, during which victims can lose their regulator and drown. One of the advantages of a full-face diving mask is prevention of regulator loss in the event of a seizure. Mouthpiece retaining straps are a relatively inexpensive alternative with a similar but less effective function. As there is an increased risk of central nervous system oxygen toxicity on deep dives, long dives and dives where oxygen-rich breathing gases are used, divers are taught to calculate a maximum operating depth for oxygen-rich breathing gases, and cylinders containing such mixtures should be clearly marked with that depth.The risk of seizure appears to be a function of dose – a cumulative combination of partial pressure and duration. The threshold for oxygen partial pressure below which seizures never occur has not been established, and may depend on many variables, some of them personal. the risk to a specific person can vary considerably depending on individual sensitivity, level of exercise, and carbon dioxide retention, which is influenced by work of breathing.In some diver training courses for these types of diving, divers are taught to plan and monitor what is called the oxygen clock of their dives. This is a notional alarm clock, which ticks more quickly at increased oxygen pressure and is set to activate at the maximum single exposure limit recommended in the National Oceanic and Atmospheric Administration Diving Manual. For the following partial pressures of oxygen the limits are: 45 minutes at 1.6 bar (160 kPa), 120 minutes at 1.5 bar (150 kPa), 150 minutes at 1.4 bar (140 kPa), 180 minutes at 1.3 bar (130 kPa) and 210 minutes at 1.2 bar (120 kPa), but it is impossible to predict with any reliability whether or when toxicity symptoms will occur. Many nitrox-capable dive computers calculate an oxygen loading and can track it across multiple dives. The aim is to avoid activating the alarm by reducing the partial pressure of oxygen in the breathing gas or by reducing the time spent breathing gas of greater oxygen partial pressure. As the partial pressure of oxygen increases with the fraction of oxygen in the breathing gas and the depth of the dive, the diver obtains more time on the oxygen clock by diving at a shallower depth, by breathing a less oxygen-rich gas, or by shortening the duration of exposure to oxygen-rich gases. This function is provided by some technical diving decompression computers and rebreather control and monitoring hardware.Diving below 56 m (184 ft) on air would expose a diver to increasing danger of oxygen toxicity as the partial pressure of oxygen exceeds 1.4 bar (140 kPa), so a gas mixture must be used which contains less than 21% oxygen (a hypoxic mixture). Increasing the proportion of nitrogen is not viable, since it would produce a strongly narcotic mixture. However, helium is not narcotic, and a usable mixture may be blended either by completely replacing nitrogen with helium (the resulting mix is called heliox), or by replacing part of the nitrogen with helium, producing a trimix.Pulmonary oxygen toxicity is an entirely avoidable event while diving. The limited duration and naturally intermittent nature of most diving makes this a relatively rare (and even then, reversible) complication for divers. Established guidelines enable divers to calculate when they are at risk of pulmonary toxicity. In saturation diving it can be avoided by limiting the oxygen content of gas in living areas to below 0.4 bar. Hyperbaric setting The presence of a fever or a history of seizure is a relative contraindication to hyperbaric oxygen treatment. The schedules used for treatment of decompression illness allow for periods of breathing air rather than 100% oxygen (oxygen breaks) to reduce the chance of seizure or lung damage. The U.S. Navy uses treatment tables based on periods alternating between 100% oxygen and air. For example, USN table 6 requires 75 minutes (three periods of 20 minutes oxygen/5 minutes air) at an ambient pressure of 2.8 standard atmospheres (280 kPa), equivalent to a depth of 18 metres (60 ft). This is followed by a slow reduction in pressure to 1.9 atm (190 kPa) over 30 minutes on oxygen. The patient then remains at that pressure for a further 150 minutes, consisting of two periods of 15 minutes air/60 minutes oxygen, before the pressure is reduced to atmospheric over 30 minutes on oxygen.Vitamin E and selenium were proposed and later rejected as a potential method of protection against pulmonary oxygen toxicity. There is however some experimental evidence in rats that vitamin E and selenium aid in preventing in vivo lipid peroxidation and free radical damage, and therefore prevent retinal changes following repetitive hyperbaric oxygen exposures. Normobaric setting Bronchopulmonary dysplasia is reversible in the early stages by use of break periods on lower pressures of oxygen, but it may eventually result in irreversible lung injury if allowed to progress to severe damage. One or two days of exposure without oxygen breaks are needed to cause such damage.Retinopathy of prematurity is largely preventable by screening. Current guidelines require that all babies of less than 32 weeks gestational age or having a birth weight less than 1.5 kg (3.3 lb) should be screened for retinopathy of prematurity at least every two weeks. The National Cooperative Study in 1954 showed a causal link between supplemental oxygen and retinopathy of prematurity, but subsequent curtailment of supplemental oxygen caused an increase in infant mortality. To balance the risks of hypoxia and retinopathy of prematurity, modern protocols now require monitoring of blood oxygen levels in premature infants receiving oxygen. Hypobaric setting In low-pressure environments oxygen toxicity may be avoided since the toxicity is caused by high partial pressure of oxygen, not merely by high oxygen fraction. This is illustrated by modern pure oxygen use in spacesuits, which must operate at low pressure (also historically, very high percentage oxygen and lower than normal atmospheric pressure was used in early spacecraft, for example, the Gemini and Apollo spacecraft). In such applications as extra-vehicular activity, high-fraction oxygen is non-toxic, even at breathing mixture fractions approaching 100%, because the oxygen partial pressure is not allowed to chronically exceed 0.3 bar (4.4 psi). Management During hyperbaric oxygen therapy, the patient will usually breathe 100% oxygen from a mask while inside a hyperbaric chamber pressurised with air to about 2.8 bar (280 kPa). Seizures during the therapy are managed by removing the mask from the patient, thereby dropping the partial pressure of oxygen inspired below 0.6 bar (60 kPa).A seizure underwater requires that the diver be brought to the surface as soon as practicable. Although for many years the recommendation has been not to raise the diver during the seizure itself, owing to the danger of arterial gas embolism (AGE), there is some evidence that the glottis does not fully obstruct the airway. This has led to the current recommendation by the Diving Committee of the Undersea and Hyperbaric Medical Society that a diver should be raised during the seizures clonic (convulsive) phase if the regulator is not in the divers mouth—as the danger of drowning is then greater than that of AGE—but the ascent should be delayed until the end of the clonic phase otherwise. Rescuers ensure that their own safety is not compromised during the convulsive phase. They then ensure that where the victims air supply is established it is maintained, and carry out a controlled buoyant lift. Lifting an unconscious body is taught by most recreational diver training agencies as an advanced skill, and for professional divers it is a basic skill, as it is one of the primary functions of the standby diver. Upon reaching the surface, emergency services are always contacted as there is a possibility of further complications requiring medical attention. The U.S. Navy has procedures for completing the decompression stops where a recompression chamber is not immediately available.The occurrence of symptoms of bronchopulmonary dysplasia or acute respiratory distress syndrome is treated by lowering the fraction of oxygen administered, along with a reduction in the periods of exposure and an increase in the break periods where normal air is supplied. Where supplemental oxygen is required for treatment of another disease (particularly in infants), a ventilator may be needed to ensure that the lung tissue remains inflated. Reductions in pressure and exposure will be made progressively, and medications such as bronchodilators and pulmonary surfactants may be used.Divers manage the risk of pulmonary damage by limiting exposure to levels shown to be generally acceptable by experimental evidence, using a system of accumulated oxygen toxicity units which are based on exposure time at specified partial pressures. In the event of emergency treatment for decompression illness, it may be necessary to exceed normal exposure limits to manage more critical symptoms.Retinopathy of prematurity may regress spontaneously, but should the disease progress beyond a threshold (defined as five contiguous or eight cumulative hours of stage 3 retinopathy of prematurity), both cryosurgery and laser surgery have been shown to reduce the risk of blindness as an outcome. Where the disease has progressed further, techniques such as scleral buckling and vitrectomy surgery may assist in re-attaching the retina. Repetitive exposure Repeated exposure to potentially toxic oxygen concentrations in breathing gas is fairly common in hyperbaric activity, particularly in hyperbaric medicine, saturation diving, underwater habitats, and repetitive decompression diving. Research at the National Oceanic and Atmospheric Administration (NOAA) by R.W. Hamilton and others determined acceptable levels of exposure for single and repeated exposures. A distinction is made between acceptable exposure for acute and chronic toxicity, but these are really the extremes of a possible continuous range of exposures. A further distinction can be made between routine exposure and exposure required for emergency treatment, where a higher risk of oxygen toxicity may be justified to achieve a reduction of a more critical injury, particularly when in a relatively safe controlled and monitored environment. The Repex (repetitive exposure) method, developed in 1988, allows oxygen toxicity dosage to be calculated using a single dose value equivalent to 1 minute at atmospheric pressure called an Oxygen Tolerance Unit (OTU), is used to avoid toxic effects over several days of operetional exposure. Some dive computers will automatically track the dosage bases on depth and selected gas mixture. The limits allow a greater exposure when the person has not been exposed recently, and daily allowable dose decreases with an increase in consecutive days with exposure. These values may not be fully supported by current data. A more recent proposal uses a simple power equation, Toxicity Index (TI) = t2 × PO2c, where t is time and c is the power term. This was derived from the chemical reactions producing reactive oxygen or nitrogen species, and has been shown to give good predictions for CNS toxicity with c = 6.8 and for pulmonary toxicity for c = 4.57.For pulmonary toxicity, time is in hours, and PO2 in atmospheres absolute, TI should be limited to 250. For CNS toxicity, time is in minutes, PO2 in atmospheres absolute, and a TI of 26,108 indicates a 1% risk. Prognosis Although the convulsions caused by central nervous system oxygen toxicity may lead to incidental injury to the victim, it remained uncertain for many years whether damage to the nervous system following the seizure could occur and several studies searched for evidence of such damage. An overview of these studies by Bitterman in 2004 concluded that following removal of breathing gas containing high fractions of oxygen, no long-term neurological damage from the seizure remains.The majority of infants who have survived following an incidence of bronchopulmonary dysplasia will eventually recover near-normal lung function, since lungs continue to grow during the first 5–7 years and the damage caused by bronchopulmonary dysplasia is to some extent reversible (even in adults). However, they are likely to be more susceptible to respiratory infections for the rest of their lives and the severity of later infections is often greater than that in their peers.Retinopathy of prematurity (ROP) in infants frequently regresses without intervention and eyesight may be normal in later years. Where the disease has progressed to the stages requiring surgery, the outcomes are generally good for the treatment of stage 3 ROP, but are much worse for the later stages. Although surgery is usually successful in restoring the anatomy of the eye, damage to the nervous system by the progression of the disease leads to comparatively poorer results in restoring vision. The presence of other complicating diseases also reduces the likelihood of a favourable outcome. Epidemiology The incidence of central nervous system toxicity among divers has decreased since the Second World War, as protocols have developed to limit exposure and partial pressure of oxygen inspired. In 1947, Donald recommended limiting the depth allowed for breathing pure oxygen to 7.6 m (25 ft), which equates to an oxygen partial pressure of 1.8 bar (180 kPa). Over time this limit has been reduced, until today a limit of 1.4 bar (140 kPa) during a recreational dive and 1.6 bar (160 kPa) during shallow decompression stops is generally recommended. Oxygen toxicity has now become a rare occurrence other than when caused by equipment malfunction and human error. Historically, the U.S. Navy has refined its Navy Diving Manual Tables to reduce oxygen toxicity incidents. Between 1995 and 1999, reports showed 405 surface-supported dives using the helium–oxygen tables; of these, oxygen toxicity symptoms were observed on 6 dives (1.5%). As a result, the U.S. Navy in 2000 modified the schedules and conducted field tests of 150 dives, none of which produced symptoms of oxygen toxicity. Revised tables were published in 2001.The variability in tolerance and other variable factors such as workload have resulted in the U.S. Navy abandoning screening for oxygen tolerance. Of the 6,250 oxygen-tolerance tests performed between 1976 and 1997, only 6 episodes of oxygen toxicity were observed (0.1%).Central nervous system oxygen toxicity among patients undergoing hyperbaric oxygen therapy is rare, and is influenced by a number of a factors: individual sensitivity and treatment protocol; and probably therapy indication and equipment used. A study by Welslau in 1996 reported 16 incidents out of a population of 107,264 patients (0.015%), while Hampson and Atik in 2003 found a rate of 0.03%. Yildiz, Ay and Qyrdedi, in a summary of 36,500 patient treatments between 1996 and 2003, reported only 3 oxygen toxicity incidents, giving a rate of 0.008%. A later review of over 80,000 patient treatments revealed an even lower rate: 0.0024%. The reduction in incidence may be partly due to use of a mask (rather than a hood) to deliver oxygen.Bronchopulmonary dysplasia is among the most common complications of prematurely born infants and its incidence has grown as the survival of extremely premature infants has increased. Nevertheless, the severity has decreased as better management of supplemental oxygen has resulted in the disease now being related mainly to factors other than hyperoxia.In 1997 a summary of studies of neonatal intensive care units in industrialised countries showed that up to 60% of low birth weight babies developed retinopathy of prematurity, which rose to 72% in extremely low birth weight babies, defined as less than 1 kg (2.2 lb) at birth. However, severe outcomes are much less frequent: for very low birth weight babies—those less than 1.5 kg (3.3 lb) at birth—the incidence of blindness was found to be no more than 8%. History Central nervous system toxicity was first described by Paul Bert in 1878. He showed that oxygen was toxic to insects, arachnids, myriapods, molluscs, earthworms, fungi, germinating seeds, birds, and other animals. Central nervous system toxicity may be referred to as the "Paul Bert effect".Pulmonary oxygen toxicity was first described by J. Lorrain Smith in 1899 when he noted central nervous system toxicity and discovered in experiments in mice and birds that 0.43 bar (43 kPa) had no effect but 0.75 bar (75 kPa) of oxygen was a pulmonary irritant. Pulmonary toxicity may be referred to as the "Lorrain Smith effect". The first recorded human exposure was undertaken in 1910 by Bornstein when two men breathed oxygen at 2.8 bar (280 kPa) for 30 minutes, while he went on to 48 minutes with no symptoms. In 1912, Bornstein developed cramps in his hands and legs while breathing oxygen at 2.8 bar (280 kPa) for 51 minutes. Smith then went on to show that intermittent exposure to a breathing gas with less oxygen permitted the lungs to recover and delayed the onset of pulmonary toxicity.Albert R. Behnke et al. in 1935 were the first to observe visual field contraction (tunnel vision) on dives between 1.0 bar (100 kPa) and 4.1 bar (410 kPa). During World War II, Donald and Yarbrough et al. performed over 2,000 experiments on oxygen toxicity to support the initial use of closed circuit oxygen rebreathers. Naval divers in the early years of oxygen rebreather diving developed a mythology about a monster called "Oxygen Pete", who lurked in the bottom of the Admiralty Experimental Diving Unit "wet pot" (a water-filled hyperbaric chamber) to catch unwary divers. They called having an oxygen toxicity attack "getting a Pete".In the decade following World War II, Lambertsen et al. made further discoveries on the effects of breathing oxygen under pressure and methods of prevention. Their work on intermittent exposures for extension of oxygen tolerance and on a model for prediction of pulmonary oxygen toxicity based on pulmonary function are key documents in the development of standard operating procedures when breathing increased pressures of oxygen. Lambertsens work showing the effect of carbon dioxide in decreasing time to onset of central nervous system symptoms has influenced work from current exposure guidelines to future breathing apparatus design.Retinopathy of prematurity was not observed before World War II, but with the availability of supplemental oxygen in the decade following, it rapidly became one of the principal causes of infant blindness in developed countries. By 1960 the use of oxygen had become identified as a risk factor and its administration restricted. The resulting fall in retinopathy of prematurity was accompanied by a rise in infant mortality and hypoxia-related complications. Since then, more sophisticated monitoring and diagnosis have established protocols for oxygen use which aim to balance between hypoxic conditions and problems of retinopathy of prematurity.Bronchopulmonary dysplasia was first described by Northway in 1967, who outlined the conditions that would lead to the diagnosis. This was later expanded by Bancalari and in 1988 by Shennan, who suggested the need for supplemental oxygen at 36 weeks could predict long-term outcomes. Nevertheless, Palta et al. in 1998 concluded that radiographic evidence was the most accurate predictor of long-term effects. Bitterman et al. in 1986 and 1995 showed that darkness and caffeine would delay the onset of changes to brain electrical activity in rats. In the years since, research on central nervous system toxicity has centred on methods of prevention and safe extension of tolerance. Sensitivity to central nervous system oxygen toxicity has been shown to be affected by factors such as circadian rhythm, drugs, age, and gender. In 1988, Hamilton et al. wrote procedures for the National Oceanic and Atmospheric Administration to establish oxygen exposure limits for habitat operations. Even today, models for the prediction of pulmonary oxygen toxicity do not explain all the results of exposure to high partial pressures of oxygen. Society and culture Recreational scuba divers commonly breathe nitrox containing up to 40% oxygen, while technical divers use pure oxygen or nitrox containing up to 80% oxygen to accelerate decompression. Divers who breathe oxygen fractions greater than of air (21%) need to be educated on the dangers of oxygen toxicity and how to manage the risk. To buy nitrox, a diver may be required to show evidence of relevant qualification.Since the late 1990s the recreational use of oxygen has been promoted by oxygen bars, where customers breathe oxygen through a nasal cannula. Claims have been made that this reduces stress, increases energy, and lessens the effects of hangovers and headaches, despite the lack of any scientific evidence to support them. There are also devices on sale that offer "oxygen massage" and "oxygen detoxification" with claims of removing body toxins and reducing body fat. The American Lung Association has stated "there is no evidence that oxygen at the low flow levels used in bars can be dangerous to a normal persons health", but the U.S. Center for Drug Evaluation and Research cautions that people with heart or lung disease need their supplementary oxygen carefully regulated and should not use oxygen bars.Victorian society had a fascination for the rapidly expanding field of science. In "Dr. Oxs Experiment", a short story written by Jules Verne in 1872, the eponymous doctor uses electrolysis of water to separate oxygen and hydrogen. He then pumps the pure oxygen throughout the town of Quiquendone, causing the normally tranquil inhabitants and their animals to become aggressive and plants to grow rapidly. An explosion of the hydrogen and oxygen in Dr Oxs factory brings his experiment to an end. Verne summarised his story by explaining that the effects of oxygen described in the tale were his own invention (they are not in any way supported by empirical evidence). There is also a brief episode of oxygen intoxication in his "From the Earth to the Moon". See also Effect of oxygen on chronic obstructive pulmonary disease Nitrogen narcosis – Reversible narcotic effects of respiratory nitrogen at elevated partial pressures References Sources Clark, James M; Thom, Stephen R (2003). "Oxygen under pressure". In Brubakk, Alf O; Neuman, Tom S (eds.). Bennett and Elliotts physiology and medicine of diving (5th ed.). United States: Saunders. pp. 358–418. ISBN 978-0-7020-2571-6. OCLC 51607923. Clark, John M; Lambertsen, Christian J (1970). "Pulmonary oxygen tolerance in man and derivation of pulmonary oxygen tolerance curves". IFEM Report No. 1-70. Philadelphia, PA: Environmental Biomedical Stress Data Center, Institute for Environmental Medicine, University of Pennsylvania Medical Center. Archived from the original on 7 October 2008. Retrieved 29 April 2008. Donald, Kenneth W (1947). "Oxygen Poisoning in Man: Part I". British Medical Journal. 1 (4506): 667–72. doi:10.1136/bmj.1.4506.667. PMC 2053251. PMID 20248086. Donald, Kenneth W (1947). "Oxygen Poisoning in Man: Part II". British Medical Journal. 1 (4507): 712–17. doi:10.1136/bmj.1.4507.712. PMC 2053400. PMID 20248096. Revised version of Donalds articles also available as: Donald, Kenneth W (1992). Oxygen and the diver. UK: Harley Swan, 237 pages. ISBN 1-85421-176-5. OCLC 26894235. Hamilton, Robert W; Thalmann, Edward D (2003). "Decompression practice". In Brubakk, Alf O; Neuman, Tom S (eds.). Bennett and Elliotts physiology and medicine of diving (5th ed.). United States: Saunders. pp. 475–79. ISBN 978-0-7020-2571-6. OCLC 51607923. Lang, Michael A, ed. (2001). DAN nitrox workshop proceedings. Durham, NC: Divers Alert Network, 197 pages. Archived from the original on 16 September 2011. Retrieved 20 September 2008. Regillo, Carl D; Brown, Gary C; Flynn, Harry W (1998). Vitreoretinal Disease: The Essentials. New York: Thieme, 693 pages. ISBN 978-0-86577-761-3. OCLC 39170393. U.S. Navy Supervisor of Diving (2011). U.S. Navy Diving Manual (PDF). SS521-AG-PRO-010 0910-LP-106-0957, revision 6 with Change A entered. U.S. Naval Sea Systems Command. Archived from the original (PDF) on 10 December 2014. Retrieved 29 January 2015. Further reading Lamb, John S. (1999). The Practice of Oxygen Measurement for Divers. Flagstaff: Best Publishing, 120 pages. ISBN 0-941332-68-3. OCLC 44018369. Lippmann, John; Bugg, Stan (1993). The Diving Emergency Handbook. Teddington, UK: Underwater World Publications. ISBN 0-946020-18-3. OCLC 52056845. Lippmann, John; Mitchell, Simon (2005). "Oxygen". Deeper into Diving (2nd ed.). Victoria, Australia: J.L. Publications. pp. 121–24. ISBN 0-9752290-1-X. OCLC 66524750. External links General The following external site is a compendium of resources: Rubicon Research Repository Archived 8 September 2012 at the Wayback Machine – Online collection of the oxygen toxicity researchSpecialised The following external sites contain resources specific to particular topics: 2008 Divers Alert Network Technical Diving Conference – Video of "Oxygen Toxicity" lecture by Dr. Richard Vann (free download, mp4, 86MB). Nosek, Thomas M. "Section 4/4ch7/s4ch7_7". Essentials of Human Physiology. Archived from the original on 24 March 2016. – Discussion of the effects of breathing oxygen on the respiratory system. Rajiah, Prabhakar (11 March 2009). "Bronchopulmonary Dysplasia". eMedicine. WebMD. Retrieved 29 June 2009. – Clinical overview with references.

Yaws

Yaws is a tropical infection of the skin, bones, and joints caused by the spirochete bacterium Treponema pallidum pertenue. The disease begins with a round, hard swelling of the skin, 2 to 5 cm (0.79 to 1.97 in) in diameter. The center may break open and form an ulcer. This initial skin lesion typically heals after 3–6 months. After weeks to years, joints and bones may become painful, fatigue may develop, and new skin lesions may appear. The skin of the palms of the hands and the soles of the feet may become thick and break open. The bones (especially those of the nose) may become misshapen. After 5 years or more, large areas of skin may die, leaving scars.Yaws is spread by direct contact with the fluid from a lesion of an infected person. The contact is usually of a nonsexual nature. The disease is most common among children, who spread it by playing together. Other related treponemal diseases are bejel (T. pallidum endemicum), pinta (T. carateum), and syphilis (T. p. pallidum). Yaws is often diagnosed by the appearance of the lesions. Blood antibody tests may be useful, but cannot separate previous from current infections. Polymerase chain reaction is the most accurate method of diagnosis.No vaccine has yet been found. Prevention is, in part, done by curing those who have the disease, thereby decreasing the risk of transmission. Where the disease is common, treating the entire community is effective. Improving cleanliness and sanitation also decreases spread. Treatment is typically with antibiotics, including: azithromycin by mouth or benzathine penicillin by injection. Without treatment, physical deformities occur in 10% of cases.Yaws is common in at least 13 tropical countries as of 2012. Almost 85% of infections occurred in three countries—Ghana, Papua New Guinea, and Solomon Islands. The disease only infects humans. Efforts in the 1950s and 1960s by the World Health Organization decreased the number of cases by 95%. Since then, cases have increased, but with renewed efforts to globally eradicate the disease by 2020. In 1995, the number of people infected was estimated at more than 500,000. In 2016, the number of reported cases was 59,000. Although one of the first descriptions of the disease was made in 1679 by Willem Piso, archaeological evidence suggests that yaws may have been present among human ancestors as far back as 1.6 million years ago. Signs and symptoms Yaws is classified as primary, secondary, and tertiary; this is useful, but people often have a mix of stages.Within 9–90 days (but usually about 21 days) of infection, a painless but distinctive "mother yaw" nodule appears. Initially reddened and inflamed, it may become a papilloma, which can then become an ulcer, possibly with a yellow crust. Mother yaws are most commonly found on the legs and ankles, and are rarely found on the genitals (unlike syphilis) The mother yaw enlarges and becomes warty in appearance. Nearby "daughter yaws" may also appear simultaneously. This primary stage resolves completely, with scarring, within 3–6 months. The scar is often pigmented. The secondary stage occurs months to two years later (but usually 1–2 months later), and may thus begin when the mother yaw has not yet healed. It happens when the bacterium spreads in the blood and lymph. It begins as multiple, pinhead-like papules; these initial lesions grow and change in appearance and may last weeks before healing, with or without scarring.Secondary yaws typically shows widespread skin lesions that vary in appearance, including "crab yaws" (areas of skin of abnormal colour) on the palms of the hands and soles of the feet (named for the crab-like gait they cause people with painful soles to assume). These may show desquamation. These secondary lesions frequently ulcerate and are then highly infectious, but heal after 6 months or more.Secondary yaws affects the skin and bones. The most common bone-related problem is periostitis, an inflammation around the bone, often occurs in the bones of the fingers and the long bones of the lower arms and legs, causing swollen fingers and limbs. This causes pain at night and thickening of the affected bones (periostitis). About 75% of infected children surveyed in Papua New Guinea reported joint pain. Swollen lymph nodes, fever, and malaise are also common.After primary and secondary yaws (and possibly, in some cases, without these phases), a latent infection develops. Within five years (rarely, within ten years) it can relapse and become active again, causing further secondary lesions, which may infect others. These relapse lesions are most commonly found around the armpits, mouth, and anus. An estimated 10% of people with yaws formerly were thought to develop tertiary disease symptoms, but more recently, tertiary yaws has been less frequently reported.Tertiary yaws can include gummatous nodules. It most commonly affects the skin. The skin of the palms and soles may thicken (hyperkeratosis). Nodules ulcerating near joints can cause tissue death. Periostitis can be much more severe. The shinbones may become bowed (saber shin) from chronic periostitis.Yaws may or may not have cardiovascular or neurological effects; definitive evidence is lacking. Rhinopharyngitis mutilans Rhinopharyngitis mutilans, also known as gangosa, is a destructive ulcerative condition that usually originates about the soft palate and spreads into the hard palate, nasopharynx, and nose, resulting in mutilating cicatrices, and outward to the face, eroding intervening bone, cartilage, and soft tissues. It occurs in late stages of yaws, usually 5 to 10 years after first symptoms of infection. This is now rare. Very rarely, yaws may cause bone spurs in the upper jaw near the nose (gondou); gondou was rare even when yaws was a common disease. Cause The disease is transmitted by skin-to-skin contact with an infective lesion, with the bacterium entering through a pre-existing cut, bite, or scratch.Early (primary and secondary) yaws lesions have a higher bacterial load, thus are more infectious. Both papillomas and ulcers are infectious. Infectivity is thought to last 12–18 months after infection, longer if a relapse occurs. Early yaws lesions are often itchy, and more lesions may form along lines that are scratched. Yaws may be evolving less conspicuous lesions.Yaws is most common among children, who spread it by playing together. It is not thought to be transmitted from mother to child in the womb. Yaws is not a venereal disease.T. pallidum pertenue has been identified in nonhuman primates (baboons, chimpanzees, and gorillas) and experimental inoculation of human beings with a simian isolate causes yaws-like disease. However, no evidence exists of cross-transmission between human beings and primates, but more research is needed to discount the possibility of a yaws animal reservoir in nonhuman primates. Diagnosis Most often the diagnosis is made clinically. Dark field microscopy of samples taken from early lesions (particularly ulcerative lesions) may show the responsible bacteria; the spirochaetes are only 0.3 µm wide by 6–20 µm long, so light-field microscopy does not suffice.A microscopic examination of a biopsy of a yaw may show skin with clear epidermal hyperplasia (a type of skin thickening) and papillomatosis (a type of surface irregularity), often with focal spongiosis (an accumulation of fluid in specific part of the epidermis). Immune system cells, neutrophils and plasma cells, accumulate in the skin, in densities that may cause microabscesses.Warthin–Starry or Levaditi silver stains selectively stain T. pallidum, and direct and indirect immunofluorescence and immunoperoxidase tests can detect polyclonal antibodies to T. pallidums. Histology often shows some spatial features which distinguish yaws from syphilis (syphilis is more likely to be found in the dermis, not the epidermis, and shows more endothelial cell proliferation and vascular obliteration).Blood-serum (serological) tests are increasingly done at the point of care. They include a growing range of treponemal and nontreponemal assays. Treponemal tests are more specific, and are positive for any one who has ever been infected with yaws; they include the Treponema pallidum particle agglutination assay. Nontreponemal assays can be used to indicate the progress of an infection and a cure, and positive results weaken and may become negative after recovery, especially after a case treated early. They include the venereal disease research laboratory (VDRL; requires microscopy) and rapid plasma reagin (RPR; naked-eye result) tests, both of which flocculate patient-derived antibodies with antigens.Serological tests cannot distinguish yaws from the closely related syphilis; no test distinguishing yaws from syphilis is widely available. The two genomes differ by about 0.2%. PCR and DNA sequencing can distinguish the two. There are also no common blood tests which distinguish among the four treponematoses: syphilis (Treponema pallidum pallidum), yaws (Treponema pallidum pertenue), bejel (Treponema pallidum endemicum), and pinta (Treponema carateum).Haemophilus ducreyi infections can cause skin conditions that mimic primary yaws. People infected with Haemophilus ducreyi lesions may or may not also have latent yaws, and thus may or may not test positive on serological tests. This was discovered in the mid-2010s. It seems that a recently diverged strain of Haemophilus ducreyi has evolved from being a sexually transmitted infection to being a skin ulcer pathogen that looks like yaws.Yaws has been reported in nonendemic countries. Treatment Treatment is normally by a single intramuscular injection of long-acting benzathine benzylpenicillin, or less commonly by a course of other antibiotics, such as azithromycin or tetracycline tablets. Penicillin has been the front-line treatment since at least the 1960s, but there is no solid evidence of the evolution of penicillin resistance in yaws.The historical strategy for the eradication of yaws (1952–1964) was: Benzathine benzylpenicillin requires a cold chain and staff who can inject it, and there is a small risk of anaphylaxis. It was also not reliably available during the 2010s; there have been supply shortages.In the 2010s, a single oral dose of azithromycin was shown to be as effective as intramuscular penicillin. Unlike penicillin, there is strong evidence that yaws is evolving antibiotic resistance to azithromycin; there are two known mutations in the bacterium, each of which can cause resistance and make the treatment ineffective. This has threatened eradication efforts.Within 8–10 hours of penicillin treatment, bacteria can no longer be found in lesion biopsies. Primary and secondary lesions usually heal in 2–4 weeks; bone pain may improve within two days. If treated early enough, bone deformities may reverse and heal. Primary and secondary stage lesions may heal completely, but the destructive changes of tertiary yaws are largely irreversible.If lesions do not heal, or RPR test results do not improve, this may indicate treatment failure or re-infection; the treatment is typically repeated. WHO guidelines says that any presumed treatment failures at 4 weeks require macrolide resistance testing. Epidemiology Because T. pallidum pertenue is temperature- and humidity-dependent, yaws is found in humid tropical forest regions in South America, Africa, Asia and Oceania.About three quarters of people affected are children under 15 years of age, with the greatest incidence in children 6–10 years old. Therefore, children are the main reservoir of infection.It is more common in remote areas, where access to treatment is poorer. It is associated with poverty and poor sanitation facilities and personal hygiene.Worldwide, almost 85% of yaws cases are in Ghana, Papua New Guinea, and the Solomon Islands. Rates in sub-Saharan Africa are low, but tend to be concentrated in specific populations. As of 2015, it is estimated that about 89 million people live in yaws-endemic areas, but data are poor, and this is likely an over-estimate.In the early 1900s, yaws was very common; in sub-saharan Africa, it was more frequently treated than malaria, sometimes making up more than half of treatments.Mass treatment campaigns in the 1950s reduced the worldwide prevalence from 50 to 150 million to fewer than 2.5 million; however, during the 1970s there were outbreaks in South-East Asia, and there have been continued sporadic cases in South America. As of 2011, it was unclear how many people worldwide were currently infected.From 2008 to 2012, 13 countries reported over 300,000 new cases to the WHO. There was no system for certifying local elimination of yaws, and it is not known whether the lack of reports from some countries is because they stopped having yaws cases or because they stopped reporting them. It is estimated that if there is not an active surveillance programme, there is less than a 1-in-2 chance that a country will successfully report yaws cases (if it gets them) in over three-quarters of countries with a history of yaws. These countries are thought to need international assistance to mount effective surveillance.Generally, yaws is not a notifiable disease. History Examination of remains of Homo erectus from Kenya, that are about 1.6 million years old, has revealed signs typical of yaws. The genetic analysis of the yaws causative bacteria—Treponema pallidum pertenue—has led to the conclusion that yaws is the most ancient of the four known Treponema diseases. All other Treponema pallidum subspecies probably evolved from Treponema pallidum pertenue. Yaws is believed to have originated in tropical areas of Africa, and spread to other tropical areas of the world via immigration and the slave trade. The latter is likely the way it was introduced to Europe from Africa in the 15th century. The first unambiguous description of yaws was made by the Dutch physician Willem Piso. Yaws was clearly described in 1679 among African slaves by Thomas Sydenham in his epistle on venereal diseases, although he thought that it was the same disease as syphilis. The causative agent of yaws was discovered in 1905 by Aldo Castellani in ulcers of patients from Ceylon.The current English name is believed to be of Carib origin, from "yaya", meaning sore.Towards the end of the Second World War yaws became widespread in the North of Malaya under Japanese occupation. After the country was liberated, the population was treated for yaws by injections of arsenic, of which there was a great shortage, so only those with stage 1 were treated. Eradication A series of WHO yaws control efforts, which began shortly after creation of the WHO in 1948, succeeded in eradicating the disease locally from many countries, but have not lasted long enough to eradicate it globally. The Global Control of Treponematoses (TCP) programme by the WHO and the UNICEF launched in 1952 and continued until 1964. A 1953 questionnaire-based estimate was that there were 50–150 million yaws cases in 90 countries. The global prevalence of yaws and the other endemic treponematoses, bejel and pinta, was reduced by the Global Control of Treponematoses (TCP) programme between 1952 and 1964 from about 50 million cases to about 2.5 million (a 95% reduction). However, "premature integration of yaws and other endemic treponematoses activities into weak primary health-care systems, and the dismantling of the vertical eradication programmes after 1964, led to the failure to finish with the remaining 5% of cases" and led to a resurgence of yaws in the 1970s, with the largest number of case found in the Western Africa region. Following the cessation of this program, resources, attention and commitment for yaws gradually disappeared and yaws remained at a low prevalence in parts of Asia, Africa, and the Americas with sporadic outbreaks. With few cases, mainly affecting poor, remote communities with little access to treatment, yaws became poorly known, yaws knowledge and skills died out even among health professionals, and yaws eradication was not seen as a high priority. Although a single injection of long-acting penicillin or other beta lactam antibiotic cures the disease and is widely available and the disease highly localised, many eradication campaigns ended in complacency and neglect; even in areas where transmission was successfully interrupted, re-introduction from infected areas occurred. Yaws eradication remained a priority in south-east Asia. In 1995, the WHO estimated 460,000 worldwide cases.In the Philippines, yaws stopped being listed as a notifiable disease in 1973; as of 2020, it is still present in the country.India implemented a successful Yaws eradication campaign that resulted in the 2016 certification by the WHO that India was free of yaws. In 1996 there were 3,571 yaws cases in India; in 1997 after a serious elimination effort began the number of cases fell to 735. By 2003 the number of cases was 46. The last clinical case in India was reported in 2003 and the last latent case in 2006; certification by the WHO was achieved in 2016.In 2012 the WHO officially targeted yaws for eradication by 2020 following the development of orally administered azithromycin as a treatment, but missed that target. The Morges approach (named after Morges, Switzerland, where a meeting on it was held) involved mass treatment with azithromycin. This was safe, but ran into problems with antibiotic resistance, and did not fully interrupt transmission.The discovery that oral antibiotic azithromycin can be used instead of the previous standard, injected penicillin, was tested on Lihir Island from 2013 to 2014; a single oral dose of the macrolide antibiotic reduced disease prevalence from 2.4% to 0.3% at 12 months. The WHO now recommends both treatment courses (oral azithromycin and injected penicillin), with oral azithromycin being the preferred treatment.As of 2020, there were 15 countries known to be endemic for yaws, with the recent discovery of endemic transmission in Liberia and the Philippines. In 2020, 82 564 cases of yaws were reported to the WHO and 153 cases were confirmed. The majority of the cases are reported from Papua New Guinea and with over 80% of all cases coming from one of three countries in the 2010–2013 period: Papua New Guinea, Solomon Islands, and Ghana. A WHO meeting report in 2018 estimated the total cost of elimination to be US$175 million (excluding Indonesia).In the South-East Asian Regional Office of the WHO, regional eradication efforts are focused on the remaining endemic countries in this region (Indonesia and East Timor) after India was declared free of yaws in 2016.Although yaws is highly localized and eradication may be feasible, humans may not be the only reservoir of infection. References External links "Treponema pallidum subsp. pertenue". NCBI Taxonomy Browser. 168.

Cutis rhomboidalis nuchae

Cutis rhomboidalis nuchae is a skin condition of the posterior neck, characterized by deep furrowing of the skin. See also List of cutaneous conditions Poikiloderma of Civatte Solar elastosis References == External links ==

Dystonia

Dystonia is a neurological hyperkinetic movement disorder in which sustained or repetitive muscle contractions result in twisting and repetitive movements or abnormal fixed postures. The movements may resemble a tremor. Dystonia is often intensified or exacerbated by physical activity, and symptoms may progress into adjacent muscles.The disorder may be hereditary or caused by other factors such as birth-related or other physical trauma, infection, poisoning (e.g., lead poisoning) or reaction to pharmaceutical drugs, particularly neuroleptics, or stress. Treatment must be highly customized to the needs of the individual and may include oral medications, chemodenervation botulinum neurotoxin injections, physical therapy, or other supportive therapies, and surgical procedures such as deep brain stimulation. Classification There are multiple types of dystonia, and many diseases and conditions may cause dystonia. Dystonia is classified by: Clinical characteristics such as age of onset, body distribution, nature of the symptoms, and associated features such as additional movement disorders or neurological symptoms, and Cause (which includes changes or damage to the nervous system and inheritance).Physicians use these classifications to guide diagnosis and treatment. Types Generalized Focal Segmental Psychogenic Acute dystonic reaction Vegetative-vascular Generalized dystonias For example, dystonia musculorum deformans (Oppenheim, Flatau-Sterling syndrome): Normal birth history and milestones Autosomal dominant Childhood onset Starts in lower limbs and spreads upwardsAlso known as torsion dystonia or idiopathic torsion dystonia (old terminology "dystonia musculorum deformans"). Focal dystonias These most common dystonias are typically classified as follows: The combination of blepharospasmodic contractions and oromandibular dystonia is called cranial dystonia or Meiges syndrome. Segmental dystonias Segmental dystonias affect two adjoining parts of the body: Hemidystonia affects an arm and foot on one side of the body. Multifocal dystonia affects many different parts of the body. Generalized dystonia affects most of the body, frequently involving the legs and back. Genetic/primary There is a group called myoclonic dystonia where some cases are hereditary and have been associated with a missense mutation in the dopamine-D2 receptor. Some of these cases have responded well to alcohol.Other genes that have been associated with dystonia include CIZ1, GNAL, ATP1A3, and PRRT2. Another report has linked THAP1 and SLC20A2 to dystonia. Signs and symptoms Symptoms vary according to the kind of dystonia involved. In most cases, dystonia tends to lead to abnormal posturing, in particular on movement. Many individuals with the condition have continuous pain, cramping, and relentless muscle spasms due to involuntary muscle movements. Other motor symptoms are possible including lip smacking.Early symptoms may include loss of precision muscle coordination (sometimes first manifested in declining penmanship, frequent small injuries to the hands, and dropped items), cramping pain with sustained use, and trembling. Significant muscle pain and cramping may result from very minor exertions like holding a book and turning pages. It may become difficult to find a comfortable position for arms and legs with even the minor exertions associated with holding arms crossed causing significant pain similar to restless leg syndrome. Affected persons may notice trembling in the diaphragm while breathing, or the need to place hands in pockets, under legs while sitting or under pillows while sleeping to keep them still and to reduce pain. Trembling in the jaw may be felt and heard while lying down, and the constant movement to avoid pain may result in the grinding and wearing down of teeth, or symptoms similar to temporomandibular joint disorder. The voice may crack frequently or become harsh, triggering frequent throat clearing. Swallowing can become difficult and accompanied by painful cramping.Electrical sensors (EMG) inserted into affected muscle groups, while painful, can provide a definitive diagnosis by showing pulsating nerve signals being transmitted to the muscles even when they are at rest. The brain appears to signal portions of fibers within the affected muscle groups at a firing speed of about 10 Hz causing them to pulsate, tremble and contort. When called upon to perform an intentional activity, the muscles fatigue very quickly and some portions of the muscle groups do not respond (causing weakness) while other portions over-respond or become rigid (causing micro-tears under load). The symptoms worsen significantly with use, especially in the case of focal dystonia, and a "mirror effect" is often observed in other body parts: Use of the right hand may cause pain and cramping in that hand as well as in the other hand and legs that were not being used. Stress, anxiety, lack of sleep, sustained use and cold temperatures can worsen symptoms.Direct symptoms may be accompanied by secondary effects of the continuous muscle and brain activity, including disturbed sleep patterns, exhaustion, mood swings, mental stress, difficulty concentrating, blurred vision, digestive problems, and short temper. People with dystonia may also become depressed and find great difficulty adapting their activities and livelihood to a progressing disability. Side-effects from treatment and medications can also present challenges in normal activities.In some cases, symptoms may progress and then plateau for years, or stop progressing entirely. The progression may be delayed by treatment or adaptive lifestyle changes, while forced continued use may make symptoms progress more rapidly. In others, the symptoms may progress to total disability, making some of the more risky forms of treatment worth considering. In some cases with patients who already have dystonia, a subsequent traumatic injury or the effects of general anesthesia during an unrelated surgery can cause the symptoms to progress rapidly.An accurate diagnosis may be difficult because of the way the disorder manifests itself. Affected individuals may be diagnosed as having similar and perhaps related disorders including Parkinsons disease, essential tremor, carpal tunnel syndrome, temporomandibular joint disorder, Tourettes syndrome, conversion disorder or other neuromuscular movement disorders. It has been found that the prevalence of dystonia is high in individuals with Huntingtons disease, where the most common clinical presentations are internal shoulder rotation, sustained fist clenching, knee flexion, and foot inversion. Risk factors for increased dystonia in patients with Huntingtons disease include long disease duration and use of antidopaminergic medication. Causes Primary dystonia is suspected when the dystonia is the only sign and there is no identifiable cause or structural abnormality in the central nervous system. Researchers suspect it is caused by a pathology of the central nervous system, likely originating in those parts of the brain concerned with motor function—such as the basal ganglia and the GABA (gamma-aminobutyric acid) producing Purkinje neurons. The precise cause of primary dystonia is unknown. In many cases it may involve some genetic predisposition towards the disorder combined with environmental conditions.Secondary dystonia refers to dystonia brought on by some identified cause, such as head injury, drug side effect (e.g. tardive dystonia), or neurological disease (e.g. Wilsons disease, stroke).Meningitis and encephalitis caused by viral, bacterial, and fungal infections of the brain have been associated with dystonia. The main mechanism is inflammation of the blood vessels, causing restriction of blood flow to the basal ganglia. Other mechanisms include direct nerve injury by the organism or a toxin, or autoimmune mechanisms.Environmental and task-related factors are suspected to trigger the development of focal dystonias because they appear disproportionately in individuals who perform high precision hand movements such as musicians, engineers, architects, and artists. Chlorpromazine can also cause dystonia, which can be often misjudged as a seizure.Neuroleptic drugs often cause dystonia, including oculogyric crisis.Malfunction of the sodium-potassium pump may be a factor in some dystonias. The Na+-K+ pump has been shown to control and set the intrinsic activity mode of cerebellar Purkinje neurons. This suggests that the pump might not simply be a homeostatic, "housekeeping" molecule for ionic gradients; but could be a computational element in the cerebellum and the brain. Indeed, an ouabain block of Na+-K+ pumps in the cerebellum of a live mouse results in it displaying ataxia and dystonia. Ataxia is observed for lower ouabain concentrations, dystonia is observed at higher ouabain concentrations. A mutation in the Na+-K+ pump (ATP1A3 gene) can cause rapid onset dystonia parkinsonism. The parkinsonism aspect of this disease may be attributable to malfunctioning Na+-K+ pumps in the basal ganglia; the dystonia aspect may be attributable to malfunctioning Na+-K+ pumps in the cerebellum (that act to corrupt its input to the basal ganglia) possibly in Purkinje neurons.Cerebellum issues causing dystonia is described by Filip et al. 2013: "Although dystonia has traditionally been regarded as a basal ganglia dysfunction, recent provocative evidence has emerged of cerebellar involvement in the pathophysiology of this enigmatic disease. It has been suggested that the cerebellum plays an important role in dystonia etiology, from neuroanatomical research of complex networks showing that the cerebellum is connected to a wide range of other central nervous system structures involved in movement control to animal models indicating that signs of dystonia are due to cerebellum dysfunction and completely disappear after cerebellectomy, and finally to clinical observations in secondary dystonia patients with various types of cerebellar lesions. It is proposed that dystonia is a large-scale dysfunction, involving not only cortico-basal ganglia-thalamo-cortical pathways, but the cortico-ponto-cerebello-thalamo-cortical loop as well. Even in the absence of traditional "cerebellar signs" in most dystonia patients, there are more subtle indications of cerebellar dysfunction. It is clear that as long as the cerebellums role in dystonia genesis remains unexamined, it will be difficult to significantly improve the current standards of dystonia treatment or to provide curative treatment." Treatment Reducing the types of movements that trigger or worsen dystonic symptoms provides some relief, as does reducing stress, getting plenty of rest, moderate exercise, and relaxation techniques. Various treatments focus on sedating brain functions or blocking nerve communications with the muscles via drugs, neuro-suppression, or denervation. All current treatments have negative side-effects and risks. A geste antagoniste is a physical gesture or position (such as touching ones chin) that temporarily interrupts dystonia, it is also known as a sensory trick. Patients may be aware of the presence of a geste antagoniste that provides some relief. Therapy for dystonia can involve prosthetics that passively simulate the stimulation. Physical intervention While research in the area of effectiveness of physical therapy intervention for dystonia remains weak, there is reason to believe that rehabilitation can benefit dystonia patients. Physical therapy can be utilized to manage changes in balance, mobility and overall function that occur as a result of the disorder. A variety of treatment strategies can be employed to address the unique needs of each individual. Potential treatment interventions include splinting, therapeutic exercise, manual stretching, soft tissue and joint mobilization, postural training and bracing, neuromuscular electrical stimulation, constraint-induced movement therapy, activity and environmental modification, and gait training.A patient with dystonia may have significant challenges in activities of daily living (ADL), an area especially suited for treatment by occupational therapy (OT). An occupational therapist (OT) may perform needed upper extremity splinting, provide movement inhibitory techniques, train fine motor coordination, provide an assistive device, or teach alternative methods of activity performance to achieve a patients goals for bathing, dressing, toileting, and other valued activities.Recent research has investigated further into the role of physiotherapy in the treatment of dystonia. A recent study showed that reducing psychological stress, in conjunction with exercise, is beneficial for reducing truncal dystonia in patients with Parkinson’s disease. Another study emphasized progressive relaxation, isometric muscle endurance, dynamic strength, coordination, balance, and body perception, seeing significant improvements to patients quality of life after 4 weeks.Since the root of the problem is neurological, doctors have explored sensorimotor retraining activities to enable the brain to "rewire" itself and eliminate dystonic movements. The work of several doctors such as Nancy Byl and Joaquin Farias has shown that sensorimotor retraining activities and proprioceptive stimulation can induce neuroplasticity, making it possible for patients to recover substantial function that was lost due to Cervical Dystonia, hand dystonia, blepharospasm, oromandibular dystonia, dysphonia and musicians dystonia.Some focal dystonias have been proven treatable through movement retraining in the Taubman approach, particularly in the case of musicians. However other focal dystonias may not respond and may even be made worse by this treatment.Due to the rare and variable nature of dystonia, research investigating the effectiveness of these treatments is limited. There is no gold standard for physiotherapy rehabilitation. To date, focal cervical dystonia has received the most research attention; however, study designs are poorly controlled and limited to small sample sizes. Medication Different medications are tried in an effort to find a combination that is effective for a specific person. Not all people respond well to the same medications. Medications that have had positive results in some include: anticholinergics (such as diphenhydramine, benzatropine, atropine), dopamine agonists (such as ropinirole and bromocriptine), and muscle relaxants (such as diazepam). AnticholinergicsMedications such as anticholinergics (benztropine), which act as inhibitors of the neurotransmitter acetylcholine, may provide some relief. In the case of an acute dystonic reaction, diphenhydramine is sometimes used (though this drug is well known as an antihistamine, in this context it is being used primarily for its anticholinergic role).. See also Procyclidine. Another which in many has shown total control of symptoms, alone or taken with other medications,often clonazepam, is gabapentin. Noting, some are generic sensitive, as with other medications, and either have to sample test each one for a successful result, or take the original version. BaclofenA baclofen pump has been used to treat patients of all ages exhibiting muscle spasticity along with dystonia. The pump delivers baclofen via a catheter to the thecal space surrounding the spinal cord. The pump itself is placed in the abdomen. It can be refilled periodically by access through the skin. Baclofen can also be taken in tablet form Botulinum toxin injectionBotulinum toxin injections into affected muscles have proved quite successful in providing some relief for around 3–6 months, depending on the kind of dystonia. Botox or Dysport injections have the advantage of ready availability (the same form is used for cosmetic surgery) and the effects are not permanent. There is a risk of temporary paralysis of the muscles being injected or the leaking of the toxin into adjacent muscle groups, causing weakness or paralysis in them. The injections must be repeated, as the effects wear off and around 15% of recipients develop immunity to the toxin. There is a Type A and a Type B toxin approved for treatment of dystonia; often, those that develop resistance to Type A may be able to use Type B. Muscle relaxantsClonazepam, a benzodiazepine, is also sometimes prescribed. However, for most, their effects are limited and side-effects like mental confusion, sedation, mood swings, and short-term memory loss occur. Parkinsonian drugsDopamine agonists: One type of dystonia, dopamine-responsive dystonia, can be completely treated with regular doses of L-DOPA in a form such as Sinemet (carbidopa/levodopa). Although this does not remove the condition, it does alleviate the symptoms most of the time. (In contrast, dopamine antagonists can sometimes cause dystonia.)Ketogenic diet One complex case study found that a ketogenic type diet may have been helpful in reducing symptoms associated with alternating hemiplegia of childhood (AHC) of a young child. However, as the researchers noted, their results could have been corollary in nature and not due to the diet itself, though future research is warranted. Surgery Surgery, such as the denervation of selected muscles, may also provide some relief; however, the destruction of nerves in the limbs or brain is not reversible and should be considered only in the most extreme cases. Recently, the procedure of deep brain stimulation (DBS) has proven successful in a number of cases of severe generalised dystonia. DBS as treatment for medication-refractory dystonia, on the other hand, may increase the risk of suicide in patients. However, reference data of patients without DBS therapy are lacking. History The Italian Bernardino Ramazzini provided one of the first descriptions of task-specific dystonia in 1713 in a book of occupational diseases, The Morbis Artificum. In chapter II of this books Supplementum, Ramazzini noted that "Scribes and Notaries" may develop "incessant movement of the hand, always in the same direction … the continuous and almost tonic strain on the muscles... that results in failure of power in the right hand". A report from the British Civil Service also contained an early description of writers cramp. In 1864, Solly coined the term "scrivener’s palsy" for this condition. These historical reports usually attributed the etiology of the motor abnormalities to overuse. Then, dystonia were reported in detail in 1911, when Hermann Oppenheim, Edward Flatau and Wladyslaw Sterling described some Jewish children affected by a syndrome that was retrospectively considered to represent familial cases of DYT1 dystonia. Some decades later, in 1975, the first international conference on dystonia was held in New York. It was then recognized that, in addition to severe generalized forms, the dystonia phenotype also encompasses poorly-progressive focal and segmental cases with onset in adulthood, such as blepharospasm, torticollis and writers cramp. These forms were previously considered independent disorders and were mainly classified among neuroses. A modern definition of dystonia was worded some years later, in 1984. During the following years it became evident that dystonia syndromes are numerous and diversified, new terminological descriptors (e.g., dystonia plus, heredodegenerative dystonias, etc.) and additional classification schemes were introduced. The clinical complexity of dystonia was then fully recognized. See also References External links A Boston Marathon record is about to be set – by a man with a movement disorder in The Washington Post GeneReview/NIH/UW entry on Dystonia Overview GeneReviews/NCBI/NIH/UW entry on Early-Onset Primary Dystonia Film on Dystonia from Public Broadcasting Service A story of one womans struggle with dystonia at MSNBC.com

Scimitar syndrome

Scimitar syndrome, or congenital pulmonary venolobar syndrome, is a rare congenital heart defect characterized by anomalous venous return from the right lung (to the systemic venous drainage, rather than directly to the left atrium). This anomalous pulmonary venous return can be either partial (PAPVR) or total (TAPVR). The syndrome associated with PAPVR is more commonly known as Scimitar syndrome after the curvilinear pattern created on a chest radiograph by the pulmonary veins that drain to the inferior vena cava. This radiographic density often has the shape of a scimitar, a type of curved sword. The syndrome was first described by Catherine Neill in 1960. Presentation The anomalous venous return forms a curved shadow on chest x-ray such that it resembles a scimitar. This is called the Scimitar Sign. Associated abnormalities include right lung hypoplasia with associated dextroposition of the heart, pulmonary artery hypoplasia and pulmonary sequestration. Incidence is around 1 per 100,000 births. Diagnosis The diagnosis is made by transthoracic or transesophageal echocardiography and selective pulmonary angiography. More recently by CT angiography or MR Angiography.Pulmonary angiography demonstrates anomalous arterial supply to right lower lobe. Treatment Surgical correction should be considered in the presence of significant left to right shunting (Qp:Qs ≥ 2:1) and pulmonary hypertension. This involves creation of an inter-atrial baffle to redirect the pulmonary venous return into the left atrium. Alternatively, the anomalous vein can be re-implanted directly into the left atrium. History Scimitar syndrome was first described by George Cooper and Raoul Chassinat in 1836 regarding a rare syndrome that has an abnormal pulmonary vein that drains into inferior vena cava below the diaphgram instead of draining into the left atrium. References Further reading == External links ==

Melioidosis

Melioidosis is an infectious disease caused by a gram-negative bacterium called Burkholderia pseudomallei. Most people exposed to B. pseudomallei experience no symptoms; however, those who do experience symptoms have signs and symptoms that range from mild such as fever and skin changes, to severe with pneumonia, abscesses, and septic shock that could cause death. Approximately 10% of people with melioidosis develop symptoms that last longer than two months, termed "chronic melioidosis".Humans are infected with B. pseudomallei by contact with contaminated soil or water. The bacteria enter the body through wounds, inhalation, or ingestion. Person-to-person or animal-to-human transmission is extremely rare. The infection is constantly present in Southeast Asia particularly in northeast Thailand and northern Australia. In temperate countries such as Europe and the United States, melioidosis cases are usually imported from countries where melioidosis is endemic. The signs and symptoms of melioidosis resemble tuberculosis and misdiagnosis is common. Diagnosis is usually confirmed by the growth of B. pseudomallei from an infected persons blood or other bodily fluid such as pus, sputum, and urine. Those with melioidosis are treated first with an "intensive phase" course of intravenous antibiotics (most commonly ceftazidime) followed by a several-months treatment course of co-trimoxazole. In countries with the advanced healthcare system, approximately 10% of people with melioidosis die from the disease. In less developed countries, the death rate could reach 40%.Efforts to prevent melioidosis include: wearing protective gear while handling contaminated water or soil, practising hand hygiene, drinking boiled water, and avoiding direct contact with soil, water, or heavy rain. There is little evidence in supporting the use of melioidosis prophylaxis in humans. The antibiotic co-trimoxazole is used as a preventative only for individuals at high risk for getting the disease after being exposed to the bacteria in laboratory settings. One study conducted in 2018 determined that the drug could be useful in preventing melioidosis in high-risk renal failure patients undergoing haemodylysis. There is no approved vaccine for melioidosis.Approximately 165,000 people are infected by melioidosis per year, resulting in about 89,000 deaths, based on a mathematical model published in 2016. Diabetes is a major risk factor for melioidosis; over half of melioidosis cases are in people with diabetes. Increased rainfall and severe weather events such as thunderstorm are associated with an increased number of melioidosis cases in endemic areas. Signs and symptoms Acute Most people exposed to B. pseudomallei experience no symptoms. The mean incubation period of acute melioidosis is 9 days (range 1–21 days). Nevertheless, symptoms of melioidosis can appear in 24 hours for those who experienced near drowning in water. Those affected present with symptoms of sepsis (predominantly fever) with or without pneumonia, or localised abscess or other focus of infection. The presence of non-specific signs and symptoms has caused melioidosis to be nicknamed "the great mimicker".Diabetes mellitus is one of the most important risk factors in developing melioidosis. The disease should be considered in anyone who has spent time in endemic areas who develops a fever, pneumonia, or abscesses in their liver, spleen, prostate, or parotid gland. The clinical manifestation of the disease can range from simple skin changes such as abscesses or ulcerations to severe organ problems. The commonest organs affected are liver, spleen, lungs, prostate, and kidneys. Among the most common features are bacteremia (in 40 to 60% of cases), pneumonia (50%), and septic shock (20%). People with only pneumonia may have a prominent cough with sputum and shortness of breath. However, those with septic shock together with pneumonia may have minimal coughing. Results of a chest X-ray can range from diffuse nodular infiltrates in those with septic shock to progressive consolidation located most commonly in the upper lobes for those with pneumonia only. Pleural effusion and empyema are more common for melioidosis affecting lower lobes of the lungs. In 10% of cases, people develop secondary pneumonia caused by other bacteria after the primary infection. In northern Australia, 60% of the infected children presented with only skin lesions, while 20% presented with pneumonia.Depending on the course of infection, other severe manifestations develop. Approximately 1 to 5% of those infected develop inflammation of the brain and brain covering or brain abscess; 14 to 28% develop pyelonephritis, kidney abscess or prostatic abscesses; 0 to 30% develop neck or salivary gland abscesses; 10 to 33% develop liver, spleen, or paraintestinal abscesses; and 4 to 14% develop septic arthritis and osteomyelitis. Rare manifestations include lymph node disease resembling tuberculosis, mediastinal masses, pericardial effusion, mycotic aneurysm, and inflammation of the pancreas. In Australia, up to 20% of infected males develop prostatic abscess which may manifests clinically as pain during urination, difficulty in passing urine, and urinary retention requiring catheterisation. Rectal examination may find enlarged prostate. In Thailand, 30% of the infected children develop parotid abscesses. Encephalomyelitis not only happens in those with risk factors, but can also occur in healthy people without risk factors. Those with melioidosis encephomyelitis tend to have normal computed tomography (CT) scans but increased T2 signal by magnetic resonance imaging (MRI), extending to the brain stem and spinal cord. Clinical signs include: unilateral upper motor neuron limb weakness, cerebellar signs, and cranial nerve palsies (VI, VII nerve palsies and bulbar palsy). Some cases presented with flaccid paralysis alone. In northern Australia, all melioidosis with encephalomyelitis cases had elevated white cells in the cerebrospinal fluid (CSF), mostly mononuclear cells with elevated CSF protein. Chronic Chronic melioidosis is usually defined by symptoms lasting greater than two months and occurs in about 10% of patients. Clinical presentations include fever, weight loss, productive cough with or without bloody sputum which may mimic tuberculosis. Additionally, long-standing abscesses at multiple body sites may also present. Tuberculosis should be considered for lymph nodes enlargement at the root of the lung. Additionally, pneumonia caused by melioidosis rarely causes scarring and calcification of the lungs, unlike tuberculosis. Latent The potential for prolonged incubation was recognized in US servicemen involved in the Vietnam War, and was referred to as the "Vietnam time-bomb". Initially, it was thought that the longest period between presumed exposure and clinical presentation is 62 years in a prisoner of war in Burma-Thailand-Malaysia. However, subsequent genotyping of the bacteria isolate from the Vietnam veteran showed that the isolate may not come from Southeast Asia, but from South America. This reinstates another report that put the longest latency period for melioidosis as 29 years. Patients with latent melioidosis may be symptom-free for decades. Less than 5% of all melioidosis cases have activation after a period of latency. Various comorbidities such as diabetes, renal failure, and alcoholism can predispose to reactivation of melioidosis. Cause Bacteria Melioidosis is caused by gram-negative, motile, saprophytic bacteria named Burkholderia pseudomallei. The bacteria are usually opportunistic, facultative intracellular pathogens. It is also aerobic and oxidase test positive. A granule at the centre of the bacterium makes it resemble a "safety pin" when Gram stained. The bacteria emit a strong soil smell after 24 to 48 hours of growth in culture, however smelling for the identification of the bacteria is not recommended for routine laboratory practice. One of the factors causing B. pseudomalleis resistance to various kinds of antibiotics is because of its production of a glycocalyx polysaccharide capsule. It is generally resistant to gentamicin and colistin but sensitive to co-amoxiclav. B. pseudomallei is a biosafety level 3 pathogen which requires specialized laboratory handling. In humans and animals, another similar organism named Burkholderia mallei is the causative agent of the disease glanders. B. pseudomallei can be differentiated from another closely related, but less pathogenic species B. thailandensis by its ability to assimilate arabinose. B. pseudomallei is highly adaptable to various host environments ranging from inside mycorrhizal fungi spores to amoeba. Its adaptability may give it a survival advantage in the human body.The genome of B. pseudomallei consists of two replicons: chromosome 1 encodes housekeeping functions of the bacteria such as cell wall synthesis, mobility, and metabolism; chromosome 2 encodes functions that allow the bacteria to adapt to various environments. Horizontal gene transfer has resulted in highly variable genomes in B. pseudomallei. Australia has been suggested as the origin for B. pseudomallei because of the high genetic variability of the bacteria found in this region. Bacteria that was introduced to Central and South America in the 17th to 19th centuries seem to have a common ancestor from Africa. B. mallei is a clone of B. pseudomallei that has lost substantial portions of its genome as it adapted to live exclusively in mammals. This makes the B. mallei genome much smaller than B. pseudomallei. Transmission B. pseudomallei is normally found in soil and surface water, and is most abundant at soil depths of 10 to 90 cm. It has been found in soils, ponds, streams, pools, stagnant water, and rice paddy fields. B. pseudomallei can survive in nutrient-poor conditions such as distilled water, desert soil, and nutrient-depleted soil for more than 16 years. It can also survive in antiseptic and detergent solutions, acidic environments (pH 4.5 for 70 days), and in environments at temperatures ranging from 24 °C (75.2 °F) to 32 °C (89.6 °F). However, the bacteria may be killed by the presence of ultraviolet light.Bacteria can enter the body through wounds, inhalation, and ingestion of contaminated soil or water. Person-to-person transmission is extremely rare. Melioidosis is a recognised disease in animals including pigs, cats, dogs, goats, sheep, horses and others. Cattle, water buffalo, and crocodiles are considered to be relatively resistant to melioidosis despite their constant exposure to mud. Birds are also considered resistant to melioidosis although several cases had been reported in Australia and aquatic birds. Transmission from animals to humans is rare.Inadequate chlorination of water supply has been associated with B. pseudomallei outbreak in Northern and Western Australia. The were also several cases of where bacteria have also been found in unchlorinated water supply in rural Thailand. Based on the whole genome sequencing of the bacteria, the variety of the bacteria B. pseudomallei in Papua New Guinea is narrow due to limited movements of the indigenous people. This findings supports the hypothesis that humans play an important role in bacterial transmission. Pathogenesis B. pseudomallei has the ability to infect various types of cells and to evade human immune responses. Bacteria first enter at a break in the skin or mucous membrane and replicate in the epithelial cells. From there, they use flagellar motility to spread and infect various cell types. In the bloodstream, the bacteria can infect both phagocytes and non-phagocytes. B. pseudomallei use their flagella to move near host cells, then attach to the cells using various adhesion proteins, including the type IV pilus protein PilA as well as adhesion proteins BoaA and BoaB. Additionally, adhesion of the bacteria partially depends on the presence of the host protein Protease-activated receptor-1 which is present on the surface of endothelial cells, platelets, and monocytes. Once bound, the bacteria enter host cells through endocytosis, ending up inside an endocytic vesicle. As the vesicle acidifies, B. pseudomallei uses its Type 3 secretion system (T3SS) to inject effector proteins into the host cell, disrupting the vesicle and allowing the bacteria to escape into the host cytoplasm. Within the host cytoplasm, the bacteria evade being killed by the host autophagy using various T3SS effector proteins. The bacteria replicate in the host cytoplasm.Inside the host cell, the bacteria move by inducing the polymerization of the host actin behind them, propelling the bacteria forward. This actin-mediated motility is accomplished with the autotransporter BimA which interacts with actin at the tail-end of the bacterium. The bacteria that has BimABm allele has higher possibility of causing neurological melioidosis, thus higher chance of death and residual disability to the host when compared to the bacteria that has BimABp variant. Propelled by actin, the bacteria push against the host membrane, creating protrusions that extend into neighbouring cells. These protrusions cause neighboring cells to fuse, leading to the formation of multinucleated giant cells (MNGCs). When MNGCs lyse, they form plaques (a central clear area with a ring of fused cells) that provide shelter for the bacteria for further replication or latent infection. This same process in infected neurons can allow bacteria to travel through nerve roots in the spinal cord and brain, leading to inflammation of the brain and spinal cord. In addition to spreading from cell to cell, the bacteria can also spread through the bloodstream, causing sepsis. The bacteria can survive in antigen-presenting cells and dendritic cells. Thus, these cells act as vehicles that transport the bacteria into the lymphatic system, causing widespread dissemination of the bacteria in the human body.While B. pseudomallei can survive in phagocytic cells, these cells can kill B. pseudomallei by several mechanisms. Macrophages activated by interferon gamma (IFN) have improved the killing of B. pseudomallei via the production of inducible nitric oxide synthase. Acidification of the endosome and degradation of the bacteria is also possible, however, the bacterial capsule and LPS makes B. pseudomallei resistant to lysosomal degradation. Once B. pseudomallei escapes into the host cytosol it can be recognized by pattern recognition receptors such as NOD-like receptors, triggering the formation of the inflammasome and activation of caspase 1, which induces death of the host cell by pyroptosis and further activation of the immune system. Several systemic host defenses also contribute to the immune response. B. pseudomallei triggers both the complement system and coagulation cascade, however the thick bacterial capsule prevent the action of the complement membrane attack complex.Additional elements of the immune system are activated by the host toll-like receptors such as TLR2, TLR4, and TLR5 that recognize the conserved pieces of the bacteria such as LPS and flagella. This activation results in the production of cytokines such as Interleukin 1 beta (IL-1β) and Interleukin 18 (IL-18). IL-18 increases IFN production through natural killer cells while IL-1beta reduces the IFN production. These immune molecules drive the recruitment of other immune cells such as neutrophils, dendritic cells, B cells, and T cells to the site of infection. T cells seem to be particularly important for controlling B. pseudomallei; T cell numbers are increased in survivors, and low T cell numbers are associated with a high risk of death from melioidosis. Despite this, HIV infection is not a risk factor for melioidosis. Although macrophages show deregulated cytokine responses in individuals with HIV infection, bacterial internalization and intracellular killing are still effective. People infected with B. pseudomallei may develop antibodies against the bacteria, and people that live in endemic areas tend to have antibodies in their blood that recognize B. pseudomallei. However, the effectiveness of these antibodies at preventing melioidosis is unclear.B. pseudomallei can remain latent in the human body for up to 29 years until it is reactivated during human immunosuppression or stress response. However, the site of bacteria during latent infection and the mechanism by which they avoid immune recognition for years are both unclear. Amongst mechanisms suggested are: residing in the nucleus of the cell to prevent being digested, entering a stage of slower growth, antibiotic resistance, and genetic adaption to the host environment. Granulomas (containing neutrophils, macrophages, lymphocytes, and multinucleated giant cells) formed at the infection site in melioidosis have been associated with latent infection in humans. Diagnosis Culture Bacterial culture has 60% sensitivity in diagnosing melioidosis. B. pseudomallei is never part of human flora. Therefore, any growth of the bacteria is diagnostic of melioidosis. Other samples such as throat, rectal swabs, pus from abscesses, and sputum can also be used for culture. However, culture from CSF is difficult because in one case series, only 29% of the neuromelioidosis cases are culture positive. When bacteria do not grow from people strongly suspected of having melioidosis, repeated cultures should be taken as subsequent cultures can become positive. B. pseudomallei can be grown on any blood agar, MacConkey agar, and agar containing antibiotics such as Ashdowns medium (containing gentamicin), and Ashdowns broth (containing colistin) for better isolation of B. pseudomallei from other types of bacteria. Agar plates for melioidosis should be incubated at 37 °C (98.6 °F) in air and inspected daily for four days. On the agar plates, B. pseudomallei forms creamy, non-haemolytic, colonies after 2 days of incubation. After 4 days of incubation, colonies appear dry and wrinkled. Colonies of B. pseudomallei that are grown on Francis medium (a modification of Ashdown medium with gentamicin concentration increased to 8 mg/L and neutral red indicator replaced with 0.2% bromocresol purple) are yellow. For laboratories located outside endemic areas, Burkholderia cepacia selective agar can be used if Ashdowns medium is not available. It is important not misinterpret the bacterial growth as Pseudomonas or Bacillus spp. Other biochemical screening tools can also be used for detecting B. pseudomallei, including the API 20NE or 20E biochemical kit combined with Gram stain, oxidase test, typical growth characteristics, and resistance to certain antibiotics of the bacteria. API 20NE biochemical kit is 99% sensitive in identifying B. pseudomallei.Molecular methods such as 16S rDNA sequencing, multiplex polymerase chain reaction (PCR), and real-time PCR can also be used to identify B. pseudomallei in culture. Other bacterial genes such as fliC genes encoding flagellin, rpsU gene encoding for ribosomal protein, and TTS genes encoding Type III secretion systems has also been employed for detection. Another method of gene detection namely multiple cross displacement amplification for the bacterial TTS1 gene detection produces results within an hour. Hematological and biochemical tests General blood tests in people with melioidosis show low white blood cell counts (indicates infection), raised liver enzymes, increased bilirubin levels (indicates liver dysfunction), and raised urea and creatinine levels (indicates kidney dysfunction). Low blood glucose and acidosis predicts a poorer prognosis in those with melioidosis. However, other tests such as C-reactive protein and procalcitonin levels are not reliable in predicting the severity of melioidosis infection. Serological tests Serological tests such as indirect haemagglutination assay (IHA) have been used to detect the presence of antibodies against B. pseudomallei. However, different groups of people have widely different levels of antibodies, so interpretation of these tests depends on location. In Australia, less than 5% of people have B. pseudomallei antibodies, so the presence of even relatively low amounts of antibody is unusual and could suggest melioidosis. In Thailand, many people have antibodies against B. pseudomallei so the diagnosis of melioidosis should not be reliant entirely on the serological tests done in endemic areas. Indirect immunofluorescent test (IFAT) uses either B. pseudomallei or B. thailandensis antigens to look for the total number of antibodies in human serum. Using IFAT is labour intensive and is not used in large scale investigations.Antigen detect tests allow rapid detection of melioidosis. Examples of antigen detection tests are: latex agglutination test and ELISA. Latex agglutination uses antibodies coated on latex beads to detect B. pseudomallei antigens in solid or liquid media, although not all the assays can detect different species of Burkholderia. Latex agglutination is useful in screening for suspected B. pseudomallei colonies. IgG and IgM ELISAs has been used to detect lipopolysaccharide (LPS) antigens of B. pseudomallei, but plagued with low sensitivity. Commercial ELISA kits for melioidosis no longer available in the market due to low sensitivity to human antibodies detection. Nevertheless, antigen detection tests may be useful in severely ill patients because the bacterial load is high enough for detection. Other methods of antigen detection such as direct immunofluorescence, antibody-sandwich ELISAs, and lateral flow immunoassays using monoclonal antibody. Microscopy By microscopy, B. pseudomallei is seen as gram-negative and rod-shaped, with a bipolar staining similar in appearance to a safety pin. Bacteria can sometimes be seen directly in clinical samples from infected people; however, identification by light microscopy is neither specific nor sensitive. Immunofluorescence microscopy is highly specific for detecting bacteria directly from clinical specimens, but has less than 50% sensitivity. Imaging Various imaging modalities can also help with the diagnosis of melioidosis. In acute melioidosis with the spreading of the bacteria through the bloodstream, the chest X-ray shows multifocal nodular lesions. It may also show merging nodules or cavitations. For those with acute melioidosis without the spread to the bloodstream, chest x-ray most commonly shows upper lobe consolidation or cavitations. In chronic melioidosis, the slowly progressing of upper lobe consolidation of the lungs resembles tuberculosis. For abscesses located in other parts of the body apart from the lungs, especially in the liver and spleen, CT scan has higher sensitivity when compared with an ultrasound scan. In liver and splenic abscesses, an ultrasound scan shows "target-like" lesions while CT scan shows "honeycomb sign" (abscess with loculations separated by thin septa) in liver abscesses. For melioidosis involving the brain, MRI have higher sensitivity than a CT scan in diagnosing the lesion. MRI shows ring-enhancing lesions for brain melioidosis. Prevention Melioidosis is a notifiable disease in Australia which enables the country to monitor disease burden and contain outbreaks. On the other hand, melioidosis is only a notifiable condition in Thailand since June 2016. However, until recently, the official notification system in Thailand has significantly underestimated the incidence of culture-positive melioidosis and its mortality. Nevertheless, Australia also embarked on awareness campaigns to increase the communitys understanding of the disease. In the United Kingdom, where reporting by laboratories is mandatory, 41.3% of cases imported since 2010 were not notified. In the United States, lab workers can handle clinical specimens of B. pseudomallei under BSL-2 conditions, while mass production of such organisms requires BSL-3 precautions. On the other hand, in other endemic areas where the B. pseudomallei samples were handled less stringently, there has been no confirmed laboratory-acquired infection reported. This phenomenon may show that the risk of infection with B. pseudomallei is less than a typical biohazard type 3 agent. There are also several cases of hospital-acquired infection of melioidosis. Therefore, healthcare providers are recommended to practice hand hygiene and universal precautions.Large-scale water chlorination has been successful at reducing B. pseudomallei in the water in Australia. In middle to low-income countries, water should be boiled before consumption. In high income countries, water could be treated with ultraviolet light for those at risk of contracting melioidosis. Those who are at high risk of contact with the bacteria should wear protective gear (such as boots and gloves) during work. Those staying in endemic areas should avoid direct contact with soil, and outdoor exposure to heavy rain or dust clouds. Bottled water or boiled water are preferred as drinking water. A study conducted from 2014 to 2018, however showed no significant differences on whether behavioural changes can reduce the risk of contracting melioidosis. Modification of behavioural changes or more frequent interventions may be needed to ensure a definite reduction in risk of getting melioidosis. Antibiotic prophylaxis Administering cotrimoxazole three times a week throughout a wet season for dialysis patients has no obvious benefit of preventing melioidosis. Besides, high cost and side effects of this drug limits its use to only those with high risk of getting melioidosis. After exposure to B. pseudomallei (particularly following a laboratory accident, penetrating injuries, exposure of mouth and eyes to contaminated materials or aerosols), treatment with antibiotics is only given when in highly selected individuals after weighing the risk of adverse effects of the drugs against the benefits from contracting melioidosis. Cotrimoxazole can be used in this context. Alternatively, co-amoxiclav and doxycycline can be used for those who are intolerant to co-trimoxazole. Low-risk individuals would receive frequent monitoring instead. Vaccination Several vaccine candidates have been tested in animal models. Nevertheless, no vaccine candidates have been tried in humans. Major hurdles of the vaccines are limited efficacy in animal models, establishing the best method of vaccine administration in humans and logistical and financial issues in establishing human trials in endemic areas. Treatment The treatment of melioidosis is divided into two stages: an intravenous intensive phase and an eradication phase to prevent recurrence. The choice of antibiotics depends upon the susceptibility of the bacteria to various antibiotics. B. pesudomallei are generally susceptible to ceftazidime, meropenem, imipenem, and co-amoxiclav. These drugs generally kill bacteria. B. pseudomallei is also susceptible to doyxcycline, chloramphenicol, and co-trimoxazole. These drugs generally inhibit the growth of the bacteria. However, the bacteria are resistant to penicillin, ampicillin, 1st and 2nd generation cephalosporin, gentamicin, streptomycin, tobramycin, macrolides, and polymyxins. On the other hand, 86% of the B. pseudomallei isolates from the region of Sarawak, Malaysia are susceptible to gentamicin and this has not been found elsewhere in other parts of the world.Prior to 1989, the standard treatment for acute melioidosis was a three-drug combination of chloramphenicol, co-trimoxazole and doxycycline; this regimen is associated with a mortality rate of 80% and is no longer used unless no other alternatives are available. All three drugs are bacteriostatic (they stop the bacterium from growing, but do not kill it) and the action of co-trimoxazole antagonizes both chloramphenicol and doxycycline. Intensive phase Intravenous ceftazidime is the current drug of choice for treatment of acute melioidosis and should be administered for at least 10 to 14 days. Meropenem, imipenem and the cefoperazone-sulbactam combination (Sulperazone) are also effective. Intravenous amoxicillin-clavulanate (co-amoxiclav) may be used if none of the above four drugs is available; co-amoxiclav prevents death from melioidosis as well as ceftazidime. Co-amoxiclav is also used if patient has allergy towards sulfonamide, unable to tolerate co-trimaxazole, in pregnant patients or in children. High dose of co-amoxiclav (20 mg/kg for amoxicillin and 5 mg/kg for clavulanate) is recommended to prevent treatment failures. Intravenous antibiotics are given for a minimum of 10 to 14 days. The median fever clearance time in melioidosis is 9 days. The treatment duration is in accordance with Darwin melioidosis treatment guidelines where there is low rate of recrudescence and relapse.Meropenem is the preferred antibiotic therapy for neurological melioidosis and those with septic shock admitted into intensive care units. Co-trimoxazole is recommended in addition to ceftazidime for neurological melioidosis, osteomyelitis, septic arthritis, skin and gastrointestinal infection, and deeply seated abscess. For deep-seated infections such as abscesses of internal organs, osteomyelitis, septic arthritis, and neurological melioidosis, the duration of antibiotics given should be longer (up to 4 to 8 weeks). The time taken for the fever to be resolved can be more than 10 days in those with deep-seated infection. According to the 2020 Revised Royal Darwin Hospital Guideline, the dosage for intravenous ceftazidime is 2g 6-hourly in adults (50 mg/kg up to 2g in children less than 15 years old). The dosage for meropenem is 1g 8-hourly in adults (25 mg/kg up to 1g in children). Acquired resistance to ceftazidime, carbapenems, and co-amoxiclav is rare in the intensive phase but resistance to cotrimoxazole during eradication therapy is technically difficult to assess. There are no differences between using cefoperazone/sulbactam or ceftazidime to treat melioidosis as both shows similar death rates and disease progression following treatment. However, data are lacking to recommend cefoperazone/sulbactam usage. For those with kidney impairment, the dosage of ceftazidime, meropenem, and co-trimoxazole should be lowered. Once the clinical condition improved, meropenem can be switched back to ceftazidime. Eradication phase Following the treatment of the acute disease, eradication treatment with co-trimoxazole is the drug of choice and should be used for 3 months (12 weeks) as all-cause mortality was lower in 12 weeks group when compared to those receiving treatment for 20 weeks. For those with neurological melioidosis and osteomyelitis, drugs should be given for more than 6 months. Co-amoxiclav and doxycycline are drugs of second choice. Co-trimoxazole should not be used in those with glucose-6-phosphate dehydrogenase deficiency as it can cause haemolytic anemia. However, in Thailand, usage of co-trimoxazole does not accompany G6PD screening. Other side effects such as rash, hyperkalemia, renal dysfunction, and gastrointestinal symptoms should prompt the reduction of co-trimoxazole doses. Chloramphenicol is no longer routinely recommended for this purpose. Co-amoxiclav is an alternative for patients unable to take co-trimoxazole and doxycycline (e.g. pregnant women and children under the age of 12), but is not as effective and has a higher relapse rate. Single-agent treatment with fluoroquinolone (e.g., ciprofloxacin) or doxycycline for the oral eradication phase is ineffective.In Australia, co-trimoxazole is used with children and pregnant mothers after the first 12 weeks of pregnancy. Meanwhile, in Thailand, co-amoxiclav is the drug of choice for children and pregnant women. B. pseudomallei rarely acquires resistance when co-amoxiclav is used. The dosing regimen for co-trimoxazole (trimethoprim/sulfamethoxazole) in eradication phase is 6/30 mg/kg, up to maximum 240/1200 mg in children, 240/1200 mg in adults weighing 40 to 60 kg, and 320/1600 mg in adults weighing more than 60 kg, taken orally every 12 hours. In both Thailand and Australia, co-trimoxazole is taken together with folic acid (0.1 mg/kg up to 5 mg in children). There are also cases where melioidosis is successfully treated with co-trimoxazole for 3 months without going through intensive therapy provided that there is only skin manifestations without the involvement of internal organs or sepsis. Resistance to cotrimoxazole is rare in Asia. Besides that, it is difficult to determine the resistance reliably because resistance to cotrimoxazole is defined when minimum inhibitory concentration (MIC) of more than 4 mg/L is required to completely inhibit the growth of 80% of the bacteria (80% inhibition point). Interpretation of 80% inhibition point is subjective and prone to human error. In 2021, European Committee on Antimicrobial Susceptibility Testing (EUCAST) released a new guideline on interpreting the susceptibility of B pseudomallei towards various antibiotics on disc susceptibility testing. The new guideline includes "S" for susceptible organism, "I" for susceptible organism only after increased exposure (when dosage or concentration of the drug increases) and "R" for resistant organism. Surgery Surgical drainage is indicated for single, large abscesses in the liver, muscle, and prostate. However, for multiple abscesses in the liver, spleen, and kidney, surgical drainage may not be possible or necessary. For septic arthritis, arthrotomy washout and drainage are required. Surgical debridement may be necessary. For those with mycotic aneurysm, urgent surgery is required for prosthetic vascular grafts. Lifelong therapy with co-trimoxazole may be needed for those with prosthetic vascular grafts according to a review of case reports in 2005. Other abscesses rarely need to be drained because most resolve with antibiotic treatment. Prostate abscess may require routine imaging. Antibiotics treatment for prostatic abscess may be enough except for abscesses more than 10 to 15 mm where surgical drainage is required. Others Several immunomodulating therapies are suggested to boost the human body immune function against the bacteria because the pathogenesis of melioidosis is thought to be contributed by defects in neutrophils. The Royal Darwin Hospital 2014 guidelines recommended granulocyte colony-stimulating factor (G-CSF) as immunomodulating therapy for those with septic shock at 300 ug daily as soon as the bacteriological laboratory flag the culture as possibly Burkholderia pseudomallei. The main contraindication of starting (G-CSF) is a heart event. The G-CSF is continued for ten days depends on clinical response or a contraindication develops such as white cell count greater than >50,000 X106/litre.Anti-PDI (programmed cell death) agents could be useful in melioidosis treatment especially for those with septic shock. This is because Burkholderia pseudomallei bacteria increases the expression of PDI-1 that regulates and inhibits the formation of T-cells that are essential for fighting against melioidosis. Prognosis In well-resourced settings, where the disease can be detected and treated early, the risk of death is 10%. In resource-poor settings, the risk of death from the disease is more than 40%.Recurrent melioidosis can occur either due to re-infection or relapse after the completion of eradication therapy. Re-infection is due to a new strain of B. pseudomallei bacteria. Meanwhile, relapse is due to failure to clear infections after the eradication therapy. Recurrent melioidosis is rare since 2014 due to improved antibiotic therapy and prolongation of the intensive phase of therapy as evident in Darwin Prospective Melioidosis Study. On the other hand, recrudescence are those who present with symptoms during the eradication therapy. Recrudescence rates may be improved by ensuring adherence to a full course of eradication therapy e.g. by reducing self-discharge against medical advice.Underlying medical conditions such as diabetes mellitus, chronic kidney disease, and cancer can worsen the long-term survival and disability of those who recover from infection. One of the complications of melioidosis is encephalomyelitis. It can cause quadriparesis (muscle weakness in all the limbs), partial flaccid paraparesis (muscle weakness of both legs), or foot drop. For those with previous melioidosis-associated bone and joint infections, complications such as sinus tract infection, bone and joint deformities with limited range of motion can occur. Epidemiology Melioidosis is an understudied disease that remains endemic in developing countries. In 2015, the International Melioidosis Society was formed to raise awareness of the disease. In 2016, a statistical model was developed which predicted that the number is 165,000 cases per year with 138,000 of those occurring in East and South Asia and the Pacific. In approximately half of those cases (54% or 89,000), people will die. Under-reporting is a common problem as only 1,300 cases were reported worldwide since 2010, which is less than 1% of the projected incidence based on the modelling. Lack of laboratory diagnostic capabilities and lack of disease awareness amongst health care providers also causes under diagnosis. Even if bacterial cultures show positive result for B. pesudomallei, they can be discarded as contaminants especially in laboratories in non-endemic areas. In 2015, it was estimated that the yearly disability-adjusted life year (DALY) was 84.3 per 100,000 people. As of 2022, melioidosis is not included in the WHO list of neglected tropical diseases. Geography Melioidosis is endemic in parts of southeast Asia (including Thailand, Laos, Singapore, Brunei, Malaysia, Myanmar and Vietnam), southern China, Taiwan northern Australia. India, and South America. Since 1991, a total of 583 cases were reported in India. Most Indian cases are located in Karnataka and Tamil Nadu. Fifty-one cases of melioidosis were reported in Bangladesh from 1961–2017. Nonetheless, lack of awareness and resources gives rise to under diagnosis of the disease in the country. The true burden of melioidosis in Africa and Middle East remain unknown due to low amount of data. Several melioidosis cases were reported over the years. Although 24 African countries and three Middle Eastern countries predicted to be endemic with melioidosis, however not a single case was reported from these specific countries. In the United States, two historical cases (1950 and 1971) and four recent cases (2010, 2011, 2013, 2020) have been reported amongst people that did not travel overseas. Despite extensive investigations, the source of melioidosis was never confirmed. One possible explanation is that importation of medicinal plant products or exotic reptiles could have resulted in the introduction of melioidosis in the United States. In 2021, there was a melioidosis outbreak in several states in the United States due to usage of contaminated aromatherapy spray imported from India. There are also cases of infection through imported tropical fishes in home aquariums. In Europe, more than half of the melioidosis cases are imported from Thailand. Age, risk factors Melioidosis is found in all age groups. For Australia and Thailand, the median age of infection is at 50 years; 5 to 10% of the patients are under 15 years. The single most important risk factor for developing melioidosis is diabetes mellitus, followed by hazardous alcohol use, chronic kidney disease, and chronic lung disease. More than 50% of people with melioidosis have diabetes; diabetics have a 12-fold increased risk of contracting melioidosis. Diabetes decreases the ability of macrophages to fight the bacteria and reduced the T helper cell production. Excessive release of Tumor necrosis factor alpha and Interleukin 12 by mononuclear cells increases the risk of septic shock. Other risk factors include thalassaemia, occupational exposure (e.g. rice paddy farmers), recreational exposure to soil, water, being male, age greater than 45 years, and prolonged steroid use/immunosuppression. However, 8% of children and 20% of adults with melioidosis have no risk factors. HIV infection does not appear to predispose to melioidosis, although several other co-infections have been reported. Infant cases have been reported possibly due to mother-to-child transmission, community-acquired infection, or healthcare-associated infection. Those who are well may also be infected with B. pseudomallei. For example, 25% of children started producing antibodies against B. pseudomallei between 6 months to 4 years of staying in endemic areas although they did not experience any melioidosis symptoms; suggesting they were exposed to it over this time. This means that many people without symptoms will test positive in serology tests in endemic areas. In Thailand, the seropositivity rate exceeds 50%, while in Australia the seropositivity rate is only 5%. The disease is clearly associated with increased rainfall, with the number of cases rising following increased precipitation. Severe rainfall increases the concentration of the bacteria in the topsoil, thus increasing thus of transmitting the bacteria through the air. A recent CDC Advisory indicated that the recent detection of the organism in the environment in Mississippi following the occurrence of two indigenous cases of melioidosis, confirms that parts of the southern USA should now be regarded as melioidosis-endemic. History Pathologist Alfred Whitmore and his assistant Krishnaswami first reported melioidosis among beggars and morphine addicts at autopsy in Rangoon, present-day Myanmar, in a report published in 1912. Whitmore was able to grow the organism in culture and its showed similarity with B. mallei, another bacteria that was known causing glanders in animals. Therefore, he named the new organism Bacillus pseudomallei. He did no further work on the organism. Arthur Conan Doyle may have read Whitmores report before writing a short story that involved the fictitious tropical disease "Tapanuli fever" in a Sherlock Holmes story titled "The Adventure of the Dying Detective" published in 1913. In the same year, melioidosis outbreak occurred inside the Institute for Medical Research (IMR), Kuala Lumpur, Malaya after its laboratory animals such as guinea pigs and rabbits were infected. William Fletcher and Ambrose Thomas Stanton, doctors who worked at the IMR, were the next ones to study the organism. They were unable identify the organism that caused the outbreak. It was only in 1917, when Fletcher isolated an organism similar to Whitmores bacillus from a Tamil rubber estate worker, the presence of the new species of bacteria was confirmed. The term "melioidosis" was first coined in 1921. The name melioidosis is derived from the Greek melis (μηλις) meaning "a distemper of asses" with the suffixes -oid meaning "similar to" and -osis meaning "a condition", that is, a condition similar to glanders. B pseudomallei is similar in clinical presentation and genome make-up with B. mallei but is distinguished from it due to epidemiological and zoonotic characteristics.The first human case of melioidosis in South Asia was reported in Sri Lanka in 1927. In 1932, Thomas and Fletcher collected 83 cases of melioidosis from literature. In this case series, there were only two survivals. Since then, more case series of melioidosis were reported. Thomas and Fletcher also pioneered the use of serological methods in diagnosing the disease. Thomas and Fletcher incorrectly believed that melioidosis infection came from human contact with rodents. However, observations on the disease noted that humans usually got it after exposure to mud or contaminated water. Besides, the organism was never grown from rats. This led to a search of the bacteria in the environment. In 1936, the first animal (pig) case of melioidosis in Africa was reported in Madagascar. In 1937, water was first identified as the habitat of B. pseudomallei. The first case of Australian melioidosis was described in an outbreak in sheep in 1949 at North Queensland. This was followed by the first case of human melioidosis at Townsville in 1950. Initially, the discovery of melioidosis in Australia had led to a debate on when and how the disease spread from Southeast Asia to a new distant environment. However, this hypothesis was later disproved in 2017 when whole genome sequencing of B. pseudomallei over 30 countries collected over 79 years suggested Australia as the early reservoir for melioidosis. In 1955, first case of local human melioidosis was reported in Thailand. During the Vietnam War from 1967 to 1973, 343 American soldiers were reported with melioidosis, with about 50 cases transmitted through inhalation. An outbreak of melioidosis at the Paris Zoo in the 1970s (known as Laffaire du jardin des plantes) was thought to have originated from an imported panda or horses from Iran. It is unclear how imported melioidosis is able to persist in a completely new environment. Eventually, the outbreak terminated by itself after a period of time. It was only during the 1980s, Infectious Disease Association of Thailand started took notice of this disease. First conference on melioidosis was held in 1985 in Thailand. It was during this meeting that collaboration between Sappasitprasong Hospital, Thailand, and Wellcome-Mahido-Oxford Tropical Medicine Research Programme was established. Such collaboration made Thailand a world leader in clinical and epidemiology research on melioidosis.In 1989, several studies conducted in Thailand demonstrated ceftazidime as an effective antibiotic against melioidosis. Ceftazidime had been shown to reduce the risk of death of melioidosis from 74% to 37%. In 1990, a non-virulent arabinose-positive B. pseudomallei was found by Vanaporn Wuthiekanun. The organism was later reclassified into a new species called B. thailandensis. This species has become a useful tool in the laboratory for the studies of the pathogenesis of B. pseudomallei. B. pseudomallei was previously classified as part of the genus Pseudomonas. In 1992, the pathogen was formally named B. pseudomallei. In 1994, First International Symposium on melioidosis was held in Kuala Lumpur where 80 delegates attended. Papers were presented and later published as a book. Subsequent congresses were held in Thailand, Australia, and Singapore once every three years. In 2002, B. pseudomallei was classified as a "Category B agent". In 2004, the complete genome of B. pseudomallei was published. In 2012, B pseudomallei was classified as a "Tier 1 select agent" by the U.S. Centers for Disease Control. In 2014, co-trimoxazole was established as the only oral eradication therapy rather than combination therapy of co-trimoxazole with doxycycline. In 2016, a statistical model was developed to predict the occurrence of global melioidosis per year. Synonyms Pseudoglanders Whitmores disease (after Captain Alfred Whitmore, who first described the disease) Nightcliff gardeners disease (Nightcliff is a suburb of Darwin, Australia where melioidosis is endemic) Paddy-field disease Morphia injectors septicaemia Biological warfare Interest in melioidosis has been expressed because it has the potential to be developed as a biological weapon. Another similar bacterium, Burkholderia mallei was used by the Germans in World War I to infect livestock shipped to Allied countries. Deliberate infection of human prisoners of war and animals using B. mallei were carried out in Chinas Pingfang District by the Japanese during World War II. The Soviet Union reportedly used B. mallei during the Soviet–Afghan War in 1982 and 1984. B. pseudomallei, like B. mallei, was studied by both the US and Soviet Union as a potential biological warfare agent, but never weaponized. Other countries such as Iran, Iraq, North Korea, and Syria may have investigated the properties of B. pseudomallei for biological weapons. The bacterium is readily available in the environment. It can also be aerosolized and transmitted via inhalation. However, the B. pseudomallei has never been used in biological warfare. The actual risk of the deliberate release of B. pseudomallei or B. mallei is unknown. References This article was adapted from the following source under a [ ] license (2022) (reviewer reports): Siang Ching Raymond Chieng (14 August 2022). "Melioidosis" (PDF). WikiJournal of Medicine. 9 (1): 4. doi:10.15347/WJM/2022.004. ISSN 2002-4436. Wikidata Q100400594. External links Resource Center for melioidosis CDC Disease Info melioidosisBurkholderia pseudomallei genomes and related information at PATRIC, a Bioinformatics Resource Center funded by NIAID

Avoidant personality disorder

Avoidant personality disorder (AvPD) is a Cluster C personality disorder characterized by excessive social anxiety and inhibition, fear of intimacy (despite an intense desire for it), severe feelings of inadequacy and inferiority, and an overreliance on avoidance of feared stimuli (e.g. self-imposed social isolation) as a maladaptive coping method. Those affected typically display a pattern of extreme sensitivity to negative evaluation and rejection, a belief that one is socially inept or personally unappealing to others, and avoidance of social interaction despite a strong desire for it. It affects an approximately equal number of men and women.People with AvPD often avoid social interaction for fear of being ridiculed, humiliated, rejected, or disliked. They typically avoid becoming involved with others unless they are certain they will not be rejected, and may also pre-emptively abandon relationships due to a real or imagined fear that they are at risk of being rejected by the other party.Childhood emotional neglect (in particular, the rejection of a child by one or both parents) and peer group rejection are associated with an increased risk for its development; however, it is possible for AvPD to occur without any notable history of abuse or neglect. Signs and symptoms Avoidant individuals are preoccupied with their own shortcomings and form relationships with others only if they believe they will not be rejected. They often view themselves with contempt, while showing a decreased ability to identify traits within themselves that are generally considered as positive within their societies. Loss and social rejection are so painful that these individuals will choose to be alone rather than risk trying to connect with others. Some with this disorder fantasize about idealized, accepting and affectionate relationships because of their desire to belong. They often feel themselves unworthy of the relationships they desire, and shame themselves from ever attempting to begin them. If they do manage to form relationships, it is also common for them to pre-emptively abandon them out of fear of the relationship failing.Individuals with the disorder tend to describe themselves as uneasy, anxious, lonely, unwanted and isolated from others. They often choose jobs of isolation in which they do not have to interact with others regularly. Avoidant individuals also avoid performing activities in public spaces for fear of embarrassing themselves in front of others. Symptoms include: Extreme shyness or anxiety in social situations, though the person feels a strong desire for close relationships Heightened attachment-related anxiety, which may include a fear of abandonment Substance use disorders Comorbidity AvPD is reported to be especially prevalent in people with anxiety disorders, although estimates of comorbidity vary widely due to differences in (among others) diagnostic instruments. Research suggests that approximately 10–50% of people who have panic disorder with agoraphobia have avoidant personality disorder, as well as about 20–40% of people who have social anxiety disorder. In addition to this, AvPD is more prevalent in people who have comorbid social anxiety disorder and generalised anxiety disorder than in those who have only one of the aforementioned conditions.Some studies report prevalence rates of up to 45% among people with generalized anxiety disorder and up to 56% of those with obsessive–compulsive disorder. Posttraumatic stress disorder is also commonly comorbid with avoidant personality disorder.Avoidants are prone to self-loathing and, in certain cases, self-harm. Substance use disorders are also common in individuals with AvPD—particularly in regard to alcohol, benzodiazepines, and opioids—and may significantly affect a patients prognosis.Earlier theorists proposed a personality disorder with a combination of features from borderline personality disorder and avoidant personality disorder, called "avoidant-borderline mixed personality" (AvPD/BPD). Causes Causes of AvPD are not clearly defined, but appear to be influenced by a combination of social, genetic and psychological factors. The disorder may be related to temperamental factors that are inherited.Specifically, various anxiety disorders in childhood and adolescence have been associated with a temperament characterized by behavioral inhibition, including features of being shy, fearful and withdrawn in new situations. These inherited characteristics may give an individual a genetic predisposition towards AvPD.Childhood emotional neglect and peer group rejection are both associated with an increased risk for the development of AvPD. Some researchers believe a combination of high-sensory-processing sensitivity coupled with adverse childhood experiences may heighten the risk of an individual developing AvPD. Subtypes Millon Psychologist Theodore Millon notes that because most patients present a mixed picture of symptoms, their personality disorder tends to be a blend of a major personality disorder type with one or more secondary personality disorder types. He identified four adult subtypes of avoidant personality disorder. Others In 1993, Lynn E. Alden and Martha J. Capreol proposed two other subtypes of avoidant personality disorder: Diagnosis ICD The World Health Organizations ICD-10 lists avoidant personality disorder as anxious (avoidant) personality disorder (F60.6). It is characterized by the presence of at least four of the following: persistent and pervasive feelings of tension and apprehension; belief that one is socially inept, personally unappealing, or inferior to others; excessive preoccupation with being criticized or rejected in social situations; unwillingness to become involved with people unless certain of being liked; restrictions in lifestyle because of need to have physical security; avoidance of social or occupational activities that involve significant interpersonal contact because of fear of criticism, disapproval, or rejection.Associated features may include hypersensitivity to rejection and criticism. It is a requirement of ICD-10 that all personality disorder diagnoses also satisfy a set of general personality disorder criteria. DSM The Diagnostic and Statistical Manual of Mental Disorders (DSM) of the American Psychiatric Association also has an avoidant personality disorder diagnosis (301.82). It refers to a widespread pattern of inhibition around people, feeling inadequate and being very sensitive to negative evaluation. Symptoms begin by early adulthood and occur in a range of situations. Four of the following seven specific symptoms should be present: Avoids occupational activities that involve significant interpersonal contact, because of fears of criticism, disapproval, or rejection is unwilling to get involved with people unless certain of being liked shows restraint within intimate relationships because of the fear of being shamed or ridiculed is preoccupied with being criticized or rejected in social situations is inhibited in new interpersonal situations because of feelings of inadequacy views self as socially inept, personally unappealing, or inferior to others is unusually reluctant to take personal risk or to engage in any new activities because they may prove embarrassing Differential diagnosis In contrast to social anxiety disorder, a diagnosis of avoidant personality disorder (AvPD) also requires that the general criteria for a personality disorder be met. According to the DSM-5, avoidant personality disorder must be differentiated from similar personality disorders such as dependent, paranoid, schizoid, and schizotypal. But these can also occur together; this is particularly likely for AvPD and dependent personality disorder. Thus, if criteria for more than one personality disorder are met, all can be diagnosed.There is also an overlap between avoidant and schizoid personality traits (see Schizoid avoidant behavior) and AvPD may have a relationship to the schizophrenia spectrum.Avoidant personality disorder must also be differentiated from the autism spectrum, specifically Asperger syndrome. Treatment Treatment of avoidant personality disorder can employ various techniques, such as social skills training, psychotherapy, cognitive therapy, and exposure treatment to gradually increase social contacts, group therapy for practicing social skills, and sometimes drug therapy.A key issue in treatment is gaining and keeping the patients trust since people with an avoidant personality disorder will often start to avoid treatment sessions if they distrust the therapist or fear rejection. The primary purpose of both individual therapy and social skills group training is for individuals with an avoidant personality disorder to begin challenging their exaggerated negative beliefs about themselves.Significant improvement in the symptoms of personality disorders is possible, with the help of treatment and individual effort. Prognosis Being a personality disorder, which is usually chronic and has long-lasting mental conditions, an avoidant personality disorder may not improve with time without treatment. Given that it is a poorly studied personality disorder and in light of prevalence rates, societal costs, and the current state of research, AvPD qualifies as a neglected disorder. Controversy There is debate as to whether avoidant personality disorder (AvPD) is distinct from social anxiety disorder. Both have similar diagnostic criteria and may share a similar causation, subjective experience, course, treatment and identical underlying personality features, such as shyness.It is contended by some that they are merely different conceptualizations of the same disorder, where avoidant personality disorder may represent the more severe form. In particular, those with AvPD experience not only more severe social phobia symptoms, but are also more depressed and more functionally impaired than patients with generalized social phobia alone. But they show no differences in social skills or performance on an impromptu speech. Another difference is that social phobia is the fear of social circumstances whereas AvPD is better described as an aversion to intimacy in relationships. Epidemiology Data from the 2001–02 National Epidemiologic Survey on Alcohol and Related Conditions indicates a prevalence of 2.36% in the American general population. It appears to occur with equal frequency in males and females. In one study, it was seen in 14.7% of psychiatric outpatients. History The avoidant personality has been described in several sources as far back as the early 1900s, although it was not so named for some time. Swiss psychiatrist Eugen Bleuler described patients who exhibited signs of avoidant personality disorder in his 1911 work Dementia Praecox: Or the Group of Schizophrenias. Avoidant and schizoid patterns were frequently confused or referred to synonymously until Kretschmer (1921), in providing the first relatively complete description, developed a distinction. See also Attachment theory Avoidance coping Counterphobic attitude Experiential avoidance Inferiority complex Sensory processing sensitivitySocial: Hermit Hikikomori Loner Recluse Solitude Taijin kyofusho References == External links ==

Pigment dispersion syndrome

Pigment dispersion syndrome (PDS) is an eye disorder that can lead to a form of glaucoma known as pigmentary glaucoma. It takes place when pigment cells slough off from the back of the iris and float around in the aqueous humor. Over time, these pigment cells can accumulate in the anterior chamber in such a way that they begin to clog the trabecular meshwork (the major site of aqueous humour drainage), which can in turn prevent the aqueous humour from draining and therefore increases the pressure inside the eye. A common finding in PDS are central, vertical corneal endothelial pigment deposits, known as Krukenberg spindle. With PDS, the intraocular pressure tends to spike at times and then can return to normal. Exercise has been shown to contribute to spikes in pressure as well. When the pressure is great enough to cause damage to the optic nerve, this is called pigmentary glaucoma. As with all types of glaucoma, when damage happens to the optic nerve fibers, the vision loss that occurs is irreversible and painless. Risk factors This condition is rare, but occurs most often in Caucasians, particularly men, and the age of onset is relatively low: mid 20s to 40s. As the crystalline lens hardens with age, the lens zonules pull away from the iris and the syndrome lessens and stops. The main risk factor is nearsightedness. Genetic factors may also play a part in the transition from syndrome to the glaucoma condition. Diagnosis Diagnosis for pigment dispersion syndrome is made with characteristic slit lamp and gonioscopy findings. Management There is no cure, but pigmentary glaucoma can be managed with eye drops or treated with simple surgeries. If caught early and monitored, chances of glaucoma are greatly reduced. A 2016 Cochrane Review sought to determine the effectiveness of YAG laser iridotomy versus no laser iridotomy for pigment dispersion syndrome and pigmentary glaucoma, in 195 participants, across five studies. No clear benefits in preventing loss of visual field were found for eyes treated with peripheral laser iridotomy. There was weak evidence suggesting that laser iridotomy could be more effective in lowering intraocular pressure in eyes versus no treatment. References == External links ==

Fibroma

Fibromas are benign tumors that are composed of fibrous or connective tissue. They can grow in all organs, arising from mesenchyme tissue. The term "fibroblastic" or "fibromatous" is used to describe tumors of the fibrous connective tissue. When the term fibroma is used without modifier, it is usually considered benign, with the term fibrosarcoma reserved for malignant tumors. Types Hard fibroma The hard fibroma (fibroma durum) consists of many fibres and few cells, e.g. in skin it is called dermatofibroma (fibroma simplex or nodulus cutaneous). A special form is the keloid, which derives from hyperplastic growth of scars. Soft fibroma The soft fibroma (fibroma molle) or fibroma with a shaft (acrochordon, skin tag, fibroma pendulans) consist of many loosely connected cells and less fibroid tissue. It mostly appears at the neck, armpits or groin. The photo shows a soft fibroma of the eyelid. Other types of fibroma The fibroma cavernosum or angiofibroma, consists of many often dilated vessels, it is a vasoactive tumor occurring almost exclusively in adolescent males. The cystic fibroma (fibroma cysticum) has central softening or dilated lymphatic vessels. The myxofibroma (fibroma myxomatodes) is produced by liquefaction of the underlying soft tissue. The cemento-ossifying fibroma is hard and fibrous, most frequently seen in the jaw or mouth, sometimes in connection with a fracture or another type of injury. Other fibromas: chondromyxoid fibroma, desmoplasmic fibroma, nonossifying fibroma, ossifying fibroma, nuchal fibroma, collagenous fibroma, fibroma of tendon sheath, perifollicular fibroma, pleomorphic fibroma, uterine fibroma, Gardner fibroma, etc. The neurofibroma is a benign nerve-sheath tumor in the peripheral nervous system. Ovarian fibroma It appears in the sex cord-stromal tumour group of ovarian neoplasms. Ovary fibromas are most frequent during middle age, and rare in children. Upon gross pathological inspection, ovary fibromas are firm and white or tan. Variants with edema are especially likely to be associated with Meigs syndrome. On microscopic examination, there are intersecting bundles of spindle cells producing collagen. There may be thecomatous areas (fibrothecoma). The presence of an ovarian fibroma can cause ovarian torsion in some cases. Treatment Benign fibromas may, but need not, be removed. Removal is usually a brief outpatient procedure or using cryotherapy in which the lesion is deep frozen (-196 degrees Celsius using liquid nitrogen) and thawed for two or more cycles, with full recovery within 3 to 4 weeks. The cryotherapy treatment needs no anesthetics and is painless. Another simple treatment is snip removal after injecting local anesthetic. See also Acrochordon (skin tags) Fibrous lesions References == External links ==

Bizarre parosteal osteochondromatous proliferation

Bizarre parosteal osteochondromatous proliferation (BPOP), also known as Noras lesion, is a type of non-cancerous bone tumor belonging to the group of cartilage tumors. It is generally seen in the tubular bones of the hands and feet, where it presents with a rapidly enlarging painless lump in a finger or toe.It is composed of bone, cartilage and spindle cells. Some people report previous trauma.Diagnosis is by medical imaging. Treatment is by surgical excision. Up to 50% recur after surgery.It is rare, and occurs more often in the 20s and 30s. Combined with subungal exostosis, it accounts for less than 5% of cartilage tumors. Males and females are affected equally. The condition was first described by Frederick E. Nora in 1983. Signs and symptoms BPOP generally presents with a 1–3 cm painless lump in a finger or more frequently a toe. Growth can be rapid. Mechanism It is composed of bone, cartilage and spindle cells. A small number of people have reported previous trauma. Diagnosis Medical imaging usually shows a well-defined wide-based bony growth on the surface of bone. Differential diagnosis BPOP is distinct from subungal exostosis. Conditions that may appear similar to BPOP include: myositis ossficans, ostechondroma, surface osteosarcoma and granulomatous infection. Treatment Treatment is by surgical excision. Outcomes Up to 50% recur after surgery. Epidemiology BPOP is rare. It is most often seen in people in their 20s and 30s. Combined with subungal exostosis, it accounts for less than 5% of cartilage tumors. Males and females are affected equally. History Bizarre parosteal osteochondromatous proliferation was first described by Frederick E. Nora in 1983. Generally in the US, it has been thought of as a mouthful and hence it is sometimes referred to as Noras lesion. Other animals In 1998 a report of a similar lesion to BPOP was reported in a wallaby. == References ==

Stomatitis

Stomatitis is inflammation of the mouth and lips. It refers to any inflammatory process affecting the mucous membranes of the mouth and lips, with or without oral ulceration.In its widest meaning, stomatitis can have a multitude of different causes and appearances. Common causes include infections, nutritional deficiencies, allergic reactions, radiotherapy, and many others. When inflammation of the gums and the mouth generally presents itself, sometimes the term gingivostomatitis is used, though this is also sometimes used as a synonym for herpetic gingivostomatitis. The term is derived from the Greek stoma (στόμα), meaning "mouth", and the suffix -itis (-ῖτις), meaning "inflammation". Causes Nutritional deficiency Malnutrition (improper dietary intake) or malabsorption (poor absorption of nutrients into the body) can lead to nutritional deficiency states, several of which can lead to stomatitis. For example, deficiencies of iron, vitamin B2 (riboflavin),: 490  vitamin B3 (niacin), vitamin B6 (pyridoxine), vitamin B9 (folic acid) or vitamin B12 (cobalamine) may all manifest as stomatitis. Iron is necessary for the upregulation of transcriptional elements for cell replication and repair. Lack of iron can cause genetic downregulation of these elements, leading to ineffective repair and regeneration of epithelial cells, especially in the mouth and lips. Many disorders which cause malabsorption can cause deficiencies, which in turn causes stomatitis. Examples include tropical sprue.: 49 Aphthous stomatitis Aphthous stomatitis (canker sores) is the recurrent appearance of mouth ulcers in otherwise healthy individuals. The cause is not completely understood, but it is thought that the condition represents a T cell mediated immune response which is triggered by a variety of factors. The individual ulcers (aphthae) recur periodically and heal completely, although in the more severe forms, new ulcers may appear in other parts of the mouth before the old ones have finished healing. Aphthous stomatitis is one of the most common diseases of the oral mucosa, and is thought to affect about 20% of the general population to some degree. The symptoms range from a minor nuisance to being disabling in their impact on eating, swallowing, and talking, and the severe forms can cause people to lose weight. There is no cure for aphthous stomatitis, and therapies are aimed at alleviating the pain, reducing the inflammation and promoting healing of the ulcers, but there is little evidence of efficacy for any treatment that has been used. Angular stomatitis Inflammation of the corners (angles) of the lips is termed angular stomatitis or angular cheilitis. In children a frequent cause is repeated lip-licking, and in adults it may be a sign of underlying iron deficiency anemia, or vitamin B deficiencies (e.g., B2-riboflavin, B9-folate, or B12-cobalamin, which in turn may be evidence of poor diets or malnutrition such as celiac disease). Also, angular cheilitis can be caused by a patients jaws at rest being overclosed due to edentulousness or tooth wear, causing the jaws to come to rest closer together than if the complete/unaffected dentition were present. This causes skin folds around the angle of the mouth which are kept moist by saliva, which in turn favours infection; mostly by Candida albicans or similar species. Treatment usually involves the administration of topical nystatin or similar antifungal agents. Another treatment can be to correct the jaw relationship with dental treatment (e.g., dentures or occlusal adjustment). Denture-related stomatitis This is a common condition present in denture wearers. It appears as reddened but painless mucosa beneath the denture. 90% of cases are associated with Candida species, and it is the most common form of oral candidiasis. Treatment is by antifungal medication and improved dental hygiene, such as not wearing the denture during sleep. Allergic contact stomatitis Allergic contact stomatitis (also termed "allergic gingivostomatitis" or "allergic contact gingivostomatitis") is a type IV (delayed) hypersensitivity reaction that occurs in susceptible atopic individuals when allergens penetrate the skin or mucosa.Allergens, which may be different for different individuals, combine with epithelial-derived proteins, forming haptens which bind with Langerhans cells in the mucosa, which in turn present the antigen on their surface to T lymphocytes, sensitizing them to that antigen and causing them to produce many specific clones. The second time that specific antigen is encountered, an inflammatory reaction is triggered at the site of exposure. Allergic contact stomatitis is less common than allergic contact dermatitis because the mouth is coated in saliva, which washes away antigens and acts as a barrier. The oral mucosa is also more vascular (has a better blood supply) than skin, meaning that any antigens are more quickly removed from the area by the circulation. Finally, there is substantially less keratin in oral mucosa, meaning that there is less likelihood that haptens will form.Allergic contact stomatitis appears as non-specific inflammation, so it may be mistaken for chronic physical irritation. There may be burning or soreness of the mouth and ulceration. Chronic exposure to the allergen may result in a lichenoid lesion. Plasma cell gingivitis may also occur, which may be accompanied by glossitis and cheilitis. Allergens that may cause allergic contact stomatitis in some individuals include cinnamaldehyde, Balsam of Peru, peppermint, mercury, gold, pyrophosphates, zinc citrate, free acrylic monomer, nickel, fluoride, and sodium lauryl sulfate. These allergens may originate from many sources, including various foods and drink, chewing gum, toothpaste, mouthwash, dental floss, dental fillings, dentures, orthodontic bands or wires, and many other sources. If the substance containing the allergen comes into contact with the lips, allergic contact cheilitis can occur, together with allergic contact stomatitis. The diagnosis is confirmed by patch test, and management is by avoidance of exposure to the allergen. Migratory stomatitis Migratory stomatitis (or geographic stomatitis) is an atypical presentation of a condition which normally presents on the tongue, termed geographic tongue. Geographic tongue is so named because there are atrophic, erythematous areas of depapillation that migrate over time, giving a map-like appearance. In migratory stomatitis, other mucosal sites in the mouth, such as the ventral surface (undersurface) of the tongue, buccal mucosa, labial mucosa, soft palate, or floor of mouth may be afflicted with identical lesions, usually in addition to the tongue. Apart from not being restricted to the tongue, migratory stomatitis is an identical condition in every regard to geographic tongue. Another synonym for geographic tongue which uses the term stomatitis is "stomatitis areata migrans". Herpetic gingivostomatitis This is inflammation of the mouth caused by herpes simplex virus. Irradiation and chemotherapy Stomatitis may also be caused by chemotherapy, or radiation therapy of the oropharyngeal area. The term mucositis is sometimes used synonymously with stomatitis, however the former usually refers to mucosal reactions to radiotherapy or chemotherapy, and may occur anywhere in the gastrointestinal tract and not just in the mouth. Necrotizing ulcerative gingivostomatitis The term necrotizing ulcerative gingivostomatitis is sometimes used as a synonym of the necrotizing periodontal disease more commonly termed necrotizing ulcerative gingivitis, or a more severe form (also termed necrotizing stomatitis). The term necrotizing gingivostomatitis is also sometimes used. Stomatitis nicotina Also called smokers palatal keratosis,: 176  this condition may occur in smokers, especially pipe smokers. The palate appears dry and cracked, and white from keratosis. The minor salivary glands appear as small, red and swollen bumps. It is not a premalignant condition, and the appearance reverses if the smoking is stopped.: 176 Chronic ulcerative stomatitis Chronic ulcerative stomatitis is a condition with specific immunopathologic features, which was first described in 1990. It is characterized by erosions and ulcerations which relapse and remit. Lesions are located on the buccal mucosa (inside of the cheeks) or on the gingiva (gums). The condition resembles oral lichen planus when biopsied. The diagnosis is made by microscopic examination of biopsy tissue: direct immunofluorescence can reveal the presence of antinuclear antibodies specifically directed against the ΔNp63α form of the p63 protein, which is normally expressed within the basal layer of stratified epithelium. Treatment with hydroxychloroquine can be effective. Plasma cell gingivostomatitis Terms such as plasma cell gingivostomatitis, atypical gingivostomatitis and idiopathic gingivostomatitis are sometimes a synonym for plasma cell gingivitis, or specifically to refer to a severe form of plasma cell gingivitis. Other forms of stomatitis Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome—occurs in children. Uremic stomatitis—a rare form of stomatitis that occurs with kidney failure. Pyostomatitis vegetans Bovine papular stomatitis References == External links ==

Paratyphoid fever

Paratyphoid fever, also known simply as paratyphoid, is a bacterial infection caused by one of the three types of Salmonella enterica. Symptoms usually begin 6–30 days after exposure and are the same as those of typhoid fever. Often, a gradual onset of a high fever occurs over several days. Weakness, loss of appetite, and headaches also commonly occur. Some people develop a skin rash with rose-colored spots. Without treatment, symptoms may last weeks or months. Other people may carry the bacteria without being affected; however, they are still able to spread the disease to others. Typhoid and paratyphoid are of similar severity. Paratyphoid and typhoid fever are types of enteric fever.Paratyphoid is caused by the bacterium Salmonella enterica of the serotypes Paratyphi A, Paratyphi B, or Paratyphi C growing in the intestines and blood. They are usually spread by eating or drinking food or water contaminated with the feces of an infected person. They may occur when a person who prepares food is infected. Risk factors include poor sanitation as is found among poor crowded populations. Occasionally, they may be transmitted by sex. Humans are the only animals infected. Diagnosis may be based on symptoms and confirmed by either culturing the bacteria or detecting the bacterial DNA in the blood, stool, or bone marrow. Culturing the bacteria can be difficult. Bone-marrow testing is the most accurate. Symptoms are similar to that of many other infectious diseases. Typhus is a different disease.While no vaccine is available specifically for paratyphoid, the typhoid vaccine may provide some benefit. Prevention includes drinking clean water, better sanitation, and better handwashing. Treatment of the disease is with antibiotics such as azithromycin. Resistance to a number of other previously effective antibiotics is common.Paratyphoid affects about six million people a year. It is most common in parts of Asia and rare in the developed world. Most cases are due to Paratyphi A rather than Paratyphi B or C. In 2015, paratyphoid fever resulted in about 29,200 deaths, down from 63,000 deaths in 1990. The risk of death is between 10 and 15% without treatment, while with treatment, it may be less than 1%. Signs and symptoms Paratyphoid fever resembles typhoid fever. Infection is characterized by a sustained fever, headache, abdominal pain, malaise, anorexia, a nonproductive cough (in early stage of illness), a relative bradycardia (slow heart rate), and hepatosplenomegaly (an enlargement of the liver and spleen). About 30% of Caucasians develop rosy spots on the central body. In adults, constipation is more common than diarrhea.Only 20 to 40% of people initially have abdominal pain. Nonspecific symptoms such as chills, sweating, headache, loss of appetite, cough, weakness, sore throat, dizziness, and muscle pains are frequently present before the onset of fever. Some very rare symptoms are psychosis (mental disorder), confusion, and seizures. Cause Paratyphoid fever is caused by any of three serovars of Salmonella enterica subsp. enterica: S. Paratyphi A, S. Paratyphi B (invalid alias S. schottmuelleri), S. Paratyphi C (invalid alias S. hirschfeldii). Transmission They are usually spread by eating or drinking food or water contaminated with the feces of an infected person. They may occur when a person who prepares food is infected. Risk factors include poor sanitation as is found among poor crowded populations. Occasionally, they may be transmitted by sex. Humans are the only animals infected. Paratyphoid B Paratyphoid B is more frequent in Europe. It can present as a typhoid-like illness, as a severe gastroenteritis or with features of both. Herpes labialis, rare in true typhoid fever, is frequently seen in paratyphoid B. Rarely a subdural empyema can occur. Diagnosis is with isolation of the agent in blood or stool and demonstration of antibodies antiBH in the Widal test. The disease responds well to chloramphenicol or co-trimoxazole. Paratyphoid C Paratyphoid C is a rare infection, generally seen in the Far East. It presents as a septicaemia with metastatic abscesses. Cholecystitis is possible in the course of the disease. Antibodies to paratyphoid C are not usually tested and the diagnosis is made with blood cultures. Chloramphenicol therapy is generally effective. Carriers Humans and, occasionally, domestic animals are the carriers of paratyphoid fever. Members of the same family can be transient or permanent carriers. In most parts of the world, short-term fecal carriers are more common than urinary carriers. The chronic urinary carrier state occurs in those who have schistosomiasis (parasitic blood fluke).Continuing to shed Salmonella Paratyphi is possible for up to one year, and during this phase, a person is considered to be a carrier. The chronic carrier state may follow acute illness, or mild or even subclinical infections. Chronic carriers are most often women who were infected in their middle age. Pathophysiology After ingestion, if the immune system is unable to stop the infection, the bacteria multiply and then spread to the bloodstream, after which the first signs of disease are observed in the form of fever. They penetrate further to the bone marrow, liver, and bile ducts, from which bacteria are excreted into the bowel contents. In the second phase of the disease, the bacteria penetrate the immune tissue of the small intestine, and the initial symptoms of small-bowel movements begin. Diagnosis Prevention Providing basic sanitation and safe drinking water and food are the keys for controlling the disease. In developed countries, enteric fever rates decreased in the past when treatment of municipal water was introduced, human feces were excluded from food production, and pasteurization of dairy products began. In addition, children and adults should be carefully educated about personal hygiene. This would include careful handwashing after defecation and sexual contact, before preparing or eating food, and especially the sanitary disposal of feces. Food handlers should be educated in personal hygiene prior to handling food or utensils and equipment. Infected individuals should be advised to avoid food preparation. Sexually active people should be educated about the risks of sexual practices that permit fecal-oral contact.Those who travel to countries with poor sanitation should receive a live attenuated typhoid vaccine—Ty21a (Vivotif), which, in addition to the protection against typhoid fever, may provide some protection against paratyphoid fever caused by the S. enterica serotypes A and B. In particular, a reanalysis of data from a trial conducted in Chile showed the Ty21a vaccine was 49% effective (95% CI: 8–73%) in preventing paratyphoid fever caused by the serotype B. Evidence from a study of international travelers in Israel also indicates the vaccine may prevent a fraction of infections by the serotype A, although no trial confirms this. This cross-protection by a typhoid vaccine is most likely due to O antigens shared between different S. enterica serotypes.Exclusion from work and social activities should be considered for symptomatic, and asymptomatic people who are food handlers, healthcare/daycare staff who are involved in patient care and/or child care, children attending unsanitary daycare centers, and older children who are unable to implement good standards of personal hygiene. The exclusion applies until two consecutive stool specimens are taken from the infected patient and are reported negative. Treatments Control requires treatment of antibiotics and vaccines prescribed by a doctor. Major control treatments for paratyphoid fever include ciprofloxacin for 10 days, ceftriaxone/cefotaxime for 14 days, or aziththromycin. Prognosis Those diagnosed with Type A of the bacterial strain rarely die from it except in rare cases of severe intestinal complications. With proper testing and diagnosis, the mortality rate falls to less than 1%. Antibiotics such as azithromycin are particularly effective in treating the disease. Epidemiology Factors outside the household, such as unclean food from street vendors and flooding, help distribute the disease from person to person. Because of poverty and poor hygiene and insanitary conditions, the disease is more common in less-industrialized countries, principally owing to the problem of unsafe drinking water, inadequate sewage disposal, and flooding. Occasionally causing epidemics, paratyphoid fever is found in large parts of Asia, Africa, and Central and South America. Many of those infected get the disease in Asian countries. About 16 million cases occur a year, which result in about 25,000 deaths worldwide. References Further reading "Typhoid and Paratyphoid Fever." Communicable Disease Management Protocol. November 2001 https://www.gov.mb.ca/health/publichealth/cdc/protocol/typhoid.pdf. "Typhoid and Paratyphoid Fever." Public Health Notifiable Disease Management Guidelines. Disease Control and Prevention. Alberta Health and Wellness: June 2013 https://web.archive.org/web/20130925214850/http://www.health.alberta.ca/documents/Guidelines-Paratyphoid-Fever-2013.pdf

Ulnar nerve entrapment

Ulnar nerve entrapment is a condition where the ulnar nerve becomes physically trapped or pinched, resulting in pain, numbness, or weakness, primarily affecting the little finger and ring finger of the hand. Entrapment may occur at any point from the spine at cervical vertebra C7 to the wrist; the most common point of entrapment is in the elbow (Cubital tunnel syndrome). Prevention is mostly through correct posture and avoiding repetitive or constant strain (e.g. "cell phone elbow"). Treatment is usually conservative, including medication, activity modification, and exercise, but may sometimes include surgery. Prognosis is generally good, with mild to moderate symptoms often resolving spontaneously. Signs and symptoms In general, ulnar neuropathy will result in symptoms in a specific anatomic distribution, affecting the little finger, the ulnar half of the ring finger, and the intrinsic muscles of the hand. The specific symptoms experienced in the characteristic distribution depend on the specific location of ulnar nerve impingement. Symptoms of ulnar neuropathy may be motor, sensory, or both depending on the location of injury. Motor symptoms consistent of muscle weakness; sensory symptoms or paresthesias consist of numbness or tingling in the areas innervated by the ulnar nerve.Proximal impingement is associated with mixed symptoms, as the proximal nerve consists of mixed sensory and motor innervation. Distal impingement is associated with variable symptoms, as the ulnar nerve separates near the hand into distinct motor and sensory branches. In cubital tunnel syndrome (a proximal impingement), sensory and motor symptoms tend to occur in a certain sequence. Initially, there may be numbness of the small and ulnar fourth finger which may be transient. If the impingement is not corrected, the numbness may become constant and progress to hand weakness. A characteristic resting hand position of "ulnar claw," where the small and ring fingers curl up, occurs late in the disease and is a sign of severe neuropathy. By contrast, in Guyons canal syndrome (distal impingement) motor symptoms and claw hand may be more pronounced, a phenomenon known as the ulnar paradox. Also, the back of the hand will have normal sensation. Diagnosis The distinct innervation of the hand usually enables diagnosis of an ulnar nerve impingement by symptoms alone. Ulnar nerve damage that causes paralysis to these muscles will result in a characteristic ulnar claw position of the hand at rest. Clinical tests such as the card test for Froments sign, can be easily performed for assessment of ulnar nerve. However, a complete diagnosis should identify the source of the impingement, and radiographic imaging may be necessary to determine or rule-out an underlying cause.Imaging studies, such as ultrasound or MRI, may reveal anatomic abnormalities or masses responsible for the impingement. Additionally, imaging may show secondary signs of nerve damage that further confirm the diagnosis of impingement. Signs of nerve damage include flattening of the nerve, swelling of the nerve proximal to site of injury, abnormal appearance of nerve, or characteristic changes to the muscles innervated by the nerve. Differential diagnoses Symptoms of ulnar neuropathy or neuritis do not necessarily indicate an actual physical impingement of the nerve; any injury to the ulnar nerve may result in identical symptoms. In addition, other functional disturbances may result in irritation to the nerve and are not true "impingement". For example, anterior dislocation and "snapping" of ulnar nerve across the medial epicondyle of the elbow joint can result in ulnar neuropathy.Entrapment of other major sensory nerves of the upper extremities result in deficits in other patterns of distribution. Entrapment of the median nerve causes carpal tunnel syndrome, which is characterized by numbness in the thumb, index, middle, and half of the ring finger. Compression of the radial nerve causes numbness of the back of the hand and thumb, and is much rarer.A simple way of differentiating between significant median and ulnar nerve injury is by testing for weakness in flexing and extending certain fingers of the hand. Median nerve injuries are associated with difficulty flexing the index and middle finger when attempting to make a fist. However, with an ulnar nerve lesion, the pinky and ring finger cannot be unflexed when attempting to extend the fingers.Some people are affected by multiple nerve compressions, which can complicate diagnosis. Classification Ulnar nerve entrapment is classified by location of entrapment. The ulnar nerve passes through several small spaces as it courses through the medial side of the upper extremity, and at these points the nerve is vulnerable to compression or entrapment—a so-called "pinched nerve". The nerve is particularly vulnerable to injury when there has been a disruption in the normal anatomy. The most common site of ulnar nerve entrapment is at the elbow, followed by the wrist.Causes or structures which have been reported to cause ulnar nerve entrapment include: Problems originating at the neck: thoracic outlet syndrome, cervical spine pathology, compression by anterior scalene muscles Problems originating in the chest: compression by pectoralis minor muscles Brachial plexus abnormalities Elbow: fractures, growth plate injuries, cubital tunnel syndrome, flexorpronator aponeurosis, arcade of Struthers Forearm: tight flexor carpi ulnaris muscles Wrist: fractures, ulnar tunnel syndrome, hypothenar hammer syndrome Artery aneurysms or thrombosis Other: Infections, tumors, diabetes, hypothyroidism, rheumatism, and alcoholism Cubital tunnel syndrome The most common location of ulnar nerve impingement at the elbow is within the cubital tunnel, and is known as cubital tunnel syndrome. The tunnel is formed by the medial epicondyle of the humerus, the olecranon process of the ulna and the tendinous arch joining the humeral and ulnar heads of the flexor carpi ulnaris muscle. While most cases of injury are minor and resolve spontaneously with time, chronic compression or repetitive trauma may cause more persistent problems. Commonly cited scenarios include: Sleeping with the arm folded behind neck, elbows bent. Pressing the elbows upon the arms of a chair while typing. Resting or bracing the elbow on the arm rest of a vehicle. Bench pressing. Intense exercising and strain involving the elbow.Compression of the ulnar nerve at the medial elbow may occasionally be caused by an epitrocheloanconeus muscle, an anatomical variant. Ulnar tunnel syndrome Ulnar nerve impingement along an anatomical space in the wrist called the ulnar canal is known as ulnar tunnel syndrome. Recognized causes of ulnar nerve impingement at this location include local trauma, fractures, ganglion cysts, and classically avid cyclists who experience repetitive trauma against bicycle handlebars. This form of ulnar neuropathy comprises two work-related syndromes: so-called "hypothenar hammer syndrome," seen in workers who repetitively use a hammer, and "occupational neuritis" due to hard, repetitive compression against a desk surface. Prevention Cubital tunnel syndrome may be prevented or reduced by maintaining good posture and proper use of the elbow and arms, such as wearing an arm splint while sleeping to maintain the arm is in a straight position instead of keeping the elbow tightly bent. A recent example of this is popularization of the concept of cell phone elbow and game hand. Treatment The most effective treatment for cubital tunnel syndrome is surgical decompression. The most safe and effective operation is in-situ decompression +/- medial epicondylectomy.For pain symptoms, medications such as NSAID, amitriptyline, or vitamin B6 supplementation may help although there is no evidence to support this claim.Mild symptoms may first be treated non-operatively, with the following: Elbow joint immobilization in extension at night +/- during the day Neural flossing/gliding exercises Strengthening/stretching exercises Activity modification (e.g. avoidance of pressure on the elbows)It is important to identify positions and activities that aggravate symptoms and to find ways to avoid them. For example, if the person experiences symptoms when holding a telephone up to the head, then the use of a telephone headset will provide immediate symptomatic relief and reduce the likelihood of further damage and inflammation to the nerve. For cubital tunnel syndrome, it is recommended to avoid repetitive elbow flexion and also avoiding prolonged elbow flexion during sleep, as this position puts stress of the ulnar nerve.Cubital tunnel decompression surgery involves an incision posteromedial to the medial epicondyle which helps avoid the medial antebrachial cutaneous nerve branches. The ulnar nerve is identified and released from its fascia proximally and distally up to the flexor carpi ulnaris heads. After release, flexion and extension of the arm are performed to ensure there is no subluxation of the ulnar nerve. Prognosis Following surgery, on average, 85% of patients report an improvement in their symptomsMost patients diagnosed with cubital tunnel syndrome have advanced disease (atrophy, static numbness, weakness) that might reflect permanent nerve damage that will not recover after surgery. When diagnosed prior to atrophy, weakness or static numbness, the disease can be arrested with treatment. Mild and intermittent symptoms often resolve spontaneously. Epidemiology People with diabetes mellitus are at higher risk for any kind of peripheral neuropathy, including ulnar nerve entrapments.Cubital tunnel syndrome is more common in people who spend long periods of time with their elbows bent, such as when holding a telephone to the head. Flexing the elbow while the arm is pressed against a hard surface, such as leaning against the edge of a table, is a significant risk factor. The use of vibrating tools at work or other causes of repetitive activities increase the risk, including throwing a baseball.Damage to or deformity of the elbow joint increases the risk of cubital tunnel syndrome. Additionally, people who have other nerve entrapments elsewhere in the arm and shoulder are at higher risk for ulnar nerve entrapment. There is some evidence that soft tissue compression of the nerve pathway in the shoulder by a bra strap over many years can cause symptoms of ulnar neuropathy, especially in very large-breasted women. See also Cervical Vertebrae Ulnar neuropathy References == External links ==

Epidermolysis bullosa acquisita

Epidermolysis bullosa acquisita, also known as acquired epidermolysis bullosa, is a longterm autoimmune blistering skin disease. It generally presents with fragile skin that blisters and becomes red with or without trauma. Marked scarring is left with thin skin, milia and nail changes. It typically begins around age 50-years.It is caused by antibodies to type VII collagen within anchoring fibril structures located at the dermoepidermal junction in skin. Damaged skin may become infected.Diagnosis is by observing the persistence of the condition, direct immunofluorescence, and detecting autoantibodies against type VII collagen. It can appear similar to porphyria cutanea tarda, pemphigoid, pemphigus, dermatitis herpetiformis, or blistering drug eruption. The condition is longterm and has no cure. A good response may be seen with corticosteroids, either alone or combined with azathioprine or dapsone.It is rare, with around 0.08 to 0.5 new cases per million people per year, and it affects males and females equally. Signs and symptoms It generally presents with fragile skin that blisters and becomes red with or without trauma. Marked scarring is left with thin skin, milia and nail changes. It typically begins around age 50-years. Cause It is caused by antibodies to type VII collagen within anchoring fibril structures located at the dermoepidermal junction in skin. Diagnosis Diagnosis is by observing the persistence of the condition, direct immunofluorescence, and detecting autoantibodies against type VII collagen. It can appear similar to porphyria cutanea tarda, pemphigoid, pemphigus, dermatitis herpetiformis, or blistering drug eruption. Treatment The condition is longterm and has no cure. A good response may be seen with corticosteroids, either alone or combined with azathioprine or dapsone. Epidemiology It is rare, with around 0.08 to 0.5 new cases per million people per year, and it affects males and females equally. See also List of cutaneous conditions List of target antigens in pemphigoid List of immunofluorescence findings for autoimmune bullous conditions List of human leukocyte antigen alleles associated with cutaneous conditions References == External links ==

Vascular myelopathy

Vascular myelopathy (vascular disease of the spinal cord) refers to an abnormality of the spinal cord in regard to its blood supply. The blood supply is complicated and supplied by two major vessel groups: the posterior spinal arteries and the anterior spinal arteries—of which the Artery of Adamkiewicz is the largest. Both the posterior and anterior spinal arteries run the entire length of the spinal cord and receive anastomotic (conjoined) vessels in many places. The anterior spinal artery has a less efficient supply of blood and is therefore more susceptible to vascular disease. Whilst atherosclerosis of spinal arteries is rare, necrosis (death of tissue) in the anterior artery can be caused by disease in vessels originating from the segmental arteries such as atheroma (arterial wall swelling) or aortic dissection (a tear in the aorta). Spinal cord infarction Anterior spinal artery syndrome Anterior spinal artery syndrome is necrosis of tissue in the anterior spinal artery or its branches. It is characterised by pain which radiates at onset and sudden quadraplegia (paralysis of all four limbs) or paraplegia (paralysis of the lower body). Within days, flaccid limbs become spastic and hyporeflexia (underactive nerve responses) turns into hyperreflexia (overactive nerve responses) and extensor plantar nerve responses. Sensory loss to pain and temperature also occurs up to the level of damage on the spinal cord, as damage to different areas will affect different parts of the body.In diagnosis, other causes of abrupt paralysis should be excluded such as cord compression, transverse myelitis (inflammation of the spinal cord) and Guillain–Barré syndrome. A specific cause of the infarction should be looked for, such as diabetes, polyarteritis nodosa (inflammatory damage of vessels) or systemic lupus erythematosus. Neurosyphilis is also a known cause. Other causes include: Treatment is supportive and aims to relieve symptoms. The prognosis is dependent upon individual circumstances and factors. Posterior spinal artery syndrome Posterior spinal artery syndrome is much rarer than its anterior counterpart as the white matter structures that are present are much less vulnerable to ischemia since they have a better blood supply. When posterior spinal artery syndrome does occur, dorsal columns are damaged and ischemia may spread into the posterior horns. Clinically the syndrome presents as a loss of tendon reflexes and loss of joint position sense Transient ischemic attack Transient ischemic attacks (TIAs) rarely affect the spinal cord and usually affect the brain; however, cases have been documented in these areas. Spinal arteriovenous malformations are the main cause and are represented later in this article. However, TIAs can result from emboli in calcific aortic disease and aortic coarctation. Spinal arteriovenous malformations Spinal arteriovenous malformations (AVMs, or angiomatous malformations) are congenital (from birth) abnormalities of blood vessels. Arteries that directly communicate with veins bypass the capillary network (which has not yet developed) and thus creates a shunt. AVMs appear as a mass of convoluted, dilated vessels. In regards to the spinal cord, they are usually located in the thoracolumbar region (between the thoracic and lumbar regions, 60% of the time), as opposed to the upper thoracic (20%) and cervical regions (approximately 15%). Cervical malformations arise from the anterior spinal artery and lie within the cord, whereas thoracolumbar malformations can be internal, external or encompass both areas of the cord.Malformations can be recognised as part of an acute illness or gradual onset disease. In diseases such as subarachnoid hemorrhage, signs and symptoms include headache, neck stiffness and back and leg pain. Extradural, subdural and intramedullary hematomas are all signs of acute cord compression. Gradual onset diseases are more common (85-90% of all diseases leading to a diagnosis of malformation) and are usually due to an increased venous pressure. Other factors such as thrombosis or arachnoiditis can be involved. A bruit (unusual blood sounds) may be heard overlying the spinal arteriovenous malformation. Very occasionally, nevus (moles) or angiolipomas are found.Myelography is used to confirm the diagnosis of AVMs and it shows snake-like vessels on the cords surface. If the myelogram is positive, angiography is required to show the extent of malformation and the exact site of the shunt. Magnetic resonance imaging (MRI) may show the appropriate area. If AVMs are left untreated, 50% of patients with gradual symptoms will be unable to walk within 3 years of onset. Surgical occlusion has been shown to halt the progression and may improve any gait or incontinence. See also Foix–Alajouanine syndrome Chronic cerebrospinal venous insufficiency Peripheral vascular disease References == External links ==

Morvans syndrome

Morvans syndrome is a rare, life-threatening autoimmune disease named after the nineteenth century French physician Augustin Marie Morvan. "La chorée fibrillaire" was first coined by Morvan in 1890 when describing patients with multiple, irregular contractions of the long muscles, cramping, weakness, pruritus, hyperhidrosis, insomnia, and delirium. It normally presents with a slow insidious onset over months to years. Approximately 90% of cases spontaneously go into remission, while the other 10% of cases lead to death.In 1890, Morvan described a patient with myokymia (muscle twitching) associated with muscle pain, excessive sweating, and disordered sleep. This rare disorder is characterized by severe insomnia, amounting to no less than complete lack of sleep (agrypnia) for weeks or months in a row, and associated with autonomic alterations consisting of profuse perspiration with characteristic skin miliaria (also known as sweat rash), tachycardia, increased body temperature, and hypertension. Patients display a remarkable hallucinatory behavior, and peculiar motor disturbances, which Morvan reported under the term “fibrillary chorea” but which are best described in modern terms as neuromyotonic discharges.The association of the disease with thymoma, tumour, autoimmune diseases, and autoantibodies suggests an autoimmune or paraneoplastic aetiology. Besides an immune-mediated etiology, it is also believed to occur in gold, mercury, or manganese poisoning. Signs and symptoms In one of the few reported cases, the subject presented with muscle weakness and fatigue, muscle twitching, excessive sweating and salivation, small joint pain, itching and weight loss. The subject also developed confusional episodes with spatial and temporal disorientation, visual and auditory hallucinations, complex behavior during sleep and progressive nocturnal insomnia associated with diurnal drowsiness. There was also severe constipation, urinary incontinence, and excessive lacrimation. When left alone, the subject would slowly lapse into a stuporous state with dreamlike episodes characterized by complex and quasi-purposeful gestures and movements (enacted dreams). Marked hyperhidrosis and excessive salivation were evident. Neurological examination disclosed diffuse muscle twitching and spontaneous and reflex myoclonus, slight muscle atrophy in the limbs, absence of tendon reflexes in the lower limbs and diffuse erythema especially on the trunk with scratching lesions of the skin. Compulsive behaviours, stereotypies and reduplicative paramnesias can be part of the CNS spectrum. Insomnia In all of the reported cases, the need for sleep was severely reduced and in some cases not necessary. The duration of sleep in one case decreased to about 2–4 hours per 24-hour period. Clinical features pertaining to insomnia include daytime drowsiness associated with a loss of ability to sleep, intermingled with confusional oneiric status, and the emergence of atypical REM sleep from wakefulness. The polysomnogram (PSG) picture of this disease is characterized by an inability to generate physiological sleep (key features are the suppression of the hallmarks of stage 2 non-REM sleep: spindles and K complexes) and by the emergence of REM sleep without atonia. The involvement of the thalamus and connected limbic structures in the pathology indicate the prominent role that the limbic thalamus plays in the pathophysiology of sleep. In a case documented in 1974, PSG findings documented the sustained absence of all sleep rhythms for up to a period of 4 months.Electroencephalography (EEG) in one case was dominated by "wakefulness" and “subwakefulness” states alternating or intermingled with short (< 1 min) atypical REM sleep phases, characterized by a loss of muscle atonia. The “subwakefulness” state was characterized by 4–6 Hz theta activity intermingled with fast activity and desynchronized lower voltage theta activity, behaviourally associated with sleep-like somatic and autonomic behavior. The subject was said to have “agrypnia excitata”, which consists of severe total insomnia of long duration associated with decreased vigilance, mental confusion, hallucinations, motor agitation, and complex motor behavior mimicking dreams, and autonomic activation. CNS and autonomic symptoms were caused by impaired corticolimbic control of the subcortical structures regulating the sleep-wake and autonomic functions. Neuromyotonia Neuromyotonia refers to muscle twitching and cramping at rest that is exacerbated with exercise. It is caused by sustained or repetitive spontaneous muscle activity of peripheral nerve origin. Myokymia, or spontaneous rippling and twitching movements of muscles, is a visible component of neuromyotonia. Electromyography (EMG) discloses spontaneous, repetitive motor unit or single fiber discharges firing in irregular rhythmic bursts at high intraburst frequencies. Some of the muscles exhibiting twitching include the bilateral gastrocnemii, quadriceps femoris, biceps brachii, and right masseter. In vivo electrophysiological studies suggest at least some dysfunction of the muscle cell membrane. In the examined muscles, no abnormal insertional activity or fibrillation potentials were noted. Nerve conduction studies were normal. Other symptoms Breathing difficulties can occur, resulting from neuromyotonic activity of the laryngeal muscles. Laryngeal spasm possibly resulting from neuromyotonia has been described previously, and this highlights that, in patients with unexplained laryngospasm, neuromytonia should be added to the list of differential diagnoses.Studies have shown subtly decreased metabolism on positron emission tomography (PET) and single photon emission computed tomography (SPECT) in the left inferior frontal and left temporal lobes. and or basal ganglia hypermetabolism. Ancillary laboratory tests including MRI and brain biopsy have confirmed temporal lobe involvement. Cranial MRI shows increased signal in the hippocampus.Cerebral spinal fluid (CSF) shows normal protein, glucose, white blood cell, and immunoglobulin G (IgG) levels, but there are weak oligoclonal bands, which are absent in the blood serum. Marked changes in circadian serum levels of neurohormones and increased levels of peripheral neurotransmitters were also observed. The absence of morphological alterations of the brain pathology, the suggestion of diffusion of IgG into the thalamus and striatum, more marked than in the cortex (consistent with effects on the thalamolimbic system) the oligoclonal bands in the CSF and the amelioration after PE all strongly support an antibody-mediated basis for the condition. Raised CSF IgG concentrations and oligoclonal bands have been reported in patients with psychosis. Anti-acetylcholine receptors (anti-AChR) antibodies have also been detected in patients with thymoma, but without clinical manifestations of myasthenia gravis. There have also been reports of non-paraneoplastic limbic encephalitis associated with raised serum VGKC suggesting that these antibodies may give rise to a spectrum of neurological disease presenting with symptoms arising peripherally, centrally, or both. Yet, in two cases, oligoclonal bands were absent in the CSF and serum, and CSF immunoglobulin profiles were unremarkable. Comorbid conditions In one case, a patient was diagnosed with both Morvans syndrome and pulmonary hyalinizing granulomas (PHG). PHG are rare fibrosing lesions of the lung, which have central whorled deposits of lamellar collagen. How these two diseases relate to one another is still unclear.Thymoma, prostate adenoma, and in situ carcinoma of the sigmoid colon have also been found in patients with Morvans Syndrome. Mechanism Antibodies against voltage-gated potassium channels (VGKC), which are detectable in about 40% of patients with acquired neuromytonia, have been implicated in Morvans pathophysiology. Raised serum levels of antibodies to VGKCs have been reported in three patients with Morvans Syndrome. Binding of serum from a patient with Morvans Syndrome to the hippocampus in a similar pattern of antibodies to known VGKC suggest that these antibodies can also cause CNS dysfunction. Additional antibodies against neuromuscular junction channels and receptors have also been described. Experimental evidence exists that these anti-VGKC antibodies cause nerve hyperexcitability by suppression of voltage gated K+ outward currents, whereas other, yet undefined humoral factors have been implicated in anti-VGKC antibody negative neuromyotonia. It is believed that antibodies to the Shaker-type K+ channels (the Kv1 family) are the type of potassium channel most strongly associated with acquired neuromyotonia and Morvans Syndrome.Whether VGKC antibodies play a pathogenic role in the encephalopathy as they do in the peripheral nervous system is as yet unclear. It has been suggested that the VGKC antibodies may cross the blood–brain barrier and act centrally, binding predominantly to thalamic and striatal neurons causing encephalopathic and autonomic features. Diagnosis Differential diagnosis The symptoms of Morvans Syndrome have been noted to bear a striking similarity to limbic encephalitis (LE). These include the CNS symptoms consisting of insomnia, hallucinations, and disorientation, as well as dementia and psychosis. Both entities can be paraneoplastic and associated with thymoma. Recently, VGKC antibodies were found in patients with LE, strengthening the hypothesis that LE and Morvans Syndrome may be closely connected. Varying symptoms may be used to determine which of the two diseases the subject has. Amnesia, seizures, and mesial temporal lobe structural abnormalities are features of LE, whereas myokymia, hyperhydrosis, and insomnia favor Morvans Syndrome. Treatment In most of the reported cases, the treatment options were very similar. Plasmapheresis alone or in combination with steroids, sometimes also with thymectomy and azathioprine, have been the most frequently used therapeutic approach in treating Morvans Syndrome. However, this does not always work, as failed response to steroids and to subsequently added plasmapheresis have been reported. Intravenous immunoglobulin was effective in one case.In one case, the dramatic response to high-dose oral prednisolone together with pulse methylprednisolone with almost complete disappearance of the symptoms within a short period should induce consideration of corticosteroids.In another case, the subject was treated with haloperidol (6 mg/day) with some improvement in the psychomotor agitation and hallucinations, but even high doses of carbamazepine given to the subject failed to improve the spontaneous muscle activity. Plasma Exchange (PE) was initiated, and after the third such session, the itching, sweating, mental disturbances, and complex nocturnal behavior improved and these symptoms completely disappeared after the sixth session, with improvement in insomnia and reduced muscle twitching. However, one month after the sixth PE session, there was a progressive worsening of insomnia and diurnal drowsiness, which promptly disappeared after another two PE sessions.In one case, high dose steroid treatment resulted in a transient improvement, but aggressive immuno-suppressive therapy with cyclophosphamide was necessary to control the disease and result in a dramatic clinical improvement.In another case, the subject was treated with prednisolone (1 mg/kg body weight) with carbamazepine, propranolol, and amitriptyline. After two weeks, improvement with decreased stiffness and spontaneous muscle activity and improved sleep was observed. After another 7–10 days, the abnormal sleep behavior disappeared completely.In another case, symptomatic improvement with plasmapheresis, thymectomy, and chronic immunosuppression provide further support for an autoimmune or paraneoplastic basis.Although thymectomy is believed to be a key element in the proposed treatment, there is a reported case of Morvans Syndrome presenting itself post-thymectomy. Epidemiology There are only about 14 reported cases of Morvans syndrome in the English literature. With only a limited number of reported cases, the complete spectrum of the central nervous system (CNS) symptomatology has not been well established. The natural history of Morvans is highly variable. Two cases have been reported to remit spontaneously. Others have required a combination of plasmapheresis and long term immunosuppression, although in one of these cases the patient died shortly after receiving plasma exchange (PE). Other fatalities without remission have been described by, amongst others, Morvan himself. References == External links ==

Calcific tendinitis

Calcific tendinitis is a common condition where calcium deposits form in a tendon, sometimes causing pain at the affected site. Deposits can occur in several places in the body, but are by far most common in the rotator cuff of the shoulder. Around 80% of those with deposits experience symptoms, typically chronic pain during certain shoulder movements, or sharp acute pain that worsens at night. Calcific tendinitis is typically diagnosed by physical exam and X-ray imaging. The disease often resolves completely on its own, but is typically treated with non-steroidal anti-inflammatory drugs to relieve pain, rest and physical therapy to promote healing, and in some cases various procedures to breakdown and/or remove the calcium deposits. Adults aged 30–50 are most commonly affected by calcific tendinitis. It is twice as common in women as men, and is not associated with exercise. Calcifications in the rotator cuff were first described by Ernest Codman in 1934. The name, "calcifying tendinitis" was coined by Henry Plenk in 1952. Signs and symptoms Up to 20% of those with calcific tendinitis have no symptoms. For those with symptoms, the symptoms vary based on the phase of the disease. In the initial "formative phase" when the calcium deposits are being formed, people rarely experience any symptoms. Those that do have symptoms tend to have intermittent shoulder pain, particularly during forward should flexion (i.e. lifting the arm in front of the body). In the "resorptive phase" when the calcium deposit is breaking down, many experience severe acute pain that worsens at night. Those affected tend to hold the shoulder rotated inwards to alleviate pain, and have difficulty lying on the affected shoulder. Some people experience heat and redness at the affected shoulder, as well as a limited range of motion. Cause Calcific tendinitis is caused by deposits of calcium phosphate crystals in the tendons of the shoulder. These deposits are most frequently found in the supraspinatus tendon (63% of the time), and less frequently in the infraspinatus tendon (7%), subacromial bursa (7%), subscapularis tendon (3%), or in both the supraspinatus and subscapularis tendons at the same time (20%).The development of calcific tendinitis is often divided into three stages. First, in the "precalcific stage", something causes tendon cells to transform into other cells that can act as sites for calcium deposition. This is followed by the two-part "calcific stage"; first calcium is deposited (the formative phase), then the body begins to break down the calcium deposit (the resporptive phase). Finally, in the "postcalcific stage" the calcium deposits are replaced with new tissue and the tendon completely heals.The cause of the calcium deposits remains unclear, although several theories have been put forward. Some theories involve the differentiation of tendon cells into other cells, namely cartilages or bone cells. Others associate the condition with cell death due to aging, wear, or lack of oxygen in the tissue; however, the disease is uncommon in the very old, not associated with exercise, and tends to resolve completely even if untreated. Diagnosis Calcific tendinitis is typically diagnosed by physical examination and X-ray imaging. During the formative phase, X-ray images typically reveal calcium deposits with uniform density and a clear margin. In the more painful resorptive phase, deposits instead appear cloudy and with unclear margins. By arthroscopy, formative stage deposits appear crystalline and chalk-like, while resorptive stage deposits appear smooth resembling toothpaste. Ultrasound is also used to locate and assess calcium deposits. In the formative stage, deposits are hyperechoic and arc-shaped; in the resorptive stage deposits are less echogenic and appear fragmented. Treatment The first line of treatment for calcific tendinitis is typically nonsteroidal anti-inflammatory drugs to relieve pain, rest for the affected joint, and sometimes physical therapy to avoid joint stiffness. For those with severe pain direct injections of steroids to the affected site are often effective for pain relief, but may interfere with reabsorption of the calcium deposit. For those whose pain doesnt improve with medication and rest, the deposit can be dissolved and removed with techniques called "ultrasound-guided needling", "barbotage", and "US-PICT" (for "ultrasound percutaneous injection in calcific tenditis"). In each, ultrasound is used to locate the deposit and guide a needle to the affected site. There saline and lidocaine are injected to dissolve the deposit, then removed to wash it away. Another common treatment is extracorporeal shockwave therapy, where pulses of sound are used to break up the deposit and promote healing. There is little standardization of energy levels, duration, and time interval of treatment; though most studies report positive outcomes with low- to medium-energy waves (below 0.28 mJ/mm2). Surgery Surgery is only recommended once 6 months of conservative, non-operative treatment has failed to reduce symptoms. Surgery is arthroscopic and involves calcification removal with or without acromioplasty of the shoulder. Additionally, debate remains over whether a complete removal of the deposits is necessary, or if equal pain relief can be obtained from a partial removal of calcium deposits.Removing the deposits either with open shoulder surgery or arthroscopic surgery are both difficult operations, but with high success rates (around 90%). About 10% require re-operation. If the deposit is large, then frequently the patient will require a rotator cuff repair to fix the defect left in the tendon when the deposit is removed or to reattach the tendon to the bone if the deposit was at the tendon insertion into the bone. Outcomes Nearly all people with calcific tendinitis recover completely with time or treatment. Treatment helps alleviate pain, but long-term follow-up studies have shown that people recover with or without treatment. Epidemiology Calcific tendinitis typically occurs in adults aged 30 to 50, and is rare in those older than 70. It is twice as common in women as men.Risk factors that increase the chance of developing calcific tendinitis include; hormonal disorders, like diabetes and hypothyroidism, autoimmune disorders, like rheumatoid arthritis, and metabolic disorders that also cause kidney stones, gallstones, and gout. Occupations that consist of repetitive overhead lifting, such as athletes or construction workers, do not seem to significantly increase the likelihood of developing calcific tendinitis. History Calcifications in the rotator cuff tendon were first described by Ernest Codman in his 1934 book The Shoulder. In 1952, in his study on x-ray therapy for people with such calcifications, Henry Plenk coined the term "calcifying tendinitis". References External links eMedicine on Calcific Tendonitis Extracorporeal shock wave therapy (subscription required)

Post-kala-azar dermal leishmaniasis

Post-kala-azar dermal leishmaniasis (PKDL) is a complication of visceral leishmaniasis (VL); it is characterised by a macular, maculopapular, and nodular rash in a patient who has recovered from VL and who is otherwise well. The rash usually starts around the mouth from where it spreads to other parts of the body depending on severity. Post-kala-azar dermal leishmaniasis (also known as "Post-kala-azar dermatosis") found mainly on the face, arms, and upper part of the trunk. It occurs years (in the Indian variation) or a few months(in the African strain) after the successful treatment of visceral leishmaniasis. It is mainly seen in Sudan and India where it follows treated VL in 50% and 5-10% of cases, respectively. Thus, it is largely restricted to areas where Leishmania donovani is the causative parasite. The interval at which PKDL follows VL is 0–6 months in Sudan and 2–3 years in India. PKDL probably has an important role in interepidemic periods of VL, acting as a reservoir for parasites. PKDL was first identified by Sir Upendranath Brahmachari, who initially called it dermal leishmanoid. He published his observations in the Indian Medical Gazette in 1922. Mechanism The cause of PKDL is uncertain. Possibilities may include use of antimonial drugs, sunburn, reinfection with kala-azar, memory T cell responses failing in certain organs; and genetic susceptibility.There is increasing evidence that the pathogenesis is largely immunologically mediated; high concentrations of interleukin 10 in the peripheral blood of VL patients predict the development of PKDL. During VL, interferon gamma is not produced by peripheral blood mononuclear cells (PBMC). After treatment of VL, PBMCs start producing interferon gamma, which coincides with the appearance of PKDL lesions due to interferon-gamma-producing cells causing skin inflammation as a reaction to persisting parasites in the skin. Diagnosis PKDL is difficult to diagnose.Diagnosis is mainly clinical, but parasites can be seen by microscopy in smears with limited sensitivity. PCR and monoclonal antibodies may detect parasites in more than 80% of cases. Serological tests and the leishmanin skin test are of limited value. Treatment Treatment is always needed in Indian PKDL; in Sudan, most cases are self-limited but severe and chronic cases are treated. Sodium stibogluconate is given at 20 mg/kg for 2 months in Sudan and for 4 months in India. Liposomal amphotericine B seems effective. Although research has brought many new insights in pathogenesis and management of PKDL, several issues in particular in relation to control remain unsolved and deserve urgent attention.Miltefosine is the only available oral medication available for VL and PKDL. While the drug works for short-term treatment of VL, PKDL would require a longer treatment of more than 28 days with this drug. Miltefosine is not recommended for use as a monotherapy to treat PKDL. Society and culture People with PKDL are a reservoir of leishmaniasis. To eliminate leishmaniasis from a population, people with PKDL must get treatment.The government of India has an kala-azar elimination program ongoing which entered a consolidation phase in 2017. See also List of cutaneous conditions == References ==

Fordyce spots

Fordyce spots (also termed Fordyce granules) are visible sebaceous glands that are present in most individuals. They appear on the genitals and/or on the face and in the mouth. They appear as small, painless, raised, pale, red or white spots or bumps 1 to 3 mm in diameter that may appear on the scrotum, shaft of the penis or on the labia, as well as the inner surface (retromolar mucosa) and vermilion border of the lips of the face. They are not associated with any disease or illness, nor are they infectious but rather they represent a natural occurrence on the body. No treatment is therefore required. Persons with this condition sometimes consult a dermatologist because they are worried they may have a sexually transmitted disease (especially genital warts) or some form of cancer.Some diseases may appear similar to Fordyce spots such as sexually transmitted diseases. Description On the shaft of the penis, Fordyce spots are more visible when the skin is stretched, and may only be noticeable during an erection. The spots can also appear on the skin of the scrotum.Oral Fordyce granules appear as rice-like granules, white or yellow-white in color. They are painless papules (small bumps), about 1–3 mm in greatest dimension. The most common site is along the line between the vermilion border and the oral mucosa of the upper lip, or on the buccal mucosa (inside the cheeks) in the commissural region, often bilaterally. They may also occur on the mandibular retromolar pad and tonsillar areas, but any oral surface may be involved. There is no surrounding mucosal change. Some patients will have hundreds of granules while most have only one or two.Occasionally, several adjacent glands will coalesce into a larger cauliflower-like cluster similar to sebaceous hyperplasia of the skin. In such an instance, it may be difficult to determine whether or not to diagnose the lesion as sebaceous hyperplasia or sebaceous adenoma. The distinction may be moot because both entities have the same treatment, although the adenoma has a greater growth potential. Sebaceous carcinoma of the oral cavity has been reported, presumably arising from Fordyce granules or hyperplastic foci of sebaceous glands.In some persons with Fordyce spots, the glands express a thick, chalky discharge when squeezed. Causes Normally, sebaceous glands are only found in association with a hair follicle.They appear to be more obvious in people with oily skin types, with some rheumatic disorders, and in hereditary nonpolyposis colorectal cancer. In the latter, the most common site for Fordyce spots is the lower gingiva (gums) and vestibular mucosa. Diagnosis Large numbers of lobules coalescing into a definitely elevated mass may be called benign sebaceous hyperplasia, and occasional small keratin-filled pseudocysts may be seen and must be differentiated from epidermoid cyst or dermoid cyst with sebaceous adnexa. The pathologist must be careful to differentiate such lesions from salivary neoplasms with sebaceous cells, such as sebaceous lymphadenoma and sebaceous carcinoma. Oral Fordyce granules are usually not biopsied because they are readily diagnosed clinically, but they are often seen as incidental findings of mucosal biopsies of the buccal, labial and retromolar mucosa. The granules are similar to normal sebaceous glands of the skin but lack hair follicles and almost always lack a ductal communication with the surface. The glands are located just beneath the overlying epithelium and often produce a local elevation of the epithelium. Individual sebaceous cells are large, with central dark nuclei and abundant foamy cytoplasm. Classification Sebaceous glands are normal structures of the skin but may also be found ectopically in the mouth, where they are referred to as oral Fordyce granules or ectopic sebaceous glands. On the foreskin they are called Tysons glands, not to be confused with hirsuties coronae glandis.When they appear on the penis, they are also called penile sebaceous glands. Treatment Most doctors consider this a normal physiological phenomenon and advise against treatment. Prognosis Fordyce spots are completely benign and require no treatment. They occur in 70 to 80 percent of adults. Often their presence is considered normal anatomic variance rather than a true medical condition. Epidemiology This variation of normal anatomy is seen in the majority of adults. It is estimated about 80% of people have oral Fordyce spots, but seldom are granules found in large numbers. They are not usually visible in children, and tend to appear at about age 3, then increasing during puberty and become more obvious in later adulthood. They are more prominent in males. History They are named after an American dermatologist, John Addison Fordyce. References External links DermAtlas: Fordyce spots Fordyce spots

Linear focal elastosis

Linear focal elastosis or elastotic striae is a skin condition that presents with asymptomatic, palpable or atrophic, yellow lines of the middle and lower back, thighs, arms and breasts. See also Skin lesion References == External links ==

Phalanx bone

The phalanges (singular: phalanx ) are digital bones in the hands and feet of most vertebrates. In primates, the thumbs and big toes have two phalanges while the other digits have three phalanges. The phalanges are classed as long bones. Structure The phalanges are the bones that make up the fingers of the hand and the toes of the foot. There are 56 phalanges in the human body, with fourteen on each hand and foot. Three phalanges are present on each finger and toe, with the exception of the thumb and large toe, which possess only two. The middle and far phalanges of the fourth and fifth toes are often fused together (symphalangism). The phalanges of the hand are commonly known as the finger bones. The phalanges of the foot differ from the hand in that they are often shorter and more compressed, especially in the proximal phalanges, those closest to the torso.A phalanx is named according to whether it is proximal, middle, or distal and its associated finger or toe. The proximal phalanges are those that are closest to the hand or foot. In the hand, the prominent, knobby ends of the phalanges are known as knuckles. The proximal phalanges join with the metacarpals of the hand or metatarsals of the foot at the metacarpophalangeal joint or metatarsophalangeal joint. The intermediate phalanx is not only intermediate in location, but usually also in size. The thumb and large toe do not possess a middle phalanx. The distal phalanges are the bones at the tips of the fingers or toes. The proximal, intermediate, and distal phalanges articulate with one another through interphalangeal joints of hand and interphalangeal joints of the foot.: 708–711 : 708–711 Bone anatomy Each phalanx consists of a central part, called the body, and two extremities. The body is flat on either side, concave on the palmar surface, and convex on the dorsal surface. Its sides are marked with rough areas giving attachment to fibrous sheaths of flexor tendons. It tapers from above downwards. The proximal extremities of the bones of the first row present oval, concave articular surfaces, broader from side to side than from front to back. The proximal extremity of each of the bones of the second and third rows presents a double concavity separated by a median ridge. The distal extremities are smaller than the proximal, and each ends in two condyles (knuckles) separated by a shallow groove; the articular surface extends farther on the palmar than on the dorsal surface, a condition best marked in the bones of the first row.In the foot, the proximal phalanges have a body that is compressed from side to side, convex above, and concave below. The base is concave, and the head presents a trochlear surface for articulation with the second phalanx. The middle are remarkably small and short, but rather broader than the proximal. The distal phalanges, as compared with the distal phalanges of the finger, are smaller and are flattened from above downward; each presents a broad base for articulation with the corresponding bone of the second row, and an expanded distal extremity for the support of the nail and end of the toe. Distal phalanx In the hand, the distal phalanges are flat on their palmar surface, small, and with a roughened, elevated surface of horseshoe form on the palmar surface, supporting the finger pulp.: 6b. 3. The Phalanges of the Hand  The flat, wide expansions found at the tips of the distal phalanges are called apical tufts. They support the fingertip pads and nails. The phalanx of the thumb has a pronounced insertion for the flexor pollicis longus (asymmetric towards the radial side), an ungual fossa, and a pair of unequal ungual spines (the ulnar being more prominent). This asymmetry is necessary to ensure that the thumb pulp is always facing the pulps of the other digits, an osteological configuration which provides the maximum contact surface with held objects.In the foot, the distal phalanges are flat on their dorsal surface. It is largest proximally and tapers to the distal end. The proximal part of the phalanx presents a broad base for articulation with the middle phalanx, and an expanded distal extremity for the support of the nail and end of the toe.: 6b. 3. The Phalanges of the Foot  The phalanx ends in a crescent-shaped rough cap of bone epiphysis — the apical tuft (or ungual tuberosity/process) which covers a larger portion of the phalanx on the volar side than on the dorsal side. Two lateral ungual spines project proximally from the apical tuft. Near the base of the shaft are two lateral tubercles. Between these a V-shaped ridge extending proximally serves for the insertion of the flexor pollicis longus. Another ridge at the base serves for the insertion of the extensor aponeurosis. The flexor insertion is sided by two fossae — the ungual fossa distally and the proximopalmar fossa proximally. Development The number of phalanges in animals is often expressed as a "phalangeal formula" that indicates the numbers of phalanges in digits, beginning from the innermost medial or proximal. For example, humans have a 2-3-3-3-3 formula for the hand, meaning that the thumb has two phalanges, whilst the other fingers each have three. In the distal phalanges of the hand the centres for the bodies appear at the distal extremities of the phalanges, instead of at the middle of the bodies, as in the other phalanges. Moreover, of all the bones of the hand, the distal phalanges are the first to ossify.: 6b. 3. The Phalanges of the Hand Function The distal phalanges of ungulates carry and shape nails and claws and these in primates are referred to as the ungual phalanges. History of phalanges Etymology The term phalanx or phalanges refers to an ancient Greek army formation in which soldiers stand side by side, several rows deep, like an arrangement of fingers or toes. In animals Most land mammals including humans have a 2-3-3-3-3 formula in both the hands (or paws) and feet. Primitive reptiles usually had the formula 2-3-4-4-5, and this pattern, with some modification, remained in many later reptiles and in the mammal-like reptiles. The phalangeal formula in the flippers of cetaceans (marine mammals) varies widely due to hyperphalangy (the increase in number of phalanx bones in the digits). In humpback whales, for example, the phalangeal formula is 0/2/7/7/3; in pilot whales the formula is 1/10/7/2/1.In vertebrates, proximal phalanges have a similar placement in the corresponding limbs, be they paw, wing or fin. In many species, they are the longest and thickest phalanx ("finger" bone). The middle phalanx also a corresponding place in their limbs, whether they be paw, wing, hoof or fin. The distal phalanges are cone-shaped in most mammals, including most primates, but relatively wide and flat in humans. Primates The morphology of the distal phalanges of human thumbs closely reflects an adaptation for a refined precision grip with pad-to-pad contact. This has traditionally been associated with the advent of stone tool-making. However, the intrinsic hand proportions of australopiths and the resemblance between human hands and the short hands of Miocene apes, suggest that human hand proportions are largely plesiomorphic (as found in ancestral species) — in contrast to the derived elongated hand pattern and poorly developed thumb musculature of other extant hominoids.In Neanderthals, the apical tufts were expanded and more robust than in modern and early upper Paleolithic humans. A proposal that Neanderthal distal phalanges was an adaptation to colder climate (than in Africa) is not supported by a recent comparison showing that in hominins, cold-adapted populations possessed smaller apical tufts than do warm-adapted populations. In non-human, living primates the apical tufts vary in size, but they are never larger than in humans. Enlarged apical tufts, to the extent they actually reflect expanded digital pulps, may have played a significant role in enhancing friction between the hand and held objects during Neolithic toolmaking.Among non-human primates phylogenesis and style of locomotion appear to play a role in apical tuft size. Suspensory primates and New World monkeys have the smallest apical tufts, while terrestrial quadrupeds and Strepsirrhines have the largest. A study of the fingertip morphology of four small-bodied New World monkey species, indicated a correlation between increasing small-branch foraging and reduced flexor and extensor tubercles in distal phalanges and broadened distal parts of distal phalanges, coupled with expanded apical pads and developed epidermal ridges. This suggests that widened distal phalanges were developed in arboreal primates, rather than in quadrupedal terrestrial primates. Cetaceans Whales exhibit hyperphalangy. Hyperphalangy is an increase in the number of phalanges beyond the plesiomorphic mammal condition of three phalanges-per-digit. Hyperphalangy was present among extinct marine reptiles -- ichthyosaurs, plesiosaurs, and mosasaurs -- but not other marine mammals, leaving whales as the only marine mammals to develop this characteristic. The evolutionary process continued over time, and a very derived form of hyperphalangy, with six or more phalanges per digit, evolved convergently in rorqual whales and oceanic dolphins, and was likely associated with another wave of signaling within the interdigital tissues. Other mammals In ungulates (hoofed mammals) the forelimb is optimized for speed and endurance by a combination of length of stride and rapid step; the proximal forelimb segments are short with large muscles, while the distal segments are elongated with less musculature. In two of the major groups of ungulates, odd-toed and even-toed ungulates, what remain of the "hands" — the metacarpal and phalangeal bones — are elongated to the extent that they serve little use beyond locomotion. The giraffe, the largest even-toed ungulate, has large terminal phalanges and fused metacarpal bones able to absorb the stress from running.The sloth spends its life hanging upside-down from branches, and has highly specialized third and fourth digits for the purpose. They have short and squat proximal phalanges with much longer terminal phalanges. They have vestigial second and fifth metacarpals, and their palm extends to the distal interphalangeal joints. The arboreal specialization of these terminal phalanges makes it impossible for the sloth to walk on the ground where the animal has to drag its body with its claws. Additional images See also Hand Foot References External links MedTerms.com Medical Dictionary

Irregular sleep–wake rhythm

Irregular sleep–wake rhythm (ISWD) is a rare form of circadian rhythm sleep disorder. It is characterized by numerous naps throughout the 24-hour period, no main nighttime sleep episode, and irregularity from day to day. Affected individuals have no pattern of when they are awake or asleep, may have poor quality sleep, and often may be very sleepy while they are awake. The total time asleep per 24 hours is normal for the persons age. The disorder is serious—an invisible disability. It can create social, familial, and work problems, making it hard for a person to maintain relationships and responsibilities, and may make a person home-bound and isolated. Causes ISWD has various causes, including neurological disorders such as dementia (particularly Alzheimers Disease), brain damage, or intellectual disabilities. It is thought that those affected have a weak circadian clock. The risk for the disorder increases with age, but only due to increased prevalence of co-morbid medical disorders. Diagnosis A sleep diary should be kept to aid in diagnosis and for chronicling the sleep schedule during treatment. Other ways to monitor the sleep schedule are actigraphy or use of a Continuous Positive Airway Pressure (CPAP) machine that can log sleeping times The following are possible warning signs: sleeping off and on in a series of naps during the day and at night, with no regular pattern but with normal total sleep time, difficulty getting restorative sleep, and excessive daytime sleepiness.Because of the changes in sleep/wake time, and because this is a rare disorder, initially it can seem like another circadian rhythm sleep disorder such as non-24-hour sleep–wake disorder or like insomnia. Initial visit with sleep physician A physician specializing in sleep medicine may ask patients about their medical history; for example: neurological problems, prescription or non-prescription medications taken, alcohol use, family history, and any other sleep problems. A thorough medical and neurological exam is indicated. The patient will be asked to complete a sleep diary, recording natural sleep and wake up times, over several weeks. Sleep rating with the Epworth Sleepiness Scale may be used. Medical testing A neurological condition or another medical problem may be suspected, in which case, blood tests, a CT scan or an MRI may be used. An overnight sleep study is usually not needed to detect this disorder, but may be indicated if other sleep disorders, such as sleep apnea and periodic limb movement disorder, seem likely. The overnight sleep study is called polysomnography. It charts brain waves, heart beat, muscle activity, and breathing during sleep. It also records arm and leg movement. It will show if there are other sleep disorders that are causing or increasing the problems with ISWD. Management Treatment for irregular sleep–wake rhythm tries to enable the body clock in the brain, such that a normal long sleep period at night can be achieved. Education about sleep hygiene is important, and counseling can be helpful. Melatonin, vitamin B12, sleep aids, wake aids, and other medications may also be used. Exposure to light during the daytime and activities occurring at regular times each day may help to restore a normal rhythm.The management of this disorder may vary for different subgroups of patients. Affected individuals with dementia should not be prescribed sleep-promoting medications (sedatives) for ISWD due to the increased prevalence of adverse effects in this group outweighing the possible benefits. Research There is currently a great deal of active research on various aspects of circadian rhythm; this often occurs at major universities in conjunction with sleep research clinics at major hospitals. An example is the program with Harvard Medical School and Brigham and Womens Hospital. This research includes programs that are staffed by researchers from various departments at the university, including psychiatry, neurology, chemistry, biology. Other major sleep research centers are in Tel Aviv in Israel, Munich in Germany and in Japan.A wide variety of sleep disorders are actively being researched. Measuring body temperature or melatonin levels may be used. Some hospitals do blood tests for melatonin levels. Saliva tests for melatonin are now available for online purchase; its metabolites can also be tested in urine. Nomenclature The current formally correct name of the disorder is Circadian Rhythm Sleep Disorder: Irregular Sleep Wake Rhythm Type. This disorder has been referred to by many other terms, including: Irregular Sleep Wake Pattern, irregular sleep wake syndrome, Irregular Sleep Wake Rhythm (ISWRD), Irregular Sleep Wake Cycle, Irregular Sleep Wake Schedule and Irregular Sleep Wake Disorder (ISWD). Sometimes the words sleep and wake are hyphenated (sleep-wake), sometimes joined with an en dash (sleep–wake) and sometimes open (sleep wake). Sometimes the words are capitalized and sometimes they are not. See also Advanced sleep phase syndrome Chronobiology Circadian rhythm Delayed sleep phase disorder References == External links ==

Fistula

A fistula (plural: fistulas or fistulae ; from Latin fistula, "tube, pipe") in anatomy is an abnormal connection between two hollow spaces (technically, two epithelialized surfaces), such as blood vessels, intestines, or other hollow organs. Types of fistula can be described by their location. Anal fistulas connect between the anal canal and the perianal skin. Anovaginal or rectovaginal fistulas occur when a hole develops between the anus or rectum and the vagina. Colovaginal fistulas occur between the colon and the vagina. Urinary tract fistulas are abnormal openings within the urinary tract or an abnormal connection between the urinary tract and another organ such as between the bladder and the uterus in a vesicouterine fistula, between the bladder and the vagina in a vesicovaginal fistula, and between the urethra and the vagina in urethrovaginal fistula. When occurring between two parts of the intestine, it is known as an enteroenteral fistula, between the small intestine and the skin as an enterocutaneous fistula, and between the colon and the skin as a colocutaneous fistula.Fistulas can result from an infection or inflammation, injury or surgery. Fistulas are sometimes surgically created as part of a treatment, for example arteriovenous fistulas for hemodialysis.Treatment for fistula varies depending on the cause and extent of the fistula, but often involves surgical intervention combined with antibiotic therapy. In some cases the fistula is temporarily covered using a fibrin glue or plug. Catheters may be required to drain a fistula.Globally, every year between 50,000 and 100,000 women are affected by fistula relating to childbirth. In botany, the term is most common in its adjectival forms, where it is used in binomial names to refer to species that are distinguished by hollow or tubular structures. Monarda fistulosa, for example, has tubular flowers. The term was first used in the 14th century. Definition A fistula is an abnormal connection between vessels or organs that do not usually connect. It can be due to a disease or trauma, or purposely surgically created. Classification Various types of fistulas include: Blind: Only one open end; may also be called sinus tracts. Complete: Both internal and external openings. Incomplete: An external skin opening that does not connect to any internal organ.Although most fistulas are in forms of a tube, some can also have multiple branches. Location Types of fistula can be described by their location. Anal fistulas connect between the epithelialized surface of the anal canal and the perianal skin. Anovaginal or rectovaginal fistulas occur when a hole develops between the anus or rectum and the vagina. Colovaginal fistulas occur between the colon and the vagina. Urinary tract fistulas are abnormal openings within the urinary tract or an abnormal connection between the urinary tract and another organ such as between the bladder and the uterus in a vesicouterine fistula, between the bladder and the vagina in a vesicovaginal fistula, and between the urethra and the vagina in urethrovaginal fistula. When occurring between two parts of the intestine, it is known as an enteroenteral fistula, between the small intestine and the skin as an enterocutaneous fistula, and between the small intestine and the colon as a colocutaneous fistula.The following list is sorted by the International Statistical Classification of Diseases and Related Health Problems. H: Diseases of the eye, adnexa, ear, and mastoid process (H04.6) Lacrimal fistula (H05.81) Carotid cavernous fistula (H70.1) Mastoid fistula Craniosinus fistula: between the intracranial space and a paranasal sinus (H83.1) Labyrinthine fistula Perilymph fistula: tear between the membranes between the middle and inner ears Preauricular fistula Preauricular fistula: usually on the top of the cristae helicis of the ears I: Diseases of the circulatory system (I25.4) Coronary arteriovenous fistula, acquired (I28.0) Arteriovenous fistula of pulmonary vessels Pulmonary arteriovenous fistula: between an artery and vein of the lungs, resulting in shunting of blood. This results in improperly oxygenated blood. (I67.1) Cerebral arteriovenous fistula, acquired (I77.0) Arteriovenous fistula, acquired (I77.2) Fistula of artery J: Diseases of the respiratory system (J86.0) Pyothorax with fistula (J95.0) Tracheoesophageal fistula, between the trachea and the esophagus. This may be congenital or acquired, for example as a complication of a tracheostomy. K: Diseases of the digestive system (K11.4) Salivary gland fistula (K31.6) Fistula of stomach and duodenum (K31.6) Gastrocolic fistula (K31.6) Gastrojejunocolic fistula – after a Billroth II a fistula forms between the transverse colon and the upper jejunum (which, post Billroth II, is attached to the remainder of the stomach). Fecal matter passes improperly from the colon to the stomach and causes halitosis. Enterocutaneous fistula: between the intestine and the skin surface, namely from the duodenum or the jejunum or the ileum. This definition excludes the fistulas arising from the colon or the appendix. Gastric fistula: from the stomach to the skin surface (K38.3) Fistula of appendix (K60) Anal and rectal fissures and fistulas (K60.3) Anal fistula (K60.5) Anorectal fistula (fecal fistula, fistula-in-ano): connecting the rectum or other anorectal area to the skin surface. This results in abnormal discharge of feces through an opening other than the anus. (K63.2) Fistula of intestine Enteroenteral fistula: between two parts of the intestine (K82.3) Fistula of gallbladder (K83.3) Fistula of bile duct Biliary fistula: connecting the bile ducts to the skin surface, often caused by gallbladder surgery Pancreatic fistula: between the pancreas and the exterior via the abdominal wall M: Diseases of the musculoskeletal system and connective tissue (M25.1) Fistula of joint N: Diseases of the urogenital system (N32.1) Vesicointestinal fistula (N36.0) Urethral fistula Innora:between the prostatic utricle and the outside of the body (N64.0) Fistula of nipple (N82) Fistulae involving female genital tract / Obstetric fistula (N82.0) Vesicovaginal fistula: between the bladder and the vagina (N82.1) Other female urinary-genital tract fistulae Cervical fistula: abnormal opening in the cervix (N82.2) Fistula of vagina to small intestine Enterovaginal fistula: between the intestine and the vagina (N82.3) Fistula of vagina to large intestine Rectovaginal: between the rectum and the vagina (N82.4) Other female intestinal-genital tract fistulae (N82.5) Female genital tract-skin fistulae (N82.8) Other female genital tract fistulae (N82.9) Female genital tract fistula, unspecified Q: Congenital malformations, deformations and chromosomal abnormalities (Q18.0) Sinus, fistula and cyst of branchial cleft Congenital preauricular fistula: A small pit in front of the ear. Also known as an ear pit or preauricular sinus. (Q26.6) Portal vein-hepatic artery fistula (Q38.0) Congenital fistula of lip (Q38.4) Congenital fistula of salivary gland (Q42.0) Congenital absence, atresia and stenosis of rectum with fistula (Q42.2) Congenital absence, atresia and stenosis of anus with fistula (Q43.6) Congenital fistula of rectum and anus (Q51.7) Congenital fistulae between uterus and digestive and urinary tracts (Q52.2) Congenital rectovaginal fistula T: External causes (T14.5) Traumatic arteriovenous fistula (T81.8) Persistent postoperative fistula Causes Disease: Infections including an anorectal abscess and inflammatory diseases including Crohns disease and ulcerative colitis can result in fistulas. Fistulas to the anus may occur in hidradenitis suppurativa. In women, fistulas can also occur following pelvic infection and inflammation. Surgical and medical treatment: Complications from gallbladder surgery can lead to biliary fistulas. As well as being congenital or resulting from trauma, arteriovenous fistulas are created purposefully for hemodialysis. Radiation therapy to the pelvis can lead to vesicovaginal fistulas. Persistent gastrocutenaous fistulas can develop after gastrostomy. Trauma: Prolonged childbirth can lead to fistulas in women, in whom abnormal connections may occur between the bladder and vagina, or the rectum and vagina. An obstetric fistula develops when blood supply to the tissues of the vagina and the bladder (and/or rectum) is cut off during prolonged obstructed labor. The tissues die and a hole forms through which urine and/or feces pass uncontrollably. Vesicovaginal and rectovaginal fistulas may also be caused by rape, in particular gang rape, and rape with foreign objects, as evidenced by the abnormally high number of women in conflict areas who have developed fistulae. In 2003, thousands of women in eastern Congo presented themselves for treatment of traumatic fistulas caused by systematic, violent gang rape, often also with sharp objects that occurred during the countrys five years of war. So many cases have been reported that the destruction of the vagina is considered a war injury and recorded by doctors as a crime of combat. Head trauma can lead to perilymph fistulas, whereas trauma to other parts of the body can cause arteriovenous fistulas. Treatment Treatment for fistula varies depending on the cause and extent of the fistula, but often involves surgical intervention combined with antibiotic therapy. In some cases the fistula is temporarily covered, using a fibrin glue or plug. Catheters may be required to drain a fistula.Surgery is often required to assure adequate drainage of the fistula (so that pus may escape without forming an abscess). Various surgical procedures are used, most commonly fistulotomy, placement of a seton (a cord that is passed through the path of the fistula to keep it open for draining), or an endorectal flap procedure (where healthy tissue is pulled over the internal side of the fistula to keep feces or other material from reinfecting the channel).Management involves treating any underlying causative condition. For example, surgical treatment of fistulae in Crohns disease can be effective, but if the Crohns disease itself is not treated, the rate of recurrence of the fistula is very high (well above 50%). Therapeutic use In people with kidney failure, requiring dialysis, a cimino fistula is often deliberately created in the arm by means of a short day surgery in order to permit easier withdrawal of blood for hemodialysis.As a radical treatment for portal hypertension, surgical creation of a portacaval fistula produces an anastomosis between the hepatic portal vein and the inferior vena cava across the omental foramen (of Winslow). This spares the portal venous system from high pressure which can cause esophageal varices, caput medusae, and hemorrhoids. Epidemiology Globally, every year between 50,000 and 100,000 women are affected by fistula relating to childbirth. Botany In botany, the term is most common in its adjectival forms, where it is used in binomial names to refer to species that are distinguished by hollow or tubular structures. Monarda fistulosa, for example, has tubular flowers; Eutrochium fistulosum has a tubular stem; Allium fistulosum has hollow or tubular leaves, and Acacia seyal subsp. fistula is the subspecies with hollow spines. Society and culture The term was first used in the 14th century. See also Obstetric fistula Alexis St. Martin Stoma (medicine) References == External links ==

Papillary thyroid cancer

Papillary thyroid cancer or papillary thyroid carcinoma is the most common type of thyroid cancer, representing 75 percent to 85 percent of all thyroid cancer cases. It occurs more frequently in women and presents in the 20–55 year age group. It is also the predominant cancer type in children with thyroid cancer, and in patients with thyroid cancer who have had previous radiation to the head and neck. It is often well-differentiated, slow-growing, and localized, although it can metastasize. Diagnosis Papillary thyroid carcinoma is usually discovered on routine examination as an asymptomatic thyroid nodule that appears as a neck mass. In some instances, the mass may have produced local symptoms. This mass is normally referred to a fine needle aspiration biopsy (FNA) for investigation. FNA accuracy is very high and it is a process widely used in these cases. Other investigation methods include ultrasound imaging and nuclear scan. The ultrasound is a useful test to distinguish solid from cystic lesions and to identify calcifications. The thyroid ultrasound is also very effective to discover microcarcinomas, which refer to very small carcinomas (<1 cm). Papillary thyroid carcinomas are also discovered when a hard nodule is found in multinodular goiter, when enlarged cervical lymph nodes are detected, or when there are unidentified metastatic lesions elsewhere in the body. Expanding lesions found in the thyroid gland, especially if they are painful, should be examined as they may indicate the presence of papillary thyroid carcinoma. Other clinical signs that could indicate papillary thyroid are fixation to the trachea, a firm neck mass, damage to recurrent laryngeal or cervical sympathetic nerves. Five percent of the population can have thyroid nodules, and the majority will be benign.Appropriate workup includes an ultrasound of the neck, followed by lab studies. Patients will usually meet with both an endocrinologist and a surgeon (head and neck surgeon or endocrine surgeon). Markers Thyroglobulin can be used as a tumor marker for well-differentiated papillary thyroid cancer. HBME-1 staining may be useful for differentiating papillary carcinomas from follicular carcinomas; in papillary lesions it tends to be positive.Reduced expression of ATP5E is significantly associated with the diagnosis of papillary thyroid cancer and may serve as an early tumor marker of the disease. Serum microRNAs have shown good diagnostic performance for distinguishing patients with papillary thyroid cancer from patients with benign thyroid nodules and healthy controls, and are suggested as novel and minimally invasive diagnostic approach in clinical practice. Pathology Papillary thyroid cancer gets its name from the papillae among its cells, visible on microscopy. Features include: Characteristic Orphan Annie eye nuclear clearings (nuclei with uniform staining, which appear empty due to powdery chromatin and marginal micronucleoli) and psammoma bodies on light microscopy. The former is useful in identifying the follicular variant of papillary thyroid carcinomas. Lymphatic spread is more common than hematogenous spread Multifocality is common The so-called lateral aberrant thyroid is usually a lymph node metastasis from a papillary thyroid carcinoma. Papillary microcarcinoma is a subset of papillary thyroid cancer defined as measuring less than or equal to 1 cm. The highest incidence of papillary thyroid microcarcinoma in an autopsy series was reported by Harach et al. in 1985, who found 36 of 101 consecutive autopsies to have an incidental microcarcinoma. Michael Pakdaman et al. report the highest incidence in a retrospective surgical series at 49.9 percent of 860 cases. Management strategies for incidental papillary microcarcinoma on ultrasound (and confirmed on FNAB) range from total thyroidectomy with radioactive iodine ablation to observation alone. Harach et al. suggest using the term "occult papillary tumor" to avoid giving patients distress over having cancer. It was Woolner et al. who first arbitrarily coined the term "occult papillary carcinoma" in 1960, to describe papillary carcinomas ≤ 1.5 cm in diameter.Several variants are recognized, although classic papillary thyroid carcinoma is the most frequent: microscopic-follicular variant, diffuse-sclerosing variant, tall-cell variant, columnar-cell variant, hobnail variant, and others. The encapsulated-follicular variant, specifically when noninvasive, has been newly reclassified as the noninvasive follicular thyroid neoplasm with papillary-like nuclear features.Although papillary carcinoma has a propensity to invade lymphatics, it is less likely to invade blood vessels. These kinds of tumors are most commonly unencapsulated, and they have a high tendency to metastasize locally to lymph nodes, which may produce cystic structures near the thyroid that are difficult to diagnose because of the paucity of malignant tissue. Furthermore, papillary tumors may metastasize to the lungs and produce a few nodules or the lung fields may exhibit a snowflake appearance throughout. Other characteristics of the papillary carcinoma is that E.M. shows increased mitochondria, increased RER, as well as increased apical microvilli. Moreover, papillary carcinomas have an indolent growth, and 40 percent of cases spread out of the capsule. Associated mutations Mutations associated with papillary thyroid cancer are mainly two forms of chromosomal translocation and one form of point mutation. These alterations lead to activation of a common carcinogenic pathway—the MAPK/ERK pathway. Chromosomal translocations involving the RET proto-oncogene (encoding a tyrosine kinase receptor that plays essential roles in the development of neuroendocrine cells) located on chromosome 10q11 occur in approximately a fifth of papillary thyroid cancers. The fusion oncoproteins generated are termed RET/PTC proteins (ret/papillary thyroid carcinoma), and constitutively activate RET and the downstream MAPK/ERK pathway. The frequency of ret/PTC translocations is significantly higher in papillary cancers arising in children and after radiation exposure. The gene NTRK1 (encoding the TrkA receptor), located on chromosome 1q, is similarly translocated in approximately 5 percent to 10 percent of papillary thyroid cancers.Approximately a third to a half of papillary thyroid carcinomas harbor point mutations in the BRAF oncogene, also activating the MAPK/ERK pathway. In those cases the BRAF mutations found were V600E mutation. After performing a multivariate analysis, it was found that the absence of tumor capsule was the only parameter associated (P=0.0005) with BRAF V600E mutation. According to recent studies, papillary cancers carrying the common V600E mutation tend to have a more aggressive long-term course. BRAF mutations are frequent in papillary carcinoma and in undifferentiated cancers that have developed from papillary tumors. Many more changes in gene expression are currently being investigated. Previous studies demonstrated the dysregulation of different microRNAs in thyroid cancer. For example, downregulation of miR-369-3p and consequent upregulation of its target TSPAN13 appear to be involved in the pathophysiology of PTC.Mitochondrial mutations: MtDNA(mitochondrial) haplogroups, characterized by unique sets of non pathological mtDNA polymorphisms can modulate the pathogenesis of different diseases in specific populations because of its influence on the expression of genes related to ROS production and OXPHOS coupling efficiency and the regulation of apoptosis. In Asian populations, haplogroup D4a is associated with an increased risk of thyroid cancer while in European populations, Haplogroup K is considered to be protective of Thyroid cancer. Treatment Surgery remains the mainstay of treatment for papillary thyroid cancer. The Revised 2009 American Thyroid Association guidelines for papillary thyroid cancer state that the initial procedure should be near-total or total thyroidectomy. Thyroid lobectomy alone may be sufficient treatment for small (<1 cm), low-risk, unifocal, intrathyroidal papillary carcinomas in the absence of prior head and neck irradiation or radiologically or clinically involved cervical nodal metastasis. Minimal disease (diameter up to 1.0 centimeters) - hemithyroidectomy (or unilateral lobectomy) and isthmectomy may be sufficient. There is some discussion whether this is still preferable over total thyroidectomy for this group of patients. Gross disease (diameter over 1.0 centimeters) - total thyroidectomy, and central compartment lymph node removal is the therapy of choice. Additional lateral neck nodes can be removed at the same time if an ultrasound guided FNA and thyroglobulin TG cancer washing was positive on the pre-operative neck node ultrasound evaluation.Arguments for total thyroidectomy are: Reduced risk of recurrence, if central compartment nodes are removed at the original surgery. 30-85% of papillary carcinoma is multifocal disease. Hemithyroidectomy may leave disease in the other lobe. However, multifocal disease in the remnant lobe may not necessarily become clinically significant or serve as a detriment to patient survival. Ease of monitoring with thyroglobulin (sensitivity for picking up recurrence is increased in presence of total thyroidectomy, and ablation of the remnant normal thyroid by low dose radioiodine 131 after following a low iodine diet (LID). Ease of detection of metastatic disease by thyroid and neck node ultrasound. Post-operative complications at high-volume thyroid surgery centers with experienced surgeons are comparable to that of hemithyroidectomy.Arguments for hemithyroidectomy: Most patients have low-risk cancer with an excellent prognosis, with similar survival outcomes in low-risk patients who undergo total thyroidectomy versus hemithyroidectomy. Less likelihood of patient requiring lifelong thyroid hormone replacement after surgery.Thyroid total body scans are less reliable at finding recurrence than TG and ultrasound. Papillary tumors tend to be more aggressive in patients over age 45. In such cases, it might be required to perform a more extensive resection including portions of the trachea. Also, the sternocleidomastoid muscle, jugular vein, and accessory nerve are to be removed if such procedure allows apparently complete tumor resection. If a significant amount of residual tumor is left in the neck, external radiotherapy has been indicated and has proven useful especially in those cases when the residual tumor does not take up radioiodine. After surgical thyroid removal, the patient waits around 4–6 weeks to then have radioiodine therapy. This therapy is intended to both detect and destroy any metastasis and residual tissue in the thyroid. The treatment may be repeated 6–12 months after initial treatment of metastatic disease where disease recurs or has not fully responded.Patients are administered hormone replacement levothyroxine for life after surgery, especially after total thyroidectomy. Chemotherapy with cisplatin or doxorubicin has proven limited efficacy, however, it could be helpful for patients with bone metastases to improve their quality of life. Patients are also prescribed levothyroxine and radioiodine after surgery. Levothyroxine influences growth and maturation of tissues and it is involved in normal growth, metabolism, and development. In case of metastases, patients are prescribed antineoplastic agents which inhibit cell growth and proliferation and help in palliating symptoms in progressive disease. After successful treatment, 35 percent of the patients may experience a recurrence within a 40-year span. Also, patients may experience a high incidence of nodule metastasis, with 35 percent cases of cervical node metastases. Approximately 20 percent of patients will develop multiple tumors within the thyroid gland.There is ongoing discussion regarding the best management regarding the optimal surgical procedure for papillary thyroid cancer. Prognosis of patients with papillary thyroid cancer is found to be dependent on the patients age, the size of the tumor, presence of metastatic disease, and the presence of tumor invasion into adjacent tissues near the thyroid gland. Recent studies have examined a more conservative approach to surgery and have demonstrated that hemithyroidectomy may be acceptable for patients with low-risk papillary thyroid cancer with tumor size 1 cm to 4 cm with no presence of invasion to tissues surrounding the thyroid or metastasis. Studies examining large databases of patients with papillary thyroid cancer have concluded that there is no survival advantage for patients with stage I papillary thyroid cancer size 1–4 cm receiving total thyroidectomy versus hemithyroidectomy. In light of this data, choosing the optimal course of surgical and medical management of papillary thyroid cancer should involve shared decision making from patient, endocrinologists, and surgeons. Prognosis Depending on source, the overall 5-year survival rate for papillary thyroid cancer is 96 percent or 97 percent, with a 10-year survival rate of 93 percent.For a more specific prognosis for individual cases, there are at minimum 13 known scoring systems for prognosis; among the more often used are: AGES - Age, Grade, Extent of disease, Size AMES - Age, Metastasis, Extent of disease, Size MACIS - Metastasis, Age at presentation, Completeness of surgical resection, Invasion (extrathyroidal), Size (this is a modification of the AGES system). It is probably the most reliable staging method available. Also known as the MAICS system. TNM staging - Tumor, node, metastasis. Remarkable about the TNM staging for (differentiated) thyroid carcinoma is that the scoring is different according to age. MACIS The MACIS system of estimating the prognosis of papillary thyroid cancer was developed by Clive S. Grant at the Mayo Clinic, and was based on careful evaluation of a large group of patients. It is probably the most reliable staging method available.It assigns scores to the main factors involved, and uses the sum of this score to calculate the prognosis: Most patients fall into the low-risk category (MACIS score less than 6.0) and are cured of the cancer at the time of surgery.Children with multiple lung metastases and/or a miliary aspect still have an excellent long-term prognosis if given adequate treatment. Stage Based on overall cancer staging into stages I to IV, papillary thyroid cancer has a 5-year survival rate of 100 percent for stages I and II, 93 percent for stage III and 51 percent for stage IV. Epidemiology According to Surveillance, Epidemiology, and End Results (SEER), the incidence of papillary cancer has increased from 4.8 to 14.9 per 100,000 from 1975 to 2012. Females are more likely to get papillary cancer when compared to males with incidence ratio of 2.5 to 1 where most of the cancers are diagnosed between 40 and 50 years old in females. However, death rates from papillary cancer remains static from 2003 to 2012 at 0.5 per 100,000 men and women. There was an increased incidence of papillary cancer from 1910 to 1960 due to the use of ionising radiation in treating childhood head and neck cancers. The incidence decreased after radiation therapy was abandoned. Environmental exposures to radiation such as atomic bombings of Hiroshima and Nagasaki and Chernobyl disaster also causes an increase in childhood papillary thyroid cancer at 5 to 20 years after the exposure to radiation. Family history of thyroid cancer syndrome such as familial adenomatous polyposis, Carney complex, Multiple endocrine neoplasia type 2 (MEN-2), Werner syndrome, and Cowden syndrome increases the risk of getting papillary cancer. References External links Thyroid cancer at DMOZ Cancer Management Handbook: Thyroid and Parathyroid Cancers Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. (January 2016). "2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer". Thyroid. 26 (1): 1–133. doi:10.1089/thy.2015.0020. PMC 4739132. PMID 26462967.

WAGR syndrome

WAGR syndrome (also known as WAGR complex, Wilms tumour-aniridia syndrome, aniridia-Wilms tumour syndrome) is a rare genetic syndrome in which affected children are predisposed to develop Wilms tumour (a tumour of the kidneys), Aniridia (absence of the coloured part of the eye, the iris), Genitourinary anomalies, and mental Retardation. The G is sometimes instead given as "gonadoblastoma," since the genitourinary anomalies can include tumours of the gonads (testes or ovaries).Some WAGR syndrome patients show severe childhood obesity and hyperphagia; the acronym WAGRO (O for obesity) has been used to describe this category and may be associated with the coinciding loss of BDNF a gene that is also on chromosome 11.The condition, first described by Miller et al. in 1964 in its association with other congenital malformations, results from a deletion on chromosome 11 resulting in the loss of several genes. As such, it is one of the best studied examples of a condition caused by loss of neighbouring (contiguous) genes.It is possible for those with WAGR syndrome to develop Wilms tumor, a rare form of kidney cancer. Signs and symptoms Newborn children with WAGR syndrome are soon noted to have aniridia. The clinical suspicion for WAGR may be increased with the presence of other genital anomalies, though genitourinary anomalies are not always present, particularly in girls.In older children, clinical diagnosis of the syndrome can be made when aniridia and one of the other features are present. While aniridia is rarely absent in WAGR syndrome, cases have been reported without it. Chromosomal analysis is necessary for definitive diagnosis. Other common eye defects include cataracts and ptosis. About 50% of people develop Wilms tumour. Pathophysiology WAGR syndrome is caused by a mutation on chromosome 11 in the 11p13 region. Specifically, several genes in this area are deleted, including the PAX6 ocular development gene and the Wilms tumour gene (WT1). Abnormalities in WT1 may also cause genitourinary anomalies. Mutations in the PAX6 gene have recently been shown to not only cause ocular abnormalities, but also problems in the brain and pancreas.The gene for brain-derived neurotrophic factor (BDNF), located on 11p14.1, has been proposed as a candidate gene for the obesity and excessive eating in a subset of WAGR patients. This strengthens the case for a role for BDNF in energy balance. Diagnosis Diagnosis for WAGR syndrome can be made by confirming microdeletion of 11p13 utilizing FISH (fluorescent in situ hybridization), the primary method of choice for diagnosis. FISH which will demonstrate a lack of a fluorescent signal coordinating to the specific location of the gene. Treatment Children with WAGR syndrome receive regular (3-4 yearly) kidney surveillance for Wilms tumour until at least the age of 6–8 years and thereafter remain under some follow-up because of the risk of late onset nephropathy (40% of patients with WAGR Syndrome over the age of 12 years). Females with WAGR syndrome may have streak ovaries, which can increase the risk for gonadoblastoma. Malformations of the vagina and/or uterus may also be present. See also Denys–Drash syndrome References External links DECIPHER database entry for WAGR syndrome

Costello syndrome

Costello syndrome, also called faciocutaneoskeletal syndrome or FCS syndrome, is a rare genetic disorder that affects many parts of the body. It is characterized by delayed development and intellectual disabilities, distinctive facial features, unusually flexible joints, and loose folds of extra skin, especially on the hands and feet.: 571  Heart abnormalities are common, including a very fast heartbeat (tachycardia), structural heart defects, and overgrowth of the heart muscle (hypertrophic cardiomyopathy). Infants with Costello syndrome may be large at birth, but grow more slowly than other children and have difficulty feeding. Later in life, people with this condition have relatively short stature and many have reduced levels of growth hormones. It is a RASopathy.Beginning in early childhood, people with specific mutations on the Costello syndrome gene variant have an increased risk of developing certain cancerous and noncancerous tumors. Small growths called papillomas are the most common noncancerous tumors seen with this condition. They usually develop around the nose and mouth. The most frequent cancerous tumor associated with Costello syndrome is a soft tissue tumor called a rhabdomyosarcoma. Other cancers also have been reported in children and adolescents with this disorder, including a tumor that arises in developing nerve cells (neuroblastoma) and a form of bladder cancer (transitional cell carcinoma). Costello syndrome was discovered by Jack Costello, a New Zealand paediatrician, in 1977. He is credited with first reporting the syndrome in the Australian Paediatric Journal, Volume 13, No.2 in 1977. Signs and symptoms Genetics Costello syndrome is caused by any of at least five different mutations in the HRAS gene on chromosome 11. This gene provides instructions for making a protein, H-Ras, that helps control cell growth and division. Mutations that cause Costello syndrome lead to the production of an H-Ras protein that is permanently active. Instead of triggering cell growth in response to particular signals from outside the cell, the overactive protein directs cells to grow and divide constantly. This unchecked cell division may predispose those affected to the development of benign and malignant tumors. It remains unclear how mutations in HRAS cause other features of Costello syndrome, but many of the signs and symptoms may result from cell overgrowth and abnormal cell division.HRAS is a proto-oncogene in which somatic mutations in healthy people can contribute to cancer. Whereas children with Costello syndrome typically have a mutation in HRAS in every cell of their bodies, an otherwise healthy person with a tumor caused in part by HRAS mutation will only have mutant HRAS within the tumor. The test for the mutation in cancer tumors can also be used to test children for Costello syndrome.Costello syndrome is inherited in an autosomal dominant manner, which means one copy of the altered gene is sufficient to cause the disorder. Almost all cases have resulted from new mutations, and occur in people with no history of the disorder in their family. This condition is rare; as of 20 April 2007, 200 to 300 cases have been reported worldwide. Diagnosis Costello Syndrome can be difficult for doctors to immediately clinically diagnose, as there are similar conditions that resemble this syndrome. A physician will start by assessing the childs height, the size of the head, and birth weight.Full genome and Exome next generation DNA testing is the primary diagnostic tool for Costello Syndrome. Treatments At the 2005 American Society of Human Genetics meeting, Francis Collins gave a presentation about a treatment he devised for children affected by Progeria. He discussed how farnesyltransferase inhibitors (FTIs) affects H-Ras. After his presentation, members of the Costello Syndrome Family Network discussed the possibility of FTIs helping children with Costello syndrome. Mark Kieran, who presented at the 1st International Costello Syndrome Research Symposium in 2007, agreed that FTIs might help children with Costello syndrome. He discussed with Costello advocates what he had learned in establishing and running the Progeria clinical trial with an FTI, to help them consider next steps.Another medication that affects H-Ras is Lovastatin, which is planned as a treatment for neurofibromatosis type I. When this was reported in mainstream news, the Costello Syndrome Professional Advisory Board was asked about its use in Costello Syndrome. Research into the effects of Lovastatin was linked with Alcino Silva, who presented his findings at the 2007 symposium. Silva also believed that the medication he was studying could help children with Costello syndrome with cognition.A third medication that might help children with Costello syndrome is a MEK inhibitor that helps inhibit the pathway closer to the cell nucleus. Research Spanish researchers reported the development of a Costello mouse, with the G12V mutation, in early 2008. Although the G12V mutation is rare among children with Costello syndrome, and the G12V mouse does not appear to develop tumors as expected, information about the mouse models heart may be transferable to humans. Italian and Japanese researchers published their development of a Costello zebrafish in late 2008, also with the G12V mutation. The advent of animal models may accelerate identification of treatment options. Historical That genetic mutations in HRAS cause Costello syndrome was first reported in 2005. These mutations, along with mutations that cause cardiofaciocutaneous syndrome, found soon after, surprised geneticists and changed how genetic syndromes can be grouped. Before this, geneticists looked for new mutations in genes with mutations that caused syndromes similar to the unknown syndrome. For example, researchers looked at and around the most common Noonan syndrome mutation, PTPN11, but did not find anything related to Costello syndrome or cardiofaciocutaneous syndrome. The first mutation that is now identified as one of the Costello syndrome alleles was found unexpectedly when Japanese researchers used the DNA of children with Costello syndrome as a control, looking for another Noonan gene Geneticists realized that the syndromes they were grouping together clinically according to their signs and symptoms were related in a way they had never realized: the mutations that cause Costello syndrome, Noonan syndrome and cardiofaciocutaneous syndromes are linked by their cellular function, not by being on or close to a gene with a known mutation. The cellular function that links them is a common signalling pathway that brings information from outside the cell to the nucleus. This pathway is called the Ras-MAP-kinase signal transduction pathway (Ras-MAPK Pathway). References Some text in this article was originally taken from http://ghr.nlm.nih.gov/condition=costellosyndrome, a public domain source External links GeneReviews: Costello Syndrome GeneReviews: Daisys battle with Costello Syndrome

Skew deviation

Skew deviation is an unusual ocular deviation (strabismus), wherein the eyes move upward (hypertropia) in opposite directions. Skew deviation is caused by abnormal prenuclear vestibular input to the ocular motor nuclei, most commonly due to brainstem or cerebellar stroke. Other causes include multiple sclerosis and head trauma. Skew deviation is usually characterized by torticollis (head tilting) and binocular torsion. The exact pathophysiology of skew deviation remains incompletely understood. Skew deviation appears to be a perturbation of the ocular tilt reaction, which is itself is most likely a vestigial righting response used to keep fish and other lateral-eyed animals properly oriented.There are three types of skew deviations:Type 1: Upward deviation of both eyes; sound-induced vestibular symptoms; both eyes show counterclockwise rotary upward rotation Type 2: Hypertropia in one eye; dorsolateral medullary infarctions; excyclotropia in the ipsilateral eye; hypertropia in the contralateral eye Type 3: Simultaneous hypertropia one eye and hypotropia in the other eye; upper brainstem lesion References Further reading Adams, Raymond D.; Victor, Maurice; Ropper, Allan H. (1997). Principles of Neurology (6 ed.). New York: McGraw Hill, Health Professions Division. ISBN 978-0-07-067439-4.

Blistering distal dactylitis

Blistering distal dactylitis is a cutaneous condition characterized by tense superficial bullae occurring on a tender erythematous base over the volar fat pad of the phalanx of a finger or thumb.: 262  The most common organism responsible for this is Beta-hemolytic Streptococci. See also List of cutaneous conditions == References ==

Mitral regurgitation

Mitral regurgitation (MR), also known as mitral insufficiency or mitral incompetence, is a form of valvular heart disease in which the mitral valve is insufficient and does not close properly when the heart pumps out blood. It is the abnormal leaking of blood backwards – regurgitation from the left ventricle, through the mitral valve, into the left atrium, when the left ventricle contracts. Mitral regurgitation is the most common form of valvular heart disease. Definition Mitral regurgitation, also known as mitral insufficiency or mitral incompetence, is the backward flow of blood from the left ventricle, through the mitral valve, and into the left atrium, when the left ventricle contracts, resulting in a systolic murmur radiating to the left armpit. Signs and symptoms Mitral regurgitation may be present for many years before any symptoms appear. The symptoms associated with MR are dependent on which phase of the disease process the individual is in. Individuals with acute MR are typically severely symptomatic and will have the signs and symptoms of acute decompensated congestive heart failure (i.e. shortness of breath, pulmonary edema, orthopnea, and paroxysmal nocturnal dyspnea). In acute cases, a murmur and tachycardia may be the only distinctive signs.Individuals with chronic compensated MR may be asymptomatic for long periods of time, with a normal exercise tolerance and no evidence of heart failure. Over time, however, there may be decompensation and patients can develop volume overload (congestive heart failure). Symptoms of entry into a decompensated phase may include fatigue, shortness of breath particularly on exertion, and leg swelling. Also, there may be development of an irregular heart rhythm known as atrial fibrillation.Findings on clinical examination depend on the severity and duration of MR. The mitral component of the first heart sound is usually soft and with a laterally displaced apex beat, often with heave. The first heart sound is followed by a high-pitched holosystolic murmur at the apex, radiating to the back or clavicular area. Its duration is, as the name suggests, the whole of systole. The loudness of the murmur does not correlate well with the severity of regurgitation. It may be followed by a loud, palpable P2, heard best when lying on the left side. A third heart sound is commonly heard.Patients with mitral valve prolapse may have a holosystolic murmur or often a mid-to-late systolic click and a late systolic murmur. Cases with a late systolic regurgitant murmur may still be associated with significant hemodynamic consequences.Mitral regurgitation as a result of papillary muscle damage or rupture may be a complication of a heart attack and lead to cardiogenic shock. Cause The mitral valve apparatus comprises two valve leaflets, the mitral annulus, which forms a ring around the valve leaflets, and the papillary muscles, which tether the valve leaflets to the left ventricle and prevent them from prolapsing into the left atrium. The chordae tendineae is also present and connects the valve leaflets to the papillary muscles. Dysfunction of any of these portions of the mitral valve apparatus can cause regurgitation.The most common cause of MR in developing countries is mitral valve prolapse. It is the most common cause of primary mitral regurgitation in the United States, causing about 50% of cases. Myxomatous degeneration of the mitral valve is more common in women as well as with advancing age, which causes a stretching of the leaflets of the valve and the chordae tendineae. Such elongation prevents the valve leaflets from fully coming together when the valve closes, causing the valve leaflets to prolapse into the left atrium, thereby causing MR.Ischemic heart disease causes MR by the combination of ischemic dysfunction of the papillary muscles, and the dilatation of the left ventricle. This can lead to the subsequent displacement of the papillary muscles and the dilatation of the mitral valve annulus.Rheumatic fever (RF), Marfans syndrome and the Ehlers–Danlos syndromes are other typical causes. Mitral valve stenosis (MVS) can sometimes be a cause of mitral regurgitation (MR) in the sense that a stenotic valve (calcified and with restricted range of movement) allows backflow (regurgitation) if it is too stiff and misshapen to close completely. Most MVS is caused by RF, so one can say that MVS is sometimes the proximal cause of MI/MR (that is, stenotic MI/MR) and that RF is often the distal cause of MVS, MI/MR, or both. MR and mitral valve prolapse are also common in Ehlers–Danlos syndromes.Secondary mitral regurgitation is due to the dilatation of the left ventricle that causes stretching of the mitral valve annulus and displacement of the papillary muscles. This dilatation of the left ventricle can be due to any cause of dilated cardiomyopathy including aortic insufficiency, nonischemic dilated cardiomyopathy, and noncompaction cardiomyopathy. Because the papillary muscles, chordae, and valve leaflets are usually normal in such conditions, it is also called functional mitral regurgitation.Acute MR is most often caused by endocarditis, mainly S. aureus. Rupture or dysfunction of the papillary muscle are also common causes in acute cases, dysfunction, which can include mitral valve prolapse. Pathophysiology The pathophysiology of MR can be broken into three phases of the disease process: the acute phase, the chronic compensated phase, and the chronic decompensated phase. Acute phase Acute MR (as may occur due to the sudden rupture of the chordae tendinae or papillary muscle) causes a sudden volume overload of both the left atrium and the left ventricle. The left ventricle develops volume overload because with every contraction it now has to pump out not only the volume of blood that goes into the aorta (the forward cardiac output or forward stroke volume) but also the blood that regurgitates into the left atrium (the regurgitant volume). The combination of the forward stroke volume and the regurgitant volume is known as the total stroke volume of the left ventricle.In the acute setting, the stroke volume of the left ventricle is increased (increased ejection fraction); this happens because of more complete emptying of the heart. However, as it progresses the LV volume increases and the contractile function deteriorates, thus leading to dysfunctional LV and a decrease in ejection fraction. The increase in stroke volume is explained by the Frank–Starling mechanism, in which increased ventricular pre-load stretches the myocardium such that contractions are more forceful.The regurgitant volume causes a volume overload and a pressure overload of the left atrium and the left ventricle. The increased pressures in the left side of the heart may inhibit drainage of blood from the lungs via the pulmonary veins and lead to pulmonary congestion. Chronic phase Compensated If the MR develops slowly over months to years or if the acute phase cannot be managed with medical therapy, the individual will enter the chronic compensated phase of the disease. In this phase, the left ventricle develops eccentric hypertrophy in order to better manage the larger than normal stroke volume. The eccentric hypertrophy and the increased diastolic volume combine to increase the stroke volume (to levels well above normal) so that the forward stroke volume (forward cardiac output) approaches the normal levels.In the left atrium, the volume overload causes enlargement of the left atrium, allowing the filling pressure in the left atrium to decrease. This improves the drainage from the pulmonary veins, and signs and symptoms of pulmonary congestion will decrease.These changes in the left ventricle and left atrium improve the low forward cardiac output state and the pulmonary congestion that occur in the acute phase of the disease. Individuals in the chronic compensated phase may be asymptomatic and have normal exercise tolerances. Decompensated An individual may be in the compensated phase of MR for years, but will eventually develop left ventricular dysfunction, the hallmark for the chronic decompensated phase of MR. It is currently unclear what causes an individual to enter the decompensated phase of this disease. However, the decompensated phase is characterized by calcium overload within the cardiac myocytes.In this phase, the ventricular myocardium is no longer able to contract adequately to compensate for the volume overload of mitral regurgitation, and the stroke volume of the left ventricle will decrease. The decreased stroke volume causes a decreased forward cardiac output and an increase in the end-systolic volume. The increased end-systolic volume translates to increased filling pressures of the left ventricle and increased pulmonary venous congestion. The individual may again have symptoms of congestive heart failure.The left ventricle begins to dilate during this phase. This causes a dilatation of the mitral valve annulus, which may worsen the degree of MR. The dilated left ventricle causes an increase in the wall stress of the cardiac chamber as well.While the ejection fraction is less in the chronic decompensated phase than in the acute phase or the chronic compensated phase, it may still be in the normal range (i.e.: > 50 percent), and may not decrease until late in the disease course. A decreased ejection fraction in an individual with MR and no other cardiac abnormality should alert the physician that the disease may be in its decompensated phase. Diagnosis There are many diagnostic tests that have abnormal results in the presence of MR. These tests suggest the diagnosis of MR and may indicate to the physician that further testing is warranted. For instance, the electrocardiogram (ECG) in long-standing MR may show evidence of left atrial enlargement and left ventricular dilatation. Atrial fibrillation may also be noted on the ECG in individuals with chronic mitral regurgitation. The ECG may not show any of these findings in the setting of acute MR. The quantification of MR usually employs imaging studies such as echocardiography or magnetic resonance angiography of the heart. Chest X-ray The chest X-ray in individuals with chronic MR is characterized by enlargement of the left atrium and the left ventricle, and then maybe calcification of the mitral valve. Echocardiogram An echocardiogram is commonly used to confirm the diagnosis of MR. Color doppler flow on the transthoracic echocardiogram (TTE) will reveal a jet of blood flowing from the left ventricle into the left atrium during ventricular systole. Also, it may detect a dilated left atrium and ventricle and decreased left ventricular function. A transesophageal echocardiogram can give clearer images if needed as the back of the heart can also be viewed. Electrocardiography P mitrale is a broad, bifid notched P wave in several or many leads with a prominent late negative component to the P wave in lead V1, and may be seen in MR, but also in mitral stenosis, and, potentially, any cause of overload of the left atrium. Quantification of mitral regurgitation The degree of severity of MR can be quantified by the regurgitant fraction, which is the percentage of the left ventricular stroke volume that regurgitates into the left atrium. regurgitant fraction = V m i t r a l − V a o r t i c V m i t r a l × 100 % {\displaystyle {\frac {V_{mitral}-V_{aortic}}{V_{mitral}}}\times 100\%} where Vmitral and Vaortic are, respectively, the volumes of blood that flow forward through the mitral valve and aortic valve during a cardiac cycle. Methods that have been used to assess the regurgitant fraction in mitral regurgitation include echocardiography, cardiac catheterization, fast CT scan, and cardiac MRI.The echocardiographic technique to measure the regurgitant fraction is to determine the forward flow through the mitral valve (from the left atrium to the left ventricle) during ventricular diastole, and comparing it with the flow out of the left ventricle through the aortic valve in ventricular systole. This method assumes that the aortic valve does not have aortic insufficiency.Another way to quantify the degree of MR is to determine the area of the regurgitant flow at the level of the valve. This is known as the regurgitant orifice area and correlates with the size of the defect in the mitral valve. One particular echocardiographic technique used to measure the orifice area is measurement of the proximal isovelocity surface area (PISA). The flaw of using PISA to determine the mitral valve regurgitant orifice area is that it measures the flow at one moment in time in the cardiac cycle, which may not reflect the average performance of the regurgitant jet. Treatment The treatment of MR depends on the acuteness of the disease and whether there are associated signs of hemodynamic compromise. In general, medical therapy is non-curative and is used for mild-to-moderate regurgitation or in patients unable to tolerate surgery.In acute MR secondary to a mechanical defect in the heart (i.e., rupture of a papillary muscle or chordae tendineae), the treatment of choice is mitral valve surgery. If the patient is hypotensive prior to the surgical procedure, an intra-aortic balloon pump may be placed in order to improve perfusion of the organs and to decrease the degree of MR. Medicine If the individual with acute MR is normotensive, vasodilators may be of use to decrease the afterload seen by the left ventricle and thereby decrease the regurgitant fraction. The vasodilator most commonly used is nitroprusside.Individuals with chronic MR can be treated with vasodilators as well to decrease afterload. In the chronic state, the most commonly used agents are ACE inhibitors and hydralazine. Studies have shown that the use of ACE inhibitors and hydralazine can delay surgical treatment of MR. The current guidelines for treatment of MR limit the use of vasodilators to individuals with hypertension, however. Any hypertension is treated aggressively, e.g. by diuretics and a low sodium diet. In both hypertensive and normotensive cases, digoxin and antiarrhythmics are also indicated. Also, chronic anticoagulation is given where there is concomitant mitral valve prolapse or atrial fibrillation. Surgery Surgery is curative of mitral valve regurgitation. There are two surgical options for the treatment of MR: mitral valve replacement and mitral valve repair. Mitral valve repair is preferred to mitral valve replacement where a repair is feasible as bioprosthetic replacement valves have a limited lifespan of 10 to 15 years, whereas synthetic replacement valves require ongoing use of blood thinners to reduce the risk of stroke. There are two general categories of approaches to mitral valve repair: resection of the prolapsed valvular segment (sometimes referred to as the "Carpentier" approach) and installation of artificial chordae to "anchor" the prolapsed segment to the papillary muscle (sometimes referred to as the "David" approach). With the resection approach, any prolapsing tissue is resected, in effect removing the hole through which the blood is leaking. In the artificial chordae approach, ePTFE (expanded polytetrafluoroethylene, or Gore-Tex) sutures are used to replace the broken or stretched chordae tendonae, bringing the natural tissue back into the physiological position, thus restoring the natural anatomy of the valve. With both techniques, an annuloplasty ring is typically secured to the annulus, or opening of the mitral valve, to provide additional structural support. In some cases, the "double orifice" (or Alfieri) technique for mitral valve repair, the opening of the mitral valve is sewn closed in the middle, leaving the two ends still able to open. This ensures that the mitral valve closes when the left ventricle pumps blood, yet allows the mitral valve to open at the two ends to fill the left ventricle with blood before it pumps. In general, mitral valve surgery requires "open-heart" surgery in which the heart is arrested and the patient is placed on a heart-lung machine (cardiopulmonary bypass). This allows the complex surgery to proceed in a still environment.Due to the physiological stress associated with open-heart surgery, elderly and very sick patients may be subject to increased risk, and may not be candidates for this type of surgery. As a consequence, there are attempts to identify means of correcting MR on a beating heart. The Alfieri technique for instance, has been replicated using a percutaneous catheter technique, which installs a "MitraClip" device to hold the middle of the mitral valve closed.Indications for surgery for chronic MR include signs of left ventricular dysfunction with ejection fraction less than 60%, severe pulmonary hypertension with pulmonary artery systolic pressure greater than 50 mmHg at rest or 60 mmHg during activity, and new-onset atrial fibrillation. Epidemiology Significant mitral valve regurgitation has a prevalence of approximately 2% of the population, affecting males and females equally. It is one of the two most common valvular heart diseases in the elderly, and the commonest type of valvular heart disease in low and middle income countries.In a study of 595 male elite football players aged 18–38 and 47 sedentary non-athletes, mitral regurgitation was found in 20% football players and 15% in control group. Football players with mitral regurgitation were found to have larger mitral annulus diameter compared to athletes without regurgitation, and left atrium diameter was larger in athletes with MR. See also Tricuspid regurgitation Aortic regurgitation Pulmonary insufficiency References == External links ==

Pyridoxine-dependent epilepsy

Pyridoxine-dependent epilepsy (PDE) is a rare genetic disorder characterized by intractable seizures in the prenatal and neonatal period. The disorder was first recognized in the 1950s, with the first description provided by Hunt et al. in 1954. More recently, pathogenic variants within the ALDH7A1 gene have been identified to cause PDE. Genetics PDE is inherited in an autosomal recessive manner and is estimated to affect around 1 in 400,000 to 700,000 births, though one study conducted in Germany estimated a prevalence of 1 in 20,000 births. The ALDH7A1 gene encodes for the enzyme antiquitin or α-aminoadipic semialdehyde dehydrogenase, which is involved with the catabolism of lysine. Treatment Patients with PDE do not respond to anticonvulsant medications, but seizures rapidly cease with therapeutic intravenous doses of vitamin B6 and remission from seizures are often maintained on daily therapeutic doses of vitamin B6. An optimal dose has not yet been established, but doses of 50–100 mg/day or 15–30 mg/kg/day have been proposed. Importantly, excessive doses of vitamin B6 can result in irreversible neurological damage, and therefore several guidelines recommend between 200 mg (neonates) and 500 mg per day as the maximal daily dose.Despite remission of seizure activity with vitamin B6 supplementation, intellectual disability is frequently seen in patients with PDE. Because the affected enzyme antiquitin is involved in the cerebral lysine degradation pathway, lysine restriction as an additional treatment modality has recently been explored. Studies have been published which demonstrate potential for improved biomarkers, development, and behavior in patients treated with lysine restriction in addition to pyridoxine supplementation. In trial, lysine restriction of 70–100 mg/kg/day in children less than 1 year of age, 45–80 mg/kg/day in children between 1–7 years of age, and 20–45 mg/kg/day in children older than 7 years of age were prescribed. Despite the potential of additional benefit from lysine restriction, vitamin B6 supplementation remains the main-stay of treatment given lack of studies thus far demonstrating the safety and efficacy of lysine restriction for this purpose. Monitoring Plasma and cerebrospinal fluid levels of pipecolic acid are frequently elevated in patients with PDE, though it is a non-specific biomarker. α-aminodipic semialdehyde is elevated in urine and plasma and is a more specific biomarker for PDE. Improvements in these biomarkers have been reported with the implementation of a lysine-restricted diet. Initial studies evaluating the safety and efficacy of lysine restriction evaluated developmental and cognitive outcomes by age-appropriate tests and parental observations. References External links GeneReview/NCBI/NIH/UW entry on Pyridoxine-Dependent Seizures Pyridoxine-dependent epilepsy. Genetics Home Reference. June 17, 2013.

Hypotension

Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the diastolic blood pressure (the bottom number), which are the maximum and minimum blood pressures, respectively. A systolic blood pressure of less than 90 millimeters of mercury (mmHg) or diastolic of less than 60 mmHg is generally considered to be hypotension. Different numbers apply to children. However, in practice, blood pressure is considered too low only if noticeable symptoms are present. Primary symptoms generally include dizziness and lightheadedness. Other symptoms include fatigue, shortness of breath, headaches, shakiness, increased thirst, irregular heartbeat, chest pain, confusion.Hypotension is the opposite of hypertension, which is high blood pressure. It is best understood as a physiological state rather than a disease. Severely low blood pressure can deprive the brain and other vital organs of oxygen and nutrients, leading to a life-threatening condition called shock. Shock is classified based on the underlying cause, including hypovolemic shock, cardiogenic shock, distributive shock, and obstructive shock.Hypotension can be caused by strenuous exercise, excessive heat, low blood volume (hypovolemia), hormonal changes, widening of blood vessels, anemia, vitamin B12 deficiency, anaphylaxis, heart problems, or endocrine problems. Some medications can also lead to hypotension. There are also syndromes that can cause hypotension in patients including orthostatic hypotension, vasovagal syncope, and other rarer conditions.For many people, excessively low blood pressure can cause dizziness and fainting or indicate serious heart, endocrine or neurological disorders.For some people who exercise and are in top physical condition, low blood pressure could be normal. A single session of exercise can induce hypotension and water-based exercise can induce a hypotensive response.Treatment of hypotension may include the use of intravenous fluids or vasopressors. When using vasopressors, trying to achieve a mean arterial pressure (MAP) of greater than 70 mmHg does not appear to result in better outcomes than trying to achieve a MAP of greater than 65 mmHg in adults. Signs and symptoms The primary symptoms of hypotension are lightheadedness or dizziness.If the blood pressure is sufficiently low, fainting (syncope) may occur.Low blood pressure is sometimes associated with certain symptoms, many of which are related to causes rather than effects of hypotension: Causes Low blood pressure can be caused by low blood volume, hormonal changes, widening of blood vessels, medicine side effects, severe dehydration, anemia, vitamin B12 deficiency, anaphylaxis, heart problems or endocrine problems.Reduced blood volume, hypovolemia, is the most common cause of hypotension. This can result from hemorrhage; insufficient fluid intake, as in starvation; or excessive fluid losses from diarrhea or vomiting. Hypovolemia can be induced by excessive use of diuretics. Low blood pressure may also be attributed to heat stroke which can be indicated by absence of perspiration, light headedness and dark colored urine.Other medications can produce hypotension by different mechanisms. Chronic use of alpha blockers or beta blockers can lead to hypotension. Beta blockers can cause hypotension both by slowing the heart rate and by decreasing the pumping ability of the heart muscle.Decreased cardiac output despite normal blood volume, due to severe congestive heart failure, large myocardial infarction, heart valve problems, or extremely low heart rate (bradycardia), often produces hypotension and can rapidly progress to cardiogenic shock. Arrhythmias often result in hypotension by this mechanism.Excessive vasodilation, or insufficient constriction of the blood vessels (mostly arterioles), causes hypotension. This can be due to decreased sympathetic nervous system output or to increased parasympathetic activity occurring as a consequence of injury to the brain or spinal cord. Dysautonomia, an intrinsic abnormality in autonomic system functioning, can also lead to hypotension. Excessive vasodilation can also result from sepsis, acidosis, or medications, such as nitrate preparations, calcium channel blockers, or AT1 receptor antagonists (Angiotensin II acts on AT1 receptors). Many anesthetic agents and techniques, including spinal anesthesia and most inhalational agents, produce significant vasodilation.Lower blood pressure is a side effect of certain herbal medicines, which can also interact with several medications. An example is the theobromine in Theobroma cacao, which lowers blood pressure through its actions as both a vasodilator and a diuretic, and has been used to treat high blood pressure. Syndromes Orthostatic hypotension Orthostatic hypotension, also called postural hypotension, is a common form of low blood pressure. It occurs after a change in body position, typically when a person stands up from either a seated or lying position. It is usually transient and represents a delay in the normal compensatory ability of the autonomic nervous system. It is commonly seen in hypovolemia and as a result of various medications. In addition to blood pressure-lowering medications, many psychiatric medications, in particular antidepressants, can have this side effect. Simple blood pressure and heart rate measurements while lying, seated, and standing (with a two-minute delay in between each position change) can confirm the presence of orthostatic hypotension. Taking these measurements is known as orthostatic vitals. Orthostatic hypotension is indicated if there is a drop of 20 mmHg in systolic pressure (and a 10 mmHg drop in diastolic pressure in some facilities) and a 20 beats per minute increase in heart rate. Vasovagal syncope Vasovagal syncope is a form of dysautonomia characterized by an inappropriate drop in blood pressure while in the upright position. Vasovagal syncope occurs as a result of increased activity of the vagus nerve, the mainstay of the parasympathetic nervous system. Patients will feel sudden, unprovoked lightheadedness, sweating, changes in vision, and finally a loss of consciousness. Consciousness will often return rapidly once patient is lying down and the blood pressure returns to normal. Other Another, but rarer form, is postprandial hypotension, a drastic decline in blood pressure that occurs 30 to 75 minutes after eating substantial meals. When a great deal of blood is diverted to the intestines (a kind of "splanchnic blood pooling") to facilitate digestion and absorption, the body must increase cardiac output and peripheral vasoconstriction to maintain enough blood pressure to perfuse vital organs, such as the brain. Postprandial hypotension is believed to be caused by the autonomic nervous system not compensating appropriately, because of aging or a specific disorder.Hypotension is a feature of Flammer syndrome, which is characterized by cold hands and feet and predisposes to normal tension glaucoma.Hypotension can be a symptom of relative energy deficiency in sport, sometimes known as the female athlete triad, although it can also affect men. Pathophysiology Blood pressure is continuously regulated by the autonomic nervous system, using an elaborate network of receptors, nerves, and hormones to balance the effects of the sympathetic nervous system, which tends to raise blood pressure, and the parasympathetic nervous system, which lowers it. The vast and rapid compensation abilities of the autonomic nervous system allow normal individuals to maintain an acceptable blood pressure over a wide range of activities and in many disease states. Even small alterations in these networks can lead to hypotension. Diagnosis For most adults, the optimal blood pressure is below 120/80 mmHg. If the systolic blood pressure is <90 mmHg or the diastolic blood pressure is <60 mmHg, it would be classified as hypotension. However, occasional blood pressure readings below 90/60 mmHg are not infrequent in the general population, and, in the absence of some pathological cause, hypotension appears to be a relatively benign condition in most people. The diagnosis of hypotension is usually made by measuring blood pressure, either non-invasively with a sphygmomanometer or invasively with an arterial catheter (mostly in an intensive care setting). Another way to diagnose low blood pressure is by using the mean arterial pressure (MAP) measured using an arterial catheter or by continuous, non-invasive hemodynamic monitoring which measures intra-operative blood pressure beat-by-beat throughout surgery. A MAP <65 mmHg is considered hypotension. Intra-operative hypotension <65 mmHg can lead to an increased risk of acute kidney injury, myocardial injury or post-operative stroke. While an incidental finding of hypotension during a routine blood pressure measurement may not be particularly worrying, a substantial drop in blood pressure following standing, exercise or eating can be asssociated with symptoms and may have implications for future health. A drop in blood pressure after standing, termed postural or othostatic hypotension, is defined as a decrease in supine-to-standing BP >20 mm Hg systolic or >10 mm Hg diastolic within 3 minutes of standing. Orthostatic hypotension is associated with increased risk of future cardiovascular events and mortality. Orthostatic vitals are frequently measured to assist with the diagnosis of orthostatic hypotension, and may involve the use of a tilt table test to evaluate vasovagal syncope. Treatment The treatment for hypotension depends on its cause. Chronic hypotension rarely exists as more than a symptom. Asymptomatic hypotension in healthy people usually does not require treatment. Adding electrolytes to a diet can relieve symptoms of mild hypotension. A morning dose of caffeine can also be effective. In mild cases, where the patient is still responsive, laying the person in dorsal decubitus (lying on the back) position and lifting the legs increases venous return, thus making more blood available to critical organs in the chest and head. The Trendelenburg position, though used historically, is no longer recommended.Hypotensive shock treatment always follows the first four following steps. Outcomes, in terms of mortality, are directly linked to the speed that hypotension is corrected. Still-debated methods are in parentheses, as are benchmarks for evaluating progress in correcting hypotension. A study on septic shock provided the delineation of these general principles. However, since it focuses on hypotension due to infection, it is not applicable to all forms of severe hypotension. Volume resuscitation (usually with crystalloid or blood products) Blood pressure support with a vasopressor (all seem equivalent with respect to risk of death, with norepinephrine possibly better than dopamine). Trying to achieve a mean arterial pressure (MAP) of greater than 70 mmHg does not appear to result in better outcomes than trying to achieve a MAP of greater than 65 mmHg in adults. Ensure adequate tissue perfusion (maintain SvO2 >70 with use of blood or dobutamine) Address the underlying problem (i.e., antibiotic for infection, stent or CABG (coronary artery bypass graft surgery) for infarction, steroids for adrenal insufficiency, etc...)The best way to determine if a person will benefit from fluids is by doing a passive leg raise followed by measuring the output from the heart. Medication Chronic hypotension sometimes requires the use of medications. Some medications that are commonly used include Fludrocortisone, Erythropoietin, and Sympathomimetics such as Midodrine and Noradrenaline and precursor (L-DOPS). Fludrocortisone is the first-line therapy (in the absence of heart failure) for patients with chronic hypotension or resistant orthostatic hypotension. It works by increasing the intravascular volume. Midodrine is a therapy used for severe orthostatic hypotension, and works by increasing peripheral vascular resistance. Noradrenaline and its precursor L-DOPS are used for primary autonomic dysfunction by increasing vascular tone. Erythropoietin is given to patients with neurogenic orthostatic hypotension and it works through increasing vascular volume and viscosity. Pediatrics The definition of hypotension changes in the pediatric population depending on the childs age as seen in the table below. The clinical history provided by the caretaker is the most important part in determining the cause of hypotension in pediatric patients. Symptoms for children with hypotension include increased sleepiness, not using the restroom as much (or at all), having difficulty breathing or breathing rapidly, or syncope. The treatment for hypotension in pediatric patients is similar to the treatment in adults by following the four first steps listed above (see Treatment). Children are more likely to undergo intubation during the treatment of hypotension because their oxygen levels drop more rapidly than adults. The closing of fetal shunts following birth can create instability in the "transitional circulation" of the fetus, and often creates a state of hypotension following birth; while many infants can overcome this hypotension through the closing of shunts, a mean blood pressure (MBP) of lower than 30 mmHg is correlated with severe cerebral injury and can be experienced by premature infants who have poor shunt closure. Etymology Hypotension, from Ancient Greek hypo-, meaning "under" or "less" + English tension, meaning "strain" or "tightness". This refers to the under-constriction of the blood vessels and arteries which leads to low blood pressure. See also Hypertension References External links Curlie.org: Hypotension

Attenuated familial adenomatous polyposis

Attenuated familial adenomatous polyposis is a form of familial adenomatous polyposis, a cancer syndrome. It is a pre-malignant disease that can develop into colorectal cancer. A patient will have fewer than a hundred polyps located typically in right side of the colon. Cancer might develop as early as the age of five, though typically presents later than classical FAP. See also Familial adenomatous polyposis Birt–Hogg–Dubé syndrome Cowden syndrome Cronkhite–Canada syndrome Juvenile polyposis MUTYH Peutz–Jeghers syndrome References == External links ==

Coccidioidomycosis

Coccidioidomycosis (, kok-SID-ee-oy-doh-my-KOH-sis), commonly known as cocci, Valley fever, as well as California fever, desert rheumatism, or San Joaquin Valley fever, is a mammalian fungal disease caused by Coccidioides immitis or Coccidioides posadasii. Coccidioidomycosis is endemic in certain parts of the United States in Arizona, California, Nevada, New Mexico, Texas, Utah, and northern Mexico.C. immitis is a dimorphic saprophytic fungus that grows as a mycelium in the soil and produces a spherule form in the host organism. It resides in the soil in certain parts of the southwestern United States, most notably in California and Arizona. It is also commonly found in northern Mexico, and parts of Central and South America. C. immitis is dormant during long dry spells, then develops as a mold with long filaments that break off into airborne spores when it rains. The spores, known as arthroconidia, are swept into the air by disruption of the soil, such as during construction, farming, low-wind or singular dust events, or an earthquake. Windstorms may also cause epidemics far from endemic areas. In December 1977, a windstorm in an endemic area around Arvin, California led to several hundred cases, including deaths, in non-endemic areas hundreds of miles away.Coccidioidomycosis is a common cause of community-acquired pneumonia in the endemic areas of the United States. Infections usually occur due to inhalation of the arthroconidial spores after soil disruption. The disease is not contagious. In some cases the infection may recur or become chronic. It was reported in 2022 that valley fever had been increasing in Californias Central Valley for years (1,000 cases in Kern county in 2014, 3,000 in 2021); experts said that cases could rise across the American west as the climate crisis makes the landscape drier and hotter. Classification After Coccidioides infection, coccidioidomycosis begins with Valley fever, which is its initial acute form. Valley fever may progress to the chronic form and then to disseminated coccidioidomycosis. Therefore, coccidioidomycosis may be divided into the following types: Acute coccidioidomycosis, sometimes described in literature as primary pulmonary coccidioidomycosis Chronic coccidioidomycosis Disseminated coccidioidomycosis, which includes primary cutaneous coccidioidomycosisValley fever is not a contagious disease. Signs and symptoms An estimated 60% of people infected with the fungi responsible for coccidioidomycosis have minimal to no symptoms, while 40% will have a range of possible clinical symptoms. Of those who do develop symptoms, the primary infection is most often respiratory, with symptoms resembling bronchitis or pneumonia that resolve over a matter of a few weeks. In endemic regions, coccidioidomycosis is responsible for 20% of cases of community-acquired pneumonia. Notable coccidioidomycosis signs and symptoms include a profound feeling of tiredness, loss of smell and taste, fever, cough, headaches, rash, muscle pain, and joint pain. Fatigue can persist for many months after initial infection. The classic triad of coccidioidomycosis known as "desert rheumatism" includes the combination of fever, joint pains, and erythema nodosum.A minority (3–5%) of infected individuals do not recover from the initial acute infection and develop a chronic infection. This can take the form of chronic lung infection or widespread disseminated infection (affecting the tissues lining the brain, soft tissues, joints, and bone). Chronic infection is responsible for most of the morbidity and mortality. Chronic fibrocavitary disease is manifested by cough (sometimes productive of mucus), fevers, night sweats and weight loss. Osteomyelitis, including involvement of the spine, and meningitis may occur months to years after initial infection. Severe lung disease may develop in HIV-infected persons. Complications Serious complications may occur in patients who have weakened immune systems, including severe pneumonia with respiratory failure and bronchopleural fistulas requiring resection, lung nodules, and possible disseminated form, where the infection spreads throughout the body. The disseminated form of coccidioidomycosis can devastate the body, causing skin ulcers, abscesses, bone lesions, swollen joints with severe pain, heart inflammation, urinary tract problems, and inflammation of the brains lining, which can lead to death. Cause Rain starts the cycle of initial growth of the fungus underneath the soil. In soil (and in agar media), Coccidioides exist in filament form. It forms hyphae in both horizontal and vertical directions. Over a prolonged dry period, cells within hyphae degenerate to form alternating barrel-shaped cells (arthroconidia) which are light in weight and carried by air currents. This happens when the soil is disturbed, often by clearing trees, construction or farming. As the population grows, so do all these activities, causing a potential cascade effect. The more land that is cleared and the more arid the soil, the riper the environment for Coccidioides. These spores can be easily inhaled unknowingly. On reaching alveoli they enlarge in size to become spherules, and internal septations develop. This division of cells is made possible by the optimal temperature inside the body. Septations develop and form endospores within the spherule. Rupture of spherules release these endospores, which in turn repeat the cycle and spread the infection to adjacent tissues within the body of the infected individual. Nodules can form in lungs surrounding these spherules. When they rupture, they release their contents into bronchi, forming thin-walled cavities. These cavities can cause symptoms including characteristic chest pain, coughing up blood, and persistent cough. In individuals with a weakened immune system, the infection can spread through the blood. The fungus can also, rarely, enter the body through a break in the skin and cause infection. Diagnosis Coccidioidomycosis diagnosis relies on a combination of an infected persons signs and symptoms, findings on radiographic imaging, and laboratory results. The disease is commonly misdiagnosed as bacterial community-acquired pneumonia. The fungal infection can be demonstrated by microscopic detection of diagnostic cells in body fluids, exudates, sputum and biopsy tissue by methods of Papanicolaou or Grocotts methenamine silver staining. These stains can demonstrate spherules and surrounding inflammation.With specific nucleotide primers, C. immitis DNA can be amplified by polymerase chain reaction (PCR). It can also be detected in culture by morphological identification or by using molecular probes that hybridize with C. immitis RNA. C. immitis and C. posadasii cannot be distinguished on cytology or by symptoms, but only by DNA PCR.An indirect demonstration of fungal infection can be achieved also by serologic analysis detecting fungal antigen or host IgM or IgG antibody produced against the fungus. The available tests include the tube-precipitin (TP) assays, complement fixation assays, and enzyme immunoassays. TP antibody is not found in cerebrospinal fluid (CSF). TP antibody is specific and is used as a confirmatory test, whereas ELISA is sensitive and thus used for initial testing.If the meninges are affected, CSF will show abnormally low glucose levels, an increased level of protein, and lymphocytic pleocytosis. Rarely, CSF eosinophilia is present. Imaging Chest X-rays rarely demonstrate nodules or cavities in the lungs, but these images commonly demonstrate lung opacification, pleural effusions, or enlargement of lymph nodes associated with the lungs. Computed tomography scans of the chest are more sensitive than chest X-rays to detect these changes. Prevention Preventing Valley fever is challenging because it is difficult to avoid breathing in the fungus should it be present; however, the public health effect of the disease is essential to understand in areas where the fungus is endemic. Enhancing surveillance of coccidioidomycosis is key to preparedness in the medical field in addition to improving diagnostics for early infections. Currently there are no completely effective preventive measures available for people who live or travel through Valley fever-endemic areas. Recommended preventive measures include avoiding airborne dust or dirt, but this does not guarantee protection against infection. People in certain occupations may be advised to wear face masks. The use of air filtration indoors is also helpful, in addition to keeping skin injuries clean and covered to avoid skin infection.In 1998–2011, there were 111,117 cases of coccidioidomycosis in the U.S. that were logged into the National Notifiable Diseases Surveillance System (NNDSS). Since many U.S. states do not require reporting of coccidioidomycosis, the actual numbers may be higher. The United States Centers for Disease Control and Prevention (CDC) called the disease a "silent epidemic" and acknowledged that there is no proven anticoccidioidal vaccine available. A 2001 cost-effectiveness analysis indicated that a potential vaccine could improve health as well as reducing total health care expenditures among infants, teens, and immigrant adults, and more modestly improve health but increase total health care expenditures in older age groups.Raising both surveillance and awareness of the disease while medical researchers are developing a human vaccine can positively contribute towards prevention efforts. Research demonstrates that patients from endemic areas who are aware of the disease are most likely to request diagnostic testing for coccidioidomycosis. Presently, Meridian Bioscience manufactures the so-called EIA test to diagnose the Valley fever, which however is known for producing a fair quantity of false positives. Currently, recommended prevention measures can include type-of-exposure-based respirator protection for persons engaged in agriculture, construction and others working outdoors in endemic areas. Dust control measures such as planting grass and wetting the soil, and also limiting exposure to dust storms are advisable for residential areas in endemic regions. Treatment Significant disease develops in fewer than 5% of those infected and typically occurs in those with a weakened immune system. Mild asymptomatic cases often do not require any treatment. Those with severe symptoms may benefit from antifungal therapy, which requires 3–6 months or more of treatment depending on the response to the treatment. There is a lack of prospective studies that examine optimal antifungal therapy for coccidioidomycosis.On the whole, oral fluconazole and intravenous amphotericin B are used in progressive or disseminated disease, or in immunocompromised individuals. Amphotericin B was originally the only available treatment, but alternatives, including itraconazole and ketoconazole, became available for milder disease. Fluconazole is the preferred medication for coccidioidal meningitis, due to its penetration into CSF. Intrathecal or intraventricular amphotericin B therapy is used if infection persists after fluconazole treatment. Itraconazole is used for cases that involve treatment of infected persons bones and joints. The antifungal medications posaconazole and voriconazole have also been used to treat coccidioidomycosis. Because the symptoms of coccidioidomycosis are similar to the common flu, pneumonia, and other respiratory diseases, it is important for public health professionals to be aware of the rise of coccidioidomycosis and the specifics of diagnosis. Greyhound dogs often get coccidioidomycosis; their treatment regimen involves 6–12 months of ketoconazole taken with food.A particular severe case of meningitis caused by valley fever initially received several incorrect diagnoses such as sinus infections and cluster headaches. The patient became unable to work during diagnosis and original search for treatments. Eventually the right treatment was found—albeit with severe side effects—requiring four pills a day and medication administered directly into the brain every 16 weeks. Toxicity Conventional amphotericin B desoxycholate (AmB: used since the 1950s as a primary agent) is known to be associated with increased drug-induced nephrotoxicity impairing kidney function. Other formulations have been developed such as lipid-soluble formulations to mitigate side-effects such as direct proximal and distal tubular cytotoxicity. These include liposomal amphotericin B, amphotericin B lipid complex such as Abelcet (brand) amphotericin B phospholipid complex also as AmBisome Intravenous, or Amphotec Intravenous (Generic; Amphotericin B Cholesteryl Sul), and amphotericin B colloidal dispersion, all shown to exhibit a decrease in nephrotoxicity. The latter was not as effective in one study as amphotericin B desoxycholate which had a 50% murine (rat and mouse) morbidity rate versus zero for the AmB colloidal dispersion.The cost of the nephrotoxic AmB deoxycholate, in 2015, for a patient of 70 kilograms (150 lb) at 1 mg/kg/day dosage, was approximately US$63.80, compared to $1318.80 for 5 mg/kg/day of the less toxic liposomal AmB. Epidemiology Coccidioidomycosis is endemic to the western hemisphere between 40°N and 40°S. The ecological niches are characterized by hot summers and mild winters with an annual rainfall of 10–50 cm. The species are found in alkaline sandy soil, typically 10–30 cm below the surface. In harmony with the mycelium life cycle, incidence increases with periods of dryness after a rainy season; this phenomenon, termed "grow and blow", refers to growth of the fungus in wet weather, producing spores which are spread by the wind during succeeding dry weather. While the majority of cases are observed in the endemic region, cases reported outside the area are generally visitors, who contact the infection and return to their native areas before becoming symptomatic. North America In the United States, C. immitis is endemic to southern and central California with the highest presence in the San Joaquin Valley. C. posadassi is most prevalent in Arizona, although it can be found in a wider region spanning from Utah, New Mexico, Texas, and Nevada. An estimated 150,000 infections occur annually, with 25,000 new infections occurring every year. The incidence of coccidioidomycosis in the United States in 2011 (42.6 per 100,000) was almost ten times higher than the incidence reported in 1998 (5.3 per 100,000). In area where it is most prevalent, the infection rate is 2-4%.Incidence varies widely across the west and southwest. In Arizona, for instance, in 2007, there were 3,450 cases in Maricopa County, which in 2007 had an estimated population of 3,880,181 for an incidence of approximately 1 in 1,125. In contrast, though southern New Mexico is considered an endemic region, there were 35 cases in the entire state in 2008 and 23 in 2007, in a region that had an estimated 2008 population of 1,984,356, for an incidence of approximately 1 in 56,695. Infection rates vary greatly by county, and although population density is important, so are other factors that have not been proven yet. Greater construction activity may disturb spores in the soil. In addition, the effect of altitude on fungi growth and morphology has not been studied, and altitude can range from sea level to 10,000 feet or higher across California, Arizona, Utah and New Mexico.In California from 2000 to 2007, there were 16,970 reported cases (5.9 per 100,000 people) and 752 deaths of the 8,657 people hospitalized. The highest incidence was in the San Joaquin Valley with 76% of the 16,970 cases (12,855) occurring in the area. Following the 1994 Northridge earthquake, there was a sudden increase of cases in the areas affected by the quake, at a pace of over 10 times baseline.There was an outbreak in the summer of 2001 in Colorado, away from where the disease was considered endemic. A group of archeologists visited Dinosaur National Monument, and eight members of the crew, along with two National Park Service workers were diagnosed with Valley fever.California state prisons, beginning in 1919, have been particularly affected by coccidioidomycosis. In 2005 and 2006, the Pleasant Valley State Prison near Coalinga and Avenal State Prison near Avenal on the western side of the San Joaquin Valley had the highest incidence in 2005, of at least 3,000 per 100,000. The receiver appointed in Plata v. Schwarzenegger issued an order in May 2013 requiring relocation of vulnerable populations in those prisons. The incidence rate has been increasing, with rates as high as 7% during 2006–2010. The cost of care and treatment is $23 million in California prisons. A lawsuit was filed against the state in 2014 on behalf of 58 inmates stating that the Avenal and Pleasant valley state prisons did not take necessary steps to prevent infections. Population risk factors There are several populations that have a higher risk for contracting coccidioidomycosis and developing the advanced disseminated version of the disease. Populations with exposure to the airborne arthroconidia working in agriculture and construction have a higher risk. Outbreaks have also been linked to earthquakes, windstorms and military training exercises where the ground is disturbed. Historically, an infection is more likely to occur in males than females, although this could be attributed to occupation rather than being sex-specific. Women who are pregnant and immediately postpartum are at a high risk of infection and dissemination. There is also an association between stage of pregnancy and severity of the disease, with third trimester women being more likely to develop dissemination. Presumably this is related to highly elevated hormonal levels, which stimulate growth and maturation of spherules and subsequent release of endospores. Certain ethnic populations are more susceptible to disseminated coccidioidomycosis. The risk of dissemination is 175 times greater in Filipinos and 10 times greater in African Americans than non-Hispanic whites. Individuals with a weakened immune system are also more susceptible to the disease. In particular, individuals with HIV and diseases that impair T-cell function. Individuals with pre-existing conditions such as diabetes are also at a higher risk. Age also affects the severity of the disease, with more than one-third of deaths being in the 65-84 age group. History The first case of what was later named coccidioidomycosis was described in 1892 in Buenos Aires by Alejandro Posadas, a medical intern at the Hospital de Clínicas "José de San Martín". Posadas established an infectious character of the disease after being able to transfer it in laboratory conditions to lab animals. In the U.S., Dr. E. Rixford, a physician from a San Francisco hospital, and T. C. Gilchrist, a pathologist at Johns Hopkins Medical School, became early pioneers of clinical studies of the infection. They decided that the causative organism was a Coccidia-type protozoan and named it Coccidioides immitis (resembling Coccidia, not mild).Dr. William Ophüls, a professor at Stanford University Hospital (San Francisco), discovered that the causative agent of the disease that was at first called Coccidioides infection and later coccidioidomycosis was a fungal pathogen, and coccidioidomycosis was also distinguished from Histoplasmosis and Blastomycosis. Further, Coccidioides immitis was identified as the culprit of respiratory disorders previously called San Joaquin Valley fever, desert fever, and Valley fever, and a serum precipitin test was developed by Charles E. Smith that was able to detect an acute form of the infection. In retrospect, Smith played a major role in both medical research and raising awareness about coccidioidomycosis, especially when he became dean of the School of Public Health at the University of California at Berkeley in 1951. Coccidioides immitis was considered by the United States during the 1950s and 1960s as a potential biological weapon. The strain selected for investigation was designated with the military symbol OC, and initial expectations were for its deployment as a human incapacitant. Medical research suggested that OC might have had some lethal effects on the populace, and Coccidioides immitis started to be classified by the authorities as a threat to public health. However, Coccidioides immitis was never weaponized to the publics knowledge, and most of the military research in the mid-1960s was concentrated on developing a human vaccine. Currently, it is not on the U.S. Department of Health and Human Services or Centers for Disease Control and Preventions list of select agents and toxins. In 2002, Coccidioides posadasii was identified as genetically distinct from Coccidioides immitis despite their morphologic similarities and can also cause coccidioidomycosis. Research As of 2013, there is no vaccine available to prevent infection with Coccidioides immitis or Coccidioides posadasii, but efforts to develop such a vaccine are underway. Other animals Valley fever is not contagious. In dogs, the most common symptom of coccidioidomycosis is a chronic cough, which can be dry or moist. Other symptoms include fever (in approximately 50% of cases), weight loss, anorexia, lethargy, and depression. The disease can disseminate throughout the dogs body, most commonly causing osteomyelitis (infection of the bone), which leads to lameness. Dissemination can cause other symptoms, depending on which organs are infected. If the fungus infects the heart or pericardium, it can cause heart failure and death.In cats, symptoms may include skin lesions, fever, and loss of appetite, with skin lesions being the most common.Other species in which Valley fever has been found include livestock such as cattle and horses; llamas; marine mammals, including sea otters; zoo animals such as monkeys and apes, kangaroos, tigers, etc.; and wildlife native to the geographic area where the fungus is found, such as cougars, skunks, and javelinas. Additional images In Popular Culture Everything in Between, a 2022 Australian feature film, contains references to coccidioidomycosis. See also Coccidioides Coccidioides immitis Coccidioides posadasii Zygomycosis Medical geology List of cutaneous conditions Thunderhead, a 1998 novel by Douglas Preston and Lincoln Child which uses the fungus and illness as a central plot point. References Further reading Twarog M, Thompson GR (2015). "Coccidioidomycosis: Recent Updates". Seminars in Respiratory and Critical Care Medicine. 36 (5): 746–755. doi:10.1055/s-0035-1562900. PMID 26398540. (Review). Stockamp NW, Thompson GR (2016). "Coccidioidomycosis". Infectious Disease Clinics of North America. 30 (1): 229–246. doi:10.1016/j.idc.2015.10.008. PMID 26739609. (Review). External links U.S. Centers for Disease Control and Prevention page on coccidioidomycosis Medline Plus Entry for coccidioidomycosis