Split (1)

train · 7.32k rows

page_title stringlengths 1 91	page_text stringlengths 0 34.2k
Adrenocortical adenoma	Adrenocortical adenoma is commonly described as a benign neoplasm emerging from the cells that comprise the adrenal cortex. Like most adenomas, the adrenocortical adenoma is considered a benign tumor since the majority of them are non-functioning and asymptomatic. Adrenocortical adenomas are classified as ACTH-independent disorders, and are commonly associated with conditions linked to hyperadrenalism such as Cushings syndrome (hypercortisolism) or Conns syndrome (hyperaldosteronism), which is also known as primary aldosteronism. In addition, recent case reports further support the affiliation of adrenocortical adenomas with hyperandrogenism or florid hyperandrogenism which can cause hyperandrogenic hirsutism in females. "Cushings syndrome" differs from the "Cushings disease" even though both conditions are induced by hypercortisolism. The term "Cushings disease" refers specifically to "secondary hypercortisolism" classified as "ACTH-dependent Cushings syndrome" caused by pituitary adenomas. In contrast, "Cushings syndrome" refers specifically to "primary hypercortisolism" classified as "ACTH-independent Cushings syndrome" caused by adrenal adenomas. Presentation Adrenal adenomas are often categorized as endocrine-inactive tumors considering that majority of them are non-functioning and asymptomatic. Functional adrenocortical adenomas demonstrate symptoms consistent with mixed endocrine syndromes. In most reported cases of adrenocortical adenoma, patients have presented with one or multiple endocrine syndromes such as hyperaldosteronism/Conns Syndrome, hypercortisolism/Cushings syndrome, hyperandrogenism/feminization, virilization, or hirsutism. Some of the common symptoms associated with adrenocortical adenomas include: Musculoskeletal Osteopenia Muscle weakness/muscle atrophyCardiovascular HypertensionEndocrine and Metabolic Obesity→More prevalent in males virilization→More prevalent in females Hyperandrogenism Irregular menstrual cyclesNeuropsychological Sleep disorders DepressionSkin Easy bruising Stretch marks Hirsutism Acne Cause Study of the reported cases indicate that most adrenocortical adenomas occur due to neoplastic proliferation of adrenal cortical cells within the three distinct layers of adrenal cortex. In humans, the adrenal cortex comprises three concentric zones including the zona glomerulosa, zona fasciculata, and zona reticularis that under normal conditions respond to bodys physiological demands for steroid hormones. The adrenal cortex is considered a dynamic organ in which senescent cells are replaced by newly differentiated cells. This constant renewal facilitates organ remodeling which contributes to dynamic characteristics of the adrenal cortex. correspondingly, the developmental physiology of the adrenal cortex is believed to play a pivotal role in formation of the adrenocortical tumors. Hence, the molecular mechanisms involved in normal development of the adrenal glands are like double edged swords that can lead to the formation of tumors within the adrenal cortex. Moreover, recent studies suggest that mutations affecting the molecular pathways of the adrenocortical region can stimulate abnormal proliferation and tumor formation. Through these studies, the cyclic AMP-dependent protein kinase A signaling has been identified as a key mediator of cortisol secretion, and the mutations associated with the dysregulation of cyclic AMP - protein kinase A pathways have been implicated in the adrenocortical pathophysiology. Pathophysiology If functional, adrenocortical adenomas can affect the normal activities of the adrenal cortex. Located within the adrenal glands are the three zones that are responsible for secretion of the three major classes of adrenal steroids. Hence, functional adrenocortical adenomas can induce over-secretion of adrenal steroids associated with pure or mixed endocrine syndromes, a condition commonly known as hyperadrenalism. Diagnosis Due to their asymptomatic nature, most reported cases of adrenal adenomas have been discerned fortuitously through autopsy, or during medical imaging, particularly CT scan (computed tomography) and magnetic resonance imaging. Hence, they have earned the title incidentaloma referring to small adenoma discovered incidentally. Though adrenocortical adenomas are considered challenging to differentiate from the normal adrenal cortex, they appear as well-circumscribed lesions once isolated.Imaging Diagnostics Computed Tomography (CT scan) Magnetic Resonance Imaging (MRI) Laboratory Tests CRH Stimulation Test High-dose-dexamethasone suppression test Gross Description Well-circumscribed lesion Size ≤ 5 cm Weight ≤ 50 grams often appear as golden-yellow color mass(may have focal dark regions corresponding to hemorrhage, lipid-depletion, and increased lipofuscin) Histopathology The microscopic histopathology analysis of the tissue samples obtained from the adrenal cortex of individuals presenting with adenoma-associated symptoms such as primary aldestronism (PA) indicates that adenoma cells are relatively larger with different cytoplasm, and increased variation in nuclear size. This indication is based on comparison between the healthy (normal) and affected (adenoma-associated) adrenal cortex tissue samples. Adrenocortical adenomas are most commonly distinguished from adrenocortical carcinomas (their malignant counterparts) by the Weiss system, as follows: Total score indicates: 0-2: Adrenocortical adenoma 3: Undetermined 4-9: Adrenocortical carcinoma Treatment Non-functioning cases of adrenocortical adenoma can be managed through long-term followups and monitoring. The treatment approach for the functioning cases of adrenocortical adenoma depends on the type of disorders they induce and their advancement. Surgical excision may be required if its presence is resulting in atrophy of the adrenal glands and the surrounding tissues.In order to acquire better treatment strategies, it is important to further examine, study and discern the distinct molecular mechanisms involved in the formation of endogenous Adrenal Adenomas, hyperplasias, and ACTH-independent Cushings Syndrome to improve the available diagnostic and prognostic markers that can assist clinicians in the management and advance-treatment of such conditions. Prognosis The long-term outlook for individuals diagnosed with non-functional adrenocortical adenoma is usually excellent. The long-term outlook for individuals diagnosed with functional adrenocortical adenoma is good with early diagnosis and treatment. Epidemiology Prevalence: Female > Male More common in adults Relatively earlier onset in females (ages ≤ 20) than males (ages ≤ 30) Most common cause of ACTH-independent Cushings syndrome See also Hyperplasia Adrenal tumor Cushings syndrome Conns syndrome Hypercortisolism Hyperaldosteronism Hyperandrogenism Adrenal gland Adrenal paraganglioma Adrenal Pheochromocytoma Adrenal ganglioneuroma References == External links ==
Pigmented purpuric dermatosis	Pigmented purpuric dermatosis refers to one of the three major classes of skin conditions characterized by purpuric skin eruptions. Pigmented purpuric dermatosis are distinguished from other purpura by size (0.3–1 cm) and are most often seen in the lower extremities.: 829 Pigmentary purpuric eruptions may present with one of several clinical patterns. There may be overlapping characteristics among pigmented purpuric dermatosis and between their signs and those of other purpuric eruptions.: 829 Examples of the pigmented purpuric dermatosis group include:: 829–30 Schambergs disease Majocchis disease (Purpura annularis telangiectodes) Gougerot-Blum syndrome (Pigmented purpuric lichenoid dermatitis) Ducas and Kapetanakis pigmented purpura Lichen aureusAlthough vascular damage may be present, it is insufficient for these conditions to be considered forms of vasculitis.A few very small non-blinded studies of treatment with narrow-band ultraviolet light have been reported as promising. See also Purpura Skin lesion List of cutaneous conditions References == External links ==
Obliterating endarteritis	Obliterating endarteritis is severe proliferating endarteritis (inflammation of the intima or inner lining of an artery) that results in an occlusion of the lumen of the artery. Obliterating endarteritis can occur due to a variety of medical conditions such as a complication of radiation poisoning, tuberculosis meningitis or a syphilis infection. == References ==
Penetrating trauma	Penetrating trauma is an open wound injury that occurs when an object pierces the skin and enters a tissue of the body, creating a deep but relatively narrow entry wound. In contrast, a blunt or non-penetrating trauma may have some deep damage, but the overlying skin is not necessarily broken and the wound is still closed to the outside environment. The penetrating object may remain in the tissues, come back out the path it entered, or pass through the full thickness of the tissues and exit from another area.A penetrating injury in which an object enters the body or a structure and passes all the way through an exit wound is called a perforating trauma, while the term penetrating trauma implies that the object does not perforate wholly through. In gunshot wounds, perforating trauma is associated with an entrance wound and an often larger exit wound. Penetrating trauma can be caused by a foreign object or by fragments of a broken bone. Usually occurring in violent crime or armed combat, penetrating injuries are commonly caused by gunshots and stabbings.Penetrating trauma can be serious because it can damage internal organs and presents a risk of shock and infection. The severity of the injury varies widely depending on the body parts involved, the characteristics of the penetrating object, and the amount of energy transmitted to the tissues. Assessment may involve X-rays or CT scans, and treatment may involve surgery, for example to repair damaged structures or to remove foreign objects. Following penetrating trauma, spinal motion restriction is associated with worse outcomes and therefore it should not be done routinely. Mechanism As a missile passes through tissue, it decelerates, dissipating and transferring kinetic energy to the tissues. The velocity of the projectile is a more important factor than its mass in determining how much damage is done; kinetic energy increases with the square of the velocity. In addition to injury caused directly by the object that enters the body, penetrating injuries may be associated with secondary injuries, due for example to a blast injury.The path of a projectile can be estimated by imagining a line from the entrance wound to the exit wound, but the actual trajectory may vary due to ricochet or differences in tissue density. In a cut, the discolouration and the swelling of the skin from a blow happens because of the ruptured blood vessels and escape of blood and fluid and other injuries that interrupt the circulation. Cavitation Permanent Low-velocity items, such as knives and swords, are usually propelled by a persons hand, and usually do damage only to the area that is directly contacted by the object. The space left by tissue that is destroyed by the penetrating object as it passes through forms a cavity; this is called permanent cavitation. Temporary High-velocity objects are usually projectiles such as bullets from high-powered rifles, such as assault rifles or sniper rifles. Bullets classed as medium-velocity projectiles include those from handguns, shotguns, and submachine guns. In addition to causing damage to the tissues they contact, medium- and high-velocity projectiles cause a secondary cavitation injury: as the object enters the body, it creates a pressure wave which forces tissue out of the way, creating a cavity which can be much larger than the object itself; this is called "temporary cavitation". The temporary cavity is the radial stretching of tissue around the bullets wound track, which momentarily leaves an empty space caused by high pressures surrounding the projectile that accelerate material away from its path.The characteristics of the tissue injured also help determine the severity of the injury; for example, the denser the tissue, the greater the amount of energy transmitted to it. Skin, muscles, and intestines absorb energy and so are resistant to the development of temporary cavitation, while organs such as the liver, spleen, kidney, and brain, which have relatively low tensile strength, are likely to split or shatter because of temporary cavitation. Flexible elastic soft tissues, such as muscle, intestine, skin, and blood vessels, are good energy absorbers and are resistant to tissue stretch. If enough energy is transferred, the liver may disintegrate. Temporary cavitation can be especially damaging when it affects delicate tissues such as the brain, as occurs in penetrating head trauma. Location Head While penetrating head trauma accounts for only a small percentage of all traumatic brain injuries (TBI), it is associated with a high mortality rate, and only a third of people with penetrating head trauma survive long enough to arrive at a hospital. Injuries from firearms are the leading cause of TBI-related deaths. Penetrating head trauma can cause cerebral contusions and lacerations, intracranial hematomas, pseudoaneurysms, and arteriovenous fistulas. The prognosis for penetrating head injuries varies widely.Penetrating facial trauma can pose a risk to the airway and breathing; airway obstruction can occur later due to swelling or bleeding. Penetrating eye trauma can cause the globe of the eye to rupture or vitreous humor to leak from it, and presents a serious threat to eyesight. Chest Most penetrating injuries are chest wounds and have a mortality rate (death rate) of under 10%. Penetrating chest trauma can injure vital organs such as the heart and lungs and can interfere with breathing and circulation. Lung injuries that can be caused by penetrating trauma include pulmonary laceration (a cut or tear) pulmonary contusion (a bruise), hemothorax (an accumulation of blood in the chest cavity outside of the lung), pneumothorax (an accumulation of air in the chest cavity) and hemopneumothorax (accumulation of both blood and air). Sucking chest wounds and tension pneumothorax may result.Penetrating trauma can also cause injuries to the heart and circulatory system. When the heart is punctured, it may bleed profusely into the chest cavity if the membrane around it (the pericardium) is significantly torn, or it may cause pericardial tamponade if the pericardium is not disrupted. In pericardial tamponade, blood escapes from the heart but is trapped within the pericardium, so pressure builds up between the pericardium and the heart, compressing the latter and interfering with its pumping. Fractures of the ribs commonly produce penetrating chest trauma when sharp bone ends pierce tissues. Abdomen Penetrating abdominal trauma (PAT) typically arises from stabbings, ballistic injuries (shootings), or industrial accidents. PAT can be life-threatening because abdominal organs, especially those in the retroperitoneal space, can bleed profusely, and the space can hold a large volume of blood. If the pancreas is injured, it may be further injured by its own secretions, in a process called autodigestion. Injuries of the liver, common because of the size and location of the organ, present a serious risk for shock because the liver tissue is delicate and has a large blood supply and capacity. The intestines, taking a large part of the lower abdomen, are also at risk of perforation. People with penetrating abdominal trauma may have signs of hypovolemic shock (insufficient blood in the circulatory system) and peritonitis (an inflammation of the peritoneum, the membrane that lines the abdominal cavity). Penetration may abolish or diminish bowel sounds due to bleeding, infection, and irritation, and injuries to arteries may cause bruits (a distinctive sound similar to heart murmurs) to be audible. Percussion of the abdomen may reveal hyperresonance (indicating air in the abdominal cavity) or dullness (indicating a buildup of blood). The abdomen may be distended or tender, signs which indicate an urgent need for surgery.The standard management of penetrating abdominal trauma was for many years mandatory laparotomy. A greater understanding of mechanisms of injury, outcomes from surgery, improved imaging and interventional radiology has led to more conservative operative strategies being adopted. Assessment and treatment Assessment can be difficult because much of the damage is often internal and not visible. The patient is thoroughly examined. X-ray and CT scanning may be used to identify the type and location of potentially lethal injuries. Sometimes before an X-ray is performed on a person with penetrating trauma from a projectile, a paper clip is taped over entry and exit wounds to show their location on the film. The patient is given intravenous fluids to replace lost blood. Surgery may be required; impaled objects are secured into place so that they do not move and cause further injury, and they are removed in an operating room. If the location of the injury is not obvious, a surgical operation called an exploratory laparotomy may be required to look for internal damage to the organs in the abdomen. Foreign bodies such as bullets may be removed, but they may also be left in place if the surgery necessary to get them out would cause more damage than would leaving them. Wounds are debrided to remove tissue that cannot survive and other material that presents risk for infection.Negative pressure wound therapy is no more effective in preventing wound infection than standard care when used on open traumatic wounds. History Before the 17th century, medical practitioners poured hot oil into wounds in order to cauterize damaged blood vessels, but the French surgeon Ambroise Paré challenged the use of this method in 1545. Paré was the first to propose controlling bleeding using ligature.During the American Civil War, chloroform was used during surgery to reduce pain and allow more time for operations. Due in part to the lack of sterile technique in hospitals, infection was the leading cause of death for wounded soldiers.In World War I, doctors began replacing patients lost fluid with salt solutions. With World War II came the idea of blood banking, having quantities of donated blood available to replace lost fluids. The use of antibiotics also came into practice in World War II. See also Aortic dissection Ballistic trauma Blunt splenic trauma Blunt trauma personal protective equipment Geriatric trauma Pediatric trauma Stab wound Transmediastinal gunshot wound References == External links ==
Iododerma	Iododermas are caused by iodides, with the most common sources of exposure being oral and intravenous contrast materials used to treat thyroid disease.: 135 The most common type of eruption is an acneiform eruption with numerous acutely inflamed follicular pustules, each surrounded by a ring of hyperemia.: 135 See also Skin lesion List of cutaneous conditions References == External links ==
Cowden syndrome	Cowden syndrome (also known as Cowdens disease and multiple hamartoma syndrome) is an autosomal dominant inherited condition characterized by benign overgrowths called hamartomas as well as an increased lifetime risk of breast, thyroid, uterine, and other cancers. It is often underdiagnosed due to variability in disease presentation, but 99% of patients report mucocutaneous symptoms by age 20–29. Despite some considering it a primarily dermatologic condition, Cowdens syndrome is a multi-system disorder that also includes neurodevelopmental disorders such as macrocephaly.The incidence of Cowdens disease is about 1 in 200,000, making it quite rare. Furthermore, early and continuous screening is essential in the management of this disorder to prevent malignancies. It is associated with mutations in PTEN on 10q23.3, a tumor suppressor gene otherwise known as phosphatase and tensin homolog, that results in dysregulation of the mTOR pathway leading to errors in cell proliferation, cell cycling, and apoptosis. The most common malignancies associated with the syndrome are adenocarcinoma of the breast (20%), followed by adenocarcinoma of the thyroid (7%), squamous cell carcinomas of the skin (4%), and the remaining from the colon, uterus, or others (1%). Signs and symptoms As Cowdens disease is a multi-system disorder, the physical manifestations are broken down by organ system: Skin Adolescent patients affected with Cowden syndrome develop characteristic lesions called trichilemmomas, which typically develop on the face, and verrucous papules around the mouth and on the ears. Oral papillomas are also common. Furthermore, shiny palmar keratoses with central dells are also present. At birth or in childhood, classic features of Cowdens include pigmented genital lesions, lipomas, epidermal nevi, and cafe-au-lait spots. Squamous cell carcinomas of the skin may also occur.Thyroid Two thirds of patients have thyroid disorders, and these typically include benign follicular adenomas or multinodular goiter of the thyroid. Additionally, Cowdens patients are more susceptible to developing thyroid cancer than the general population. It is estimated that less than 10 percent of individuals with Cowden syndrome may develop follicular thyroid cancer. Cases of papillary thyroid cancer have been reported as well.Female and Male Genitourinary Females have an elevated risk of developing endometrial cancers, which is highest for those under the age of 50. Currently, it is not clear whether uterine leiomyomata (fibroids) or congenital genitourinary abnormalities occur at an increased rate in Cowden syndrome patients as compared to the general population. The occurrence of multiple testicular lipomas, or testicular lipomatosis, is a characteristic finding in male patients with Cowden syndrome.Gastrointestinal Polyps are extremely common as they are found in about 95% of Cowden syndrome patients undergoing a colonoscopy. They are numerous ranging from a few to hundreds, usually of the hamartomatous subtype, and distributed across the colon as well as other areas within the gastrointestinal tract. Other types of polyps that may be encountered less frequently include ganglioneuromatous, adenomatous, and lymphoid polyps. Diffuse glycogenic acanthosis of the esophagus is another gastrointestinal manifestation associated with Cowden syndrome.Breast Females are at an increased risk of developing breast cancer, which is the most common malignancy observed in Cowdens patients. Although some cases have been reported, there is not enough evidence to indicate an association between Cowden syndrome and the development of male breast cancer. Up to 75% demonstrate benign breast conditions such as intraductal papillomatosis, fibroadenomas, and fibrocystic changes. However, there is currently not enough evidence to determine if benign breast disease occurs more frequently in Cowdens patients as compared to individuals without a hereditary cancer syndrome.Central Nervous System Macrocephaly is observed in 84% of patients with Cowden syndrome. It typically occurs due to an abnormally enlarged brain, or megalencephaly. Patients may also exhibit dolichocephaly. Varying degrees of autism spectrum disorder and intellectual disability have been reported as well. Lhermitte-Duclos disease is a benign cerebellar tumor that typically does not manifest until adulthood in patients with Cowden syndrome. Genetics Cowden syndrome is inherited in an autosomal dominant fashion. Germline mutations in PTEN (phosphatase and tensin homolog), a tumor suppressor gene, are found in up to 80% of Cowdens patients. Several other hereditary cancer syndromes, such as Bannayan-Riley-Ruvalcaba syndrome, have been associated with mutations in the PTEN gene as well. PTEN negatively regulates the cytoplasmic receptor tyrosine kinase pathway, which is responsible for cell growth and survival, and also functions to repair errors in DNA. Thus, in the absence of this protein, cancerous cells are more likely to develop, survive, and proliferate.Recently, it was discovered that germline heterozygous mutations in SEC23B, a component of coat protein complex II vesicles secreted from the endoplasmic reticulum, are associated with Cowden syndrome. A possible interplay between PTEN and SEC23B has recently been suggested, given emerging evidence of each having a role in ribosome biogenesis, but this has not been conclusively determined. Diagnosis The revised clinical criteria for the diagnosis of Cowdens syndrome for an individual is dependent on either one of the following: 1) 3 major criteria are met or more that must include macrocephaly, Lhermitte-Duclos, or GI hamartomas 2) two major and three minor criteria. The major and minor criteria are listed below: Screening The management of Cowden syndrome centers on the early detection and prevention of cancer types that are known to occur as part of this syndrome. Specific screening guidelines for Cowden syndrome patients have been published by the National Comprehensive Cancer Network (NCCN). Surveillance focuses on the early detection of breast, endometrial, thyroid, colorectal, renal, and skin cancer. See below for a complete list of recommendations from the NCCN: Treatment Malignancies that occur in Cowden syndrome are usually treated in the same fashion as those that occur sporadically in patients without a hereditary cancer syndrome. Two notable exceptions are breast and thyroid cancer. In Cowden syndrome patients with a first-time diagnosis of breast cancer, treatment with mastectomy of the involved breast as well as prophylactic mastectomy of the uninvolved contralateral breast should be considered. In the setting of thyroid cancer or a follicular adenoma, a total thyroidectomy is recommended even in cases where it appears that only one lobe of the thyroid is affected. This is due to the high likelihood of recurrence as well as the difficulty in distinguishing a benign from malignant growth with a hemithyroidectomy alone. The benign mucocutaneous lesions observed in Cowden syndrome are typically not treated unless they become symptomatic or disfiguring. If this occurs, numerous treatment options, including topical agents, cryosurgery, curettage, laser ablation, and excision, may be utilized. History Cowden Syndrome was described in 1963, when Lloyd and Dennis described a novel inherited disease that predisposed to cancer. It was named after the Cowden family, in which it was discovered. They described the various clinical features including "adenoid facies; hypoplasia of the mandible and maxilla; a high-arch palate; hypoplasia of the soft palate and uvula; microstomia; papillomatosis of the lips and oral pharynx; scrotal tongue; [and] multiple thyroid adenomas."The genetic basis of Cowden Syndrome was revealed in 1997, when germline mutations in a locus at 10q23 were associated to the novel PTEN tumor suppressor. See also List of cutaneous neoplasms associated with systemic syndromes References Further reading External links GeneReviews/NCBI/NIH/UW entry on PTEN Hamartoma Tumor Syndrome (PHTS)
Oncogenic osteomalacia	Oncogenic osteomalacia, also known as oncogenic hypophosphatemic osteomalacia, is an uncommon disorder resulting in increased renal phosphate excretion, hypophosphatemia and osteomalacia. It may be caused by a phosphaturic mesenchymal tumor. Signs and symptoms Adult patients may present with worsening musculoskeletal symptoms, muscle weakness, myalgias, bone pains and fatigue which are followed by recurrent fractures. Children present with difficulty in walking, stunted growth and deformities of the skeleton (features of rickets). There can also be a significant delay between the beginning of symptoms to diagnosis, which research reflects as being between 2.5 to 28 years. Cause Tumor-induced osteomalacia is usually referred to as a paraneoplastic phenomenon, however, the tumors are usually benign and the symptomatology is due to osteomalacia or rickets. A benign mesenchymal or mixed connective tissue tumor (usually phosphaturic mesenchymal tumor and hemangiopericytoma) are the most common associated tumors. Association with mesenchymal malignant tumors, such as osteosarcoma and fibrosarcoma, has also been reported. Locating the tumor can prove to be difficult and may require whole body MRI. Some of the tumors express somatostatin receptors and may be located by octreotide scanning. A phosphaturic mesenchymal tumor is an extremely rare benign neoplasm of soft tissue and bone that inappropriately produces fibroblast growth factor 23. This tumor may cause tumor-induced osteomalacia, a paraneoplastic syndrome, by the secretion of FGF23, which has phosphaturic activity (by inhibition of renal tubular reabsorption of phosphate and renal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D). The paraneoplastic effects can be debilitating and are only reversed on discovery and surgical resection of the tumor. Pathogenesis FGF23 (fibroblast growth factor 23) inhibits phosphate transport in the renal tubule and reduces calcitriol production by the kidney. Tumor production of FGF23, Secreted frizzled-related protein 4 and matrix extracellular phosphoglycoprotein (MEPE) have all been identified as possible causative agents for the hypophosphatemia. Diagnosis Biochemical studies reveal hypophosphatemia (low blood phosphate), elevated alkaline phosphatase and low serum 1,25 dihydroxyvitamin D levels. Routine laboratory tests may not include serum phosphate levels and this can result in considerable delay in diagnosis. Even when low phosphate is measured, its significance is often overlooked. The next most appropriate test is measurement of urine phosphate levels. If there is inappropriately high urine phosphate (phosphaturia) in the setting of low serum phosphate (hypophosphatemia), there should be a high suspicion for tumor-induced osteomalacia. FGF23 (see below) can be measured to confirm the diagnosis but this test is not widely available. Once hypophosphatemia and phosphaturia have been identified, begin a search for the causative tumor, which may be small and difficult to detect. Gallium-68 DOTA-Octreotate (DOTA-TATE) positron emission tomography (PET) scanning is the best way to locate these tumors. If this scan is not available, other options include Indium-111 Octreotide (Octreoscan) SPECT/CT, whole body CT or MRI imaging. Differential diagnosis Serum chemistries are identical in tumor-induced osteomalacia, X-linked hypophosphatemic rickets (XHR) and autosomal dominant hypophosphatemic rickets (ADHR). A negative family history can be useful in distinguishing tumor induced osteomalacia from XHR and ADHR. If necessary, genetic testing for PHEX (phosphate regulating gene with homologies to endopeptidase on the X-chromosome) can be used to conclusively diagnose XHR and testing for the FGF23 gene will identify patients with ADHR. Treatment Resection of the tumor is the ideal treatment and results in correction of hypophosphatemia (and low calcitriol levels) within hours of resection. Resolution of skeletal abnormalities may take many months. If the tumor cannot be located, begin treatment with calcitriol (1–3 µg/day) and phosphate supplementation (1–4 g/day in divided doses). Tumors that express somatostatin receptors may respond to treatment with octreotide. If hypophosphatemia persists despite calcitriol and phosphate supplementation, administration of cinacalcet has been shown to be useful. References Further reading == External links ==
Cataract	A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble with bright lights, and trouble seeing at night. This may result in trouble driving, reading, or recognizing faces. Poor vision caused by cataracts may also result in an increased risk of falling and depression. Cataracts cause half of all cases of blindness and 33% of visual impairment worldwide.Cataracts are most commonly due to aging but may also occur due to trauma or radiation exposure, be present from birth, or occur following eye surgery for other problems. Risk factors include diabetes, longstanding use of corticosteroid medication, smoking tobacco, prolonged exposure to sunlight, and alcohol. The underlying mechanism involves accumulation of clumps of protein or yellow-brown pigment in the lens that reduces transmission of light to the retina at the back of the eye. Diagnosis is by an eye examination.Prevention includes wearing sunglasses and a wide brimmed hat, eating leafy vegetables and fruits, and avoiding smoking. Early on the symptoms may be improved with glasses. If this does not help, surgery to remove the cloudy lens and replace it with an artificial lens is the only effective treatment. Cataract surgery is not readily available in many countries, and surgery is needed only if the cataracts are causing problems and generally results in an improved quality of life.About 20 million people worldwide are blind due to cataracts. It is the cause of approximately 5% of blindness in the United States and nearly 60% of blindness in parts of Africa and South America. Blindness from cataracts occurs in about 10 to 40 per 100,000 children in the developing world, and 1 to 4 per 100,000 children in the developed world. Cataracts become more common with age. In the United States, cataracts occur in 68% of those over the age of 80 years. Additionally they are more common in women, and less common in Hispanic and Black people. Signs and symptoms Signs and symptoms vary depending on the type of cataract, though considerable overlap occurs. People with nuclear sclerotic or brunescent cataracts often notice a reduction of vision. Nuclear cataracts typically cause greater impairment of distance vision than of near vision. Those with posterior subcapsular cataracts usually complain of glare as their major symptom.The severity of cataract formation, assuming no other eye disease is present, is judged primarily by a visual acuity test. Other symptoms include frequent changes of glasses and colored halos due to hydration of lens.Congenital cataracts can result in amblyopia if not treated in a timely manner. Causes Age Age is the most common cause of cataracts. Lens proteins denature and degrade over time, and this process is accelerated by diseases such as diabetes mellitus and hypertension. Environmental factors, including toxins, radiation, and ultraviolet light have cumulative effects which are worsened by the loss of protective and restorative mechanisms due to alterations in gene expression and chemical processes within the eye.Oxidative stress is an important pathogenic mechanism in cataract formation (see for review). Senile cataracts are associated with a decrease in antioxidant capacity in the lens. An increase in oxidative stress in the lens or a decrease in the ability to remove reactive oxygen species can lead to the lens becoming more opaque. Trauma Blunt trauma causes swelling, thickening, and whitening of the lens fibers. While the swelling normally resolves with time, the white color may remain. In severe blunt trauma, or in injuries that penetrate the eye, the capsule in which the lens sits can be damaged. This damage allows fluid from other parts of the eye to rapidly enter the lens leading to swelling and then whitening, obstructing light from reaching the retina at the back of the eye. Cataracts may develop in 0.7 to 8.0% of cases following electrical injuries. Blunt trauma can also result in star- (stellate) or petal-shaped cataracts. Radiation Cataracts can arise as an effect of exposure to various types of radiation. X-rays, one form of ionizing radiation, may damage the DNA of lens cells. Ultraviolet light, specifically UVB, has also been shown to cause cataracts, and some evidence indicates sunglasses worn at an early age can slow its development in later life. Microwaves, a type of nonionizing radiation, may cause harm by denaturing protective enzymes (e.g., glutathione peroxidase), by oxidizing protein thiol groups (causing protein aggregation), or by damaging lens cells via thermoelastic expansion. The protein coagulation caused by electric and heat injuries whitens the lens. This same process is what makes the clear albumen of an egg become white and opaque during cooking. Genetics The genetic component is strong in the development of cataracts, most commonly through mechanisms that protect and maintain the lens. The presence of cataracts in childhood or early life can occasionally be due to a particular syndrome. Examples of chromosome abnormalities associated with cataracts include 1q21.1 deletion syndrome, cri-du-chat syndrome, Down syndrome, Pataus syndrome, trisomy 18 (Edwards syndrome), and Turners syndrome, and in the case of neurofibromatosis type 2, juvenile cataract on one or both sides may be noted. Examples of single-gene disorder include Alports syndrome, Conradis syndrome, cerebrotendineous xanthomatosis, myotonic dystrophy, and oculocerebrorenal syndrome or Lowe syndrome. Skin diseases The skin and the lens have the same embryological origin and so can be affected by similar diseases. Those with atopic dermatitis and eczema occasionally develop shield ulcer cataracts. Ichthyosis is an autosomal recessive disorder associated with cuneiform cataracts and nuclear sclerosis. Basal-cell nevus and pemphigus have similar associations. Smoking and alcohol Cigarette smoking has been shown to double the rate of nuclear sclerotic cataracts and triple the rate of posterior subcapsular cataracts. Evidence is conflicting over the effect of alcohol. Some surveys have shown a link, but others which followed people over longer terms have not. Inadequate vitamin C Low vitamin C intake and serum levels have been associated with greater cataract rates. However, use of supplements of vitamin C has not demonstrated benefit. Medications Some medications, such as systemic, topical, or inhaled corticosteroids, may increase the risk of cataract development. Corticosteroids most commonly cause posterior subcapsular cataracts. People with schizophrenia often have risk factors for lens opacities (such as diabetes, hypertension, and poor nutrition) but antipsychotic medications are unlikely to contribute to cataract formation. Miotics and triparanol may increase the risk. Post-operative Nearly every person who undergoes a vitrectomy—without ever having had cataract surgery—will experience progression of nuclear sclerosis after the operation. This may be because the native vitreous humor is different from the solutions used to replace the vitreous (vitreous substitutes), such as BSS Plus. This may also be because the native vitreous humour contains ascorbic acid which helps neutralize oxidative damage to the lens and because conventional vitreous substitutes do not contain ascorbic acid. Accordingly, for phakic patients requiring a vitrectomy it is becoming increasingly common for ophthalmologists to offer the vitrectomy combined with prophylactic cataract surgery to prevent cataract formation. Other diseases Diagnosis Classification Cataracts may be partial or complete, stationary or progressive, hard or soft. Histologically, the main types of age-related cataracts are nuclear sclerosis, cortical, and posterior subcapsular.Nuclear sclerosis is the most common type of cataract, and involves the central or nuclear part of the lens. This eventually becomes hard, or sclerotic, due to condensation on the lens nucleus and the deposition of brown pigment within the lens. In its advanced stages, it is called a brunescent cataract. In early stages, an increase in sclerosis may cause an increase in refractive index of the lens. This causes a myopic shift (lenticular shift) that decreases hyperopia and enables presbyopic patients to see at near without reading glasses. This is only temporary and is called second sight.Cortical cataracts are due to the lens cortex (outer layer) becoming opaque. They occur when changes in the fluid contained in the periphery of the lens causes fissuring. When these cataracts are viewed through an ophthalmoscope, or other magnification system, the appearance is similar to white spokes of a wheel. Symptoms often include problems with glare and light scatter at night.Posterior subcapsular cataracts are cloudy at the back of the lens adjacent to the capsule (or bag) in which the lens sits. Because light becomes more focused toward the back of the lens, they can cause disproportionate symptoms for their size.An immature cataract has some transparent protein, but with a mature cataract, all the lens protein is opaque. In a hypermature or Morgagnian cataract, the lens proteins have become liquid. Congenital cataract, which may be detected in adulthood, has a different classification and includes lamellar, polar, and sutural cataracts.Cataracts can be classified by using the lens opacities classification system LOCS III. In this system, cataracts are classified based on type as nuclear, cortical, or posterior. The cataracts are further classified based on severity on a scale from 1 to 5. The LOCS III system is highly reproducible. Prevention Risk factors such as UVB exposure and smoking can be addressed. Although no means of preventing cataracts has been scientifically proven, wearing sunglasses that counteract ultraviolet light may slow their development. While adequate intake of vitamins A, C, and E may protect against the risk of cataracts, clinical trials have shown no benefit from supplements, although the evidence is mixed, but weakly positive, for a potential protective effect of the carotenoids, lutein and zeaxanthin. Treatment Surgical The appropriateness of surgery depends on a persons particular functional and visual needs and other risk factors. Cataract removal can be performed at any stage and no longer requires ripening of the lens. Surgery is usually "outpatient" and usually performed using local anesthesia. About 9 of 10 patients can achieve a corrected vision of 20/40 or better after surgery.Several recent evaluations found that cataract surgery can meet expectations only when significant functional impairment due to cataracts exists before surgery. Visual function estimates such as VF-14 have been found to give more realistic estimates than visual acuity testing alone. In some developed countries, a trend to overuse cataract surgery has been noted, which may lead to disappointing results.Phacoemulsification is the most widely used cataract surgery in the developed world. This procedure uses ultrasonic energy to emulsify the cataract lens. Phacoemulsification typically comprises six steps: Anaesthetic – The eye is numbed with either a subtenon injection around the eye (see: retrobulbar block) or topical anesthetic eye drops. The former also provides paralysis of the eye muscles. Corneal incision – Two cuts are made at the margin of the clear cornea to allow insertion of instruments into the eye. Capsulorhexis – A needle or small pair of forceps is used to create a circular hole in the capsule in which the lens sits. Phacoemulsification – A handheld ultrasonic probe is used to break up and emulsify the lens into liquid using the energy of ultrasound waves. The resulting emulsion is sucked away. Irrigation and aspiration – The cortex, which is the soft outer layer of the cataract, is aspirated or sucked away. Fluid removed is continually replaced with a saline solution to prevent collapse of the structure of the anterior chamber (the front part of the eye). Lens insertion – A plastic, foldable lens is inserted into the capsular bag that formerly contained the natural lens. Some surgeons also inject an antibiotic into the eye to reduce the risk of infection. The final step is to inject salt water into the corneal wounds to cause the area to swell and seal the incision.A Cochrane review found little to no difference in visual acuity as a function of the size of incisions made for phacoemulsification in the range from ≤ 1.5 mm to 3.0 mm. Extracapsular cataract extraction (ECCE) consists of removing the lens manually, but leaving the majority of the capsule intact. The lens is expressed through a 10- to 12-mm incision which is closed with sutures at the end of surgery. ECCE is less frequently performed than phacoemulsification, but can be useful when dealing with very hard cataracts or other situations where emulsification is problematic. Manual small incision cataract surgery (MSICS) has evolved from ECCE. In MSICS, the lens is removed through a self-sealing scleral tunnel wound in the sclera which, ideally, is watertight and does not require suturing. Although "small", the incision is still markedly larger than the portal in phacoemulsion. This surgery is increasingly popular in the developing world where access to phacoemulsification is still limited.Intracapsular cataract extraction (ICCE) is rarely performed. The lens and surrounding capsule are removed in one piece through a large incision while pressure is applied to the vitreous membrane. The surgery has a high rate of complications. Prognosis Postoperative care The postoperative recovery period (after removing the cataract) is usually short. The patient is usually ambulatory on the day of surgery, but is advised to move cautiously and avoid straining or heavy lifting for about a month. The eye is usually patched on the day of surgery and use of an eye shield at night is often suggested for several days after surgery.In all types of surgery, the cataractous lens is removed and replaced with an artificial lens, known as an intraocular lens, which stays in the eye permanently. Intraocular lenses are usually monofocal, correcting for either distance or near vision. Multifocal lenses may be implanted to improve near and distance vision simultaneously, but these lenses may increase the chance of unsatisfactory vision. Complications Serious complications of cataract surgery include retinal detachment and endophthalmitis. In both cases, patients notice a sudden decrease in vision. In endophthalmitis, patients often describe pain. Retinal detachment frequently presents with unilateral visual field defects, blurring of vision, flashes of light, or floating spots.The risk of retinal detachment was estimated as about 0.4% within 5.5 years, corresponding to a 2.3-fold risk increase compared to naturally expected incidence, with older studies reporting a substantially higher risk. The incidence is increasing over time in a somewhat linear manner, and the risk increase lasts for at least 20 years after the procedure. Particular risk factors are younger age, male sex, longer axial length, and complications during surgery. In the highest risk group of patients, the incidence of pseudophakic retinal detachment may be as high as 20%.The risk of endophthalmitis occurring after surgery is less than one in 1000.Corneal edema and cystoid macular edema are less serious but more common, and occur because of persistent swelling at the front of the eye in corneal edema or back of the eye in cystoid macular edema. They are normally the result of excessive inflammation following surgery, and in both cases, patients may notice blurred, foggy vision. They normally improve with time and with application of anti-inflammatory drops. The risk of either occurring is around one in 100. It is unclear whether NSAIDs or corticosteroids are superior at reducing postoperative inflammation.Posterior capsular opacification, also known as after-cataract, is a condition in which months or years after successful cataract surgery, vision deteriorates or problems with glare and light scattering recur, usually due to thickening of the back or posterior capsule surrounding the implanted lens, so-called posterior lens capsule opacification. Growth of natural lens cells remaining after the natural lens was removed may be the cause, and the younger the patient, the greater the chance of this occurring. Management involves cutting a small, circular area in the posterior capsule with targeted beams of energy from a laser, called Nd:YAG laser capsulotomy, after the type of laser used. The laser can be aimed very accurately, and the small part of the capsule which is cut falls harmlessly to the bottom of the inside of the eye. This procedure leaves sufficient capsule to hold the lens in place, but removes enough to allow light to pass directly through to the retina. Serious side effects are rare. Posterior capsular opacification is common and occurs following up to one in four operations, but these rates are decreasing following the introduction of modern intraocular lenses together with a better understanding of the causes.Vitreous touch syndrome is a possible complication of intracapsular cataract extraction. Epidemiology Age-related cataracts are responsible for 51% of world blindness, about 20 million people. Globally, cataracts cause moderate to severe disability in 53.8 million (2004), 52.2 million of whom are in low and middle income countries.In many countries, surgical services are inadequate, and cataracts remain the leading cause of blindness. Even where surgical services are available, low vision associated with cataracts may still be prevalent as a result of long waits for, and barriers to, surgery, such as cost, lack of information and transportation problems. In the United States, age-related lens changes have been reported in 42% between the ages of 52 and 64, 60% between the ages 65 and 74, and 91% between the ages of 75 and 85. Cataracts affect nearly 22 million Americans age 40 and older. By age 80, more than half of all Americans have cataracts. Direct medical costs for cataract treatment are estimated at $6.8 billion annually.In the eastern Mediterranean region, cataracts are responsible for over 51% of blindness. Access to eye care in many countries in this region is limited. Childhood-related cataracts are responsible for 5–20% of world childhood blindness. History Cataract surgery was first described by the Ayurvedic physician, Suśruta (about 5th century BCE) in Sushruta Samhita in ancient India. Most of the methods mentioned focus on hygiene. Follow-up treatments include bandaging of the eye and covering the eye with warm butter. References to cataracts and their treatment in Ancient Rome are also found in 29 AD in De Medicinae, the work of the Latin encyclopedist Aulus Cornelius Celsus. Archaeological evidence of eye surgery in the Roman era also exists.Galen of Pergamon (ca. 2nd century CE), a prominent Greek physician, surgeon and philosopher, performed an operation similar to modern cataract surgery. Using a needle-shaped instrument, Galen attempted to remove the cataract-affected lens of the eye.Muslim ophthalmologist Ammar Al-Mawsili, in his The Book of Choice in Ophthalmology, written circa 1000 CE, wrote of his invention of a syringe and the technique of cataract extraction while experimenting with it on a patient. Etymology "Cataract" is derived from the Latin cataracta, meaning "waterfall", and from the Ancient Greek καταρράκτης (katarrhaktēs), "down-rushing", from καταράσσω (katarassō) meaning "to dash down" (from kata-, "down"; arassein, "to strike, dash"). As rapidly running water turns white, so the term may have been used metaphorically to describe the similar appearance of mature ocular opacities. In Latin, cataracta had the alternative meaning "portcullis" and the name possibly passed through French to form the English meaning "eye disease" (early 15th century), on the notion of "obstruction". Early Persian physicians called the term nazul-i-ah, or "descent of the water"—vulgarised into waterfall disease or cataract—believing such blindness to be caused by an outpouring of corrupt humour into the eye. Research N-Acetylcarnosine drops have been investigated as a medical treatment for cataracts. The drops are believed to work by reducing oxidation and glycation damage in the lens, particularly reducing crystallin crosslinking. Some benefit has been shown in small manufacturer-sponsored randomized controlled trials but further independent corroboration is still required.Femtosecond laser mode-locking, used during cataract surgery, was originally used to cut accurate and predictable flaps in LASIK surgery, and has been introduced to cataract surgery. The incision at the junction of the sclera and cornea and the hole in capsule during capsulorhexis, traditionally made with a handheld blade, needle, and forceps, are dependent on skill and experience of the surgeon. Sophisticated three-dimensional images of the eyes can be used to guide lasers to make these incisions. A Nd:YAG laser can also then break up the cataract as in phacoemulsification.Stem cells have been used in a clinical trial for lens regeneration in twelve children under the age of two with cataracts present at birth. The children were followed for six months, so it is unknown what the long-term results will be, and it is unknown if this procedure would work in adults. See also Galactosemic cataract Intraocular lens References External links Cataract at Curlie Pictures of different types of cataracts
Hereditary coproporphyria	Hereditary coproporphyria (HCP) is a disorder of heme biosynthesis, classified as an acute hepatic porphyria. HCP is caused by a deficiency of the enzyme coproporphyrinogen oxidase, coded for by the CPOX gene, and is inherited in an autosomal dominant fashion, although homozygous individuals have been identified. Unlike acute intermittent porphyria, individuals with HCP can present with cutaneous findings similar to those found in porphyria cutanea tarda in addition to the acute attacks of abdominal pain, vomiting and neurological dysfunction characteristic of acute porphyrias. Like other porphyrias, attacks of HCP can be induced by certain drugs, environmental stressors or diet changes. Biochemical and molecular testing can be used to narrow down the diagnosis of a porphyria and identify the specific genetic defect. Overall, porphyrias are rare diseases. The combined incidence for all forms of the disease has been estimated at 1:20,000. The exact incidence of HCP is difficult to determine, due to its reduced penetrance. Signs and symptoms Clinically, patients affected with HCP present similarly to those with other acute porphyrias, such as acute intermittent porphyria (AIP) and variegate porphyria (VP). Patients with HCP and VP can present with symptoms shared between the acute and cutaneous porphyrias. This includes the acute attacks of abdominal pain, nausea, vomiting, diarrhea, tachycardia, hypertension and seizures, as well as the cutaneous findings seen in porphyria cutanea tarda (PCT), namely increased skin fragility, bullous lesions after exposure to sunlight and increased scarring.Individuals with HCP may be asymptomatic in the absence of triggering factors. Common triggers include certain drugs, alcohol, hormonal changes, and dietary changes. Sunlight and other ultraviolet light can trigger the skin manifestations. Homozygous individuals for CPOX mutations can present with these findings at an earlier age than heterozygotes. Genetics HCP is caused by mutations in CPOX, which codes for the enzyme coproporphyrinogen oxidase. This enzyme is responsible for the sixth step in the heme biosynthetic pathway, converting coproporphyrinogen III to protoporphyrinogen IX. CPOX is located at 3q11.2-q12.1, has 6 introns and 7 exons and produces an mRNA strand that is 2675 bases in length. It is inherited in an autosomal dominant fashion, meaning that a deficiency of 50% of the normal enzyme activity is enough to cause symptoms. As reproductive fitness is not impacted, homozygous affected individuals have been reported. Along with other acute porphyrias HCP demonstrates reduced penetrance, meaning not all individuals who carry a disease-causing mutation will express symptoms.Individuals who are homozygous for a specific mutation (K404E) or compound heterozygous with a null allele in CPOX have a more severe erythropoietic porphyria, harderoporphyria, characterized by neonatal jaundice, hyperbilirubinemia, hepatosplenomegaly and skin lesions upon exposure to ultraviolet light. HCP is a rare disease, but the exact incidence is difficult to determine due to the reduced penetrance of the acute porphyrias. Overall, the incidence of all porphyrias is estimated at 1:20,000 in the United States. The incidence of harderoporphyria is even lower, with less than 10 cases reported worldwide. Diagnosis The diagnosis of any porphyria is often delayed due to the rarity of the disease as well as the varied and non-specific findings that patients present with. Bedside measurement of urine porphobilinogen is recommended as a screening test for patients suspected of having an acute porphyria. Elevated porphobilinogen is indicative of an acute porphyria, and additional testing can be done to narrow down the specific type.The identification of a specific porphyria is based on the results of laboratory findings, including blood, urine and stool tests. HCP can be distinguished from most other acute porphyrias by the cutaneous findings. VP presents similarly, but can be distinguished based on urine and stool porphyrin analysis, typically done using high performance liquid chromatography with fluorescence detection. The results of biochemical testing for porphyrias are most informative when samples are collected during an acute attack. Typically, the distinguishing metabolite for HCP and VP is the presence of protoporphyrin in the plasma and feces of individuals affected with VP.Elevated coproporphyrin is a common finding in urine, known as coproporphyrinuria as it is the predominant porphyrin species in urine. This is a non-specific finding that is not necessarily due to an acute porphyria. Coproporphyrinuria can be caused by other stressors to the heme biosynthetic pathway, such as liver disease, lead poisoning and certain bone marrow disorders. Treatment There is no cure for HCP caused by the deficient activity of coproporphyrinogen oxidase. Treatment of the acute symptoms of HCP is the same as for other acute porphyrias. Intravenous hemin (as heme arginate or hematin) is the recommended therapy for acute attacks. Acute attacks can be severe enough to cause death if not treated quickly and correctly. Hospitalization is typically required for administration of hemin, and appropriate drug selection is key to avoid exacerbating symptoms with drugs that interact poorly with porphyrias. Proper drug selection is most difficult when it comes to treatment of the seizures that can accompany HCP, as most anti-seizure medications can make the symptoms worse. Gabapentin and levetiracetam are two anti-seizure drugs that are thought to be safe.In patients where management of symptoms is difficult even with hemin, liver transplant is an option before the symptoms have progressed to advanced paralysis. Combined liver and kidney transplants are sometimes undertaken in people with kidney failure.Long term treatment of acute porphyrias is centered on the avoidance of acute attacks by eliminating precipitating factors, such as drugs, dietary changes, and infections. Females often have attacks coincident with their menstrual cycle, which can be managed effectively with hormonal birth control. Because of the reduced penetrance of HCP, family members of a patient may carry the same mutation without ever presenting with symptoms. Molecular analysis of CPOX is the best way to identify these patients, as they will not express a biochemical phenotype on laboratory testing unless they are symptomatic. Identification of asymptomatic patients allows them to adjust their lifestyle to avoid common triggering factors. References External links Porphyria at NLM Genetics Home Reference Coproporphyria at NIHs Office of Rare Diseases MedlinePlus Encyclopedia: Porphyria
Dehydration	In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mild dehydration can also be caused by immersion diuresis, which may increase risk of decompression sickness in divers. Most people can tolerate a 3-4% decrease in total body water without difficulty or adverse health effects. A 5-8% decrease can cause fatigue and dizziness. Loss of over ten percent of total body water can cause physical and mental deterioration, accompanied by severe thirst. Death occurs at a loss of between fifteen and twenty-five percent of the body water. Mild dehydration is characterized by thirst and general discomfort and is usually resolved with oral rehydration. Dehydration can cause hypernatremia (high levels of sodium ions in the blood) and is distinct from hypovolemia (loss of blood volume, particularly blood plasma). Signs and symptoms The hallmarks of dehydration include thirst and neurological changes such as headaches, general discomfort, loss of appetite, decreased urine volume (unless polyuria is the cause of dehydration), confusion, unexplained tiredness, purple fingernails, and seizures. The symptoms of dehydration become increasingly severe with greater total body water loss. A body water loss of 1-2%, considered mild dehydration, is shown to impair cognitive performance. While in people over age 50, the bodys thirst sensation diminishes with age, a study found that there was no difference in fluid intake between young and old people. Many older people have symptoms of dehydration. Dehydration contributes to morbidity in the elderly population, especially during conditions that promote insensible free water losses, such as hot weather. A Cochrane review on this subject defined water-loss dehydration as "people with serum osmolality of 295 mOsm/kg or more" and found that the main symptom in the elderly (people aged over 65) was fatigue. Cause Risk factors for dehydration include but are not limited to: exerting oneself in hot and humid weather, habitation at high altitudes, endurance athletics, elderly adults, infants, children and people living with chronic illnesses.Dehydration can also come as a side effect from many different types of drugs and medications.In the elderly, blunted response to thirst or inadequate ability to access free water in the face of excess free water losses (especially hyperglycemia related) seem to be the main causes of dehydration. Excess free water or hypotonic water can leave the body in two ways – sensible loss such as osmotic diuresis, sweating, vomiting and diarrhea, and insensible water loss, occurring mainly through the skin and respiratory tract. In humans, dehydration can be caused by a wide range of diseases and states that impair water homeostasis in the body. These occur primarily through either impaired thirst/water access or sodium excess. Diagnosis Definition Dehydration occurs when water intake does not replace free water lost due to normal physiologic processes, including breathing, urination, perspiration, or other causes, including diarrhea, and vomiting. Dehydration can be life-threatening when severe and lead to seizures or respiratory arrest, and also carries the risk of osmotic cerebral edema if rehydration is overly rapid.The term "dehydration" has sometimes been used incorrectly as a proxy for the separate, related condition of hypovolemia, which specifically refers to a decrease in volume of blood plasma. The two are regulated through independent mechanisms in humans; the distinction is important in guiding treatment. Prevention For routine activities, thirst is normally an adequate guide to maintain proper hydration. Minimum water intake will vary individually depending on weight, environment, diet, and genetics. With exercise, exposure to hot environments, or a decreased thirst response, additional water may be required. In athletes in competition, drinking to thirst optimizes performance and safety, despite weight loss, and as of 2010, there was no scientific study showing that it is beneficial to stay ahead of thirst and maintain weight during exercise.In warm or humid weather, or during heavy exertion, water loss can increase markedly, because humans have a large and widely variable capacity for sweating. Whole-body sweat losses in men can exceed 2 L/h during competitive sport, with rates of 3–4 L/h observed during short-duration, high-intensity exercise in the heat. When such large amounts of water are being lost through perspiration, electrolytes, especially sodium, are also being lost.In most athletes exercising and sweating for 4–5 hours with a sweat sodium concentration of less than 50 mmol/L, the total sodium lost is less than 10% of total body stores (total stores are approximately 2,500 mmol, or 58 g for a 70-kg person). These losses appear to be well tolerated by most people. The inclusion of sodium in fluid replacement drinks has some theoretical benefits and poses little or no risk, so long as these fluids are hypotonic (since the mainstay of dehydration prevention is the replacement of free water losses). Treatment The most effective treatment for minor dehydration is widely considered to be drinking water and reducing fluid loss. Plain water restores only the volume of the blood plasma, inhibiting the thirst mechanism before solute levels can be replenished. Solid foods can contribute to fluid loss from vomiting and diarrhea. Urine concentration and frequency will return to normal as dehydration resolves.In some cases, correction of a dehydrated state is accomplished by the replenishment of necessary water and electrolytes (through oral rehydration therapy, or fluid replacement by intravenous therapy). As oral rehydration is less painful, non-invasive, inexpensive, and easier to provide, it is the treatment of choice for mild dehydration. Solutions used for intravenous rehydration must be isotonic or hypertonic. Pure water injected into the veins will cause the breakdown (lysis) of red blood cells (erythrocytes).When fresh water is unavailable (e.g. at sea or in a desert), seawater or drinks with significant alcohol concentration will worsen dehydration. Urine contains a lower solute concentration than seawater; this requires the kidneys to create more urine to remove the excess salt, causing more water to be lost than was consumed from seawater. If a person is dehydrated and taken to a medical facility, IVs can also be used.For severe cases of dehydration where fainting, unconsciousness, or other severely inhibiting symptoms are present (the patient is incapable of standing or thinking clearly), emergency attention is required. Fluids containing a proper balance of replacement electrolytes are given orally or intravenously with continuing assessment of electrolyte status; complete resolution is normal in all but the most extreme cases. See also Hydrational fluids Terminal dehydration Dryness (medical) Hypernatremia References Further reading External links Definition of dehydration by the U.S. National Institutes of Healths MedlinePlus medical encyclopedia
Perineal hernia	Perineal hernia is a hernia involving the perineum (pelvic floor). The hernia may contain fluid, fat, any part of the intestine, the rectum, or the bladder. It is known to occur in humans, dogs, and other mammals, and often appears as a sudden swelling to one side (sometimes both sides) of the anus. A common cause of perineal hernia is surgery involving the perineum. Perineal hernia can be caused also by excessive straining to defecate. Other causes include prostate or urinary disease, constipation, anal sac disease (in dogs), and diarrhea. Atrophy of the levator ani muscle and disease of the pudendal nerve may also contribute to a perineal hernia. In humans In humans, a major cause of perineal hernia is perineal surgery without adequate reconstruction. In some cases, particularly surgeries to remove the coccyx and distal sacrum, adequate reconstruction is very difficult to achieve. The posterior perineum is a preferred point of access for surgery in the pelvic cavity, particularly in the presacral space. Surgeries here include repair of rectal prolapse and anterior meningocele, radical perineal prostatectomy, removal of tumors including sacrococcygeal teratoma, and coccygectomy. Perineal hernia is a common complication of coccygectomy in adults, but not in infants and children (see coccygectomy). The standard surgical technique for repair of perineal hernia uses a prosthetic mesh, but this technique has a high rate of failure due to insufficient anchoring. Promising techniques to reduce the rate of failure include an orthopedic anchoring system, a gluteus maximus muscle flap, an acellular human dermis graft, and an acellular pig collagen graft. In dogs and cats In dogs, perineal hernia usually is found on the right side. Most cases are in older intact (not neutered) male dogs (93 percent in one study). Breeds that may be at risk include Welsh Corgis, Boxers, Australian Kelpies, Boston Terriers, Collies, Dachshunds, Old English Sheepdogs, and Pekingese. Perineal hernias are rare in female dogs and uncommon in cats. Dogs with benign prostatic hyperplasia have been found to have increased relaxin levels and suspected subsequent weakening of the pelvic diaphragm. In cats, perineal hernias are seen most commonly following perineal urethrostomy surgery or secondary to megacolon. Medical treatment consists of treatment of the underlying disease, enemas, and stool softeners. Because only about 20 percent of cases treated medically are free of symptoms, surgery is often necessary. Recurrence is common with or without surgery. Several surgeries have been described for perineal hernias in dogs. The current standard involves transposition of the internal obturator muscle. This technique has a lower recurrence and complication rate than traditional hernia repair. A new technique uses porcine small intestinal submucosa as a biomaterial to help repair the defect. This is can also be done in combination with internal obturator muscle transposition, especially when that muscle is weak. == References ==
Borderline lepromatous leprosy	Borderline lepromatous leprosy is a skin condition with numerous, symmetrical skin lesions.: 346 See also Leprosy Cutaneous conditions References == External links ==
Road rash	Road rash is a colloquial term for skin injury caused by abrasion with road surfaces, often as a consequence of cycling and motorcycling accidents. It may also result from running, inline skating, roller skating, skateboarding, and longboarding accidents. The term may be applied to both a fresh injury and also to the scar tissue left by an old injury. Symptoms may include pain and heavy bleeding. Motorcyclists can reduce the risks of road rash by wearing appropriate motorcycle personal protective equipment such as a full face helmet, protective clothing, gloves, dusters and boots. Similarly, inline skaters can reduce their chance of such abrasion injuries by wearing protective knee and elbow pads. Road rash is often termed gravel rash in the United Kingdom. The term is old and is mentioned in Rudyard Kiplings Kim (1901). According to the OED it first appeared in print in the Hottens Dictionary of Modern Slang, Cant, and Vulgar Words (2nd Ed, 1860). References External links Abrasions and Road rash Road rash - abrasion treatment
Sturge–Weber syndrome	Sturge–Weber syndrome, sometimes referred to as encephalotrigeminal angiomatosis, is a rare congenital neurological and skin disorder. It is one of the phakomatoses and is often associated with port-wine stains of the face, glaucoma, seizures, intellectual disability, and ipsilateral leptomeningeal angioma (cerebral malformations and tumors). Sturge–Weber syndrome can be classified into three different types. Type 1 includes facial and leptomeningeal angiomas as well as the possibility of glaucoma or choroidal lesions. Normally, only one side of the brain is affected. This type is the most common. Type 2 involvement includes a facial angioma (port wine stain) with a possibility of glaucoma developing. There is no evidence of brain involvement. Symptoms can show at any time beyond the initial diagnosis of the facial angioma. The symptoms can include glaucoma, cerebral blood flow abnormalities and headaches. More research is needed on this type of Sturge–Weber syndrome. Type 3 has leptomeningeal angioma involvement exclusively. The facial angioma is absent and glaucoma rarely occurs. This type is only diagnosed via brain scan.Sturge–Weber is an embryonal developmental anomaly resulting from errors in mesodermal and ectodermal development. Unlike other neurocutaneous disorders (phakomatoses), Sturge–Weber occurs sporadically (i.e., does not have a hereditary cause). It is caused by a mosaic, somatic activating mutation occurring in the GNAQ gene. Imaging findings may include tram track calcifications on CT, pial angiomatosis, and hemicerebral atrophy. Signs and symptoms Sturge–Weber syndrome is usually manifested at birth by a port-wine stain on the forehead and upper eyelid of one side of the face, or the whole face. The birthmark can vary in color from light pink to deep purple and is caused by an overabundance of capillaries around the ophthalmic branch of the trigeminal nerve, just under the surface of the face. There is also malformation of blood vessels in the pia mater overlying the brain on the same side of the head as the birthmark. This causes calcification of tissue and loss of nerve cells in the cerebral cortex.Neurological signs include seizures that begin in infancy and may worsen with age. Convulsions usually happen on the side of the body opposite the birthmark, and vary in severity. There may also be muscle weakness on the side of the body opposite the birthmark.Some children will have developmental delays and cognitive delays; about 50% will have glaucoma (optic neuropathy often associated with increased intraocular pressure), which can be present at birth or develop later. Glaucoma can be expressed as leukocoria, which should suggest further evaluation for retinoblastoma. Increased pressure within the eye can cause the eyeball to enlarge and bulge out of its socket (buphthalmos).Sturge–Weber syndrome rarely affects other body organs. Cause The blood vessel formations associated with SWS start in the fetal stage. Around the sixth week of development, a network of nerves develops around the area that will become a babys head. Normally, this network goes away in the ninth week of development. In babies with SWS due to mutation of gene GNAQ, this network of nerves doesnt go away. This reduces the amount of oxygen and blood flowing to the brain, which can affect brain tissue development. Diagnosis CT and MRI are most often used to identify intracranial abnormalities. When a child is born with a facial cutaneous vascular malformation covering a portion of the upper or the lower eyelids, imaging should be performed to screen for intracranial leptomeningeal angiomatosis. The haemangioma present on the surface of the brain is in the vast majority of cases on the same side as the birth mark and gradually results in calcification of the underlying brain and atrophy of the affected region. Treatment Treatment for Sturge–Weber syndrome is symptomatic. Laser treatment may be used to lighten or remove the birthmark. Anticonvulsant medications may be used to control seizures. Doctors recommend early monitoring for glaucoma, and surgery may be performed on more serious cases. When one side of the brain is affected and anticonvulsants prove ineffective, the standard treatment is neurosurgery to remove or disconnect the affected part of the brain (hemispherectomy). Physical therapy should be considered for infants and children with muscle weakness. Educational therapy is often prescribed for those with intellectual disability or developmental delays, but there is no complete treatment for the delays. Brain surgery involving removing the portion of the brain that is affected by the disorder can be successful in controlling the seizures so that the patient has only a few seizures that are much less intense than pre-surgery. Surgeons may also opt to "switch-off" the affected side of the brain.Latanoprost (Xalatan), a prostaglandin, may significantly reduce IOP (intraocular pressure) in patients with glaucoma associated with Sturge–Weber syndrome. Latanoprost is commercially formulated as an aqueous solution in a concentration of 0.005% preserved with 0.02% benzalkonium chloride (BAC). The recommended dosage of latanoprost is one drop daily in the evening, which permits better diurnal IOP control than does morning instillation. Its effect is independent of ethnicity, gender or age, and it has few to no side effects. Contraindications include a history of cystic macular edema (CME), epiretinal membrane formation, vitreous loss during cataract surgery, history of macular edema associated with branch retinal vein occlusion, history of anterior uveitis, and diabetes mellitus. It is also wise to advise patients that unilateral treatment can result in heterochromia or hypertrichosis that may become cosmetically objectionable. Prognosis Although it is possible for the birthmark and atrophy in the cerebral cortex to be present without symptoms, most infants will develop convulsive seizures during their first year of life. There is a greater likelihood of intellectual impairment when seizures are resistant to treatment. Studies do not support the widely held belief that seizure frequency early in life in patients who have SWS is a prognostic indicator. Epidemiology It occurs in approximately 1 in 50,000 newborns. Eponym It is named for William Allen Sturge and Frederick Parkes Weber. Society and culture The Sturge-Weber Foundations (The SWF) international mission is to improve the quality of life and care for people with Sturge–Weber syndrome and associated port wine birthmark conditions. It supports affected individuals and their families with education, advocacy, and research to promote effective management and awareness. The SWF was founded by Kirk and Karen Ball, who began searching for answers after their daughter was diagnosed with Sturge–Weber syndrome at birth. The SWF was incorporated in the US in 1987 as an International 501(c)(3) non-profit organization. In 1992, the mission was expanded to include individuals with capillary vascular birthmarks, Klippel Trenaunay (KT) and Port Wine Birthmarks.The Hemispherectomy Foundation was formed in 2008 to assist families with children who have Sturge–Weber syndrome and other conditions that require hemispherectomy. The Brain Recovery Project was formed in 2011 to fund research and establish rehabilitation protocols to help children who have had hemispherectomy surgery reach their full potential.Sturge Weber UK (SWUK), formerly Sturge-Weber Foundation UK, is a volunteer-run registered charity formed in 1990. The charity exists to support those affected by Sturge Weber syndrome, promote research into the condition and raise awareness of the condition amongst both public and professionals. The charity was instrumental in setting up a specialist Sturge Weber clinic at Great Ormond Street Hospital. References Further reading Greenwood M, Meechan JG (July 2003). "General medicine and surgery for dental practitioners Part 4: Neurological disorders". Br Dent J. 195 (1): 19–25. doi:10.1038/sj.bdj.4810275. PMID 12856021. Fig. 2 A patient with Sturge Weber Syndrome {{cite journal}}: External link in \|quote= (help) External links sturge_weber at NINDS
Aggressive periodontitis	Aggressive periodontitis describes a type of periodontal disease and includes two of the seven classifications of periodontitis as defined by the 1999 classification system: Localized aggressive periodontitis (LAP) Generalized aggressive periodontitis (GAP)LAP is localised to first molar or incisor interproximal attachment loss, whereas GAP is the interproximal attachment loss affecting at least three permanent teeth other than incisors and first molar. The prevalence of LAP is less than 1% and that of GAP is 0.13%. Approximately 0.1% of white Caucasians (with 0.1% in northern and in central Europe, 0.5% in southern Europe, and 0.1-0.2% in North America) and 2.6% of black Africans may have LAP. Estimates of the disease prevalence are 1-5% in the African population and in groups of African descent, 2.6% in African-Americans, 0.5-1.0% in Hispanics in North America, 0.3-2.0% in South America, and 0.2-1.0% in Asia. On the other hand, in Asia, the prevalence rate of 1.2% for LAP and 0.6% for GAP in Baghdad and Iran population, and 0.47% in Japanese population.Therefore, the prevalence of LAP varies considerably between continents, and differences in race or ethnicity seem to be a major contributing factor.Aggressive periodontitis is much less common than chronic periodontitis and generally affects younger patients than does the chronic form.[2][3] Around 1 in every 1000 patients experience more rapid loss of attachment. Males seem to be at higher risk of GAP than femalesThe localized and generalized forms are not merely different in extent; they differ in etiology and pathogenesis. Etiology Microbiology Of the microflora characterised in aggressive periodontitis, approximately 65-75% of bacteria are Gram-negative bacilli, with few spirochaetes or motile rods present. Aggressive periodontitis is often characterised by a rapid loss of periodontal attachment associated with highly pathogenic bacteria and an impaired immune response. Various studies have associated Aggregatibacter actinomycetemcomitans, formerly known as Actinobacillus actinomycetemcomitans, with aggressive periodontitis. An early study dating back to 1983 explains its prevalence and documents its role in localised aggressive periodontitis.Virulence factors are the attributes of microorganisms that enable it to colonise a particular niche in its host, overcome the host defences and initiate a disease process. Fives Taylor et al. (2000) have categorised the virulence factors of Aggregatibacter actinomycetemcomitans as follows. Samaranayake notes the evidence for the specific involvement of Aggregatibacter actinomycetemcomitans includes: an increased incidence of it found in subgingival plaque obtained from lesional sites, high level of its antibody which tends to fall following successful treatment, its possession of a wide range of potentially pathogenic products and its elimination with concordant disease regression, following treatment with successful periodontal therapy and adjunctive tetracycline.Porphyromonas gingivalis is a Gram-negative anaerobe associated with the pathogenicity of periodontal disease, and aggressive periodontitis is no exception. Greater numbers of both Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were found in active, destructive periodontal lesions in comparison to non-active sites.Capnocytophaga spp are implicated as prime periodontal pathogens, especially in localised aggressive periodontitis. Both Capnocytophaga spp and Prevotella intermedia were the most frequently detected microorganisms in a study, which also noted that Capnocytophaga spp was the most prominent bacteria in subgingival samples of patients with aggressive periodontitis.An impaired ability of peripheral blood lymphocytes to react to chemotactic stimuli is found in the majority of patients with aggressive periodontitis. As well as Aggregatibacter actinomycetemcomitans being associated with this, the synergism of the disease also accounts for both Capnocytophaga spp and Porphyromonas gingivalis. Pathophysiology Aggressive periodontitis is a multifactorial disease with many complex interactions including host factors, microbiology and genetics. Host defences involve multiple factors; saliva, epithelium, inflammatory response, immune response and chemical mediators. The inflammatory exudate in the gingival tissues and gingival crevicular fluid is mostly polymorph neutrophils but also includes B cells and plasma cells. The neutrophils may show an intrinsic functional defect and respond abnormally when challenged by certain pathogens. The plasma cells produce specific antibodies in response to the periodontal pathogens, which diffuse into the gingival crevicular fluid. They produce mainly IgG, with some IgA. It has been suggested that these gingival crevicular fluid antibody levels could be potentially useful in the development of a vaccine. Patients with localised aggressive periodontitis have large amount of Aggregatibacter actinomycetemcomitans specific IgG2. This is suggested to be protective against wider spread periodontal breakdown. However, patients with generalized aggressive periodontitis have decreased ability to mount high titres of IgG to Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. It has also been found that a low T-helper to T-suppressor ratio is found in aggressive periodontitis which may alter local immune regulation. Monocytes respond to bacterial and inflammatory stimuli with very high levels of local release inflammatory mediators and induce hyper-inflammatory reaction with activation of tissue degrading matrix-metalloproteinases. These is also evidence they produce increased amounts IL-1α and IL-1β which cause osteoclastic bone resorption. These amounts are greatly reduced following treatment.Studies of families, twins and sibling pairs have provided strong evidence for a genetic basis for aggressive periodontitis. A persons genetic predisposition to the condition is determined by a single gene of major effect, inherited as an autosomal dominant trait. However, for the disease process to initiate the person must be exposed to the presence of periodontal pathogens and potentially also various environmental factors. Smoking is a generalized risk factor for generalized forms of aggressive periodontitis. Studies found that smokers have more affected teeth than non-smokers and high levels of attachment loss. This is due to the suppression of serum IgG2 and antibody against Aggregatibacter actinomycetemcomitans found in smokers. Features According to the 1999 International Workshop for the Classification of Periodontal Diseases, aggressive periodontitis was defined according to 3 primary features, in contrast to chronic periodontitis. These features are common for both localized and generalized form of disease. Primary features Patients are clinically healthy.Patients do not have any underlying systemic disease that would contribute to aggressive periodontitis. For instance, diabetes is proved to be associated with periodontitis- it is a major risk factor when glycaemic control is poor. The rate of loss of attachment and bone loss is rapid.Loss of attachment refers to the destruction of periodontium whereas the bone refers to the alveolar bone supporting the teeth. The loss can be determined by using a calibrated periodontal probe and taking radiographs of the dentition. Usually the loss of attachment is greater than 2mm per year. Aggressive periodontitis runs in the patients family.Familial aggregation of aggressive periodontitis is often discovered by taking a thorough medical history of the patient. The patient is said to have a high genetic susceptibility to aggressive periodontitis. Many studies have shown that genetic factors contribute to the pathogenesis of this disease. In this case, the manifestation of aggressive periodontitis is believed to be the result of genetic mutation, combined with environmental factors. Secondary features Secondary features are characteristics which are frequently seen but not always present in every patient diagnosed with aggressive periodontitis. The severity of periodontal tissue destruction is out of proportion to amount of bacteria present.The amount of bacteria is often indicated by the level of dental plaque. This feature implies that when aggressive periodontitis is present, loss of attachment and bone loss tend to occur even if the plaque level is low. High levels of Aggregatibacter (or Actinobacillus) actinomycetemcomitans and, in some populations, Porphyromonas gingivalis.These gram-negative microbes are considered the chief aetiological agent of aggressive periodontitis. They are implicated in the development of aggressive periodontitis by triggering inflammatory response in periodontal tissue. There are abnormalities associated with phagocytes.Phagocytes are essential in resolving inflammation. The impairment of their phagocytic activity results in persistent inflammation in periodontal tissues. Hyper-responsive macrophage phenotype.Due to the increased responsiveness, the macrophages produce excessive levels of inflammatory mediator and cytokine, such as prostaglandin E2 (PGE2) and interleukin-1β (IL-1B). Their hyperactivity is associated with periodontal tissue destruction and bone loss. Progression of attachment loss and bone loss may be self-arresting.In some patients, the disease may burnout without any cause-related therapy. Caries levels have seen to be lower in cases of aggressive periodontitis.Staging Cases of aggressive periodontitis have been staged into Stage I, II and III based on the severity of the cases. The staging index was proposed based on clinical features, radiological features and possible risk factors. The proposed index was validated with 10 cases of aggressive periodontitis followed for 10 years. Clinical and radiographic features Localized aggressive periodontitis Clinical features LAP begins around the age of puberty where there is interproximal loss of attachment of the first molar, and or incisors. on at least two permanent teeth (one which is a first molar) and no involvement of more than two teeth other than the first molars and incisors, lack of inflammation and evidence of deep periodontal pocket with advanced bone loss. There is also a relatively fast progression of periodontal tissue loss.With an increase in the age of the patient, there may be progression of the disease involving the adjacent teeth and lead to the patient developing GAP. The periodontal tissue also exhibits minimal signs of inflammation clinically and show a robust response with serum antibodies to pathogens.The amount of plaque present is inconsistent with the amount and severity of tissue destruction but with a high plaque pathogenicity due to the presence of increased levels of bacteria like Aggregatibacter actinomycetemcomitans (A.a) and Porphyromonas Gingivalis (P.g).Secondary features of LAP may also be present including; diastema formation with disto-labial migration of the incisors increased mobility of the affected teeth, sensitivity due to exposed root, deep dull pain that radiates to the jaw periodontal abscess with lymph node enlargement Radiographic features Radiographically, the periodontal lesion often presents with alveolar bone loss in a horizontal pattern at the interproximal surface of the permanent first molars and usually horizontal bone pattern of bone loss at the interproximal surface of the incisors as the bone is thinner than at the interproximal surface of the molars.The alveolar bone loss patterns are usually bilateral and similar on both sides and has been referred to as being a mirror-image pattern.In advanced cases the alveolar bone loss may be depicted as a horizontal bone loss pattern radiographically. Generalized aggressive periodontitis Clinical features Mostly in individuals under 30 years oldIn GAP, the clinical appearance of the disease resembles chronic periodontitis. The difference is that individuals affected by GAP are much younger and the progression of disease appears more rapid. There is a poor serum response against infecting agentsDestruction is present that is not in balance with the amount of local irritants present Generalized inter-proximal attachment loss on 3 or more permanent teeth, excluding the first molars or incisorsThe main distinction between the localized and generalized form of AgP lies in the number of teeth affected. GAP brings about attachment loss involving more than 30% of sites on teeth; effectively being at least three permanent teeth other than the first molars or incisors. Episodic nature of attachment loss Two main tissue responses have been found in GAP cases:Tissue may have severe acute inflammation and often presents with an angry red appearance and ulceration. There may be spontaneous bleeding or suppuration. This response is known to be present in the destructive phase, where there is presence of bone and attachment loss. The other response is known as a period of quiescence, where gingival tissue may appear with no inflammation, pink appearance with some possible stippling. In addition to this mild appearance there may be deep pockets upon probing. Radiographic features The key diagnostic feature of AgP is vertical bone loss around teeth including the first molars and incisors. This tends to begin around puberty in otherwise healthy individuals. There may be an appearance of "arc-shaped loss of alveolar bone extending from the distal surface of the second premolar to the mesial surface of the second molar". In GAP, generalized bone destruction is present that ranges from mild crestal bone resorption to severe alveolar bone destruction, depending on the severity of the disease. There may be a combination of vertical and horizontal bone loss defects. Screening Early diagnosis of aggressive periodontitis is important as it can cause rapid permanent destruction of the periodontal tissues. It is essential that all patients undergo a routine periodontal examination to screen for any form of periodontal disease during a dental checkup. Clinical examination At the start of the clinical examination of the gingival and periodontal tissues, the dental practitioner would look at the appearance of the gingiva first. A healthy periodontium in a Caucasian would appear stippled and pink with a knife edge margin where it abuts the tooth (pigmentation may differ in other races). After that, gingival probing depths would be checked. This would normally be carried out using a basic periodontal probe (WHO CPI). On probing, patients with AgP should have evidence of significant periodontal pocket depths and loss of attachment (LOA). Dental practitioners should also be aware of false pocketing around erupting/newly erupted teeth in the mixed dentition phase and also in the presence of gingival inflammation. The presence of bleeding on probing (BOP) should be noted which is an indicator of active disease. Radiographs Radiographic assessment should be carried out for patients with evidence of periodontitis to observe alveolar bone levels which can help to identify signs of AgP. In healthy periodontal tissues, the distance from the amelocemental junction (ACJ) to the alveolar bone crest is typically in the order of 1mm in young people. If the distance between the ACJ and alveolar bone crest is more than 2-3mm then there is a possible suggestion of AgP. In addition to that, presence of angular or vertical bone loss (especially at 6s) and arrowhead or furcation lesions are also a strong suggestion of AgP. Strong family association It is also important for a dental practitioner to check for family history of periodontal disease for each patient. This is because AgP may have an autosomal dominant inheritance pattern which suggests that up to 50% of siblings could be affected if one parent has the disease. Careful interpretation of the history is required but it may provide vital evidence in diagnosing AgP. If a case of Agp is diagnosed, it is important to screen the patients family members as well for AgP. Early detection of AgP allows intervention to be carried out before extensive periodontal destruction has taken place which further simplifies treatment. Treatment Following the initial assessment and diagnosis of AgP, a treatment plan is usually developed for each individual undergoing therapy. As the overall treatment concepts and goals for AgP are not significantly different from that of chronic periodontitis, the different treatment phases (cause related therapy; re-examination for response to therapy; definitive therapy; and maintenance) are similar for both types of periodontitis. Nevertheless, the considerable amount of bone loss relative to the young age of the individual in AgP necessitates an often more aggressive treatment approach, to halt further periodontal destruction and regain as much periodontal attachment as possible. The objective of treatment is to create a conducive clinical condition for retaining as many teeth, for as long as possible. Cause Related Therapy This stage involves discussion of the disease with the patient. Oral Hygiene Instructions: The clinician should advise the patient of his intrinsic susceptibility to plaque, which his body induces a strong, pro-inflammatory response to. It is thus essential to keep his oral hygiene immaculate. This involve going over both smooth surfaces (tooth brushing instructions) and the use of interproximal aids (e.g. floss). Smoking cessation (if applicable): Smoking is a significant risk factor for AgP, with patients who smoke having more affected teeth with loss of clinical attachment and more bone loss than non-smoking patients with AgP. Non-smokers also tend to have a better response to periodontal therapy as compared to smokers. As such, individuals must be advised of the benefits of smoking cessation and the otherwise potential risks of a worsening periodontal condition. Removal of plaque retentive factors: Local plaque retentive factors such as mal-positioned teeth, overhanging restorations, crown and bridgework, partial dentures and fixed/removable orthodontic appliances can increase the risk of periodontal disease and prevent successful treatment and resolution of associated pockets. Prior to starting periodontal treatment, any overhanging or poorly contoured restorations should be modified or replaced. Instructions should also be given on how to clean adequately around fixed restorations and appliances, and how to clean removable prostheses. These intra-oral appliances should also be well-designed and fitting.The periodontal therapy carried out at this stage is of a non-surgical approach, which is aimed at the removal of supra- and sub-gingival plaque and calculus deposits, to decrease the microbial load, bacteria biofilm, and calculus from the periodontally involved sites. Scale and Polish Root Surface Debridement (RSD) Antibiotics: There is evidence that the additional use of systemic antibiotics in conjunction with non-surgical periodontal treatment results in a more favourable clinical response, as compared to just periodontal treatment alone, as it helps to suppress pathogenic bacteria and create a health-associated biofilm. There have been many antibiotic regimes proposed for the treatment of AgP. However, the combination of choice according to current research is a combination of amoxicillin (500 mg, thrice/day) and metronidazole (200 mg, thrice/day), for 7 days, starting on the day of the final debridement. Doxycycline (100 mg, once/day, with a starting first dose of 200 mg) is the choice of antibiotics for patients allergic to penicillin. Light Amplification by Stimulated Emission of Radiation (LASER) Therapy Photodynamic Therapy (PDT): This potentially has all the advantages of low-level LASER therapy, which allows the disinfection of periodontal pocket and the eradication of bacteria in areas of difficult access, without the thermal damage to tissues associated with the high-powered LASER. A significant reduction in the aggregatibacter actinomycetemcomitans count following PDT suggests that the use of PDT in conjunction with conventional non-surgical periodontal treatment can potentially result in a more effective treatment. Considering the global issue of antibiotic resistance, further development and research in PDT successes may prove to present it an ideal adjunct to conventional non-surgical periodontal therapy, as compared to the use of systemic antibiotics. Re-examination/Response to Therapy This stage of treatment involves the reassessment of the individuals compliance (i.e. level of oral hygiene) and the tissue response to the treatment. This is carried out 10–12 weeks following RSD. If the disease is stabilised, the treatment progresses on to the maintenance stage. In the case where the disease is not stabilised, the cause of failure should be considered, and the treatment progresses on to the stage of definitive therapy, if the cause is correctable. Definitive Therapy Further RSD at sites which require treatment Use of Locally Delivered Antimicrobials (LDA) as an adjunct to non-surgical periodontal treatment: For use in deep pockets which fail to respond to repeated non-surgical treatment in patients with adequate oral hygiene. Currently, the available LDA include tetracycline, minocycline, chlorhexidine gluconate and doxycycline, with the mode of delivery being in the form of fibers, chips, polymers and trays. There has yet to be much research into the effects of LDA in AgP, but current studies report an insignificant difference to the adjunctive effect of systemic antibiotics. Periodontal surgery: If it is a localised problem and if the case is non-response to non-surgical treatment despite the oral hygiene being consistently excellent. This could involve an open flap debridement with or without regenerative procedures, with the aim of gaining access and visibility to root and furcation areas so that a thorough instrumentation and debridement can be carried out. Regenerative surgical therapy currently available include the use of bone replacement grafts, barrier membranes or guided tissue regeneration (GTR), biologic modifiers like growth and differentiation factors (GDF), and extracellular matrix proteins like enamel matrix proteins (EMD). There is however, a great variation in periodontal gains reported in the literature available, signifying that results are not entirely predictable. Maintenance Periodontal treatment may help to stabilise the disease, but it does not change ones susceptibility to the disease. Given the high susceptibility for disease progression of the individual with AgP, there is a higher risk of disease recurrence. It is thus necessary to attend frequent review appointments at the dentist to ensure there is no relapse of the disease, and that the periodontal health is maintained after active periodontal therapy. == References ==
Spondyloepiphyseal dysplasia congenita	Spondyloepiphyseal dysplasia congenita (abbreviated to SED more often than SDC) is a rare disorder of bone growth that results in dwarfism, characteristic skeletal abnormalities, and occasionally problems with vision and hearing. The name of the condition indicates that it affects the bones of the spine (spondylo-) and the ends of bones (epiphyses), and that it is present from birth (congenital). The signs and symptoms of spondyloepiphyseal dysplasia congenita are similar to, but milder than, the related skeletal disorders achondrogenesis type 2 and hypochondrogenesis. Spondyloepiphyseal dysplasia congenita is a subtype of collagenopathy, types II and XI. Presentation People with spondyloepiphyseal dysplasia are short-statured from birth, with a very short trunk and neck and shortened limbs. Their hands and feet, however, are usually average-sized. This type of dwarfism is characterized by a normal spinal column length relative to the femur bone. Adult height ranges from 0.9 meters (35 inches) to just over 1.4 meters (55 inches). Curvature of the spine (such as kyphoscoliosis and lordosis) progresses during childhood and can cause problems with breathing. Changes in the spinal bones (vertebrae) in the neck may also increase the risk of spinal cord damage. Other skeletal signs include flattened vertebrae (platyspondyly), a hip joint deformity in which the upper leg bones turn inward (coxa vara), and an inward- and downward-turning foot (called clubfoot). Decreased joint mobility and arthritis often develop early in life. Medical texts often state a mild and variable change to facial features, including cheekbones close to the nose appearing flattened, although this appears to be unfounded. Some infants are born with an opening in the roof of the mouth, which is called a cleft palate. Severe nearsightedness (high myopia) is sometimes present, as are other eye problems that can affect vision such as detached retinas. About one-quarter of people with this condition have mild to moderate hearing loss. Causes Spondyloepiphyseal dysplasia congenita is one of a spectrum of skeletal disorders caused by mutations in the COL2A1 gene. The protein made by this gene forms type II collagen, a molecule found mostly in cartilage and in the clear gel that fills the eyeball (the vitreous). Type II collagen is essential for the normal development of bones and other connective tissues. Mutations in the COL2A1 gene interfere with the assembly of type II collagen molecules, which prevents bones from developing properly and causes the signs and symptoms of this condition.Spondyloepiphyseal dysplasia congenita is inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to cause the disorder. Management There is no treatment for the underlying condition. Supportive/symptomatic treatment is based on the traits present in each person with the condition. Notable people Michael Dunn, American actor, Tony winner, Wild Wild West, Star Trek Warwick Davis, English actor and TV presenter References Spranger: Bone Dysplasias, Urban & Fischer 2002, ISBN 3-437-21430-6 Further reading GeneReviews/NIH/NCBI/UW entry on X-Linked Spondyloepiphyseal Dysplasia Tarda OMIM entries on X-Linked Spondyloepiphyseal Dysplasia Tarda == External links ==
Cyclotropia	Cyclotropia is a form of strabismus in which, compared to the correct positioning of the eyes, there is a torsion of one eye (or both) about the eyes visual axis. Consequently, the visual fields of the two eyes appear tilted relative to each other. The corresponding latent condition – a condition in which torsion occurs only in the absence of appropriate visual stimuli – is called cyclophoria. Cyclotropia is often associated with other disorders of strabism, can result in double vision, and can cause other symptoms, in particular head tilt.In some cases, subjective and objective cyclodeviation may result from surgery for oblique muscle disorders; if the visual system cannot compensate for it, cyclotropia and rotational double vision (cyclodiplopia) may result. The role of cyclotropia in vision disorders is not always correctly identified. In several cases of double vision, once the underlying cyclotropia was identified, the condition was solved by surgical cyclotropia correction.Conversely, artificially causing cyclotropia in cats leads to reduced vision acuity, resulting in a defect similar to strabismic amblyopia. Diagnosis Cyclotropia can be detected using subjective tests such as the Maddox rod test, the Bagolini striated lens test, the phase difference haploscope of Aulhorn, or the Lancaster red-green test (LRGT). Among these, the LRGT is the most complete. Cyclotropia can also be diagnosed using a combination of subjective and objective tests. Before surgery, both subjective and objective torsion should be assessed.Experiments have also been made on whether cyclic deviations can be assessed by purely photographic means. Treatment If only small amounts of torsion are present, cyclotropia may be without symptoms entirely and may not need correction, as the visual system can compensate small degrees of torsion and still achieve binocular vision (see also: cyclodisparity, cyclovergence). The compensation can be a motor response (visually evoked cyclovergence) or can take place during signal processing in the brain. In patients with cyclotropia of vascular origin, the condition often improves spontaneously.Cyclotropia cannot be corrected with prism spectacles in the way other eye position disorders are corrected. (Nonetheless two Dove prisms can be employed to rotate the visual field in experimental settings.) For cyclodeviations above 5 degrees, surgery has normally been recommended. Depending on the symptoms, the surgical correction of cyclotropia may involve a correction of an associated vertical deviation (hyper- or hypotropia), or a Harada–Ito procedure or another procedure to rotate the eye inwards, or yet another procedure to rotate it outwards. A cyclodeviation may thus be corrected at the same time with a correction of a vertical deviation (hyper- or hypotropia); cyclodeviations without any vertical deviation can be difficult to manage surgically, as the correction of the cyclodeviation may introduce a vertical deviation. References Further reading Lemos, João; Eggenberger, Eric: Clinical utility and assessment of cyclodeviation, Current Opinion in Ophthalmology, November 2013, Volume 24, Issue 6, pp. 558–565 doi:10.1097/ICU.0000000000000003 == External links ==
Pederasty	Pederasty or paederasty (US: or UK: ) is a sexual relationship between an adult man and a pubescent or adolescent boy. The term pederasty is primarily used to refer to historical practices of certain cultures, particularly ancient Greece and ancient Rome. In most countries today such relationships are illegal. The local age of consent determines whether a person is considered legally competent to consent to sexual acts, and whether such contact is child sexual abuse or statutory rape. An adult engaging in sexual activity with a minor may be considered abusive by medical authorities for a variety of reasons, including the age of the minor, the likelihood of the minor developing one or more mental disorders, such as post-traumatic stress disorder, physical injury to the minor, and the minors propensity for further victimization in adulthood. Etymology and usage Pederasty derives from the combination of Ancient Greek: παίδ-, romanized: paid-, lit. boy, child (stem) with ἐραστής, erastēs, lover (cf. eros). Late Latin pæderasta was borrowed in the 16th century directly from Platos classical Greek in The Symposium. (Latin transliterates αί as æ.) The word first appeared in the English language during the Renaissance, as pæderastie (e.g. in Samuel Purchas Pilgrimes), in the sense of sexual relations between men and boys. The Oxford English Dictionary defines it as "Homosexual relations between a man and a boy; homosexual anal intercourse, usually with a boy or younger man as the passive partner". History Ancient Greece Pederasty in ancient Greece was a socially acknowledged romantic relationship between an adult male (the erastes) and a younger male (the eromenos), usually in his teens. It was characteristic of the Archaic and Classical periods. The influence of pederasty on Greek culture of these periods was so pervasive that it has been called "the principal cultural model for free relationships between citizens."Some scholars locate its origin in initiation ritual, particularly rites of passage on Crete, where it was associated with entrance into military life and the religion of Zeus. It has no formal existence in the Homeric epics, and seems to have developed in the late 7th century BC as an aspect of Greek homosocial culture, which was characterized also by athletic and artistic nudity, delayed marriage for aristocrats, symposia, and the social seclusion of women. Pederasty was both idealized and criticized in ancient literature and philosophy. The argument has recently been made that idealization was universal in the Archaic period; criticism began in Athens as part of the general Classical Athenian reassessment of Archaic culture.Scholars have debated the role or extent of pederasty, which is likely to have varied according to local custom and individual inclination. Athenian law, for instance, recognized both consent and age as factors in regulating sexual behavior.Enid Bloch argues that many Greek boys in these relationships may have been traumatized by knowing that they were violating social customs, since the "most shameful thing that could happen to any Greek male was penetration by another male." She further argues that vases showing "a boy standing perfectly still as a man reaches out for his genitals" indicate the boy may have been "psychologically immobilized, unable to move or run away." One vase shows a young man or boy running away from Eros, the Greek god of desire. Ancient Rome In Latin, mos Graeciae or mos Graecorum ("Greek custom" or "the way of the Greeks") refers to a variety of behaviors the ancient Romans regarded as Greek, including but not confined to sexual practice.: 72 Homosexual behaviors at Rome were acceptable only within an inherently unequal relationship; male Roman citizens retained their masculinity as long as they took the active, penetrating role, and the appropriate male sexual partner was a prostitute or slave, who would nearly always be non-Roman. In Archaic and classical Greece, paiderasteia had been a formal social relationship between freeborn males; taken out of context and refashioned as the luxury product of a conquered people, pederasty came to express roles based on domination and exploitation.: 37, 40–41 et passim Slaves often were given, and prostitutes sometimes assumed Greek names regardless of their ethnic origin; the boys (pueri) to whom the poet Martial is attracted have Greek names. The use of slaves defined Roman pederasty; sexual practices were "somehow Greek" when they were directed at "freeborn boys openly courted in accordance with the Hellenic tradition of pederasty".: 17 Effeminacy or a lack of discipline in managing ones sexual attraction to another male threatened a mans "Roman-ness" and thus might be disparaged as "Eastern" or "Greek". Fears that Greek models might "corrupt" traditional Roman social codes (the mos maiorum) seem to have prompted a vaguely documented law (Lex Scantinia) that attempted to regulate aspects of homosexual relationships between freeborn males and to protect Roman youth from older men emulating Greek customs of pederasty.: 27 Theologian Edith Humphrey commented that "the Graeco-Roman ideal regarding homosexuality entailed erotic love, not of children, but of young (teenage) males of the same age that a young woman would be given in marriage, and that frequently the more mature male was only slightly older than the partner." Modern view In the modern world, an adult engaging in sexual activity with a minor may be considered child sexual abuse or statutory rape, depending upon the local age of consent. Age of consent laws exist because minors are considered incapable of meaningfully consenting to sexual activity until they reach a certain age. Prepubescent and adolescent children are not socially equal to adults, and abusers emotionally manipulate the children they victimize.: 65–66 These laws aim to give the minor some protection against predatory or exploitative sexual interaction with adults.The effects of child sexual abuse can include depression, post-traumatic stress disorder, anxiety, complex post-traumatic stress disorder, propensity to further victimization in adulthood, and physical injury to the child, among other problems.Modern sexual abusers who prefer boys may describe themselves as "boy lovers", and sometimes appeal to practices in Ancient Greece as a justification. See also References == External links ==
Hypoaldosteronism	Hypoaldosteronism is an endocrinological disorder characterized by decreased levels of the hormone aldosterone. Similarly, isolated hypoaldosteronism is the condition of having lowered aldosterone without corresponding changes in cortisol. (The two hormones are both produced by the adrenals.) Presentation Causes There are several causes for this condition, including adrenal insufficiency, congenital adrenal hyperplasia, and some medications such as certain diuretics, NSAIDs, and ACE inhibitors. Primary aldosterone deficiencyPrimary adrenal insufficiency Congenital adrenal hyperplasia (21 but not 11β and 17) Aldosterone synthase deficiencySecondary aldosterone deficiencySecondary adrenal insufficiency Diseases of the pituitary or hypothalamusHyporeninemic hypoaldosteronism (due to decreased angiotensin 2 production as well as intra-adrenal dysfunction)Renal dysfunction-most commonly diabetic nephropathy NSAIDs Ciclosporin Mechanism Hypoaldosteronism may result in high blood potassium and is the cause of type 4 renal tubular acidosis, sometimes referred to as hyperkalemic RTA or tubular hyperkalemia. However, the acidosis, if present, is often mild. It can also cause urinary sodium wasting, leading to volume depletion and hypotension.When adrenal insufficiency develops rapidly, the amount of Na+ lost from the extracellular fluid exceeds the amount excreted in the urine, indicating that Na+ also must be entering cells. When the posterior pituitary is intact, salt loss exceeds water loss and the plasma Na+ falls. However, the plasma volume also is reduced, resulting in hypotension, circulatory insufficiency, and, eventually, fatal shock. These changes can be prevented to a degree by increasing the dietary NaCl intake. Rats survive indefinitely on extra salt alone, but in dogs and most humans, the amount of supplementary salt needed is so large that it is almost impossible to prevent eventual collapse and death unless mineralocorticoid treatment is also instituted. Diagnosis Patients with a suspected diagnosis of hypoaldosteronism are often screened with simple blood tests. Potassium levels, plasma aldosterone concentration and plasma renin activity are the three most useful in the first instance. Low aldosterone levels in the presence of high renin activity, often with low sodium, high potassium, is associated with primary hypoaldosteronism. Secondary hypoaldersteronism may be suspected if renin activity is low with low aldosterone concentrations. The plasma aldosterone-to-renin ratio is calculated to determine if levels are sufficiently deranged to consider a diagnosis of hypoaldosteronism.If screening test is suggestive, a more definitive diagnosis is made by performing a saline suppression test, ambulatory salt loading test, or fludrocortisone suppression test. Imaging to detect an Adrenocortical adenoma may also be considered. Treatment Aldosterone deficiency should be treated with a mineralocorticoid (such as fludrocortisone), as well as possibly a glucocorticoid for cortisol deficiency if present. Hyporeninemic hypoaldosteronism is amenable to fludrocortisone treatment, but the accompanying hypertension and edema can prove a problem in these patients, so often a diuretic (such as the thiazide diuretic, bendrofluazide, or a loop diuretic, such as furosemide) is used to control the hyperkalemia. See also Addisons disease Adrenal gland Hyperaldosteronism Pseudohypoaldosteronism References == External links ==
Multidrug-resistant tuberculosis	Multidrug-resistant tuberculosis (MDR-TB) is a form of tuberculosis (TB) infection caused by bacteria that are resistant to treatment with at least two of the most powerful first-line anti-TB medications (drugs): isoniazid and rifampin. Some forms of TB are also resistant to second-line medications, and are called extensively drug-resistant TB (XDR-TB).Tuberculosis is caused by infection with the bacterium Mycobacterium tuberculosis. Almost one in four people in the world are infected with TB bacteria. Only when the bacteria become active do people become ill with TB. Bacteria become active as a result of anything that can reduce the persons immunity, such as HIV, advancing age, diabetes or other immunocompromising illnesses. TB can usually be treated with a course of four standard, or first-line, anti-TB drugs (i.e., isoniazid, rifampin, pyrazinamide and ethambutol).However, beginning with the first antibiotic treatment for TB in 1943, some strains of the TB bacteria developed resistance to the standard drugs through genetic changes (see mechanisms.) Currently the majority of multidrug-resistant cases of TB are due to one strain of TB bacteria called the Beijing lineage. This process accelerates if incorrect or inadequate treatments are used, leading to the development and spread of multidrug-resistant TB (MDR-TB). Incorrect or inadequate treatment may be due to use of the wrong medications, use of only one medication (standard treatment is at least two drugs), or not taking medication consistently or for the full treatment period (treatment is required for several months). Treatment of MDR-TB requires second-line drugs (i.e., fluoroquinolones, aminoglycosides, and others), which in general are less effective, more toxic and much more expensive than first-line drugs. Treatment schedules for MDR-TB involving fluoroquinolones and aminoglycosides can run for 2 years, compared to the 6 months of first-line drug treatment, and cost over US$100,000. If these second-line drugs are prescribed or taken incorrectly, further resistance can develop leading to XDR-TB. Resistant strains of TB are already present in the population, so MDR-TB can be directly transmitted from an infected person to an uninfected person. In this case a previously untreated person develops a new case of MDR-TB. This is known as primary MDR-TB, and is responsible for up to 75% of cases. Acquired MDR-TB develops when a person with a non-resistant strain of TB is treated inadequately, resulting in the development of antibiotic resistance in the TB bacteria infecting them. These people can in turn infect other people with MDR-TB.MDR-TB caused an estimated 600,000 new TB cases and 240,000 deaths in 2016 and MDR-TB accounts for 4.1% of all new TB cases and 19% of previously treated cases worldwide. Globally, most MDR-TB cases occur in South America, Southern Africa, India, China, and the former Soviet Union.Treatment of MDR-TB requires treatment with second-line drugs, usually four or more anti-TB drugs for a minimum of 6 months, and possibly extending for 18–24 months if rifampin resistance has been identified in the specific strain of TB with which the patient has been infected. Under ideal program conditions, MDR-TB cure rates can approach 70%. Mechanism of drug resistance The TB bacterium has natural defenses against some drugs, and can acquire drug resistance through genetic mutations. The bacterium does not have the ability to transfer genes for resistance between organisms through plasmids (see horizontal transfer). Some mechanisms of drug resistance include: Cell wall: The cell wall of M. tuberculosis (TB) contains complex lipid molecules which act as a barrier to stop drugs from entering the cell. Drug modifying & inactivating enzymes: The TB genome codes for enzymes (proteins) that inactivate drug molecules. These enzymes are usually phosphorylate, acetylate, or adenylate drug compounds. Drug efflux systems: The TB cell contains molecular systems that actively pump drug molecules out of the cell. Mutations: Spontaneous mutations in the TB genome can alter proteins which are the target of drugs, making the bacteria drug-resistant.One example is a mutation in the rpoB gene, which encodes the beta subunit of the bacteriums RNA polymerase. In non-resistant TB, rifampin binds the beta subunit of RNA polymerase and disrupt transcription elongation. Mutation in the rpoB gene changes the sequence of amino acids and eventual conformation of the beta subunit. In this case rifampin can no longer bind or prevent transcription, and the bacterium is resistant.Other mutations make the bacterium resistant to other drugs. For example, there are many mutations that confer resistance to isoniazid (INH), including in the genes katG, inhA, ahpC and others. Amino acid replacements in the NADH binding site of InhA apparently result in INH resistance by preventing the inhibition of mycolic acid biosynthesis, which the bacterium uses in its cell wall. Mutations in the katG gene make the enzyme catalase peroxidase unable to convert INH to its biologically active form. Hence, INH is ineffective and the bacterium is resistant. The discovery of new molecular targets is essential to overcome drug-resistance problems.In some TB bacteria, the acquisition of these mutations can be explained by other mutations in the DNA recombination, recognition and repair machinery. Mutations in these genes allow the bacteria to have a higher overall mutation rate and to accumulate mutations that cause drug resistance more quickly. Extensively drug-resistant TB MDR-TB can become resistant to the major second-line TB drug groups: fluoroquinolones (moxifloxacin, ofloxacin) and injectable aminoglycoside or polypeptide drugs (amikacin, capreomycin, kanamycin). When MDR-TB is resistant to at least one drug from each group, it is classified as extensively drug-resistant tuberculosis (XDR-TB).WHO has revised the definitions of pre-XDR-TB and XDR-TB in 2021 as following:Pre-XDR-TB: TB caused by Mycobacterium tuberculosis (M.tuberculosis) strains that fulfill the definition of MDR/RR-TB and which are also resistant to any fluoroquinolone. XDR-TB: TB caused by Mycobacterium tuberculosis (M. tuberculosis) strains that fulfill the definition of MDR/RR-TB and which are also resistant to any fluoroquinolone and at least one additional Group A drug. The Group A drugs are currently levofloxacin or moxifloxacin, bedaquiline and linezolid, therefore XDR-TB is MDR/RR-TB that is resistant to a fluoroquinolone and at least one of bedaquiline or linezolid (or both). In a study of MDR-TB patients from 2005 to 2008 in various countries, 43.7% had resistance to at least one second-line drug. About 9% of MDR-TB cases are resistant to a drug from both classes and classified as XDR-TB.In the past 10 years TB strains have emerged in Italy, Iran, India, and South Africa which are resistant to all available first and second line TB drugs, classified as totally drug-resistant tuberculosis, though there is some controversy over this term. Increasing levels of resistance in TB strains threaten to complicate the current global public health approaches to TB control. New drugs are being developed to treat extensively resistant forms but major improvements in detection, diagnosis, and treatment will be needed. Prevention There are several ways that drug resistance to TB, and drug resistance in general, can be prevented: Rapid diagnosis & treatment of TB: One of the greatest risk factors for drug-resistant TB is problems in treatment and diagnosis, especially in developing countries. If TB is identified and treated soon, drug resistance can be avoided. Completion of treatment: Previous treatment of TB is an indicator of MDR TB. If the patient does not complete their antibiotic treatment, or if the physician does not prescribe the proper antibiotic regimen, resistance can develop. Also, drugs that are of poor quality or less in quantity, especially in developing countries, contribute to MDR TB. Identifying and diagnosing patients with HIV/AIDS as soon as possible. They lack the immunity to fight the TB infection and are at great risk of developing drug resistance. Identifying contacts who could have contracted TB: family members, people in close contact, etc. Research: Much research and funding is needed in the diagnosis, prevention and treatment of TB and MDR TB."Opponents of a universal tuberculosis treatment, reasoning from misguided notions of cost-effectiveness, fail to acknowledge that MDRTB is not a disease of poor people in distant places. The disease is infectious and airborne. Treating only one group of patients looks inexpensive in the short run, but will prove disastrous for all in the long run."— Paul Farmer DOTS-Plus Community-based treatment programs such as DOTS-Plus, a MDR-TB-specialized treatment using the popular Directly Observed Therapy – Short Course (DOTS) initiative, have shown considerable success in the world. In these locales, these programs have proven to be a good option for proper treatment of MDR-TB in poor, rural areas. A successful example has been in Lima, Peru, where the program has seen cure rates of over 80%.However, TB clinicians have expressed concern in the DOTS program administered in the Republic of Georgia because it is anchored in a passive case finding. This means that the system depends on patients coming to health care providers, without conducting compulsory screenings. As medical anthropologists like Erin Koch have shown, this form of implementation does not suit all cultural structures. They urge that the DOTS protocol be constantly reformed in the context of local practices, forms of knowledge and everyday life.Erin Koch has used Paul Farmers concept of "structural" violence as a perspective for understanding how "institutions, environment, poverty, and power reproduce, solidify, and naturalize the uneven distribution of disease and access to resources". She has also studied the effectiveness of the DOTS protocol in the widespread disease of tuberculosis in the Georgian prison system. Unlike the DOTS passive case finding used for the general Georgian public, the multiple-level surveillance in the prison system has proven more successful in reducing the spread of tuberculosis while increasing rates of cure.Koch critically notes that because the DOTS protocol aims to change the individuals behavior without addressing the need to change the institutional, political, and economic contexts, certain limitations arise, such as MDR tuberculosis. Treatment Usually, multidrug-resistant tuberculosis can be cured with long treatments of second-line drugs, but these are more expensive than first-line drugs and have more adverse effects. The treatment and prognosis of MDR-TB are much more akin to those for cancer than to those for infection. MDR-TB has a mortality rate of about 15% with treatment, which further depends on a number of factors, including: How many drugs the organism is resistant to (the fewer the better) How many drugs the patient is given (patients treated with five or more drugs do better) The expertise and experience of the physician responsible How co-operative the patient is with treatment (treatment is arduous and long, and requires persistence and determination on the part of the patient) Whether the patient is HIV-positive or not (HIV co-infection is associated with increased mortality).The majority of patients with multidrug-resistant tuberculosis do not receive treatment, as they are found in underdeveloped countries or in poverty. Denial of treatment remains a difficult human rights issue, as the high cost of second-line medications often precludes those who cannot afford therapy.A study of cost-effective strategies for tuberculosis control supported three major policies. First, the treatment of smear-positive cases in DOTS programs must be the foundation of any tuberculosis control approach, and should be a basic practice for all control programs. Second, there is a powerful economic case for treating smear-negative and extra-pulmonary cases in DOTS programs along with treating smear-negative and extra-pulmonary cases in DOTS programs as a new WHO "STOP TB" approach and the second global plan for tuberculosis control. Last, but not least, the study shows that significant scaling-up of all interventions is needed in the next 10 years if the millennium development goal and related goals for tuberculosis control are to be achieved. If the case detection rate can be improved, this will guarantee that people who gain access to treatment facilities are covered and that coverage is widely distributed to people who do not now have access.In general, treatment courses are measured in months to years; MDR-TB may require surgery, and death rates remain high despite optimal treatment. However, good outcomes for patients are still possible.The treatment of MDR-TB must be undertaken by physicians experienced in the treatment of MDR-TB. Mortality and morbidity in patients treated in non-specialist centers are significantly higher than those of patients treated in specialist centers. Treatment of MDR-TB must be done on the basis of sensitivity testing: it is impossible to treat such patients without this information. When treating a patient with suspected MDR-TB, pending the result of laboratory sensitivity testing, the patient could be started on SHREZ (Streptomycin+ isonicotinyl Hydrazine+ Rifampicin+Ethambutol+ pyraZinamide) and moxifloxacin with cycloserine. There is evidence that previous therapy with a drug for more than a month is associated with diminished efficacy of that drug regardless of in vitro tests indicating susceptibility. Hence, a detailed knowledge of the treatment history of each patient is essential. In addition to the obvious risks (i.e., known exposure to a patient with MDR-TB), risk factors for MDR-TB include HIV infection, previous incarceration, failed TB treatment, failure to respond to standard TB treatment, and relapse following standard TB treatment. A gene probe for rpoB is available in some countries. This serves as a useful marker for MDR-TB, because isolated RMP resistance is rare (except when patients have a history of being treated with rifampicin alone). If the results of a gene probe (rpoB) are known to be positive, then it is reasonable to omit RMP and to use SHEZ+MXF+cycloserine. The reason for maintaining the patient on INH is that INH is so potent in treating TB that it is foolish to omit it until there is microbiological proof that it is ineffective (even though isoniazid resistance so commonly occurs with rifampicin resistance). For treatment of RR- and MDT-TB, WHO treatment guidelines are as follows: "a regimen with at least five effective TB medicines during the intensive phase is recommended, including pyrazinamide and four core second-line TB medicines – one chosen from Group A, one from Group B, and at least two from Group C3 (conditional recommendation, very low certainty in the evidence). If the minimum number of effective TB medicines cannot be composed as given above, an agent from Group D2 and other agents from Group D3 may be added to bring the total to five. It is recommended that the regimen be further strengthened with high-dose isoniazid and/or ethambutol (conditional recommendation, very low certainty in the evidence)." Medicines recommended are the following: Group A: Fluoroquinolones (levofloxacin,moxifloxicin), linezolid, bedaquiline Group B: clofazimine, cycloserine/terizidone Group C: Other core second-line agents (ethambutol, delamanid, pyrazinamide, imipenem-cilastatin/meropenem, amikacin/streptomycin, ethionamide/prothionamide, p-aminosalicylic acid)For patients with RR-TB or MDR-TB, "not previously treated with second-line drugs and in whom resistance to fluoroquinolones and second-line injectable agents was excluded or is considered highly unlikely, a shorter MDR-TB regimen of 9–12 months may be used instead of the longer regimens (conditional recommendation, very low certainty in the evidence)."In general, resistance to one drug within a class means resistance to all drugs within that class, but a notable exception is rifabutin: Rifampicin-resistance does not always mean rifabutin-resistance, and the laboratory should be asked to test for it. It is possible to use only one drug within each drug class. If it is difficult finding five drugs to treat then the clinician can request that high-level INH-resistance be looked for. If the strain has only low-level INH-resistance (resistance at 0.2 mg/L INH, but sensitive at 1.0 mg/L INH), then high dose INH can be used as part of the regimen. When counting drugs, PZA and interferon count as zero; that is to say, when adding PZA to a four-drug regimen, another drug must be chosen to make five. It is not possible to use more than one injectable (STM, capreomycin or amikacin), because the toxic effect of these drugs is additive: If possible, the aminoglycoside should be given daily for a minimum of three months (and perhaps thrice weekly thereafter). Ciprofloxacin should not be used in the treatment of tuberculosis if other fluoroquinolones are available. As of 2008, Cochrane reports that trials of other fluoroquinolones are ongoing.There is no intermittent regimen validated for use in MDR-TB, but clinical experience is that giving injectable drugs for five days a week (because there is no-one available to give the drug at weekends) does not seem to result in inferior results. Directly observed therapy helps to improve outcomes in MDR-TB and should be considered an integral part of the treatment of MDR-TB.Response to treatment must be obtained by repeated sputum cultures (monthly if possible). Treatment for MDR-TB must be given for a minimum of 18 months and cannot be stopped until the patient has been culture-negative for a minimum of nine months. It is not unusual for patients with MDR-TB to be on treatment for two years or more.Patients with MDR-TB should be isolated in negative-pressure rooms, if possible. Patients with MDR-TB should not be accommodated on the same ward as immunosuppressed patients (HIV-infected patients, or patients on immunosuppressive drugs). Careful monitoring of compliance with treatment is crucial to the management of MDR-TB (and some physicians insist on hospitalisation if only for this reason). Some physicians will insist that these patients remain isolated until their sputum is smear-negative, or even culture-negative (which may take many months, or even years). Keeping these patients in hospital for weeks (or months) on end may be a practical or physical impossibility, and the final decision depends on the clinical judgement of the physician treating that patient. The attending physician should make full use of therapeutic drug monitoring (in particular, of the aminoglycosides) both to monitor compliance and to avoid toxic effects. Some supplements may be useful as adjuncts in the treatment of tuberculosis, but, for the purposes of counting drugs for MDR-TB, they count as zero (if four drugs are already in the regimen, it may be beneficial to add arginine or vitamin D or both, but another drug will be needed to make five). Supplements are: arginine (peanuts are a good source), vitamin D,Dzherelo,V5 Immunitor.The drugs listed below have been used in desperation, and it is uncertain as to whether they are effective at all. They are used when it is not possible to find five drugs from the list above. imipenem,co-amoxiclav,clofazimine,prochlorperazine,metronidazole.On 28 December 2012, the U.S. Food and Drug Administration (FDA) approved bedaquiline (marketed as Sirturo by Johnson & Johnson) to treat multidrug-resistant tuberculosis, the first new treatment in 40 years. Sirturo is to be used in a combination therapy for patients who have failed standard treatment and have no other options. Sirturo is an adenosine triphosphate synthase (ATP synthase) inhibitor.The following drugs are experimental compounds that are not commercially available, but may be obtained from the manufacturer as part of a clinical trial or on a compassionate basis. Their efficacy and safety are unknown: pretomanid (manufactured by Novartis, developed in partnership with TB Alliance), and delamanid. In cases of extremely resistant disease, surgery to remove infection portions of the lung is, in general, the final option. The center with the largest experience in this is the National Jewish Medical and Research Center in Denver, Colorado. In 17 years of experience, they have performed 180 operations; of these, 98 were lobectomies and 82 were pneumonectomies. There is a 3.3% operative mortality, with an additional 6.8% dying following the operation; 12% experienced significant morbidity (in particular, extreme breathlessness). Of 91 patients who were culture-positive before surgery, only 4 were culture-positive after surgery.The resurgence of tuberculosis in the United States, the advent of HIV-related tuberculosis, and the development of strains of TB resistant to the first-line therapies developed in recent decades—serve to reinforce the thesis that Mycobacterium tuberculosis, the causative organism, makes its own preferential option for the poor. The simple truth is that almost all tuberculosis deaths result from a lack of access to existing effective therapy.Treatment success rates remain unacceptably low globally with variation between regions. 2016 data published by the WHO reported treatment success rates of multidrug-resistant TB globally. For those started on treatment for multidrug-resistant TB 56% successfully completed treatment, either treatment course completion or eradication of disease; 15% of those died while in treatment; 15% were lost to follow-up; 8% had treatment failure and there was no data on the remaining 6%. Treatment success rate was highest in the World Health Organization Mediterranean region at 65%. Treatment success rates were lower than 50% in the Ukraine, Mozambique, Indonesia and India. Areas with poor TB surveillance infrastructure had higher rates of loss to follow-up of treatment.57 countries reported outcomes for patients started on extreme-drug resistant Tuberculosis, this included 9258 patients. 39% completed treatment successfully, 26% of patients died and treatment failed for 18%. 84% of the extreme Drug resistant Cohort was made up of only three countries; India, Russian Federation and Ukraine. Shorter treatment regimes for MDR-TB have been found to be beneficial having higher treatment success rates. Epidemiology Cases of MDR tuberculosis have been reported in every country surveyed. MDR-TB most commonly develops in the course of TB treatment, and is most commonly due to doctors giving inappropriate treatment, or patients missing doses or failing to complete their treatment. Because MDR tuberculosis is an airborne pathogen, persons with active, pulmonary tuberculosis caused by a multidrug-resistant strain can transmit the disease if they are alive and coughing. TB strains are often less fit and less transmissible, and outbreaks occur more readily in people with weakened immune systems (e.g., patients with HIV). Outbreaks among non immunocompromised healthy people do occur, but are less common.As of 2013, 3.7% of new tuberculosis cases have MDR-TB. Levels are much higher in those previously treated for tuberculosis - about 20%. WHO estimates that there were about 0.5 million new MDR-TB cases in the world in 2011. About 60% of these cases occurred in Brazil, China, India, the Russian Federation and South Africa alone. In Moldova, the crumbling health system has led to the rise of MDR-TB. In 2013, the Mexico–United States border was noted to be "a very hot region for drug resistant TB", though the number of cases remained small.It has been known for many years that INH-resistant TB is less virulent in guinea pigs, and the epidemiological evidence is that MDR strains of TB do not dominate naturally. A study in Los Angeles, California, found that only 6% of cases of MDR-TB were clustered. Likewise, the appearance of high rates of MDR-TB in New York City in the early 1990s was associated with the explosion of AIDS in that area. In New York City, a report issued by city health authorities states that fully 80 percent of all MDR-TB cases could be traced back to prisons and homeless shelters. When patients have MDR-TB, they require longer periods of treatment—about two years of multidrug regimen. Several of the less powerful second-line drugs, which are required to treat MDR-TB, are also more toxic, with side effects such as nausea, abdominal pain, and even psychosis. The Partners in Health team had treated patients in Peru who were sick with strains that were resistant to ten and even twelve drugs. Most such patients require adjuvant surgery for any hope of a cure. Somalia MDR-TB is widespread in Somalia, where 8.7% of newly discovered TB cases are resistant to Rifampicin and Isoniazid, in patients which were treated previously the share was 47%.Refugees from Somalia brought an until then unknown variant of MDR tuberculosis with them to Europe. A few number of cases in four different countries were considered by the European Centre for Disease Prevention and Control to pose no risk to the native population. Russian prisons One of the so-called "hot-spots" of drug-resistant tuberculosis is within the Russian prison system. Infectious disease researchers Nachega & Chaisson report that 10% of the one million prisoners within the system have active TB. One of their studies found that 75% of newly diagnosed inmates with TB are resistant to at least one drug; 40% of new cases are multidrug-resistant. In 1997, TB accounted for almost half of all Russian prison deaths, and as Bobrik et al. point out in their public health study, the 90% reduction in TB incidence contributed to a consequential fall in the prisoner death rate in the years following 1997. Baussano et al. articulate that concerning statistics like these are especially worrisome because spikes in TB incidence in prisons are linked to corresponding outbreaks in surrounding communities. Additionally, rising rates of incarceration, especially in Central Asian and Eastern European countries like Russia, have been correlated with higher TB rates in civilian populations. Even as the DOTS program is expanded throughout Russian prisons, researchers such as Shin et al. have noted that wide-scale interventions have not had their desired effect, especially with regard to the spread of drug-resistant strains of TB. Contributing factors There are several elements of the Russian prison system that enable the spread of MDR-TB and heighten its severity. Overcrowding in prisons is especially conducive to the spread of tuberculosis; an inmate in a prison hospital has (on average) 3 meters of personal space, and an inmate in a correctional colony has 2 meters. Specialized hospitals and treatment facilities within the prison system, known as TB colonies, are intended to isolate infected prisoners to prevent transmission; however, as Ruddy et al. demonstrate, there are not enough of these colonies to sufficiently protect staff and other inmates. Additionally, many cells lack adequate ventilation, which increases likelihood of transmission. Bobrik et al. have also noted food shortages within prisons, which deprive inmates of the nutrition necessary for healthy functioning.Comorbidity of HIV within prison populations has also been shown to worsen health outcomes. Nachega & Chaisson articulate that while HIV-infected prisoners are not more susceptible MDR-TB infection, they are more likely to progress to serious clinical illness if infected. According to Stern, HIV infection is 75 times more prevalent in Russian prison populations than in the civilian population. Therefore, prison inmates are both more likely to become infected with MDR-TB initially and to experience severe symptoms because of previous exposure to HIV. Shin et al. emphasize another factor in MDR-TB prevalence in Russian prisons: alcohol and substance use. Ruddy et al. showed that risk for MDR-TB is three times higher among recreational drug users than non-users. Shin et al.s study demonstrated that alcohol usage was linked to poorer outcomes in MDR-TB treatment; they also
Multidrug-resistant tuberculosis	noted that a majority of subjects within their study (many of whom regularly used alcohol) were nevertheless cured by their aggressive treatment regimen.Non-compliance with treatment plans is often cited as a contributor to MDR-TB transmission and mortality. Indeed, of the 80 newly released TB-infected inmates in Fry et al.s study, 73.8% did not report visiting a community dispensary for further treatment. Ruddy et al. cite release from facilities as one of the main causes of interruption in prisoners TB treatment, in addition to non-compliance within the prison and upon reintegration into civilian life. Fry et al.s study also listed side effects of TB treatment medications (especially in HIV positive individuals), financial worries, housing insecurities, family problems, and fear of arrest as factors that prevented some prisoners from properly adhering to TB treatment. They also note that some researchers have argued that the short-term gains TB-positive prisoners receive, such as better food or work exclusion, may dis-incentivize becoming cured. In their World Health Organization article, Gelmanova et al. posit that non-adherence to TB treatment indirectly contributes to bacterial resistance. Although ineffective or inconsistent treatment does not "create" resistant strains, mutations within the high bacterial load in non-adherent prisoners can cause resistance. Nachega & Chaisson argue that inadequate TB control programs are the strongest driver of MDR-TB incidence. They note that prevalence of MDR-TB is 2.5 times higher in areas of poorly controlled TB. Russian-based therapy (i.e., not DOTS) has been criticized by Kimerling et al. as "inadequate" in properly controlling TB incidence and transmission. Bobrik et al. note that treatment for MDR-TB is equally inconsistent; the second-line drugs used to treat the prisoners lack specific treatment guidelines, infrastructure, training, or follow-up protocols for prisoners reentering civilian life. Policy impacts As Ruddy et al. note in their scholarly article, Russias recent penal reforms will greatly reduce the number of inmates inside prison facilities and thus increase the number of ex-convicts integrated into civilian populations. Because the incidence of MDR-TB is strongly predicted by past imprisonment, the health of Russian society will be greatly impacted by this change. Formerly incarcerated Russians will re-enter civilian life and remain within that sphere; as they live as civilians, they will infect others with the contagions they were exposed to in prison. Researcher Vivian Stern argues that the risk of transmission from prison populations to the general public calls for an integration of prison healthcare and national health services to better control both TB and MDR-TB. While second-line drugs necessary for treating MDR-TB are arguably more expensive than a typical regimen of DOTS therapy, infectious disease specialist Paul Farmer posits that the outcome of leaving infected prisoners untreated could cause a massive outbreak of MDR-TB in civilian populations, thereby inflicting a heavy toll on society. Additionally, as MDR-TB spreads, the threat of the emergence of totally-drug-resistant TB becomes increasingly apparent. See also 2007 tuberculosis scare Drug resistance MRSA Vancomycin-resistant enterococcus (VRE) Totally drug-resistant tuberculosis (TDR-TB) Medicines Patent Pool References NotesFarmer, Paul (1999). Infections and inequalities : the modern plagues. Berkeley, California, United States: University of California Press. ISBN 978-0-520-22913-6. Farmer, Paul (2005). Pathologies of Power: health, human rights, and the new war on the poor. Berkeley, California, United States: University of California Press. ISBN 978-0-520-93147-3. Garrett, Laurie (1994). The coming plague : newly emerging diseases in a world out of balance. New York, New York, United States: Farrar, Straus and Giroux. ISBN 978-0-374-12646-9. Garrett, Laurie (2000). Betrayal of trust: the collapse of global public health. New York, New York, United States: Hyperion Books. ISBN 978-0-7868-6522-2. External links Video: Drug-Resistant TB in Russia 24 July 2007, Woodrow Wilson Center event featuring Salmaan Keshavjee and Murray Feshbach TB Drug Resistance Mutation Database MDR-TB : a story of Hope, Struggle & Triumph MDR-TB (DOTS Plus) protocol followed under RNTCP in India (PDF) "The Strange, Isolated Life of a Tuberculosis Patient in the 21st Century", Buzzfeed
Marcus Gunn phenomenon	Marcus Gunn phenomenon is an autosomal dominant condition with incomplete penetrance, in which nursing infants will have rhythmic upward jerking of their upper eyelid. This condition is characterized as a synkinesis: when two or more muscles that are independently innervated have either simultaneous or coordinated movements.Common physiologic examples of synkineses occur during sucking, chewing, or conjugate eye movements. There are also several abnormal cranial nerve synkineses, both acquired and congenital. Marcus Gunn jaw-winking is an example of a pathologic congenital synkinesis. First described by the ophthalmologist Marcus Gunn in 1883, this condition presents in approximately 5% of neonates with congenital ptosis. This condition has been associated with amblyopia (in 54% of cases), anisometropia (26%), and strabismus (56%). Presentation Behavioral and social implications Although treatment may be unnecessary, there may be social implications, especially in young children when venturing from a supportive home environment to a public environment (e.g., starting school). Continued support, including monitoring behavior and educating the child about his or her appearance as seen by others, is encouraged. Gradual or sudden withdrawal from interaction with others is a sign that may or may not be related to such behavior. Studies are being conducted to elucidate these implications. Pathophysiology It has been postulated that the synkinesis is due to damage to cranial nerve nuclei, caused by peripheral nerve injury and the nuclear lesion releases evolutionarily older [neural] mechanisms with their tendency toward associated movements, and so primitive reflexes are not inhibited.Marcus Gunn jaw-winking is an exaggeration of a very weak physiologic co-contraction that has been disinhibited secondary to a congenital brain stem lesion. The stimulation of the trigeminal nerve by contraction of the pterygoid muscles of jaw results in the excitation of the branch of the oculomotor nerve that innervates the levator palpebrae superioris ipsilaterally (on the same side of the face), so the patient will have rhythmic upward jerking of their upper eyelid.There are two major groups of trigemino-oculomotor synkineses: 1) External pterygoid-levator synkinesis is when the eyelid raises upon: Jaw thrust to opposite side (homolateral external pterygoid) Jaw is projected forward (bilateral external pterygoid) Mouth is opened widely2) Internal pterygoid-levator synkinesis is when the eyelid raises upon teeth clenching External pterygoid-levator synkinesis is the more common group. Treatment Treatment is usually unnecessary. In severe cases, surgery with a bilateral levator excision and frontalis brow suspension may be used. Inverse Marcus Gunn phenomenon Inverse Marcus Gunn phenomenon is a rare condition that causes the eyelid to fall upon opening of the mouth. In this case, trigeminal innervation to the pterygoid muscles of the jaw is associated with an inhibition of the branch of the oculomotor nerve to the levator palpebrae superioris, as opposed to stimulation in Marcus Gunn jaw-winking. References == External links ==
Cystic hygroma	A cystic hygroma is an abnormal growth that usually appears on a babys neck or head. It consists of one or more cysts and tends to grow larger over time. The disorder usually develops while the fetus is still in the uterus, but can also appear after birth.Also known as cystic lymphangioma and macrocystic lymphatic malformation, the growth is often a congenital lymphatic lesion of many small cavities (multiloculated) that can arise anywhere, but is classically found in the left posterior triangle of the neck and armpits. The malformation contains large cyst-like cavities containing lymph, a watery fluid that circulates throughout the lymphatic system. Microscopically, cystic hygroma consists of multiple locules filled with lymph. Deep locules are quite big, but they decrease in size towards the surface. Cystic hygromas are benign, but can be disfiguring. It is a condition which usually affects children; very rarely it can be present in adulthood.Currently, the medical field prefers to use the term lymphatic malformation, because the term cystic hygroma means water tumor. Lymphatic malformation is more commonly used now because it is a sponge-like collection of abnormal growth that contains clear lymphatic fluid. The fluid collects within the cysts or channels, usually in the soft tissue. Cystic hygromas occur when the lymphatic vessels that make up the lymphatic system are not formed properly. The two types of lymphatic malformations are macrocystic (large cysts) and microcystic (small cysts) lymphatic malformations. A person may have only one kind of the malformation or can have a mixture of both macro- and microcysts. Cystic hygroma can be associated with a nuchal lymphangioma or a fetal hydrops. Additionally, it can be associated with Down syndrome, Turner syndrome, or Noonan syndrome. If it is diagnosed in the third trimester, then chances of association with Down syndrome are increased, but if diagnosed in the second trimester, then it is associated with Turner syndrome. A lethal version of this condition exists, known as Cowchock–Wapner–Kurtz syndrome, that, in addition to cystic hygroma, includes cleft palate and lymphedema, a condition of localized edema and tissue swelling caused by a compromised lymphatic system. Signs and symptoms Cystic hygromas are increasingly diagnosed by prenatal ultrasonography. A common sign is a neck growth. It may be found at birth, or discovered later in an infant after an upper respiratory tract infection. Cystic hygromas can grow very large and may affect breathing and swallowing. Some symptoms may include a mass or lump in the mouth, neck, cheek, or tongue. It feels like a large, fluid-filled sac. In addition, cystic hygromas can be found in other body parts, such as the arms, chest, legs, groin, and buttocks. Cystic hygromas are also often seen in Turners syndrome, although a patient who does not have the syndrome can present with this condition. Diagnosis Lymphatic malformations may be detected in the human fetus by ultrasound if they are of sufficient size. Detection of a cystic malformation may prompt further investigation, such as amniocentesis, to evaluate for genetic abnormalities in the fetus. Lymphatic malformations may be discovered postnatally or in older children/adults, and most commonly present as a mass or as an incidental finding during medical imaging. Verification of the diagnosis may require more testing, as multiple cystic masses can arise in children. Imaging, such as ultrasound or MRI, may provide more information as to the size and extent of the lesion. Treatment A baby with a prenatally diagnosed cystic hygroma should be delivered in a major medical center equipped to deal with neonatal complications, such as a neonatal intensive care unit. An obstetrician usually decides the method of delivery. If the cystic hygroma is large, a cesarean section may be performed. After birth, infants with a persistent cystic hygroma must be monitored for airway obstruction. A thin needle may be used to reduce the volume of the cystic hygroma to prevent facial deformities and airway obstruction. Close observation of the baby by a neonatologist after birth is recommended. If resolution of the cystic hygroma does not occur before birth, a pediatric surgeon should be consulted.Cystic hygromas that develop in the third trimester, after 30 weeks gestation, or in the postnatal period are usually not associated with chromosome abnormalities. A chance exists of recurrence after surgical removal of the cystic hygroma. The chance depends on the extent of the cystic hygroma and whether its wall was completely removed.Treatments for removal of cystic hygroma are surgery or sclerosing agents, which include: Bleomycin Doxycycline Ethanol (pure) Picibanil (OK-432) Sodium tetradecyl sulfate Progression with surgeries See also Branchial cleft cyst Ranula Thyroglossal duct cyst Lymphangioma References == External links ==
Light chain deposition disease	Light chain deposition disease (LCDD) is a rare blood cell disease which is characterized by deposition of fragments of infection-fighting immunoglobulins, called light chains (LCs), in the body. LCs are normally cleared by the kidneys, but in LCDD, these light chain deposits damage organs and cause disease. The kidneys are almost always affected and this often leads to kidney failure. About half of people with light chain deposition disease also have a plasma cell dyscrasia, a spectrum of diseases that includes multiple myeloma, Waldenströms macroglobulinemia, and the monoclonal gammopathy of undetermined significance premalignant stages of these two diseases. Unlike in AL amyloidosis, in which light chains are laid down in characteristic amyloid deposits, in LCDD, light chains are deposited in non-amyloid granules. Signs and symptoms The kidney is the organ most frequently affected. Proteinuria, the presence of protein in the urine, is characteristic. More than 90% of people with LCDD develop kidney failure, often with rapid progression of disease.Light chains may be deposited in many other organs and may or may not result in any symptoms. Other than the kidneys, liver and heart are the most commonly involved organs. Deposition of light chains in the liver may lead to hepatomegaly, an enlarged liver, or rarely portal hypertension or liver failure. The heart is affected in up to 80% of patients with LCDD, and may cause arrhythmias and congestive heart failure. Cause Diagnosis A number of laboratory tests are required in order to assist in diagnosing LCDD. Blood and urine samples are collected for evaluation of kidney and liver function and determination of the presence of a monoclonal protein. Imaging studies such as echocardiography and an ultrasound of the abdomen will be performed. A CT scan, magnetic resonance imaging (MRI) or positron emission tomography (PET) may also be indicated. In patients with LCDD, a biopsy of the affected organ will show deposited light chains. A bone marrow biopsy will be done in order to rule out multiple myeloma. Treatment Decreasing production of the organ-damaging light chains is the treatment goal. Options include chemotherapy using bortezomib, autologous stem cell transplantation, immunomodulatory drugs, and kidney transplant.There is no standard treatment for LCDD. High-dose melphalan in conjunction with autologous stem cell transplantation has been used in some patients. A regimen of bortezomib and dexamethasone has also been examined. Prognosis The median time to progression to end stage renal disease is 2.7 years. After 5 years, about 37% of patients with LCDD are alive and do not have end stage renal disease. References External links National Institutes of Health Genetic and Rare Diseases Information Center Emedicine
Hemangioendothelioma	Hemangioendotheliomas are a family of vascular neoplasms of intermediate malignancy. Signs and symptoms They have been described as masses that fall between a hemangioma and angiosarcoma. They are vascular tumors that commonly present with an enlarging mass and most commonly involve the lungs, liver, and musculoskeletal system, although many other body sites have been reported, including the head and neck, intestines, lymph nodes, pleura, retroperitoneum, heel, stomach. Cause Possibly Bartonella spp bacteraemia Diagnosis Classification Hemangioendotheliomas may be classified as: Epithelioid hemangioendothelioma is an uncommon vascular tumor of intermediate malignancy that was first described by Steven Billings, Andrew Folpe, and Sharon Weiss in 2003. These tumors are so named because their histologic appearance resembles a proliferation of epithelioid cells, with polygonal shape and eosinophilic cytoplasm. Composite hemangioendothelioma is a low-grade angiosarcoma typically occurring in adults, although it has been described in infancy.: 601 Spindle-cell hemangioendothelioma) is a vascular tumor that was first described in 1986 by Sharon Weiss, M.D., and commonly presents in a child or young adult who develops blue nodules of firm consistency on a distal extremity.: 599 These tumors were reclassified by Dr. Weiss in 1996 as "spindle cell hemangioma", rather than hemangioendothelioma, due to the excellent prognosis observed in a group of 78 patients. Retiform hemangioendothelioma (also known as a "Hobnail hemangioendothelioma") is a low-grade angiosarcoma, first described in 1994, presenting as a slow-growing exophytic mass, dermal plaque, or subcutaneous nodule.: 601 Kaposiform hemangioendothelioma (also known as "Infantile kaposiform hemangioendothelioma") is an uncommon vascular tumor, first described by Niedt, Greco, et al. (Hemangioma with Kaposis sarcoma-like features: report of two cases.(Niedt GW, Greco MA, Wieczorek R, Blanc WA, Knowles DM 2nd. that affects infants and young children, with rare cases having also been reported in adults. Pediatr Pathol. 1989;9(5):567-75.): 596 : 1782 Endovascular papillary angioendothelioma, also known as "Dabska tumor", "papillary intralymphatic angioendothelioma" (PILA), "Dabska-type hemangioendothelioma", "hobnail hemangioendothelioma", and "malignant endovascular papillary angioendothelioma", is a rare low-grade angiosarcoma: 601 of lymphatic channels. Approximately 30 such tumors have been described in the medical literature. Although included in the World Health Organization tumor classification, there is uncertainty as to whether EPA is a distinct entity or a heterogenous group of tumours. The lesion usually presents as a slow-growing tumor of the skin and subcutaneous tissues of the head, neck, or extremity, of infants or young children.: 601 However, EPA has involved the testicle, deep muscle tissue as a neoplastic transformation of a larger existing benign cavernous hemangioma, bone and spleen, and has been found in adults. Some reports indicate a good prognosis but metastasis is occasionally seen. Infantile hemangioendothelioma is a rare benign vascular tumour arising from mesenchymal tissue and is usually located in the liver. It often presents in infancy with cardiac failure because of extensive arteriovenous shunting within the lesion. It is the third most common liver tumor in children, the most common benign vascular tumor of the liver in infancy, and the most common symptomatic liver tumor during the first 6 months of life. These hemangioendotheliomas have 2 growth phases: an initial rapid growth phase, which is followed by a period of spontaneous involution (usually within the first 12 to 18 months of life). Detection of the hemangioendothelioma within the first 6 months of life is attributed to the initial rapid growth during this time; however, the tumor has been detected with fetal ultrasonography. Histopathologically, there are 2 types of hepatic hemangioendotheliomas: Type I: Hemagioendotheliomas of this type have multiple vascular channels that are formed by an immature endothelial lining with stromal separation from bile ductules. Type II: These hemangioendotheliomas have an appearance that is more disorganized and hypercellular, and there are no bile ductules.In children, distinguishing between a primary malignant liver tumor (hepatoblastoma) and a benign primary hepatic lesion (hemangioendothelioma) is crucial. The absence of urinary catecholamines supports the diagnosis of hemangioendothelioma. In patients with hemangioendotheliomas, elevations in α1-fetoprotein levels are milder than those found in patients with hepatoblastomas. Infantile hepatic hemangioendothelioma is strongly suggested by the presence of a vascular lesion on imaging studies. A complex, heterogeneous mass is often seen on ultrasonograms; a complex tumor that lacks central enhancement can be see on CT scans; and the vascular nature of the lesion along with dilation of the aorta proximal to the origin of the celiac artery and a decrease in the diameter distally, indicating significant shunting, is seen on angiograms. Because most hemangioendotheliomas in infants sponanteously involute and regress within the first 12 to 18 months of life, asymptomatic lesions are generally managed conservatively. Infants who have severe anemia and/or thrombocytopenia can be given blood products; for those who have cardiac failure, diuretics and digoxin are often given. To stop further growth and to speed regression of lesions in infants with more significant clinical sequelae, treatment with corticosteroids or interferon-α-2a is administered. To slow the growth of tumors that are rapidly enlarging, chemotherapy and radiation therapy have been used. Surgical resection, partial hepatectomy, and embolization of afferent vessels should be considered for severe cases. Treatment Treatment is varied and depends on the site and extent of tumor involvement, sites of metastasis, and specific individual factors. Surgical resection, radiotherapy, and chemotherapy have all been used to treat these masses, although studies on survival have yet to be conducted to delineate various treatment regimens. Kaposiform hemangioendothelioma might respond to chemotherapy or antiangiogenic therapies. Recently propanolol and steroids have been shown to be very effective in kaposiform hemangioendothelioma. References == External links ==
Acrocraniofacial dysostosis	Acrocraniofacial dysostosis, also known as Kaplan Plauchu Fitch syndrome is a very rare hereditary disorder which is characterized by cranio-facial dysmorphisms, hearing loss, digital clubbing, and osseous anomalies. Only 2 cases have been described in medical literature. Description The following is a list of the symptoms of the disorder: Cranio-facial Acrocephaly Hypertelorism Ptosis Proptosis Down-slanting parpebral fissures High nasal bridge Nostril anteversion Short philtrum Cleft palate Micrognathia Ear abnormalities Preauricular sinus or cyst Auditory Hearing loss Osseous Metatarsus adductus First brachymetacarpia First brachymetatarsia Proximally placed first toes Craniosynostosis Pectus excavatum Partial duplication of the thumbs distal phalanx Malleus and incus dysplasia Tall lumbar vertebrae associated with increased interpedicular distance Discovery This disorder was first discovered in 1988 by Kaplan et al. when they described two sisters born to consanguineous parents with all the symptoms mentioned above. They suggested this disorder to be inherited in an autosomal recessive fashion. == References ==
Splenic lymphoma with villous lymphocytes	Splenic lymphoma with villous lymphocytes is a rare type of lymphoma that involves mature B cells. Older names include lymphoma simulating hairy cell leukemia and lymphoplasmacytic lymphoma with circulating villous lymphocytes. The characteristic villous lymphocytes will appear in a blood smear of the peripheral blood of patients with this type of lymphoma. These lymphocytes will have an oval nucleus with the “cobblestone” pattern of nuclear chromatin typical of more mature lymphoid cells. The cytoplasmic projections, or villi, are found in a polar distribution. Whether this condition is identical to splenic marginal zone lymphoma, or only highly similar, is a matter of debate. == References ==
Drug-induced purpura	Drug-induced purpura is a skin condition that may be related to platelet destruction, vessel fragility, interference with platelet function, or vasculitis.: 824 See also Food-induced purpura Rumpel-Leede sign Skin lesion == References ==
Calculus (dental)	In dentistry, calculus or tartar is a form of hardened dental plaque. It is caused by precipitation of minerals from saliva and gingival crevicular fluid (GCF) in plaque on the teeth. This process of precipitation kills the bacterial cells within dental plaque, but the rough and hardened surface that is formed provides an ideal surface for further plaque formation. This leads to calculus buildup, which compromises the health of the gingiva (gums). Calculus can form both along the gumline, where it is referred to as supragingival ("above the gum"), and within the narrow sulcus that exists between the teeth and the gingiva, where it is referred to as subgingival ("below the gum"). Calculus formation is associated with a number of clinical manifestations, including bad breath, receding gums and chronically inflamed gingiva. Brushing and flossing can remove plaque from which calculus forms; however, once formed, calculus is too hard (firmly attached) to be removed with a toothbrush. Calculus buildup can be removed with ultrasonic tools or dental hand instruments (such as a periodontal scaler). Etymology The word comes from Latin calculus "small stone", from calx "limestone, lime", probably related to Greek χάλιξ chalix "small stone, pebble, rubble", which many trace to a Proto-Indo-European root for "split, break up". Calculus was a term used for various kinds of stones. This spun off many modern words, including "calculate" (use stones for mathematical purposes), and "calculus", which came to be used, in the 18th century, for accidental or incidental mineral buildups in human and animal bodies, like kidney stones and minerals on teeth.Tartar, on the other hand, originates in Greek as well (tartaron), but as the term for the white encrustation inside casks, aka potassium bitartrate commonly known as cream of tartar. This came to be a term used for calcium phosphate on teeth in the early 19th century. Calculus composition Calculus is composed of both inorganic (mineral) and organic (cellular and extracellular matrix) components. The mineral proportion of calculus ranges from approximately 40–60%, depending on its location in the dentition, and consists primarily of calcium phosphate crystals organized into four principal mineral phases, listed here in order of decreasing ratio of phosphate to calcium: whitlockite, Ca9(Mg,Fe)(PO4)6(PO3OH) hydroxyapatite, Ca5(PO4)3OH octacalcium phosphate, Ca8H2(PO4)6 · 5 H2O and brushite, CaHPO4 · 2 H2OThe organic component of calculus is approximately 85% cellular and 15% extracellular matrix. Cell density within dental plaque and calculus is very high, consisting of an estimated 200,000,000 cells per milligram. The cells within calculus are primarily bacterial, but also include at least one species of archaea (Methanobrevibacter oralis) and several species of yeast (e.g., Candida albicans). The organic extracellular matrix in calculus consists primarily of proteins and lipids (fatty acids, triglycerides, glycolipids, and phospholipids), as well as extracellular DNA. Trace amounts of host, dietary, and environmental microdebris are also found within calculus, including salivary proteins, plant DNA, milk proteins, starch granules, textile fibers, and smoke particles. Calculus formation The processes of calculus formation from dental plaque are not well understood. Supragingival calculus formation is most abundant on the buccal (cheek) surfaces of the maxillary (upper jaw) molars and on the lingual (tongue) surfaces of the mandibular (lower jaw) incisors. These areas experience high salivary flow because of their proximity to the parotid and sublingual salivary glands. Subgingival calculus forms below the gumline and is typically darkened in color by the presence of black-pigmented bacteria, whose cells are coated in a layer of iron obtained from heme during gingival bleeding. Dental calculus typically forms in incremental layers that are easily visible using both electron microscopy and light microscopy. These layers form during periodic calcification events of the dental plaque, but the timing and triggers of these events are poorly understood. The formation of calculus varies widely among individuals and at different locations within the mouth. Many variables have been identified that influence the formation of dental calculus, including age, gender, ethnic background, diet, location in the oral cavity, oral hygiene, bacterial plaque composition, host genetics, access to professional dental care, physical disabilities, systemic diseases, tobacco use, and drugs and medications. Clinical significance Plaque accumulation causes the gingiva to become irritated and inflamed, and this is referred to as gingivitis. When the gingiva become so irritated that there is a loss of the connective tissue fibers that attach the gums to the teeth and bone that surrounds the tooth, this is known as periodontitis. Dental plaque is not the sole cause of periodontitis; however it is many times referred to as a primary aetiology. Plaque that remains in the oral cavity long enough will eventually calcify and become calculus. Calculus is detrimental to gingival health because it serves as a trap for increased plaque formation and retention; thus, calculus, along with other factors that cause a localized build-up of plaque, is referred to as a secondary aetiology of periodontitis. When plaque is supragingival, the bacterial content contains a great proportion of aerobic bacteria and yeast, or those bacteria which utilize and can survive in an environment containing oxygen. Subgingival plaque contains a higher proportion of anaerobic bacteria, or those bacteria which cannot exist in an environment containing oxygen. Several anaerobic plaque bacteria, such as Porphyromonas gingivalis, secrete antigenic proteins that trigger a strong inflammatory response in the periodontium, the specialized tissues that surround and support the teeth. Prolonged inflammation of the periodontium leads to bone loss and weakening of the gingival fibers that attach the teeth to the gums, two major hallmarks of periodontitis. Supragingival calculus formation is nearly ubiquitous in humans, but to differing degrees. Almost all individuals with periodontitis exhibit considerable subgingival calculus deposits. Dental plaque bacteria have been linked to cardiovascular disease and mothers giving birth to pre-term low weight infants, but there is no conclusive evidence yet that periodontitis is a significant risk factor for either of these two conditions. Prevention Toothpaste with pyrophosphates or zinc citrate has been shown to produce a statistically significant reduction in plaque accumulation, but the effect of zinc citrate is so modest that its clinical importance is questionable. Some calculus may form even without plaque deposits, by direct mineralisation of the pellicle. Calculus in other animals Calculus formation in other animals is less well studied than in humans, but it is known to form in a wide range of species. Domestic pets, such as dogs and cats, frequently accumulate large calculus deposits. Animals with highly abrasive diets, such as ruminants and equids, rarely form thick deposits and instead tend to form thin calculus deposits that often have a metallic or opalescent sheen. In animals, calculus should not be confused with crown cementum, a layer of calcified dental tissue that encases the tooth root underneath the gingival margin and is gradually lost through periodontal disease. Archaeological significance Dental calculus has been shown to contain well preserved microparticles, DNA and protein in archaeological samples. The information these molecules contain can reveal information about the oral microbiome of the host and the presence of pathogens. It is also possible to identify dietary sources as well as study dietary shifts and occasionally evidence of craft activities. Sub-gingival calculus formation and chemical dissolution Sub-gingival calculus is composed almost entirely of two components: fossilized anaerobic bacteria whose biological composition has been replaced by calcium phosphate salts, and calcium phosphate salts that have joined the fossilized bacteria in calculus formations. The initial attachment mechanism and the development of mature calculus formations are based on electrical charge. Unlike calcium phosphate, the primary component of teeth, calcium phosphate salts exist as electrically unstable ions. The following minerals are detectable in calculus by X-ray diffraction: brushite (CaHPO4 · 2 H2O), octacalcium phosphate (Ca8H2(PO4)6 · 5 H2O), magnesium-containing whitlockite (Ca9(Mg,Fe)(PO4)6(PO3OH)), and carbonate-containing hydroxyapatite (approximately Ca5(PO4)3OH but containing some carbonate).The reason fossilized bacteria are initially attracted to one part of the subgingival tooth surface over another is not fully understood; once the first layer is attached, ionized calculus components are naturally attracted to the same places due to electrical charge. The fossilized bacteria pile on top of one another, in a rather haphazard manner. All the while, free-floating ionic components fill in the gaps left by the fossilized bacteria. The resultant hardened structure can be compared to concrete; with the fossilized bacteria playing the role of aggregate, and the smaller calcium phosphate salts being the cement. The once purely electrical association of fossilized bacteria then becomes mechanical, with the introduction of free-floating calcium phosphate salts. The "hardened" calculus formations are at the heart of periodontal disease and treatment. Removal of calculus after formation The College of Registered Dental Hygienists of Alberta defines a dental hygienist as "a health care professional whose work focuses on the oral health of an individual or community." These dental professionals aim to improve oral health by educating patients on the prevention and management of oral disease. Dental hygienists can be found performing oral health services in various settings, including private dental offices, schools, and other community settings, such as long-term care facilities. As mentioned above in the clinical significance section, plaque and calculus deposits are a major etiological factor in the development and progression of oral disease. An important part of the scope of practice of a dental hygienist is the removal of plaque and calculus deposits. This is achieved through the use of specifically designed instruments for debridement of tooth surfaces. Treatment with these types of instruments is necessary as calculus deposits cannot be removed by brushing or flossing alone. To effectively manage disease or maintain oral health, thorough removal of calculus deposits should be completed at frequent intervals. The recommended frequency of dental hygiene treatment can be made by a registered professional, and is dependent on individual patient needs. Factors that are taken into consideration include an individuals overall health status, tobacco use, amount of calculus present, and adherence to a professionally recommended home care routine.Hand instruments are specially designed tools used by dental professionals to remove plaque and calculus deposits that have formed on the teeth. These tools include scalers, curettes, jaquettes, hoes, files and chisels. Each type of tool is designed to be used in specific areas of the mouth. Some commonly used instruments include sickle scalers which are designed with a pointed tip and are mainly used supragingivally. Curettes are mainly used to remove subgingival calculus, smooth root surfaces and to clean out periodontal pockets. Curettes can be divided into two subgroups: universals and area specific instruments. Universal curettes can be used in multiple areas, while area specific instruments are designed for select tooth surfaces. Gracey curettes are a popular type of area specific curettes. Due to their design, area specific curettes allow for better adaptation to the root surface and can be slightly more effective than universals. Hoes, chisels, and files are less widely used than scalers and curettes. These are beneficial when removing large amounts of calculus or tenacious calculus that cannot be removed with a curette or scaler alone. Chisels and hoes are used to remove bands of calculus, whereas files are used to crush burnished or tenacious calculus.For hand instrumentation to be effective and efficient, it is important for clinicians to ensure that the instruments being used are sharp. It is also important for the clinician to understand the design of the hand instruments to be able to adapt them properly.Ultrasonic scalers, also known as power scalers, are effective in removing calculus, stain, and plaque. These scalers are also useful for root planing, curettage, and surgical debridement. Not only is tenacious calculus and stain removed more effectively with ultrasonic scalers than with hand instrumentation alone, it is evident that the most satisfactory clinical results are when ultrasonics are used in adjunct to hand instrumentation. There are two types of ultrasonic scalers; piezoelectric and magnetostrictive. Oscillating material in both of these handpieces cause the tip of the scaler to vibrate at high speeds, between 18,000 and 50,000 Hz. The tip of each scaler uses a different vibration pattern for removal of calculus. The magnetostrictive power scaler vibration is elliptical, activating all sides of the tip, whereas the piezoelectric vibration is linear and is more active on the two sides of the tip.Special tips for ultrasonic scalers are designed to address different areas of the mouth and varying amounts of calculus buildup. Larger tips are used for heavy subgingival or supragingival calculus deposits, whereas thinner tips are designed more for definitive subgingival debridement. As the high frequency vibrations loosen calculus and plaque, heat is generated at the tip. A water spray is directed towards the end of the tip to cool it as well as irrigate the gingiva during debridement. Only the first 1–2 mm of the tip on the ultrasonic scaler is most effective for removal, and therefore needs to come into direct contact with the calculus to fracture the deposits. Small adaptations are needed in order to keep the tip of the scaler touching the surface of the tooth, while overlapping oblique, horizontal, or vertical strokes are used for adequate calculus removal.Current research on potentially more effective methods of subgingival calculus removal focuses on the use of near-ultraviolet and near-infrared lasers, such as Er,Cr:YSGG lasers. The use of lasers in periodontal therapy offers a unique clinical advantage over conventional hand instrumentation, as the thin and flexible fibers can deliver laser energy into periodontal pockets that are otherwise difficult to access. Near-infrared lasers, such as the Er,CR:YSGG laser, have been proposed as an effective adjunct for calculus removal as the emission wavelength is highly absorbed by water, a large component of calculus deposits. An optimal output power setting of 1.0-W with the near-infrared Er,Cr:YSGG laser has been shown to be effective for root scaling. Near-ultraviolet lasers have also shown promise as they allow the dental professional to remove calculus deposits quickly, without removing underlying healthy tooth structure, which often occurs during hand instrumentation. Additionally, near-ultraviolet lasers are effective at various irradiation angles for calculus removal. Discrepancies in the efficiency of removal are due to the physical and optical properties of the calculus deposits, not to the angle of laser use. Dental hygienists must receive additional theoretical and clinical training on the use of lasers, where legislation permits. See also Calculus (medicine) Toothbrush Dental caries Teeth cleaning == References ==
Endogenous depression	Endogenous depression (melancholia) is an atypical sub-class of major depressive disorder (clinical depression). It could be caused by genetic and biological factors. Endogenous depression occurs due to the presence of an internal (cognitive, biological) stressor instead of an external (social, environmental) stressor. Endogenous depression includes patients with treatment-resistant, non-psychotic, major depressive disorder, characterized by abnormal behavior of the endogenous opioid system but not the monoaminergic system. Symptoms vary in severity, type, and frequency and can be attributed to cognitive, social, biological, or environmental factors that result in persistent feelings of sadness and distress. Since symptoms are due to a biological phenomenon, prevalence rates tend to be higher in older adults. Due to this fact, biological-focused treatment plans are often used in therapy to ensure the best prognosis.Endogenous depression was part of the Kraepelinian dichotomy system. Signs and symptoms The forefront indication that a depressive episode is manifesting is the sudden loss of energy or motivation in daily routines. When this occurs, it is not uncommon for individuals to seek medical attention with excessive worrying or anxiety that a more severe, physiological disease may be the underlying issue. However, without an actual disease present, this neurotic thinking often results in severe anxiety, sleep disturbance, and mood swings which may hinder social relationships. Individuals with endogenous depression may experience inconsistencies in symptom severity which is often the reason for delayed treatment. If left untreated, symptoms may progress to a major depressive episode. Risk factors Endogenous depression occurs as the results of an internal stressor—commonly cognitive or biological—and not an external factor. Potential risk factors include these cognitive or biological factors. Patients with endogenous depression often are more likely to have a positive family history of disorders and fewer psychosocial and environmental factors that cause their symptoms. A family history of depression and perceived poor intimate relationships are internal risk factors associated with this type of depression. It is important to know these risk factors in order to take steps to recognize and help prevent this illness. Treatment Clinicians generally favor treatments such as antidepressant and mood-stabilizing medication and electroconvulsive therapy (ECT). ECT is an effective treatment option for endogenous depression. Both medication and ECT can be used in the short-term to treat acute episodes of endogenous depression, and in the long-term to reduce the risk of recurrence. During the first two decades of the 21st century, a new promising alternative/adjunctive depression treatment method known as transcranial magnetic stimulation, or TMS as its more commonly known, has become available. Prevalence This type of depression often occurs due to biological reasons. Since symptoms are due to an internal phenomena, prevalence rates tend to be higher in older adults and more prevalent among women. Although endogenous depression has been associated with increased age, there have been few attempts to evaluate this fully. More research is needed to indicate factual prevalence rates on this type of depression in society. History Endogenous depression was initially considered valuable as a means of diagnostic differentiation with reactive depression. While the latters onset could be attributed to adverse life events and treated with talk therapy, the former would indicate treatment with antidepressants. Indeed, this view of endogenous depression is at the root of the popular view that mood disorders are a reflection of a chemical imbalance in the brain. More recent research has shown that the probability of an endogenous depression patient experiencing an adverse life event prior to a depressive episode is roughly the same as for a reactive depression patient and the efficacy of antidepressant therapy bears no statistical correlation with the patients diagnostic classification along this axis. See also Biopsychiatry controversy Biological psychiatry References External links Classification of depression on NetDoctor Endogenous Depression Information Endogenous Depression Help Resources
Catecholaminergic polymorphic ventricular tachycardia	Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited genetic disorder that predisposes those affected to potentially life-threatening abnormal heart rhythms or arrhythmias. The arrhythmias seen in CPVT typically occur during exercise or at times of emotional stress, and classically take the form of bidirectional ventricular tachycardia or ventricular fibrillation. Those affected may be asymptomatic, but they may also experience blackouts or even sudden cardiac death. CPVT is caused by genetic mutations affecting proteins that regulate the concentrations of calcium within cardiac muscle cells. The most commonly identified gene is RYR2, which encodes a protein included in an ion channel known as the ryanodine receptor; this channel releases calcium from a cells internal calcium store, the sarcoplasmic reticulum, during every heartbeat. CPVT is often diagnosed from an ECG recorded during an exercise tolerance test, but it may also be diagnosed with a genetic test. The condition is treated with medication including beta-adrenoceptor blockers or flecainide, or with surgical procedures including sympathetic denervation and implantation of a defibrillator. It is thought to affect as many as one in ten thousand people and is estimated to cause 15% of all unexplained sudden cardiac deaths in young people. The condition was first defined in 1978, and the underlying genetics were described in 2001. Signs and symptoms Although individuals with CPVT may not experience any symptoms, the most commonly reported symptoms are blackouts or sudden loss of consciousness, referred to as syncope. These blackouts often occur during exercise or as a response to emotional stress—situations in which chemical messengers known as catecholamines, such as adrenaline, are released within the body. Blackouts may be misinterpreted as being caused by simple faints or epilepsy, often leading to delays in reaching the correct diagnosis. In a third of those affected, the first manifestation of the disease may be cardiac arrest, potentially leading to sudden death. This can occur in very young children, presenting as sudden infant death syndrome or cot death. Approximately 30% of those with CPVT will have a family member who has experienced blackouts, seizures, or sudden death in response to exercise or stress.In those with CPVT, catecholamine release can lead to an abnormal heart rhythm or arrhythmia known as ventricular tachycardia. The ventricular tachycardia may take a characteristic form known as bidirectional ventricular tachycardia. This form of ventricular tachycardia occurs relatively infrequently, but if seen is suggestive of an underlying diagnosis of CPVT or the related condition Andersen-Tawil syndrome. These ventricular arrhythmias in some cases terminate by themselves, causing a blackout from which the person then recovers. However, if the abnormal heart rhythm continues, it can degenerate into a more dangerous arrhythmia known as ventricular fibrillation causing a cardiac arrest and, if untreated, sudden death.There are typically very few abnormal signs on clinical examination in persons with CPVT. However, those with CPVT may develop a less serious heart rhythm disturbance called atrial fibrillation, which can be detected on examination as an irregular pulse. Furthermore, approximately 20% of those with CPVT have a slow resting heart rate known as a sinus bradycardia. Mechanism Excitation-contraction coupling The arrhythmias that those with CPVT experience are caused by abnormalities in the way that cardiac muscle cells control their levels of calcium. Calcium interacts with the protein fibres or myofibrils inside the cell that allow the cell to contract, and the concentration of calcium within each cell needs to be tightly regulated. During each heartbeat, the concentration of calcium must rise to allow the muscle to contract and then fall to allow the muscle to relax, a process achieved by using a store within the cell known as the sarcoplasmic reticulum. At the start of each heartbeat, calcium is released from the sarcoplasmic reticulum through specialised channels known as ryanodine receptors. Ryanodine receptors open when the concentration of calcium near the channel increases. This happens when, in response to an electrical signal from the cell membrane called an action potential, a small amount of calcium flows across the cell membrane into the cell through L-type calcium channels, many of which are located on specialised inpouchings of the membrane called T-tubules designed to bring these surface ion channels close to the sarcoplasmic reticulum.The increase in calcium concentration triggers ryanodine receptors on the sarcoplasmic reticulum to release a puff of calcium known as a calcium spark. Each spark triggers the release of further sparks from neighbouring ryanodine receptors to create an organised rise of calcium throughout the cell known as a calcium transient. At the end of each heartbeat, calcium is pumped back by a protein called SERCA along with its regulatory protein phospholamban. The calcium is then held within the sarcoplasmic reticulum by a protein called calsequestrin.Fine-tuning of this process can be achieved by phosphorylating these proteins. As an example, during exercise catecholamines activate beta-adrenoceptors on the cell surface, which trigger protein kinase A to phosphorylate the L-type calcium channel, increasing the flow of calcium into the cell. Simultaneously, phosphorylation of the regulatory protein phospholamban causes more calcium to be drawn up into the sarcoplasmic reticulum. The overall effect of this is to generate a larger calcium transient with each beat, leading to a more forceful contraction. Calcium-dependent arrhythmias Alterations to the proteins involved in excitation-contraction coupling can disrupt this carefully regulated process. In those with CPVT, the normally tight regulation of calcium can become deranged, leading to arrhythmias. While calcium is generally released from the sarcoplasmic reticulum in response to an action potential, calcium sparks can also occur spontaneously. In a healthy heart, a spontaneous calcium spark is generally an isolated event and goes no further, but if ryanodine receptors or the proteins that regulate them are abnormal, these sparks can trigger releases from neighbouring ryanodine receptors which spread throughout the cell as a calcium wave. These calcium waves are much more likely to occur when cardiac muscle cells are stimulated by catecholamines such as adrenaline, which increase the concentration of calcium within the sarcoplasmic reticulum and sensitise the ryanodine receptors. The uncontrolled wave of calcium can be forced out through the cell membrane via the sodium-calcium exchanger, causing an electric current known as a delayed afterdepolarisation. Afterdepolarisations, if large enough, can trigger additional action potentials, premature ventricular contractions, or sustained arrhythmias. Causes CPVT can be caused by mutations in several genes, all of which are responsible for regulating the concentrations of calcium within cardiac muscle cells. The most commonly identified genetic mutation in CPVT is a mutation in the RYR2 gene that encodes the cardiac ryanodine receptor, responsible for releasing calcium from the sarcoplasmic reticulum. Mutations associated with CPVT have also been identified in the CASQ2 gene which encodes calsequestrin, a protein that binds calcium within the sarcoplasmic reticulum. Other genes associated with rarer, atypical forms of CPVT include TECRL encoding Trans-2,3-enoyl-CoA reductase-like protein, CALM1, CALM2 and CALM3 all encoding Calmodulin, and TRDN encoding Triadin. CPVT1: RYR2 mutations The most commonly identified genetic mutations in those with CPVT occur in the RYR2 gene which encodes the cardiac ryanodine receptor. Mutations in this gene lead to an autosomal dominant form of typical CPVT known as CPVT1. While the precise effect differs between specific mutations in this gene, many RYR2 mutations cause the ryanodine receptor to open in response to lower concentrations of calcium—the threshold for calcium release is lower. As a result, the sarcoplasmic reticulum spontaneously releases calcium through these abnormal ryanodine receptors when the concentration of calcium within the sarcoplasmic reticulum rises, a process known as store-overload induced calcium release. Sarcoplasmic reticulum calcium content increases in response to stimulation from catecholamines, explaining why arrhythmias in those with CPVT occur at times when catecholamine levels are elevated. Some suggest that the increased sensitivity to calcium occurs only when the ryanodine receptor is phosphorylated by protein kinase A, while other suggest that the increased sensitivity also occurs under resting conditions.Two theories have been proposed for the underlying mechanism by which mutations in RYR2 promote store-overload induced calcium release: domain unzipping and FKBP12.6 unbinding. Domain unzipping refers to the separation of two important regions of the ryanodine receptor, the N-terminus and the central domain. Through this mechanism, a mutation might destabilise the ryanodine receptors closed state and increase its sensitivity to calcium. A second potential mechanism involves the regulatory protein FKBP12.6, a protein that binds to and stabilises the ryanodine receptor. The binding of FKBP12.6 to the ryanodine receptor is regulated by phosphorylation. Phosphorylation by protein kinase A leads to the dissociation of FKBP12.6, rendering the ryanodine receptor more sensitive to cytosolic calcium. RYR2 mutations may interfere with the binding of FKB12.6 to the ryanodine receptor and thereby increase sensitivity to calcium. It is likely that FKBP12.6 plays a role in some CPVT mutations but not others.RYR2 mutations responsible for CPVT are mainly found in four major domains of the gene. Mutations affecting domains III and IV of the gene (corresponding to the N-terminal region of the protein and cytosolic linker respectively) occur in 46% of cases. Mutations are seen less frequently affecting domains I and II, both of which encode sections of the N-terminal region of the protein. RYR2 mutations associated with CPVT that occur outside these four domains are very rare, being responsible for as few as 10% of reported cases. RYR2 mutations are most often missense mutations, such as single nucleotide substitutions causing one amino acid to be replaced by another, although in-frame substitutions and duplications have been described. More damaging nonsense mutations have not been reported in association with CPVT, potentially because these variants may lead to different cardiac diseases such as cardiomyopathies. CPVT2: CASQ2 mutations Mutations in the CASQ2 gene are associated with an autosomal recessive form of typical CPVT known as CPVT2. This gene encodes calsequestrin, the major calcium-binding protein and calcium buffer within the sarcoplasmic reticulum. Mutations in CASQ2 account for only 3-5% of cases of CPVT. Fourteen mutations in CASQ2 have been identified in association with CPVT. Two of these are nonsense mutations causing the protein to be abnormally short, and two are deletion mutations, while ten are missense mutations that substitute one amino acid for another in the chain forming the protein.Mutations in CASQ2 cause a decrease in sarcoplasmic reticulum calcium-buffering capacity. This means that abrupt changes in sarcoplasmic total calcium will be buffered less and therefore translate to larger shifts in free calcium. The higher peaks in free calcium have greater potential to cause store-overload induced calcium release from the sarcoplasmic reticulum, leading to afterdepolarisations.In addition to its role as a calcium buffer, calsequestrin also regulates the release of calcium from the sarcoplasmic reticulum by directly modulating ryanodine receptors. When the concentration of calcium is low, calsequestrin monomers form a complex with the proteins triadin and junctin, which inhibit ryanodine receptors. However, at high calcium concentrations, calsequestrin forms polymers that dissociate from the ryanodine receptor channel complex, removing the inhibitory response and increasing the sensitivity of the ryanodine receptor to spontaneously releasing calcium.Decreased CASQ2 is also associated with high levels of calreticulin, a protein which among other roles regulates the reuptake of calcium into the sarcoplasmic reticulum by SERCA. In the absence of CASQ2, calreticulin levels increase and provide some compensatory calcium binding within the sarcoplasmic reticulum. It is possible that calreticulin may contribute to the generation of arrhythmias seen in association with CASQ2 mutations. Diagnosis CPVT may be challenging to diagnose as the structure of the heart appears normal in those affected by the condition when assessed using an echocardiogram, cardiac MRI scan or cardiac CT scan, while the electrical function of the heart also appears normal at rest when assessed using a standard 12-lead ECG. However, in response to exercise or catecholamines such as adrenaline, abnormal heart rhythms such as bidirectional ventricular tachycardia or frequent polymorphic ventricular ectopic beats may be seen. 12-lead ECG The resting 12-lead ECG is a useful test to differentiate CPVT from other electrical diseases of the heart that can cause similar abnormal heart rhythms. Unlike conditions such as long QT syndrome and Brugada syndrome, the resting 12-lead ECG in those with CPVT is generally normal. However, approximately 20% of those affected have a slow resting heart rate or sinus bradycardia. Exercise and other provocative testing Exercise testing, commonly performed on a treadmill or stationary bicycle, can help to diagnose CPVT. During the test, those with CPVT often experience ectopic beats, which may progress to bidirectional and then polymorphic ventricular tachycardia as the intensity of exercise increases. Some of those suspected of having CPVT, such as young children, may not be able to perform an exercise tolerance test. In these cases, alternative forms of testing include adrenaline provocation testing, during which adrenaline is infused into a vein at gradually increasing doses under close supervision and ECG monitoring. Additionally, long term or Holter ECG monitoring can be performed, although this form of testing is less likely to detect an arrhythmia. Invasive electrophysiological studies do not provide useful information to help diagnose CPVT or to assess the risk of life-threatening arrhythmias. Genetic testing CPVT can also be diagnosed by identifying a disease-causing mutation in a gene associated with CPVT using genetic testing. This technique may be the only way to identify the condition in someone suspected of having CPVT who has died, and in this case may be known as a molecular autopsy. Treatment Treatments for CPVT aim to prevent lethal abnormal heart rhythms from occurring, and to rapidly restore a normal rhythm if they do occur. As the arrhythmias in CPVT generally occur at times when the heart is exposed to high levels of adrenaline or other similar chemical messengers (catecholamines), many treatments for CPVT aim to lower the levels of catecholamines the heart is exposed to or block their effects on the heart.The first-line treatment for those with CPVT involves lifestyle advice. This includes avoiding competitive sports, very strenuous exercise and highly stressful environments, as high levels of adrenaline can occur in these settings, which can provoke arrhythmias. Medication Several medications can be useful for those with CPVT. The mainstays of treatment are beta blockers, which block the effects of adrenaline and other catecholamines on the heart, reducing the chance of abnormal heart rhythms developing. Of all the beta blockers, nadolol has been proven to be the most effective for treating CPVT. This drug lowers the heart rate to a greater extent than other beta blockers and only needs to be taken once daily, reducing the risk of missed doses. Nadolol may be difficult to obtain and is not available in all countries, and an alternative beta blocker suitable for use in CPVT may be propranolol, which however has a more complex dosing regimen. Recently published data suggest that the use of selective beta blockers, such as atenolol, bisoprolol, or metoprolol, is associated with very high treatment failure rates.Flecainide is a class 1c antiarrhythmic drug that is recommended for those with CPVT who experience abnormal heart rhythms despite taking a beta blocker. Flecainide reduces the risk of arrhythmias in those with CPVT, but it remains uncertain how Flecainide achieves this. Some have suggested that Flecainide directly interacts with the cardiac ryanodine receptor, which is frequently abnormal in those with CPVT, while other suggest that the anti-arrhythmic effects of Flecainide rely entirely on its sodium channel blocking effects.Verapamil is a calcium channel antagonist that, when combined with a beta blocker, may reduce the risk of arrhythmias in patients with CPVT. Propafenone is another antiarrhythmic that may reduce the risk of arrhythmias, potentially through direct effects on the ryanodine receptor. Sympathetic denervation Some persons with CPVT continue to experience life-threatening arrhythmias despite pharmaceutical therapy. In this case a surgical procedure can be used to affect nerves supplying the heart that communicate using catecholamines. A collection of nerves known as the sympathetic nervous system supply the heart as well as other organs. These nerves, when activated, encourage the heart to beat harder and faster. The sympathetic nervous system uses noradrenaline, a catecholamine, as a chemical messenger or neurotransmitter, which can promote arrhythmias in those with CPVT.To prevent this, a region of the sympathetic nervous system can be intentionally damaged in an operation known as cardiac sympathetic denervation or sympathectomy. While the sympathetic nervous system feeds into the heart from both sides, often only the left sided nerves are targeted during sympathectomy, although destruction of the nerves on both sides may be required. Through this process, sympathectomy is effective at decreasing, but not abolishing, the risk of further life-threatening arrhythmias. Implantable cardioverter-defibrillator While medication and sympathectomy aim to prevent abnormal heart rhythms from occurring in the first place, an implantable defibrillator (ICD) may be used to treat arrhythmias that medication has failed to prevent and restore a normal heart rhythm. These devices, usually implanted under the skin at the front of the chest below the shoulder, can continuously monitor the heart for abnormal heart rhythms. If a life-threatening arrhythmia is detected, the device can deliver a small electric shock to terminate the abnormal rhythm and restart the heart.Implantable defibrillators are often recommended for those with CPVT who have experienced blackouts, ventricular arrhythmias or cardiac arrest despite taking appropriate medication. These devices are life-saving, as it has been shown that their use confers a significant survival benefit in patients with CPVT. It has been suggested that the resulting surge of adrenaline caused by the pain of an electric shock from the device could theoretically bring on a cycle of recurrent arrhythmias and shocks known as an electrical storm, and therefore it is strongly recommended that those with an ICD implanted for CPVT take a beta blocker to dampen the effects of adrenaline. Prognosis A significant proportion of those with CPVT will experience a life-threatening abnormal heart rhythm, with estimates of this risk ranging from 13 to 20% over the course of 7–8 years. Life-threatening arrhythmias are more likely to occur if CPVT has been diagnosed in childhood, if a person with CPVT does not take beta blockers, and if arrhythmias occur on exercise testing despite taking beta blockers.During treatment with nadolol, the preferred beta blocker for the treatment of CPVT, event rates have been estimated to be 0.8% per year. In patients treated with beta blockers, life-threatening arrhythmias are more likely if a person had already survived a cardiac arrest, had a syncope, or are carriers of disease-causing mutations affecting the highly conserved terminal portion of RYR2 gene, called the C-terminal domain (amino acids 4889–4969). Epidemiology CPVT is estimated to affect 1 in 10,000 people. Symptoms from CPVT are typically first seen in the first or second decade of life, and more than 60% of affected individuals experience their first episode of syncope or cardiac arrest by age 20. Syncope during exercise or strong emotion should be considered a red flag, as it is a characteristic of the disease. Lastly, a small number of patients may present later in life, and genetic testing in these patients frequently fails to identify a causative gene. History In 1960, Norwegian cardiologist Knut Berg published a report on three sisters who had blackouts during exercise or emotional stress in what is now recognised as the first description of CPVT. The bidirectional ventricular tachycardia associated with this condition was described in 1975. The term "Catecholaminergic Polymorphic Ventricular Tachycardia" was first used in 1978. In 1999, the first genetic mutation causing CPVT to be identified was localised to chromosome 1q42-q43, which was found to be a variant in the RYR2 gene in 2001. Ongoing research aims to identify better treatments for CPVT, to increase understanding of the mechanisms of arrhythmia, and to identify other genes causing the condition. References == External links ==
Complete androgen insensitivity syndrome	Complete androgen insensitivity syndrome (CAIS) is an AIS condition that results in the complete inability of the cell to respond to androgens. As such, the insensitivity to androgens is only clinically significant when it occurs in individuals who are exposed to significant amounts of testosterone at some point in their lives. The unresponsiveness of the cell to the presence of androgenic hormones prevents the masculinization of male genitalia in the developing fetus, as well as the development of male secondary sexual characteristics at puberty, but does allow, without significant impairment, female genital and sexual development in those with the condition. All human fetuses begin fetal development looking similar, with both the Müllerian duct system (female) and the Wolffian duct system (male) developing. It is at the seventh week of gestation that the bodies of unaffected individuals with the XY karyotype begin their masculinization: i.e., the Wolffian duct system is promoted and the Müllerian duct system is suppressed (the reverse happens with typically developing females). This process is triggered by androgens produced by the gonads, which in individuals with the XX karyotype had earlier become ovaries, but in XY individuals typically had become testicles due to the presence of the Y Chromosome. The cells of unaffected XY individuals then masculinize by, among other things, enlarging the genital tubercle into a penis, which in females becomes the clitoris, while what in females becomes the labia fuses to become the scrotum of males (where the testicles will later descend). Individuals affected by CAIS develop a normal external female habitus, despite the presence of a Y chromosome, but internally, they will lack a uterus, and the vaginal cavity will be shallow, while the gonads, having been turned into testicles rather than ovaries in the earlier separate process also triggered by their Y chromosome, will remain undescended in the place where the ovaries would have been. This results not only in infertility in individuals with CAIS, but also presents a risk of gonadal cancer later on in life.CAIS is one of the three categories of androgen insensitivity syndrome (AIS) since AIS is differentiated according to the degree of genital masculinization: complete androgen insensitivity syndrome (CAIS) when the external genitalia is that of a typical female, mild androgen insensitivity syndrome (MAIS) when the external genitalia is that of a typical male, and partial androgen insensitivity syndrome (PAIS) when the external genitalia is partially, but not fully masculinized.Androgen insensitivity syndrome is the largest single entity that leads to 46, XY undermasculinization. Signs and symptoms Physical Individuals with complete androgen insensitivity syndrome (grades 6 and 7 on the Quigley scale) are born phenotypically female, without any signs of genital masculinization, despite having a 46,XY karyotype. Symptoms of CAIS do not appear until puberty, which may be slightly delayed, but is otherwise normal except for absent menses and diminished or absent secondary terminal hair. Axillary hair (i.e. armpit hair) fails to develop in one third of all cases. External genitalia is normal, although the labia and clitoris are sometimes underdeveloped. Vaginal depth varies widely for CAIS women, but is typically shorter than unaffected women; one study of eight women with CAIS measured the average vaginal depth to be 5.9 cm (vs. 11.1 ± 1.0 cm for unaffected women ). In some extreme cases, the vagina has been reported to be aplastic (resembling a "dimple"), though the exact incidence of this is unknown.The gonads in these women are not ovaries, but instead, are testes; 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. They may be located intra-abdominally, at the internal inguinal ring, or may herniate into the labia majora, often leading to the discovery of the condition. Testes in affected women have been found to be atrophic upon gonadectomy.Testosterone produced by the testes cannot be directly used due to the mutant androgen receptor that characterizes CAIS; instead, it is aromatized into estrogen, which effectively feminizes the body and accounts for the normal female phenotype observed in CAIS. However, up to 5% of individuals with CAIS do not have an AR mutation. The receptor in question is encoded by the AR gene located on the X chromosome at Xq11–12. At least 15 different mutations were known in 2003, and they are all recessive, which makes the disease to follow X-linked recessive inheritance.Immature sperm cells in the testes do not mature past an early stage, as sensitivity to androgens is required in order for spermatogenesis to complete. Germ cell malignancy risk, once thought to be relatively high, is now thought to be approximately 2%. Wolffian structures (the epididymides, vasa deferentia, and seminal vesicles) are typically absent, but will develop at least partially in approximately 30% of cases, depending on which mutation is causing the CAIS. The prostate, like the external male genitalia, cannot masculinize in the absence of androgen receptor function, and thus remains in the female form.The Müllerian system (the fallopian tubes, uterus, and upper portion of the vagina) typically regresses due to the presence of anti-Müllerian hormone originating from the Sertoli cells of the testes. These women are thus born without fallopian tubes, a cervix, or a uterus, and the vagina ends "blindly" in a pouch. Müllerian regression does not fully complete in approximately one third of all cases, resulting in Müllerian "remnants". Although rare, a few cases of women with CAIS and fully developed Müllerian structures have been reported. In one exceptional case, a 22-year-old with CAIS was found to have a normal cervix, uterus, and fallopian tubes. In an unrelated case, a fully developed uterus was found in a 22-year-old adult with CAIS.Other subtle differences that have been reported include slightly longer limbs and larger hands and feet due to a proportionally greater stature than unaffected women, larger teeth, minimal or no acne, well developed breasts, and a greater incidence of meibomian gland dysfunction (i.e. dry eye syndromes and light sensitivity). Endocrine Hormone levels have been reported in gonadally intact CAIS women in a number of studies. Hormone levels are similar to those of males, including high testosterone levels and relatively low estradiol levels. However, luteinizing hormone (LH) levels are elevated while sex hormone-binding globulin (SHBG) levels are more consistent with those of females. Women with CAIS have low levels of progesterone similarly to males. The production rates of testosterone, estradiol, and estrone have been reported to be higher in gonadally intact CAIS women than in men. Comorbidity All forms of androgen insensitivity, including CAIS, are associated with infertility, though exceptions have been reported for both the mild and partial forms.CAIS is associated with a decreased bone mineral density. Some have hypothesized that the decreased bone mineral density observed in women with CAIS is related to the timing of gonadectomy and inadequate estrogen supplementation. However, recent studies show that bone mineral density is similar whether gonadectomy occurs before or after puberty, and is decreased despite estrogen supplementation, leading some to hypothesize that the deficiency is directly attributable to the role of androgens in bone mineralization.CAIS is also associated with an increased risk for gonadal tumors (e.g. germ cell malignancy) in adulthood if gonadectomy is not performed. The risk of malignant germ cell tumors in women with CAIS increases with age and has been estimated to be 3.6% at 25 years and 33% at 50 years. The incidence of gonadal tumors in childhood is thought to be relatively low; a recent review of the medical literature found that only three cases of malignant germ cell tumors in prepubescent girls have been reported in association with CAIS in the last 100 years. Some have estimated the incidence of germ cell malignancy to be as low as 0.8% before puberty.Vaginal hypoplasia, a relatively frequent finding in CAIS and some forms of PAIS, is associated with sexual difficulties including vaginal penetration difficulties and dyspareunia.At least one study indicates 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. Lifespan is not thought to be affected by AIS.Despite the well-developed breasts in CAIS women, and for reasons that are not well-understood, breast cancer has never been reported in CAIS women and does not seem to occur or occurs only rarely. Only a case report of juvenile fibroadenoma exists. A few cases of breast cancer have been reported in individuals with partial androgen insensitivity syndrome however. Diagnosis CAIS can only be diagnosed in normal phenotypic females. It is not usually suspected unless the menses fail to develop at puberty, or an inguinal hernia presents during premenarche. As many as 1–2% of prepubertal girls that present with an inguinal hernia will also have CAIS.A diagnosis of CAIS or Swyer syndrome can be made in utero by comparing a karyotype obtained by amniocentesis with the external genitalia of the fetus during a prenatal ultrasound. Many infants with CAIS do not experience the normal, spontaneous neonatal testosterone surge, a fact which can be diagnostically exploited by obtaining baseline luteinizing hormone and testosterone measurements, followed by a human chorionic gonadotropin (hGC) stimulation test.The main differentials for CAIS are complete gonadal dysgenesis (Swyer syndrome) and Müllerian agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome or MRKH). Both CAIS and Swyer syndrome are associated with a 46,XY karyotype, whereas MRKH is not; MRKH can thus be ruled out by checking for the presence of a Y chromosome, which can be done either by fluorescence in situ hybridization (FISH) analysis or on full karyotype. Swyer syndrome is distinguished by the presence of a uterus, poor breast development and shorter stature. The diagnosis of CAIS is confirmed when androgen receptor (AR) gene sequencing reveals a mutation, although up to 5% of individuals with CAIS do not have an AR mutation.Up until the 1990s, a CAIS diagnosis was often hidden from the affected individual, the individuals family, or both. It is current practice to disclose the genotype at the time of diagnosis, particularly when the affected girl is at least of adolescent age. If the affected individual is a child or infant, it is generally up to the parents, often in conjunction with a psychologist, to decide when to disclose the diagnosis. 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 and sexuality Most individuals with CAIS are raised as females. They are born phenotypically female and are usually heterosexual with a female gender identity; However, at least two case studies have reported male gender identity in individuals with CAIS. Dilation therapy Most cases of vaginal hypoplasia associated with CAIS can be corrected using non-surgical pressure dilation methods. The elastic nature of vaginal tissue, as demonstrated by its ability to accommodate the differences in size between a tampon, a penis, and a babys head, make dilation possible even in cases when the vaginal depth is significantly compromised. Treatment compliance is thought to be critical to achieve satisfactory results. Dilation can also be achieved via the Vecchietti procedure, which stretches vaginal tissues into a functional vagina using a traction device that is anchored to the abdominal wall, subperitoneal sutures, and a mold that is placed against the vaginal dimple. Vaginal stretching occurs by increasing the tension on the sutures, which is performed daily. The non-operative pressure dilation method is currently recommended as the first choice, since it is non-invasive, and highly successful. Vaginal dilation should not be performed before puberty. Gonadectomy While it is often recommended that women with CAIS eventually undergo gonadectomy to mitigate cancer risk, there are differing opinions regarding the necessity and timing of gonadectomy. The risk of malignant germ cell tumors in women with CAIS increases with age and has been estimated to be 3.6% at 25 years and 33% at 50 years. However, only three cases of malignant germ cell tumors in prepubescent girls with CAIS have been reported in the last 100 years. The youngest of these girls was 14 years old. If gonadectomy is performed early, then puberty must be artificially induced using gradually increasing doses of estrogen. If gonadectomy is performed late, then puberty will occur on its own, due to the aromatization of testosterone into estrogen. At least one organization, the Australasian Paediatric Endocrine Group, classifies the cancer risk associated with CAIS as low enough to recommend against gonadectomy, although it warns that the cancer risk is still elevated above the general population, and that ongoing cancer monitoring is essential. Some choose to perform gonadectomy if and when inguinal hernia presents. Estrogen replacement therapy is critical to minimize bone mineral density deficiencies later in life. Hormone replacement therapy Some have hypothesized that supraphysiological levels of estrogen may reduce the diminished bone mineral density associated with CAIS. Data has been published that suggests affected women who were not compliant with estrogen replacement therapy, or who had a lapse in estrogen replacement, experienced a more significant loss of bone mineral density. Progestin replacement therapy is seldom initiated, due to the absence of a uterus. Androgen replacement has been reported to increase a sense of well-being in gonadectomized women with CAIS, although the mechanism by which this benefit is achieved is not well understood. Counseling It is no longer common practice to hide a diagnosis of CAIS from the affected individual or her family. Parents of children with CAIS need considerable support in planning and implementing disclosure for their child once the diagnosis has been established. For parents with young children, information disclosure is an ongoing, collaborative process requiring an individualized approach that evolves in concordance with the childs cognitive and psychological development. In all cases, the assistance of a psychologist experienced in the subject is recommended. Neovaginal construction Many surgical procedures have been developed to create a neovagina, as none of them is ideal. Surgical intervention should only be considered 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, an absorbable adhesion barrier (Interceed, made by Johnson & Johnson), buccal mucosa, amnion, dura mater. or with the support of vaginal stents/expanders. Success of such methods should be determined by sexual function, and not just by vaginal length, 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), which requires additional surgery to correct. Vaginal dilators are required postoperatively to prevent vaginal stenosis from scarring. Inflatable vaginal stents are placed in the vagina deflated and then gently inflated. 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. Prognosis Challenges presented to people affected by this condition include: psychologically coming to terms with the condition, difficulties with sexual function, infertility. Long-term studies indicate that with appropriate medical and psychological treatment, women with CAIS can be satisfied with their sexual function and psychosexual development. CAIS women can lead active lives and expect a normal lifespan. Epidemiology It is estimated that CAIS occurs in 1 in 20,400 to 1 in 99,000 individuals with a 46,XY karyotype. Nomenclature Historically, CAIS has been referred to in the literature under a number of other names, including testicular feminization [syndrome] (deprecated) and Morris syndrome. PAIS has also been referred to as Reifenstein syndrome, which should not be confused with CAIS. History The first definitive description of CAIS was reported in 1817. The condition became more widely known after it was reviewed and named testicular feminization by American gynecologist John McLean Morris in 1953. People with CAIS Georgiann Davis Seven Graham Eden Atwood See also Complete estrogen insensitivity syndrome References External links InformationAn Australian parent/patient booklet on CAIS (archived) The Secret of My Sex news article Women With Male DNA All Female news article at ABCnews.com
Buschke–Ollendorff syndrome	Buschke–Ollendorff syndrome (BOS) is a rare genetic disorder associated with LEMD3. It is believed to be inherited in an autosomal dominant manner. It is named for Abraham Buschke and Helene Ollendorff Curth, who described it in a 45-year-old woman. Its frequency is almost 1 case per every 20,000 people, and it is equally found in both males and females. Signs and symptoms The signs and symptoms of this condition are consistent with the following (possible complications include aortic stenosis and hearing loss): Osteopoikilosis Bone pain Connective tissue nevi Metaphysis abnormality Pathogenesis Buschke–Ollendorff syndrome is caused by one important factor: mutations in the LEMD3 gene (12q14), located on chromosome 12.Among the important aspects of Buschke–Ollendorff syndrome condition, genetically speaking are: LEMD3 (protein) referred also as MAN1, is an important protein in inner nuclear membrane. LEMD3 gene gives instructions for producing protein that controls signaling for transforming growth factor-beta. LEMD3 gene helps in the bone morphogenic protein pathway Both of the above pathways help grow new bone cells BMP and TGF-β pathways controls SMADs proteins, which then bind to DNA LEMD3 once mutated, causes a reduction of the protein, which in turn causes excess of the above two pathways. Diagnosis The diagnosis of this condition can be ascertained via several techniques one such method is genetic testing, as well as: X-ray Ultrasound Histological test Differential diagnosis The differential diagnosis for an individual believed to have Buschke–Ollendorff syndrome is the following: Melorheostosis Sclerotic bone metastases. Treatment In terms of the treatment of Buschke–Ollendorff syndrome, should the complication of aortic stenosis occur then surgery may be required.Treatment for hearing loss may also require surgical intervention. See also Osteopoikilosis List of cutaneous conditions Melorheostosis References Further reading Pope, V.; Dupuis, L.; Kannu, P.; Mendoza-Londono, R.; Sajic, D.; So, J.; Yoon, G.; Lara-Corrales, I. (2016). "Buschke-Ollendorff syndrome: a novel case series and systematic review". The British Journal of Dermatology. 174 (4): 723–729. doi:10.1111/bjd.14366. ISSN 1365-2133. PMID 26708699. S2CID 24066368. Helander, Martti Kormano, Ilmari Lindgren; with the collaboration of Inkeri; Lindgren, Ilmari (1999). Radiological findings in skin diseases and related conditions. Stuttgart: Thieme. ISBN 9783131161215. Retrieved 3 February 2018. External links Media related to Buschke–Ollendorff syndrome at Wikimedia Commons
Superior oblique myokymia	Superior oblique myokymia is a neurological disorder affecting vision and was named by Hoyt and Keane in 1970.It is a condition that presents as repeated, brief episodes of movement, shimmering or shaking of the vision of one eye, a feeling of the eye trembling, or vertical/tilted vision. It can present as one or more of these symptoms. Diagnosis is most often made by the elimination of other conditions, disorders or diseases. Onset usually occurs in adulthood, and the course is benign and is not commonly associated with other disorders. Causes In 1983, Bringewald postulated that superior oblique myokymia resulted from vascular compression of the trochlear nerve (fourth cranial nerve), which controls the action of the superior oblique muscle in the eye. By 1998, there had been only one reported case of compression of the trochlear nerve by vessels. More recently, magnetic resonance imaging experiments have shown that neurovascular compression at the root exit zone of the trochlear nerve can result in superior oblique myokymia. Diagnosis Treatment Treatment can include pharmaceutical or surgical means. The drug carbamazepine (Tegretol) has been used successfully. Other drugs with variable success include gabapentin and, recently, memantine. Successful surgery options include superior oblique tenectomy accompanied by inferior oblique myectomy. However, "[o]verall, the bulk of the ophthalmic literature would agree with the viewpoint that invasive craniotomy surgical procedures should be justified only by the presence of intractable and absolutely unbearable symptoms."Samii et al. and Scharwey and Samii described a patient who had superior oblique myokymia for 17 years. The interposition of a Teflon pad between the trochlear nerve and a compressing artery and vein at the nerves exit from the midbrain led to a remission lasting for a follow-up of 22 months. References == External links ==
Familial hyperaldosteronism	Familial hyperaldosteronism is a group of inherited conditions in which the adrenal glands, which are small glands located on top of each kidney, produce too much of the hormone aldosterone. Excess aldosterone causes the kidneys to retain more salt than normal, which in turn increases the bodys fluid levels and causes high blood pressure. People with familial hyperaldosteronism may develop severe high blood pressure, often early in life. Without treatment, hypertension increases the risk of strokes, heart attacks, and kidney failure. There are other forms of hyperaldosteronism that are not inherited.This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. The various types of familial hyperaldosteronism have different genetic causes.It is unclear how common these diseases are. All together they appear to make up less than 1% of cases of hyperaldosteronism. Types Familial hyperaldosteronism is categorized into three types, distinguished by their clinical features and genetic causes. Type I In familial hyperaldosteronism type I, hypertension generally appears in childhood to early adulthood and can range from mild to severe. This type can be treated with steroid medications called glucocorticoids, so it is also known as glucocorticoid remediable aldosteronism (GRA). Type II In familial hyperaldosteronism type II, hypertension usually appears in early to middle adulthood and does not improve with glucocorticoid treatment. Type III In most with familial hyperaldosteronism type III, the adrenal glands are enlarged up to six times their normal size. These affected have severe hypertension that starts in childhood. The hypertension is difficult to treat and often results in damage to organs such as the heart and kidneys. Rarely, individuals with type III have milder symptoms with treatable hypertension and no adrenal gland enlargement. Cause This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. The various types of familial hyperaldosteronism have different genetic causes. Familial hyperaldosteronism type I is caused by the abnormal joining together (fusion) of two similar genes called CYP11B1 and CYP11B2, which are located close together on chromosome 8. These genes provide instructions for making two enzymes that are found in the adrenal glands.The CYP11B1 gene provides instructions for making an enzyme called 11-beta-hydroxylase. This enzyme helps produce hormones called cortisol and corticosterone. The CYP11B2 gene provides instructions for making another enzyme called aldosterone synthase, which helps produce aldosterone. When CYP11B1 and CYP11B2 are abnormally fused together, too much aldosterone synthase is produced. This overproduction causes the adrenal glands to make excess aldosterone, which leads to the signs and symptoms of familial hyperaldosteronism type I.Familial hyperaldosteronism type III is caused by mutations in the KCNJ5 gene. The KCNJ5 gene provides instructions for making a protein that functions as a potassium channel, which means that it transports positively charged atoms (ions) of potassium into and out of cells. In the adrenal glands, the flow of ions through potassium channels produced from the KCNJ5 gene is thought to help regulate the production of aldosterone. Mutations in the KCNJ5 gene likely result in the production of potassium channels that are less selective, allowing other ions (predominantly sodium) to pass as well. The abnormal ion flow results in the activation of biochemical processes (pathways) that lead to increased aldosterone production, causing the hypertension associated with familial hyperaldosteronism type III.The genetic cause of familial hyperaldosteronism type II is unknown. Diagnosis Treatment See also 18-Hydroxycortisol 18-Hydroxycorticosterone References External links This article incorporates text from the United States National Library of Medicine ([1]), which is in the public domain.
Encephalocraniocutaneous lipomatosis	Encephalocraniocutaneous lipomatosis (ECCL), is a rare condition primarily affecting the brain, eyes, and skin of the head and face. It is characterized by unilateral subcutaneous and intracranial lipomas, alopecia, unilateral porencephalic cysts, epibulbar choristoma and other ophthalmic abnormalities. It was named after Haberland and Perou who first described it. Signs and Symptoms Eighty to ninety percent of those with encephalocraniocutaneous lipomatosis are unable to produce and keep fat tissue and have multiple lipomas. Other types of growths, including jaw tumours, may also occur.Approximately two thirds of individuals with Encephalocraniocutaneous lipomatosis have intracranial and/or intraspinal lipomas. They also have an increased risk of developing a form of brain cancer known as a glioma. Other neurological issues that can occur include seizures, spasticity and variable intellectual disability. However, approximately one third of effected individuals have typical intelligence.The most common ocular abnormality in encephalocraniocutaneous lipomatosis is a form of benign growth called a choristoma which can occur in one or both eyes. These may effect vision. Other ocular symptoms include abnormally small eyes, small pupils, iris hypoplasia, sclerocornea, hypertrophic conjunctivae, an absent macular reflex and anterior chamber anomalies. There may be eyelid colobomas and short or abnormal palpebral fissures. Skin tags often grow around the eyelids. Cause History This condition was first described in 1970. See also Nevus psiloliparus References == External links ==
Osteochondroma	Osteochondromas are the most common benign tumors of the bones. The tumors take the form of cartilage-capped bony projections or outgrowth on the surface of bones exostoses. It is characterized as a type of overgrowth that can occur in any bone where cartilage forms bone. Tumors most commonly affect long bones about the knee and in the forearm. Additionally, flat bones such as the pelvis and scapula (shoulder blade) may be affected. Hereditary multiple exostoses usually present during childhood. Yet, the vast majority of affected individuals become clinically manifest by the time they reach adolescence. Osteochondromas occur in 3% of the general population and represent 35% of all benign tumors and 8% of all bone tumors. The majority of these tumors are solitary non-hereditary lesions and approximately 15% of osteochondromas occur as hereditary multiple exostoses preferably known as hereditary multiple osteochondromas (HMOs). Osteochondromas do not result from injury and the exact cause remains unknown. Recent research has indicated that multiple osteochondromas is an autosomal dominant inherited disease. Germ line mutations in EXT1 and EXT2 genes located on chromosomes 8 and 11 have been associated with the cause of the disease. The treatment choice for osteochondroma is surgical removal of solitary lesion or partial excision of the outgrowth, when symptoms cause motion limitations or nerve and blood vessel impingements. In hereditary multiple exostoses the indications of surgery are based upon multiple factors that are taken collectively, namely: patients age, tumor location and number, accompanying symptomatology, esthetic concerns, family history and underlying gene mutation. A variety of surgical procedures have been employed to remedy hereditary multiple exostoses such as osteochondroma excision, bone lengthening, corrective osteotomy and hemiepiphysiodesis. Sometimes a combination of the previous procedures is used. The indicators of surgical success in regard to disease and patient characteristics are greatly disputable. Because most studies of hereditary multiple exostoses are retrospective and of limited sample size with missing data, the best evidence for each of the currently practiced surgical procedures is lacking. Signs and symptoms Limited normal functions and movements are caused by osteochondromas growing slowly and inwardly. The majority of osteochondromas are symptomless and are found incidentally. Each individual with osteochondroma may experience symptoms differently and most of the time individuals will experience no symptoms at all. Some of the most common symptoms are a hard immobile painless palpable mass, adjacent muscle soreness, and pressure or irritation with heavy exercising. Major symptoms arise when complications such as fractures, bone deformity or mechanical joint problems occur. If the occurrence of an osteochondroma is near a nerve or a blood vessel, the affected limb can experience numbness, weakness, loss of pulse or color change. Periodic changes in the blood flow can also take place. Approximately 20% of patients experiencing nerve compression commonly acknowledge vascular compression, arterial thrombosis, aneurysm, and pseudoaneurysm. Formation of pseudoaneurysm and venous thrombosis lead to claudication, pain, acute ischemia, and symptoms of phlebitis. If the tumor is found under a tendon, it can cause pain during movement causing restriction of joint motion. Pain can also occur due to bursal inflammation, swelling or fracture at the base of the tumor stalk. Some of the clinical signs and symptoms of malignant osteochondroma are pain, swelling, and mass enlargement. Mechanism Osteochondromas are long and slender, pedunculated on a stalk often taking the shape of a cauliflower. The cartilage cap is covered by fibrous perichondrium and continues with the periosteum of the underlying bone. The cartilage cap is less than 2 cm thick and the thickness decreases with age. A cap more than 2 cm thick, indicates malignant transformation of a tumor. The cartilage cap merges with the epiphyseal area of the long bones called spongiosa. In the spongiosa, the chondrocytes are arranged in accordance with the epiphyseal growth plate. The spongiosa of the stalk continues with the underlying cancellous bone. Fractures within the stalk causes fibroblastic proliferation and formation of a new bone. Development of bursa takes place over the osteochondroma, which is attached to the perichondrium of the cap. Inflammation of the bone is indicated by the bursal wall lined by the synovium. As a result, patients may have swelling for years related to the location and site of the lesion indicative of mechanical obstruction, nerve impingement, pseudoaneurysm of the overlying vessel, fracture at the stalk of the lesion, or formation of bursa over the osteochondroma. Heparan sulphate (HS) are glycosaminoglycans which are involved in the formation of proteoglycans. The biosynthesis of HS takes place in the Golgi apparatus and endoplasmic reticulum, where glycosaminoglycans chains are maintained by type II glycosyltransferases encoded by EXOSTOSIN genes EXT1 and EXT2. Decreased levels of HS leads to mutations in EXT1 or EXT2 causing skeletal abnormality. The underlying mechanism for solitary and multiple osteochondromas have been associated with genetic alterations in EXT1 or EXT2 genes located on chromosomes 8 and 11. Approximately 65% of osteochondromas arise in the EXT1 gene loci on chromosome 8 and 35% arise in EXT2 gene loci on chromosome 11. About 70–75% of multiple osteochondromas are caused by point mutations, often involving deletion of single or multiple axons as found in 10% of all hereditary cases. In about 10–15% of all cases no genomic alterations are detected. The mechanism behind the formation of multiple osteochondroma is large genomic deletions of EXT1 and EXT2 genes. The identified mechanism behind solitary osteochondromas is the homozygous deletions of the EXT1 gene. However, the exact cause of osteochondroma is unknown. Additionally, the molecular basis of genetics and clinical variability of multiple osteochondroma as well as the underlying causes for the malignant transformation and the onset of osteochondroma in EXT negative patients is also currently unknown. Diagnosis Osteochondromas are often asymptomatic and may not cause any kind of discomfort. They are often found accidentally when an X-ray is done for an unrelated reason. X-rays are the first tests performed that characterize a lesion. They show a clear picture of dense structures of bones, and will also indicate bone growth pertaining to osteochondroma. Computed tomography (CT) scan can identify the bony lesion in great details and show the presence of calcification. These tests also provide great details, especially in soft tissues with the aide of cross-sectional images. Magnetic resonance imaging (MRI) is the most accurate method for detecting bone masses in symptomatic cases to depict precise morphology of a tumor. It is used to verify if the palpable mass is continuous with the cortex of the affected bone and to differentiate an osteochondroma from other lesions on the surface of the bone. MRI can also be used to look for cartilage on the surface of tumor and can depict any vascular complications caused by the tumor. An MRI can identify tumors of the spinal column and is often used to diagnose low grade osteosarcoma. Ultrasound is done if aneurysms or pseudoaneurysms and venous or arterial thrombosis is suspected. Ultrasound is an accurate method for examining the cartilaginous cap of the osteochondroma. It is also a way of pinpointing bursitis. However, it cannot be used to predict if the growth of tumor is inward in regards to the cap. Angiography is used to detect vascular lesions caused by osteochondroma due to ossified cartilaginous cap. It is also used to characterize malignant transformation lesions through neovascularity. Clinical testing such as sequence analysis can be done of the entire coding regions of both EXT1 and EXT2 to detect mutations. A biopsy of the tissue sample of the tumor can also be taken to check for cancer.Tests for osteochondroma can also identify diseases such as secondary peripheral chondrosarcoma and multiple osteochondromatosis. In large, secondary chondrosarcoma arises at the site of osteochondroma due to increased thickness of the cartilage cap indicating potential malignant transformation. The symptoms of multiple osteochondromatosis are similar to solitary osteochondroma, but they are often more severe. Painless bumps can arise at the site of tumor and pain and other discomforts can also take place if pressure is put on the soft tissues, nerves, or blood vessels. Dysplasia Epiphysealis Hemimelica (DEH) or Trevors disease and metachondromatosis (MC) are considered differential diagnosis of both solitary and hereditary osteochondromas. DEH is described as a type of over growth at one or more epiphyses. Similar to osteochondroma, DEH is diagnosed prior to 15 years of age and the growth of lesions end at puberty, when the growth plates close. Metachondromatosis is a rare disorder that exhibit symptoms of both multiple osteochondromas and enchondromas in children and is also inherited in autosomal dominant mode.A type that contains fat is known as an osteolipochondroma (osteo, bone, lipos, fat, + chondros, cartilage, oma, tumor). Treatment Osteochondromas are benign lesions and do not affect life expectancy. Complete excision of osteochondroma is curative and the reoccurrences take place when the removal of tumor is incomplete. Multiple reoccurrences in a well-excised lesion indicate that it may be malignant. The risk of malignant transformation takes place in 1–5% of individuals. If any symptoms of cancerous tumor takes place, then the patient should be evaluated by a bone specialist. No treatment is necessary for Solitary osteochondromas that are asymptomatic. Treatments for solitary osteochondroma are careful observation over time and taking regular x-rays to monitor any changes in the tumor. If the lesion is causing pain with activity, nerve or vessel impingement, or if the bone growth has fully matured and the presence of a large cartilage cap is prominent, then it is advised that the tumor be surgically removed.Osteochondromas have a low rate of malignancy (<1%) and resection of the tumor is suggested if symptoms such as pain, limitation of movement, or impingement on nerves or vessels occur. Resection of the tumor also takes place when the tumor increases in size and progresses towards malignancy. During surgical resection, the entire lesion along with the cartilaginous cap should be removed to minimize any chances of reoccurrences. Surgical treatment becomes the sole treatment of choice if common complications such as fractures, symptoms of peripheral nerves such as paresthesia, paraplegia, peroneal neuropathy, and upper limb neuropathy take place. A prophylactic resection is suggested if the lesion lies next to a vessel.Depending on the size and location of the tumor, the time it takes to return to normal daily activities varies between individuals. Limitation on some activities is advised if pain or discomfort persists after surgical excision. Research Research done using Zebrafish dackel (dak) have shown that in EXT2-/- Zebrafish, chondrocytes fail to undergo terminal differentiation and bone formation fails to progress from pre-osteoblasts stage to osteoblasts. Instead, abnormal lipid deposition and premature adipocyte differentiation takes place. The expression of xbp1, master regulator of osterix gets reduced, suggesting that unfolded proteins responses may play a role in pathogenesis of multiple osteochondroma. The research concludes that heparan sulphates are required for terminal differentiation and formation of scaffold that is needed for bone development. At least one copy of EXT2 gene is needed for proper bone development and to maintain the balance between bone and fat cell lineages. Due to homozygous loss of EXT2 function, leads to imbalance between cartilage, bone, and fat cell lineages. These observations in null zebrafish points toward the musculoskeletal defects observed in patients with multiple osteochondroma. Due to the findings of bone-fat imbalance in Zebra fish model, future studies should address status of lipid composition in patients with multiple osteochondroma. Research conducted using sequencing methods has identified a novel frame shift mutation at the glycosyltransferase domain (c.1457insG) located at codon 486 of exon 6 of the EXT1 gene, that causes multiple osteochondromas. This study was conducted in two multiple osteochondroma (MO) patients from the Chinese descent (same family) and the results were validated with four other members of the same MO family and 200 unrelated healthy subjects. The results of the mutations were validated using two different sequencing methods (Exome and Sanger). The results of immunohistochemistry and multiple sequence alignment supports the cause of MO being a mutation in EXT1 gene. However, the exact molecular mechanism of multiple osteochondroma remains unclear. The EXT1 gene encodes the endoplasmic reticulum-resident type II transmembrane glycosyltransferase, which catalyzes polymerization of heparin sulfate chain at the endoplasmic reticulum and the Golgi apparatus. Heparin sulfate regulates signal transduction during chondrocyte differentiation, ossification, and apoptosis. Malfunction in heparin sulfate synthesis causes chondrocytes to rapidly differentiate. Based on these results future studies should elucidate the underlying molecular mechanism of the glycosyltransferase domain of the EXT1 and its involvement in the development of multiple osteochondromas. Osteochondromas are associated with secondary peripheral chondrosarcomas, but the pathogenesis of the malignant bone tumor remains unknown. Research has demonstrated that chondrocytes with dysfunctional EXT1 is present in solitary osteochondromas, but the EXT1 is functional in sporadic (solitary) secondary peripheral chondrosarcomas. Research indicates that osteochondromas creates a special niche in which wild type cells are mixed in with EXT functional cells. Then these EXT functional cells undergo other mutations, that give rise to secondary peripheral chondrosarcoma, indicating the involvement of an alternative mechanism for the pathogenesis of secondary peripheral chondrosarcoma. Future studies should address the contributing gene that causes the formation of peripheral chondrosarcoma. It should also illustrate what causes chondrocytes functional with EXT1 and EXT2 within the osteochondroma to become more susceptible to mutations leading to malignancy. References External links Humpath #2790 (Pathology images) American Academy of Orthopedic Surgeons
Multiple myeloma	Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, anemia, kidney dysfunction, and infections may occur. Complications may include amyloidosis.The cause of multiple myeloma is unknown. Risk factors include obesity, radiation exposure, family history, and certain chemicals. Multiple myeloma may develop from monoclonal gammopathy of undetermined significance that progresses to smoldering myeloma. The abnormal plasma cells produce abnormal antibodies, which can cause kidney problems and overly thick blood. The plasma cells can also form a mass in the bone marrow or soft tissue. When one tumor is present, it is called a plasmacytoma; more than one is called multiple myeloma. Multiple myeloma is diagnosed based on blood or urine tests finding abnormal antibodies, bone marrow biopsy finding cancerous plasma cells, and medical imaging finding bone lesions. Another common finding is high blood calcium levels.Multiple myeloma is considered treatable, but generally incurable. Remissions may be brought about with steroids, chemotherapy, targeted therapy, and stem cell transplant. Bisphosphonates and radiation therapy are sometimes used to reduce pain from bone lesions.Globally, multiple myeloma affected 488,000 people and resulted in 101,100 deaths in 2015. In the United States, it develops in 6.5 per 100,000 people per year and 0.7% of people are affected at some point in their lives. It usually occurs around the age of 60 and is more common in men than women. It is uncommon before the age of 40. Without treatment, the median survival in the prechemotherapy era was about 7 months. After the introduction of chemotherapy, prognosis improved significantly with a median survival of 24 to 30 months and a 10-year survival rate of 3%. Even further improvements in prognosis have occurred because of the introduction of newer biologic therapies and better salvage options, with median survivals now exceeding 60 to 90 months. With current treatments, survival is usually 4–5 years. The five-year survival rate is about 54%. The word myeloma is from the Greek myelo- meaning "marrow" and -oma meaning "tumor". Signs and symptoms Because many organs can be affected by myeloma, the symptoms and signs vary greatly. Fatigue and bone pain are the most common symptoms at presentation. The CRAB criteria encompass the most common signs of multiple myeloma:: 651 Calcium: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL) Renal insufficiency: creatinine clearance <40 mL per minute or serum creatinine >1.77 mol/L (>2 mg/dL) Anemia: hemoglobin value of >2g/dL below the lowest limit of normal, or a hemoglobin value <10g/dL Bone lesions: osteolytic lesions on skeletal radiography, CT, or PET/CT Bone pain Bone pain affects almost 70% of people with multiple myeloma and is one of the most common symptoms.: 653 Myeloma bone pain usually involves the spine and ribs, and worsens with activity. Persistent, localized pain may indicate a pathological bone fracture. Involvement of the vertebrae may lead to spinal cord compression or kyphosis. Myeloma bone disease is due to the overexpression of receptor activator for nuclear factor κ B ligand (RANKL) by bone marrow stroma. RANKL activates osteoclasts, which resorb bone. The resultant bone lesions are lytic (cause breakdown) in nature, and are best seen in plain radiographs, which may show "punched-out" resorptive lesions (including the "raindrop" appearance of the skull on radiography). The breakdown of bone also leads to the release of calcium ions into the blood, leading to hypercalcemia and its associated symptoms. Anemia The anemia found in myeloma is usually normocytic and normochromic. It results from the replacement of normal bone marrow by infiltrating tumor cells and inhibition of normal red blood cell production (hematopoiesis) by cytokines. Impaired kidney function Impaired kidney function may develop, either acutely or chronically, and with any degree of severity. The most common cause of kidney failure in multiple myeloma is due to proteins secreted by the malignant cells. Myeloma cells produce monoclonal proteins of varying types, most commonly immunoglobulins (antibodies) and free light chains, resulting in abnormally high levels of these proteins in the blood. Depending on the size of these proteins, they may be excreted through the kidneys. Kidneys can be damaged by the effects of proteins or light chains. Increased bone resorption leads to hypercalcemia and causes nephrocalcinosis, thereby contributing to kidney failure. Amyloidosis is a distant third in the causation. People with amyloidosis have high levels of amyloid protein that can be excreted through the kidneys and cause damage to the kidneys and other organs.Light chains produce myriad effects that can manifest as the Fanconi syndrome (type II kidney tubular acidosis). Infection The most common infections are pneumonias and pyelonephritis. Common pneumonia pathogens include S. pneumoniae, S. aureus, and K. pneumoniae, while common pathogens causing pyelonephritis include E. coli and other Gram-negative organisms. The greatest risk period for the occurrence of infection is in the initial few months after the start of chemotherapy. The increased risk of infection is due to immune deficiency. Although the total immunoglobulin level is typically elevated in multiple myeloma, the majority of the antibodies are ineffective monoclonal antibodies from the clonal plasma cell. A selected group of people with documented hypogammaglobulinemia may benefit from replacement immunoglobulin therapy to reduce the risk of infection. Neurological symptoms Some symptoms (e.g., weakness, confusion, and fatigue) may be due to anemia or hypercalcemia. Headache, visual changes, and retinopathy may be the result of hyperviscosity of the blood depending on the properties of the paraprotein. Finally, radicular pain, loss of bowel or bladder control (due to involvement of spinal cord leading to cord compression) or carpal tunnel syndrome, and other neuropathies (due to infiltration of peripheral nerves by amyloid) may occur. It may give rise to paraplegia in late-presenting cases.When the disease is well-controlled, neurological symptoms may result from current treatments, some of which may cause peripheral neuropathy, manifesting itself as numbness or pain in the hands, feet, and lower legs. Mouth The initial symptoms may involve pain, numbness, swelling, expansion of the jaw, tooth mobility, and radiolucency. Multiple myeloma in the mouth can mimic common teeth problems like periapical abscess or periodontal abscess, gingivitis, periodontitis, or other gingival enlargement or masses. Cause The cause of multiple myeloma is generally unknown. Risk factors Monoclonal gammopathy of undetermined significance (MGUS) increases the risk of developing multiple myeloma. MGUS transforms to multiple myeloma at the rate of 1% to 2% per year, and almost all cases of multiple myeloma are preceded by MGUS. Smoldering multiple myeloma increases the risk of developing multiple myeloma. Individuals diagnosed with this premalignant disorder develop multiple myeloma at a rate of 10% per year for the first 5 years, 3% per year for the next 5 years, and then 1% per year. Obesity is related to multiple myeloma with each increase of body mass index by five increasing the risk by 11%.Studies have reported a familial predisposition to myeloma. Hyperphosphorylation of a number of proteins—the paratarg proteins—a tendency that is inherited in an autosomal dominant manner, appears a common mechanism in these families. This tendency is more common in African-American with myeloma and may contribute to the higher rates of myeloma in this group. Epstein–Barr virus Rarely, Epstein–Barr virus (EBV) is associated with multiple myeloma, particularly in individuals who have an immunodeficiency due to e.g. HIV/AIDS, organ transplantation, or a chronic inflammatory condition such as rheumatoid arthritis. EBV-positive multiple myeloma is classified by the World Health Organization (2016) as one form of the Epstein–Barr virus-associated lymphoproliferative diseases and termed Epstein–Barr virus-associated plasma cell myeloma. EBV-positive disease is more common in the plasmacytoma rather than multiple myeloma form of plasma cell cancer. Tissues involved in EBV+ disease typically show foci of EBV+ cells with the appearance of rapidly proliferating immature or poorly differentiated plasma cells. The cells express products of EBV genes such as EBER1 and EBER2. While the EBV contributes to the development and/or progression of most Epstein–Barr virus-associated lymphoproliferatve diseases, its role in multiple myeloma is not known. However, people who are EBV-positive with localized plasmacytoma(s) are more likely to progress to multiple myeloma compared to people with EBV-negative plasmacytoma(s). This suggest that EBV may have a role in the progression of plasmacytomas to systemic multiple myeloma. Pathophysiology B lymphocytes start in the bone marrow and move to the lymph nodes. As they progress, they mature and display different proteins on their cell surfaces. When they are activated to secrete antibodies, they are known as plasma cells. Multiple myeloma develops in B lymphocytes after they have left the part of the lymph node known as the germinal center. The normal cell type most closely associated with MM cells is generally taken to be either an activated memory B cell or the precursor to plasma cells, the plasmablast.The immune system keeps the proliferation of B cells and the secretion of antibodies under tight control. When chromosomes and genes are damaged, often through rearrangement, this control is lost. Often, a promoter gene moves (or translocates) to a chromosome, where it stimulates an antibody gene to overproduction. A chromosomal translocation between the immunoglobulin heavy chain gene (on chromosome 14, locus q32) and an oncogene (often 11q13, 4p16.3, 6p21, 16q23 and 20q11) is frequently observed in people with multiple myeloma. This mutation results in dysregulation of the oncogene which is thought to be an important initiating event in the pathogenesis of myeloma. The result is a proliferation of a plasma cell clone and genomic instability that leads to further mutations and translocations. The chromosome 14 abnormality is observed in about 50% of all cases of myeloma. Deletion of (parts of) chromosome 13 is also observed in about 50% of cases. Production of cytokines (especially IL-6) by the plasma cells causes much of their localised damage, such as osteoporosis, and creates a microenvironment in which the malignant cells thrive. Angiogenesis (the generation of new blood vessels) is increased. The produced antibodies are deposited in various organs, leading to kidney failure, polyneuropathy, and various other myeloma-associated symptoms. Epigenetics In a study that investigated the DNA methylation profile of multiple myeloma cells and normal plasma cells, a gradual demethylation from stem cells to plasma cells was observed. The observed methylation pattern of CpG within intronic regions with enhancer-related chromatin marks in multiple myeloma is similar to undifferentiated precursor and stem cells. These results may represent a de novo epigenetic reprogramming in multiple myeloma, leading to the acquisition of a methylation pattern related to stemness. Other studies have identified a multiple myeloma specific gene silencing pattern associated with the polycomb repressive complex 2 (PRC2). Increased expression of the PRC2 subunit, EZH2 have been described to be a common feature in multiple myeloma, resulting in an accumulation and redistribution of histone H3 lysine 27 trimethylation which advances with disease severity. Genetics Chromosomal abnormalities commonly found in this disease, like trisomy of multiple odd-numbered chromosomes, t(11;14), and del(13q), are not associated with a worse prognosis. However, about 25% of patients with newly diagnosed disease have abnormalities associated with a worse prognosis, like t(4;14), t(14;16), and del(17p). Other less common abnormalities associated with a worse prognosis include t(14;20) and ≥4 copies of 1q.: 1730–1 Associated genetic mutations include ATM, BRAF, CCND1, DIS3, FAM46C, KRAS, NRAS and TP53. Development The genetic and epigenetic changes occur progressively. The initial change, often involving one chromosome 14 translocation, establishes a clone of bone marrow plasma cells that causes the asymptomatic disorder MGUS, which is a premalignant disorder characterized by increased numbers of plasma cells in the bone marrow or the circulation of a myeloma protein immunoglobulin. Further genetic or epigenic changes produce a new clone of bone marrow plasma cells, usually descendant from the original clone, that causes the more serious, but still asymptomatic premalignant disorder smoldering multiple myeloma. This myeloma is characterized by a rise in the number of bone marrow plasma cells or levels of the circulating myeloma protein above that seen in MGUS. Subsequent genetic and epigenetic changes lead to a new, more aggressive clone of plasma cells, which cause further rises in the level of the circulating myeloma protein, further rises in the number of bone marrow plasma cells, or the development of one or more of a specific set of "CRAB" symptoms, which are the basis for diagnosing malignant multiple myeloma and treating the disease. In a small percentage of multiple myeloma cases, further genetic and epigenetic changes lead to the development of a plasma cell clone that moves from the bone marrow into the circulatory system, invades distant tissues, and thereby causes the most malignant of all plasma cell dyscrasias, plasma cell leukemia. Thus, a fundamental genetic instability in plasma cells or their precursors leads to the progression: Monoclonal gammopathy of undetermined significance → smoldering multiple myeloma → multiple myeloma → plasma cell leukemia Being asymptomatic, monoclonal gammopathy of undetermined significance and smoldering multiple myeloma are typically diagnosed fortuitously by detecting a myeloma protein on serum protein electrophoresis tests done for other purposes. MGUS is a relatively stable condition afflicting 3% of people aged 50 and 5% of people aged 70; it progresses to multiple myeloma at a rate of 0.5–1% cases per year; smoldering multiple myeloma does so at a rate of 10% per year for the first 5 years, but then falls off sharply to 3% per year for the next 5 years and thereafter to 1% per year.Overall, some 2–4% of multiple myeloma cases eventually progress to plasma cell leukemia. Diagnosis Blood tests The globulin level may be normal in established disease. A doctor may request protein electrophoresis of the blood and urine, which might show the presence of a paraprotein (monoclonal protein, or M protein) band, with or without reduction of the other (normal) immunoglobulins (known as immune paresis). One type of paraprotein is the Bence Jones protein, which is a urinary paraprotein composed of free light chains. Quantitative measurements of the paraprotein are necessary to establish a diagnosis and to monitor the disease. The paraprotein is an abnormal immunoglobulin produced by the tumor clone. In theory, multiple myeloma can produce all classes of immunoglobulin, but IgG paraproteins are most common, followed by IgA and IgM. IgD and IgE myeloma are very rare. In addition, light and or heavy chains (the building blocks of antibodies) may be secreted in isolation: κ- or λ-light chains or any of the five types of heavy chains (α-, γ-, δ-, ε- or μ-heavy chains). People without evidence of a monoclonal protein may have "nonsecretory" myeloma (not producing immunoglobulins); this represents about 3% of all people with multiple myeloma.Additional findings may include a raised calcium level (when osteoclasts are breaking down bone, releasing it into the bloodstream), raised serum creatinine level due to reduced kidney function, which is mainly due to casts of paraprotein deposition in the kidney, although the cast may also contain complete immunoglobulins, Tamm-Horsfall protein and albumin.Other useful laboratory tests include quantitative measurement of IgA, IgG, and IgM to look for immune paresis, and beta-2 microglobulin, which provides prognostic information. On peripheral blood smear, the rouleaux formation of red blood cells is commonly seen, though this is not specific. The recent introduction of a commercial immunoassay for measurement of free light chains potentially offers an improvement in monitoring disease progression and response to treatment, particularly where the paraprotein is difficult to measure accurately by electrophoresis (for example in light chain myeloma, or where the paraprotein level is very low). Initial research also suggests that measurement of free light chains may also be used, in conjunction with other markers, for assessment of the risk of progression from MGUS to multiple myeloma.This assay, the serum free light chain assay, has recently been recommended by the International Myeloma Working Group for the screening, diagnosis, prognosis, and monitoring of plasma cell dyscrasias. Histopathology A bone marrow biopsy is usually performed to estimate the percentage of bone marrow occupied by plasma cells. This percentage is used in the diagnostic criteria for myeloma. Immunohistochemistry (staining particular cell types using antibodies against surface proteins) can detect plasma cells that express immunoglobulin in the cytoplasm and occasionally on the cell surface; myeloma cells are often CD56, CD38, CD138, and CD319 positive and CD19, CD20, and CD45 negative. Flow cytometry is often used to establish the clonal nature of the plasma cells, which will generally express only kappa or lambda light chain. Cytogenetics may also be performed in myeloma for prognostic purposes, including a myeloma-specific fluorescent in situ hybridization and virtual karyotype. The plasma cells seen in multiple myeloma have several possible morphologies. First, they could have the appearance of a normal plasma cell, a large cell two or three times the size of a peripheral lymphocyte. Because they are actively producing antibodies, the Golgi apparatus typically produces a light-colored area adjacent to the nucleus, called a perinuclear halo. The single nucleus (with inside a single nucleolus with vesicular nuclear chromatin) is eccentric, displaced by an abundant cytoplasm. Other common morphologies seen, but which are not usual in normal plasma cells, include: Bizarre cells, which are multinucleated Mott cells, containing multiple clustered cytoplasmic droplets or other inclusions (sometimes confused with auer rods, commonly seen in myeloid blasts) Flame cells, having a fiery red cytoplasmHistorically, the CD138 has been used to isolate myeloma cells for diagnostic purposes. However, this antigen disappears rapidly ex vivo. Recently, however, the surface antigen CD319 (SLAMF7) was discovered to be considerably more stable and allows robust isolation of malignant plasma cells from delayed or even cryopreserved samples.The prognosis varies widely depending upon various risk factors. The Mayo Clinic has developed a risk-stratification model termed Mayo Stratification for Myeloma and Risk-adapted Therapy (mSMART), which divides people into high-risk and standard-risk categories. People with deletion of chromosome 13 or hypodiploidy by conventional cytogenetics, t(4;14), t(14;16), t(14;20) or 17p- by molecular genetic studies, or with a high plasma cell labeling index (3% or more) are considered to have high-risk myeloma. Medical imaging The diagnostic examination of a person with suspected multiple myeloma typically includes a skeletal survey. This is a series of X-rays of the skull, axial skeleton, and proximal long bones. Myeloma activity sometimes appears as "lytic lesions" (with local disappearance of normal bone due to resorption). And on the skull X-ray as "punched-out lesions" (raindrop skull). Lesions may also be sclerotic, which is seen as radiodense. Overall, the radiodensity of myeloma is between −30 and 120 Hounsfield units (HU). Magnetic resonance imaging is more sensitive than simple X-rays in the detection of lytic lesions, and may supersede a skeletal survey, especially when vertebral disease is suspected. Occasionally, a CT scan is performed to measure the size of soft-tissue plasmacytomas. Bone scans are typically not of any additional value in the workup of people with myeloma (no new bone formation; lytic lesions not well visualized on bone scan). Diagnostic criteria In 2003, the IMG agreed on diagnostic criteria for symptomatic myeloma, asymptomatic myeloma, and MGUS, which was subsequently updated in 2009: Symptomatic myeloma (all three criteria must be met): Clonal plasma cells >10% on bone marrow biopsy or (in any quantity) in a biopsy from other tissues (plasmacytoma) A monoclonal protein (myeloma protein) in either serum or urine and it has to be more than 3g/dL (except in cases of true nonsecretory myeloma) Evidence of end-organ damage felt related to the plasma cell disorder (related organ or tissue impairment, CRAB): HyperCalcemia (corrected calcium >2.75 mmol/L, >11 mg/dL) Renal failure (kidney insufficiency) attributable to myeloma Anemia (hemoglobin <10 g/dL) Bone lesions (lytic lesions or osteoporosis with compression fractures)Note: Recurrent infections alone in a person who has none of the CRAB features is not sufficient to make the diagnosis of myeloma. People who lack CRAB features, but have evidence of amyloidosis, should be considered as amyloidosis and not myeloma. CRAB-like abnormalities are common with numerous diseases, and these abnormalities must be felt to be directly attributable to the related plasma cell disorder and every attempt made to rule out other underlying causes of anemia, kidney failure, etc. In 2014, the IMWG updated their criteria further to include biomarkers of malignancy. These biomarkers are >60% clonal plasma cells, a serum involved / uninvolved free light chain ratio ≥ 100 (the concentration of the involved free light chain must be ≥ 100 mg/L) and more than one focal lesion ≥ 5 mm by MRI. Together, these biomarkers and the CRAB criteria are known as myeloma-defining events (MDEs). A person must have >10 % clonal plasma cells and any MDE to be diagnosed with myeloma. The biomarker criteria were added so that smouldering people with multiple myeloma at high risk of developing multiple myeloma could be diagnosed before organ damage occurred, so they would therefore have a better prognosis. Asymptomatic/smoldering myeloma: Serum M protein >30 g/L (3 g/dL) or Clonal plasma cells >10% on bone marrow biopsy and No myeloma-related organ or tissue impairment Monoclonal gammopathy of undetermined significance (MGUS): Serum paraprotein <30 g/L (3 g/dL) and Clonal plasma cells <10% on bone marrow biopsy and No myeloma-related organ or tissue impairment or a related B-cell lymphoproliferative disorderRelated conditions include solitary plasmacytoma (a single tumor of plasma cells, typically treated with irradiation), plasma cell dyscrasia (where only the antibodies produce symptoms, e.g., AL amyloidosis), and peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes. Staging In multiple myeloma, staging helps with prognostication but does not guide treatment decisions. The Durie-Salmon staging system was used historically and was replaced by the International Staging System (ISS), published by the International Myeloma Working Group In 2005. The revised ISS (R-ISS) was published in 2015 and incorporates cytogenetics and lactate dehydrogenase (LDH).: 1730–1 : 732–3 Stage I: β2 microglobulin (β2M) < 3.5 mg/L, albumin ≥ 3.5 g/dL, normal cytogenetics, no elevated LDH Stage II: Not classified under Stage I or Stage III Stage III: β2M ≥ 5.5 mg/L and either elevated LDH or high-risk cytogenetics [t(4,14), t(14,16), and/or del(17p)] Prevention The risk of multiple myeloma can be reduced slightly by maintaining a normal body weight. Treatment Treatment is indicated in myeloma with symptoms. If there are no symptoms, but a paraprotein typical of myeloma and diagnostic bone marrow is present without end-organ damage, treatment is usually deferred or restricted to clinical trials. Treatment for multiple myeloma is focused on decreasing the clonal plasma cell population and consequently decrease the symptoms of disease. Chemotherapy Initial Initial treatment of multiple myeloma depends on the persons age and other illnesses present. The preferred treatment for those under the age of 65 is high-dose chemotherapy, commonly with bortezomib-based regimens, and lenalidomide–dexamethasone, to be followed by a stem cell transplant. A 2016 study concluded that stem cell transplant is the preferred treatment of multiple myeloma. There are two types of stem cell transplants to treat multiple myeloma. In autologous hematopoietic stem-cell transplantation (ASCT) – the patients own stem cells are collected from the patients own blood. The patient is given high-dose chemotherapy, and the patients stem cells are then transplanted back into the patient. The process is not curative, but does prolong overall survival and complete remission. In allogeneic stem-cell transplantation, a healthy donors stem cells are transplanted into the affected person. Allogenic stem-cell transplantation has the potential for a cure, but is used in a very small percentage of people (and in the relapsed setting, not as part of initial treatment). Furthermore, a 5–10% treatment-associated mortality rate is associated with allogeneic stem-cell transplant. People over age 65 and people with significant concurrent illnesses often cannot tolerate stem-cell transplantation. For these people, the standard of care has been chemotherapy with melphalan and prednisone. Recent studies among this population suggest improved outcomes with new chemotherapy regimens, e.g., with bortezomib. Treatment with bortezomib, melphalan, and prednisone had an estimated overall survival of 83% at 30 months, lenalidomide plus low-dose dexamethasone an 82% survival at 2 years, and melphalan, prednisone, and lenalidomide had a 90% survival at 2 years. Head-to-head studies comparing these regimens have not
Multiple myeloma	been performed as of 2008.There is support for continuous therapies with multiple drug combinations of antimyeloma drugs bortezomib, lenalidomide and thalidomide as initial treatment for transplant-ineligible multiple myeloma. Further clinical studies are required to determine the potential harms of these drugs and the effect on the persons quality of life. A 2009 review noted, "Deep venous thrombosis and pulmonary embolism are the major side effects of thalidomide and lenalidomide. Lenalidomide causes more myelosuppression, and thalidomide causes more sedation. Chemotherapy-induced peripheral neuropathy and thrombocytopenia are major side effects of bortezomib."Treatment of related hyperviscosity syndrome may be required to prevent neurologic symptoms or kidney failure. Maintenance Most people, including those treated with ASCT, relapse after initial treatment. Maintenance therapy using a prolonged course of low-toxicity medications is often used to prevent relapse. A 2017 meta-analysis showed that post-ASCT maintenance therapy with lenalidomide improved progression-free survival and overall survival in people at standard risk. A 2012 clinical trial showed that people with intermediate- and high-risk disease benefit from a bortezomib-based maintenance regimen. Relapse Reasons for relapse include disease evolution, either from the selective pressure applied by treatment or by de novo mutations and/or if disease was inadequately represented in the initial biopsy. Relapse within the first 18 months of diagnosis is considered as functional high risk multiple myeloma. Depending on the persons condition, the prior treatment modalities used and the duration of remission, options for relapsed disease include retreatment with the original agent, use of other agents (such as melphalan, cyclophosphamide, thalidomide, or dexamethasone, alone or in combination), and a second ASCT. Later in the course of the disease, it becomes refractory (resistant) to formerly effective treatment. This stage is referred to as relapsed/refractory multiple myeloma (RRMM). Treatment modalities that are commonly use to treat RRMM include dexamethasone, proteasome inhibitors (e.g. bortezomib and carfilzomib), immunomodulatory imide drugs (e.g. thalidomide, lenalidomide, and pomalidomide), and certain monoclonal antibodies (e.g. against CD38 and CD319). Survival expectancy has risen in recent years, and new treatments are under development.Kidney failure in multiple myeloma can be acute (reversible) or chronic (irreversible). Acute kidney failure typically resolves when the calcium and paraprotein levels are brought under control. Treatment of chronic kidney failure is dependent on the type of kidney failure and may involve dialysis. Several newer options are approved for the management of advanced disease: belantamab mafodotin — a monoclonal antibody against B-cell maturation antigen (BCMA), also known as CD269, indicated for the treatment of adults with relapsed or refractory multiple myeloma who have received at least four prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. carfilzomib—a proteasome inhibitor that is indicated: as a single agent in people who have received one or more lines of therapy in combination with dexamethasone or with lenalidomide and dexamethasone in people who have received one to three lines of therapy daratumumab—a monoclonal antibody against CD38 indicated in people who have received at least three prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent or who are double refractory to a proteasome inhibitor and an immunomodulatory agent elotuzumab—an immunostimulatory humanized monoclonal antibody against SLAMF7 (also known as CD319) indicated in combination with lenalidomide and dexamethasone in people who have received one to three prior therapies isatuximab—a monoclonal antibody against CD38 indicated in combination with pomalidomide and dexamethasone for the treatment of adults with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor. ixazomib—an orally available proteasome inhibitor indicated in combination with lenalidomide and dexamethasone in people who have received at least one prior therapy panobinostat—an orally available histone deacetylase inhibitor used in combination with bortezomib and dexamethasone in people who have received at least two prior chemotherapy regimens, including bortezomib and an immunomodulatory agent selinexor—an orally available selective inhibitor of nuclear export indicated in combination with dexamethasone in people who have received at least four prior therapies and whose disease does not respond to at least two proteasome inhibitors, two immunomodulatory agents and an anti-CD38 monoclonal antibody idecabtagene vicleucel—first cell-based gene therapy was approved by FDA in 2021 for the treatment of adults with relapsed or refractory multiple myeloma who have received at least four prior therapies Stem cell transplant Stem cell transplant can be used to treat multiple myeloma. Stem cell transplants come with a risk of a graft-versus-host-disease. Mesenchymal stromal cells may reduce the all-cause mortality if they are used for a therapeutic reason and the therapeutic use of MSCs may increase the complete response of acute and chronic GvHD, but the evidence is very uncertain. The evidence suggests that MSCs for prophylactic reason result in little to no difference in the all-cause mortality, in the relapse of malignant diseases and in the incidence of acute GvHD. The evidence suggests that MSCs for prophylactic reason reduce the incidence of chronic GvHD. Gene therapy idecabtagene vicleucel (Abecma) – first cell-based gene therapy was approved by FDA in 2021 for the treatment of adults with relapsed or refractory multiple myeloma who have received at least four prior therapies ciltacabtagene autoleucel (Carvykti) was approved for medical use in the United States in February 2022. Ciltacabtagene autoleucel is indicated for the treatment of adults with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Other measures In addition to direct treatment of the plasma cell proliferation, bisphosphonates (e.g., pamidronate or zoledronic acid) are routinely administered to prevent fractures; they have also been observed to have a direct antitumor effect even in people without known skeletal disease. If needed, red blood cell transfusions or erythropoietin can be used for management of anemia. Side effects Chemotherapies and stem cell transplants can cause unwanted bleedings and may require platelet transfusions. It was seen that platelet transfusions for people undergoing a chemotherapy or a stem cell transplantation for the prevention of bleeding events had different effects on the number of participants with a bleeding event, the number of days on which a bleeding occurred, the mortality secondary to bleeding and the number of platelet transfusions depending on the way they were used (therapeutic, depending on a threshold, different dose schedules or prophylactic). Supportive treatment Adding physical exercises to the standard treatment for adult patients with haematological malignancies like multiple myeloma may result in little to no difference in the mortality, in the quality of life and in the physical functioning. These exercises may result in a slight reduction in depression. Furthermore, aerobic physical exercises probably reduce fatigue. The evidence is very uncertain about the effect and serious adverse events Palliative care Multiple national cancer treatment guidelines recommend early palliative care for people with advanced multiple myeloma at the time of diagnosis and for anyone who has significant symptoms.Palliative care is appropriate at any stage of multiple myeloma and can be provided alongside curative treatment. In addition to addressing symptoms of cancer, palliative care helps manage unwanted side effects, such as pain and nausea related to treatments. Teeth Oral prophylaxis, hygiene instruction and elimination of sources of infection within the mouth before beginning cancer treatment, can reduce the risk of infectious complications. Before starting bisphosphonates therapy, the persons dental health should be evaluated to assess the risk factors to prevent the development of medication-related osteonecrosis of the jaw (MRONJ). If there are any symptoms or radiographic appearance of MRONJ like jaw pain, loose tooth, mucosal swelling, early referral to an oral surgeon is recommended. Dental extractions should be avoided during the active period of treatment and treat the tooth with nonsurgical root canal treatment instead. Prognosis Overall the 5-year survival rate is around 54% in the United States. With high-dose therapy followed by ASCT, the median survival has been estimated in 2003 to be about 4.5 years, compared to a median around 3.5 years with "standard" therapy.The international staging system can help to predict survival, with a median survival (in 2005) of 62 months for stage-1 disease, 45 months for stage-2 disease, and 29 months for stage-3 disease. The median age at diagnosis is 69 years. Genetic testing SNP array karyotyping can detect copy number alterations of prognostic significance that may be missed by a targeted FISH panel. Epidemiology Globally, multiple myeloma affected 488,000 people and resulted in 101,100 deaths in 2015. This is up from 49,000 in 1990. United States In the United States in 2016, an estimated 30,330 new cases and 12,650 deaths were reported. These numbers are based on assumptions made using data from 2011, which estimated the number of people affected as 83,367 people, the number of new cases as 6.1 per 100,000 people per year, and the mortality as 3.4 per 100,000 people per year. Multiple myeloma is the second-most prevalent blood cancer (10%) after non-Hodgkins lymphoma. It represents about 1.8% of all new cancers and 2.1% of all cancer deaths.Multiple myeloma affects slightly more men than women. African Americans and native Pacific Islanders have the highest reported number of new cases of this disease in the United States and Asians the lowest. Results of one study found the number of new cases of myeloma to be 9.5 cases per 100,000 African Americans and 4.1 cases per 100,000 Caucasian Americans. Among African Americans, myeloma is one of the top-10 causes of cancer death. UK Myeloma is the 17th-most common cancer in the UK: around 4,800 people were diagnosed with the disease in 2011. It is the 16th-most common cause of cancer death: around 2,700 people died of it in 2012. Other animals Multiple myeloma has been diagnosed in dogs, cats, and horses.In dogs, multiple myeloma accounts for around 8% of all haemopoietic tumors. Multiple myeloma occurs in older dogs and is not particularly associated with either males or females. No breeds appear overrepresented in case reviews that have been conducted. Diagnosis in dogs is usually delayed due to the initial nonspecificity and range of clinical signs possible. Diagnosis usually involves bone-marrow studies, X-rays, and plasma-protein studies. In dogs, protein studies usually reveal the monoclonal gammaglobulin elevation to be IgA or IgG in equal number of cases. In rare cases the globulin elevation is IgM, which is referred to as Waldenströms macroglobulinemia. The prognosis for initial control and return to good quality of life in dogs is good; 43% of dogs started on a combination chemotherapeutic protocol achieved complete remission. Long-term survival is normal, with a median of 540 days reported. The disease eventually recurs, becoming resistant to available therapies. The complications of kidney failure, sepsis, or pain can lead to an animals death, frequently by euthanasia. See also References External links Multiple myeloma at Curlie
Myocarditis	Myocarditis, also known as inflammatory cardiomyopathy, is an acquired cardiomyopathy due to inflammation of the heart muscle. Symptoms can include shortness of breath, chest pain, decreased ability to exercise, and an irregular heartbeat. The duration of problems can vary from hours to months. Complications may include heart failure due to dilated cardiomyopathy or cardiac arrest.Myocarditis is most often due to a viral infection. Other causes include bacterial infections, certain medications, toxins and autoimmune disorders. A diagnosis may be supported by an electrocardiogram (ECG), increased troponin, heart MRI, and occasionally a heart biopsy. An ultrasound of the heart is important to rule out other potential causes such as heart valve problems.Treatment depends on both the severity and the cause. Medications such as ACE inhibitors, beta blockers, and diuretics are often used. A period of no exercise is typically recommended during recovery. Corticosteroids or intravenous immunoglobulin (IVIG) may be useful in certain cases. In severe cases an implantable cardiac defibrillator or heart transplant may be recommended.In 2013, about 1.5 million cases of acute myocarditis occurred. While people of all ages are affected, the young are most often affected. It is slightly more common in males than females. Most cases are mild. In 2015 cardiomyopathy, including myocarditis, resulted in 354,000 deaths up from 294,000 in 1990. The initial descriptions of the condition are from the mid-1800s. Signs and symptoms The signs and symptoms associated with myocarditis are varied, and relate either to the actual inflammation of the myocardium or to the weakness and dysfunction of the heart muscle that is secondary to the inflammation. While myocarditis may develop over periods ranging from hours to months, patients typically present with signs and symptoms that resemble heart failure, including the following: Since myocarditis is often due to a viral illness, many patients experience symptoms consistent with a recent viral infection including a fever, rash, loss of appetite, abdominal pain, vomiting, diarrhea, joint pains, and easily becoming tired. Additionally, myocarditis is often associated with pericarditis, and many people with myocarditis present with signs and symptoms that suggest myocarditis and pericarditis at the same time.Children primarily present with the aforementioned symptoms associated with a viral infection. Since they overlap with many other illnesses, this can make it more challenging to diagnose myocarditis in younger patients. Later stages of the illness can involve the respiratory system and lead to increased work of breathing. These are often mistaken for asthma.Myocarditis can be distinguished as either fulminant or acute based on the severity of symptoms on presentation, as well as the time course over which symptoms develop and persist. This categorization can help predict the treatment, outcomes, and complications of myocarditis. Fulminant myocarditis is defined as sudden and severe myocarditis that is associated with signs and symptoms of heart failure while at rest. More specifically, fulminant myocarditis is characterized by a distinct, rapid onset of severe heart failure symptoms, such as shortness of breath and chest pain, that develop over the course of hours to days. Additionally, treatment requires the use of medications or mechanical devices to improve heart function.Acute non-fulminant myocarditis has a less distinct onset in contrast to fulminant myocarditis, and evolves over days to months. While the symptoms of acute myocarditis overlap with those of fulminant myocarditis, they do not typically occur at rest, and treatment does not require the use of mechanical circulatory support. Causes While many causes of myocarditis are known, there are many cases in which a causative agent cannot be identified. In Europe and North America, viruses are common culprits. Worldwide, however, the most common cause is Chagas disease, an illness endemic to Central and South America that results from infection with the protozoan Trypanosoma cruzi. Overall, myocarditis can be caused by infections, immune conditions, toxins, drug reactions, and physical injuries to the heart. These different etiologies are detailed below. Myocarditis is a rare adverse side effect from mRNA COVID-19 vaccines. Infections The most common causes of myocarditis are infectious organisms. Viral infections are the most common cause in developed countries, with a majority of cases being caused by those with single-stranded RNA genetic information such as Coxsackie viruses (especially Coxsackie B3 and B5). Globally, Chagas disease is the leading cause of myocarditis, which results from infection with the protozoan Trypanosoma cruzi. Bacteria can also result in myocarditis, although it is rare in patients with normal heart function and without a preexisting immunodeficiency. A list of the most relevant infectious organisms is below. Viral: adenovirus, parvovirus B19, coxsackie virus, rubella virus, polio virus, Epstein-Barr virus, hepatitis C virus, and severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2, causing COVID-19) Protozoan: Trypanosoma cruzi and Toxoplasma gondii (causing Chagas disease and toxoplasmosis, respectively) Bacterial: Brucella, Corynebacterium diphtheriae, Neisseria gonorrhoeae, Haemophilus influenzae, Actinomyces, Tropheryma whipplei, Vibrio cholerae, Borrelia burgdorferi, Leptospira, Rickettsia, Mycoplasma pneumoniae Fungal: Aspergillus Parasitic: Ascaris, Echinococcus granulosus, Paragonimus westermani, Schistosoma, Taenia solium, Trichinella spiralis, visceral larva migrans, Wuchereria bancrofti Immune conditions Allergic reaction (e.g., to acetazolamide or amitriptyline) Kawasaki disease Autoimmunity (scleroderma, lupus, sarcoidosis, and systemic vasculitides) Toxic shock syndrome Drug reactions and toxins Anthracyclines and other forms of chemotherapy Antipsychotics including clozapine Alcohol Stimulants such as mephedrone and cocaine Arsenic Carbon monoxide Snake venom Heavy metals (copper or iron) Vaccination Myocarditis and pericarditis can be a rare side effect of some vaccines like the smallpox vaccine. Some COVID-19 vaccination doses carry a very small risk (33 per million overall) of causing myocarditis and pericarditis, more so in young men at repeated administration. According to a meta-analysis that does not differentiate between the two mRNA-vaccines BNT162b2 and mRNA-1273, the risk is less than that associated with COVID-19 itself. In adolescent males aged 16 to 17 years the crude reporting rate of myocarditis was 105.9 per million doses of the BNT162b2 vaccine. Physical injuries Electric shock Hyperpyrexia, and radiation Mechanism Most forms of myocarditis involve the infiltration of heart tissues by one or two types of pro-inflammatory blood cells, lymphocytes and macrophages plus two respective descendants of these cells, NK cells and macrophages. Eosinophilic myocarditis is a subtype of myocarditis in which cardiac tissue is infiltrated by another type of pro-inflammatory blood cell, the eosinophil. Eosinophilic myocarditis is further distinguished from non-eosinophilic myocarditis by having a different set of causes and recommended treatments. Coxsackie B, specifically B3 and B5, has been found to interact with coxsackievirus-adenovirus receptor (CAR) and decay-accelerating factor (DAF). However, other proteins have also been identified that allow Coxsackieviruses to bind to cardiac cells. The natural function of CAR and mechanism that the Coxsackievirus uses to infect the cardiac muscle is still unknown. The mechanism by which coxsackie B viruses (CBVs) trigger inflammation is believed to be through the recognition of CBV virions by Toll-like receptors.The binding of the SARS-CoV-2 virus through ACE2 receptors present in heart tissue may be responsible for direct viral injury leading to myocarditis. In a study done during the SARS outbreak, SARS virus RNA was ascertained in the autopsy of heart specimens in 35% of the patients who died due to SARS. It was also observed that an already diseased heart has increased expression of ACE2 receptor contrasted to healthy individuals. Hyperactive immune responses in COVID-19 Patients may lead to the initiation of the cytokine storm. This excess release of cytokines may lead to myocardial injury. Diagnosis Myocarditis refers to an underlying process that causes inflammation and injury of the heart. It does not refer to inflammation of the heart as a consequence of some other insult. Many secondary causes, such as a heart attack, can lead to inflammation of the myocardium and therefore the diagnosis of myocarditis cannot be made by evidence of inflammation of the myocardium alone.Myocardial inflammation can be suspected on the basis of electrocardiographic (ECG) results, elevated C-reactive protein (CRP) and/or erythrocyte sedimentation rate (ESR), and increased IgM (serology) against viruses known to affect the myocardium. Markers of myocardial damage (troponin or creatine kinase cardiac isoenzymes) are elevated.The ECG findings most commonly seen in myocarditis are diffuse T wave inversions; saddle-shaped ST-segment elevations may be present (these are also seen in pericarditis).The gold standard is the biopsy of the myocardium, in general done in the setting of angiography. A small tissue sample of the endocardium and myocardium is taken and investigated. The cause of the myocarditis can be only identified by a biopsy. Endomyocardial biopsy samples are assessed for histopathology (how the tissue looks like under the microscope): myocardial interstitium may show abundant edema and inflammatory infiltrate, rich in lymphocytes and macrophages. Focal destruction of myocytes explains the myocardial pump failure. In addition samples may be assessed with immunohistochemistry to determine which types of immune cells are involved in the reaction and how they are distributed. Furthermore, PCR and/or RT-PCR may be performed to identify particular viruses. Finally, further diagnostic methods like microRNA assays and gene-expression profile may be performed.Cardiac magnetic resonance imaging (cMRI or CMR) has been shown to be very useful in diagnosing myocarditis by visualizing markers for inflammation of the myocardium. Consensus criteria for the diagnosis of myocarditis by CMR were published in 2009. Treatment While myocarditis has many etiologies and a variable constellation of signs and symptoms, there are few causes that are treatable and thus the main focus is on symptom management. In cases with biopsy-proven myocarditis, the causative cell type can indicate potentially beneficial treatments. These treatments typically consist of corticosteroids, or medications with known benefits in certain autoimmune and systemic conditions. In a majority of cases, the main therapies are used to support patients and are dependent on the severity of symptoms and the time course across which myocarditis develops. Supportive therapies can be divided into two broad categories, medications and mechanical support, since there has yet to be any demonstrated benefits from complementary therapies. Medication The specific medications that are used to support patients are directly related to the cause of the symptom or sign. Just as the symptoms of myocarditis mirror those of congestive heart failure, so too do the therapies. Additionally, the order in which therapies are used depends on the degree of heart dysfunction, with stabilization of patient blood pressure and breathing taking highest priority when present. This can involve the use of inotropes, or medications that make the heart contract with greater force, as well as antiarrhythmic drugs such as adenosine or carvedilol. In patients that have stable and adequate heart function, further treatments are based on heart failure guidelines. ACE inhibitors can have a protective benefit to the heart, so they are typically used in any patient with symptomatic myocarditis. Simultaneously, beta blockers are used in patients that can tolerate their heart beating at a slower rate. Shortness of breath at rest and swelling can be relieved with diuretics such as furosemide, and the addition of aldosterone receptor blockers can augment the diuresis while preventing the excess loss of potassium. In patients with symptoms while resting, additional medications can be added such as digoxin. Mechanical support Mechanical support is used in cases of myocarditis in which medications alone do not lead to adequate heart function and the body requires additional support to achieve organ perfusion. Myocarditis cases that require mechanical circulatory support are categorized as fulminant by definition. People that require additional support with their heart function can benefit from the use of ventricular assist devices like intra-aortic balloon pumps. In people with myocarditis severe enough to cause cardiac arrest, extracorporeal membrane oxygenation (ECMO) is used to adequately pump blood and provide oxygen if needed. Both ventricular assist devices and ECMO can be used as bridge therapy until heart transplantation in patients that are candidates. Heart transplantation is reserved for those that do not respond to the aforementioned conventional medical therapies. Prognosis The prognosis associated with myocarditis is stratified by the severity and time course along which symptoms develop. In addition to symptom severity, there are also several indicators of heart function that can be used to predict patient outcomes, many of which are part of the standard evaluation of patients presenting with cardiovascular dysfunction. An electrocardiogram is one of the most common screening tools used in cases of suspected cardiac pathology, such as myocarditis. The findings that correlate with poorer outcomes are non-specific and include widened QRS complexes and QT intervals, partial or complete atrial-ventricular heart block, and malignant ventricular arrhythmias like sustained ventricular tachycardia or ventricular fibrillation. Electrocardiogram findings of ST elevations with upward concavity and an early repolarization pattern, however, were associated with a better cardiovascular prognosis in general.In cases of acute myocarditis, cardiac magnetic resonance imaging can reveal several prognostic indicators that, similar to ECGs, are non-specific and reflect poorer cardiac physiology. Late gadolinium enhancement on cardiac MRI demonstrates perturbations in extracellular volume as a result of cell necrosis or edema, and is significantly associated with increases in all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events. The association was strongest with any late gadolinium enhancement, but remained true for findings of anterolateral-specific enhancement. A similar relationship was found between a left ventricular ejection fraction < 50%, increased mortality, and increased major adverse cardiovascular events.Myocarditis has been reported to be a major cause of sudden cardiac death (SCD) in infants, adolescents, and young adults, but the reported rates show wide variation (1 to 14 percent) among young people depending on differences in SCD definition and classification/ definition of myocarditis post-mortem as well as inhomogeneity in the study populations. And one has also to distinguish between studies about myocarditis in general and fulminant myocarditis. Epidemiology The exact incidence of myocarditis is unknown since many cases are not associated with any symptoms. However, in series of routine autopsies, 1–9% of all patients had evidence of myocardial inflammation. The prevalence rate of myocarditis is estimated to be about 22 cases per 100,000 persons annually. Fulminant myocarditis, the most severe subtype, has been shown to occur in up to 2.5% of known myocarditis presentations. When looking at different causes of myocarditis, viral infection is the most prevalent, especially in children; however, the prevalence rate of myocarditis is often underestimated since the condition is easily overlooked. Viral myocarditis being an outcome of viral infection depends heavily on genetic host factors and the pathogenicity unique to the virus. If one tests positive for an acute viral infection, clinical developments have discovered that 1-5% of said population may show some form of myocarditis.In regard to the population affected, myocarditis is more common in pregnant women, children, and those who are immunocompromised. Myocarditis, however, has shown to be more common in the male population than in the female. Multiple studies report a 1:1.3-1.7 female-male ratio of prevalence of myocarditis. In young adults, up to 20% of all cases of sudden death are due to myocarditis. Young males specifically have a higher incidence rate than any other population due to their testosterone levels creating a greater inflammatory response that increases the chance of cardiac pathologies. While males tend to have a higher risk of developing myocarditis, females tend to display more severe signs and symptoms, such as ventricular tachycardia and ventricular fibrillation, but do so at an older age. Among patients with HIV, myocarditis is the most common cardiac pathological finding at autopsy, with a prevalence of 50% or more.Myocarditis is the third most common cause of death among young adults with a cumulative incidence rate globally of 1.5 cases per 100,000 persons annually. Myocarditis accounts for approximately 20% of sudden cardiac death in a variety of populations, including adults under the age of 40, young athletes, United States Air Force recruits, and elite Swedish orienteers. With individuals who develop myocarditis, the first year is difficult as a collection of cases have shown there is a 20% mortality rate. Myocarditis in COVID-19 One notable instance of viral myocarditis is the involvement of the SARS-CoV-2 virus; myocarditis from SARS-CoV-2 is associated with a spectrum of severities from asymptomatic to fulminant, and is a complication in approximately 2-7% of COVID-19 cases. History Cases of myocarditis have been documented as early as the 1600s, but the term "myocarditis", implying an inflammatory process of the myocardium, was introduced by German physician Joseph Friedrich Sobernheim in 1837. However, the term has been confused with other cardiovascular conditions, such as hypertension and ischemic heart disease. Following admonition regarding the indiscriminate use of myocarditis as a diagnosis from authorities such as British cardiologist Sir Thomas Lewis and American cardiologist and a co-founder of the American Heart Association Paul White, myocarditis was under-diagnosed.Although myocarditis is clinically and pathologically clearly defined as "inflammation of the myocardium", its definition, classification, diagnosis, and treatment are subject to continued controversy, but endomyocardial biopsy has helped define the natural history of myocarditis and clarify clinicopathological correlations. See also Viral cardiomyopathy Eosinophilic myocarditis Myopericarditis References External links Myocarditis at eMedicine
Lymphomatoid papulosis	Lymphomatoid papulosis (LyP) is a rare skin disorder. The overall prevalence rate of lymphomatoid papulosis is estimated at 1.2 to 1.9 cases per 1,000,000 population. [This is a widespread misinterpretation of a 1992 study saying "the period prevalence rate of lymphomatoid papulosis was estimated to be 1.9 per 1,000,000 population for Massachusetts and 1.2 per 1,000,000 population for Pennsylvania". The authors of that study said clearly "Our estimate of 1.2-1.9 cases per 1,000,000 population should be considered a minimum estimate of the prevalence rate". That estimate was based on the 78 patients involved in the study, not the LvP population. The study recruited 11 patients from Massachusetts and 15 from Pennsylvania ]. This rare condition has only been studied in depth since 1968. Presentation It can appear very similar to anaplastic large cell lymphoma. Type "A" is CD30 positive, while type "B" is CD30 negative.It has been described as "clinically benign but histologically malignant." Treatment It may respond to methotrexate or PUVA. Prognosis It can evolve into lymphoma. See also Cutaneous T-cell lymphoma Parapsoriasis Secondary cutaneous CD30+ large cell lymphoma List of cutaneous conditions References == External links ==
Hyperhidrosis	Hyperhidrosis is a condition characterized by abnormally increased sweating, in excess of that required for regulation of body temperature. Although primarily a benign physical burden, hyperhidrosis can deteriorate quality of life from a psychological, emotional, and social perspective. This excess of sweat happens even if the person is not engaging in tasks that require muscular effort, and it does not depend on the exposure to heat. Common places to sweat can include underarms, face, neck, back, groin, feet, and hands. It has been called by some researchers the silent handicap.Both diaphoresis and hidrosis can mean either perspiration (in which sense they are synonymous with sweating) or excessive perspiration, in which case they refer to a specific, narrowly defined, clinical disorder. Classification Hyperhidrosis can either be generalized, or localized to specific parts of the body. Hands, feet, armpits, groin, and the facial area are among the most active regions of perspiration due to the high number of sweat glands (eccrine glands in particular) in these areas. When excessive sweating is localized (e.g. palms, soles, face, underarms, scalp) it is referred to as primary hyperhidrosis or focal hyperhidrosis. Excessive sweating involving the whole body is termed generalized hyperhidrosis or secondary hyperhidrosis. It is usually the result of some other, underlying condition. Primary or focal hyperhidrosis may be further divided by the area affected, for instance, palmoplantar hyperhidrosis (symptomatic sweating of only the hands or feet) or gustatory hyperhidrosis (sweating of the face or chest a few moments after eating certain foods).Hyperhidrosis can also be classified by onset, either congenital (present at birth) or acquired (beginning later in life). Primary or focal hyperhidrosis usually starts during adolescence or even earlier and seems to be inherited as an autosomal dominant genetic trait. It must be distinguished from secondary hyperhidrosis, which can start at any point in life. Secondary hyperhidrosis may be due to a disorder of the thyroid or pituitary glands, diabetes mellitus, tumors, gout, menopause, certain drugs, or mercury poisoning.One classification scheme uses the amount of skin affected. In this scheme, excessive sweating in an area of 100 square centimeters (16 square inches) or more is differentiated from sweating that affects only a small area.Another classification scheme is based on possible causes of hyperhidrosis. Causes The cause of primary hyperhidrosis is unknown. Anxiety or excitement can exacerbate the condition. A common complaint of patients is they get nervous because they sweat, then sweat more because they are nervous. Other factors can play a role, including certain foods and drinks, nicotine, caffeine, and smells. Similarly, secondary (generalized) hyperhidrosis has many causes including certain types of cancer, disturbances of the endocrine system, infections, and medications. Primary Primary (focal) hyperhidrosis has many causes. Idiopathic unilateral circumscribed hyperhidrosis Reported association with: Blue rubber bleb nevus Glomus tumor POEMS syndrome Burning feet syndrome (Gopalans) Trench foot Causalgia Pachydermoperiostosis Pretibial myxedema Gustatory sweating associated with: Encephalitis Syringomyelia Diabetic neuropathies Herpes zoster (shingles) Parotitis Parotid abscesses Thoracic sympathectomy Auriculotemporal or Freys syndrome Miscellaneous Lacrimal sweating (due to postganglionic sympathetic deficit, often seen in Raeders syndrome) Harlequin syndrome Emotional hyperhidrosis Cancer A variety of cancers have been associated with the development of secondary hyperhidrosis including lymphoma, pheochromocytoma, carcinoid tumors (resulting in carcinoid syndrome), and tumors within the thoracic cavity. Endocrine Certain endocrine conditions are also known to cause secondary hyperhidrosis including diabetes mellitus (especially when blood sugars are low), acromegaly, hyperpituitarism, pheochromocytoma (tumor of the adrenal glands, present in 71% of patients) and various forms of thyroid disease. Medications Use of selective serotonin reuptake inhibitors (e.g., sertraline) is a common cause of medication-induced secondary hyperhidrosis. Other medications associated with secondary hyperhidrosis include tricyclic antidepressants, stimulants, opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), glyburide, insulin, anxiolytic agents, adrenergic agonists, and cholinergic agonists. Miscellaneous In people with a history of spinal cord injuries Autonomic dysreflexia Orthostatic hypotension Posttraumatic syringomyelia Associated with peripheral neuropathies Familial dysautonomia (Riley-Day syndrome) Congenital autonomic dysfunction with universal pain loss Exposure to cold, notably associated with cold-induced sweating syndrome Associated with probable brain lesions Episodic with hypothermia (Hines and Bannick syndrome) Episodic without hypothermia Olfactory Associated with systemic medical problems Parkinsons disease Fibromyalgia Congestive heart failure Anxiety Obesity Menopausal state Night sweats Compensatory Infantile acrodynia induced by chronic low-dose mercury exposure, leading to elevated catecholamine accumulation and resulting in a clinical picture resembling pheochromocytoma. Febrile diseases Vigorous exercise A hot, humid environment Diagnosis Symmetry of excessive sweating in hyperhidrosis is most consistent with primary hyperhidrosis. To diagnose this condition, a dermatologist gives the patient a physical exam. This includes looking closely at the areas of the body that sweat excessively. A dermatologist also asks very specific questions. This helps the doctor understand why the patient has excessive sweating. Sometimes medical testing is necessary. Some patients require a test called the sweat test. This involves coating some of their skin with a powder that turns purple when the skin gets wet. Excessive sweating affecting only one side of the body is more suggestive of secondary hyperhidrosis and further investigation for a neurologic cause is recommended. Treatment Antihydral cream is one of the solutions prescribed for hyperhidrosis for palms. Topical agents for hyperhidrosis therapy include formaldehyde lotion, topical anticholinergics etc. These agents reduce perspiration by denaturing keratin, in turn occluding the pores of the sweat glands. They have a short-lasting effect. Formaldehyde is classified as a probable human carcinogen. Contact sensitization is increased, especially with formalin. Aluminium chlorohydrate is used in regular antiperspirants. However, hyperhidrosis requires solutions or gels with a much higher concentration. These antiperspirant solutions or hyperhidrosis gels are especially effective for treatment of axillary or underarm regions. Normally it takes around three to five days to see improvement. The most common side-effect is skin irritation. For severe cases of plantar and palmar hyperhidrosis, there has been some success with conservative measures such as higher strength aluminium chloride antiperspirants. Treatment algorithms for hyperhidrosis recommend topical antiperspirants as the first line of therapy for hyperhidrosis. Both the International Hyperhidrosis Society and the Canadian Hyperhidrosis Advisory Committee have published treatment guidelines for focal hyperhidrosis that are said to be evidence-based. Prescription medications called anticholinergics, often taken by mouth, are sometimes used in the treatment of both generalized and focal hyperhidrosis. Anticholinergics used for hyperhidrosis include propantheline, glycopyrronium bromide or glycopyrrolate, oxybutynin, methantheline, and benzatropine. Use of these drugs can be limited, however, by side-effects, including dry mouth, urinary retention, constipation, and visual disturbances such as mydriasis (dilation of the pupils) and cycloplegia. For people who find their hyperhidrosis is made worse by anxiety-provoking situations (public speaking, stage performances, special events such as weddings, etc.), taking an anticholinergic medicine before the event may be helpful.Several anticholinergic drugs can reduce hyperhidrosis. Oxybutynin (brand name Ditropan) is one that has shown promise, although it can have side-effects, such as drowsiness, visual symptoms and dryness of the mouth and other mucous membranes. Glycopyrrolate is another drug sometimes used. It is said to be nearly as effective as oxybutynin, but has similar side-effects. In 2018, the U.S. Food and Drug Administration (FDA) approved a glycopyrronium bromide-containing disposable cloth (brand name Qbrexza) for the treatment of primary axillary hyperhidrosis.For peripheral hyperhidrosis, some chronic patients have found relief by simply ingesting crushed ice water. Ice water helps to cool excessive body heat during its transport through the blood vessels to the extremities, effectively lowering overall body temperature to normal levels within ten to thirty minutes. Procedures Injections of botulinum toxin type A can be used to block neural control of sweat glands. The effect can last from 3–9 months depending on the site of injections. This use has been approved by the U.S. Food and Drug Administration (FDA). The duration of the beneficial effect in primary palmar hyperhidrosis has been found to increase with repetition of the injections. The Botox injections tend to be painful. Various measures have been tried to minimize the pain, one of which is the application of ice. This was first demonstrated by Khalaf Bushara and colleagues as the first nonmuscular use of BTX-A in 1993. BTX-A has since been approved for the treatment of severe primary axillary hyperhidrosis (excessive underarm sweating of unknown cause), which cannot be managed by topical agents.A microwave-based device has been tried for excessive underarm perspiration and appears to show promise.Tap water iontophoresis as a treatment for palmoplantar hyperhidrosis was originally described in the 1950s. Studies showed positive results and good safety with tap water iontophoresis. One trial found it decreased sweating by about 80%. Surgery Sweat gland removal or destruction is one surgical option available for axillary hyperhidrosis (excessive underarm perspiration). There are multiple methods for sweat gland removal or destruction, such as sweat gland suction, retrodermal curettage, and axillary liposuction, Vaser, or Laser Sweat Ablation. Sweat gland suction is a technique adapted for liposuction.The other main surgical option is endoscopic thoracic sympathectomy (ETS), which cuts, burns, or clamps the thoracic ganglion on the main sympathetic chain that runs alongside the spine. Clamping is intended to permit the reversal of the procedure. ETS is generally considered a "safe, reproducible, and effective procedure and most patients are satisfied with the results of the surgery". Satisfaction rates above 80% have been reported, and are higher for children. The procedure brings relief from excessive hand sweating in about 85–95% of patients. ETS may be helpful in treating axillary hyperhidrosis, facial blushing and facial sweating, but failure rates in patients with facial blushing and/or excessive facial sweating are higher and such patients may be more likely to experience unwanted side effects.ETS side-effects have been described as ranging from trivial to devastating. The most common side-effect of ETS is compensatory sweating (sweating in different areas than prior to the surgery). Major problems with compensatory sweating are seen in 20–80% of patients undergoing the surgery. Most people find the compensatory sweating to be tolerable while 1–51% claim that their quality of life decreased as a result of compensatory sweating." Total body perspiration in response to heat has been reported to increase after sympathectomy. The original sweating problem may recur due to nerve regeneration, sometimes as early as 6 months after the procedure.Other possible side-effects include Horners Syndrome (about 1%), gustatory sweating (less than 25%) and excessive dryness of the palms (sandpaper hands). Some patients have experienced cardiac sympathetic denervation, which can result in a 10% decrease in heart rate both at rest and during exercise, resulting in decreased exercise tolerance.Percutaneous sympathectomy is a minimally invasive procedure similar to the botulinum method, in which nerves are blocked by an injection of phenol. The procedure provides temporary relief in most cases. Some physicians advocate trying this more conservative procedure before resorting to surgical sympathectomy, the effects of which are usually not reversible. Prognosis Hyperhidrosis can have physiological consequences such as cold and clammy hands, dehydration, and skin infections secondary to maceration of the skin. Hyperhidrosis can also have devastating emotional effects on ones individual life.Those with hyperhidrosis may have greater stress levels and more frequent depression.Excessive sweating or focal hyperhidrosis of the hands interferes with many routine activities, such as securely grasping objects. Some people with focal hyperhidrosis sufferers avoid situations where they will come into physical contact with others, such as greeting a person with a handshake. Hiding embarrassing sweat spots under the armpits limits the affected persons arm movements and pose. In severe cases, shirts must be changed several times during the day and require additional showers both to remove sweat and control body odor issues or microbial problems such as acne, dandruff, or athletes foot. Additionally, anxiety caused by self-consciousness to the sweating may aggravate the sweating. Excessive sweating of the feet makes it harder for patients to wear slide-on or open-toe shoes, as the feet slide around in the shoe because of sweat.Some careers present challenges for people with hyperhidrosis. For example, careers that require the use of a knife may not be safely performed by people with excessive sweating of the hands. The risk of dehydration can limit the ability of some to function in extremely hot (especially if also humid) conditions. Even the playing of musical instruments can be uncomfortable or difficult because of sweaty hands. Epidemiology It is estimated that the incidence of focal hyperhidrosis may be as high as 2.8% of the population of the United States. It affects men and women equally, and most commonly occurs among people aged 25–64 years, though some may have been affected since early childhood. About 30–50% of people have another family member affected, implying a genetic predisposition.In 2006, researchers at Saga University in Japan reported that primary palmar hyperhidrosis maps to gene locus 14q11.2–q13. References == External links ==
Entropion	Entropion is a medical condition in which the eyelid (usually the lower lid) folds inward. It is very uncomfortable, as the eyelashes continuously rub against the cornea causing irritation. Entropion is usually caused by genetic factors. This is different from when an extra fold of skin on the lower eyelid causes lashes to turn in towards the eye (epiblepharon). In epiblepharons, the eyelid margin itself is in the correct position, but the extra fold of skin causes the lashes to be misdirected. Entropion can also create secondary pain of the eye (leading to self trauma, scarring of the eyelid, or nerve damage). The upper or lower eyelid can be involved, and one or both eyes may be affected. When entropion occurs in both eyes, this is known as "bilateral entropion". Repeated cases of trachoma infection may cause scarring of the inner eyelid, which may cause entropion. In human cases, this condition is most common to people over 60 years of age. Symptoms Symptoms of entropion include: Redness and pain around the eye Sensitivity to light and wind Sagging skin around the eye Eye watering Decreased vision, especially if the cornea is damaged Causes Congenital Aging creating loose skin and stretched and loose ligaments and muscles (senile entropion). Scarring (mechanical entropion) Spasm An eye infection called trachoma is still common in North Africa and South Asia and this can cause scarring of the inner eyelid, which may cause friction and entropion. Treatment Treatment is a relatively simple surgery in which excess skin of the outer lids is removed or tendons and muscles are shortened with one or two stitches. General anesthesia is sometimes used before local anesthetics are injected into the muscles around the eye. Prognosis is excellent if surgery is performed before the cornea is damaged. Entropion in other species Entropion has been documented in most dog breeds, although there are some breeds (particularly purebreds) that are more commonly affected than others. These include the Akita, Pug, Chow Chow, Shar Pei, St. Bernard, Cocker Spaniel, Boxer, English Springer Spaniel, Welsh Springer Spaniel, Labrador Retriever, Cavalier King Charles Spaniel, Neapolitan Mastiff, Bull Mastiff, Great Dane, Irish Setter, Shiba Inu, Rottweiler, Poodle and particularly Bloodhound. The condition is usually present by six months of age. If left untreated, the condition can cause such trauma to the eye that it will require removal. Entropion has also been seen in cat breeds. Typically it is secondary to trauma or infection leading to chronic eyelid changes. It is also seen secondary to enophthalmos. Primary entropion might also be encountered : the brachycephalic breeds (mostly the Persian) and the Maine Coon are predisposed.Upper-lid entropion involves the eyelashes rubbing on the eye, but the lower lid usually has no eyelashes, so little or no hair rubs on the eye. Surgical correction is used in more severe cases. A number of techniques for surgical correction exist. The Hotz-Celsus technique involves the removal of strip of skin and orbicularis oculi muscle parallel to the affected portion of the lid and then the skin is sutured. Alternative techniques such as the Wyman technique focus on tightening the lower eyelid. This technique is not as effective in cases of enophthalmos.Shar Peis, who often are affected as young as two or three weeks old, respond well to temporary eyelid tacking. The entropion is often corrected after three to four weeks, and the sutures are removed. See also Ectropion References External links HumansMedline Plus - Entropion
Canine degenerative myelopathy	Canine degenerative myelopathy, also known as chronic degenerative radiculomyelopathy, is an incurable, progressive disease of the canine spinal cord that is similar in many ways to amyotrophic lateral sclerosis (ALS). Onset is typically after the age of 7 years and it is seen most frequently in the German shepherd dog, Pembroke Welsh corgi, and boxer dog, though the disorder is strongly associated with a gene mutation in SOD1 that has been found in 43 breeds as of 2008, including the wire fox terrier, Chesapeake Bay retriever, Rhodesian ridgeback, and Cardigan Welsh corgi. Progressive weakness and incoordination of the rear limbs are often the first signs seen in affected dogs, with progression over time to complete paralysis. Myelin is an insulating sheath around neurons in the spinal cord. One proposed cause of degenerative myelopathy is that the immune system attacks this sheath, breaking it down. This results in a loss of communication between nerves in lower body of the animal and the brain. Testing The Orthopedic Foundation for Animals has a DNA saliva test to screen for the mutated gene that has been seen in dogs with degenerative myelopathy. Now that a test is available the disease can be bred out of breeds with a high preponderance. The test is only recommended for predisposed breeds, but can be performed on DNA from any dog on samples collected through swabbing the inside of the animals cheek with a sterile cotton swab or through venipuncture. The test determines whether the mutated copy of SOD1 is present in the DNA sample submitted. It must be interpreted with caution by a veterinary clinician in combination with the animals clinical signs and other lab test results. The results reported are: Normal / Normal (N/N, or clear): The dog does not have the mutation and is extremely unlikely to develop degenerative myelopathy. There have been cases, however, in which dogs that tested clear were found to have DM upon necropsy. Normal / Abnormal (N/A or carrier): The dog has one mutated copy of the gene (is heterozygous) and is a carrier but will not have degenerative myelopathy though there has now been some cases of heterozygous carriers developing DM. It will be possible for it to pass the mutation to offspring. A thorough examination of the dogs pedigree and DNA testing should be undertaken prior to breeding a dog with this result. Abnormal / Abnormal (A/A or At Risk): The dog has two copies (is homozygous) for the mutation and is at risk for degenerative myelopathy. Genetics Breeding risks for degenerative myelopathy can be calculated using the Punnett Square: If both parents are clear (N/N) then all of the puppies will be clear. If one parent is a carrier (N/A) and one is clear (N/N) each puppy has a 50% chance of being clear and a 50% chance of being a carrier. If both parents are carriers (N/A) each puppy has a 25% chance of being clear (N/N), 50% chance of being a carrier (N/A), and 25% chance of being affected and carrier (A/A) If one parent is clear (N/N) and one parent is affected (A/A) then all puppies will be carriers (N/A) If one parent is a carrier (N/A) and one is at risk (A/A) each puppy has a 50% chance of being a carrier(N/A) and 50% chance of being affected and carrier (A/A) If both parents are at risk (A/A) then all puppies will be affected and carrier (A/A) Symptoms Degenerative myelopathy initially affects the back legs and causes muscle weakness and loss, and lack of coordination. These cause a staggering affect that may appear to be arthritis. The dog may drag one or both rear paws when it walks. This dragging can cause the nails of one foot to be worn down. The condition may lead to extensive paralysis of the back legs. As the disease progresses, the animal may display symptoms such as incontinence and has considerable difficulties with both balance and walking. If allowed to progress, the animal will show front limb involvement and extensive muscle atrophy and paralysis. Eventually cranial nerve or respiratory muscle involvement necessitates euthanasia or long term palliative care.Progression of the disease is generally slow but highly variable. The animal could be crippled within a few months, or may survive as long as three years or more. Causes The etiology of this disease is unknown. Recent research has shown that a mutation in the SOD1 gene is a risk factor for developing degenerative myelopathy in several breeds. Mutations in SOD1 are also associated with familial amyotrophic lateral sclerosis (Lou Gehrigs disease) in people. More than 100 SOD1 gene mutations are involved in human familial amyotrophic lateral sclerosis (ALS), and the pathologic spinal lesions of ALS are similar to those of canine DM, making canine DM a potentially useful animal model of ALS. Known causes of spinal cord dysfunction should be excluded before accepting the diagnosis of degenerative myelopathy; disc disease (protrusions) or spinal cord tumors can cause compression of the spinal cord with similar signs to degenerative myelopathy. Treatment Degenerative myelopathy is an irreversible, progressive disease that cannot currently be cured. There are no treatments that have been clearly shown to stop or slow progression of DM. Exercise Exercise has been recommended to maintain the dogs ability to walk. Physiotherapy may prolong the length of time that the dog remains mobile and increase survival time. Canine hydrotherapy (swimming) may be more useful than walking. Use of a belly sling or hand-held harness allows the handler the ability to support the dogs hind legs for exercising or going up and down stairs. A 2-wheel dog cart, or "dog wheelchair" can allow the dog to remain active and maintain its quality of life once signs of weakness or paralysis of the hind limbs is detected. Prognosis The prognosis for the disease is generally poor. Aggressive therapy may be used to combat the disease, but even this puts the life expectancy at only around 14 months. It is recommended to put the dog to sleep at around 12 months, to prevent unnecessary suffering that comes from the disease. Some dogs have lived for many years with the disease, with one female boxer even living for 11 years. Without treatment, survival is around 3 months. The disease progresses rapidly without treatment, but this option arguably comes with less suffering. The dog begins to realize it is ill during the late stages. Some dogs have even appeared to be combating the disease on their own, walking on their own and doing exercise. The record survival without treatment is 14 years. Sources External links "How to Care for a Dog with Degenerative Myelopathy Video". Retrieved 2013-07-19. "Degenerative Myelopathy Symptoms, Diagnosis and Treatment Video". Retrieved 2011-06-18. "Degenerative myelopathy in Canis familiaris". Online Mendelian Inheritance in Animals (OMIA). Retrieved 2008-07-25. "Degenerative Myelopathy". Canine Genetic Diseases Network. University of Missouri College of Veterinary Medicine. Retrieved 2007-07-02. "DM of the German Shepherd Dog". Retrieved 2013-07-12.
Hidrocystoma	Hidrocystoma (also known as cystadenoma, a Molls gland cyst, and a sudoriferous cyst) is an adenoma of the sweat glands.: 787 Hidrocystomas are cysts of sweat ducts, usually on the eyelids.: 664 They are not tumours (a similar-sounding lesion called hidroadenoma is a benign tumour). The three types of "sweat" glands are: True sweat glands or eccrine glands, sebaceous glands, which have an oily secretion around hair follicles, and apocrine glands, which have more oily product than eccrine glands and are found on the face, armpit, and groin. Hidrocystomas usually arise from apocrine glands. They are also called cysts of Moll or sudoriferous cysts. A type of hidroadenoma that arises from eccrine glands is uncommon. Other related conditions on the eyelids include chalazion (a granulomatous reaction to sebaceous glands on the eyelid), lacrimal duct cysts (cysts related to tear ducts), and nasolacrimal duct cysts (the nasolacrimal duct drains tears into the nose via a punctum on the lower eyelid). Additional images See also Syringoma Acrospiroma Seborrheic keratosis List of cutaneous conditions List of cutaneous neoplasms associated with systemic syndromes References == External links ==
Osteochondritis	Osteochondritis is a painful type of osteochondrosis where the cartilage or bone in a joint is inflamed.It often refers to osteochondritis dissecans (OCD). The term dissecans refers to the "creation of a flap of cartilage that further dissects away from its underlying subchondral attachments (dissecans)".The other recognized types of osteochondritis are osteochondritis deformans juvenilis (osteochondritis of the capitular head of the epiphysis of the femur) and osteochondritis deformans juvenilis dorsi (osteochondrosis of the spinal vertebrae, also known as Scheuermanns disease).Osteochondritis, and especially osteochondritis dissecans, can manifest in animals as a primary cause of elbow dysplasia, a chronic condition in some dog breeds. References == External links ==
Renal physiology	Renal physiology (Latin rēnēs, "kidneys") is the study of the physiology of the kidney. This encompasses all functions of the kidney, including maintenance of acid-base balance; regulation of fluid balance; regulation of sodium, potassium, and other electrolytes; clearance of toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood pressure; production of various hormones, such as erythropoietin; and activation of vitamin D. Much of renal physiology is studied at the level of the nephron, the smallest functional unit of the kidney. Each nephron begins with a filtration component that filters the blood entering the kidney. This filtrate then flows along the length of the nephron, which is a tubular structure lined by a single layer of specialized cells and surrounded by capillaries. The major functions of these lining cells are the reabsorption of water and small molecules from the filtrate into the blood, and the secretion of wastes from the blood into the urine. Proper function of the kidney requires that it receives and adequately filters blood. This is performed at the microscopic level by many hundreds of thousands of filtration units called renal corpuscles, each of which is composed of a glomerulus and a Bowmans capsule. A global assessment of renal function is often ascertained by estimating the rate of filtration, called the glomerular filtration rate (GFR). Formation of urine The kidneys ability to perform many of its functions depends on the three fundamental functions of filtration, reabsorption, and secretion, whose sum is called renal clearance or renal excretion. That is: Urinary excretion rate = Filtration rate – Reabsorption rate + Secretion rateAlthough the strictest sense of the word excretion with respect to the urinary system is urination itself, renal clearance is also conventionally called excretion (for example, in the set term fractional excretion of sodium). Filtration The blood is filtered by nephrons, the functional units of the kidney. Each nephron begins in a renal corpuscle, which is composed of a glomerulus enclosed in a Bowmans capsule. Cells, proteins, and other large molecules are filtered out of the glomerulus by a process of ultrafiltration, leaving an ultrafiltrate that resembles plasma (except that the ultrafiltrate has negligible plasma proteins) to enter Bowmans space. Filtration is driven by Starling forces. The ultrafiltrate is passed through, in turn, the proximal convoluted tubule, the loop of Henle, the distal convoluted tubule, and a series of collecting ducts to form urine. Reabsorption Tubular reabsorption is the process by which solutes and water are removed from the tubular fluid and transported into the blood. It is called reabsorption (and not absorption) both because these substances have already been absorbed once (particularly in the intestines) and because the body is reclaiming them from a postglomerular fluid stream that is well on its way to becoming urine (that is, they will soon be lost to the urine unless they are reclaimed). Reabsorption is a two-step process beginning with the active or passive extraction of substances from the tubule fluid into the renal interstitium (the connective tissue that surrounds the nephrons), and then the transport of these substances from the interstitium into the bloodstream. These transport processes are driven by Starling forces, diffusion, and active transport. Indirect reabsorption In some cases, reabsorption is indirect. For example, bicarbonate (HCO3−) does not have a transporter, so its reabsorption involves a series of reactions in the tubule lumen and tubular epithelium. It begins with the active secretion of a hydrogen ion (H+) into the tubule fluid via a Na/H exchanger: In the lumen The H+ combines with HCO3− to form carbonic acid (H2CO3) Luminal carbonic anhydrase enzymatically converts H2CO3 into H2O and CO2 CO2 freely diffuses into the cell In the epithelial cell Cytoplasmic carbonic anhydrase converts the CO2 and H2O (which is abundant in the cell) into H2CO3 H2CO3 readily dissociates into H+ and HCO3− HCO3− is facilitated out of the cells basolateral membrane Influence of hormones Some key regulatory hormones for reabsorption include: aldosterone, which stimulates active sodium reabsorption (and water as a result) antidiuretic hormone, which stimulates passive water reabsorptionBoth hormones exert their effects principally on the collecting ducts. Tubular secretion occurs simultaneously during reabsorption of filtrate. Substances, generally produced by body or the by-products of cell metabolism that can become toxic in high concentration, and some drugs (if taken). These all are secreted into the lumen of renal tubule. Tubular secretion can be either active or passive or co-transport. Substances mainly secreted into renal tubule are; H+, K+, NH3, urea, creatinine, histamine and drugs like penicillin. Tubular secretion occurs at Proximal Convoluted Tubule (PCT) and Distal Convoluted Tubule (DCT); for example, at proximal convoluted tubule, potassium is secreted by means of sodium-potassium pump, hydrogen ion is secreted by means of active transport and co-transport, i.e. antiporter, and ammonia diffuses into renal tubule. Other functions Hormone secretion The kidneys secrete a variety of hormones, including erythropoietin, calcitriol, and renin. Erythropoietin is released in response to hypoxia (low levels of oxygen at tissue level) in the renal circulation. It stimulates erythropoiesis (production of red blood cells) in the bone marrow. Calcitriol, the activated form of vitamin D, promotes intestinal absorption of calcium and the renal reabsorption of phosphate. Renin is an enzyme which regulates angiotensin and aldosterone levels. Maintaining homeostasis The kidney is responsible for maintaining a balance of the following substances: The body is very sensitive to its pH. Outside the range of pH that is compatible with life, proteins are denatured and digested, enzymes lose their ability to function, and the body is unable to sustain itself. The kidneys maintain acid-base homeostasis by regulating the pH of the blood plasma. Gains and losses of acid and base must be balanced. Acids are divided into "volatile acids" and "nonvolatile acids". See also titratable acid. The major homeostatic control point for maintaining this stable balance is renal excretion. The kidney is directed to excrete or retain sodium via the action of aldosterone, antidiuretic hormone (ADH, or vasopressin), atrial natriuretic peptide (ANP), and other hormones. Abnormal ranges of the fractional excretion of sodium can imply acute tubular necrosis or glomerular dysfunction. Acid-base Two organ systems, the kidneys and lungs, maintain acid-base homeostasis, which is the maintenance of pH around a relatively stable value. The lungs contribute to acid-base homeostasis by regulating carbon dioxide (CO2) concentration. The kidneys have two very important roles in maintaining the acid-base balance: to reabsorb and regenerate bicarbonate from urine, and to excrete hydrogen ions and fixed acids (anions of acids) into urine. Osmolality The kidneys help maintain the water and salt level of the body. Any significant rise in plasma osmolality is detected by the hypothalamus, which communicates directly with the posterior pituitary gland. An increase in osmolality causes the gland to secrete antidiuretic hormone (ADH), resulting in water reabsorption by the kidney and an increase in urine concentration. The two factors work together to return the plasma osmolality to its normal levels. ADH binds to principal cells in the collecting duct that translocate aquaporins to the membrane, allowing water to leave the normally impermeable membrane and be reabsorbed into the body by the vasa recta, thus increasing the plasma volume of the body. There are two systems that create a hyperosmotic medulla and thus increase the body plasma volume: Urea recycling and the single effect. Urea is usually excreted as a waste product from the kidneys. However, when plasma blood volume is low and ADH is released the aquaporins that are opened are also permeable to urea. This allows urea to leave the collecting duct into the medulla, creating a hyperosmotic solution that "attracts" water. Urea can then re-enter the nephron and be excreted or recycled again depending on whether ADH is still present or not. The single effect describes the fact that the ascending thick limb of the loop of Henle is not permeable to water but is permeable to sodium chloride. This allows for a countercurrent exchange system whereby the medulla becomes increasingly concentrated, but at the same time setting up an osmotic gradient for water to follow should the aquaporins of the collecting duct be opened by ADH. Blood pressure Although the kidney cannot directly sense blood, long-term regulation of blood pressure predominantly depends upon the kidney. This primarily occurs through maintenance of the extracellular fluid compartment, the size of which depends on the plasma sodium concentration. Renin is the first in a series of important chemical messengers that make up the renin–angiotensin system. Changes in renin ultimately alter the output of this system, principally the hormones angiotensin II and aldosterone. Each hormone acts via multiple mechanisms, but both increase the kidneys absorption of sodium chloride, thereby expanding the extracellular fluid compartment and raising blood pressure. When renin levels are elevated, the concentrations of angiotensin II and aldosterone increase, leading to increased sodium chloride reabsorption, expansion of the extracellular fluid compartment, and an increase in blood pressure. Conversely, when renin levels are low, angiotensin II and aldosterone levels decrease, contracting the extracellular fluid compartment, and decreasing blood pressure. Glucose formation The kidney in humans is capable of producing glucose from lactate, glycerol and glutamine. The kidney is responsible for about half of the total gluconeogenesis in fasting humans. The regulation of glucose production in the kidney is achieved by action of insulin, catecholamines and other hormones. Renal gluconeogenesis takes place in the renal cortex. The renal medulla is incapable of producing glucose due to absence of necessary enzymes. Measurement of renal function A simple means of estimating renal function is to measure pH, blood urea nitrogen, creatinine, and basic electrolytes (including sodium, potassium, chloride, and bicarbonate). As the kidney is the most important organ in controlling these values, any derangement in these values could suggest renal impairment. There are several more formal tests and ratios involved in estimating renal function: == References ==
Retained placenta	Retained placenta is a condition in which all or part of the placenta or membranes remain in the uterus during the third stage of labour. Retained placenta can be broadly divided into: failed separation of the placenta from the uterine lining placenta separated from the uterine lining but retained within the uterusA retained placenta is commonly a cause of postpartum haemorrhage, both primary and secondary.Retained placenta is generally defined as a placenta that has not undergone placental expulsion within 30 minutes of the baby’s birth where the third stage of labor has been managed actively. Signs and symptoms Risks of retained placenta include hemorrhage and infection. After the placenta is delivered, the uterus should contract down to close off all the blood vessels inside the uterus. If the placenta only partially separates, the uterus cannot contract properly, so the blood vessels inside will continue to bleed. A retained placenta thereby leads to hemorrhage. Management Drugs, such as intraumbilical or intravenous oxytocin, are often used in the management of placental retention. It is useful ensuring the bladder is empty. However, ergometrine should not be given as it causes tonic uterine contractions which may delay placental expulsion. Controlled cord traction has been recommended as a second alternative after more than 30 minutes have passed after stimulation of uterine contractions, provided the uterus is contracted. Manual extraction may be required if cord traction also fails, or if heavy ongoing bleeding occurs. There is currently uncertainty about the effectiveness of anaesthesia or analgesia for manual extraction, in terms of pain and the risk of postpartum haemorrhage. Very rarely a curettage is necessary to ensure that no remnants of the placenta remain (in rare conditions with very adherent placenta such as a placenta accreta). However, in birth centers and attended home birth environments, it is common for licensed care providers to wait for the placentas birth up to 2 hours in some instances. Other animals Retention of fetal membranes (afterbirth) is observed more frequently in cattle than in other animals. In a normal condition, a cow’s placenta is expelled within a 12-hour period after calving. == References ==
Viral pneumonia	Viral pneumonia is a pneumonia caused by a virus. Pneumonia is an infection that causes inflammation in one or both of the lungs. The pulmonary alveoli fill with fluid or pus making it difficult to breathe. Pneumonia can be caused by bacteria, viruses, fungi or parasites. Viruses are the most common cause of pneumonia in children, while in adults bacteria are a more common cause. Signs and symptoms Symptoms of viral pneumonia include fever, non-productive cough, runny nose, and systemic symptoms (e.g. myalgia, headache). Different viruses cause different symptoms. Diagnosis Diagnosis, like with any infection, relies on the detection of the infectious cause. With viral pneumonia, samples are taken from the upper and/or lower respiratory tracts. The samples can then be run through polymerase chain reaction (PCR), allowing for amplification of the virus as that allows better detection if present in the sample. Other ways for a diagnosis to be obtained is by ordering a chest x-ray, blood tests, pulse oximetry, and a medical/family history to see if there are any known risks or previous exposures to a person with viral pneumonia. If the person is in serious condition and in the hospital there are more invasive studies that can be run to diagnosis the person. Cause Common causes of viral pneumonia are: Influenza virus A and B Respiratory syncytial virus (RSV) Human parainfluenza viruses (in children) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Rarer viruses that commonly result in pneumonia include: Adenoviruses (in military recruits) Metapneumovirus Severe acute respiratory syndrome coronavirus (SARS-CoV) Middle East respiratory syndrome virus (MERS-CoV) HantavirusesViruses that primarily cause other diseases, but sometimes cause pneumonia include: Herpes simplex virus (HSV), mainly in newborns or young children Varicella-zoster virus (VZV) Measles virus Rubella virus Cytomegalovirus (CMV), mainly in people with immune system problems Smallpox virus Dengue virusThe most commonly identified agents in children are respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses. History In the pre-antibiotic age, pneumonias had been treated with specific anti-serums of highly variable therapeutic effect and undesirable side-effects (a practice eliminated by the advent of sulfamides in 1936 and the beginning availability of penicillin in the 1940s). Viral pneumonia was first described by Hobart Reimann in 1938, in an article published by JAMA, An Acute Infection of the Respiratory Tract with Atypical Pneumonia: a disease entity probably caused by a filtrable virus. Reimann, Chairman of the Department of Medicine at Jefferson Medical College, had established the practice of routinely typing the pneumococcal organism in cases where pneumonia presented. Out of this work, the distinction between viral and bacterial strains was noticed. Pathophysiology Viruses must invade cells in order to reproduce. Typically, a virus will reach the lungs by traveling in droplets through the mouth and nose with inhalation. There, the virus invades the cells lining the airways and the alveoli. This invasion often leads to cell death either through direct killing by the virus or by self-destruction through apoptosis. Further damage to the lungs occurs when the immune system responds to the infection. White blood cells, in particular lymphocytes, are responsible for activating a variety of chemicals (cytokines) which cause leaking of fluid into the alveoli. The combination of cellular destruction and fluid-filled alveoli interrupts the transportation of oxygen into the bloodstream. In addition to the effects on the lungs, many viruses affect other organs and can lead to illness affecting many different bodily functions. Some viruses also make the body more susceptible to bacterial infection; for this reason, bacterial pneumonia often complicates viral pneumonia. Prevention The best prevention against viral pneumonia is vaccination against influenza, chickenpox (varicella zoster), herpes zoster, measles, respiratory syncytial virus vaccine (RSV), rubella, and adenovirus vaccine. Besides vaccination there are no other ways to prevent viral pneumonia besides basic hygiene skills like covering the mouth when coughing or sneezing, staying home when sick, and washing your hands frequently. Treatment In cases of viral pneumonia where influenza A or B are thought to be causative agents, patients who are seen within 48 hours of symptom onset may benefit from treatment with oseltamivir, or zanamivir, or peramivir. Respiratory syncytial virus (RSV) has no direct acting treatments, but ribavirin is indicated for severe cases. Ribavirin has also been known to be used as a treatment for Parainfluenza Virus, and Adenovirus. Herpes simplex virus and varicella-zoster virus infections are usually treated with acyclovir, whilst ganciclovir is used to treat cytomegalovirus. There is no known efficacious treatment for pneumonia caused by SARS coronavirus, MERS coronavirus, or hantavirus. Other forms of care are largely supportive like oxygen supplementation, treatment of comorbidities, and controlling other symptoms, fever and cough, with medications. Epidemiology There are roughly 450 million cases of pneumonia every year. Of those case, viral pneumonia counts for about 200 million cases which includes about 100 million children and 100 million adults. Viral pneumonia is more prevalent in the very young, less than 5 years old, and in the very old, more than 75 years old. Developing countries have a higher rate of incidence when it comes to viral pneumonia. On average, developing countries have an incidence rate five times higher than that of developed countries. Being pregnant can also affect the chances of developing viral pneumonia. As with all infectious diseases, viral pneumonia preys on the immunocompromised as well as individuals with one or more comorbidities especially those with: Trauma Severe burns Diabetes Malnutrition Poverty Environmental Exposure Group living References == External links ==
Cutaneous diphtheria infection	Cutaneous diphtheria is an infection of the skin by Corynebacterium diphtheriae.: 265 It is also known as "desert sore". See also Diphtheria Skin lesion == References ==
Diastasis recti	Diastasis recti, or rectus abdominis diastasis, is defined as a gap of about 2.7 cm or greater between the two sides of the rectus abdominis muscle. The distance between the right and left rectus abdominis muscles is created by the stretching of the linea alba, a connective collagen sheath created by the aponeurosis insertions of the transverse abdominis, internal oblique, and external oblique. This condition has no associated morbidity or mortality.Diastasis of the rectus abdominis muscle most frequently occurs in newborns and pregnant women; however, it may occur in any adult woman or man. In the newborn, the rectus abdominis is not fully developed and may not be sealed together at midline. Diastasis recti is more common in premature newborns. In pregnant or postpartum women, the condition is caused by the stretching of the rectus abdominis by the growing uterus. It is more common in multiparous women (women who have had multiple pregnancies) owing to repeated episodes of stretching. When the defect occurs during pregnancy, the uterus can sometimes be seen bulging through the abdominal wall beneath the skin. Non-pregnant women are more susceptible to develop diastasis recti when over the age of 35 or with high birth weight of child, multiple birth pregnancy, or multiple pregnancies. Additional causes can be attributed to excessive abdominal exercises after the first trimester of pregnancy.Strength training of all the core muscles, including the abdominis recti muscle, may or may not reduce the size of the gap in pregnant or postpartum women. Crunches may increase the diastasis recti separation. All corrective exercises should be in the form of pulling in the abdominal muscles rather than pushing them outwards. In extreme cases diastasis recti is corrected with a cosmetic surgery procedure known as an abdominoplasty by creating a plication, or folding, of the linea alba and suturing it together, which results in a tighter abdominal wall. Presentation A diastasis recti may appear as a ridge running down the midline of the abdomen, anywhere from the xiphoid process to the umbilicus. It becomes more prominent with straining and may disappear when the abdominal muscles are relaxed. The medial borders of the right and left halves of the muscle may be palpated during contraction of the rectus abdominis. The condition can be diagnosed by physical exam, and must be differentiated from an epigastric hernia or incisional hernia, if the patient has had abdominal surgery. Hernias may be ruled out using ultrasound.In infants, they typically result from a minor defect of the linea alba between the rectus abdominis muscles. This allows tissue from inside the abdomen to herniate anteriorly. On infants, this may manifest as an apparent bubble under the skin of the belly between the umbilicus and xiphisternum (bottom of the breastbone).Examination is performed with the subject lying on the back, knees bent at 90° with feet flat, head slightly lifted placing chin on chest. With muscles tense, the examiner then places fingers in the ridge that is presented. Measurement of the width of separation is determined by the number of fingertips that can fit within the space between the left and right rectus abdominis muscles. Separation consisting of a width of 2 fingertips (approximately 1 1/2 centimeters) or more is the determining factor for diagnosing diastasis recti. Diagnosis Diastasis recti can be diagnosed by physical examination, which may include measuring the distance between the rectus abdominis muscles at rest and during contraction at several levels along the linea alba. Abdominal ultrasonography provides objective evidence for the diagnosis, and also confirms that the bulge is not a hernia. An abdominal CT scan is an acceptable alternative to an ultrasound. Treatment During pregnancy - No treatment is necessary for women while they are still pregnant. After delivery - Typically the separation of the abdominal muscles will lessen in the mother within the first 8 weeks after childbirth; however, the connective tissue remains stretched for many. The weakening of the musculature may also cause lower back pain, weakened pelvic alignment, and altered posture. In children - Complications include development of an umbilical or ventral hernia, which is rare and can be corrected with surgery. If an infant with the condition develops vomiting, or redness or pain in the abdominal area, medical attention should be sought. Strength training A systematic review of the evidence found that exercise may or may not reduce the size of the gap in pregnant or postpartum women. The authors looked at 8 studies totaling 336 women and concluded: "Due to the low number and quality of included articles, there is insufficient evidence to recommend that exercise may help to prevent or reduce DRAM," or diastasis of the rectus abdominis muscles, also stating that "non-specific exercise may or may not help to prevent or reduce DRAM during the ante- and postnatal periods."However, a study conducted by the Columbia University Program in Physical Therapy stated: "Ninety percent of non‐exercising pregnant women exhibited DRA while only 12.5% of exercising women had the condition. The mean DRA located 4.5 cm above the umbilicus was 9.6 mm (± 6.6) for the exercise group and 38.9 mm (± 17.8) for the non‐exercise group. The mean DRA located at the umbilicus was 11.4 mm (± 3.82) for the exercise group and 59.5 mm (± 23.6) for the non‐exercise group. The mean DRA located 4.5 cm below the umbilicus was 8.2 mm (± 7.4) for the exercise group and 60.4 (± 29.0) for the non‐exercise group."Nevertheless, the following exercises are often recommended to help build abdominal strength, which may or may not help reduce the size of diastasis recti: Core contraction – In a seated position, place both hands on abdominal muscles. Take small controlled breaths. Slowly contract the abdominal muscles, pulling them straight back towards the spine. Hold the contraction for 30 seconds, while maintaining the controlled breathing. Complete 10 repetitions. Seated squeeze - Again in a seated position, place one hand above the belly button, and the other below the belly button. With controlled breaths, with a mid-way starting point, pull the abdominals back toward the spine, hold for 2 seconds and return to the mid-way point. Complete 100 repetitions. Head lift – In a lying down position, knees bent at 90° angle, feet flat, slowly lift the head, chin toward your chest, (concentrate on isolation of the abdominals to prevent hip-flexors from being engaged), slowly contract abdominals toward floor, hold for two seconds, lower head to starting position for 2 seconds. Complete 10 repetitions. Upright push-up – A stand-up push-up against the wall, with feet together arms-length away from wall, place hands flat against the wall, contract abdominal muscles toward spine, lean body towards wall, with elbows bent downward close to body, pull abdominal muscles in further, with controlled breathing. Release muscles as you push back to starting position. Complete 20 repetitions. Squat against the wall – Also known as a seated squat, stand with back against the wall, feet out in front of body, slowly lower body to a seated position so knees are bent at a 90° angle, contracting abs toward spine as you raise body back to standing position. Optionally, this exercise can also be done using an exercise ball placed against the wall and the lower back. Complete 20 repetitions. Squat with squeeze – A variation to the "squat against the wall" is to place a small resistance ball between the knees, and squeeze the ball while lowering the body to the seated position. Complete 20 repetitions.Incorrect exercises, including crunches, can increase the diastasis recti separation. All corrective exercises should be in the form of pulling in the abdominal muscles rather than pushing them outwards. Consultation of a professional physiotherapist is recommended for correct exercise routines.Furthermore, in a review of treatment methods for diastasis recti abdominis, besides strengthening exercises there are other options to treat DRA by postural training; education and training for proper lifting mechanisms; manual therapy (which includes soft tissue mobilization); myofascial release; Noble technique (i.e., manual approximation of abdominal muscles during partial sit-up); and abdominal bracing and taping. Other techniques to strengthen abdominal muscles are using Pilates and functional training.In addition to the above exercises, the Touro College study concluded the "quadruped" position yielded the most effective results. A quadruped position is defined as "a human whose body weight is supported by both arms as well as both legs". In this position, the subject would start with a flat back, then slowly tilt the head down, and round the spine, contracting the abdominal muscles towards the spine, holding this position for 5 seconds, then releasing back to starting position. Complete two sets of 10 repetitions. Surgery In extreme cases, diastasis recti is corrected with a cosmetic surgery procedure known as an abdominoplasty by creating a plication or folding of the linea alba and suturing together. This creates a tighter abdominal wall. There are two surgical methods: one through plication of the anterior rectus sheath, which is most commonly used to repair DRAM; and the other through hernia repair, considering suture closure of the hernia sac combined with mesh reinforcement. Two studies showed few post-operative complications.In adult females, a laparoscopic "Venetian blind" technique can be used for plication of the recti. References == External links ==
Optic neuropathy	Optic neuropathy is damage to the optic nerve from any cause. The optic nerve is a bundle of millions of fibers in the retina that sends visual signals to the brain. [1]. Damage and death of these nerve cells, or neurons, leads to characteristic features of optic neuropathy. The main symptom is loss of vision, with colors appearing subtly washed out in the affected eye. A pale disc is characteristic of long-standing optic neuropathy. In many cases, only one eye is affected and patients may not be aware of the loss of color vision until the doctor asks them to cover the healthy eye. Optic neuropathy is often called optic atrophy, to describe the loss of some or most of the fibers of the optic nerve. Ischemic optic neuropathy In ischemic optic neuropathies, there is insufficient blood flow (ischemia) to the optic nerve. The anterior optic nerve is supplied by the short posterior ciliary artery and choroidal circulation, while the retrobulbar optic nerve is supplied intraorbitally by a pial plexus, which arises from the ophthalmic artery, internal carotid artery, anterior cerebral artery, and anterior communicating arteries. Ischemic optic neuropathies are classified based on the location of the damage and the cause of reduced blood flow, if known. Anterior ischemic optic neuropathy (AION) includes diseases that affect the optic nerve head and cause swelling of the optic disc. These diseases often cause sudden rapid visual loss in one eye. Inflammatory diseases of the blood vessels, like giant-cell arteritis, polyarteritis nodosa, Churg–Strauss syndrome, granulomatosis with polyangiitis, and rheumatoid arthritis can cause arteritic AIONs (AAION). The vast majority of AIONs are nonarteritic AIONs (NAION). The most common acute optic neuropathy in patients over 50 years of age, NAION has an annual incidence of 2.3-10.2/100,000. NAION presents as a painless loss of vision, often when awakening, that occurs over hours to days. Most patients lose the lower half of their visual field (an inferior altitudinal loss), though superior altitudinal loss is also common. The pathophysiology of NAION is unknown, but it is related to poor circulation in the optic nerve head. NAION is often associated with diabetes mellitus, elevated intraocular pressure (acute glaucoma, eye surgery), high cholesterol, hypercoagulable states, a drop in blood pressure (bleeding, cardiac arrest, peri-operative esp. cardiac and spine procedures), and sleep apnea. Rarely, amiodarone, interferon-alpha, and erectile dysfunction drugs have been associated with this disease. Posterior ischemic optic neuropathy is a syndrome of sudden visual loss with optic neuropathy without initial disc swelling with subsequent development of optic atrophy. This can occur in patients who are predisposed to AAION and NAION as described above as well as those who had cardiac and spine surgery or serious episodes of hypotension. Radiation optic neuropathy (RON) is also thought to be due to ischemia of the optic nerve that occurs 3 months to 8 or more years after radiation therapy to the brain and orbit. It occurs most often around 1.5 years after treatment and results in irreversible and severe vision loss, which may also be associated with damage to the retina (radiation retinopathy). This is thought to be due to damage to dividing glial and vascular endothelial cells. RON can present with transient visual loss followed by acute painless visual loss in one or both eyes several weeks later. The risk of RON is significantly increased with radiation doses over 50 Gy. Optic neuritis Optic neuritis is inflammation of the optic nerve, which is associated with swelling and destruction of the myelin sheath covering the optic nerve. Young adults, usually females, are most commonly affected. Symptoms of optic neuritis in the affected eye include pain on eye movement, sudden loss of vision, and decrease in color vision (especially reds). Optic neuritis, when combined with the presence of multiple demyelinating white matter brain lesions on MRI, is suspicious for multiple sclerosis. Several causes and clinical courses are possible for the optic neuritis. It can be classified in: Single isolated optic neuritis (SION) relapsing isolated optic neuritis (RION) chronic relapsing inflammatory optic neuropathy (CRION) the neuromyelitis optica (NMO) spectrum disorder multiple sclerosis associated optic neuritis (MSON) unclassified optic neuritis (UCON) forms.Medical examination of the optic nerve with an ophthalmoscope may reveal a swollen optic nerve, but the nerve may also appear normal. Presence of an afferent pupillary defect, decreased color vision, and visual field loss (often central) are suggestive of optic neuritis. Recovery of visual function is expected within 10 weeks. However, attacks may lead to permanent axonal loss and thinning of the retinal nerve fiber layer. Compressive optic neuropathy Tumors, infections, and inflammatory processes can cause lesions within the orbit and, less commonly, the optic canal. These lesions may compress the optic nerve, resulting optic disc swelling and progressive visual loss. Implicated orbital disorders include optic gliomas, meningiomas, hemangiomas, lymphangiomas, dermoid cysts, carcinoma, lymphoma, multiple myeloma, inflammatory orbital pseudotumor, and thyroid ophthalmopathy. Patients often have bulging out of the eye (proptosis) with mild color deficits and almost normal vision with disc swelling. Infiltrative optic neuropathy The optic nerve can be infiltrated by a variety of processes, including tumors, inflammation, and infections. Tumors that can infiltrate the optic nerve can be primary (optic gliomas, capillary hemangiomas, and cavernous hemangiomas) or secondary (metastatic carcinoma, nasopharyngeal carcinoma, lymphoma, and leukemia). The most common inflammatory disorder that infiltrates the optic nerve is sarcoidosis. Opportunistic fungi, viruses, and bacteria may also infiltrate the optic nerve. The optic nerve may be elevated if the infiltration occurs in the proximal portion of the nerve. The appearance of the nerve on examination depends on the portion of the nerve that is affected. Traumatic optic neuropathy The optic nerve can be damaged when exposed to direct or indirect injury. Direct optic nerve injuries are caused by trauma to the head or orbit that crosses normal tissue planes and disrupts the anatomy and function of the optic nerve; e.g., a bullet or forceps that physically injures the optic nerve. Indirect injuries, like blunt trauma to the forehead during a motor vehicle accident, transmit force to the optic nerve without transgressing tissue planes. This type of force causes the optic nerve to absorb excess energy at the time of impact. The most common site of injury of the optic nerve is the intracanalicular portion of the nerve. Deceleration injuries from motor vehicle or bicycle accidents account for 17 to 63 percent of cases. Falls are also a common cause, and optic neuropathy most commonly occurs when there is a loss of consciousness associated with multi-system trauma and serious brain injury. In less than three percent of patients, an orbital hemorrhage after an injection behind the eye (retrobulbar block) can cause injury to the optic nerve, but this is readily manageable if it does not involve direct optic nerve injury and is caught early. The role of high-dose steroids and orbital decompression in treating these patients is controversial and, if administered, must be done very soon after injury with minimal effects. In patients with an orbital fracture, vomiting or nose blowing can force air into the orbit and possibly compromise the integrity of the optic nerve. Mitochondrial optic neuropathies Mitochondria play a central role in maintaining the life cycle of retinal ganglion cells because of their high energy dependence. Mitochondria are made within the central somata of the retinal ganglion cell, transported down axons, and distributed where they are needed. Genetic mutations in mitochondrial DNA, vitamin depletion, alcohol and tobacco abuse, and use of certain drugs can cause derangements in efficient transport of mitochondria, which can cause a primary or secondary optic neuropathy. Nutritional optic neuropathies A nutritional optic neuropathy may be present in a patient with obvious evidence of under-nutrition (weight loss and wasting). Months of depletion are usually necessary to deplete body stores of most nutrients. Undernourished patients often have many vitamin and nutrient deficiencies and have low serum protein levels. However, the optic neuropathy associated with pernicious anemia and vitamin B12 deficiency can even be seen in well-nourished individuals. Gastric bypass surgery may also cause a vitamin B12 deficiency from poor absorption. Patients who have nutritional optic neuropathy may notice that colors are not as vivid or bright as before and that the color red is washed out. This normally occurs in both eyes at the same time and is not associated with any eye pain. They might initially notice a blur or fog, followed by a drop in vision. While vision loss may be rapid, progression to blindness is unusual. These patients tend to have blind spots in the center of their vision with preserved peripheral vision. In most cases, the pupils continue to respond normally to light. Toxic optic neuropathies The most recognized cause of toxic optic neuropathy is methanol poisoning. This can be a life-threatening event that normally accidentally occurs when the person mistook or substituted, methanol for ethyl alcohol. The patient initially has nausea and vomiting, followed by respiratory distress, headache, and visual loss 18–48 hours after consumption. Without treatment, patients can go blind, and their pupils will dilate and stop reacting to light. Ethylene glycol, a component of automobile antifreeze, is a poison that is toxic to the whole body including the optic nerve. Consumption can be fatal, or recovery can occur with permanent neurologic and ophthalmologic deficits. While the visual loss is not very common, increased intracranial pressure can cause bilateral optic disc swelling from cerebral edema. A clue to the cause of intoxication is the presence of oxalate crystals in the urine. Like methanol intoxication, treatment is ethanol consumption. Ethambutol, a drug commonly used to treat tuberculosis, is notorious for causing toxic optic neuropathy. Patients with vision loss from ethambutol toxicity lose vision in both eyes equally. This initially presents with problems with colors (dyschromatopsia) and can leave central visual deficits. If vision loss occurs while using ethambutol, it would be best to discontinue this medication under a doctors supervision. Vision can improve slowly after discontinuing ethambutol but rarely returns to baseline. Amiodarone is an antiarrhythmic medication commonly used for abnormal heart rhythms (atrial or ventricular tachyarrhythmias). Most patients on this medication get corneal epithelial deposits, but this medication has also been controversially associated with NAION. Patients on amiodarone with new visual symptoms should be evaluated by an ophthalmologist. Tobacco exposure, most commonly through pipe and cigar smoking, can cause optic neuropathy. Middle-aged or elderly men are often affected and present with painless, slowly progressive, color distortion and visual loss in both eyes. The mechanism is unclear, but this has been reported to be more common in individuals who are already suffering from malnutrition. Hereditary optic neuropathies The inherited optic neuropathies typically manifest asa symmetric bilateral central visual loss. Optic nerve damage in most inherited optic neuropathies is permanent and progressive. Lebers hereditary optic neuropathy (LHON) is the most frequently occurring mitochondrial disease, and this inherited form of acute or subacute vision loss predominantly affects young males. LHON usually presents with rapid vision loss in one eye followed by involvement of the second eye (usually within months). Visual acuity often remains stable and poor (around or below 20/200) with a residual central visual field defect. Patients with the 14484/ND6 mutation are most likely to have visual recovery. Dominant optic atrophy is an autosomal dominant disease caused by a defect in the nuclear gene OPA1. A slowly progressive optic neuropathy, dominant optic atrophy, usually presents in the first decade of life and is bilaterally symmetrical. Examination of these patients shows loss of visual acuity, temporal pallor of the optic discs, centrocecal scotomas with peripheral sparing, and subtle impairments in color vision. Behrs syndrome is a rare autosomal recessive disorder characterized by early-onset optic atrophy, ataxia, and spasticity. Berk–Tabatznik syndrome is a condition that shows symptoms of short stature, congenital optic atrophy and brachytelephalangy. This condition is extremely rare. Optic nerve The optic nerve contains axons of nerve cells that emerge from the retina, leave the eye at the optic disc, and go to the visual cortex where input from the eye is processed into vision. There are 1.2 million optic nerve fibers that derive from the retinal ganglion cells of the inner retina. Treatments While optic neuropathy cannot be outright cured, there are surgical options to alleviate pain and symptoms associated with such diseases. The Endoscopic Endonasal Approach method (EEA) is a preferred method of relieving pressure associated with tumors formed in the brain that press upon the optic nerve. It is a minimally invasive surgery. However, due to the genetic and developmental nature of most causes of optic neuropathy, no other surgeries have been proven to cure these diseases. See also Optic neuritis Ophthalmoplegia Glaucoma References External links NCBI Genetic Testing Registry
Peritonitis	Peritonitis is inflammation of the localized or generalized peritoneum, the lining of the inner wall of the abdomen and cover of the abdominal organs. Symptoms may include severe pain, swelling of the abdomen, fever, or weight loss. One part or the entire abdomen may be tender. Complications may include shock and acute respiratory distress syndrome.Causes include perforation of the intestinal tract, pancreatitis, pelvic inflammatory disease, stomach ulcer, cirrhosis, or a ruptured appendix. Risk factors include ascites (the abnormal build-up of fluid in the abdomen) and peritoneal dialysis. Diagnosis is generally based on examination, blood tests, and medical imaging.Treatment often includes antibiotics, intravenous fluids, pain medication, and surgery. Other measures may include a nasogastric tube or blood transfusion. Without treatment death may occur within a few days. About 20% of people with cirrhosis who are hospitalized have peritonitis. Signs and symptoms Abdominal pain The main manifestations of peritonitis are acute abdominal pain, abdominal tenderness, abdominal guarding, rigidity, which are exacerbated by moving the peritoneum, e.g., coughing (forced cough may be used as a test), flexing ones hips, or eliciting the Blumberg sign (meaning that pressing a hand on the abdomen elicits less pain than releasing the hand abruptly, which will aggravate the pain, as the peritoneum snaps back into place). Rigidity is highly specific for diagnosing peritonitis (specificity: 76–100%). The presence of these signs in a person is sometimes referred to as peritonism. The localization of these manifestations depends on whether peritonitis is localized (e.g., appendicitis or diverticulitis before perforation), or generalized to the whole abdomen. In either case, pain typically starts as a generalized abdominal pain (with involvement of poorly localizing visceral innervation of the visceral peritoneal layer), and may become localized later (with involvement of the somatic innervation of the parietal peritoneal layer). Peritonitis is an example of an acute abdomen. Other symptoms Diffuse abdominal rigidity (abdominal guarding) is often present, especially in generalized peritonitis Fever Sinus tachycardia Development of ileus paralyticus (i.e., intestinal paralysis), which also causes nausea, vomiting and bloating Reduced or no passage of abdominal gas and bowel sound Complications Sequestration of fluid and electrolytes, as revealed by decreased central venous pressure, may cause electrolyte disturbances, as well as significant hypovolemia, possibly leading to shock and acute kidney failure. A peritoneal abscess may form (e.g., above or below the liver, or in the lesser omentum) Sepsis may develop, so blood cultures should be obtained. Complicated peritonitis typically involves multiple organs. Causes Infection Perforation of part of the gastrointestinal tract is the most common cause of peritonitis. Examples include perforation of the distal esophagus (Boerhaave syndrome), of the stomach (peptic ulcer, gastric carcinoma), of the duodenum (peptic ulcer), of the remaining intestine (e.g., appendicitis, diverticulitis, Meckel diverticulum, inflammatory bowel disease (IBD), intestinal infarction, intestinal strangulation, colorectal carcinoma, meconium peritonitis), or of the gallbladder (cholecystitis). Other possible reasons for perforation include abdominal trauma, ingestion of a sharp foreign body (such as a fish bone, toothpick or glass shard), perforation by an endoscope or catheter, and anastomotic leakage. The latter occurrence is particularly difficult to diagnose early, as abdominal pain and ileus paralyticus are considered normal in people who have just undergone abdominal surgery. In most cases of perforation of a hollow viscus, mixed bacteria are isolated; the most common agents include Gram-negative bacilli (e.g., Escherichia coli) and anaerobic bacteria (e.g., Bacteroides fragilis). Fecal peritonitis results from the presence of faeces in the peritoneal cavity. It can result from abdominal trauma and occurs if the large bowel is perforated during surgery. Disruption of the peritoneum, even in the absence of perforation of a hollow viscus, may also cause infection simply by letting micro-organisms into the peritoneal cavity. Examples include trauma, surgical wound, continuous ambulatory peritoneal dialysis, and intra-peritoneal chemotherapy. Again, in most cases, mixed bacteria are isolated; the most common agents include cutaneous species such as Staphylococcus aureus, and coagulase-negative staphylococci, but many others are possible, including fungi such as Candida. Spontaneous bacterial peritonitis (SBP) is a peculiar form of peritonitis occurring in the absence of an obvious source of contamination. It occurs in people with ascites, including children. Intra-peritoneal dialysis predisposes to peritoneal infection (sometimes named "primary peritonitis" in this context). Systemic infections (such as tuberculosis) may rarely have a peritoneal localisation. Pelvic inflammatory disease Non-infection Leakage of sterile body fluids into the peritoneum, such as blood (e.g., endometriosis, blunt abdominal trauma), gastric juice (e.g., peptic ulcer, gastric carcinoma), bile (e.g., liver biopsy), urine (pelvic trauma), menstruum (e.g., salpingitis), pancreatic juice (pancreatitis), or even the contents of a ruptured dermoid cyst. It is important to note that, while these body fluids are sterile at first, they frequently become infected once they leak out of their organ, leading to infectious peritonitis within 24 to 48 hours. Sterile abdominal surgery, under normal circumstances, causes localised or minimal generalised peritonitis, which may leave behind a foreign body reaction or fibrotic adhesions. However, peritonitis may also be caused by the rare case of a sterile foreign body inadvertently left in the abdomen after surgery (e.g., gauze, sponge). Much rarer non-infectious causes may include familial Mediterranean fever, TNF receptor associated periodic syndrome, porphyria, and systemic lupus erythematosus. Risk factors Previous history of peritonitis History of alcoholism Liver disease Fluid accumulation in the abdomen Weakened immune system Pelvic inflammatory disease Diagnosis A diagnosis of peritonitis is based primarily on the clinical manifestations described above. Rigidity (involuntary contraction of the abdominal muscles) is the most specific exam finding for diagnosing peritonitis. If focal peritonitis is detected, further work-up should be done. If diffuse peritonitis is detected, then urgent surgical consultation should be obtained, and may warrant surgery without further investigations. Leukocytosis, hypokalemia, hypernatremia, and acidosis may be present, but they are not specific findings. Abdominal X-rays may reveal dilated, edematous intestines, although such X-rays are mainly useful to look for pneumoperitoneum, an indicator of gastrointestinal perforation. The role of whole-abdomen ultrasound examination is under study and is likely to expand in the future. Computed tomography (CT or CAT scanning) may be useful in differentiating causes of abdominal pain. If reasonable doubt still persists, an exploratory peritoneal lavage or laparoscopy may be performed. In people with ascites, a diagnosis of peritonitis is made via paracentesis (abdominal tap): More than 250 polymorphonuclear cells per μL is considered diagnostic. In addition, Gram stain is almost always negative, whereas culture of the peritoneal fluid can determine the microorganism responsible and determine their sensitivity to antimicrobial agents. Pathology In normal conditions, the peritoneum appears greyish and glistening; it becomes dull 2–4 hours after the onset of peritonitis, initially with scarce serous or slightly turbid fluid. Later on, the exudate becomes creamy and evidently suppurative; in people who are dehydrated, it also becomes very inspissated. The quantity of accumulated exudate varies widely. It may be spread to the whole peritoneum, or be walled off by the omentum and viscera. Inflammation features infiltration by neutrophils with fibrino-purulent exudation. Treatment Depending on the severity of the persons state, the management of peritonitis may include: Antibiotics are usually administered intravenously, but they may also be infused directly into the peritoneum. The empiric choice of broad-spectrum antibiotics often consist of multiple drugs, and should be targeted against the most likely agents, depending on the cause of peritonitis (see above); once one or more agents grow in cultures isolated, therapy will be target against them. Gram positive and gram negative organisms must be covered. Out of the cephalosporins, cefoxitin and cefotetan can be used to cover gram positive bacteria, gram negative bacteria, and anaerobic bacteria. Beta-lactams with beta lactamase inhibitors can also be used, examples include ampicillin/sulbactam, piperacillin/tazobactam, and ticarcillin/clavulanate. Carbapenems are also an option when treating primary peritonitis as all of the carbapenems cover gram positives, gram negatives, and anaerobes except for ertapenem. The only fluoroquinolone that can be used is moxifloxacin because this is the only fluoroquinolone that covers anaerobes. Finally, tigecycline is a tetracycline that can be used due to its coverage of gram positives and gram negatives. Empiric therapy will often require multiple drugs from different classes. Surgery (laparotomy) is needed to perform a full exploration and lavage of the peritoneum, as well as to correct any gross anatomical damage that may have caused peritonitis. The exception is spontaneous bacterial peritonitis, which does not always benefit from surgery and may be treated with antibiotics in the first instance. Prognosis If properly treated, typical cases of surgically correctable peritonitis (e.g., perforated peptic ulcer, appendicitis, and diverticulitis) have a mortality rate of about <10% in otherwise healthy people. The mortality rate rises to 35% in peritonitis patients who develop sepsis, and patients who have underlying renal insufficiency and complications have a higher mortality rate. Etymology The term "peritonitis" comes from Greek περιτόναιον peritonaion "peritoneum, abdominal membrane" and -itis "inflammation". References == External links ==
Ainhum	Ainhum (from Portuguese, pronounced /aj.ˈɲũ/), also known as dactylolysis spontanea, is a painful constriction of the base of the fifth toe frequently followed by bilateral spontaneous autoamputation a few years later. Signs and symptoms The groove begins on the lower and internal side of the base of the fifth toe, usually according to the plantar-digital fold. The groove becomes gradually deeper and more circular. The rate of spread is variable, and the disease may progress to a full circle in a few months, or still be incomplete after years. In about 75 percent of cases both feet are affected, though not usually to the same degree. There is no case reported where it begins in any other toe than the fifth, while there is occasionally a groove on the fourth or third toe. The distal part of the toe swells and appears like a small potato. The swelling is due to lymphatic edema distal to the constriction. After a time crusts can appear in the groove which can be infected with staphylococcus. While the groove becomes deeper, compression of tendons, vessels and nerves occurs. Bone is absorbed by pressure, without any evidence of infection. After a certain time all structures distal the stricture are reduced to an avascular cord. The toe’s connection to the foot becomes increasingly slender, and if it is not amputated, it spontaneously drops off without any bleeding. Normally it takes about five years for an autoamputation to occur. Cole describes four stages of ainhum: Pain is present in about 78% of cases. Slight pain is present in the earliest stage of ainhum, caused by pressure on the underlying nerves. Fracture of the phalanx or chronic sepsis is accompanied with severe pain. Cause The true cause of ainhum remains unclear. It is not due to infection by parasites, fungi, bacteria or virus, and it is not related to injury. Walking barefoot in childhood had been linked to this disease, but ainhum also occurs in patients who have never gone barefoot. Race seems to be one of the most predisposing factors and it may have a genetic component, since it has been reported to occur within families. Dent et al. discussed a genetically caused abnormality of the blood supply to the foot. It has been related to inadequate posterior tibial artery circulation and absence of plantar arch. Diagnosis Histolopathology Histology shows a change in the prickle cell layer, and this is responsible for the laying down of condensed keratin causing the groove. The junctional tissue is reduced to a slender fibrous thread, almost avascular, and all the tissues beyond the constricting band is repressed by a fibro-fatty mass covered by hyperkeratotic integument. Imaging Soft tissue constriction on the medial aspect of the fifth toe is the most frequently presented radiological sign in the early stages. Distal swelling of the toe is considered to be a feature of the disease. In grade III lesions osteolysis is seen in the region of the proximal interphalangeal joint with a characteristic tapering effect. Dispersal of the head of the proximal phalanx is frequently seen. Finally, after autoamputation, the base of the proximal phalanx remains. Radiological examination allows early diagnosis and staging of ainhum. Early diagnosis is crucial to prevent amputation. Doppler shows decreased blood flow in posterior tibial artery. Differential diagnosis Ainhum is an acquired and progressive condition, and thus differs from congenital annular constrictions. Ainhum has been much confused with similar constrictions caused by other diseases such as leprosy, diabetic gangrene, syringomyelia, scleroderma or Vohwinkel syndrome. In this case, it is called pseudo-ainhum, treatable with minor surgery or intralesional corticosteroids, as with ainhum. It has even been seen in psoriasis or it is acquired by the wrapping toes, penis or nipple with hairs, threads or fibers. Oral retinoids, such as tretinoin, and antifibrotic agents like tranilast have been tested for pseudo-ainhum. Impending amputation in Vohwinkel syndrome can sometimes be aborted by therapy with oral etretinate. It is rarely seen in the United States but often discussed in the international medical literature. Prevention Wearing shoes to protect barefoot trauma has shown decrease in incidence in ainhum. Congenital pseudoainhum cannot be prevented and can lead to serious birth defects. Treatment Incisions across the groove turned out to be ineffective. Excision of the groove followed by z-plasty could relieve pain and prevent autoamputation in Grade I and Grade II lesions. Grade III lesions are treated with disarticulating the metatarsophalangeal joint. This also relieves pain, and all patients have a useful and stable foot. Intralesional injection of corticosteroids is also helpful. Epidemiology Ainhum predominantly affects black people, living in West Africa, South America and India. In Nigeria it is a common disease with an incidence of 1.7 per thousand. In tropical and subtropical climates, its incidence has been reported as between 0.015 percent and 2.0 percent of the population. Up to now only a few cases had been reported in Europe. Ainhum usually affects people between 20 and 50 years. The average age is about thirty-eight. The youngest recorded patient was seven years old. It is more common in men than in women (2:1), and is often familial. History The first description of ainhum in the West appears to have been provided by English surgeon Robert Clarke, who made a passing reference to "dry gangrene of the little toe" as a common occurrence in the Gold Coast in an 1860 report to the Epidemiological Society of London, but did not recognize it as a distinct entity and believed it to be a consequence of "suppressed yaws". Ainhum was first recognized as a distinct disease and described as such in detail by Brazilian physician Jose Francisco da Silva Lima (1826–1910), in 1867. The name "ainhum" (from the Yoruba ayùn, meaning "to saw" or "to file") was used to refer to the disease by Yoruba speakers in Bahia, Brazil, where Silva Lima practiced.The first histological studies of ainhum were conducted by O. E. H. Wucherer and published in 1872, and the first imaging studies were conducted in 1924. References == External links ==
Paget–Schroetter disease	Paget–Schroetter disease (also known as venous thoracic outlet syndrome) is a form of upper extremity deep vein thrombosis (DVT), a medical condition in which blood clots form in the deep veins of the arms. These DVTs typically occur in the axillary and/or subclavian veins. Signs and symptoms The condition is relatively rare. It usually presents in young and otherwise healthy patients, and also occurs more often in males than females. The syndrome also became known as "effort-induced thrombosis" in the 1960s, as it has been reported to occur after vigorous activity, though it can also occur due to anatomic abnormality such as clavicle impingement or spontaneously. It may develop as a sequela of thoracic outlet syndrome. It is differentiated from secondary causes of upper extremity thrombosis caused by intravascular catheters. Paget–Schroetter syndrome was described once for a viola player who suddenly increased practice time 10-fold, creating enough repetitive pressure against the brachiocephalic and external jugular veins to cause thrombosis.Symptoms may include sudden onset of pain, warmth, redness, blueness and swelling in the arm. Diagnosis is usually confirmed with an ultrasound. These DVTs have the potential to cause a pulmonary embolism. Diagnosis Duplex ultrasonography MR Venography Prevention Prevention of Paget–Schroetter disease can be accomplished by gradual increases in activity and by avoiding strenuous upper extremity activity. Treatment The traditional treatment for thrombosis is the same as for a lower extremity DVT, and involves systemic anticoagulation to prevent a pulmonary embolus. Some have also recommended thrombolysis with catheter directed alteplase or mechanical thrombectomy with a large bore catheter and manual aspiration providing definitive intervention with an endovascular approach. If there is thoracic outlet syndrome or other anatomical cause then surgery can be considered to correct the underlying defect. History The condition is named after two men. James Paget first proposed the idea of venous thrombosis causing upper extremity pain and swelling, and Leopold von Schrötter later linked the clinical syndrome to thrombosis of the axillary and subclavian veins. References == External links ==
Flashing	Flashing may refer to: Technology Firmware#Flashing, overwriting an EEPROM module in a device BIOS flashing, overwriting a BIOS image Flashing (cinematography), a technique that desaturates the color so that one sees more in shadowed areas Flashing (weatherproofing), construction material used to prevent the passage of water around objects Flash evaporation, causing evaporation by lowering a fluids pressure below its vapour pressure Flashing light, such as a light bulb or computers cursor Flash (manufacturing), excess material attached to a moulded product which must usually be removed Other Flashing (horse) Flashing, a 1981 album by Himiko Kikuchi Exhibitionism, sexual body exposure Indecent exposure, inappropriate public nudity Headlight flashing, to alert other drivers Facing (retail), moving shelved products to the front See also Flash (disambiguation)
Alcohol abuse	Alcohol abuse encompasses a spectrum of unhealthy alcohol drinking behaviors, ranging from binge drinking to alcohol dependence, in extreme cases resulting in health problems for individuals and large scale social problems such as alcohol-related crimes. Alcohol abuse was a psychiatric diagnosis in the DSM-IV, and has been merged with alcohol dependence into alcohol use disorder in the DSM-5.Globally, excessive alcohol consumption is the seventh leading risk factor for both death and the burden of disease and injury. In short, except for tobacco, alcohol accounts for a higher burden of disease than any other drug. Alcohol use is a major cause of preventable liver disease worldwide, and alcoholic liver disease is the main alcohol-related chronic medical illness. Millions of people of all ages, from adolescents to the elderly, engage in unhealthy drinking. Alcohol use disorder can affect people from all walks of life. There are many factors that play a role in causing someone to have an alcohol use disorder: genetics, psychiatric conditions, trauma, environmental issues, and even parental drinking habits. Definitions Risky drinking (also called hazardous drinking) is defined by drinking above the recommended limits: greater than 14 standard drinks units per week or greater than 4 standard drinks on a single occasion in men greater than 7 standard drinks units per week or greater than 3 standard drinks on a single occasion in women any drinking in pregnant women or persons < 21 years oldBinge drinking is a pattern of alcohol consumption that brings blood alcohol concentration ≥ 0.08%, usually corresponding to ≥ 5 standard drinks on a single occasion in men ≥ 4 standard drinks on a single occasion in womenIn the DSM-IV, alcohol abuse and alcohol dependence were defined as distinct disorders from 1994 to 2013. The DSM-5 combined those two disorders into alcohol use disorder with sub-classifications of severity. The DSM-IV definition is no longer used. There is no "alcoholism" diagnosis in medical care. Alcohol misuse is a term used by United States Preventive Services Task Force to describe a spectrum of drinking behaviors that encompass risky drinking, alcohol abuse, and alcohol dependence (similar meaning to alcohol use disorder but not a term used in DSM). Signs and symptoms Individuals with an alcohol use disorder will often complain of difficulty with interpersonal relationships, problems at work or school, and legal problems. Additionally, people may complain of irritability and insomnia. Alcohol abuse is also an important cause of chronic fatigue. Signs of alcohol abuse are related to alcohols effects on organ systems. However, while these findings are often present, they are not necessary to make a diagnosis of alcohol abuse. Signs of alcohol abuse show its drastic effects on the central nervous system, including inebriation and poor judgment; chronic anxiety, irritability, and insomnia. Alcohols effects on the liver include elevated liver function tests (classically AST is at least twice as high as ALT). Prolonged use leads to cirrhosis and liver failure. With cirrhosis, patients develop an inability to process hormones and toxins. The skin of a patient with alcoholic cirrhosis can feature spider angiomas, palmar erythema and — in acute liver failure — jaundice and ascites. The derangements of the endocrine system lead to the enlargement of the male breasts. The inability to process toxins leads to liver disease, such as hepatic encephalopathy.Alcohol abuse can result in brain damage which causes impairments in executive functioning such as impairments to working memory and visuospatial function, and can cause an abnormal personality as well as affective disorders to develop. Binge drinking is associated with individuals reporting fair to poor health compared to non-binge drinking individuals and which may progressively worsen over time. Alcohol also causes impairment in a persons critical thinking. A persons ability to reason in stressful situations is compromised, and they seem very inattentive to what is going on around them. Social skills are significantly impaired in people who have alcoholism due to the neurotoxic effects of alcohol on the brain, especially the prefrontal cortex area of the brain. The prefrontal cortex is responsible for cognitive functions such as working memory, impulse control and decision making. This region of the brain is vulnerable to chronic alcohol-induced oxidative DNA damage. The social skills that are impaired by alcohol abuse include impairments in perceiving facial emotions, difficulty with perceiving vocal emotions and theory of mind deficits; the ability to understand humour is also impaired in alcohol abusers. Adolescent binge drinkers are most sensitive to damaging neurocognitive functions especially executive functions and memory. People who abuse alcohol are less likely to survive critical illness with a higher risk for having sepsis and were more likely to die during hospitalization.A smaller volume of consumed alcohol has a greater impact on the older adult than it does on a younger individual. As a result, the American Geriatrics Society recommends for an older adult with no known risk factors less than one drink a day or fewer than two drinks per occasion regardless of gender. Violence Alcohol abuse is significantly associated with suicide and violence. Alcohol is the most significant health concern in Native American communities because of very high rates of alcohol dependence and abuse; up to 80 percent of suicides and 60 percent of violent acts are a result of alcohol abuse in Native American communities.In the United States alcohol-related violence is related to more severe injuries and chronic cases. Pregnancy Alcohol abuse among pregnant women causes their baby to develop fetal alcohol syndrome. Fetal alcohol syndrome is the pattern of physical abnormalities and the impairment of mental development which is seen with increasing frequency among children with alcoholic mothers. Alcohol exposure in a developing fetus can result in slowed development of the fetal brain, resulting in severe retardation or death. Surviving infants may have severe abnormalities such as abnormal eyes, fissures, lips and incomplete cerebella. Some infants may develop lung disease. It is even possible that the baby throughout pregnancy will develop heart defects such as ventricular septal defect or atrial septal defect. Experts suggest that pregnant women take no more than one unit of alcohol per day. However, other organizations advise complete abstinence from alcohol while pregnant. Adolescence Adolescence and the onset of puberty have both a physiological and social impact on a developing person. About half of grade 12 students have been drunk, and a third binge drink. About 3% drink every day. One of these social impacts is the increase in risk-taking behaviors, such as the emergence of alcohol use. Children aged 16 and under who consume alcohol heavily display symptoms of conduct disorder. Its symptoms include troublesome behaviour in school, constantly lying, learning disabilities and social impairments.Alcohol abuse during adolescence greatly increases the risk of developing an alcohol use disorder in adulthood due to changes to neurocircuitry that alcohol abuse causes in the vulnerable adolescent brain. Younger ages of initial consumption among males in recent studies has shown to be associated with increased rates of alcohol abuse within the general population.Societal inequalities (among other factors) have influenced an adolescents decision to consume alcohol. One study suggests that girls were scrutinized for "drinking like men", whereas magazines that target the male population sent underlying messages to boys and or men that drinking alcohol was "masculine". (Bogren, 2010) Causes The cause of alcohol abuse is complex. Alcohol abuse is related to economic and biological origins and is associated with adverse health consequences. Peer pressure influences individuals to abuse alcohol; however, most of the influence of peers is due to inaccurate perceptions of the risks of alcohol abuse. According to Gelder, Mayou and Geddes (2005) easy accessibility of alcohol is one of the reasons people engage in alcohol abuse as this substance is easily obtained in shops. Another influencing factor among adolescents and college students are the perceptions of social norms for drinking; people will often drink more to keep up with their peers, as they believe their peers drink more than they actually do. They might also expect to drink more given the context (e.g. sporting event, house party, etc.). This perception of norms results in higher alcohol consumption than is normal. Alcohol abuse is also associated with acculturation, because social and cultural factors such as an ethnic groups norms and attitudes can influence alcohol abuse. Mental illness A person misusing alcohol may be doing so because they find alcohols effects provide relief from a psychological problem, such as anxiety or depression. Often both the alcohol misuse and psychological problems need to be treated at the same time.The numbing effects of alcohol and narcotics can become a coping strategy for traumatized people who are unable to dissociate themselves from the trauma. However, the altered or intoxicated state of the abuser prevents the full consciousness necessary for healing. Puberty Gender differences may affect drinking patterns and the risk for developing alcohol use disorders. Sensation-seeking behaviors have been previously shown to be associated with advanced pubertal maturation, as well as the company of deviant peers. Early pubertal maturation, as indicated by advanced morphological and hormonal development, has been linked to increased alcohol usage in both male and female individuals. Additionally, when controlling for age, this association between advanced development and alcohol use still held true. Mechanisms Excessive alcohol use causes neuroinflammation and leads to myelin disruptions and white matter loss. The developing adolescent brain is at increased risk of brain damage and other long-lasting alterations to the brain. Adolescents with an alcohol use disorder damage the hippocampal, prefrontal cortex, and temporal lobes. Chronic alcohol exposure can result in increased DNA damage in the brain, as well as reduced DNA repair and increased neuronal cell death. Alcohol metabolism generates genotoxic acetaldehyde and reactive oxygen species.Until recently, the underlying mechanisms mediating the link between pubertal maturation and increased alcohol use in adolescence was poorly understood. Now research has suggested that sex steroid hormone levels may play a role in this interaction. When controlling for age, it was demonstrated that elevated estradiol and testosterone levels in male teenagers undergoing pubertal development was linked to increased alcohol consumption. It has been suggested that sex hormones promote alcohol consumption behaviors in teens by stimulating areas in the male adolescent brain associated with reward processing. The same associations with hormone levels were not demonstrated in females undergoing pubertal development. It is hypothesized that sex steroid hormones, such as testosterone and estradiol, are stimulating areas in the male brain that function to promote sensation-seeking and status-seeking behaviors and result in increased alcohol usage.Additionally, the enzyme TTTan aromatase, which functions in the male brain to convert testosterone to estradiols, has been linked to addictive and reward-seeking behaviors. Therefore, the increased activity of the enzyme may be influencing male adolescent alcohol-usage behaviors during pubertal development. The underlying mechanisms for female alcohol consumption and abuse is still under examination, but is believed to be largely influenced by morphological, rather than hormonal, changes during puberty as well as the presence of deviant peer groups.The brain goes through dynamic changes during adolescence as a result of advancing pubertal maturation, and alcohol can damage long- and short-term growth processes in teenagers. The rapid effect of drugs releases the neurotransmitter dopamine which acts as reinforcement for the behavior.Alcohol is the most recreationally used drug internationally, throughout history it has played a variety of roles, from medicine to a mood enhancer. Alcoholism and alcohol abuse however have undergone rigorous examination as a disease which has pervasive physiological and biosocial implications. The genesis and maintenance of the disease involves the mind, body, society and culture. A common anthropological approach to understanding alcoholism is one which relates to a social factor, and this is cross-cultural studies. The description and analysis of the degree of possibilities in drinking and its results among various populations indeed constitutes one of anthropologys major contributions to the field of alcohol studies. Understanding interactions between factors and evaluating ideas regarding how alcohol usage correlates to other cultural elements requires a number of cross-cultural comparisons. Anthropologists have analyzed a large global sample of cultures examining the association between particular traits for each which relate to the cultural components of alcoholism, these include significant measures which emphasize the social system, reliance and anxiety and strength as physical and social measures. These are the primary drivers of consuming alcohol affecting individuals on a psychosocial level.Individualistic cultures such as the United States or Australia are amongst some of the highest consumers of alcohol in the whole world, however this rate of consumption does not necessarily coincide with the rate of abuse as countries like Russia which are highly collectivist see the highest rates of Alcoholism. Research suggests that people who score highly on individualism, a trait commonly fostered by the culture, report a lower rate of alcohol abuse and alcohol related disorders so much so that the association was negative, however a higher average consumption of alcohol per week. It is implied that individuals will drink more in a given setting, or on average because they are less receptive towards negative social attitudes surrounding excessive consumption. This however acts on another component, by where individualism protects from maladaptive consumption by lowering the need to drink socially. The final axis by which individualism protects from abusive consumption is that it promotes higher degrees of individualization and achievement values which promote personally suited rewards, this allow the individual to be more cognizant of potential alcohol abuse, and therefore protect from damaging mentalities in those who already identify as drinkers.Alcohol abuse also has a variety of biosocial implications, such as the physiologically effects of a detox, how the detox period interacts with ones social life and how these interactions can make beating alcoholism a complex, difficult process. Alcohol abuse can lead to a number of physical issues and may even create a mental health condition, leading to a double classification for the alcoholic. The stress, the social perceptions of these issues may reinforce abusive drinking habits. Alcoholism is the most severe form of alcohol dependence and abuse, it is often in fact a complicated hereditary disease. While it can run it families this is only a correlation and does not prove that the inherited factors play a role. Genetic influences on its genesis are suggested by numerous different sources of evidence. Alcoholism among adopted people has a stronger correlation with their biological parents than with their adopted parents, according to adoption research. Alcohol especially has a large effect on young and developing brains and chances of further abuse, the culture surrounding the acceptable age of drinking therefore can be a biosocial factor. This however isnt always preventable, alcohol when consumed during pregnancy is profoundly damaging. The umbilical cord allows the mothers blood alcohol to reach the infant. Consumption of alcohol during pregnancy can result in miscarriage, and a number of physical and cognitive that can last a lifetime to the child. Therefore the biological implications of alcohol abuse are also further reaching than just the physical issues experienced by the consumer. Diagnosis DSM-IV Alcohol abuse was defined in the DSM-IV as a maladaptive pattern of drinking. For its diagnosis, at least one of the following criteria had to be fulfilled in the last 12 months: Recurrent use of alcohol resulting in a failure to fulfill major role obligations at work, school, or home Recurrent alcohol use in situations in which it is physically hazardous Recurrent alcohol-related legal problems Continued alcohol use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of alcohol DSM-5 The alcohol abuse diagnosis is no longer used in the DSM-5 (released in 2013), it is now part of the alcohol use disorder diagnosis. Of the four alcohol abuse criteria, all except the one referring to alcohol-related legal problems are included in the alcohol use disorder criteria. Screening The Alcohol Use Disorders Identification Test (AUDIT) is considered the most accurate alcohol screening tool for identifying potential alcohol misuse, including dependence. It was developed by the World Health Organisation, designed initially for use in primary healthcare settings with supporting guidance. Prevention Preventing or reducing the harm has been called for via increased taxation of alcohol, stricter regulation of alcohol advertising, and the provision of brief Interventions. Brief Interventions for alcohol abuse reduce the incidence of unsafe sex, sexual violence, unplanned pregnancy, and, likely, STD transmission. Information and education on social norms and the harms associated with alcohol abuse delivered via the internet or face-to-face has not been found to result in any meaningful benefit in changing harmful drinking behaviours in young people.According to European law, individuals who are suffering from alcohol abuse or other related problems cannot be given a drivers license, or if in possession of a license cannot get it renewed. This is a way to prevent individuals driving under the influence of alcohol, but does not prevent alcohol abuse per se.An individuals need for alcohol can depend on their familys alcohol use history. For instance, if it is discovered that their family history with alcohol has a strong pattern, there might be a need for education to be set in place to reduce the likelihood of reoccurrence (Powers, 2007). However, studies have established that those with alcohol abuse tend to have family members who try to provide help. On many of these occasions, the family members would try to help the individual to change or to help improve the individuals lifestyle. Treatment Youth treatment and intervention should focus on eliminating or reducing the effects of adverse childhood experiences, like childhood maltreatment, since these are common risk factors contributing to the early development of alcohol abuse. Approaches like contingency management and motivational interviewing have shown to be effective means of treating substance abuse in impulsive adolescents by focusing on positive rewards and redirecting them towards healthier goals. Educating youth about what is considered heavy drinking along with helping them focus on their own drinking behaviors has been shown to effectively change their perceptions of drinking and could potentially help them to avoid alcohol abuse. Completely stopping the use of alcohol, or "abstinence", is the ideal goal of treatment. The motivation required to achieve abstinence is dynamic; family, friends and health practitioners play a role in affecting this motivation.Some people who abuse alcohol may be able to reduce the amount they drink, also called "drinking in moderation". If this method does not work, the person may need to try abstinence. Abstinence has been regularly achieved by many alcoholics in Alcoholics Anonymous.Mindfulness-based intervention programs (that encourage people to be aware of their own experiences in the present moment and of emotions that arise from thoughts) can reduce the consumption of alcohol.A major barrier to seeking treatment for those struggling with alcohol abuse is the stigma associated with alcohol abuse itself. Those who struggle with alcohol abuse are less likely to utilize substance (or alcohol) abuse treatment services when they perceived higher stigma with alcohol abuse. The stigmatization of individuals who abuse alcohol has been linked to increased levels of depression, increased levels of anxiety, decreased levels of self-esteem, and poor sleeping habits. While negative thoughts and views around the subject of alcohol abuse can keep those struggling with this issue from seeking the treatment they need, there have been several things that have been found to reduce this stigma. Social support can be an effective tool for counteracting the harmful effects of stigma and shame on those struggling with alcohol abuse. Social support can help push those struggling with alcohol abuse to overcome the negative connotation associated with their struggle and finally seek the treatment that they need. Prognosis Alcohol abuse during adolescence, especially early adolescence (i.e. before age 15), may lead to long-term changes in the brain which leaves them at increased risk of alcoholism in later years; genetic factors also influence age of onset of alcohol abuse and risk of alcoholism. For example, about 40 percent of those who begin drinking alcohol before age 15 develop alcohol dependence in later life, whereas only 10 percent of those who did not begin drinking until 20 years or older developed an alcohol problem in later life. It is not entirely clear whether this association is causal, and some researchers have been known to disagree with this view.Alcohol use disorders often cause a wide range of cognitive impairments that result in significant impairment of the affected individual. If alcohol-induced neurotoxicity has occurred a period of abstinence for on average a year is required for the cognitive deficits of alcohol abuse to reverse.College/university students who are heavy binge drinkers (three or more times in the past two weeks) are 19 times more likely to be diagnosed with alcohol dependence, and 13 times more likely to be diagnosed with alcohol abuse compared to non-heavy episodic drinkers, though the direction of causality remains unclear. Occasional binge drinkers (one or two times in the past two weeks), were found to be four times more likely to be diagnosed with alcohol abuse or dependence compared to non-heavy episodic drinkers. Epidemiology Alcohol abuse is said to be most common in people aged between 15 and 24 years, according to Moreira 2009. However, this particular study of 7275 college students in England collected no comparative data from other age groups or countries. Causes of alcohol abuse are complex and are likely the combination of many factors, from coping with stress to childhood development. The US Department of Health & Human Services identifies several factors influencing adolescent alcohol use, such as risk-taking, expectancies, sensitivity and tolerance, personality and psychiatric comorbidity, hereditary factors, and environmental aspects.Studies show that child maltreatment such as neglect, physical, and/or sexual abuse, as well as having parents with alcohol abuse problems, increases the likelihood of that child developing alcohol use disorders later in life. According to Shin, Edwards, Heeren, & Amodeo (2009), underage drinking is more prevalent among teens that experienced multiple types of childhood maltreatment regardless of parental alcohol abuse, putting them at a greater risk for alcohol use disorders. Genetic and environmental factors play a role in the development of alcohol use disorders, depending on age. The influence of genetic risk factors in developing alcohol use disorders increase with age ranging from 28% in adolescence and 58% in adults. Societal and economic costs Alcohol abuse is associated with many accidents, fights, and offences, including criminal. Alcohol is responsible in the world for 1.8 million deaths and results in disability in approximately 58.3 million people. Approximately 40 percent of the 58.3 million people disabled through alcohol abuse are disabled due to alcohol-related neuropsychiatric disorders. Alcohol abuse is highly associated with adolescent suicide. Adolescents who abuse alcohol are 17 times more likely to commit suicide than adolescents who dont drink. Additionally, alcohol abuse increases the risk of individuals either experiencing or perpetrating sexual violence. Alcohol availability and consumption rates and alcohol rates are positively associated with violent crimes, through specifics differ between particular countries and cultures. By country According to studies of present and former alcoholic drinkers in Canada, 20% of them are aware that their drinking has negatively impacted their lives in various vital areas including finances, work and relationships.Problems caused by alcohol abuse in Ireland cost about 3.7 billion euro in 2007.In South Africa, where HIV infection is epidemic, alcohol abusers exposed themselves to double the risk of this infection.The introduction of alcopops, sweet and pleasantly flavoured alcoholic drinks, was responsible for half of the increase in alcohol abuse in 15- and 16-year-olds, according to one survey in Sweden. In the case of girls, the alcopops, which disguise the taste of alcohol, were responsible for two thirds of the increase. The introduction of alcopops to Sweden was a result of Sweden joining the European Union and adopting the entire European Union law.Alcohol misuse costs the United Kingdoms National Health Service £3 billion per year. The cost to employers is 6.4 billion pounds sterling per year. These figures do not include the crime and social problems associated with alcohol misuse. The number of women regularly drinking alcohol has almost caught up with men.In the United States, many people are arrested for drinking and driving. Also, people under the influence of alcohol commit a large portion of various violent crimes, including child abuse, homicide and suicide. In addition, people of minority groups are affected by alcohol-related problems disproportionately, with the exception of Asian Americans. According to criminologist Hung‐En Sung "alcohol is the most widely abused psychoactive substance in the United States". See also 0-0-1-3 – a United States Air Force program for alcohol abuse prevention Drunken monkey hypothesis References Further reading Christopher M. Finan (2017). Drunks: An American History. Beacon Press. ISBN 978-0807001790. External links dassa.sa.gov.au Rethinking Drinking, National Institute on Alcohol Abuse and Alcoholism Alcohol and Crime: Data from 2002 to 2008 Bureau of Justice Statistics Healthy Youth! Alcohol & Drug Abuse – U.S. Centers for Disease Control (CDC)
White dot syndromes	White dot syndromes are inflammatory diseases characterized by the presence of white dots on the fundus, the interior surface of the eye. The majority of individuals affected with white dot syndromes are younger than fifty years of age. Some symptoms include blurred vision and visual field loss. There are many theories for the etiology of white dot syndromes including infectious, viral, genetics and autoimmune. Classically recognized white dot syndromes include: Acute posterior multifocal placoid pigment epitheliopathy Birdshot chorioretinopathy Multiple evanescent white dot syndrome Acute zonal occult outer retinopathy Multifocal choroiditis and panuveitis Punctate inner choroiditis Serpiginous choroiditis Specific white dot syndromes Specific characteristics regarding the white dots and predicted etiology are presented of selected diseases. Acute posterior multifocal placoid pigment epitheliopathy Acute posterior multifocal placoid pigment epitheliopathy primarily occurs in adults (with a mean age of 27). Symptoms include blurred vision in both eyes, but the onset may occur at a different time in each eye. There are yellow-white placoid lesions in the posterior pole at the level of the retinal pigment epithelium. Some suggest a genetic predisposition to the disease, while others postulate an abnormal immune response to a virus. Birdshot choroidopathy Multiple evanescent white dot syndrome Multiple evanescent white dot syndrome occurs mostly in females. Symptoms include a sudden loss of central vision, but patients eventually regain normal vision. The white dots are small and located in the posterior pole at the level of the retinal pigment epithelium. The white dots may disappear after the first few weeks of the disease. The cause is generally unknown, but a viral illness has been reported prior to multiple evanescent white dot syndrom in one-third of cases. Since the disease occurs primarily in females, hormonal status might be a contributing factor. Acute zonal occult outer retinopathy Some discrepancy exists as to whether acute zonal occult outer retinopathy is considered a white dot syndrome. However, it may definitely be related to other diseases included in the white dot syndrome group. Acute zonal occult outer retinopathy occurs in young to middle age adults and may eventually progress to retinal cell death. Symptoms include acute visual field loss and photopsias. Suspected causes include autoimmune, viral, and fungal. Multifocal choroiditis and panuveitis Multifocal choroiditis occurs mainly in myopic females. The fundus presents with yellow or gray lesions (white dots) at the level of the choroid and retinal pigment epithelium. The size of the white dots are between 50 and 500 micrometres and localized in the macula. The disease is characterized by vitritis and anterior chamber inflammation. Decreased vision due to vitreous inflammation may occur. Unlike multiple evanescent white dot syndrome, multifocal choroiditis is a chronic disorder and macular scarring contributes to severe visual loss. Theories regarding the cause include an exogenous pathogen sensitizing an individual to antigens within photoreceptors, retinal pigment epithelium, or choroid. Punctate inner choroiditis Punctate inner choroiditis is an inflammatory choroiditis which occurs mainly in young females. Symptoms include blurred vision and scotomas. Gray-white or yellow lesions are mainly present in the posterior pole and are between 100 and 300 micrometres in size. Punctate inner choroiditis is one of the so-called White dot syndromes which come under the heading posterior uveitis. The appearance of punctate (punched out) areas is at the level of the inner choroid. These lesions are typically located centrally at the back of the eye, or the posterior pole. Serpiginous choroiditis Serpiginous choroiditis, also known as geographic or helicoid choroidopathy, is an uncommon chronic progressive inflammatory condition affecting adult men and women equally in the second to seventh decades of life. Nature of white dots The white dots of the white dot syndromes are lesions that vary in their location in the fundus and in most cases tend to disappear. White dots appear early in the disease stages of punctate inner choroiditis and multiple evanescent white dot syndrome. In this case, the white dot is localized in the posterior pole, small (between 25 and 100 μm), and do not clump together. In contrast, white dots appear later in the disease stages of birdshot choroidopathy, serpiginous choroiditis, and acute posterior multifocal placoid pigment epitheliopathy. The white dots in these diseases may be present throughout the entire fundus, larger (50 to 500 μm), and tend to clump together. Among all these syndromes, there exists some retinal vessel inflammation. The differences in the dots are usually in the size, position, and depth of the lesion within the choroid.The way in which the dots form in some of the white dot syndromes has been reported. The dot appears as a small granuloma which is composed of lymphocytes and macrophages. The lesion may occur within the choroid, between Bruchs membrane and retinal pigment epithelium, or between the retinal pigment epithelium and photoreceptors. Despite the differences in location, the white dots all are of similar composition. The center of the lesion consists of macrophages and epithelioid cells. CD4+ T cells are on the periphery of the granuloma. Benezra has theorized that a large amount of CD8+ T suppressor cells are observed in the later stages of the disease in order to down regulate the inflammatory immune reaction.The formation of a granuloma occurs when activated antigen presenting cells, specifically dendritic cells, "bind to T cells and induce…the release of pro-inflammatory cytokines and chemokines." This response attracts additional antigen presenting cells and will eventually become a granuloma. Choroidal dendritic cells span several levels within the choroid and also associate with the retinal pigment epithelium. Usually, the dendritic cells disappear after removing the antigen. If removal did not occur, the formation of a granuloma would result. The white color of the dots when illuminated may be due to the granulomas composed only of "white cells". Each granuloma will disappear leaving no trace of its presence but in some cases it may leave a punched out scar. It is important to note that the formation of white dots may occur more frequently but is undetected. In normal cases, inflammation of the retina or choroid does not occur. Muller and retinal pigment epithelium cells normally release immunosuppressive factors, but certain combinations of cytokines may stimulate retinal pigment epithelium cells to release factors encouraging inflammation.Generally, mild intraocular inflammation results in a small, discrete, evanescent lesions. Larger dots, having less discrete borders, are the result of high intensity intraocular inflammation. In essence, an immune response with the normal amount and appropriate cytokine release will result in small white dots and a misregulated response eventually will produce scarring of the retinal tissue. Treatment is required in the latter case to combat loss of vision. The white dots usually disappear naturally. Corticosteroids have been shown to speed up this process. The differences in the immune response of each patient may contribute to the differences seen between the white dot syndromes. Distinct diseases Due to the number of common features among the multiple syndromes, many suggest that the white dot syndromes are not distinct and represent a spectrum of one disease. Gass described the AZOOR complex which consists of multiple evanescent white dot syndrome, nultifocal choroiditis, punctate inner choroiditis, acute idiopathic blind spot enlargement, acute macular neuroretinopathy, acute annular outer retinopathy, and acute zonal occult outer retinopathy. He suggested these diseases represent one disease due to common factors such as a high occurrence in females, unexplained visual field loss, and reduced electroretinographic amplitudes. Reddy et al. conducted a study on the blind spots in multifocal choroiditis, punctate inner choroiditis, multiple evanescent white dot syndrome, and diffuse subretinal fibrosis syndrome. Clinical and electroretinographic evidence suggested the diseases are distinct. However, numerous differences do occur in fundus appearance, the clinical course of the diseases, and electrophysiology. Suspected etiology One cause of the White Dot Syndromes as suggested by Gass involves viral or infectious agents. Specifically pertaining to the AZOOR complex, Gass has postulated that a virus may enter the retina at the optic head and the infection may spread from one photoreceptor to another. Some unexplained features include the development of more than one disease in the same patient and the majority of cases occurring in females. According to Beckers common genetic hypothesis, "unlike mendelian genetic disorders, common autoimmune and inflammatory diseases arise from combinatorial interactions of common non-disease specific loci, disease specific loci, and specific environmental triggers." An important aspect of this hypothesis pertains to the existence of common non-disease genes that predispose patients to autoimmune diseases. Jampol and Becker insinuate that common susceptibility genes are present in patients affected by white dot syndromes. The presence of environmental triggers, such as viral infections, immunizations, and stress, and interactions with other genes contribute to the development of the white dot syndromes. Additionally, Jampol and Becker hypothesize that the predisposing genetic loci can be identified.Gass points to a lack of evidence in support of the Becker theory. Instead, Gass highlights that although evidence indicates that patients with acute zonal occult outer retinopathy have a greater chance of developing autoimmune diseases, this does not mean that the complex of disorders are autoimmune diseases. This is supported by the difficulty in detecting "retinal autoantibodies" in patients with acute zonal occult outer retinopathy.Two other diseases which also present with white dots on the fundus are retinitis punctata albescens and fundus albipunctatus. These diseases are not white dot syndromes, but have much more defined etiology. Retinitis punctata albescens is caused by mutations in RLBP1, the gene for retinaldehyde binding protein 1. In comparison, fundus albipunctatus is caused by mutations in RDH5 gene for an 11-cis-RDH in retinal pigment epithelium cells. See also Ophthalmology Retina Retinal pigment epithelium References External links PIC Society, a UK based support group and discussion forum for people with a diagnosis of punctate inner choroidopathy Birdshot Uveitis Society, a UK based support group and discussion forum for people with a diagnosis of birdshot chorioretinopathy
Paroxysmal nonkinesigenic dyskinesia	Paroxysmal Nonkinesigenic Dyskinesia (PNKD) is an episodic movement disorder first described by Mount and Reback in 1940 under the name "Familial paroxysmal choreoathetosis". It is a rare hereditary disease that affects various muscular and nervous systems in the body, passing to roughly fifty percent of the offspring. Signs and symptoms The condition manifests itself as attacks lasting from a few minutes to several hours. Episodes only happen when the individual is awake, and they remain conscious throughout the attack. Symptoms are most severe in youth and lessen with age. Sufferers can have multiple attacks on a daily basis or may have periods of weeks or months between attacks. Symptoms experienced during attacks can vary and include dystonia, chorea, athetosis, ballismus, or a combination. Genetics It has been mapped to chromosome 2q31-36.It has been associated with PNKD. Risk triggers While not the same in all people, there are several common triggers that can precipitate an attack: Moderate to high consumption of stimulants, such as alcohol, caffeine, or nicotine. Low amounts of energy due to hunger, lack of sleep, illness, or physical fatigue. Moderate to high presence of stress. Menstruation and ovulation. Diagnosis Treatment Most pharmacological treatments work poorly, but the best treatment is a low dosage of clonazepam, a muscle relaxant. Patients may also benefit from other benzodiazepines, phenobarbital, and other anticonvulsants such as valproic acid. Affected individuals have reported garlic to be effective for softening the attacks, but no studies have been done on this. References == External links ==
Trichilemmal cyst	A trichilemmal cyst is a common cyst that forms from a hair follicle, most often on the scalp, and is smooth, mobile, and filled with keratin, a protein component found in hair, nails, skin, and horns. Trichilemmal cysts are clinically and histologically distinct from trichilemmal horns, hard tissue that is much rarer and not limited to the scalp. Rarely, these cysts may grow more extensively and form rapidly multiplying trichilemmal tumors, also called proliferating trichilemmal cysts, which are benign, but may grow aggressively at the cyst site. Very rarely, trichilemmal cysts can become cancerous. Classification Trichilemmal cysts may be classified as sebaceous cysts, although technically speaking are not sebaceous. "True" sebaceous cysts, which originate from sebaceous glands and which contain sebum, are relatively rare and are known as steatocystoma simplex or, if multiple, as steatocystoma multiplex. Medical professionals have suggested that the term "sebaceous cyst" be avoided since it can be misleading.: 31 In practice, however, the term is still often used for epidermoid and pilar cysts. Pathogenesis Trichilemmal cysts are derived from the outer root sheath of the hair follicle. Their origin is currently unknown, but they may be produced by budding from the external root sheath as a genetically determined structural aberration. They arise preferentially in areas of high hair follicle concentrations, so 90% of cases occur on the scalp. They are solitary in 30% and multiple in 70% of cases.Histologically, they are lined by stratified squamous epithelium that lacks a granular cell layer and are filled with compact "wet" keratin. Areas consistent with proliferation can be found in some cysts. In rare cases, this leads to formation of a tumor, known as a proliferating trichilemmal cyst. The tumor is clinically benign, although it may display nuclear atypia, dyskeratotic cells, and mitotic figures. These features can be misleading, and a diagnosis of squamous cell carcinoma may be mistakenly rendered. Treatment Surgical excision is required to treat a trichilemmal cyst. The method of treatment varies depending on the physicians training. Most physicians perform the procedure under local anesthetic. Others prefer a more conservative approach. This involves the use of a small punch biopsy about one-fourth the diameter of the cyst. The punch biopsy is used to enter the cyst cavity. The contents of the cyst are emptied, leaving an empty sac. As the pilar cyst wall is the thickest and most durable of the many varieties of cysts, it can be grabbed with forceps and pulled out of the small incision. This method is best performed on cysts larger than a pea that have formed a thick enough wall to be easily identified after the sac is emptied. Small cysts have thin walls, so are easily fragmented on traction. This increases the likelihood of cyst recurrence. This method often results in only a small scar, and very little if any bleeding. See also Proliferating epidermoid cyst List of cutaneous conditions References == External links ==
Solar urticaria	Solar urticaria (SU) is a rare condition in which exposure to ultraviolet or UV radiation, or sometimes even visible light, induces a case of urticaria or hives that can appear in both covered and uncovered areas of the skin. It is classified as a type of physical urticaria. The classification of disease types is somewhat controversial. One classification system distinguished various types of SU based on the wavelength of the radiation that causes the breakout; another classification system is based on the type of allergen that initiates a breakout.The agent in the human body responsible for the reaction to radiation, known as the photoallergen, has not yet been identified. The disease itself can be difficult to diagnose properly because it is so similar to other dermatological disorders, such as polymorphic light eruption or PMLE. The most helpful test is a diagnostic phototest, a specialized test which confirms the presence of an abnormal sunburn reaction. Once recognized, treatment of the disease commonly involves the administration of antihistamines, and desensitization treatments such as phototherapy. In more extreme cases, the use of immunosuppressive drugs and even plasmapheresis may be considered.The initial discovery of the disease is credited to P. Merklen in 1904, but it did not have a name until the suggestion of "solar urticaria" was given by Duke in 1923. However, their research contributed to the study of this uncommon disease. More than one hundred cases have been reported in the past century. Signs and symptoms Generally, the areas affected are exposed skin not usually protected by clothing; however it can also occur in areas covered by clothing. Areas constantly subjected to the suns rays may only be slightly affected if at all. People with extreme cases will also have reactions to artificial light sources that emit a UV wavelength. Parts of the body only thinly covered can also potentially be subjected to an outbreak. Life with SU can be difficult. Patients are subject to constant itching and pain, as within minutes of the initial exposure to UV radiation a rash will appear. The urticarial reaction begins in the form of pruritus, later progressing to erythema and edema in the exposed areas of the skin. If vast areas of the body are affected, the loss of fluid into the skin could lead to light-headedness, headache, nausea, and vomiting. Extremely rarely, patients have been reported to experience an increase in heart rate that can cause a stroke or heart attack due to the body cavity swelling. Other rare side effects can be bronchospasm and glucose instability issues. Also, if a large area of the body is suddenly exposed the person may be subject to an anaphylactic reaction. Once free of exposure, the rash will usually fade away within several hours; rare and extreme cases can take a day or two to normalize depending on severity of the reaction. Causes Solar urticaria is an immunoglobulin E-mediated hypersensitivity that can be introduced through primary or secondary factors, or induced by exogenous photosensitization. Primary SU is believed to be a type I hypersensitivity (a mild to severe reaction to an antigen including anaphylaxis) in which an antigen, or substance provoking an immune response, is "induced by UV or visible radiation." Secondary SU can occur when a person comes into contact with chemicals such as tar, pitch, and dyes. People who use drugs such as benoxaprofen or patients with erythropoietic protoporphyria may also contract this secondary form. These items that cause this photosensitivity are exogenous photosensitizers because they are outside of the body and cause it to have a greater sensitivity to light.Also, there have been a few unorthodox (unusual) causes of solar urticaria. For those susceptible to visible light, white T-shirts may increase the chances of experiencing an outbreak. In one case, doctors found that the white T-shirt absorbed UVA radiation from the sun and transformed it into visible light which caused the reaction. Another patient was being treated with the antibiotic tetracycline for a separate dermatological disorder and broke out in hives when exposed to the sun, the first case to implicate tetracycline as a solar urticaria inducing agent.It is not yet known what specific agent in the body brings about the allergic reaction to the radiation. When patients with SU were injected with an irradiated autologous serum, many developed urticaria within the area of injection. When people who did not have SU were injected, they did not demonstrate similar symptoms. This indicates that the reaction is only a characteristic of the patients with solar urticaria and that it is not phototoxic. It is possible that this photoallergen is located on the binding sites of IgE that are found on the surface of mast cells. The photoallergen is believed to begin its configuration through the absorption of radiation by a chromophore. The molecule, because of the radiation, is transformed resulting in the formation of a new photoallergen. Diagnosis Solar urticaria can be difficult to diagnose, but its presence can be confirmed by the process of phototesting. There are several forms of these tests including photopatch tests, phototests, photoprovocation tests, and laboratory tests. All of these are necessary to determine the exact condition of the patient. Photopatch tests are patch tests conducted when it is believed that a patient is experiencing certain symptoms due to an allergy that will only occur when in contact with sunlight. After the procedure, the patient is given a low dosage of UVA radiation. Another test known as a phototest is the most useful in identifying solar urticaria. In this test, one centimeter segments of skin are subject to varying amounts of UVA and UVB radiation in order to determine the specific dosage of the certain form of radiation that causes the urticaria to form. When testing for its less intense form (fixed solar urticaria), phototesting should be conducted only in the areas where the hives have appeared to avoid the possibility of getting false-negative results.A third form of testing is the photoprovocation test which is used to identify disorders instigated by sun burns. The process of this test involves exposing one area of a patients arm to certain dosage of UVB radiation and one area on the other arm to a certain dosage of UVA radiation. The amount of radiation that the patient is exposed to is equal to that "received in an hour of midday summer sun." If the procedure produces a rash, then the patient will undergo a biopsy. Finally, there are laboratory tests which generally involve procedures such as blood, urine, and fecal biochemical tests. In some situations, a skin biopsy may be performed. Classification Solar urticaria, due to its particular features, is considered to be a type of physical urticaria or light sensitivity. Physical urticaria arises from physical factors in the environment, which in the case of solar urticaria is UV radiation or light. SU may be classified based on the wavelength of the radiative energy that causes the allergic reaction; known as Harbers classification, six types have been identified in this system. Type I solar urticaria is caused by UVB (ultraviolet B) radiation, with wavelengths ranging from 290 to 320 nm. Type II is induced by UVA (ultraviolet A) radiation with wavelengths that can range from 320 to 400 nm. The wavelength range of type III and IV spans from 400 to 500 nm, while type V can be caused by UVB radiation to visible light (280–600 nm). Type VI has only been known to occur at 400 nm.Another classification distinguishes two types. The first is a hypersensitivity caused by a reaction to photoallergens located only in people with SU; while the second is caused by photoallergens that can be found in both people with SU and people without it.A subgroup of solar urticaria, fixed solar urticaria, has also been identified. It is a rare, less intense form of the disease with wheals (swollen areas of the skin) that affect certain, fixed areas of the body. Fixed solar urticaria is induced by a broad spectrum of radiative energy with wavelengths ranging from 300 to 700 nm. Differential diagnosis Polymorphous light eruption (PMLE) is the easiest disease to mistake for solar urticaria because the locations of the lesions are similar (the V of the neck and the arms). However, patients with SU are more likely to develop lesions on the face. Also, a reaction with PMLE will take a greater amount of time to appear than with solar urticaria. Lupus erythematosus has been mistaken for SU; however, lesions from lupus erythematosus will take a longer amount of time to go away. Furthermore, when being tested for the two diseases, patients with SU have a reaction immediately while patients with lupus erythematosus will have a delayed reaction. Patients who have experienced solar urticarial symptoms from a young age could mistakenly be thought to have erythropoietic protoporphyria. However, the main symptom for this disease is pain and patients with have been found to have abnormal levels of protoporphyrin in their blood while these levels are normal in SU patients. Finally, cholinergic urticaria, or urticaria induced by heat, can occasionally appear to be solar urticaria because the heat from the sun will cause a person with the disease to have a reaction. Management Antihistamines Histamines are proteins associated with many allergic reactions. When the UV radiation or light comes in contact with a person with solar urticaria, histamine is released from mast cells. When this occurs, the permeability of vessels near the area of histamine release is increased. This allows blood fluid to enter the vessels and cause inflammation. Antihistamines suppress the activity of the histamine.Diphenhydramine, a first-generation H1 receptor antagonist or medicine that combats the H1 receptor that is associated with many allergic reactions, has been found to be the most potent antihistamine for this particular disease. Patients prescribed 50 milligrams four times per day have been able to sustain normal exposure to the sun without developing a reaction. Patients with less potent forms of solar urticaria such as fixed solar urticaria can be treated with the medication fexofenadine, which may also be used prophylactically to prevent recurrence. Desensitization This form of treatment is meant to reduce the intensity or altogether eliminate the allergic reactions people have by gradually increasing exposure to the form of radiation that brings about the reaction. In the case of solar urticaria, phototherapy and photochemotherapy are the two major desensitization treatments.Phototherapy can be used for prevention. Exposure to a certain form of light or UV radiation enables the patient to build up a tolerance and outbreaks can be reduced. This type of treatment is generally conducted in the spring. However, the benefits of this therapy only last for two to three days.Photochemotherapy, or PUVA, is considered superior to phototherapy because it produces a longer-lasting tolerance of the radiation that initiates the outbreak. When treatment first begins, the main goal is to build up the patients tolerance to UVA radiation enough so that they can be outdoors without having an episode of solar urticaria. Therefore, treatments are regulated at three per week while constantly increasing the exposure to UVA radiation. Once the patient has reached an adequate level of desensitization, treatments are reduced to once or twice per week. Immunoglobulin E (IgE) Therapy Some patients and researchers have successfully treated solar urticaria with Omalizumab (trade name Xolair) which is commonly used to treat Idiopathic Urticaria. Omalizumab is a recombinant humanized monoclonal antibody against IgE. It acts by binding free IgE at the same site that IgE would bind to its high-affinity receptor (FcεRI) on mast cells, thereby reducing free IgE in the serum Immunosuppression Doctors will sometimes prescribe immunosuppressive drugs such as prednisolone and ciclosporin if the patient has an intense form of solar urticaria. However, the side effects of these medicines can be severe which is why they are reserved for the most extreme of cases. Plasmapheresis In more extreme cases, plasmapheresis can be considered. This technique is used to remove the blood plasma or fluid in the red blood cells and then return the cells to the body. It "removes a circulating factor from the blood that may be involved in causing the urticaria," but is still being tested and is not always effective. When the treatment is a success, the patients photosensitivity is decreased to the degree that they can undergo PUVA which can result in the relief of the urticarial outbreaks for an extended period of time. The major setback to this treatment is that the side effects can be severe and may include anaphylactoid reactions. Epidemiology In the United States, only about 4% of patients with photosensitive disorders are reported to have been diagnosed with solar urticaria. Internationally, the number is slightly larger at 5.3%. Solar urticaria may occur in all races but studies monitoring 135 African Americans and 110 Caucasians with photodermatoses found that 2.2% of the African Americans had SU and 8% of the Caucasians had the disease showing that Caucasians have a better chance of getting the disease. The age ranges anywhere from 5–70 years old, but the average age is 35 and cases have been reported with children that are still in infancy. Solar urticaria accounts for less than one percent of the many documented urticaria cases. To put that into a better perspective, since its first documented case in Japan in 1916, over one hundred other instances of the disease have been reported. History Solar urticaria was first identified by P. Merklen in 1904. Just a year later, in 1905, Ward became the first to induce urticaria through exposure to the sun in a controlled environment. The first documented case came in Japan in 1916. The name "solar urticaria" was proposed in 1923. In 1928 urticaria was induced for the first time. This was carried out by phototesting with increasing amounts of radiation of varying wavelengths. In 1942 the disease was passively transferred to normal volunteers using serum from patients with solar urticaria. References == External links ==
Buccal bifurcation cyst	Buccal bifurcation cyst is an inflammatory odontogenic cyst, of the paradental cysts family, that typically appears in the buccal bifurcation region of the mandibular first molars in the second half of the first decade of life. Infected cysts may be associated with pain. Management Although the treatment of the cyst was previously enuclation of the cyst with removal of the involved tooth or enuclation with root-canal treatment, the current management is enuclation with the preservation of the involved tooth. However, recent evidence suggests self-resolution of this type of cyst, thus close observation with meticulous oral hygiene measures can be employed unless the cyst is infected and symptomatic. == References ==
Familial amyloid polyneuropathy	Familial amyloid polyneuropathy, also called transthyretin-related hereditary amyloidosis, transthyretin amyloidosis abbreviated also as ATTR (hereditary form), or Corino de Andrades disease, is an autosomal dominant neurodegenerative disease. It is a form of amyloidosis, and was first identified and described by Portuguese neurologist Mário Corino da Costa Andrade, in 1952. FAP is distinct from senile systemic amyloidosis (SSA), which is not inherited, and which was determined to be the primary cause of death for 70% of supercentenarians who have been autopsied. FAP can be ameliorated by liver transplantation. Presentation Usually manifesting itself between 20 and 40 years of age, it is characterized by pain, paresthesia, muscular weakness and autonomic dysfunction. In its terminal state, the kidneys and the heart are affected. FAP is characterized by the systemic deposition of amyloidogenic variants of the transthyretin protein, especially in the peripheral nervous system, causing a progressive sensory and motor polyneuropathy. Cause FAP is caused by a mutation of the TTR gene, located on human chromosome 18q12.1-11.2. A replacement of valine by methionine at position 30 (TTR V30M) is the mutation most commonly found in FAP. The transthyretin protein is a tetramer. The tetramer has to dissociate into misfolded monomers to aggregate into a variety of structures including amyloid fibrils. Because most patients are heterozygotes, they deposit both mutant and wild type TTR subnits.FAP is inherited in an autosomal dominant manner. This means that the defective gene responsible for the disorder is located on an autosome (chromosome 18 is an autosome), and only one copy of the defective gene is sufficient to cause the disorder, when inherited from a parent who has the disorder. Diagnosis Clinical suspicion for FAP is raised on the basis of a family history of neuropathy and physical exam showing signs of neuropathy. Diagnosis can be made using genetic testing to identify mutations in the TTR gene, but may include other corroborative investigation. Nerve conduction testing typically shows an axonal polyneuropathy, with sensory involvement greater than motor. Superimposed mononeuropathies may also be evident, such as a median mononeuropathy at the wrist (carpal tunnel syndrome). Electromyography (EMG) may show evidence of chronic denervation and reinnervation. Autonomic testing, including quantitative sweat testing, can reveal involvement of the autonomic nervous system. Occasionally, biopsy of skin, nerve, or muscle may be performed, which can show signs of denervation and amyloid deposition with response to anti-TTR antibodies. Additional testing should be performed to identify involvement of the heart or kidneys.Sudomotor function through electrochemical skin conductance may provide a measure of subclinical autonomic involvement. Treatments The medication tafamidis has been approved for the treatment of transthyretin familial amyloid polyneuropathy in Europe. Studies have found that it delays neurological problems when started early. The US Food and Drug Administrations Peripheral and Central Nervous System Drugs Advisory Committee rejected the drug in June 2012, in a 13-4 vote. The committee stated that there was not enough evidence supporting efficacy of the drug, and requested additional clinical trials.In August 2018, the FDA approved patisiran, an siRNA-based treatment, at an expected cost of up to $450,000 per year.In August 2021 six patients with hereditary ATTR amyloidosis with polyneuropathy were given doses of NTLA-2001, based on a CRISPR gene editing system. Researchers reported mild adverse events and decreases in serum misfolded transthyretin protein concentrations through targeted knockout. Prognosis In the absence of a liver transplant, FAP is invariably fatal, usually within a decade. The disadvantage of liver transplantation is that approximately 10% of the subjects die from the procedure or complications resulting from the procedure, which is a form of gene therapy wherein the liver expressing wild type and mutant TTR is replaced by a liver only expressing wild type TTR. Moreover, transplanted patients must take immune suppressants (medications) for the remainder of their life, which can lead to additional complications. In late 2011, the European Medicines Agency approved the transthyretin kinetic stabilizer Tafamidis or Vyndaqel discovered by Jeffery W. Kelly and developed by FoldRx pharmaceuticals (acquired by Pfizer in 2010) for the treatment of FAP based on clinical trial data. Tafamidis (20 mg once daily) slowed the progression of FAP over a 36-month period and importantly reversed the weight loss and muscle wasting associated with disease progression. Epidemiology This disease is endemic in Portuguese locations Póvoa de Varzim and Vila do Conde (Caxinas), with more than 1000 affected people, coming from about 500 families, where 70% of the people develop the illness. ll the analysed Portuguese families presented the same haplotype (haplotype I) associated with the Met 30 mutation. In northern Sweden, more specifically Skellefteå (it is locally called "Skelleftesjukan", the Skellefteå disease), 1.5% of the population has the mutated gene. There are many other populations in the world who exhibit the illness after having developed it independently. References External links GeneReviews/NIH/NCBI/UW entry on Familial Transthyretin Amyloidosis
Cerocorticium molle	Cerocorticium molle is a species of crust fungus in the family Meruliaceae. Taxonomy The fungus was first described by Miles Berkeley and Moses Ashley Curtis in 1868 as Corticium molle. They described the fruit body of the type specimen as resembling "a thin coating of wax poured over the surface". It was transferred to genus Cerocorticium by Walter Jülich in 1975. Habitat and distribution Cerocorticium molle grows on the dead bark and wood of a variety of angiosperms, and it has occasionally been recorded growing on or under the bark of living trees. It is found in tropical and subtropical regions of Africa, Asia, North America, and South America. == References ==
Paraphrenia	Paraphrenia is a mental disorder characterized by an organized system of paranoid delusions with or without hallucinations (the positive symptoms of schizophrenia) and without deterioration of intellect or personality (its negative symptom).This disorder is also distinguished from schizophrenia by a lower hereditary occurrence, less premorbid maladjustment, and a slower rate of progression. Onset of symptoms generally occurs later in life, near the age of 60. The prevalence of the disorder among the elderly is between 0.1% and 4%.Paraphrenia is not included in the DSM-5; psychiatrists often diagnose patients presenting with paraphrenia as having atypical psychosis, delusional disorder, psychosis not otherwise specified, schizoaffective disorders, and persistent persecutory states of older adults. Recently, mental health professionals have also been classifying paraphrenia as very late-onset schizophrenia-like psychosis.In the Russian psychiatric manuals, paraphrenia (or paraphrenic syndrome) is the last stage of development of paranoid schizophrenia. "Systematized paraphrenia" (with systematized delusions i. e. delusions with complex logical structure) and "expansive-paranoid paraphrenia" (with expansive/grandiose delusions and persecutory delusions) are the variants of paranoid schizophrenia (F20.0). Sometimes systematized paraphrenia can be seen with delusional disorder (F22.0). The word is from Ancient Greek: παρά – beside, near + φρήν – intellect, mind. Signs and symptoms The main symptoms of paraphrenia are paranoid delusions and hallucinations. The delusions often involve the individual being the subject of persecution, although they can also be erotic, hypochondriacal, or grandiose in nature. The majority of hallucinations associated with paraphrenia are auditory, with 75% of patients reporting such an experience; however, visual, tactile, and olfactory hallucinations have also been reported. The paranoia and hallucinations can combine in the form of “threatening or accusatory voices coming from neighbouring houses [and] are frequently reported by the patients as disturbing and undeserved". Patients also present with a lack of symptoms commonly found in other mental disorders similar to paraphrenia. There is no significant deterioration of intellect, personality, or habits and patients often remain clean and mostly self-sufficient. Patients also remain oriented well in time and space.Paraphrenia is different from schizophrenia because, while both disorders result in delusions and hallucinations, individuals with schizophrenia exhibit changes and deterioration of personality whereas individuals with paraphrenia maintain a well-preserved personality and affective response. Causes Neurological Paraphrenia is often associated with a physical change in the brain, such as a tumor, stroke, ventricular enlargement, or neurodegenerative process. Research that reviewed the relationship between organic brain lesions and the development of delusions suggested that "brain lesions which lead to subcortical dysfunction could produce delusions when elaborated by an intact cortex". Predisposing factors Many patients who present with paraphrenia have significant auditory or visual loss, are socially isolated with a lack of social contact, do not have a permanent home, are unmarried and without children, and have maladaptive personality traits. While these factors do not cause paraphrenia, they do make individuals more likely to develop the disorder later in life. Diagnosis While the diagnosis of paraphrenia is absent from recent revisions of the DSM and the ICD, many studies have recognized the condition as "a viable diagnostic entity that is distinct from schizophrenia, with organic factors playing a role in a significant portion of patients." As such, paraphrenia is seen as being distinct from both schizophrenia and progressive dementia in old age. Ravindran (1999) developed a list of criteria for the diagnosis of paraphrenia, which agrees with much of the research done up to the time it was published. 1. A delusional disorder of at least six months duration characterized by the following: a. Preoccupation with one or more semisystematized delusions, often accompanied by auditory hallucinations. b. Affect notably well-preserved and appropriate. Ability to maintain rapport with others. c. None of i. Intellectual deterioration ii. Visual hallucinations iii. Incoherence iv. Flat or grossly inappropriate affect v. Grossly disorganized behavior at times other than during the acute episode. d. Disturbance of behavior understandable in relation to the content of the delusions and hallucinations. e. Only partly meets criterion A for schizophrenia. No significant organic brain disorder. Management Research suggests that paraphrenics respond well to antipsychotic drug therapy if doctors can successfully achieve sufficient compliance. Herbert found that Stelazine combined with Disipal was an effective treatment. It promoted the discharging of patients and kept discharged patients from being readmitted later. While behavior therapy may help patients reduce their preoccupation with delusions, psychotherapy is not currently of primary value. Prognosis Individuals who develop paraphrenia have a life expectancy similar to the normal population. Recovery from the psychotic symptoms seems to be rare, and in most cases paraphrenia results in in-patient status for the remainder of the life of the patient. Patients experience a slow deterioration of cognitive functions and the disorder can lead to dementia in some cases, but this development is no greater than the normal population. Epidemiology Studies suggest that the prevalence of paraphrenia in the elderly population is around 2–4%. Sex differences While paraphrenia can occur in both men and women, it is more common in women, even after the difference has been adjusted for life expectancies. The ratio of women with paraphrenia to men with paraphrenia is anywhere from 3:1 to 45:2. Age It is seen mainly in patients over the age of 60, but has been known to occur in patients in their 40s and 50s. Personality type and living situation It is suggested that individuals who develop paraphrenia later in life have premorbid personalities, and can be described as “quarrelsome, religious, suspicious or sensitive, unsociable and cold-hearted.” Many patients were also described as being solitary, eccentric, isolated and difficult individuals; these characteristics were also long-standing rather than introduced by the disorder. Most of the traits recognized prior to the onset of paraphrenia in individuals can be grouped as either paranoid or schizoid. Patients presenting with paraphrenia were most often found to be living by themselves (either single, widowed, or divorced). There have also been reports of low marriage rate among paraphrenics and these individuals also have few or no children (possibly because of this premorbid personality). Physical factors The development of paranoia and hallucinations in old age have been related to both auditory and visual impairment, and individuals with paraphrenia often present with one or both of these impairments. Hearing loss in paraphrenics is associated with early age of onset, long duration, and profound auditory loss. History The term paraphrenia was originally popularized by Karl Ludwig Kahlbaum in 1863 to describe the tendency of certain psychiatric disorders to occur during certain transitional periods in life (describing paraphrenia hebetica as the insanity of the adolescence and paraphrenia senilis as the insanity of the elders.The term was also used by Sigmund Freud for a short time starting in 1911 as an alternative to the terms schizophrenia and dementia praecox, which in his estimation did not correctly identify the underlying condition, and by Emil Kraepelin in 1912/3, who changed its meaning to describe paraphrenia as it is understood today, as a small group of individuals that have many of the symptoms of schizophrenia with a lack of deterioration and thought disorder. Kraepelins study was discredited by Wilhelm Mayer in 1921 when he conducted a follow-up study using Kraepelins data. His study suggested that there was little to no discrimination between schizophrenia and paraphrenia; given enough time, patients presenting with paraphrenia will merge into the schizophrenic pool. However, Meyers data are open to various interpretations. In 1952, Roth and Morrissey conducted a large study in which they surveyed the mental hospital admissions of older patients. They characterized patients as having "paraphrenic delusions which… occurred in each case in the setting of a well-preserved intellect and personality, were often ‘primary’ in character, and were usually associated with the passivity failings or other volitional disturbances and hallucinations in clear consciousness pathognomonic of schizophrenia".In recent medicine, the term paraphrenia has been replaced by the diagnosis of "very late-onset schizophrenia-like psychosis" and has also been called "atypical psychoses, delusional disorder, psychoses not otherwise specified, schizoaffective disorders, and persistent persecutory states of older adults" by psychotherapists. Current studies, however, recognize the condition as "a viable diagnostic entity that is distinct from schizophrenia, with organic factors playing a role in a significant portion of patients." References External links Harris, M. J.; Jeste, D. V. (1988). "Late-onset schizophrenia: an overview". Schizophrenia Bulletin. 14 (1): 39–55. doi:10.1093/schbul/14.1.39. PMID 3291094. Canadian Journal of Psychiatry, March 1999, Paraphrenia redefined Dilip V. Jeste; Jane S. Paulsen; M. Jackuelyn Harris. "Late-Onset Schizophrenia and Other Related Psychoses". www.acnp.org. Archived from the original on 2010-03-08. Retrieved 2009-12-26.
Placental insufficiency	Placental insufficiency or utero-placental insufficiency is the failure of the placenta to deliver sufficient nutrients to the fetus during pregnancy, and is often a result of insufficient blood flow to the placenta. The term is also sometimes used to designate late decelerations of fetal heart rate as measured by cardiotocography or an NST, even if there is no other evidence of reduced blood flow to the placenta, normal uterine blood flow rate being 600mL/min. Causes The following characteristics of placentas have been said to be associated with placental insufficiency, however all of them occur in normal healthy placentas and full term healthy births, so none of them can be used to accurately diagnose placental insufficiency: Abnormally thin placenta (less than 1 cm) Circumvallate placenta (1% of normal placentas) Amnion cell metaplasia, (amnion nodosum) (present in 65% of normal placentas) Increased syncytial knots Calcifications Infarcts due to focal or diffuse thickening of blood vessels Villi capillaries occupying about 50% of the villi volume or when <40% of capillaries are on the villous peripheryPlacental insufficiency should not be confused with complete placental abruption, in which the placenta separates off the uterine wall, which immediately results in no blood flow to the placenta, which leads to immediate fetal demise. In the case of a marginal, incomplete placental abruption of less than 50%, usually weeks of hospitalization precedes delivery and outcomes are not necessarily affected by the partial abruption. Pathophysiology Maternal effects Several aspects of maternal adaptation to pregnancy are affected by dysfunction of placenta. Maternal arteries fail to transform into low-resistance vessels (expected by 22–24 weeks of gestation). This increases vascular resistance in fetoplacental vascular bed eventually leading to reduction in metabolically active mass of placenta like a vicious cycle. Fetal effects Placental insufficiency can affect the fetus, causing fetal distress. Placental insufficiency may cause oligohydramnios, preeclampsia, miscarriage or stillbirth. Placental insufficiency is most frequent cause of asymmetric IUGR. Fetal metabolic changes Metabolic changes occurring in uteroplacental insufficiency: Fetal hormonal changes Decrease in overall thyroid function is correlated with fetal hypoxemia. Serum glucagon, adrenaline, noradrenaline levels increase, eventually causing peripheral glycogenolysis and mobilization of fetal hepatic glycogen stores. Fetal hematologic changes Fetal hypoxemia triggers erythropoietin release. This stimulates RBC production from medullary and extramedullary sites and eventually results in polycythemia. Oxygen carrying capacity of blood is thus increased. Prolonged tissue hypoxemia may cause early release of erythrocytes from maturation sites and thus count of nucleated RBCs in blood increases. These factors, increase in blood viscosity, decrease in cell membrane fluidity and platelet aggregation are important precursors in accelerating placental vascular occlusion. Fetal immunological changes There is decrease in immunoglobulin, absolute B-cell counts and total WBC count. T-helper and cytotoxic T-cells are suppressed in proportion of degree of acidemia. These conditions lead to higher infection susceptibility of infant after delivery. Fetal cardiovascular changes There is decrease in magnitude of umbilical venous volume flow. In response to this, the proportion of umbilical venous blood diverted to fetal heart increases. This eventually leads to elevation of pulmonary vascular resistance and increased right ventricular afterload. This fetal cerebral redistribution of blood flow is an early response to placental insufficiency. Blood flow is selectively redirected to the myocardium, adrenal glands, and in particular to the brain in a brain-sparing effect.In late stage, the redistribution becomes ineffective, there is decrease in cardiac output, ineffective preload handling and elevation of central venous pressure. This deterioration in circulation may ultimately lead to tricuspid insufficiency and death of the fetus. Peripheral circulatory disturbances also accompany these central circulatory changes. Fetal behavioral changes Chronic hypoxemia leads to delay in all aspects of CNS maturation. With worsening fetal hypoxemia, there is decline in fetal activity. With further hypoxemia, fetal breathing ceases. Gross body movements and tone decrease further. Fetal heart rate decreases due to spontaneous deceleration due to direct depression of cardiac contractility. This leads to intrauterine fetal death. Risk of later metabolic disease According to the theory of thrifty phenotype, placental insufficiency triggers epigenetic responses in the fetus that are otherwise activated in times of chronic food shortage. If the offspring actually develops in an environment rich in food it may be more prone to metabolic disorders, such as obesity and type II diabetes. Diagnosis The following tests have been promoted as supposedly diagnosing placental insufficiency, but all have been unsuccessful at predicting stillbirth due to placental insufficiency: Placental grading Amniotic fluid index Fetal biophysical profile test scoring Doppler velocimetry Routine ultrasound scanning Detection and management of maternal diabetes mellitus Antenatal fetal heart rate monitoring using cardiotocography Vibroacoustic stimulation, fetal movement counting Home vs. hospital-based bed rest and monitoring in high-risk pregnancy In-hospital fetal surveillance unit Use of the partograph during labor Cardiotocography during labor with or without pulse oximetry See also Small for gestational age References == External links ==
Tubulocystic renal cell carcinoma	Tubulocystic renal cell carcinoma is rare subtype of renal cell carcinoma. == References ==
Keratomalacia	Keratomalacia is an eye disorder that results from vitamin A deficiency. Vitamin A is required to maintain specialized epithelia (such as in the cornea and conjunctiva). The precise mechanism is still not known, but vitamin A is necessary for the maintenance of the specialized epithelial surfaces of the body. A lack of vitamin A leads to atrophic changes in the normal mucosal surface, with loss of goblet cells, and replacement of the normal epithelium by an inappropriate keratinized stratified squamous epithelium. In addition, the substantia propria of the cornea breaks down and liquefies, resulting in keratomalacia.The resulting cornea becomes totally opaque, which is one of the most common reasons for blindness around the world, particularly in developing countries. See also Acute promyelocytic leukemia Keratoconjunctivitis sicca Xerophthalmia References External links patient.co.uk
Propionic acidemia	Propionic acidemia, also known as propionic aciduria or propionyl-CoA carboxylase deficiency (PCC deficiency), is a rare autosomal recessive metabolic disorder, classified as a branched-chain organic acidemia.The disorder presents in the early neonatal period with poor feeding, vomiting, lethargy, and lack of muscle tone. Without treatment, death can occur quickly, due to secondary hyperammonemia, infection, cardiomyopathy, or brain damage. Symptoms and signs Propionic acidemia is characterized almost immediately in newborns. Symptoms include poor feeding, vomiting, dehydration, acidosis, low muscle tone (hypotonia), seizures, and lethargy. The effects of propionic acidemia quickly become life-threatening. Long-term complications can include chronic kidney disease, cardiomyopathy, and prolonged QTc interval. Pathophysiology In healthy individuals, enzyme propionyl-CoA carboxylase converts propionyl-CoA to methylmalonyl-CoA. This is one of many steps in the process of converting certain amino acids and fats into energy. Individuals with propionic acidemia cannot perform this conversion because the enzyme propionyl-CoA carboxylase is nonfunctional. The essential amino acids valine, methionine, isoleucine, and threonine can not be converted and this leads to a buildup of propionyl-CoA. Instead of being converted to methylmalonyl-CoA, propionyl-CoA is then converted into propionic acid, which builds up in the bloodstream. This in turn causes an accumulation of dangerous acids and toxins, which can cause damage to the organs.In many cases, propionic acidemia can damage the brain, heart, kidney, liver, cause seizures and delays to normal development such as walking or talking. The patient may need to be hospitalized to prevent breakdown of proteins within the body. Dietary needs must be closely managed.Mutations in both copies of the PCCA or PCCB genes cause propionic acidemia. These genes contain instructions to form alpha- and beta-subunits of PCC, the enzyme called propionyl-CoA carboxylase. PCC is required for the normal breakdown of the essential amino acids valine, isoleucine, threonine, and methionine, as well as certain odd-chained fatty-acids. Mutations in the PCCA or PCCB genes disrupt the function of the enzyme, preventing these acids from being metabolized. As a result, propionyl-CoA, propionic acid, ketones, ammonia, and other toxic compounds accumulate in the blood, causing the signs and symptoms of propionic acidemia. Hyperammonemia develops due to the inhibitory effects of propionyl-CoA on N-Acetylglutamate synthase, indirectly resulting in slowing of the urea cycle. Diagnosis Elevated metabolites of propionic acid (for example, 3-hydroxypropionate, methylcitrate, tiglylglycine, propionylglycine) found in blood and urine along with normal biotinidase levels. Management Patients with propionic acidemia should be started as early as possible on a low protein diet. In addition to a protein mixture that is devoid of methionine, threonine, valine, and isoleucine, the patient should also receive L-carnitine treatment and should be given antibiotics 10 days per month in order to remove the intestinal propiogenic flora. The patient should have diet protocols prepared for them with a “well day diet” with low protein content, a “half emergency diet” containing half of the protein requirements, and an “emergency diet” with no protein content. These patients are under the risk of severe hyperammonemia during infections that can lead to comatose states.Liver transplant is gaining a role in the management of these patients, with small series showing improved quality of life. Epidemiology Propionic acidemia is inherited in an autosomal recessive pattern and is found in about 1 in 35,000 live births in the United States. The condition appears to be more common in Saudi Arabia, with a frequency of about 1 in 3,000. The condition also appears to be common in Amish, Mennonite and other populations with higher frequency of consanguinuity. History In 1957, a male child was born with poor mental development, repeated attacks of acidosis, and high levels of ketones and glycine in the blood. Upon dietary testing, Dr. Barton Childs discovered that his symptoms worsened when given the amino acids leucine, isoleucine, valine, methionine, and threonine. In 1961, the medical team at Johns Hopkins Hospital in Baltimore, Maryland published the case, calling the disorder ketotic hyperglycinemia. In 1969, using data from the original patients sister, scientists established that propionic acidemia was a recessive disorder, and that propionic acidemia and methylmalonic acidemia are caused by deficiencies in the same enzyme pathway. See also Methylmalonic acidemia Isovaleric acidemia Maple syrup urine disease References External links Propionic acidemia at NLM Genetics Home Reference Propionic acidemia at NIHs Office of Rare Diseases "Propionic acidemia". Orphanet.
Sacrococcygeal teratoma	Sacrococcygeal teratoma (SCT) is a type of tumor known as a teratoma that develops at the base of the coccyx (tailbone) and is thought to be primarily derived from remnants of the primitive streak. Sacrococcygeal teratomas are benign 75% of the time, malignant 12% of the time, and the remainder are considered "immature teratomas" that share benign and malignant features. Benign sacrococcygeal teratomas are more likely to develop in younger children who are less than 5 months old, and older children are more likely to develop malignant sacrococcygeal teratomas. The Currarino syndrome, due to an autosomal dominant mutation in the MNX1 gene, consists of a presacral mass (usually a mature teratoma or anterior meningocele), anorectal malformation and sacral dysgenesis. Presentation Complications Maternal complications of pregnancy may include mirror syndrome. Maternal complications of delivery may include a Cesarean section or, alternatively, a vaginal delivery with mechanical dystocia.Complications of the mass effect of a teratoma in general are addressed on the teratoma page. Complications of the mass effect of a large SCT may include hip dysplasia, bowel obstruction, urinary obstruction, hydronephrosis and hydrops fetalis. Even a small SCT can produce complications of mass effect, if it is presacral (Altman Type IV). In the fetus, severe hydronephrosis may contribute to inadequate lung development. Also in the fetus and newborn, the anus may be imperforate.Later complications of the mass effect and/or surgery may include neurogenic bladder, other forms of urinary incontinence, fecal incontinence, and other chronic problems resulting from accidental damage to or sacrifice of nerves and muscles within the pelvis. Removal of the coccyx may include additional complications. In one review of 25 patients, however, the most frequent complication was an unsatisfactory appearance of the surgical scar. Late effects Late effects are of two kinds: consequences of the tumor itself, and consequences of surgery and other treatments for the tumor.Complications of not removing the coccyx may include both recurrence of the teratoma and metastatic cancer. Late malignancies usually involve incomplete excision of the coccyx and are adenocarcinoma.Although functional disability in survivors is common, a small comparative study found a nonsignificant difference between SCT survivors and a matched control group. In rare cases, pelvic scarring may necessitate that a pregnant woman who is a SCT survivor deliver her baby by Cesarean section. Cause SCT is seen in 1 in every 35,000 live births, and is the most common tumor presenting in newborn humans. Most SCTs are found in babies and children, but SCTs have been reported in adults and the increasingly routine use of prenatal ultrasound exams has dramatically increased the number of diagnosed SCTs presenting in fetuses. Like other teratomas, an SCT can grow very large. Unlike other teratomas, an SCT sometimes grows larger than the rest of the fetus. Sacrococcygeal teratomas are the most common type of germ cell tumors (both benign and malignant) diagnosed in neonates, infants, and children younger than 4 years. SCTs occur more often in girls than in boys; ratios of 3:1 to 4:1 have been reported.Historically, sacrococcygeal teratomas present in 2 clinical patterns related to the childs age, tumor location, and likelihood of tumor malignancy. With the advent of routine prenatal ultrasound examinations, a third clinical pattern is emerging. Fetal tumors present during prenatal ultrasound exams, with or without maternal symptoms. SCTs found during routine exams tend to be small and partly or entirely external. The internal SCTs are not easily seen via ultrasound, unless they are large enough to reveal their presence by the abnormal position of the fetal urinary bladder and other organs, but large fetal SCTs frequently produce maternal complications which necessitate non-routine, investigative ultrasounds. Neonatal tumors present at birth protruding from the sacral site and are usually mature or immature teratomas. Among infants and young children, the tumor presents as a palpable mass in the sacropelvic region compressing the bladder or rectum. These pelvic tumors have a greater likelihood of being malignant. An early survey found that the rate of tumor malignancy was 48% for girls and 67% for boys older than 2 months at the time of sacrococcygeal tumor diagnosis, compared with a malignant tumor incidence of 7% for girls and 10% for boys younger than 2 months at the time of diagnosis. The pelvic site of the primary tumor has been reported to be an adverse prognostic factor, most likely caused by a higher rate of incomplete resection. In older children and adults, the tumor may be mistaken for a pilonidal sinus, or it may be found during a rectal exam or other evaluation. Diagnosis During prenatal ultrasound, an SCT having an external component may appear as a fluid-filled cyst or a solid mass sticking out from the fetus body. Fetal SCTs that are entirely internal may be undetected if they are small; detection (or at least suspicion) is possible when the fetal bladder is seen in an abnormal position, due to the SCT pushing other organs out of place. At birth, the usual presentation is a visible lump or mass under the skin at the top of the buttocks crease. If not visible, it can sometimes be felt; gently prodded, it feels somewhat like a hardboiled egg. A small SCT, if it is entirely inside the body, may not present for years, until it grows large enough to cause pain, constipation and other symptoms of a large mass inside the pelvis, or until it begins to extend out of the pelvis. Even a relatively large SCT may be missed, if it is internal, because the bony pelvis conceals and protects it. Mediastinal tumors, including teratomas, are similarly concealed and protected by the rib cage. Some SCTs are discovered when a child begins to talk at about age 2 years and complains of their bottom hurting or feeling "poopy" when they ride in a car seat. Other tumors can occur in the sacrococcygeal and/or presacral regions and hence must be ruled out to obtain a differential diagnosis. These include extraspinal ependymoma, ependymoblastoma, neuroblastoma and rhabdomyosarcoma. Smaller SCTs with an external component, seen in prenatal ultrasounds or at birth, often are mistaken for spina bifida. Cystic SCT and terminal myelocystocele are especially difficult to distinguish; for more accurate diagnosis, MRI has been recommended. Treatment The preferred first treatment for SCT is complete surgical removal (i.e., complete resection). The preferred approach to a small SCT is through the perineum; a large SCT may require an additional approach through the abdomen. Resection should include the coccyx and may also include portions of the sacrum. The surgery should include reattachment of the small muscles and ligaments formerly attached to the coccyx, in effect reconstructing the posterior perineum. If not, there is an increased risk of perineal hernia later in life. SCTs are classified morphologically according to their relative extent outside and inside the body: Altman type I — entirely outside, sometimes attached to the body only by a narrow stalk Altman type II — mostly outside Altman type III — mostly inside Altman type IV — entirely inside; this is also known as a presacral teratoma or retrorectal teratomaThe Altman type is significant in the contexts of management of labor and delivery, surgical approach, and complications of SCT. Serial ultrasound and MRI monitoring of SCTs in fetuses in utero has demonstrated that the Altman type can change over time. As the tumor grows, it can push between other organs and through the perineum to the body surface where the tumor appears as a bulge covered only by skin. Sometimes, the tumor bulge later slips back inside the perineum. Like all teratomas, a sacrococcygeal teratoma has the potential to be malignant, and the standard of care requires long-term followup by an oncologist. Management of fetal SCTs Management of most fetal SCTs involves watchful waiting prior to any treatment. An often used decision tree is as follows: Perform detailed ultrasound exam including fetal echocardiogram and Doppler flow analysis If fetal high output failure, placentomegaly, or hydrops If fetus not mature, perform pregnancy termination or fetal intervention Else fetus mature, perform emergency Cesarean section Else no emergent problems, perform serial non-stress tests and ultrasound biophysical profiles and plan delivery, as follows If emergent problems develop, return to top of decision tree Else if SCT over 5–10 cm or polyhydramnios, perform early (37 weeks gestation) elective Cesarean section Else SCT small and no complications, permit term spontaneous vaginal deliveryEmergent problems include maternal mirror syndrome, polyhydramnios, and preterm labor. Poor management decisions, including interventions that are either premature or delayed, can have dire consequences. A very small retrospective study of 9 babies with SCTs greater than 10 cm diameter reported slightly higher survivorship in babies remaining in utero slightly longer.In many cases, a fetus with a small SCT (under 5 or 10 cm) may be delivered vaginally. Prior to the advent of prenatal detection and hence scheduled C-section, 90% of babies diagnosed with SCT were born full term. Management of adult SCTs SCTs are very rare in adults, and as a rule these tumors are benign and have extremely low potential for malignancy. This estimation of potential is based on the idea that because the tumor existed for decades prior to diagnosis, without becoming malignant, it has little or no potential to ever become malignant. For this reason, and because coccygectomy in adults has greater risks than in babies, some surgeons prefer not to remove the coccyx of adult survivors of SCT. There are case reports of good outcomes. See also Sacrococcygeal symphysis References == External links ==
Solitary cutaneous leiomyoma	Solitary cutaneous leiomyoma typically presents as a deeply circumscribed, freely movable, rounded nodule ranging from 2 to 15 mm in diameter, with overlying skin that may have a reddish or violaceous tint.: 627 See also Multiple cutaneous leiomyoma Leiomyoma Skin lesion == References ==
Amoebic liver abscess	A amoebic liver abscess is a type of liver abscess caused by amebiasis. It is the involvement of liver tissue by trophozoites of the organism Entamoeba histolytica and of its abscess due to necrosis. Presentation Approximately 90% of patients with E histolytica are asymptomatic. The two most common manifestations of E histolytica include colitis (bloody stool with mucus, abdominal pain, and/or diarrhea), and discovery of a liver abscess on imaging. Liver abscess commonly present as right upper quadrant abdominal pain and fever, with worsening features associated with abscess rupture. Symptoms Pain right hypochondrium referred to the right shoulder Pyrexia (100.4 F) Profuse sweating and rigors Loss of weight Earthy complexion Signs Pallor Tenderness and rigidity in right hypochondrium Palpable liver Intercostal tenderness Basal lung signs Diagnosis Diagnosis is primarily made by identifying stool ova and parasites on stool antigen testing in the presence of colitis, or E histolytica serology. Blood ceruloplasmin Haemoglobin estimation Stools examination (trophozoites and cysts) Radiography Aspiration exploratory Medical ultrasonography and CT scanning Sigmoidoscopy Liver function tests Serological tests Rodent models Due to the difficulty of exploring host and amebic factors involved in the pathogenesis of amebic liver abscess in humans, most studies have been conducted with animal models (e.g., mice, gerbils, and hamsters). Histopathological findings revealed that the chronic phase of amebic liver abscess in humans corresponds to lytic or liquefactive necrosis, whereas in rodent models there is granulomatous inflammation. However, the use of animal models has provided important information on molecules and mechanisms of the host/parasite interaction in amebic liver abscess. References == External links ==
Carotid artery dissection	Carotid artery dissection is a separation of the layers of the artery wall supplying oxygen-bearing blood to the head and brain and is the most common cause of stroke in young adults. (Dissection is a blister-like de-lamination between the outer and inner walls of a blood vessel, generally originating with a partial leak in the inner lining.)Dissection may occur after physical trauma to the neck, such as a blunt injury (e.g. traffic collision), strangulation, but may also happen spontaneously. Signs and symptoms The signs and symptoms of carotid artery dissection may be divided into ischemic and non-ischemic categories:Non-ischemic signs and symptoms: Localised headache, particularly around one of the eyes Neck pain Swollen tongue Decreased pupil size with drooping of the upper eyelid (Horner syndrome) Pulsatile tinnitusIschemic signs and symptoms: Temporary vision loss Ischemic stroke Causes The causes of internal carotid artery dissection can be broadly categorized into two classes: spontaneous or traumatic. Spontaneous Once considered uncommon, spontaneous carotid artery dissection is an increasingly recognized cause of stroke that preferentially affects the middle-aged.The incidence of spontaneous carotid artery dissection is low, and incidence rates for internal carotid artery dissection have been reported to be 2.6 to 2.9 per 100,000.Observational studies and case reports published since the early 1980s show that patients with spontaneous internal carotid artery dissection may also have a history of stroke in their family and/or hereditary connective tissue disorders, such as Marfan syndrome, Ehlers-Danlos syndrome, autosomal dominant polycystic kidney disease, pseudoxanthoma elasticum, fibromuscular dysplasia, and osteogenesis imperfecta type I. IgG4-related disease involving the carotid artery has also been observed as a cause.However, although an association with connective tissue disorders does exist, most people with spontaneous arterial dissections do not have associated connective tissue disorders. Also, the reports on the prevalence of hereditary connective tissue diseases in people with spontaneous dissections are highly variable, ranging from 0% to 0.6% in one study to 5% to 18% in another study.Internal carotid artery dissection can also be associated with an elongated styloid process (known as Eagle syndrome when the elongated styloid process causes symptoms). Traumatic Carotid artery dissection is thought to be more commonly caused by severe violent trauma to the head and/or neck. An estimated 0.67% of patients admitted to the hospital after major motor vehicle accidents were found to have blunt carotid injury, including intimal dissections, pseudoaneurysms, thromboses, or fistulas. Of these, 76% had intimal dissections, pseudoaneurysms, or a combination of the two. Sports-related activities such as surfing and Jiu-Jitsu have been reported as causes of carotid artery dissection. The probable mechanism of injury for most internal carotid injuries is rapid deceleration, with resultant hyperextension and rotation of the neck, which stretches the internal carotid artery over the upper cervical vertebrae, producing an intimal tear. After such an injury, the patient may remain asymptomatic, have a hemispheric transient ischemic event, or have a stroke.Artery dissection has also been reported in association with some forms of neck manipulation. There is significant controversy about the level of risk of stroke from neck manipulation. It may be that manipulation can cause dissection, or it may be that the dissection is already present in some people who seek manipulative treatment. At this time, conclusive evidence does not exist to support either a strong association between neck manipulation and stroke, or no association. Pathophysiology Arterial dissection of the carotid arteries occurs when a small tear forms in the innermost lining of the arterial wall (known as the tunica intima). Blood is then able to enter the space between the inner and outer layers of the vessel, causing narrowing (stenosis) or complete occlusion. The stenosis that occurs in the early stages of arterial dissection is a dynamic process and some occlusions can return to stenosis very quickly. When complete occlusion occurs, it may lead to ischaemia. Often, even a complete occlusion is totally asymptomatic because bilateral circulation keeps the brain well perfused. However, when blood clots form and break off from the site of the tear, they form emboli, which can travel through the arteries to the brain and block the blood supply to the brain, resulting in an ischaemic stroke, otherwise known as a cerebral infarction. Blood clots, or emboli, originating from the dissection are thought to be the cause of infarction in the majority of cases of stroke in the presence of carotid artery dissection. Cerebral infarction causes irreversible damage to the brain. In one study of patients with carotid artery dissection, 60% had infarcts documented on neuroimaging. Treatment The goal of treatment is to prevent the development or continuation of neurologic deficits. Treatments include observation, anti-platelet agents, anticoagulation, stent implantation, carotid endarterectomy, and carotid artery ligation. Epidemiology 70% of patients with carotid arterial dissection are between the ages of 35 and 50, with a mean age of 47 years. See also Aortic dissection Vertebral artery dissection References == External links ==
Ebsteins anomaly	Ebsteins anomaly is a congenital heart defect in which the septal and posterior leaflets of the tricuspid valve are displaced towards the apex of the right ventricle of the heart. It is classified as a critical congenital heart defect accounting for <1% of all congenital heart defects presenting in ≈1 per 200,000 live births. Ebstein anomaly is the congenital heart lesion most commonly associated with supraventricular tachycardia. Signs and symptoms The annulus of the valve is still in the normal position. The valve leaflets, however, are to a varying degree, attached to the walls and septum of the right ventricle. A subsequent "atrialization" of a portion of the morphologic right ventricle (which is then contiguous with the right atrium) is seen. This causes the right atrium to be large and the anatomic right ventricle to be small in size. S3 heart sound S4 heart sound Triple or quadruple gallop due to widely split S1 and S2 sounds plus a loud S3 and/or S4 Systolic murmur of tricuspid regurgitation = Holosystolic or early systolic murmur along the lower left sternal border depending on the severity of the regurgitation Right atrial hypertrophy Right ventricular conduction defects Wolff-Parkinson-White syndrome often accompanies Related abnormalities While Ebsteins anomaly is defined as the congenital displacement of the tricuspid valve towards the apex of the right ventricle, it is often associated with other abnormalities. Anatomic abnormalities Typically, anatomic abnormalities of the tricuspid valve exist, with enlargement of the anterior leaflet of the valve. The other leaflets are described as being plastered to the endocardium. Tethering the underlying ventricular wall is the most common for the posterior and septal leaflets, and sail-like anterior leaflets may be tethered to the RV free wall also. About 50% of individuals with Ebsteins anomaly have an associated shunt between the right and left atria, either an atrial septal defect or a patent foramen ovale. Electrophysiologic abnormalities About 50% of individuals with Ebsteins anomaly have an accessory pathway with evidence of Wolff-Parkinson-White syndrome, secondary to the atrialized right ventricular tissue. This can lead to abnormal heart rhythms including atrioventricular re-entrant tachycardia. Other abnormalities that can be seen on the ECG include: signs of right atrial enlargement or tall and broad Himalayan P waves first degree atrioventricular block manifesting as a prolonged PR-interval low amplitude QRS complexes in the right precordial leads atypical right bundle branch block T wave inversion in V1-V4 and Q waves in V1-V4 and II, III and aVF. Risk factors An enlargement of the aorta may occur; an increased risk of abnormality is seen in babies of women taking lithium during the first trimester of pregnancy (though some have questioned this) and in those with Wolff-Parkinson-White syndrome. Diagnosis Diagnosis is mainly depends on Echocardiography Chest x will shows cardiomegaly Treatment Medication Ebsteins cardio physiology typically presents as an (antidromic) AV reentrant tachycardia with associated pre-excitation. In this setting, the preferred medication treatment agent is procainamide. Since AV-blockade may promote conduction over the accessory pathway, drugs such as beta blockers, calcium channel blockers, and digoxin are contraindicated. If atrial fibrillation with pre-excitation occurs, treatment options include procainamide, flecainide, propafenone, dofetilide, and ibutilide, since these medications slow conduction in the accessory pathway causing the tachycardia and should be administered before considering electrical cardioversion. Intravenous amiodarone may also convert atrial fibrillation and/or slow the ventricular response. Surgery The Canadian Cardiovascular Society (CCS) recommends surgical intervention for these indications: Limited exercise capacity (NYHA III-IV) Increasing heart size (cardiothoracic ratio greater than 65%) Important cyanosis (resting oxygen saturation less than 90% - level B) Severe tricuspid regurgitation with symptoms Transient ischemic attack or strokeThe CCS further recommends patients who require operation for Ebsteins anomaly should be operated on by congenital heart surgeons who have substantial specific experience and success with this operation. Every effort should be made to preserve the native tricuspid valve. History Ebsteins anomaly was named after Wilhelm Ebstein, who in 1866 described the heart of the 19-year-old Joseph Prescher. References == External links ==
Obturator hernia	An obturator hernia is a rare type of hernia of the pelvic floor in which pelvic or abdominal contents protrudes through the obturator foramen. Because of differences in anatomy, it is much more common in women, especially multiparous and older women who have recently lost much weight. The diagnosis is often made intraoperatively after presenting with bowel obstruction. The Howship–Romberg sign is suggestive of an obturator hernia, exacerbated by thigh extension, medial rotation and abduction. It is characterized by lancinating pain in the medial thigh/obturator distribution, extending to the knee; caused by hernia compression of the obturator nerve. References == External links ==
Tyrosinemia	Tyrosinemia or tyrosinaemia is an error of metabolism, usually inborn, in which the body cannot effectively break down the amino acid tyrosine. Symptoms of untreated tyrosinemia include liver and kidney disturbances. Without treatment, tyrosinemia leads to liver failure. Today, tyrosinemia is increasingly detected on newborn screening tests before any symptoms appear. With early and lifelong management involving a low-protein diet, special protein formula, and sometimes medication, people with tyrosinemia develop normally, are healthy, and live normal lives. Cause All tyrosinemias result from dysfunction of various genes in the phenylalanine and tyrosine catabolic pathway, and are inherited in an autosomal-recessive pattern.Type I tyrosinemia results from a mutation in the FAH gene, which encodes the enzyme fumarylacetoacetase. As a result of FAH deficiency, the substrate fumarylacetoacetate can accumulate in proximal renal tubular cells and hepatocytes, resulting in damage to the kidney and liver, respectively.Type II tyrosinemia results from a mutation in the TAT gene, which encodes the enzyme tyrosine aminotransferase. As a result of TAT deficiency, the substrate tyrosine accumulates, causing ophthalmologic and dermatologic abnormalities.Type III tyrosinemia results from a mutation in the HPD gene, which encodes the enzyme 4-hydroxyphenylpyruvate dioxygenase. Type III tyrosinemia is the rarest of the three conditions, with only a few cases ever reported. Most of those cases have included intellectual disability and neurologic dysfunction. Diagnosis Types Type I tyrosinemia can be detected via blood tests for the presence of a fumarylacetoacetate metabolite, succinylacetone, which is considered a pathognomonic indicator for the disease.Type II tyrosinemia can be detected via the presence of significantly elevated plasma tyrosine levels, and the diagnosis can be confirmed by detection of a mutation in TAT in cultured fibroblasts.Type III tyrosinemia can be diagnosed by detection of a mutation in HPD in cultured fibroblasts. Treatment Treatment varies depending on the specific type; a low-protein diet combined with the use of a specially engineered formula to supply protein is required in most cases. Experience with nitisinone has shown it to be effective, especially when started within the first month of life, and it is now the standard course of treatment. It is a 4-hydroxyphenylpyruvate dioxygenase inhibitor indicated for the treatment of hereditary tyrosinemia type 1 (HT-1) in combination with dietary restriction of tyrosine and phenylalanine. Liver transplant is indicated for patients with tyrosinemia type I who do not respond to nitisinone, as well as those with acute liver failure and hepatomas. See also Alkaptonuria Inborn error of metabolism Ochronosis References External links GeneReview/NCBI/NIH/UW entry on Tyrosinemia Type 1 Tyrosinemia on Genetic Home Reference
Diplacusis	Diplacusis, also known as diplacusis binauralis, binauralis disharmonica or interaural pitch difference (IPD), is a hearing disorder whereby a single auditory stimulus is perceived as different pitches between ears. It is typically experienced as a secondary symptom of sensorineural hearing loss, although not all patients with sensorineural hearing loss experience diplacusis or tinnitus. The onset is usually spontaneous and can occur following an acoustic trauma, for example an explosive noise, or in the presence of an ear infection. Sufferers may experience the effect permanently, or it may resolve on its own. Diplacusis can be particularly disruptive to individuals working within fields requiring acute audition, such as musicians, sound engineers or performing artists. Diplacusis of pure tones The term diplacusis has been used in cases which people with unilateral cochlear hearing losses or asymmetrical hearing losses, the same tone presented alternately to the two ears may be perceived as having different pitches in the two ears. The magnitude of the shift can be measured by getting the subject to adjust the frequency of a tone in one ear until its pitch matches that of the tone in the other ear. On presentation of a single tone alternating between ears (i.e. 1000 Hz left, 1000 Hz right, 1000 Hz left, ...), a given person will consistently mismatch these sinusoids the same amount between trials if doing a pitch-matching task. For example, a 1000 Hz tone in an unaffected ear may be heard as a slightly different pitch in the opposite ear, or have an imperfect tonal quality in the affected ear. Biological explanation via theories of pitch of pure tones There are two theories on the cause of diplacusis: place theory and temporal theory. Place theory posits that the cause is looking for the edge of the wave for the pitch and could explain diplacusis as a small differences between the two cochleas.Temporal theory posits that the cause is from looking at the phase locking to tell what the pitch is. This theory has a difficult time explaining diplacusis. There are some examples of pitch which do not have an "edge" on the basilar membrane, which this would account for—e.g., white noise, clicks, etc. Both theories are under debate. Effects of sensorineural hearing loss Normal human ears can discriminate between two frequencies that differ by as little as 0.2%. If one ear has normal thresholds while the other has sensorineural hearing loss (SNHL), diplacusis may be present, as much as 15–20% (for example 200 Hz one ear => 240 Hz in the other). The pitch may be difficult to match because the SNHL ear hears the sound "fuzzy". Bilateral SNHL gives less diplacusis, but pitch distortions may persist. This may cause problems with music and speech understanding. Treatment Treatment of diplacusis includes a full medical and audiological examination that may explain the nature of the problem. If needed, amplification may relieve the symptoms of diplacusis. Therapy in helping the patient understand the cause of the symptom and tinnitus retraining may provide some relief. In at least some cases, amplification makes no difference and there is no treatment other than waiting for natural resolution. Some individuals may find the provided amplification also increases the audibility of their pitch discrepancy. If onset is linked to an underlying medical cause, i.e. sudden sensorineural hearing loss, appropriate medical treatment is recommended. Etymology Diplacusis is from the Greek words "diplous" (double) and "akousis" (hearing). See also Hearing Hearing loss Pitch (psychophysics) Auditory system External sources Diplacusis: I. Historical Review Turner, Christopher. "Perception of Pitch." Wendell Johnson Speech and Hearing Center, Iowa City. Dec. 2008. Plack et al. (ed.). Pitch : Neural coding and perception. Springer. 2005. == References ==
Trigeminal trophic syndrome	Trigeminal trophic syndrome is a rare disease caused by the interruption of peripheral or central sensory pathways of the trigeminal nerve. A slowly enlarging, uninflammed ulcer can occur in the area that has had trigeminal nerve damage; including but not limited to the cheek beside the ala nasi.: 65 These sores affect the skin supplied by the sensory component of the trigeminal nerve. Similar lesions may also occur in the corners of the eyes, inside the ear canal, on the scalp or inside the mouth.It has been stated that the ulceration is due to the constant "picking" of the patient. While this does occur, the picking behavior is an incomplete explanation of the disease presentation: the lack of feeling or pain allows the patient to continue scratching or picking the area, and, although there is no feeling, there is constant neuropathic pain.Sixty cases were reported from 1982 to 2002. See also Trigeminal neuralgia (Tic douloureux) Skin lesion List of cutaneous conditions Somatosensory system == References ==
Pulmonary contusion	A pulmonary contusion, also known as lung contusion, is a bruise of the lung, caused by chest trauma. As a result of damage to capillaries, blood and other fluids accumulate in the lung tissue. The excess fluid interferes with gas exchange, potentially leading to inadequate oxygen levels (hypoxia). Unlike pulmonary laceration, another type of lung injury, pulmonary contusion does not involve a cut or tear of the lung tissue. A pulmonary contusion is usually caused directly by blunt trauma but can also result from explosion injuries or a shock wave associated with penetrating trauma. With the use of explosives during World Wars I and II, pulmonary contusion resulting from blasts gained recognition. In the 1960s its occurrence in civilians began to receive wider recognition, in which cases it is usually caused by traffic accidents. The use of seat belts and airbags reduces the risk to vehicle occupants. Diagnosis is made by studying the cause of the injury, physical examination and chest radiography. Typical signs and symptoms include direct effects of the physical trauma, such as chest pain and coughing up blood, as well as signs that the body is not receiving enough oxygen, such as cyanosis. The contusion frequently heals on its own with supportive care. Often nothing more than supplemental oxygen and close monitoring is needed; however, intensive care may be required. For example, if breathing is severely compromised, mechanical ventilation may be necessary. Fluid replacement may be required to ensure adequate blood volume, but fluids are given carefully since fluid overload can worsen pulmonary edema, which may be lethal. The severity ranges from mild to severe: small contusions may have little or no impact on health, yet pulmonary contusion is the most common type of potentially lethal chest trauma. It occurs in 30–75% of severe chest injuries. The risk of death following a pulmonary contusion is between 14 and 40%. Pulmonary contusion is usually accompanied by other injuries. Although associated injuries are often the cause of death, pulmonary contusion is thought to cause death directly in a quarter to half of cases. Children are at especially high risk for the injury because the relative flexibility of their bones prevents the chest wall from absorbing force from an impact, causing it to be transmitted instead to the lung. Pulmonary contusion is associated with complications including pneumonia and acute respiratory distress syndrome, and it can cause long-term respiratory disability. Classification Pulmonary contusion and laceration are injuries to the lung tissue. Pulmonary laceration, in which lung tissue is torn or cut, differs from pulmonary contusion in that the former involves disruption of the macroscopic architecture of the lung, while the latter does not. When lacerations fill with blood, the result is pulmonary hematoma, a collection of blood within the lung tissue. Contusion involves hemorrhage in the alveoli (tiny air-filled sacs responsible for absorbing oxygen), but a hematoma is a discrete clot of blood not interspersed with lung tissue. A collapsed lung can result when the pleural cavity (the space outside the lung) accumulates blood (hemothorax) or air (pneumothorax) or both (hemopneumothorax). These conditions do not inherently involve damage to the lung tissue itself, but they may be associated with it. Injuries to the chest wall are also distinct from but may be associated with lung injuries. Chest wall injuries include rib fractures and flail chest, in which multiple ribs are broken so that a segment of the ribcage is detached from the rest of the chest wall and moves independently. Signs and symptoms Presentation may be subtle; people with mild contusion may have no symptoms at all. However, pulmonary contusion is frequently associated with signs (objective indications) and symptoms (subjective states), including those indicative of the lung injury itself and of accompanying injuries. Because gas exchange is impaired, signs of low blood oxygen saturation, such as low concentrations of oxygen in arterial blood gas and cyanosis (bluish color of the skin and mucous membranes) are commonly associated. Dyspnea (painful breathing or difficulty breathing) is commonly seen, and tolerance for exercise may be lowered. Rapid breathing and a rapid heart rate are other signs. With more severe contusions, breath sounds heard through a stethoscope may be decreased, or rales (an abnormal crackling sound in the chest accompanying breathing) may be present. People with severe contusions may have bronchorrhea (the production of watery sputum). Wheezing and coughing are other signs. Coughing up blood or bloody sputum is present in up to half of cases. Cardiac output (the volume of blood pumped by the heart) may be reduced, and hypotension (low blood pressure) is frequently present. The area of the chest wall near the contusion may be tender or painful due to associated chest wall injury. Signs and symptoms take time to develop, and as many as half of cases are asymptomatic at the initial presentation. The more severe the injury, the more quickly symptoms become apparent. In severe cases, symptoms may occur as quickly as three or four hours after the trauma. Hypoxemia (low oxygen concentration in the arterial blood) typically becomes progressively worse over 24–48 hours after injury. In general, pulmonary contusion tends to worsen slowly over a few days, but it may also cause rapid deterioration or death if untreated. Causes Pulmonary contusion is the most common injury found in blunt chest trauma, occurring in 25–35% of cases. It is usually caused by the rapid deceleration that results when the moving chest strikes a fixed object. About 70% of cases result from motor vehicle collisions, most often when the chest strikes the inside of the car. Falls, assaults, and sports injuries are other causes. Pulmonary contusion can also be caused by explosions; the organs most vulnerable to blast injuries are those that contain gas, such as the lungs. Blast lung is severe pulmonary contusion, bleeding, or edema with damage to alveoli and blood vessels, or a combination of these. This is the primary cause of death among people who initially survive an explosion. Unlike other mechanisms of injury in which pulmonary contusion is often found alongside other injuries, explosions can cause pulmonary contusion without damage to the chest wall.In addition to blunt trauma, penetrating trauma can cause pulmonary contusion. Contusion resulting from penetration by a rapidly moving projectile usually surrounds the path along which the projectile traveled through the tissue. The pressure wave forces tissue out of the way, creating a temporary cavity; the tissue readily moves back into place, but it is damaged. Pulmonary contusions that accompany gun and knife wounds are not usually severe enough to have a major effect on outcome; penetrating trauma causes less widespread lung damage than does blunt trauma. An exception is shotgun wounds, which can seriously damage large areas of lung tissue through a blast injury mechanism. Mechanism The physical processes behind pulmonary contusion are poorly understood. However, it is known that lung tissue can be crushed when the chest wall bends inward on impact. Three other possible mechanisms have been suggested: the inertial effect, the spalling effect, and the implosion effect. In the inertial effect, the lighter alveolar tissue is sheared from the heavier hilar structures, an effect similar to diffuse axonal injury in head injury. It results from the fact that different tissues have different densities, and therefore different rates of acceleration or deceleration. In the spalling effect, lung tissue bursts or is sheared where a shock wave meets the lung tissue, at interfaces between gas and liquid. The alveolar walls form such a gas-liquid interface with the air in the alveoli. The spalling effect occurs in areas with large differences in density; particles of the denser tissue are spalled (thrown) into the less dense particles. The implosion effect occurs when a pressure wave passes through a tissue containing bubbles of gas: the bubbles first implode, then rebound and expand beyond their original volume. The air bubbles cause many tiny explosions, resulting in tissue damage; the overexpansion of gas bubbles stretches and tears alveoli. This effect is thought to occur microscopically when the pressure in the airways increases sharply.Contusion usually occurs on the lung directly under the site of impact, but, as with traumatic brain injury, a contrecoup contusion may occur at the site opposite the impact as well. A blow to the front of the chest may cause contusion on the back of the lungs because a shock wave travels through the chest and hits the curved back of the chest wall; this reflects the energy onto the back of the lungs, concentrating it. (A similar mechanism may occur at the front of the lungs when the back is struck.)The amount of energy transferred to the lung is determined in a large part by the compliance (flexibility) of the chest wall. Childrens chests are more flexible because their ribs are more elastic and there is less ossification of their intercostal cartilage. Therefore, their chest walls bend, absorbing less of the force and transmitting more of it to the underlying organs. An adults more bony chest wall absorbs more of the force itself rather than transmitting it. Thus children commonly get pulmonary contusions without fractures overlying them, while elderly people are more likely to develop fractures than contusions. One study found that pulmonary contusions were accompanied by fractures 62% of the time in children and 80% of the time in adults. Pathophysiology Pulmonary contusion results in bleeding and fluid leakage into lung tissue, which can become stiffened and lose its normal elasticity. The water content of the lung increases over the first 72 hours after injury, potentially leading to frank pulmonary edema in more serious cases. As a result of these and other pathological processes, pulmonary contusion progresses over time and can cause hypoxia (insufficient oxygen). Bleeding and edema In contusions, torn capillaries leak fluid into the tissues around them. The membrane between alveoli and capillaries is torn; damage to this capillary–alveolar membrane and small blood vessels causes blood and fluids to leak into the alveoli and the interstitial space (the space surrounding cells) of the lung. With more severe trauma, there is a greater amount of edema, bleeding, and tearing of the alveoli. Pulmonary contusion is characterized by microhemorrhages (tiny bleeds) that occur when the alveoli are traumatically separated from airway structures and blood vessels. Blood initially collects in the interstitial space, and then edema occurs by an hour or two after injury. An area of bleeding in the contused lung is commonly surrounded by an area of edema. In normal gas exchange, carbon dioxide diffuses across the endothelium of the capillaries, the interstitial space, and across the alveolar epithelium; oxygen diffuses in the other direction. Fluid accumulation interferes with gas exchange, and can cause the alveoli to fill with proteins and collapse due to edema and bleeding. The larger the area of the injury, the more severe respiratory compromise will be. Consolidation and collapse Pulmonary contusion can cause parts of the lung to consolidate, alveoli to collapse, and atelectasis (partial or total lung collapse) to occur. Consolidation occurs when the parts of the lung that are normally filled with air fill with material from the pathological condition, such as blood. Over a period of hours after the injury, the alveoli in the injured area thicken and may become consolidated. A decrease in the amount of surfactant produced also contributes to the collapse and consolidation of alveoli; inactivation of surfactant increases their surface tension. Reduced production of surfactant can also occur in surrounding tissue that was not originally injured.Inflammation of the lungs, which can result when components of blood enter the tissue due to contusion, can also cause parts of the lung to collapse. Macrophages, neutrophils, and other inflammatory cells and blood components can enter the lung tissue and release factors that lead to inflammation, increasing the likelihood of respiratory failure. In response to inflammation, excess mucus is produced, potentially plugging parts of the lung and leading to their collapse. Even when only one side of the chest is injured, inflammation may also affect the other lung. Uninjured lung tissue may develop edema, thickening of the septa of the alveoli, and other changes. If this inflammation is severe enough, it can lead to dysfunction of the lungs like that seen in acute respiratory distress syndrome. Ventilation/perfusion mismatch Normally, the ratio of ventilation to perfusion is about one-to-one; the volume of air entering the alveoli (ventilation) is about equal to that of blood in the capillaries around them (perfusion). This ratio is reduced in pulmonary contusion; fluid-filled alveoli cannot fill with air, oxygen does not fully saturate the hemoglobin, and the blood leaves the lung without being fully oxygenated. Insufficient inflation of the lungs, which can result from inadequate mechanical ventilation or an associated injury such as flail chest, can also contribute to the ventilation/perfusion mismatch. As the mismatch between ventilation and perfusion grows, blood oxygen saturation is reduced. Pulmonary hypoxic vasoconstriction, in which blood vessels near the hypoxic alveoli constrict (narrow their diameter) in response to the lowered oxygen levels, can occur in pulmonary contusion. The vascular resistance increases in the contused part of the lung, leading to a decrease in the amount of blood that flows into it, directing blood to better-ventilated areas. Although reducing blood flow to the unventilated alveoli is a way to compensate for the fact that blood passing unventilated alveoli is not oxygenated, the oxygenation of the blood remains lower than normal. If it is severe enough, the hypoxemia resulting from fluid in the alveoli cannot be corrected just by giving supplemental oxygen; this problem is the cause of a large portion of the fatalities that result from trauma. Diagnosis To diagnose pulmonary contusion, health professionals use clues from a physical examination, information about the event that caused the injury, and radiography. Laboratory findings may also be used; for example, arterial blood gasses may show insufficient oxygen and excessive carbon dioxide even in someone receiving supplemental oxygen. However, blood gas levels may show no abnormality early in the course of pulmonary contusion. X-ray Chest X-ray is the most common method used for diagnosis, and may be used to confirm a diagnosis already made using clinical signs. Consolidated areas appear white on an X-ray film. Contusion is not typically restricted by the anatomical boundaries of the lobes or segments of the lung. The X-ray appearance of pulmonary contusion is similar to that of aspiration, and the presence of hemothorax or pneumothorax may obscure the contusion on a radiograph. Signs of contusion that progress after 48 hours post-injury are likely to be actually due to aspiration, pneumonia, or ARDS.Although chest radiography is an important part of the diagnosis, it is often not sensitive enough to detect the condition early after the injury. In a third of cases, pulmonary contusion is not visible on the first chest radiograph performed. It takes an average of six hours for the characteristic white regions to show up on a chest X-ray, and the contusion may not become apparent for 48 hours. When a pulmonary contusion is apparent in an X-ray, it suggests that the trauma to the chest was severe and that a CT scan might reveal other injuries that were missed with X-ray. Computed tomography Computed tomography (CT scanning) is a more sensitive test for pulmonary contusion, and it can identify abdominal, chest, or other injuries that accompany the contusion. In one study, chest X-ray detected pulmonary contusions in 16.3% of people with serious blunt trauma, while CT detected them in 31.2% of the same people. Unlike X-ray, CT scanning can detect the contusion almost immediately after the injury. However, in both X-ray and CT a contusion may become more visible over the first 24–48 hours after trauma as bleeding and edema into lung tissues progress. CT scanning also helps determine the size of a contusion, which is useful in determining whether a patient needs mechanical ventilation; a larger volume of contused lung on CT scan is associated with an increased likelihood that ventilation will be needed. CT scans also help differentiate between contusion and pulmonary hematoma, which may be difficult to tell apart otherwise. However, pulmonary contusions that are visible on CT but not chest X-ray are usually not severe enough to affect outcome or treatment. Ultrasound Pulmonary ultrasound, performed at the bedside or on the accident scene, is being explored as a diagnosis for pulmonary contusion. Its use is still not widespread, being limited to facilities which are comfortable with its use for other applications, like pneumothorax, airway management, and hemothorax. Accuracy has been found to be comparable to CT scanning. Prevention Prevention of pulmonary contusion is similar to that of other chest trauma. Airbags in combination with seat belts can protect vehicle occupants by preventing the chest from striking the interior of the vehicle during a collision, and by distributing forces involved in the crash more evenly across the body. However, in rare cases, an airbag causes pulmonary contusion in a person who is not properly positioned when it deploys. Child restraints such as carseats protect children in vehicle collisions from pulmonary contusion. Equipment exists for use in some sports to prevent chest and lung injury; for example, in softball the catcher is equipped with a chest protector. Athletes who do not wear such equipment, such as basketball players, can be trained to protect their chests from impacts. Protective garments can also prevent pulmonary contusion in explosions. Although traditional body armor made from rigid plates or other heavy materials protects from projectiles generated by a blast, it does not protect against pulmonary contusion, because it does not prevent the blasts shock wave from being transferred to the lung. Special body armor has been designed for military personnel at high risk for blast injuries; these garments can prevent a shock wave from being propagated across the chest wall to the lung, and thus protect wearers from blast lung injuries. These garments alternate layers of materials with high and low acoustic impedance (the product of a materials density and a waves velocity through it) in order to "decouple" the blast wave, preventing its propagation into the tissues. Treatment No treatment is known to speed the healing of a pulmonary contusion; the main care is supportive. Attempts are made to discover injuries accompanying the contusion, to prevent additional injury, and to provide supportive care while waiting for the contusion to heal. Monitoring, including keeping track of fluid balance, respiratory function, and oxygen saturation using pulse oximetry is also required as the patients condition may progressively worsen. Monitoring for complications such as pneumonia and acute respiratory distress syndrome is of critical importance. Treatment aims to prevent respiratory failure and to ensure adequate blood oxygenation. Supplemental oxygen can be given and it may be warmed and humidified. When the contusion does not respond to other treatments, extracorporeal membranous oxygenation may be used, pumping blood from the body into a machine that oxygenates it and removes carbon dioxide prior to pumping it back in. Ventilation Positive pressure ventilation, in which air is forced into the lungs, is needed when oxygenation is significantly impaired. Noninvasive positive pressure ventilation including continuous positive airway pressure (CPAP) and bi-level positive airway pressure (BiPAP), may be used to improve oxygenation and treat atelectasis: air is blown into the airways at a prescribed pressure via a face mask. Noninvasive ventilation has advantages over invasive methods because it does not carry the risk of infection that intubation does, and it allows normal coughing, swallowing, and speech. However, the technique may cause complications; it may force air into the stomach or cause aspiration of stomach contents, especially when level of consciousness is decreased.People with signs of inadequate respiration or oxygenation may need to be intubated and mechanically ventilated. Mechanical ventilation aims to reduce pulmonary edema and increase oxygenation. Ventilation can reopen collapsed alveoli, but it is harmful for them to be repeatedly opened, and positive pressure ventilation can also damage the lung by overinflating it. Intubation is normally reserved for when respiratory problems occur, but most significant contusions do require intubation, and it may be done early in anticipation of this need. People with pulmonary contusion who are especially likely to need ventilation include those with prior severe lung disease or kidney problems; the elderly; those with a lowered level of consciousness; those with low blood oxygen or high carbon dioxide levels; and those who will undergo operations with anesthesia. Larger contusions have been correlated with a need for ventilation for longer periods of time.Pulmonary contusion or its complications such as acute respiratory distress syndrome may cause lungs to lose compliance (stiffen), so higher pressures may be needed to give normal amounts of air and oxygenate the blood adequately. Positive end-expiratory pressure (PEEP), which delivers air at a given pressure at the end of the expiratory cycle, can reduce edema and keep alveoli from collapsing. PEEP is considered necessary with mechanical ventilation; however, if the pressure is too great it can expand the size of the contusion and injure the lung. When the compliance of the injured lung differs significantly from that of the uninjured one, the lungs can be ventilated independently with two ventilators in order to deliver air at different pressures; this helps avoid injury from overinflation while providing adequate ventilation. Fluid therapy The administration of fluid therapy in individuals with pulmonary contusion is controversial. Excessive fluid in the circulatory system (hypervolemia) can worsen hypoxia because it can cause fluid leakage from injured capillaries (pulmonary edema), which are more permeable than normal. However, low blood volume (hypovolemia) resulting from insufficient fluid has an even worse impact, potentially causing hypovolemic shock; for people who have lost large amounts of blood, fluid resuscitation is necessary. A lot of the evidence supporting the idea that fluids should be withheld from people with pulmonary contusion came from animal studies, not clinical trials with humans; human studies have had conflicting findings on whether fluid resuscitation worsens the condition. Current recommendations suggest giving enough fluid to ensure sufficient blood flow but not giving any more fluid than necessary. For people who do require large amounts of intravenous fluid, a catheter may be placed in the pulmonary artery to measure the pressure within it. Measuring pulmonary artery pressure allows the clinician to give enough fluids to prevent shock without exacerbating edema. Diuretics, drugs that increase urine output to reduce excessive fluid in the system, can be used when fluid overload does occur, as long as there is not a significant risk of shock. Furosemide, a diuretic used in the treatment of pulmonary contusion, also relaxes the smooth muscle in the veins of the lungs, thereby decreasing pulmonary venous resistance and reducing the pressure in the pulmonary capillaries. Supportive care Retaining secretions in the airways can worsen hypoxia and lead to infections. Thus, an important part of treatment is pulmonary toilet, the use of suction, deep breathing, coughing, and other methods to remove material such as mucus and blood from the airways. Chest physical therapy makes use of techniques such as breathing exercises, stimulation of coughing, suctioning, percussion, movement, vibration, and drainage to rid the lungs of secretions, increase oxygenation, and expand collapsed parts of the lungs. People with pulmonary contusion, especially those who do not respond well to other treatments, may be positioned with the uninjured lung lower than the injured one to improve oxygenation. Inadequate pulmonary toilet can result in pneumonia. People who do develop infections are given antibiotics. No studies have yet shown a benefit of using antibiotics as a preventative measure before infection occurs, although some doctors do recommend prophylactic antibiotic use even without scientific evidence of its benefit. However, this can cause the development of antibiotic resistant strains of bacteria, so giving antibiotics without a clear need is normally discouraged. For people who are at especially high risk of developing infections, the sputum can be cultured to test for the presence of infection-causing bacteria; when they are present, antibiotics are used.Pain control is another means to facilitate the elimination of secretions. A chest wall injury can make coughing painful, increasing the likelihood that secretions will accumulate in the airways. Chest injuries also contribute to hypoventilation (inadequate breathing) because the chest wall movement involved in breathing adequately is painful. Insufficient expansion of the chest may lead to atelectasis, further reducing oxygenation of the blood. Analgesics (pain medications) can be given to reduce pain. Injection of anesthetics into nerves in the chest wall, called nerve blockade, is another approach to pain management; this does not depress respiration the way some pain medications can. Prognosis Pulmonary contusion usually resolves itself without causing permanent complications; however it may also have long-term ill effects on respiratory function. Most contusions resolve in five to seven days after the injury. Signs detectable by radiography are usually gone within 10 days after the injury—when they are not, other conditions, such as pneumonia, are the likely cause. Chronic lung disease correlates with the size of the contusion and can interfere with an individuals ability to return to work. Fibrosis of the lungs can occur, resulting in dyspnea (shortness of breath), low blood oxygenation, and reduced functional residual capacity for as long as six years after the injury. As late as four years post-injury, decreased functional residual capacity has been found in most pulmonary contusion patients studied. During the six months after pulmonary contusion, up to 90% of people have difficulty breathing. In some cases, dyspnea persists for an indefinite period. Contusion can also permanently reduce the compliance of the lungs. Complications Pulmonary contusion can result in respiratory failure—about half of such cases occur within a few hours of the initial trauma. Other severe complications, including infections and acute respiratory distress syndrome (ARDS) occur in up to half of cases. Elderly people and those who have heart, lung, or kidney disease prior to the injury are more likely to stay longer in hospital and have complications from the injury. Complications occur in 55% of people with heart or lung disease and 13% of those without. Of people with pulmonary contusion alone, 17% develop ARDS, while 78% of people with at least two additional injuries develop the condition. A larger contusion is associated with an increased risk. In one study, 82% of people with 20% or more of the lung volume affected developed ARDS, while only 22% of people with less than 20% did so.Pneumonia, another potential complication, develops in as many as 20% of people with pulmonary contusion. Contused lungs are less able to remove bacteria than uninjured lungs, predisposing them to infection. Intubation and mechanical ventilation further increase the risk of developing pneumonia; the tube is passed through the nose or mouth into the airways, potentially tracking bacteria from the mouth or sinuses into them. Also, intubation prevents coughing, which would clear bacteria-laden secretions from the airways, and secretions pool near the tubes cuff and allow bacteria to grow. The sooner the endotracheal tube is removed, the lower the risk of pneumonia, but if it is removed too early and has to be put back in, the risk of pneumonia rises. People who are at risk for pulmonary aspiration (e.g. those with lowered level of consciousness due to head injuries) are especially likely to get pneumonia. As with ARDS, the chances of developing pneumonia increase with the size of the contusion. Children and adults have been found to have similar rates of complication with pneumonia and ARDS. Associated injuries A large amount of force is required to cause pulmonary contusion; a person injured with such force is likely to have other types of injuries as well. In fact, pulmonary contusion can be used to gauge the severity of trauma. Up to three quarters of cases are accompanied by other chest injuries, the most common of these being hemothorax and pneumothorax. Flail chest is usually associated with significant pulmonary contusion, and the contusion, rather than the chest wall injury, is
Pulmonary contusion	often the main cause of respiratory failure in people with these injuries. Other indications of thoracic trauma may be associated, including fracture of the sternum and bruising of the chest wall. Over half of fractures of the scapula are associated with pulmonary contusion. The contusion is frequently found underlying fracture sites. When accompanied by a fracture, it is usually concentrated into a specific location—the contusion is more diffuse when there is no fracture. Pulmonary lacerations may result from the same blunt or penetrating forces that cause contusion. Lacerations can result in pulmonary hematomas; these are reported to develop in 4–11% of pulmonary contusions. Epidemiology Pulmonary contusion is found in 30–75% of severe cases of chest injury, making it the most common serious injury to occur in association with thoracic trauma. Of people who have multiple injuries with an injury severity score of over 15, pulmonary contusion occurs in about 17%. It is difficult to determine the death rate (mortality) because pulmonary contusion rarely occurs by itself. Usually, deaths of people with pulmonary contusion result from other injuries, commonly traumatic brain injury. It is controversial whether pulmonary contusion with flail chest is a major factor in mortality on its own or whether it merely contributes to mortality in people with multiple injuries. The estimated mortality rate of pulmonary contusion ranges from 14 to 40%, depending on the severity of the contusion itself and on associated injuries. When the contusions are small, they do not normally increase the chance of death or poor outcome for people with blunt chest trauma; however, these chances increase with the size of the contusion. One study found that 35% of people with multiple significant injuries including pulmonary contusion die. In another study, 11% of people with pulmonary contusion alone died, while the number rose to 22% in those with additional injuries. Pulmonary contusion is thought to be the direct cause of death in a quarter to a half of people with multiple injuries (polytrauma) who die. An accompanying flail chest increases the morbidity and mortality to more than twice that of pulmonary contusion alone.Pulmonary contusion is the most common cause of death among vehicle occupants involved in accidents, and it is thought to contribute significantly in about a quarter of deaths resulting from vehicle collisions. As vehicle use has increased, so has the number of auto accidents, and with it the number of chest injuries. However an increase in the number of airbags installed in modern cars may be decreasing the incidence of pulmonary contusion. Use of child restraint systems has brought the approximate incidence of pulmonary contusion in children in vehicle accidents from 22% to 10%.Differences in the bodies of children and adults lead to different manifestations of pulmonary contusion and associated injuries; for example, children have less body mass, so the same force is more likely to lead to trauma in multiple body systems. Since their chest walls are more flexible, children are more vulnerable to pulmonary contusion than adults are, and thus suffer from the injury more commonly. Pulmonary contusion has been found in 53% of children with chest injuries requiring hospitalization. Children in forceful impacts suffer twice as many pulmonary contusions as adults with similar injury mechanisms, yet have proportionately fewer rib fractures. The rates of certain types of injury mechanisms differ between children and adults; for example, children are more often hit by cars as pedestrians. Some differences in childrens physiology might be advantageous (for example they are less likely to have other medical conditions), and thus they have been predicted to have a better outcome. However, despite these differences, children with pulmonary contusion have similar mortality rates to adults. History In 1761, the Italian anatomist Giovanni Battista Morgagni was first to describe a lung injury that was not accompanied by injury to the chest wall overlying it. Nonetheless, it was the French military surgeon Guillaume Dupuytren who is thought to have coined the term pulmonary contusion in the 19th century. It still was not until the early 20th century that pulmonary contusion and its clinical significance began to receive wide recognition. With the use of explosives during World War I came many casualties with no external signs of chest injury but with significant bleeding in the lungs. Studies of World War I injuries by D.R. Hooker showed that pulmonary contusion was an important part of the concussive injury that results from explosions.Pulmonary contusion received further attention during World War II, when the bombings of Britain caused blast injuries and associated respiratory problems in both soldiers and civilians. Also during this time, studies with animals placed at varying distances from a blast showed that protective gear could prevent lung injuries. These findings suggested that an impact to the outside of the chest wall was responsible for the internal lesions. In 1945, studies identified a phenomenon termed "wet lung", in which the lungs accumulated fluid and were simultaneously less able to remove it. They attributed the respiratory failure often seen in blunt chest trauma in part to excessive fluid resuscitation, and the question of whether and how much to administer fluids has remained controversial ever since.During the Vietnam War, combat again provided the opportunity for study of pulmonary contusion; research during this conflict played an important role in the development of the modern understanding of its treatment. The condition also began to be more widely recognized in a non-combat context in the 1960s, and symptoms and typical findings with imaging techniques such as X-ray were described. Before the 1960s, it was believed that the respiratory insufficiency seen in flail chest was due to "paradoxical motion" of the flail segment of the chest wall (the flail segment moves in the opposite direction as the chest wall during respiration), so treatment was aimed at managing the chest wall injury, not the pulmonary contusion. For example, positive pressure ventilation was used to stabilize the flail segment from within the chest. It was first proposed in 1965 that this respiratory insufficiency is most often due to injury of the lung rather than to the chest wall, and a group led by J.K. Trinkle confirmed this hypothesis in 1975. Hence the modern treatment prioritizes the management of pulmonary contusion. Animal studies performed in the late 1960s and 1970s shed light on the pathophysiological processes involved in pulmonary contusion. Studies in the 1990s revealed a link between pulmonary contusion and persistent respiratory difficulty for years after the injury in people in whom the injury coexisted with flail chest. In the next decade studies demonstrated that function in contused lungs improves for years after the injury. References External links Chest Trauma - pulmonary contusion, trauma.org
Dandruff	Dandruff is a skin condition that mainly affects the scalp. Symptoms include flaking and sometimes mild itchiness. It can result in social or self-esteem problems. A more severe form of the condition, which includes inflammation of the skin, is known as seborrhoeic dermatitis.The cause is unclear, but believed to involve a number of genetic and environmental factors; the condition may worsen in the winter. It is not due to poor hygiene, and the underlying mechanism involves the excessive growth of skin cells. Diagnosis is based on symptoms.There is no known cure for dandruff. Antifungal cream, such as ketoconazole, or salicylic acid may be used to try to improve the condition. Dandruff affects about half of adults, with males more often affected than females. In addition, people in all areas of the world are affected. Onset is usually at puberty, and it becomes less common after the age of 50. Signs and symptoms The main symptoms of dandruff are an itchy scalp and flakiness. Red and greasy patches of skin and a tingly feeling on the skin are also symptoms. Causes The cause is unclear but believed to involve a number of genetic and environmental factors. As the skin layers continually replace themselves, cells are pushed outward where they die and flake off. For most individuals, these flakes of skin are too small to be visible. However, certain conditions cause cell turnover to be unusually rapid, especially in the scalp. It is hypothesized that for people with dandruff, skin cells may mature and be shed in 2–7 days, as opposed to around a month in people without dandruff. The result is that dead skin cells are shed in large, oily clumps, which appear as white or grayish flakes on the scalp, skin and clothes. According to one study, dandruff has been shown to be possibly the result of three factors: Skin oil, commonly referred to as sebum or sebaceous secretions The metabolic by-products of skin micro-organisms (most specifically Malassezia yeasts) Individual susceptibility and allergy sensitivity. Microorganisms Older literature cites the fungus Malassezia furfur (previously known as Pityrosporum ovale) as the cause of dandruff. While this species does occur naturally on the skin surface of people both with and without dandruff, in 2007, it was discovered that the responsible agent is a scalp specific fungus, Malassezia globosa, that metabolizes triglycerides present in sebum by the expression of lipase, resulting in a lipid byproduct: oleic acid. During dandruff, the levels of Malassezia increase by 1.5 to 2 times its normal level. Oleic acid penetrates the top layer of the epidermis, the stratum corneum, and evokes an inflammatory response in susceptible people which disturbs homeostasis and results in erratic cleavage of stratum corneum cells. Seborrhoeic dermatitis In seborrhoeic dermatitis, redness and itching frequently occur around the folds of the nose and eyebrow areas, not just the scalp. Dry, thick, well-defined lesions consisting of large, silvery scales may be traced to the less common condition of scalp psoriasis. Inflammation can be characterized by redness, heat, pain or swelling, and can cause sensitivity. Inflammation and extension of scaling outside the scalp exclude the diagnosis of dandruff from seborrhoeic dermatitis. However, many reports suggest a clear link between the two clinical entities - the mildest form of the clinical presentation of seborrhoeic dermatitis as dandruff, where the inflammation is minimal and remain subclinical.Seasonal changes, stress, and immunosuppression seem to affect seborrheic dermatitis. Mechanism Dandruff scale is a cluster of corneocytes, which have retained a large degree of cohesion with one another and detach as such from the surface of the stratum corneum. A corneocyte is a protein complex that is made of tiny threads of keratin in an organised matrix. The size and abundance of scales are heterogeneous from one site to another and over time. Parakeratotic cells often make up part of dandruff. Their numbers are related to the severity of the clinical manifestations, which may also be influenced by seborrhea. Treatment Shampoos use a combination of special ingredients to control dandruff. Antifungals Antifungal treatments including ketoconazole, zinc pyrithione and selenium disulfide have been found to be effective. Ketoconazole appears to have a longer duration of effect. Ketoconazole is a broad spectrum antimycotic agent that is active against Candida and M. furfur. Of all the antifungals of the imidazole class, ketoconazole has become the leading contender among treatment options because of its effectiveness in treating seborrheic dermatitis as well.Ciclopirox (topical route) may also be used as an anti-dandruff agent. However, it is mostly sold as cream and its main use is for treating athletes foot, jock itch, and ringworm. Coal tar Coal tar causes the skin to shed dead cells from the top layer and slows skin cell growth. Essential oils Essential oils, such as tea tree oil (for composition, see ISO 4730:2017), are found to be effective in the treatment of dandruff, but more research is required. Etymology According to the Oxford English Dictionary, the word dandruff is first attested in 1545, but is still of unknown etymology. References == External links ==
Specific phobia	Specific phobia is an anxiety disorder, characterized by an extreme, unreasonable, and irrational fear associated with a specific object, situation, or concept which poses little or no actual danger. Specific phobia can lead to avoidance of the object or situation, persistence of the fear, and significant distress or problems functioning associated with the fear. A phobia can be the fear of anything. Although fears are common and normal, a phobia is an extreme type of fear where great lengths are taken to avoid being exposed to the particular danger. Phobias are considered the most common psychiatric disorder, affecting about 10% of the population in the US, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), (among children, 5%; among teens, 16%). About 75% of patients have more than one specific phobia. It can be described as when patients are anxious about a particular situation. It causes a great load of difficulty in life. Patients have a lot of distress or interference when functioning in their daily life. Unreasonable or irrational fears get in the way of daily routines, work, and relationships due to the effort that a patient makes to avoid the terrifying feelings associated with the fear.Females are twice as likely to be diagnosed than males with a specific phobia (although this can depend on the stimulus).Children and adolescents who are diagnosed with a specific phobia are at an increased risk for additional psychopathology later in life. Signs and symptoms Fear, discomfort or anxiety may be triggered both by the presence and the anticipation of the specific object or situation. The main behavioral sign of a specific phobia is avoidance. The fear or anxiety associated with specific phobia can also manifest in physical symptoms such as an increased heart rate, shortness of breath, muscle tension, sweating, or a desire to escape the situation. Causes The exact cause of specific phobias is not known. The mechanisms for development of specific phobias can be distinguished between innate (genetic and neurobiological) factors, and learned factors. In neurobiology, one explanation proposed for specific phobia is that the typical activation of the amygdala in response to stimuli may be exaggerated due to pathological changes. According to this theory, a deficiency in amygdala habituation may also contribute to the persistence of non-experiential phobia. Certain phobias that are less lethal (e.g. dogs) seem to be more frequently observed and easily acquired in comparison to potentially lethal fears which are more relevant to developed human society (e.g. cars and guns). This was theorised to be due to biological adaptation being passed through evolution which makes recent threats less prone to easy acquisition. However, a 2014 study found evidence against this evolutionary theory, which stated: "Our findings are inconsistent with the hypothesis that fears/phobias of individual stimuli result from genetic and environmental factors unique to that stimulus. Instead, we observed substantial sharing of risk factors across individual fears." There is also evidence for the validity of a genetic component contributing to blood-injection-injury phobias and animal phobias, although this evidence did not support the idea that other specific phobias had genetic influence. Blood-injection-injury phobias are also believed to be the most heritable among specific phobias.The classical conditioning model of learning has also been used to suggest that a phobia will be learned when an event that causes a fear or anxiety reaction is paired with a neutral event. An example of this model is when being near a dog (neutral event) is paired with the emotional experience of being bitten by a dog, resulting in a chronic fear which is described as a specific phobia to dogs. An alternative proposed mechanism of association is through observational learning. According to this theory, a person may internalize another persons fears about a specific object or situation through observation of their reactions. Diagnosis Diagnosis in the ICD or the DSM requires a marked fear, anxiety or avoidance that is long-lasting (greater than six months) and consistently occurs in the presence of the feared object or situation. The DSM-5 that the fears should be out of proportion to the danger posed, compared to the ICD-10 which specifies that the symptoms must be excessive or unreasonable. Minor differences have persisted between the ICD-11 and DSM-5.In the DSM-5, there are several types which specific phobia can be classified under: Animal type – Including fear of spiders (arachnophobia), insects (entomophobia), or dogs (cynophobia). Natural environment type – Including fear of water (aquaphobia), heights (acrophobia), lightning and thunderstorms (astraphobia), or aging (gerascophobia). Situational type – Including the fear of small confined spaces (claustrophobia), or the dark (nyctophobia). Blood/injection/injury type – Including fear of medical procedures, including needles and injections (trypanophobia), fear of blood (hemophobia) and fear of getting injured (traumatophobia). Other – Situations which can lead to choking or vomiting, and childrens fears of loud sounds or costumed characters.Although the avoidance resulting from specific phobia is comparable to other anxiety disorders, differential diagnosis is done through examining underlying causes for the behavior. Agoraphobia is also considered distinct from specific phobia, along with substance use disorders, and avoidant personality disorder. The occurrence of panic attacks is not itself a symptom of specific phobias and falls under the criteria of panic disorder. Treatment There are a variety of treatment options available for specific phobias, most of which focus on psychosocial interventions. Different psychological treatments have varying levels of effects depending on the specific phobia being addressed. Cognitive behavioral therapy (CBT) Cognitive behavioral therapy is a short term, skills-focused therapy that aims to help people diffuse unhelpful emotional responses by helping people consider them differently or change their behavior. CBT represents the gold standard and first line of therapy in specific phobias. CBT is effective in treating specific phobias primarily through exposure and cognitive strategies to overcome a persons anxiety. Computer-assisted treatment programs, self-help manuals, and delivery by a trained practitioner are all methods of accessing CBT. A single session of CBT in one of these modalities can be effective for individuals who have a specific phobia. Exposure therapy Exposure therapy is a particularly effective form of CBT for many specific phobias, however, treatment acceptance and high drop-out rates have been noted as concerns. In addition, a third of people who complete exposure therapy as a treatment for specific phobia may not respond, regardless of the type of exposure therapy. Other interventions have been successful for particular types of specific phobia, such as virtual reality exposure therapy (VRET) for spider, dental, and height phobias, applied muscle tension (AMT) for needle phobia, and psychoeducation with relaxation exercises for fear of childbirth. With exposure therapy, a type of cognitive-behavioural therapy, clinically significant improvement was experienced by up to 90% of patients. While very long-term outcomes remain unknown, many of the benefits of exposure therapy persisted after one year. Treatment may be more successful at reducing symptoms in people with low trait anxiety, high motivation, and high self-efficacy entering exposure therapy. In addition, high cortisol levels, high heart rate variation, evoking disgust, avoiding relaxation, focusing on cognitive changes, context variation, sleep, and memory-enhancing drugs can also reduce symptoms following exposure therapy.Exposure can be "live"(in real life) or imaginal (in ones imagination) and can involve: Systematic desensitization—A therapy that exposes the person to increasing levels of vivid stimuli gradually and frequently, while instructed to relax. Flooding—A therapy that exposes the person with a specific phobia to the most fearful stimulus first (i.e. the most intense part of the phobia). Patients are at great risk for dropping out of treatment as this method repeatedly exposes the patient to the fear. Modeling—This method includes the clinician approaching the feared stimuli while the patient observes and tries to repeat the approach themselves.Exposures that are imaginal are less effective.Specifically for acrophobia, in-vivo exposure (exposure to real-world height-scenarios while maintaining anxiety at controlled levels) has been shown to significantly improve measures of anxiety in the short-term, but this effect decreased over a longer term. Likewise, virtual reality exposure was statistically significant in some measures of anxiety reduction, but not others. Pharmacotherapeutics As of late 2020, there is limited evidence for the use of pharmacotherapy in the treatment of specific phobia. Pharmacological treatments are typically used in combination with behaviorally-focused psychotherapy, as introducing pharmacological interventions independently may result in relapsing of symptoms. Different treatments are better suited for certain types of specific phobia. For instance, beta blockers are useful in those with performance anxiety. The selective serotonin re-uptake inhibitors (SSRIs), paroxetine and escitalopram, have shown preliminary efficacy in small randomized controlled clinical trials. However, these trials were too small to show any definitive benefits of anxiolytic medication alone in treating phobia. Benzodiazepines are occasionally used for acute symptom relief, but have not been shown to be effective for long-term treatment. There are some findings suggesting that adjuvant use of the NMDA receptor partial agonist, d-cycloserine, with virtual reality exposure therapy may improve specific phobia symptoms more than virtual reality exposure therapy alone. As of 2020, studies on the use of adjunct d-cycloserine are inconclusive. Prognosis The majority of those that develop a specific phobia first experience symptoms in childhood. Often individuals will experience symptoms periodically with periods of remission before complete remission occurs. However, specific phobias that continue into adulthood are likely to experience a more chronic course. Specific phobias in older adults has been linked with a decrease in quality of life. Those with specific phobias are at an increased risk of suicide. Greater impairment is found in those that have multiple phobias. Response to treatment is relatively high but many do not seek treatment due to lack of access, ability to avoid phobia, or unwilling to face feared object for repeated CBT sessions. Epidemiology Specific phobia is estimated to affect 6-12% of people at some point in their life. There may be a large amount of underreporting of specific phobias as many people do not seek treatment, with some surveys conducted in the US finding that 70% of the population reports having one or more unreasonable fears.Specific phobias have a lifetime prevalence rate of 7.4% and a one-year prevalence of 5.5% according to data collected from 22 different countries. The usual age of onset is childhood to adolescence. During childhood and adolescence, the incidence of new specific phobias is much higher in females than males. The peak incidence for specific phobias amongst females occurs during reproduction and childrearing, possibly reflecting an evolutionary advantage. There is an additional peak in incidence, reaching nearly 1% per year, during old age in both men and women, possibly reflective of newly occurring physical conditions or adverse life events. The development of phobias varies with subtypes, with animal and blood injection phobias typically beginning in childhood (ages 5–12), whereas development of situational specific phobias (i.e., fear of flying) usually occurs in late adolescence and early adulthood.In the US, the lifetime prevalence rate is 12.5% and a one-year prevalence rate of 9.1%. An estimated 12.5% of U.S. adults experience specific phobia at some time in their lives and the prevalence is approximately double in females compared to males. An estimated 19.3% of adolescents experience specific phobia, but the difference between males and females is not as pronounced. See also List of phobias Phobia References External links Encyclopedia of Mental Disorders – Specific phobias
Copra itch	Copra itch is a skin condition that occurs on persons handling copra who are subject to Tyrophagus longior mite bites.: 454 See also Coolie itch Skin lesion == References ==
Blue baby syndrome	Blue baby syndrome can refer to conditions that cause cyanosis, or blueness of the skin, in babies as a result of low oxygen levels in the blood. This term has traditionally been applied to cyanosis as a result of: Cyanotic heart disease, which is a category of congenital heart defect that results in low levels of oxygen in the blood. This can be caused by either reduced blood flow to the lungs or mixing of oxygenated and deoxygenated blood. Methemoglobinemia, which is a disease defined by high levels of methemoglobin in the blood. Increased levels of methemoglobin prevent oxygen from being released into the tissues and result in hypoxemia.Although these are the most common causes of cyanosis, there are other potential factors that can cause a blue tint to a babys skin or mucous membranes. These factors include hypoventilation, perfusion or ventilation differences in the lungs, and poor cardiac output of oxygenated blood, among others. The blue baby syndrome or cyanosis occurs when absolute amount of deoxygenated hemoglobin >3g/dL which is typically reflected with an O2 saturation of <85%.Both of these conditions cause cyanosis, or a bluish discoloration of skin or mucous membranes. Normally, oxygenated blood appears red and deoxygenated blood has more of a blue appearance. In babies with low levels of oxygen or mixing of oxygenated and deoxygenated blood, the blood can have a blue or purple color, causing cyanosis. Signs and symptoms The main sign of blue baby syndrome is cyanosis. Depending on the underlying cause of the cyanosis, additional symptoms may be: Rapid heartbeat Rapid respiratory rate Failure to thrive Shortness of breath Nasal flaring Lethargy Seizures Causes Blue baby syndrome has been attributed to cyanotic congenital heart diseases and methemoglobinemia, however there are additional causes that could result in a baby becoming cyanotic, such as: Decreased blood perfusion Pulmonary/lung disorders (ex: Pulmonary hypertension, cystic fibrosis) Disordered control of breathing (ex: Cyanotic breath-holding spells, seizures) Airway obstruction Respiratory distress syndrome Mechanism Cyanotic heart disease Specific types of congenital heart defects that cause blood to pass directly from the right side of the heart to the left side result in cyanosis. In these defects, some of the blood that is pumped to the body has not been oxygenated by the lungs and therefore will appear more blue. Infants with these types of heart defects may have a constant bluish tint to their skin, or they may have temporary episodes of cyanosis. The degree of cyanosis is dependent on how much deoxygenated blood is mixed with oxygenated blood before being pumped to the body. Cardiac conditions in which there is decreased blood flow to the lungs such as, tetralogy of Fallot or pulmonary valve atresia, result in less blood becoming oxygenated. There are also cardiac conditions such as transposition of the great arteries or truncus arteriosus, that results in an overall increase in blood flow to the lungs but with limited flow of the oxygenated blood to the rest of the body. Conditions in which there is poor blood flow to the systemic circulation, such as coarctation of the aorta suggests that the body does not receive the oxygenated blood it requires with resultant cyanosis.The five most common cyanotic heart defects that may result in Blue Baby Syndrome include the following: Methemoglobinemia Methemoglobinemia which can be acquired or congenital, occurs when the iron in hemoglobin is oxidized from Fe2+ to Fe3+, leading to poor binding of oxygen. Additionally, the oxygen that is already bound is held more tightly to the hemoglobin due to a higher affinity, resulting in less oxygen delivery. A methemoglobin level >1.5g/dL causes cyanosis. The most common congenital cause is a deficiency in the enzyme cytochrome b5 reductase which reduces methemoglobin in the blood. However, in infants the most common cause of methemoglobinemia is acquired through the ingestion of nitrates through well water or foods. Infants younger than 4 months are at greater risk given that they drink more water per body weight, they have a lower NADH- cytochrome b5 reductase activity, and they have a higher level of fetal hemoglobin which converts more easily to methemoglobin. Additionally, infants are at an increased risk after an episode of gastroenteritis due to the production of nitrites by bacteria. The sources of nitrate can include fertilizers used in agricultural lands, waste dumps or pit latrines. For example, nitrate levels are subject to monitoring to comply with drinking water quality standards in the United States and other countries. The link between blue baby syndrome and nitrates in drinking water is widely accepted, but some studies indicate that other contaminants, or dietary nitrate sources, may also play a role in the syndrome. Diagnosis When diagnosing blue baby syndrome, it is important to perform a thorough history and physical exam. When obtaining the history, it is important to determine the timing of symptoms and to ask about risk factors/exposures, such as prenatal history or access to well-water. On physical exam it is important to visualize where the cyanosis is present to differentiate between peripheral and central cyanosis. Central cyanosis is typically visible as a blueish discoloration over the entire body and mucous membranes. In contrast, peripheral cyanosis typically has a blueish discoloration over the extremities. Cyanosis can be noted in babies around the lips, tongue, and sublingual area, where the skin is thinnest. In addition, it is important to observe the infant for signs of respiratory distress, visualized as nasal flaring, subcostal retractions, etc. Examination should include a respiratory and cardiac assessment.One of the key tools in diagnosing is a pulse oximeter to determine oxygen saturation. While severe cyanosis can be easily noticed, an oxygen saturation as low as 80% causes only mild clinical cyanosis that is difficult to see. Additionally an arterial blood gas is useful, for example in the case of methemoglobinemia the PO2 can be expected to be normal even with a low oxygen saturation. Additional work up includes a complete blood count, blood glucose, blood culture, chest x-ray, and an echocardiography.Babies with cyanosis due to congenital heart disease usually present with symptoms hours to days after birth. In addition to cyanosis, they often show signs of tachypnea (fast breathing), a heart murmur, and decreased peripheral pulses. If congenital heart disease is suspected in a newborn, doctors will likely perform several tests to evaluate the heart, including a chest x-ray, echocardiogram, and electrocardiogram. In tetralogy of Fallot, episodes in which infants become cyanotic are called tet spells, typically occurring during feeding or crying. When older, children may squat to feel relief since this increases the systemic vascular resistance causing more blood to go towards the lungs, resulting in increased oxygenation.Babies with cyanosis due to methemoglobinemia also usually present with cyanosis in the neonatal period, but pulse oximetry may be falsely elevated and does not always reveal low blood oxygen saturation. . A co-oximeter can be used to detect levels of methemoglobin in the blood if methemoglobinemia is suspected, by seeing the difference between oxygen saturation on an arterial blood gas and the measurement on a co-oximeter. Additionally, a direct methemoglobin level can be obtained. Prevention/Screening The United States Environmental Protection Agency has established a maximum contaminant level of 10 mg/L for nitrate and 1 mg/L for nitrite due to the potential harmful effects in infants.A screening tool has been developed to screen for critical cardiac defects, which refers to cardiac lesions that require surgery or intervention in the 1st year of life. Screening for critical congenital heart defect should be done on all newborns after 24hours or shortly before discharge. Oxygen saturation is measured in the right hand and either foot.A screening is considered positive if: Oxygen saturation <90% in either extremity, Oxygen saturation 90-94% in both extremities on 3 measurements separated by an hour each, Oxygen saturation difference >3% between both extremities on 3 measurements separated by an hour each. Management Treatment for blue baby syndrome will depend on the underlying cause. When evaluating a patient for cyanosis or respiratory distress, vital signs should be monitored, especially the patients heart rate and oxygen saturation. It is beneficial to have vascular access established. In newborns, the pulse oximeter is typically placed on the right hand to determine pre-ductal oxygenation, referring to oxygenation before the ductus arteriosus (connection between aorta and pulmonary artery). This gives the oxygenation level the heart and brain receive. Traditionally, supplemental oxygen is given in an escalating manner beginning with free-flowing oxygen, progressing to positive pressure ventilation or continuous positive airway pressure, and ending with mechanical intubation. The goal oxygen saturation is between 85 and 95%. If an infant requires supplemental oxygen for a prolonged time it should be heated and humidified to avoid heat loss. Cyanotic heart disease Some babies born with cyanotic heart disease are treated with prostaglandin E1 after birth to keep the ductus arteriosus open and allow for more oxygenated blood to be pumped to the body. Many also receive oxygen therapy to increase the percentage of oxygen in the blood. Most of these babies will require surgery during infancy to correct their structural heart defect. Severe methemoglobinemia The first-line treatment for severe methemoglobinemia is methylene blue, a medication that will reduce methemoglobin in the blood. This is possible because methylene blue oxidizes NADPH, which in turn can convert methemoglobin back to hemoglobin. Epidemiology Out of all the babies born with congenital heart defects, about 25% have cyanosis as a result. Tetralogy of Fallot is the most common cyanotic cardiac heart defect.Methemoglobinemia is considered to be rare, with acquired methemoglobinemia encountered more than the congenital form. Outcomes In the case of cyanotic causing heart defects, about 75% of infants survive to 1 year of age and 69% survive to 18 years of age. These individuals have an increased risk of developmental delay, heart failure, or heart rhythm disorders.Methemoglobinemia responds well to treatment, its prognosis is associated with the level of methemoglobinemia and the degree of end organ damage it can cause. Death can occur when levels reach 70%. History The first successful operation to treat blue baby syndrome caused by Tetralogy of Fallot occurred at Johns Hopkins University in 1944. Through a collaboration between pediatric cardiologist Helen Taussig, surgeon Alfred Blalock, and surgical technician Vivien Thomas, the Blalock-Thomas-Taussig shunt was created. Dr. Taussig had recognized that children with Tetralogy of Fallot who also had a patent ductus arteriosus (PDA) typically lived longer, so the trio tried to create the same effect as a PDA by joining the subclavian artery to the pulmonary artery, relieving the childs cyanosis. The operation was published in the Journal of the American Medical Association in 1945 and impacted management of blue babies around the world.Anna was the name of the dog who was the first survivor of the surgery, considered an experimental procedure at the time. Anna survived the first pulmonary bypass after having been operated on twice. The second operation was required to replace the original stitches with flexible ones. After their success with Anna, Blalock and Thomas had the courage to perform the very first open heart surgery on Eileen Saxon in 1944. In 1950, Annas story was made into a movie, and the film has been shown to various schools and other groups. == References ==
Pentalogy of Cantrell	Pentalogy of Cantrell (or thoraco-abdominal syndrome) is a rare congenital syndrome that causes defects involving the diaphragm, abdominal wall, pericardium, heart and lower sternum. Presentation There are five characteristic findings in pentalogy of Cantrell: an abdominal wall defect, lower sternal defect, congenital heart malformations, absence of the diaphragmatic pericardium, and an anterior diaphragmatic defect.Abdominal wall defects in pentalogy of Cantrell occur above the umbilicus (supraumbilical) and in the midline, and have a wide range of presentations. Diastasis recti, hernias, and omphalocele have all been described in conjunction with the pentalogy.Sternal defects too have a range of presentations, from absence of the xiphoid process to shortened or cleft sternum. If the sternal defect is large enough, the neonate may have ectopia cordis, in which the heart is located outside of the thorax.Many congenital heart malformations have been described in conjunction with pentalogy of Cantrell. The most common is ventricular septal defect, found in 72% of cases. Others include atrial septal defect, cardiac diverticulum, pulmonic stenosis, double outlet right ventricle, tetralogy of Fallot, dextrocardia, and transposition of the great vessels. Causes Most cases of pentalogy of Cantrell are idiopathic (no known cause). However, some cases have been described with a genetic linkage to a locus at Xq25-q26.1. Epidemiology Pentalogy of Cantrell occurs in 1/65,000 to 1/200,000 live births. History It was first characterized in 1958.A 2010 study concluded that the 13th-century Christian saint Rose of Viterbo died of complications of Pentalogy of Cantrell. References == External links ==
Kniest dysplasia	Kniest dysplasia is a rare form of dwarfism caused by a mutation in the COL2A1 gene on chromosome 12. The COL2A1 gene is responsible for producing type II collagen. The mutation of COL2A1 gene leads to abnormal skeletal growth and problems with hearing and vision. What characterizes Kniest dysplasia from other type II osteochondrodysplasia is the level of severity and the dumb-bell shape of shortened long tubular bones.This condition was first described by Dr. Wilhelm Kniest in 1952, publishing the case history of a 3 1⁄2 year-old girl. Dr. Kniest noticed that his patient had bone deformities and restricted joint mobility. The patient also had short stature and later developed blindness, resulting from retinal detachment and glaucoma. Upon analysis of the patients DNA in 1992, sequencing revealed deletion of a 28 base pair sequence encompassing a splice site in exon 12 and a G to A transition in exon 50 of the COL2A1 gene.This condition is very rare and occurs less than 1 in 1,000,000 people. Males and females have equal chances of having this condition. Currently, there is no cure for Kniest dysplasia. Alternative names for Kniest Dysplasia can include Kniest syndrome, swiss cheese cartilage syndrome, Kniest chondrodystrophy, or metatrophic dwarfism type II. Signs and symptoms Because collagen plays an important role in the development of the body, people with Kniest Dysplasia will typically have their first symptoms at birth. These symptoms can include: Musculoskeletal Problems Short limbs Shortened body trunk Flattened bones in the spine (platyspondyly) kyphoscoliosis Scoliosis (Lateral curvature of the spine) Early development of arthritis Respiratory problems Respiratory tract infection Difficulty breathing Eye problems Severe myopia (near-sightedness) Cataract (cloudiness in the lens of the eye) Cranial structure may elongate the eyeball, causing a thinning of the retina, thereby predisposing retinal detachment Hearing problems progressive hearing loss ear infectionsMost symptoms are chronic and will continue to worsen as the individual ages. It is essential to have regular checkups with general doctors, orthopedist, ophthalmologists, and/or otorhinolaryngologists. This will help to detect whether there are any changes that could cause concern. Genetics Mechanism Studies have shown that a mutated COL2A1 gene is responsible for all type II chondroldysplasias, including Kniest dysplasia. It is believed that point mutations or the alteration of splice sites in COL2A1 domains will result in Kniest Dysplasia. The COL2A1 domain typically spans between exon 12 and 24. Mutations that occur at a splice donor site results in the loss of function at that site. This leads to the skipping of the exon and deletion of amino acids. The loss of these amino acids result in an abnormal procollagen II structure. The structure is not stable like the normal procollagen II structure and is normally degraded at a faster rate. Diagnosis Family/medical history Kniest dysplasia is an autosomal dominant condition. This means that the person only needs to have one copy of the mutated gene in order to have the condition. People with a family history are at a higher risk of having the disease than people with no family history. A random mutation in the gene can cause a person with no family history to also have the condition. Diagnostic techniques A combination of medical tests are used to diagnosis Kniest dysplasia. These tests can include: Computer Tomography Scan (CT scan) - This test uses multiple images taken at different angles to produce a cross-sectional image of the body. Magnetic Resonance Imaging (MRI) - This technique proves detailed images of the body by using magnetic fields and radio waves. EOS Imaging - EOS imaging provides information on how musculoskeletal system interacts with the joints. The 3D image is scanned while the patient is standing and allows the physician to view the natural, weight-bearing posture. X-rays - X-ray images will allow the physician to have a closer look on whether or not the bones are growing abnormally.The images taken will help to identify any bone anomalies. Two key features to look for in a patient with Kniest dysplasia is the presence of dumb-bell shaped femur bones and coronal clefts in the vertebrae. Other features to look for include: Platyspondyly (flat vertebral bodies) Kyphoscoliosis (abnormal rounding of the back and lateral curvature of the spine) Abnormal growth of epiphyses, metaphyses, and diaphysis Short tubular bones Narrowed joint spacesGenetic Testing - A genetic sample may be taken in order to closely look at the patients DNA. Finding an error in the COL2A1 gene will help identify the condition as a type II chondroldysplasia. Treatment Because Kniest dysplasia can affect various body systems, treatments can vary between non-surgical and surgical treatment. Patients will be monitored over time, and treatments will be provided based on the complications that arise. Surgical Spinal Fusion for patients with severe kyphoscoliosis Extension Osteotomy to help treat progressive joint limitation Surgical realignment Retinal Detachment repair Myringotomy (surgical procedure to relieve pressure by draining fluid from the eardrum) Non-surgical Routine monitoring Oxygen support, CPAP, Bipap, Mechanical Ventilation Physical therapy BracingLike treatment options, the prognosis is dependent on the severity of the symptoms. Despite the various symptoms and limitations, most individuals have normal intelligence and can lead a normal life. Recent research A recent article in 2015 reported a persistent notochord in a fetus at 23 weeks of gestation. The fetus had an abnormal spine, shortened long bones and a left clubfoot. After running postmortem tests and ultrasound, the researchers believed that the fetus suffered from hypochondrogenesis. Hypochondrogenesis is caused when type II collagen is abnormally formed due to a mutation in the COL2A1 gene. Normally, the cartilaginous notochord develops into the bony vertebrae in a human body. The COL2A1 gene results in malformed type II collagen, which is essential in the transition from collagen to bone. This is the first time that researchers found a persistent notochord in a human body due to a COL2A1 mutation. Eponym It is named for Wilhelm Kniest. == References ==
Low-set ears	Low-set ears are a clinical feature in which the ears are positioned lower on the head than usual. They are present in many congenital conditions. Low-set ears are defined as outer ears positioned two or more standard deviations lower than the population average. Clinically, if the point at which the helix of the outer ear meets the cranium is at or below the line connecting the inner canthi of eyes(bicanthal plane), the ears are considered low set.Low-set ears can be associated with conditions such as: Down syndrome Turner syndrome Noonan syndrome Patau syndrome DiGeorge syndrome Cri du chat syndrome Edwards syndrome Fragile X syndrome Okamoto syndromeIt is usually bilateral, but it can be unilateral in Goldenhar syndrome. See also LEOPARD syndrome References == External links ==
Pulpitis	Pulpitis is inflammation of dental pulp tissue. The pulp contains the blood vessels, the nerves, and connective tissue inside a tooth and provides the tooth’s blood and nutrients. Pulpitis is mainly caused by bacterial infection which itself is a secondary development of caries (tooth decay). It manifests itself in the form of a toothache. Signs and symptoms Increased sensitivity to stimuli, specifically hot and cold, is a common symptom of pulpitis. A prolonged throbbing pain may be associated with the disease. However, pulpitis can also occur without any pain.Reversible pulpitis is characterised by intermittent, brief discomfort initiated by a hot, cold or sweet stimulus. The pain evoked is of short duration and there is no lingering or spontaneous pain. The pain ceases within a short period after removal of the stimulus. With a reversible pulpitis, sleep is usually not affected and no analgesics are necessary. Usually, no atypical change is evident on the radiograph. Pulp vitality tests are positive and it is possible to preserve a healthy vital pulp. Irreversible pulpitis, in contrast, is characterised by a constant severe pain that arises without provocation. Characteristics may include sharp pain upon thermal stimulus, lingering thermal pain, spontaneity, and referred pain. Sometimes, the pain may be accentuated by postural changes such as lying down or bending over. If a stimulus is applied, the pain persists for minutes or hours after removal of the stimulus. These indicate that the vital inflamed pulp is not capable of healing and it is often indicated for the pulp to be removed as it is too damaged. Sleep may be disturbed and over-the-counter painkillers are often taken in an attempt to provide relief, but are usually ineffective. Causes Pulpitis may be caused by bacteria from dental caries that penetrate through the enamel and dentin to reach the pulp, or it may be mechanical, a result of trauma, such as physical damage to the tooth. Inflammation is commonly associated with a bacterial infection but can also be due to other insults such as repetitive trauma or in rare cases periodontitis. The inflammation of dental pulp is mainly caused by an opportunistic infection of the pulp by a commensal oral microorganism. To reach the pulp, the most common route of the microorganism is through dental caries as well as from trauma, dentinal cracks and exposed dentin. Exposed dentin gives the microorganisms access to the pulp of the tooth through the dentinal tubules. In the case of penetrating decay, the pulp chamber is no longer sealed off from the environment of the oral cavity.When the pulp becomes inflamed, pressure begins to build up in the pulp cavity, exerting pressure on the nerve of the tooth and the surrounding tissues. Pressure from inflammation can cause mild to extreme pain, depending upon the severity of the inflammation and the bodys response. Unlike other parts of the body where pressure can dissipate through the surrounding soft tissues, the pulp cavity is very different. It is surrounded by dentin, a hard tissue that does not allow for pressure dissipation, so increased blood flow, a hallmark of inflammation, will cause pain.The infection can also come from the apical foramen of the root. Cells in the dental pulp trigger an immune response from the invasion of foreign microorganisms. The inflammation of the pulp is a side effect of the immune response and causes pain.Pulpitis can often create so much pressure on the tooth nerve that the individual will have trouble locating the source of the pain, confusing it with neighboring teeth, called referred pain. The pulp cavity inherently provides the body with an immune system response challenge, which makes it very difficult for a bacterial infection to be eliminated.If the teeth are denervated, this can lead to irreversible pulpitis, depending on the area, rate of infection, and length of injury. This is why people who have lost their dental innervation have a reduced healing ability and increased rate of tooth injury. Thus, as people age, their gradual loss of innervation leads to pulpitis. Responses Inflammatory response In the pulp, just as in other areas of the body, inflammation can be present. Inflammation of the pulp does not take place until the bacteria in the decay have reached the pulp. Bacterial products may reach the pulp much earlier and begin the inflammatory response. The inflammation may be acute or chronic because just like other tissues in the body, the pulp will react to irritants with innate and/or adaptive immune responses.Innate immunity in the pulp is not specific but uses receptors to recognize molecular patterns common to microbes to initiate bacterial killing (phagocytosis). The components of the innate response of the dentin/pulp complex to caries include at least the following six: (1) outward flow of dentinal fluid; (2) odontoblasts; (3) neuropeptides and neurogenic inflammation; (4) innate immune cells, including immature dendritic cells (DCs), natural killer (NK) cells, and T cells, as well as (5) their cytokines and (6) chemokines. Although the first two items are not classic components of innate immunity, they are uniquely involved in the initial inflammatory response to caries.Odontoblasts, (the cells that form dentin) have cellular processes that extend into dentinal tubules and are the first to encounter the caries bacterial antigens. They express low levels of interleukin 8 (IL-8) and genes related to chemokines and chemokine receptors. The odontoblasts have been shown to attract immature dendritic cells.Dendritic cells (DCs) are a heterogeneous leukocyte (white blood cell) population. DCs in healthy peripheral tissues (steady state) are in an immature state. The cells are capable of sensing microbes as well as antigen capture and processing capabilities. A rapid accumulation of pulpal DCs has been observed beneath cavity preparations, and an increased number of DCs accumulated under caries. Immature DCs are therefore considered to be part of the innate phase of pulpal immune response.Persistent infection leads to the activation of adaptive immunity. A transition to an adaptive immune response will take place in the dental pulp as the caries and bacteria approach the pulp. Antigens are recognized individually and lines of lymphocytes are developed to produce specific antibodies which attach to the recognized cells and initiate their destruction. Phagocytes remove the remains. B cells and T cells are the major lymphocytes involved.A variety of cytokines have been observed in the pulp. Patients with symptomatic and asymptomatic irreversible pulpitis have been shown to have an almost 23-fold increase in the cytokine IL-8 in the pulp. Cytokines in the pulp interact with each other. The ultimate effect on pulpal inflammation and healing is dependent upon the integrated actions of these inflammatory mediators.In addition to the lymphocytes, macrophages also provide defense against certain intracellular pathogens. Activated macrophages can function as class II antigen-presenting cells, similar to pulpal dendritic and B cells. In addition, activated macrophages secrete many inflammatory mediators.Macrophages in the pulp become activated after receiving two signals. The first is a priming stimulus and the second is an activating signal. The priming stimulus is secreted by activated T-helper cells. The activating stimulus may include bacterial lipopolysaccharides, muramyl dipeptide, and other chemical mediators.Macrophages are professional phagocytes in innate immune responses. Activated macrophages are effective killers that eliminate pathogens in both innate and adaptive immune responses, and are also important in tissue homeostasis, through the clearance of senescent cells, and in remodeling and repair of tissue after inflammation. The number of macrophages increases with the progression of caries and is always higher than that of DCs at all stages of the caries invasion. Neurological responses According to the Brännströms hydrodynamic theory, activated nociceptors from fluid movement and other irritants through the patent dentine tubules result in pulp pain. Unmyelinated, slow conducting C-fibers aid in feeling a slowset, burning pain. According to neuronal studies, 70-80% of pulpal axons are unmyelinated. Highly myelinated Aδ-fibers, which allow for fast conduction, are responsible for the sharp, shooting pain.Thus, the stimulus intensities are based on various fibers. Fast-conducting Aβ and Aδ-fibers provide the lowest stimulus intensities (typically referred to as prepain sensations), and those sensations eventually receive higher stimulation levels. The dull aches are associated with C-fibers and slow Aδ-fibers. As inflammation intensifies, the A-fibers are increasingly activated. C-fiber innervation and Aδ-fibers are polymodal receptors that are sensitive to capsaicin and inflammatory mediators.The pain mechanisms associated with pulpitis are similar to those of the rest of the body (i.e. receptors, intracellular signaling, transmitters, etc.). The inflammatory mediators act on specific receptors relating to nociceptive neurons, leading to the production of second messengers and activation of phospholipases and protein kinases. The second messengers regulate receptors ion channels that deal with sensitization. The ion channels open based on pain stimuli propagating action potentials in sensory neurons.In order for excitability and conduction to occur, voltage-gated sodium channels must be activated. Changes in sodium channel (NaCH) expression occur after inflammatory lesions, which may generate different pain states seen when neuronal fibers are activated. Studies have been done on major NaCh isoforms to examine expression patterns. Nav1.6 nodal accumulations do not vary in size or immunofluorescence staining activity in typical or atypical nodal sites; however, the proportion of typical nodal sites decreases and increase in atypical nodes in painful tooth samples compared to normal tooth samples. Nav1.7 has an increased expression in typical and atypical nodal sites in painful samples. As a result, an increased co-expression of multiple isoforms at demyelinating nodal sites in painful dental pulp. This isoforms of sodium channels may be a main factor in pain sensations due to their production of axonal excitability properties.Neuropeptides are increasingly being researched for having a role in molecular mechanisms involved with pain, including ion channels and inflammation. Substance P (SP) is a neuropeptide produced by capsaicin neuron cell bodies (localized in trigeminal ganglia and dorsal root) and plays a major role in dental pain and inflammation. Other peptides include cGRP, galanin, somatostatin, and neurokinin A-B. The biological effects of SP are expressed by the binding of specific G protein-coupled NK receptors. Interaction with SP receptors induces vasodilation and allows for plasma extravasation and mastocyte degranulation. SP is highly expressed in dental pulp and dentin. When pain, thermal, and/or chemical stimulation is present, SP production and release increases. Current studies focus on whether controlling Substance P expression may control tooth pain.In addition, dental caries is more likely to develop pulpitis due to less time for the dental pulp to react and protect itself by occluding the dentinal tubules. Based on the tooth injury, sensory nerve fibers react to pulpitis by growing terminal branches into the adjacent surviving pulp, which also changes the cytochemical phenotype. This neural growth typically lasts few a few days and function and form is retained. Thus, pain is poorly localized, and the level of pain stemming from pulpitis varies based on severity, quality, duration, onset, trigger. As caries invades dentin, the number of permeable dentinal tubules correlates with the degree of pain. Intrapulp pressure have an effect on the sensory nerves of varying diameters: blocking larger diameter Aδ-fibres and activating smaller C-fibers. Under hypoxic environments and pulp degeneration (symptom of pulpitis), C-fibers may still function. Once reparative dentin forms, odontoblasts associated with the dentin change, and the pulpal fibroblasts lose p75 expression, which is a neurotrophin receptor. Diagnosis Pulp sensibility tests are routinely used in the diagnosis of pulpitis. Pulp testing is combined with information taken from history, examination and other special investigations such as radiographs in order to reach a diagnosis. Pulp sensibility tests assess the pulp’s sensory response to a stimulus. There are 3 general types: Thermal: Agents are applied to increase or decrease the temperature of a tooth and stimulate a pulp sensory response.Cold tests: Most commonly, ethyl chloride is sprayed onto a small ball of cotton wool and is applied to the tooth, which produces intense cold. Alternatively, CO2 snow and other refrigerants such as dichlorodifluoromethane (DDM) have been shown to be effective. Heat tests: Gutta percha can be heated and directly applied to the tooth to produce heat. Electrical pulp test: Electric pulp testing (EPT) has been available for over a century and is used by dentists worldwide. It is used to determine the health of the pulp and pulp-related pain.EPT is based on the stimulation of sensory nerves in the pulp. It does not provide information on vascular supply to the pulp. The probe tip of the test device is placed directly onto the tooth surface and an electrical stimulus is produced. This stimulus causes an ionic change across the neural membrane, inducing an action potential in the myelinated nerves. The threshold of pain is determined by increasing the voltage. A tingling sensation is felt once the voltage reaches the pain threshold. This threshold level varies between patients, and is affected by factors such as age, pain perception, tooth surface conduction and resistance. The requirements of an EPT are appropriate application method, careful interpretation of the results, and an appropriate stimulus. EPT must be done with tooth isolation and conduction media. Key factors in pulp testing are the enamel and dentine thickness, and the number of nerve fibers in the underlying the pulp. EPT is not used in patients with orthodontic bands or crowned teeth, as the current may be conducted to adjacent teeth, resulting in false-positive responses. Pulp nerve fibers also respond to lower current intensities and only a small number of pulpal nerves are required to create responses when electrical stimulation is applied. This means that EPT may result in false-positive responses in teeth with pulpal necrosis. Furthermore, as pulpal and periodontal nerve thresholds overlap, the periodontal nerves may give a false indication of tooth sensibility.Possible explanations for false-positives include: Response caused by conduction of the current because of periodontal or gingival issues Breakdown products associated with pulp necrosis may be able to conduct electric current next to infected and hypersensitive pulp tissue Inflamed pulp tissue may still be present Metallic restorations or orthodontic gear are still presentStudies have indicated that there is little correlation between histopathological status of the pulp and clinical information. A negative EPT response showed localized necrosis in 25.7% of cases and 72% of cases. Thus, 97.7% of cases with a negative response to EPT indicated that a root canal treatment should be carried out. Test cavity: The preparation of a test cavity involves cutting into the dentine of a tooth to determine whether the sensory element of the pulp is still functioning. Test cavity preparation is a last resort as this method is considered invasive and irreversible. It is also unlikely that this procedure would provide any more information than thermal and electric pulp sensibility tests. Therefore, test cavities are not generally used in practice as a means of testing pulp sensibility. Treatment Once the pulp has become inflamed, the tooth can be diagnostically divided into two categories: reversible pulpitis and irreversible pulpitis Reversible This is the condition where the pulp is inflamed and is actively responding to an irritant. This may include a carious lesion that has not reached the pulp. Symptoms include transient pain or sensitivity resulting from many stimuli, notably hot, cold, sweet, water and touch. The pulp is still considered to be vital. This means that once the irritant is eliminated, usually by removal of decay and the placement of a restoration, that the pulp will return to its normal, healthy state. When it becomes painful and decayed the tooth may become known as a "hot tooth" and local anesthetic may not work as well. Irreversible This is the condition where the pulp is irreversibly damaged. The pulp cannot recover from the insult and damage. For example, decay that has reached the pulp of the tooth introduces bacteria into the pulp. The pulp is still alive, but the introduction of bacteria into the pulp will not allow the pulp to heal and it will ultimately result in necrosis, or death, of the pulp tissue.Symptoms associated with irreversible pulpitis may include dull aching, pain from hot or cold (though cold may actually provide relief) lingering pain after removal of a stimulus, spontaneous pain, or referred pain.Clinical signs may include reduced response to electronic pulp testing and painful response to thermal stimuli. Today electronic pulp testers are rarely used for diagnosis of the reversibility of pulpitis due to their unreliable nature. Instead they should only be used to test the vitality of teeth. The pulp of a tooth with irreversible pulpitis may not be left alone to heal. That is at least the general viewpoint of the dental profession, and not every dentist would agree that a dead tooth must be treated. No statistics are known but it is possible to have a trouble-free tooth after irreversible pulpitis, albeit a dead tooth. The tooth may be endodontically treated whereby the pulp is removed and replaced by gutta percha. An alternative is extraction of the tooth. This may be required if there is insufficient coronal tissue remaining for restoration once the root canal therapy has been completed. References == External links ==
Greater trochanteric pain syndrome	Greater trochanteric pain syndrome (GTPS), a form of bursitis, is inflammation of the trochanteric bursa, a part of the hip. This bursa is at the top, outer side of the femur, between the insertion of the gluteus medius and gluteus minimus muscles into the greater trochanter of the femur and the femoral shaft. It has the function, in common with other bursae, of working as a shock absorber and as a lubricant for the movement of the muscles adjacent to it.Occasionally, this bursa can become inflamed and clinically painful and tender. This condition can be a manifestation of an injury (often resulting from a twisting motion or from overuse), but sometimes arises for no obviously definable cause. The symptoms are pain in the hip region on walking, and tenderness over the upper part of the femur, which may result in the inability to lie in comfort on the affected side.More often the lateral hip pain is caused by disease of the gluteal tendons that secondarily inflames the bursa. This is most common in middle-aged women and is associated with a chronic and debilitating pain which does not respond to conservative treatment. Other causes of trochanteric bursitis include uneven leg length, iliotibial band syndrome, and weakness of the hip abductor muscles.Greater trochanteric pain syndrome can remain incorrectly diagnosed for years, because it shares the same pattern of pain with many other musculoskeletal conditions. Thus people with this condition may be labeled malingerers, or may undergo many ineffective treatments due to misdiagnosis. It may also coexist with low back pain, arthritis, and obesity. Signs and symptoms The primary symptom is hip pain, especially hip pain on the outer (lateral) side of the joint. This pain may appear when the affected person is walking or lying down on that side. Diagnosis A doctor may begin the diagnosis by asking the patient to stand on one leg and then the other, while observing the effect on the position of the hips. Palpating the hip and leg may reveal the location of the pain, and range-of-motion tests can help to identify its source.X-rays, ultrasound and magnetic resonance imaging may reveal tears or swelling. But often these imaging tests do not reveal any obvious abnormality in patients with documented GTPS. Prevention Because wear on the hip joint traces to the structures that support it (the posture of the legs, and ultimately, the feet), proper fitting shoes with adequate support are important to preventing GTPS. For someone who has flat feet, wearing proper orthotic inserts and replacing them as often as recommended are also important preventive measures.Strength in the core and legs is also important to posture, so physical training also helps to prevent GTPS. But it is equally important to avoid exercises that damage the hip. Treatment Conservative treatments have a 90% success rate and can include any or a combination of the following: pain relief medication, NSAIDs, physiotherapy, shockwave therapy (SWT) and corticosteroid injection. Surgery is usually for cases that are non-respondent to conservative treatments and is often a combination of bursectomy, iliotibial band (ITB) release, trochanteric reduction osteotomy or gluteal tendon repair. A 2011 review found that traditional nonoperative treatment helped most patients, low-energy SWT was a good alternative, and surgery was effective in refractory cases and superior to corticosteroid therapy and physical therapy. There are numerous case reports in which surgery has relieved GTPS, but its effectiveness is not documented in clinical trials as of 2009.The primary treatment is rest. This does not mean bed rest or immobilizing the area but avoiding actions which result in aggravation of the pain. Icing the joint may help. A non-steroidal anti-inflammatory drug may relieve pain and reduce the inflammation. If these are ineffective, the definitive treatment is steroid injection into the inflamed area. Physical therapy to strengthen the hip muscles and stretch the iliotibial band can relieve tension in the hip and reduce friction. The use of point ultrasound may be helpful, and is undergoing clinical trials.In extreme cases, where the pain does not improve after physical therapy, cortisone shots, and anti-inflammatory medication, the inflamed bursa can be removed surgically. The procedure is known as a bursectomy. Tears in the muscles may also be repaired, and loose material from arthritic degeneration of the hip removed. At the time of bursal surgery, a very close examination of the gluteal tendons will reveal sometimes subtle and sometimes very obvious degeneration and detachment of the gluteal tendons. If this detachment is not repaired, removal of the bursa alone will make little or no difference to the symptoms.The bursa is not required, so the main potential complication is potential reaction to anaesthetic. The surgery can be performed arthroscopically and, consequently, on an outpatient basis. Patients often have to use crutches for a few days following surgery up to a few weeks for more involved procedures. See also Snapping hip syndrome References == External links ==
Mallory–Weiss syndrome	Mallory–Weiss syndrome or gastro-esophageal laceration syndrome refers to bleeding from a laceration in the mucosa at the junction of the stomach and esophagus. This is usually caused by severe vomiting because of alcoholism or bulimia, but can be caused by any condition which causes violent vomiting and retching such as food poisoning. The syndrome presents with hematemesis. The laceration is sometimes referred to as a Mallory–Weiss tear. Signs and symptoms Mallory–Weiss Syndrome often presents as an episode of vomiting up blood (hematemesis) after violent retching or vomiting, but may also be noticed as old blood in the stool (melena), and a history of retching may be absent. In most cases, the bleeding stops spontaneously after 24–48 hours, but endoscopic or surgical treatment is sometimes required. The condition is rarely fatal. Causes It is often associated with alcoholism and eating disorders and there is some evidence that presence of a hiatal hernia is a predisposing condition. Forceful vomiting causes tearing of the mucosa at the junction. NSAID abuse is also a rare association. In rare instances some chronic disorders like Ménières disease that cause long term nausea and vomiting could be a factor. The tear involves the mucosa and submucosa but not the muscular layer (contrast to Boerhaave syndrome which involves all the layers). Most patients are between the ages of 30 and 50 years, although it has been reported in infants aged as young as 3 weeks, as well as in older people Hyperemesis gravidarum, which is severe morning sickness associated with vomiting and retching in pregnancy, is also a known cause of Mallory–Weiss tear. Diagnosis Definitive diagnosis is by endoscopy. Proper history taking by the medical doctor to distinguish other conditions that cause haematemesis but definitive diagnosis is by conducting esophagogastroduodenoscopy. Treatment Treatment is usually supportive as persistent bleeding is uncommon. However cauterization or injection of epinephrine to stop the bleeding may be undertaken during the index endoscopy procedure. Very rarely embolization of the arteries supplying the region may be required to stop the bleeding. If all other methods fail, high gastrostomy can be used to ligate the bleeding vessel. A Blakemore tube will not be able to stop bleeding as here the bleeding is arterial and the pressure in the balloon is not sufficient to overcome the arterial pressure. History The condition was first described in 1929 by G. Kenneth Mallory and Soma Weiss in 15 alcoholic patients. See also Boerhaave syndrome – Full thickness esophageal ruptures are also often secondary to vomiting/retching. Hematemesis References == External links ==
Malignant histiocytosis	Malignant histiocytosis is a rare hereditary disease found in the Bernese Mountain Dog and humans, characterized by histiocytic infiltration of the lungs and lymph nodes. The liver, spleen, and central nervous system can also be affected. Histiocytes are a component of the immune system that proliferate abnormally in this disease. In addition to its importance in veterinary medicine, the condition is also important in human pathology. Histiocytic disorders A histiocyte is a differentiated tissue cell that has its origin in the bone marrow. The source for histiocytes is the monocyte/macrophage line. Monocytes (found in the blood) and macrophages (found in tissue) are responsible for phagocytosis (ingestion) of foreign material in the body. Langerhans cells are dendritic cells found in the skin and function by internalizing antigens (foreign particles) and presenting them to T cells. They arise from monocytes. Histiocytic disorders refer to diseases that are caused by abnormal behavior of these cells. They include the following: Reactive diseases of Langerhans cells (most important feature in immune histochemistry is expression of E-cadherin) Histiocytomas Reactive histiocytosis (immunohistochemical features show that interstitial/dermal DCs are involved) Cutaneous histiocytosis (CH) Systemic histiocytosis (SH) Reactive diseases of macrophages Hemophagocytic syndrome – a condition where macrophages phagocytose myeloid and erythroid precursors (similar to hemophagocytic lymphohistiocytosis in humans) Histiocytic sarcoma complex (immunohistochemical features of dendritic cells, possibly interdigitating or perivascular DCs) Malignant histiocytosis Diffuse histiocytic sarcoma Localized histiocytic sarcoma Malignant diseases of macrophages Histiocytic lymphoma Breed disposition Up to 25 percent of Bernese Mountain Dogs may develop malignant histiocytosis in their lifetime. Other breeds with a possible genetic tendency toward malignant histiocytosis include Rottweilers, Flat-Coated Retrievers, and Golden Retrievers. Signs and symptoms The disease in the lungs is characterized by enlargement of the tracheobronchial lymph nodes and infiltration of the lungs, sometimes leading to lung lobe consolidation and pleural effusion. Signs and symptoms include cough, loss of appetite, weight loss, anemia, and difficulty breathing. Seizures and rear limb weakness can be seen. Invasion of the bone marrow can cause pancytopenia. Diagnosis requires a biopsy. Treatment Treatment with chemotherapy has been used with some success, particularly using lomustine, prednisone, doxorubicin, and cyclophosphamide. Because of the rapid progression of this aggressive disease, the prognosis is very poor. Other histiocytic diseases in Bernese Mountain Dogs A similar disease is diffuse histiocytic sarcoma, a term used to designate a localized histiocytic sarcoma that has spread throughout the body. Other signs and symptoms include weight loss and loss of appetite. See also Histiocytosis References == External links ==
Chorionic hematoma	Chorionic hematoma is the pooling of blood (hematoma) between the chorion, a membrane surrounding the embryo, and the uterine wall. It occurs in about 3.1% of all pregnancies, it is the most common sonographic abnormality and the most common cause of first trimester bleeding. Cause and diagnosis Chorionic hematomas can be caused by the separation of the chorion from the endometrium (inner membrane of the uterus). Hematomas are classified by their location between tissue layers: Subchorionic hematomas, the most common type, are between the chorion and endometrium. Retroplacental hematomas are entirely behind the placenta and not touching the gestational sac. Subamniotic or preplacental hematomas are contained within amnion and chorion. Rare.Most patients with a small subchorionic hematoma are asymptomatic. Symptoms include vaginal bleeding, abdominal pain, premature labor and threatened miscarriage.Ultrasonography is the preferred method of diagnosis. A chorionic hematoma appears on ultrasound as a hypoechoic crescent adjacent to the gestational sac. The hematoma is considered small if it is under 20% of the size of the sac and large if it is over 50%. Prognosis and treatment The presence of subchorionic bleeding around the gestational sac does not have a significant association with miscarriage overall. However, the case of intrauterine hematoma observed before 9 weeks of gestational age has been associated with an increased risk of miscarriage. In one study women who complied with instructions for bed rest for the duration of bleeding had a lower rate of miscarriage and a higher rate of term pregnancy than non-compliant women. The study had several limitations; results were severely confounded by inherent differences between compliant and non-compliant women. == References ==
Rumination syndrome	Rumination syndrome, or merycism, is a chronic motility disorder characterized by effortless regurgitation of most meals following consumption, due to the involuntary contraction of the muscles around the abdomen. There is no retching, nausea, heartburn, odour, or abdominal pain associated with the regurgitation, as there is with typical vomiting, and the regurgitated food is undigested. The disorder has been historically documented as affecting only infants, young children, and people with cognitive disabilities (the prevalence is as high as 10% in institutionalized patients with various mental disabilities). It is increasingly being diagnosed in a greater number of otherwise healthy adolescents and adults, though there is a lack of awareness of the condition by doctors, patients and the general public. Rumination syndrome presents itself in a variety of ways, with especially high contrast existing between the presentation of the typical adult patient without a mental disability and the presentation of an adult with a mental disability. Like related gastrointestinal disorders, rumination can adversely affect normal functioning and the social lives of individuals. It has been linked with depression. Little comprehensive data regarding rumination syndrome in otherwise healthy individuals exists because most people are private about their illness and are often misdiagnosed due to the number of symptoms and the clinical similarities between rumination syndrome and other disorders of the stomach and esophagus, such as gastroparesis and bulimia nervosa. These symptoms include the acid-induced erosion of the esophagus and enamel, halitosis, malnutrition, severe weight loss and an unquenchable appetite. Individuals may begin regurgitating within a minute following ingestion, and the full cycle of ingestion and regurgitation can mimic the binging and purging of bulimia. Diagnosis of rumination syndrome is non-invasive and based on a history of the individual. Treatment is promising, with upwards of 85% of individuals responding positively to treatment, including infants and mentally disabled people. Signs and symptoms While the number and severity of symptoms vary among individuals, repetitive regurgitation of undigested food (known as rumination) after the start of a meal is always present. In some individuals, the regurgitation is small, occurring over a long period of time following ingestion, and can be rechewed and swallowed. In others, the amount can be bilious and short-lasting, and must be expelled. While some only experience symptoms following some meals, most experience episodes following any ingestion, from a single bite to a large meal. However, some long-term patients will find a select couple of food or drink items that do not trigger a response. Unlike typical vomiting, regurgitation is typically described as effortless and unforced. There is seldom nausea preceding the expulsion, and the undigested food lacks the bitter taste and odour of stomach acid and bile.Symptoms can begin to manifest at any point from the ingestion of the meal to 120 minutes thereafter. However, the more common range is between 30 seconds to 1 hour after the completion of a meal. Symptoms tend to cease when the ruminated contents become acidic.Abdominal pain (38.1%), lack of fecal production or constipation (21.1%), nausea (17.0%), diarrhea (8.2%), bloating (4.1%), and dental decay (3.4%) are also described as common symptoms in day-to-day life. These symptoms are not necessarily prevalent during regurgitation episodes, and can happen at any time. Weight loss is often observed (42.2%) at an average loss of 9.6 kilograms, and is more common in cases where the disorder has gone undiagnosed for a longer period of time, though this may be expected of the nutrition deficiencies that often accompany the disorder as a consequence of its symptoms. Depression has also been linked with rumination syndrome, though its effects on rumination syndrome are unknown.Acid erosion of the teeth can be a feature of rumination, as can halitosis (bad breath). Causes The cause of rumination syndrome is unknown. However, studies have drawn a correlation between hypothesized causes and the history of patients with the disorder. In infants and the cognitively impaired, the disease has normally been attributed to overstimulation and under-stimulation from parents and caregivers, causing the individual to seek self-gratification and self-stimulus due to the lack or abundance of external stimuli. The disorder has also commonly been attributed to a bout of illness, a period of stress in the individuals recent past, and to changes in medication.In adults and adolescents, hypothesized causes generally fall into one of either category: habit-induced, and trauma-induced. Habit-induced individuals generally have a history of bulimia nervosa or of intentional regurgitation (magicians and professional regurgitators, for example), which though initially self-induced, forms a subconscious habit that can continue to manifest itself outside the control of the affected individual. Trauma-induced individuals describe an emotional or physical injury (such as recent surgery, psychological distress, concussions, deaths in the family, etc.), which preceded the onset of rumination, often by several months. Pathophysiology Rumination syndrome is a poorly understood disorder, and a number of theories have speculated the mechanisms that cause the regurgitation, which is a unique symptom to this disorder. While no theory has gained a consensus, some are more notable and widely published than others.The most widely documented mechanism is that the ingestion of food causes gastric distention, which is followed by abdominal compression and the simultaneous relaxation of the lower esophageal sphincter (LES). This creates a common cavity between the stomach and the oropharynx that allows the partially digested material to return to the mouth. There are several offered explanations for the sudden relaxation of the LES. Among these explanations is that it is a learned voluntary relaxation, which is common in those with or having had bulimia. While this relaxation may be voluntary, the overall process of rumination is still generally involuntary. Relaxation due to intra-abdominal pressure is another proposed explanation, which would make abdominal compression the primary mechanism. The third is an adaptation of the belch reflex, which is the most commonly described mechanism. The swallowing of air immediately prior to regurgitation causes the activation of the belching reflex that triggers the relaxation of the LES. Patients often describe a feeling similar to the onset of a belch preceding rumination. Diagnosis Rumination syndrome is diagnosed based on a complete history of the individual. Costly and invasive studies such as gastroduodenal manometry and esophageal pH testing are unnecessary and will often aid in misdiagnosis. Based on typical observed features, several criteria have been suggested for diagnosing rumination syndrome. The primary symptom, the regurgitation of recently ingested food, must be consistent, occurring for at least six weeks of the past twelve months. The regurgitation must begin within 30 minutes of the completion of a meal. Patients may either chew the regurgitated matter or expel it. The symptoms must stop within 90 minutes, or when the regurgitated matter becomes acidic. The symptoms must not be the result of a mechanical obstruction, and should not respond to the standard treatment for gastroesophageal reflux disease.In adults, the diagnosis is supported by the absence of classical or structural diseases of the gastrointestinal system. Supportive criteria include a regurgitant that does not taste sour or acidic, is generally odourless, is effortless, or at most preceded by a belching sensation, that there is no retching preceding the regurgitation, and that the act is not associated with nausea or heartburn.Patients visit an average of five physicians over 2.75 years before being correctly diagnosed with rumination syndrome. Differential diagnosis Rumination syndrome in adults is a complicated disorder whose symptoms can mimic those of several other gastroesophageal disorders and diseases. Bulimia nervosa and gastroparesis are especially prevalent among the misdiagnoses of rumination.Bulimia nervosa, among adults and especially adolescents, is by far the most common misdiagnosis patients will hear during their experiences with rumination syndrome. This is due to the similarities in symptoms to an outside observer—"vomiting" following food intake—which, in long-term patients, may include ingesting copious amounts to offset malnutrition, and a lack of willingness to expose their condition and its symptoms. While it has been suggested that there is a connection between rumination and bulimia, unlike bulimia, rumination is not self-inflicted. Adults and adolescents with rumination syndrome are generally well aware of their gradually increasing malnutrition, but are unable to control the reflex. In contrast, those with bulimia intentionally induce vomiting, and seldom re-swallow food.Gastroparesis is another common misdiagnosis. Like rumination syndrome, patients with gastroparesis often bring up food following the ingestion of a meal. Unlike rumination, gastroparesis causes vomiting (in contrast to regurgitation) of food, which is not being digested further, from the stomach. This vomiting occurs several hours after a meal is ingested, preceded by nausea and retching, and has the bitter or sour taste typical of vomit. Classification Rumination syndrome is a condition which affects the functioning of the stomach and esophagus, also known as a functional gastroduodenal disorder. In patients that have a history of eating disorders, Rumination syndrome is grouped alongside eating disorders such as bulimia and pica, which are themselves grouped under non-psychotic mental disorder. In most healthy adolescents and adults who have no mental disability, Rumination syndrome is considered a motility disorder instead of an eating disorder, because the patients tend to have had no control over its occurrence and have had no history of eating disorders. Treatment and prognosis There is presently no known cure for rumination. Proton pump inhibitors and other medications have been used to little or no effect. Treatment is different for infants and mentally disabled adults than for adults and adolescents of typical intelligence. Among infants and mentally disabled adults, behavioral and mild aversion training has been shown to cause improvement in most cases. Aversion training involves associating the ruminating behavior with negative results, and rewarding good behavior and eating. Placing a sour or bitter taste on the tongue when the individual begins the movements or breathing patterns typical of his or her ruminating behavior is the generally accepted method for aversion training, although some older studies advocate the use of pinching. In patients of normal intelligence, rumination is not an intentional behavior and is habitually reversed using diaphragmatic breathing to counter the urge to regurgitate. Alongside reassurance, explanation and habit reversal, patients are shown how to breathe using their diaphragms prior to and during the normal rumination period. A similar breathing pattern can be used to prevent normal vomiting. Breathing in this method works by physically preventing the abdominal contractions required to expel stomach contents. Supportive therapy and diaphragmatic breathing has shown to cause improvement in 56% of cases, and total cessation of symptoms in an additional 30% in one study of 54 adolescent patients who were followed up 10 months after initial treatments. Patients who successfully use the technique often notice an immediate change in health for the better. Individuals who have had bulimia or who intentionally induced vomiting in the past have a reduced chance for improvement due to the reinforced behavior. The technique is not used with infants or young children due to the complex timing and concentration required for it to be successful. Most infants grow out of the disorder within a year or with aversive training. Epidemiology Rumination disorder was initially documented as affecting newborns, infants, children and individuals with mental and functional disabilities (cognitively disabled). It has since been recognized to occur in both males and females of all ages and cognitive abilities.Among cognitively disabled people, it is described with almost equal prevalence among infants (6–10% of the population) and institutionalized adults (8–10%). In infants, it typically occurs within the first 3–12 months of age.The occurrence of rumination syndrome within the general population has not been defined. Rumination is sometimes described as rare, but has also been described as not rare, but rather rarely recognized. The disorder has a female predominance. The typical age of adolescent onset is 12.9, give or take 0.4 years (±), with males affected sooner than females (11.0 ± 0.8 for males versus 13.8 ± 0.5 for females).There is little evidence concerning the impact of hereditary influence in rumination syndrome. However, case reports involving entire families with rumination exist. History The term rumination is derived from the Latin word ruminare, which means to chew the cud. First described in ancient times, and mentioned in the writings of Aristotle, rumination syndrome was clinically documented in 1618 by Italian anatomist Fabricus ab Aquapendente, who wrote of the symptoms in a patient of his.Among the earliest cases of rumination was that of a physician in the nineteenth century, Charles-Édouard Brown-Séquard, who acquired the condition as the result of experiments upon himself. As a way of evaluating and testing the acid response of the stomach to various foods, the doctor would swallow sponges tied to a string, then intentionally regurgitate them to analyze the contents. As a result of these experiments, the doctor eventually regurgitated his meals habitually by reflex.Numerous case reports exist from before the twentieth century, but were influenced greatly by the methods and thinking used in that time. By the early twentieth century, it was becoming increasingly evident that rumination presented itself in a variety of ways in response to a variety of conditions. Although still considered a disorder of infancy and cognitive disability at that time, the difference in presentation between infants and adults was well established.Studies of rumination in otherwise healthy adults became decreasingly rare starting in the 1900s, and the majority of published reports analyzing the syndrome in mentally healthy patients appeared thereafter. At first, adult rumination was described and treated as a benign condition. It is now described as otherwise. While the base of patients to examine has gradually increased as more and more people come forward with their symptoms, awareness of the condition by the medical community and the general public is still limited. In other animals The chewing of cud by animals such as cows, goats, and giraffes is considered normal behavior. These animals are known as ruminants. Such behavior, though termed rumination, is not related to human rumination syndrome, but is ordinary. Involuntary rumination, similar to what is seen in humans, has been described in gorillas and other primates. Macropods such as kangaroos also regurgitate, re-masticate, and re-swallow food, but these behaviors are not essential to their normal digestive process, are not observed as predictably as the ruminants, and hence were termed "merycism" in contrast with "true rumination". See also Professional regurgitator References External links Pediatrics - Rumination Syndrome - The Mayo Clinic. Website provides an overview of the effect of the disorder on children. Rumination disorder - Web MD. Provides a general overview of the disease.
Glioma	A glioma is a type of tumor that starts in the glial cells of the brain or the spine. Gliomas comprise about 30 percent of all brain tumors and central nervous system tumours, and 80 percent of all malignant brain tumours. Signs and symptoms Symptoms of gliomas depend on which part of the central nervous system is affected. A brain glioma can cause headaches, vomiting, seizures, and cranial nerve disorders as a result of increased intracranial pressure. A glioma of the optic nerve can cause visual loss. Spinal cord gliomas can cause pain, weakness, or numbness in the extremities. Gliomas do not usually metastasize by the bloodstream, but they can spread via the cerebrospinal fluid and cause "drop metastases" to the spinal cord. Complex visual hallucinations have been described as a symptom of low-grade glioma.A child who has a subacute disorder of the central nervous system that produces cranial nerve abnormalities (especially of cranial nerve VII and the lower bulbar nerves), long-tract signs, unsteady gait secondary to spasticity, and some behavioral changes is most likely to have a pontine glioma. Causes Hereditary disorders The exact causes of gliomas are not known. Hereditary disorders such as neurofibromatoses (type 1 and type 2) and tuberous sclerosis complex are known to predispose to their development. Different oncogenes can cooperate in the development of gliomas. Diet Some studies of diet and vitamin supplementation appear to point out that dietary N-nitroso compounds may affect the risk of both childhood and adult brain tumors. Researchers have observed in some studies that brain tumor patients (or their mothers) have generally consumed more cured foods (also known as Curing) than control groups. Recently, Drs. Lee, Wrensch and others found that adults with glioma were more likely to consume diets high in cured foods and low in vitamin C-rich fruits and vegetables, and to consume diets high in nitrites and low in vitamin C. The effect was more pronounced in men than women. However, the pattern of increased risk with increased consumption of cured foods, and decreased risk with greater consumption of fruits, vegetables, and antioxidant vitamins is compatible with other cancer studies that show increased consumption of vegetables and possibly of fruits is associated with decreased cancer risk. Radiation A link between gliomas and electromagnetic radiation from cell phones has not been conclusively proven. It was considered possible, though several large studies have found no conclusive evidence, as summarized by the NIHs National Cancer Institute review of the topic and its numerous citations, and the FCC. However, further research is still being pursued to obtain more robust evidence and verify that there is no relationship (the NIHs National Institute of Environmental Health Sciences most recent press release discussed an ongoing study showing mildly positive results, although it appears there may have been issues with the control group dying prematurely). Infection with cytomegalovirus Some studies have reported that glioblastomas are infected with cytomegalovirus, with suggestions that this may speed the development of tumors. However, this is a controversial opinion, with recent in-depth studies failing to find an association between viral infection and glioma growth. There is also evidence that previous studies may have been impacted by false-positive antibody staining artifacts. Other causes Though some studies have shown that farmers have higher rates of gliomas compared to the general population, exposure to farm animals or manure is not associated with glioma. Later studies have not found an association between farming and gliomas; similar conflicting data concerns teachers and glioma. More consistent data show that architects, surveyors, retail workers, butchers, and engineers have higher rates of gliomas. Most studies have found that pesticide exposure is probably not a cause of glioma, though a minority of studies have found an association. Inherited polymorphisms of the DNA repair genes Germ-line (inherited) polymorphisms of the DNA repair genes ERCC1, ERCC2 (XPD) and XRCC1 increase the risk of glioma. This indicates that altered or deficient repair of DNA damage contributes to the formation of gliomas. DNA damages are a likely major primary cause of progression to cancer in general. Excess DNA damages can give rise to mutations through translesion synthesis. Furthermore, incomplete DNA repair can give rise to epigenetic alterations or epimutations. Such mutations and epimutations may provide a cell with a proliferative advantage which can then, by a process of natural selection, lead to progression to cancer.Epigenetic repression of DNA repair genes is often found in progression to sporadic glioblastoma. For instance, methylation of the DNA repair gene MGMT promoter was observed in 51% to 66% of glioblastoma specimens. In addition, in some glioblastomas, the MGMT protein is deficient due to another type of epigenetic alteration. MGMT protein expression may also be reduced due to increased levels of a microRNA that inhibits the ability of the MGMT messenger RNA to produce the MGMT protein. Zhang et al. found, in the glioblastomas without methylated MGMT promoters, that the level of microRNA miR-181d is inversely correlated with protein expression of MGMT and that the direct target of miR-181d is the MGMT mRNA 3UTR (the three prime untranslated region of MGMT messenger RNA).Epigenetic reductions in expression of another DNA repair protein, ERCC1, were found in an assortment of 32 gliomas. For 17 of the 32 (53%) of the gliomas tested, ERCC1 protein expression was reduced or absent. In the case of 12 gliomas (37.5%) this reduction was due to methylation of the ERCC1 promoter. For the other 5 gliomas with reduced ERCC1 protein expression, the reduction could have been due to epigenetic alterations in microRNAs that affect ERCC1 expression.When expression of DNA repair genes is reduced, DNA damages accumulate in cells at a higher than normal level, and such excess damages cause increased frequencies of mutation. Mutations in gliomas frequently occur in either isocitrate dehydrogenase (IDH) 1 or 2 genes. One of these mutations (mostly in IDH1) occurs in about 80% of low grade gliomas and secondary high-grade gliomas. Wang et al. pointed out that IDH1 and IDH2 mutant cells produce an excess metabolic intermediate, 2-hydroxyglutarate, which binds to catalytic sites in key enzymes that are important in altering histone and DNA promoter methylation. Thus, mutations in IDH1 and IDH2 generate a "DNA CpG island methylator phenotype or CIMP" that causes promoter hypermethylation and concomitant silencing of tumor suppressor genes such as DNA repair genes MGMT and ERCC1. On the other hand, Cohen et al. and Molenaar et al. pointed out that mutations in IDH1 or IDH2 can cause increased oxidative stress. Increased oxidative damage to DNA could be mutagenic. This is supported by an increased number of DNA double-strand breaks in IDH1-mutated glioma cells. Thus, IDH1 or IDH2 mutations act as driver mutations in glioma carcinogenesis, though it is not clear by which role they are primarily acting. A study, involving 51 patients with brain gliomas who had two or more biopsies over time, showed that mutation in the IDH1 gene occurred prior to the occurrence of a p53 mutation or a 1p/19q loss of heterozygosity, indicating that an IDH1 mutation is an early driver mutation. Pathophysiology High-grade gliomas are highly vascular tumors and have a tendency to infiltrate diffusely. They have extensive areas of necrosis and hypoxia. Often, tumor growth causes a breakdown of the blood–brain barrier in the vicinity of the tumor. As a rule, high-grade gliomas almost always grow back even after complete surgical excision, so are commonly called recurrent cancer of the brain.Conversely, low-grade gliomas grow slowly, often over many years, and can be followed without treatment unless they grow and cause symptoms.Several acquired (not inherited) genetic mutations have been found in gliomas. Tumor suppressor protein 53 (p53) is mutated early in the disease. p53 is the "guardian of the genome", which, during DNA and cell duplication, makes sure the DNA is copied correctly and destroys the cell (apoptosis) if the DNA is mutated and cannot be fixed. When p53 itself is mutated, other mutations can survive. Phosphatase and tensin homolog (PTEN), another tumor suppressor gene, is itself lost or mutated. Epidermal growth factor receptor, a growth factor that normally stimulates cells to divide, is amplified and stimulates cells to divide too much. Together, these mutations lead to cells dividing uncontrollably, a hallmark of cancer. In 2009, mutations in IDH1 and IDH2 were found to be part of the mechanism and associated with a less favorable prognosis. Diagnosis Classification Gliomas are classified by cell type, by grade, and by location. By type of cell Gliomas are named according to the specific type of cell with which they share histological features, but not necessarily from which they originate. The main types of glioma are: Ependymomas: ependymal cells Astrocytomas: astrocytes (glioblastoma multiforme is a malignant astrocytoma and the most common primary brain tumor among adults). Oligodendrogliomas: oligodendrocytes Brainstem glioma: develop in the brain stem Optic nerve glioma: develop in or around the optic nerve Mixed gliomas, such as oligoastrocytomas, contain cells from different types of glia By grade Gliomas are further categorized according to their grade, which is determined by pathologic evaluation of the tumor. The neuropathological evaluation and diagnostics of brain tumor specimens is performed according to WHO Classification of Tumours of the Central Nervous System. Biologically benign gliomas [WHO grade I] are comparatively low risk and can be removed surgically depending on their location Low-grade gliomas [WHO grade II] are well-differentiated (not anaplastic); these tend to exhibit benign tendencies and portend a better prognosis for the patient. However, they have a uniform rate of recurrence and increase in grade over time so should be classified as malignant. High-grade [WHO grades III–IV] gliomas are undifferentiated or anaplastic; these are malignant and carry a worse prognosis.Of numerous grading systems in use, the most common is the World Health Organization (WHO) grading system for astrocytoma, under which tumors are graded from I (least advanced disease—best prognosis) to IV (most advanced disease—worst prognosis). By location Gliomas can be classified according to whether they are above or below a membrane in the brain called the tentorium. The tentorium separates the cerebrum (above) from the cerebellum (below). The supratentorial is above the tentorium, in the cerebrum, and mostly found in adults (70%). The infratentorial is below the tentorium, in the cerebellum, and mostly found in children (70%). The pontine tumors are located in the pons of the brainstem. The brainstem has three parts (pons, midbrain, and medulla); the pons controls critical functions such as breathing, making surgery on these extremely dangerous. Treatment Treatment for brain gliomas depends on the location, the cell type, and the grade of malignancy. Often, treatment is a combined approach, using surgery, radiation therapy, and chemotherapy. A prolonged survival was observed when treating with radiotherapy and concomitant temozolomide. Radiotherapy was given for 5 days a week for 6 week, with a total of 60 Gy. Temozolomide was given daily during the treatment of radiotherapy, at a dose of 75 mg per square meter of body surface area per day. When radiotherapy ended additionally six cycles of temozolomide were given, for five days during each cycle of 28 days. The radiation therapy is in the form of external beam radiation or the stereotactic approach using radiosurgery. Spinal cord tumors can be treated by surgery and radiation. Temozolomide is a chemotherapy drug which can be administered easily in an outpatient setting and is able to cross the blood–brain barrier effectively. Treatment via immunotherapy may help some gliomas. Experimental therapies like oncolytic viruses have shown potential therapeutic benefits in clinical trials but has not been approved for use in clinic. Refractory disease For recurrent high-grade glioblastoma, recent studies have taken advantage of angiogenic blockers such as bevacizumab in combination with conventional chemotherapy, with encouraging results. Relative effectiveness A 2017 meta-analysis compared surgical resection versus biopsy as the initial surgical management option for a person with a low-grade glioma. Results show the evidence is insufficient to make a reliable decision. The relative effectiveness of surgical resection compared to biopsy for people with malignant glioma (high-grade) is unknown.For high-grade gliomas, a 2003 meta-analysis compared radiotherapy with radiotherapy and chemotherapy. It showed a small but clear improvement from using chemotherapy with radiotherapy. A 2019 meta-analysis suggested that for people with less aggressive gliomas, radiotherapy may increase the risk of long term neurocognitive side effects. Whilst, evidence is uncertain on whether there are long term neurocognitive side effects associated with chemoradiotherapy.Temozolomide is effective for treating Glioblastoma Multiforme (GBM) compared to radiotherapy alone. A 2013 meta-analysis showed that Temozolomide prolongs survival and delays progression, but is associated with an increase in side effects such as blood complications, fatigue, and infection. For people with recurrent GBM, when comparing temozolomide with chemotherapy, there may be an improvement in the time-to-progression and the persons quality of life, but no improvement in overall survival, with temozolomide treatment. Evidence suggests that for people with recurrent high-grade gliomas who have not had chemotherapy before, there are similar survival and time-to-progression outcomes between treatment with temozolomide or the chemotherapy multidrug known as PCV (procarvazine, lomustine and vincristine).A mutational analysis of 23 initial low-grade gliomas and recurrent tumors from the same patients has challenged the benefits and usage of Temozolomide. The study showed that when lower-grade brain tumors of patients are removed and patients are further treated with Temozolomide, 6 out of 10 times the recurrent tumors were more aggressive and acquired alternative and more mutations. As one of the last authors, Costello, stated "They had a 20- to 50-fold increase in the number of mutations. A patient who received surgery alone who might have had 50 mutations in the initial tumor and 60 in the recurrence. But patients who received TMZ might have 2,000 mutations in the recurrence." Further, new mutations were verified to carry known signatures of Temozolomide induced mutations. The research suggests that Temozolomide for the treatment of certain brain tumors should be thoroughly thought. Unjudicious usage of Temozolomide might lower the prognosis of the patients further, or increase their burden. Further understanding of the mechanisms of Temozolomide induced mutations and novel combination approaches could be promising. Prognosis Prognosis of gliomas is given in relation to what grade (as scored by the World Health Organization system) of tumour the patient presents with. Typically, any tumour presenting as above WHO grade I (i.e. a malignant tumour as opposed to a benign tumour) will have a prognosis resulting in eventual death, varying from years (WHO grade II/III) to months (WHO grade IV). Prognosis can also be given based on cellular subtype, which may also impact prognosis. Low grade For low-grade tumors, the prognosis is somewhat more optimistic. Patients diagnosed with a low-grade glioma are 17 times as likely to die as matched patients in the general population. The age-standardized 10-year relative survival rate was 47%. One study reported that low-grade oligodendroglioma patients have a median survival of 11.6 years; another reported a median survival of 16.7 years. Unfortunately, approximately 70% of low-grade (WHO grade-II) will progress to high-grade tumours within 5–10 years High grade This group comprises anaplastic astrocytomas and glioblastoma multiforme. Whereas the median overall survival of anaplastic (WHO grade III) gliomas is approximately 3 years, glioblastoma multiforme has a poor median overall survival of c. 15 months.Postoperative conventional daily radiotherapy improves survival for adults with good functional well‐being and high grade glioma compared to no postoperative radiotherapy. Hypofractionated radiation therapy has similar efficacy for survival as compared to conventional radiotherapy, particularly for individuals aged 60 and older with glioblastoma. Diffuse intrinsic pontine glioma Diffuse intrinsic pontine glioma primarily affects children, usually between the ages of 5 and 7. The median survival time with DIPG is under 12 months. Surgery to attempt tumour removal is usually not possible or advisable for DIPG. By their very nature, these tumours invade diffusely throughout the brain stem, growing between normal nerve cells. Aggressive surgery would cause severe damage to neural structures vital for arm and leg movement, eye movement, swallowing, breathing, and even consciousness. Trials of drug candidates have been unsuccessful. The disease is primarily treated with radiation therapy alone. IDH1 and IDH2-mutated glioma Patients with glioma carrying mutations in either IDH1 or IDH2 have a relatively favorable survival, compared with patients with glioma with wild-type IDH1/2 genes. In WHO grade III glioma, IDH1/2-mutated glioma have a median prognosis of ~3.5 years, whereas IDH1/2 wild-type glioma perform poor with a median overall survival of c. 1.5 years. In glioblastoma, the difference is larger. There, IDH1/2 wild-type glioblastoma have a median overall survival of 1 year, whereas IDH1/2-mutated glioblastoma have a median overall survival of more than 3 years. References External links Glioma at the Human Protein Atlas American Brain Tumor Association: Malignant Gliomas Brain and Spinal Tumors: Hope Through Research (National Institute of Neurological Disorders and Stroke) WHO Classification of Glioma Glioma Images MedPix Database
Calcinosis	Calcinosis is the formation of calcium deposits in any soft tissue. It is a rare condition that has many different causes. These range from infection and injury to systemic diseases like kidney failure. Types Dystrophic calcification The most common type of calcinosis is dystrophic calcification. This type of calcification can occur as a response to any soft tissue damage, including that involved in implantation of medical devices. Metastatic calcification Metastatic calcification involves a systemic calcium excess imbalance, which can be caused by hypercalcemia, kidney failure, milk-alkali syndrome, lack or excess of other minerals, or other causes. Tumoral calcinosis The cause of the rare condition of tumoral calcinosis is not entirely understood. It is generally characterized by large, globular calcifications near joints. See also Calcification Calcinosis cutis Dermatomyositis Fahrs syndrome Hyperphosphatemia Primrose syndrome Scleroderma References External links Media related to Calcinosis at Wikimedia Commons
Subdural effusion	Subdural effusion refers to an effusion in the subdural space, usually of cerebrospinal fluid.It is sometimes treated with surgery. See also Cerebrospinal fluid leak References == External links ==
Cracked nipple	Cracked nipple (nipple trauma or nipple fissure) is a condition that can occur in breastfeeding women as a result of a number of possible causes. Developing a cracked nipple can result in soreness, dryness or irritation to, or bleeding of, one or both nipples during breastfeeding. The mother with a cracked nipple can have severe nipple pain when the baby is nursing. This severe pain is a disincentive for continued breastfeeding. The crack can appear as a cut across the tip of the nipple and may extend to its base. Cracked nipple develop after the birth of the infant and is managed with pharmacological and nonpharmacological treatment. Signs and symptoms Cracked nipples are classified as a breast disorder. The nipple is not only the structure to deliver milk to the infant, it also contains small, sebaceous glands or Montgomery glands to lubricate the skin of the areola. Cracked nipples are most often associated with breastfeeding and appear as cracks or small lacerations or breaks in the skin of the nipple. In some instances an ulcer will form. The nipple in a nursing mother is in regular contact with a nursing infant. Cracked nipples are trauma to the nipple and can be quite painful. Cracked nipples typically appear three to seven days after the birth.If the nipples appears to be wedge-shaped, white and flattened, this may indicate that the latch is not good and there is a potential of developing cracked nipples. Complications Bacteria can enter the breast through cracked nipples, which increase the risk of mastitis. Candida infection (thrush) of the nipple can also occur, resulting in deep-pink, cracked, and sore nipples. Contraindications for breastfeeding Because cracked nipples can result in the infant being exposed to blood, women with certain blood-borne diseases may be advised to stop breastfeeding if they have a cracked nipple. It has been found safe for breastfeeding mothers with hepatitis B and cracked nipples to breastfeed. In the event that a nursing woman experiences cracked and bleeding nipples or breast inflammation within one to two weeks immediately following an acute Toxoplasmosis infection (when the organism is still circulating in her bloodstream), it is theoretically possible that she could transmit Toxoplasma gondii to the infant through her breast milk. Immune suppressed women could have circulating Toxoplasma for even longer periods of time. However, the likelihood of human milk transmission is very small. Transmission risk of HIV increases if the mother has cracked and bleeding nipples An uncommon infection in the mother, Chagas disease, can be transmitted to the nursing infant via cracked nipples. Women with hepatitis C are advised to abstain from breastfeeding if their nipples are cracked or bleeding. Cause Some studies indicate that cracked nipples are caused by poor latch. Yet other causes could be poor positioning, use of a feeding bottle, breast engorgement, inexperience, semi-protruding nipples, use of breast pumps and light pigmentation of the nipples. Breast engorgement is also a main factor in altering the ability of the infant to latch-on. Engorgement changes the shape and curvature of the nipple region by making the breast inflexible, flat, hard, and swollen. The nipples on an engorged breast are flat.When the baby is latched on correctly, the nipple is located against the soft palate in the back of the babys mouth. When the nipple is near the front of the mouth and being pinched against the hard palate, this will cause pain and development of cracked nipples. One cause of painful, cracked nipples is the incorrect positioning and incorrect latching on to the breast by the infant. The baby can create cracked nipples due to the strong sucking pressure, stretching and pulling the nipple, the friction and rubbing of skin to skin. The cause of sore, cracked nipples can also be from a yeast or Candida infection in the baby or the mother or both. Thrush can develop after the use of antibiotics. For first-time breastfeeding mothers, it normally takes a few tries before the latch is right, which can make the nipples tender and sore the first few days. If the nipples become cracked or bleed, the latch may need to be corrected. Women are advised to keep on breastfeeding, as it will actually help the nipples heal. A little breast milk or purified lanolin cream or ointment helps the healing process.If a feeding bottle is used in addition to breastfeeding, cracked nipples may result because the different sucking techniques required for the bottle and the breast vary. Bottle-feeding babies uses his or her tongue to regulate the flow of milk. This same technique will cause friction on the nipple while breastfeeding. This, in turn, encourages the continued use of the bottle with less time breastfeeding.Pain caused by cracked nipples can sometimes lead to the cessation of breast-feeding. In addition to cracks, blisters or ulcers can form. Prevention The nipples of nursing mothers naturally make a lubricant to prevent drying, cracking, or infections. Cracked nipples may be able to be prevented by: Avoid soaps and harsh washing or drying of the breasts and nipples. This can cause dryness and cracking. Rubbing a little breast milk on the nipple after feeding to protect it. Keeping the nipples dry to prevent cracking and infection. Using seashells to keep nipples healthy through continuous contact with breast milkRoman chamomile is sometimes used as a remedy in alternative medicine to treat cracked nipples by a topical application. However, there is no scientific evidence for its efficacy, and is in fact considered unsafe for use during pregnancy. Treatment Cracked nipples can be treated with 100% lanolin. Glycerin nipple pads can be chilled and placed over the nipples to help soothe and heal cracked or painful nipples. If the cause of cracked nipples is from thrush, treatment is usually begun with nystatin. If the mother is symptomatic then the mother and the baby can be treated. Continuing to breastfeed will actually help the nipples heal. A little breast milk or purified lanolin cream or ointment helps the healing process. Breastfeeding professionals that include nurses, midwives and lactation consultants are able to assist in the treatment of cracked nipples.Advice from others is abundant but there have been some treatments that have been identified as not being effective in healing or preventing cracked nipples. These ineffective treatments are keeping the breastfeeding short and using a nipple guard. Keeping the feedings short so that the nipples can rest is not effective in relieving the pain of cracked nipples and it could have a negative effect on the milk supply. Nipple shields do not improve latching on. Epidemiology In a survey in New York City, 35% of nursing mothers stopped breastfeeding after one week due to the pain of cracked nipples. Thirty percent stopped breastfeeding between weeks one and three. Another survey of breastfeeding mothers in Brazil reported that there was 25% higher risk of interruption of exclusive breastfeeding when the women had cracked nipples. Mothers with higher education levels were more likely to continue breastfeeding despite the pain of cracked nipples. Society and culture The importance of preventing cracked nipples while breastfeeding has been reported. In an informal survey of breastfeeding in the UK, some mothers reported that they stopped breastfeeding because the cracked nipples made it too painful. See also List of cutaneous conditions References Bibliography Henry, Norma (2016). RN maternal newborn nursing : review module. Stilwell, KS: Assessment Technologies Institute. ISBN 9781565335691. Dennis, Cindy-Lee; Jackson, Kim; Watson, Jo (2014-12-15). "The Cochrane Library". Cochrane Database of Systematic Reviews (12): CD007366. doi:10.1002/14651858.cd007366.pub2. PMID 25506813. == External links ==
Twin	Twins are two offspring produced by the same pregnancy. Twins can be either monozygotic (identical), meaning that they develop from one zygote, which splits and forms two embryos, or dizygotic (non-identical or fraternal), meaning that each twin develops from a separate egg and each egg is fertilized by its own sperm cell. Since identical twins develop from one zygote, they will share the same sex, while fraternal twins may or may not. In rare cases twins can have the same mother and different fathers (heteropaternal superfecundation). In contrast, a fetus that develops alone in the womb (the much more common case, in humans) is called a singleton, and the general term for one offspring of a multiple birth is a multiple. Unrelated look-alikes whose resemblance parallels that of twins are referred to as doppelgängers. Statistics The human twin birth rate in the United States rose 76% from 1980 through 2009, from 9.4 to 16.7 twin sets (18.8 to 33.3 twins) per 1,000 births. The Yoruba people have the highest rate of twinning in the world, at 45–50 twin sets (90–100 twins) per 1,000 live births, possibly because of high consumption of a specific type of yam containing a natural phytoestrogen which may stimulate the ovaries to release an egg from each side. In Central Africa, there are 18–30 twin sets (or 36–60 twins) per 1,000 live births. In North America, South Asia (India, Pakistan, Bangladesh, Nepal), and Southeast Asia, the lowest rates are found; only 6 to 9 twin sets per 1,000 live births. North America and Europe have intermediate rates of 9 to 16 twin sets per 1,000 live births.Multiple pregnancies are much less likely to carry to full term than single births, with twin pregnancies lasting on average 37 weeks, three weeks less than full term. Women who have a family history of fraternal twins have a higher chance of producing fraternal twins themselves, as there is a genetically linked tendency to hyper-ovulate. There is no known genetic link for identical twinning. Other factors that increase the odds of having fraternal twins include maternal age, fertility drugs and other fertility treatments, nutrition, and prior births. Some women intentionally turn to fertility drugs in order to conceive twins. Types and zygosity The vast majority of twins are either dizygotic (fraternal) or monozygotic (identical). Less common variants are discussed further down the article. Fraternal twins can be any of the following: Female–female twins: Sometimes called sororal twins (25%). Male–male twins: Sometimes called fraternal twins (25%). Female-male twins: This is the most common pairing (50%), simply by virtue of it encompassing both "female-male" (25%) and "male-female" (25%) twins.Among non-twin births, male singletons are slightly (about five percent) more common than female singletons. The rates for singletons vary slightly by country. For example, the sex ratio of birth in the US is 1.05 males/female, while it is 1.07 males/female in Italy. However, males are also more susceptible than females to die in utero, and since the death rate in utero is higher for twins, it leads to female twins being more common than male twins.Zygosity is the degree of identity in the genome of twins. Dizygotic (fraternal) twins Dizygotic (DZ) or fraternal twins (also referred to as "non-identical twins", "dissimilar twins", "biovular twins", and, informally in the case of females, "sororal twins") usually occur when two fertilized eggs are implanted in the uterus wall at the same time. When two eggs are independently fertilized by two different sperm cells, fraternal twins result. The two eggs, or ova, form two zygotes, hence the terms dizygotic and biovular. Fraternal twins are, essentially, two ordinary siblings who happen to develop in the womb together and who are born at the same time, since they arise from two separate eggs fertilized by two separate sperm, just like ordinary siblings. This is the most common type of twin.Dizygotic twins, like any other siblings, will practically always have different sequences on each chromosome, due to chromosomal crossover during meiosis. Dizygotic twins share only 50 percent of each others genes, which resemble amongst siblings that are conceived and born at different times. Like any other siblings, dizygotic twins may look similar, particularly as they are the same age. However, dizygotic twins may also look very different from each other (for example, be of opposite sexes). Studies show that there is a genetic proclivity for dizygotic twinning. However, it is only the mother who has any effect on the chances of having such twins; there is no known mechanism for a father to cause the release of more than one ovum. Dizygotic twinning ranges from six per thousand births in Japan (similar to the rate of monozygotic twins) to 14 and more per thousand in some African countries.Dizygotic twins are also more common for older mothers, with twinning rates doubling in mothers over the age of 35. With the advent of technologies and techniques to assist women in getting pregnant, the rate of fraternals has increased markedly. Monozygotic (identical) twins Monozygotic (MZ) or identical twins occur when a single egg is fertilized to form one zygote (hence, "monozygotic") which then divides into two separate embryos. The chances of having identical twins is relatively rare — around 3 or 4 in every 1,000 births. Mechanism Regarding spontaneous or natural monozygotic twinning, a recent theory proposes that monozygotic twins are probably formed when a blastocyst contains two inner cell masses (ICM), each of which will lead to a separate fetus, rather than by the embryo splitting while hatching from the zona pellucida (the gelatinous protective coating around the blastocyst).Monozygotic twins may also be created artificially by embryo splitting. It can be used as an expansion of in vitro fertilization (IVF) to increase the number of available embryos for embryo transfer. Incidence Monozygotic twinning occurs in birthing at a rate of about 3 in every 1000 deliveries worldwide (about 0.3% of the world population).The likelihood of a single fertilization resulting in monozygotic twins is uniformly distributed in all populations around the world. This is in marked contrast to dizygotic twinning, which ranges from about six per thousand births in Japan (almost similar to the rate of identical twins, which is around 4–5) to 15 and more per thousand in some parts of India and up to over 20 in some Central African countries. The exact cause for the splitting of a zygote or embryo is unknown. IVF techniques are more likely to create dizygotic twins. For IVF deliveries, there are nearly 21 pairs of twins for every 1,000. Genetic and epigenetic similarity Monozygotic twins are genetically nearly identical and they are always the same sex unless there has been a mutation during development. The children of monozygotic twins test genetically as half-siblings (or full siblings, if a pair of monozygotic twins reproduces with another pair or with the same person), rather than first cousins. Identical twins do not have the same fingerprints however, because even within the confines of the womb, the fetuses touch different parts of their environment, giving rise to small variations in their corresponding prints and thus making them unique.Monozygotic twins always have the same genotype. Normally due to an environmental factor or the deactivation of different X chromosomes in female monozygotic twins, and in some extremely rare cases, due to aneuploidy, twins may express different sexual phenotypes, normally from an XXY Klinefelter syndrome zygote splitting unevenly.Monozygotic twins, although genetically very similar, are not genetically exactly the same. The DNA in white blood cells of 66 pairs of monozygotic twins was analyzed for 506,786 single-nucleotide polymorphisms known to occur in human populations. Polymorphisms appeared in 2 of the 33 million comparisons, leading the researchers to extrapolate that the blood cells of monozygotic twins may have on the order of one DNA-sequence difference for every 12 million nucleotides, which would imply hundreds of differences across the entire genome. The mutations producing the differences detected in this study would have occurred during embryonic cell-division (after the point of fertilization). If they occur early in fetal development, they will be present in a very large proportion of body cells. Another cause of difference between monozygotic twins is epigenetic modification, caused by differing environmental influences throughout their lives. Epigenetics refers to the level of activity of any particular gene. A gene may become switched on, switched off, or could become partially switched on or off in an individual. This epigenetic modification is triggered by environmental events. Monozygotic twins can have markedly different epigenetic profiles. A study of 80 pairs of monozygotic twins ranging in age from three to 74 showed that the youngest twins have relatively few epigenetic differences. The number of epigenetic differences increases with age. Fifty-year-old twins had over three times the epigenetic difference of three-year-old twins. Twins who had spent their lives apart (such as those adopted by two different sets of parents at birth) had the greatest difference. However, certain characteristics become more alike as twins age, such as IQ and personality.In January 2021, new research from a team of researchers in Iceland was published in the journal Nature Genetics suggesting that identical twins may not be quite as identical as previously thought. The four-year study of monozygotic (identical) twins and their extended families revealed that these twins have genetic differences that begin in the early stages of embryonic development. Polar body and semi-identical twins A 1981 study of a deceased triploid XXX twin fetus without a heart showed that although its fetal development suggested that it was an identical twin, as it shared a placenta with its healthy twin, tests revealed that it was probably a polar body twin. The authors were unable to predict whether a healthy fetus could result from a polar body twinning. However, a study in 2012 found that it is possible for a polar body to result in a healthy fetus.In 2003, a study argued that many cases of triploidy arise from sesquizygotic (semi-identical) twinning. Sesquizygotic twin type See Semi-identical (sesquizygotic) twins below, under Unusual twinnings. Degree of separation The degree of separation of the twins in utero depends on if and when they split into two zygotes. Dizygotic twins were always two zygotes. Monozygotic twins split into two zygotes at some time very early in the pregnancy. The timing of this separation determines the chorionicity (the number of placentae) and amniocity (the number of sacs) of the pregnancy. Dichorionic twins either never divided (i.e.: were dizygotic) or they divided within the first 4 days. Monoamnionic twins divide after the first week. In very rare cases, twins become conjoined twins. Non-conjoined monozygotic twins form up to day 14 of embryonic development, but when twinning occurs after 14 days, the twins will likely be conjoined. Furthermore, there can be various degrees of shared environment of twins in the womb, potentially leading to pregnancy complications. It is a common misconception that two placentas automatically implies dizygotic twins, but if monozygotic twins separate early enough, the arrangement of sacs and placentas in utero is in fact indistinguishable from that of dizygotic twins. Demographics A 2006 study has found that insulin-like growth factor present in dairy products may increase the chance of dizygotic twinning. Specifically, the study found that vegan mothers (who exclude dairy from their diets) are one-fifth as likely to have twins as vegetarian or omnivore mothers, and concluded that "Genotypes favoring elevated IGF and diets including dairy products, especially in areas where growth hormone is given to cattle, appear to enhance the chances of multiple pregnancies due to ovarian stimulation."From 1980 to 1997, the number of twin births in the United States rose 52%. This rise can at least partly be attributed to the increasing popularity of fertility drugs and procedures such as IVF, which result in multiple births more frequently than unassisted fertilizations do. It may also be linked to the increase of growth hormones in food. Ethnicity About 1 in 90 human births (1.1%) results from a twin pregnancy. The rate of dizygotic twinning varies greatly among ethnic groups, ranging as high as about 45 per 1000 births (4.5%) for the Yoruba to 10% for Linha São Pedro, a tiny Brazilian settlement which belongs to the city of Cândido Godói. In Cândido Godói, one in five pregnancies has resulted in twins. The Argentine historian Jorge Camarasa has put forward the theory that experiments of the Nazi doctor Josef Mengele could be responsible for the high ratio of twins in the area. His theory was rejected by Brazilian scientists who had studied twins living in Linha São Pedro; they suggested genetic factors within that community as a more likely explanation. A high twinning rate has also been observed in other places of the world, including: Igbo-Ora in Nigeria Kodinhi, located in Kerala, India Mohammadpur Umri, located in Uttar Pradesh, IndiaThe widespread use of fertility drugs causing hyperovulation (stimulated release of multiple eggs by the mother) has caused what some call an "epidemic of multiple births". In 2001, for the first time ever in the US, the twinning rate exceeded 3% of all births. Nevertheless, the rate of monozygotic twins remains at about 1 in 333 across the globe. In a study on the maternity records of 5750 Hausa women living in the Savannah zone of Nigeria, there were 40 twins and 2 triplets per 1000 births. Twenty-six percent of twins were monozygotic. The incidence of multiple births, which was about five times higher than that observed in any western population, was significantly lower than that of other ethnic groups, who live in the hot and humid climate of the southern part of the country. The incidence of multiple births was related to maternal age but did not bear any association to the climate or prevalence of malaria.Twins are more common in people of African descent. Predisposing factors The predisposing factors of monozygotic twinning are unknown. Dizygotic twin pregnancies are slightly more likely when the following factors are present in the woman: She is of West African descent (especially Yoruba) She is between the age of 30 and 40 years She is greater than average height and weight She has had several previous pregnancies.Women undergoing certain fertility treatments may have a greater chance of dizygotic multiple births. In the United States it has been estimated that by 2011 36% of twin births resulted from conception by assisted reproductive technology.The risk of twin birth can vary depending on what types of fertility treatments are used. With in vitro fertilisation (IVF), this is primarily due to the insertion of multiple embryos into the uterus. Ovarian hyperstimulation without IVF has a very high risk of multiple birth. Reversal of anovulation with clomifene (trade names including Clomid) has a relatively less but yet significant risk of multiple pregnancy. Delivery interval A 15-year German study of 8,220 vaginally delivered twins (that is, 4,110 pregnancies) in Hesse yielded a mean delivery time interval of 13.5 minutes. The delivery interval between the twins was measured as follows: Within 15 minutes: 75.8% 16–30 minutes: 16.4% 31–45 minutes: 4.3% 46–60 minutes: 1.7% Over 60 minutes: 1.8% (72 instances)The study stated that the occurrence of complications "was found to be more likely with increasing twin-to-twin delivery time interval" and suggested that the interval be kept short, though it noted that the study did not examine causes of complications and did not control for factors such as the level of experience of the obstetrician, the wish of the women giving birth, or the "management strategies" of the procedure of delivering the second twin. There have also been cases in which twins are born a number of days apart. Possibly the worldwide record for the duration of the time gap between the first and the second delivery was the birth of twins 97 days apart in Cologne, Germany, the first of which was born on November 17, 2018. Complications during pregnancy Vanishing twins Researchers suspect that as many as 1 in 8 pregnancies start out as multiples, but only a single fetus is brought to full term, because the other fetus has died very early in the pregnancy and has not been detected or recorded. Early obstetric ultrasonography exams sometimes reveal an "extra" fetus, which fails to develop and instead disintegrates and vanishes in the uterus. There are several reasons for the "vanishing" fetus, including it being embodied or absorbed by the other fetus, placenta or the mother. This is known as vanishing twin syndrome. Also, in an unknown proportion of cases, two zygotes may fuse soon after fertilization, resulting in a single chimeric embryo, and, later, fetus. Conjoined twins Conjoined twins (or the once-commonly used term "siamese") are monozygotic twins whose bodies are joined together during pregnancy. This occurs when the zygote starts to split after day 12 following fertilization and fails to separate completely. This condition occurs in about 1 in 50,000 human pregnancies. Most conjoined twins are now evaluated for surgery to attempt to separate them into separate functional bodies. The degree of difficulty rises if a vital organ or structure is shared between twins, such as the brain, heart, liver or lungs. Chimerism A chimera is an ordinary person or animal except that some of their parts actually came from their twin or from the mother. A chimera may arise either from monozygotic twin fetuses (where it would be impossible to detect), or from dizygotic fetuses, which can be identified by chromosomal comparisons from various parts of the body. The number of cells derived from each fetus can vary from one part of the body to another, and often leads to characteristic mosaicism skin coloration in human chimeras. A chimera may be intersex, composed of cells from a male twin and a female twin. In one case DNA tests determined that a woman, Lydia Fairchild, mystifyingly, was not the mother of two of her three children; she was found to be a chimera, and the two children were conceived from eggs derived from cells of their mothers twin. Parasitic twins Sometimes one twin fetus will fail to develop completely and continue to cause problems for its surviving twin. One fetus acts as a parasite towards the other. Sometimes the parasitic twin becomes an almost indistinguishable part of the other, and sometimes this needs to be treated medically. Partial molar twins A very rare type of parasitic twinning is one where a single viable twin is endangered when the other zygote becomes cancerous, or "molar". This means that the molar zygotes cellular division continues unchecked, resulting in a cancerous growth that overtakes the viable fetus. Typically, this results when one twin has either triploidy or complete paternal uniparental disomy, resulting in little or no fetus and a cancerous, overgrown placenta, resembling a bunch of grapes. Miscarried twin Occasionally, a woman will suffer a miscarriage early in pregnancy, yet the pregnancy will continue; one twin was miscarried but the other was able to be carried to term. This occurrence is similar to the vanishing twin syndrome, but typically occurs later, as the twin is not reabsorbed. Low birth weight It is very common for twins to be born at a low birth weight. More than half of twins are born weighing less than 5.5 pounds (2.5 kg), while the average birth weight of a healthy baby should be around 6–8 pounds (3–4 kg). This is largely due to the fact that twins are typically born premature. Premature birth and low birth weights, especially when under 3.5 pounds (1.6 kg), can increase the risk of several health-related issues, such as vision and hearing loss, mental disabilities, and cerebral palsy. There is an increased possibility of potential complications as the birth weight of the baby decreases. Twin-to-twin transfusion syndrome Monozygotic twins who share a placenta can develop twin-to-twin transfusion syndrome. This condition means that blood from one twin is being diverted into the other twin. One twin, the donor twin, is small and anemic, the other, the recipient twin, is large and polycythemic. The lives of both twins are endangered by this condition. Stillbirths Stillbirths occurs when a fetus dies after 20 weeks of gestation. There are two types of stillbirth, including intrauterine death and intrapartum death. Intrauterine death occurs when a baby dies during late pregnancy. Intrapartum death, which is more common, occurs when a baby dies while the mother is giving birth. The cause of stillbirth is often unknown, but the rate of babies who are stillborn is higher in twins and multiple births. Caesareans or inductions are advised after 38 weeks of pregnancy for twins, because the risk of stillbirth increases after this time. Heterotopic pregnancy Heterotopic pregnancy is an exceedingly rare type of dizygotic twinning in which one twin implants in the uterus as normal and the other remains in the fallopian tube as an ectopic pregnancy. Ectopic pregnancies must be resolved because they can be life-threatening to the mother. However, in most cases, the intrauterine pregnancy can be salvaged. Management of birth For otherwise healthy twin pregnancies where both twins are head down a trial of vaginal delivery is recommended at between 37 and 38 weeks. Vaginal delivery in this case does not worsen the outcome for the infant as compared with Caesarean section. There is controversy on the best method of delivery where the first twin is head first and the second is not. When the first twin is not head down a caesarean section is often recommended. It is estimated that 75% of twin pregnancies in the United States were delivered by caesarean section in 2008. In comparison, the rate of caesarean section for all pregnancies in the general population varies between 14% and 40%. In twins that share the same placenta, delivery may be considered at 36 weeks. For twins who are born early, there is insufficient evidence for or against placing preterm stable twins in the same cot or incubator (co-bedding). Human twin studies Twin studies are utilized in an attempt to determine how much of a particular trait is attributable to either genetics or environmental influence. These studies compare monozygotic and dizygotic twins for medical, genetic, or psychological characteristics to try to isolate genetic influence from epigenetic and environmental influence. Twins that have been separated early in life and raised in separate households are especially sought-after for these studies, which have been used widely in the exploration of human nature. Classical twin studies are now being supplemented with molecular genetic studies which identify individual genes. Unusual twinnings Bi-paternal twins This phenomenon is known as heteropaternal superfecundation. One 1992 study estimates that the frequency of heteropaternal superfecundation among dizygotic twins, whose parents were involved in paternity suits, was approximately 2.4%; see the references section, below, for more details.Dizygotic twins from biracial couples can sometimes be mixed twins, which exhibit differing ethnic and racial features. One such pairing was born in London in 1993 to a white mother and Caribbean father. Monozygotic twins of different sexes Among monozygotic twins, in extremely rare cases, twins have been born with different sexes (one male, one female). When monozygotic twins are born with different sexes it is because of chromosomal defects. The probability of this is so small that multiples having different sexes is universally accepted as a sound basis for in utero clinical determination that the multiples are not monozygotic. Another abnormality that can result in monozygotic twins of different sexes is if the egg is fertilized by a male sperm but during cell division only the X chromosome is duplicated. This results in one normal male (XY) and one female with Turner syndrome (45,X). In these cases, although the twins did form from the same fertilized egg, it is incorrect to refer to them as genetically identical, since they have different karyotypes. Semi-identical (sesquizygotic) twins Monozygotic twins can develop differently, due to their genes being differently activated. More unusual are "semi-identical twins", also known as "sesquizygotic". As of 2019, only two cases have been reported. These "half-identical twins" are hypothesized to occur when an unfertilized egg cleaves into two identical attached ova, both of which are viable for fertilization. Both ova are then fertilized, each by a different sperm, and the coalesced zygotes undergo further cell duplications developing as a chimeric blastomere. If this blastomere then undergoes a twinning event, two embryos will be formed, with different paternal genetic information and identical maternal genetic information. This results in a set of twins with identical gene sequence from the mothers side, but different sequences from the fathers side. Cells in each fetus carry chromosomes from either sperm, resulting in chimeras. This form had been speculated until only recently being recorded. In 2007, a study reported a case of a pair of living twins, which shared an identical set of maternal chromosomes, while each having a distinct set of paternal chromosomes, albeit from the same man, and thus they most likely share half of their fathers genetic makeup. The twins were both found to be chimeras. One was an intersex XX, and one a XY male. The exact mechanism of fertilization could not be determined but the study stated that it was unlikely to be a case of polar body twinning.In 2019, a second case of sesquizygotic twins was reported and molecular evidence of the phenomenon was documented by Gabbett and Fisk. In this case, the twins shared 100% of their maternal chromosomes and 78% of their paternal genomic information. The authors postulate two sperm from the same man fertilized an ovum simultaneously. The chromosomes assorted themselves through heterogonesis to form three cell lines. The purely paternal cell line died out due to genomic imprinting lethality, while the other two cell lines, each conisiting of the same maternal DNA but only 50% identical paternal DNA, formed a morula which subsequently split into twins Mirror image twins Mirror image twins result when a fertilized egg splits later in the embryonic stage than normal timing, around day 9–12. This type of twinning could exhibit characteristics with reversed asymmetry, such as opposite dominant handedness, dental structure, or even organs (situs inversus). If the split occurs later than this time period, the twins risk being conjoined. There is no DNA-based zygosity test that can determine if twins are indeed mirror image. The term "mirror image" is used because the twins, when facing each
Twin	other, appear as matching reflections. Language development There have been many studies highlighting the development of language in twins compared to single-born children. These studies have converged on the notion that there is a greater rate of delay in language development in twins compared to their single-born counterparts. The reasons for this phenomenon are still in question; however, cryptophasia was thought to be the major cause. Idioglossia is defined as a private language that is usually invented by young children, specifically twins. Another term to describe what some people call "twin talk" is cryptophasia where a language is developed by twins that only they can understand. The increased focused communication between two twins may isolate them from the social environment surrounding them. Idioglossia has been found to be a rare occurrence and the attention of scientists has shifted away from this idea. However, there are researchers and scientists that say cryptophasia or idioglossia is not a rare phenomenon. Current research is looking into the impacts of a richer social environment for these twins to stimulate their development of language. Animals Twins are common in many mammal species, including cats, sheep, ferrets, giant pandas,Cow,dolphins, dogs, deer, marmosets, tamarins, and elephants. The incidence of twinning among cattle is about 1–4%, and research is underway to improve the odds of twinning, which can be more profitable for the breeder if complications can be sidestepped or managed. A female calf that is the twin of a bull becomes partially masculinized and is known as a freemartin. See also References Further reading Bacon, Kate. Twins in Society: Parents, Bodies, Space, and Talk (Palgrave Macmillan; 2010) 221 pages; explores the experience of child twins, adult twins, and parents of twins, with a focus on Britain. Nieuwint, Aggie; Van Zalen-Sprock, Rieteke; Hummel, Pieter; Pals, Gerard; Van Vugt, John; et al. (1999). "Identical twins with discordant karyotypes". Prenatal Diagnosis. 19 (1): 72–6. doi:10.1002/(SICI)1097-0223(199901)19:1<72::AID-PD465>3.0.CO;2-V. PMID 10073913. S2CID 19112883. Wenk RE, Houtz T, Brooks M, Chiafari FA (1992). "How frequent is heteropaternal superfecundation?". Acta Geneticae Medicae et Gemellologiae. 41 (1): 43–7. doi:10.1017/S000156600000249X. PMID 1488855. S2CID 23507167. Girela, Eloy; Lorente, Jose A.; Alvarez, J. Carlos; Rodrigo, Maria D.; Lorente, Miguel; et al. (1997). "Indisputable double paternity in dizygous twins". Fertility and Sterility. 67 (6): 1159–61. CiteSeerX 10.1.1.378.4082. doi:10.1016/S0015-0282(97)81456-2. PMID 9176461. Shinwell ES, Reichman B, Lerner-Geva L, Boyko V, Blickstein I (September 2007). ""Masculinizing" effect on respiratory morbidity in girls from unlike-sex preterm twins: a possible transchorionic paracrine effect". Pediatrics. 120 (3): e447–53. doi:10.1542/peds.2006-3574. PMID 17766488. S2CID 20498737. Retrieved 2008-10-06. Lummaa V, Pettay JE, Russell AF (June 2007). "Male twins reduce fitness of female co-twins in humans". Proceedings of the National Academy of Sciences of the United States of America. 104 (26): 10915–20. Bibcode:2007PNAS..10410915L. doi:10.1073/pnas.0605875104. PMC 1904168. PMID 17576931. Schein, Elyse; Paula Bernstein (2007). Identical Strangers: A Memoir of Twins Separated and Reunited. New York: Random House. ISBN 978-1-4000-6496-0. OCLC 123390922. Helle, Samuli; Virpi Lummaa; Jukka Jokela (2004). "Selection for Increased Brood Size in Historical Human Populations" (PDF). Evolution. 58 (2): 430–436. doi:10.1111/j.0014-3820.2004.tb01658.x. PMID 15068359. S2CID 9460009. Archived from the original (PDF) on 2008-10-02. Retrieved 2008-10-02. "TWINS Guide to the First Year" (PDF). TWINS Magazine. Fort Collins, Colorado. 2008. Archived from the original (PDF) on 2008-10-30. Retrieved 2008-10-06. Samson, Jennifer. "Facts About Multiples: An Encyclopedia of Multiple Birth Records". Archived from the original on 2009-10-15. Retrieved 2008-10-18. Taylor, Ally. "Twin Zygosity Test for Dichorionic Diamniotic (Di/Di) Twins! Zygosity Reveal". Retrieved 2018-03-30. Am J Med Genet C Semin Med Genet. 2009 May 15;151C(2):136-41. Not really identical: epigenetic differences in monozygotic twins and implications for twin studies in psychiatry. Haque FN, Gottesman II, Wong AH. Twin brothers promoted as Majors General together. Seneviratne brothers, who are twins and joined the Army on a same day, were promoted to the rank of Major General, again on the same day. == External links ==
Primary juvenile glaucoma	Primary juvenile glaucoma is glaucoma that develops due to ocular hypertension and is evident either at birth or within the first few years of life. It is caused due to abnormalities in the anterior chamber angle development that obstruct aqueous outflow in the absence of systemic anomalies or other ocular malformation. Presentation The typical infant who has congenital glaucoma usually is initially referred to an ophthalmologist because of apparent corneal edema. The commonly described triad of epiphora (excessive tearing), blepharospasm and photophobia may be missed until the corneal edema becomes apparent. Systemic associations Two of the more commonly encountered disorders that may be associated with congenital glaucoma are Aniridia and Sturge-Weber syndrome. Genetics JOAG is an autosomal dominant condition. The primary cause is the myocilin protein dysfunction. Myocilin gene mutations are identified in approximately 10% of patients affected by juvenile glaucoma. Diagnosis The diagnosis is clinical. The intraocular pressure (IOP) can be measured in the office in a conscious swaddled infant using a Tonopen or hand-held Goldmann tonometer. Usually, the IOP in normal infants is in the range of 11-14 mmHg. Buphthalmos and Haabs striae can often be seen in case of congenital glaucoma. Differential diagnosis Corneal cloudiness may have myriad of causes. Corneal opacity that results from hereditary dystrophies is usually symmetric. Corneal enlargement may result from megalocornea, a condition in which the diameter of the cornea is larger than usual and the eye is otherwise normal. Treatment The preferred treatment of congenital glaucoma is surgical, not medical. The initial procedures of choice are goniotomy or trabeculotomy if the cornea is clear, and trabeculectomy ab externo if the cornea is hazy. The success rates are similar for both procedures in patients with clear corneas. Trabeculectomy and shunt procedures should be reserved for those cases in which goniotomy or trabeculotomy has failed. Cyclophotocoagulation is necessary in some intractable cases but should be avoided whenever possible because of its potential adverse effects on the lens and the retina. Epidemiology In the United States, the incidence of primary congenital glaucoma is about one in 10,000 live births. Worldwide, the incidence ranges from a low of 1:22,000 in Northern Ireland to a high of 1:2,500 in Saudi Arabia and 1:1,250 in Romania. In about two-thirds of cases, it is bilateral. The distribution between males and females varies with geography. In North America and Europe, it is more common in boys, whereas in Japan it is more common in girls. Congenital glaucomaIncidence: one in every 10000-15000 live births. Bilateral in up to 80% of cases. Most cases are sporadic (90%). However, in the remaining 10% there appears to be a strong familial component. See also Axenfeld syndrome Peters-plus syndrome Weill–Marchesani syndrome References Further reading Lively GD, Alward, WL, Fingert JH. Juvenile open-angle glaucoma: 22-year-old Caucasian female referred in 1990 for evaluation of elevated intraocular pressure (IOP). EyeRounds.org. September 17, 2008. External links 231300 137750; MYOC 137750; CYP1B1 Juvenile Glaucoma at eMedicine on eMedicine Glaucoma for Children on AAPOS. Congenital Primary Glaucoma on patient.info GeneReview/NCBI/NIH/UW entry on Primary Congenital Glaucoma Glaucoma entry on PGCFA

Subsets and Splits

No saved queries yet

Save your SQL queries to embed, download, and access them later. Queries will appear here once saved.