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Chemosis	Chemosis is the swelling (or edema) of the conjunctiva. The term derives from the Greek chem- meaning chemical and -osis meaning denoting action. A chemical reaction, or in this case, a chemical reaction of the conjunctiva which is due to the oozing of exudate from abnormally permeable capillaries. In general, chemosis is a nonspecific sign of eye irritation. The outer surface covering appears to have fluid in it. The conjunctiva becomes swollen and gelatinous in appearance. Often, the eye area swells so much that the eyes become difficult or impossible to close fully. Sometimes, it may also appear as if the eyeball has moved slightly backwards from the white part of the eye due to the fluid filled in the conjunctiva all over the eyes except the iris. The iris is not covered by this fluid and so it appears to be moved slightly inwards. Causes It is usually caused by allergies or viral infections, often inciting excessive eye rubbing. Chemosis is also included in the Chandler Classification system of orbital infections. If chemosis has occurred due to excessive rubbing of the eye, the first aid to be given is a cold water wash for eyes.Other causes of chemosis include: Superior vena cava obstruction, accompanied by facial oedema Hyperthyroidism, associated with exophthalmos, periorbital puffiness, lid retraction, and lid lag Cavernous sinus thrombosis, associated with infection of the paranasal sinuses, proptosis, periorbital oedema, retinal haemorrhages, papilledema, extraocular movement abnormalities, and trigeminal nerve sensory loss Carotid-cavernous fistula - classic triad of chemosis, pulsatile proptosis, and ocular bruit Cluster headache Trichinellosis Systemic lupus erythematosus (SLE) Angioedema Acute glaucoma Panophthalmitis Orbital cellulitis Gonorrheal conjunctivitis Dacryocystitis Spitting cobra venom to the eye High concentrations of phenacyl chloride in chemical mace spray Urticaria Trauma HSV Keratitis Post surgical Mucor Rhabdomyosarcoma of the orbit Diagnosis An eye doctor may most often diagnose chemosis by doing a physical examination of the affected area. They can also ask questions about the severity and length of other symptoms. Treatment Treatment depends on the cause of the chemosis. References == External links ==
Peyronies disease	Peyronies disease is a connective tissue disorder involving the growth of fibrous plaques in the soft tissue of the penis. Specifically, scar tissue forms in the tunica albuginea, the thick sheath of tissue surrounding the corpora cavernosa, causing pain, abnormal curvature, erectile dysfunction, indentation, loss of girth and shortening.It is estimated to affect between .4 to 20% of men. The condition becomes more common with age. Signs and symptoms A certain degree of curvature of the penis is considered normal, as many people are born with this benign condition, commonly referred to as congenital curvature. The disease may cause pain; hardened, big, cord-like lesions (scar tissue known as "plaques"); or abnormal curvature of the penis when erect due to chronic inflammation of the tunica albuginea (CITA).Although the popular conception of Peyronies disease is that it always involves curvature of the penis, the scar tissue sometimes causes divots or indentations rather than curvature. The condition may also make sexual intercourse painful and/or difficult, though it is unclear whether some men report satisfactory or unsatisfactory intercourse in spite of the disorder. The disorder is confined to the penis, although a substantial number of men with Peyronies exhibit concurrent connective tissue disorders in the hand, and to a lesser degree, in the feet. About 30 percent of men with Peyronies disease develop fibrosis in other elastic tissues of the body, such as on the hand or foot, including Dupuytrens contracture of the hand. An increased incidence in genetically related males suggests a genetic component. It can affect men of any race and age. Psychosocial Peyronies disease can also have psychological effects. While most men will continue to be able to have sexual relations, they are likely to experience some degree of erectile dysfunction. It is not uncommon to exhibit depression or withdrawal from their sexual partners. Causes The underlying cause of Peyronies disease is unknown. Although, it is likely due to a buildup of plaque inside the penis due to repeated mild sexual trauma or injury during sexual intercourse or physical activity.Risk factors include diabetes mellitus, Dupuytrens contracture, plantar fibromatosis, penile trauma, smoking, excessive alcohol consumption, genetic predisposition, and European heritage. Diagnosis A urologist may be able to diagnose the disease and suggest treatment. An ultrasound can provide conclusive evidence of Peyronies disease, ruling out congenital curvature or other disorders. Ultrasonography On penile ultrasonography, the typical appearance is hyperechoic focal thickening of the tunica albuginea. Due to associated calcifications, the imaging of patients with Peyronies disease shows acoustic shadowing, as illustrated in figures below. Less common findings, attributed to earlier stages of the disease (still mild fibrosis), are hypoechoic lesions with focal thickening of the paracavernous tissues, echoic focal thickening of the tunica without posterior acoustic shadowing, retractile isoechoic lesions with posterior attenuation of the beam, and focal loss of the continuity of the tunica albuginea. In the Doppler study, increased flow around the plaques can suggest inflammatory activity and the absence of flow can suggest disease stability. Ultrasound is useful for the identification of lesions and to determine their relationship with the neurovascular bundle. Individuals with Peyronies disease can present with erectile dysfunction, often related to venous leakage, due to insufficient drainage at the site of the plaque. Although plaques are more common on the dorsum of the penis, they can also be seen on the ventral face, lateral face, or septum. Treatment Medication and supplements Many oral treatments have been studied but results so far have been mixed. Some consider the use of nonsurgical approaches to be controversial.Vitamin E supplementation has been studied for decades, and some success has been reported in older trials; those successes have not been reliably repeated in larger, newer studies. The use of Interferon-alpha-2b in the early stages of the disease has been studied; as of 2007, its efficacy was questionable.Collagenase clostridium histolyticum is reported to help by breaking down the excess collagen in the penis. It was approved for treatment of Peyronies disease by the FDA in 2013. Physical therapy and devices There is moderate evidence that penile traction therapy is a well-tolerated, minimally invasive treatment; there is uncertainty about the optimal duration of stretching per day and per course of treatment, and the treatment course is difficult. Focused shockwave therapy Focused extracorporeal shockwave therapy is a non-invasive treatment option that involves passing acoustic pulses through the plaque, which can break it down over a series of six to twelve sessions. The treatment is most effective in men with mild to moderate Peyronies. Surgery Surgery such as the "Nesbit operation", which is named after Reed M. Nesbit (1898–1979), an American urologist at University of Michigan), is considered a last resort and should only be performed by highly skilled urological surgeons knowledgeable in specialized corrective surgical techniques. A penile implant may be appropriate in advanced cases. Epidemiology It is estimated to affect between .4 to 20% of men. The condition becomes more common with age. The mean age at onset of disease is 55–60 years although many cases have been recorded in adolescence and early 20’s.The overall prevalence of PD is about .4 to 20 percent in men. Rates range from 3.2 percent in a community-based survey of 4432 men (mean age of sample 57.4) to 16 percent among 488 men undergoing evaluation for erectile dysfunction (mean age 52.8). The prevalence of PD among the 4432 men in the community based study who responded by self report positively for palpable plaque, newly occurring angulation or curvature and painful erection was 1.5 percent between the ages of 30 and 39, 3 percent between 40 and 49, 3 percent between 50 and 59, 4 percent between 60 and 69, and 6.5 percent over 70. In 534 men undergoing routine prostate screening for cancer detection (without a specific urologic complaint), the prevalence of PD was 8.9 percent. In this study, the mean age of those with PD was 68.2 years compared with 61.8 years of those without PD. History The condition was first described in 1561 in correspondence between Andreas Vesalius and Gabriele Falloppio and separately by Gabriele Falloppio. The condition is named for François Gigot de la Peyronie, who described it in 1743. References External links Medscape Urology overview of Peyronies disease
Potter sequence	Potter sequence is the atypical physical appearance of a baby due to oligohydramnios experienced when in the uterus. It includes clubbed feet, pulmonary hypoplasia and cranial anomalies related to the oligohydramnios. Oligohydramnios is the decrease in amniotic fluid volume sufficient to cause deformations in morphogenesis of the baby. Oligohydramnios is the cause of Potter sequence but there are many things that can lead to oligohydramnios. It can be caused by renal diseases such as bilateral renal agenesis (BRA), atresia of the ureter or urethra causing obstruction of the urinary tract, polycystic or multicystic kidney diseases, renal hypoplasia, amniotic rupture, toxemia, or uteroplacental insufficiency from maternal hypertension. The term Potter sequence was initially intended to only refer to cases caused by BRA; however, it is now commonly used by many clinicians and researchers to refer to any case that presents with oligohydramnios or anhydramnios regardless of the source of the loss of amniotic fluid. Types Since its initial characterization, Potter sequence has been defined into five distinct subclassifications. There are those in the medical and research fields that use the term Potter sequence to specifically refer to only cases of BRA, while other groups use the term to loosely refer to all instances of oligohydramnios and anhydramnios regardless of the specific cause. The assignment of nomenclature to the various causes (types) was employed in order to help clarify these discrepancies, but these subclassifications and nomenclature system have not caught on in the medical and research communities. Signs and symptoms The failure of the metanephros to develop in cases of BRA and some cases involving unilateral renal agenesis (URA) is due primarily to the failure of the mesonephric duct to produce a ureteric bud capable of inducing the metanephric mesenchyme. The failed induction will thereby cause the subsequent degeneration of the metanephros by apoptosis and other mechanisms. The mesonephric duct(s) of the agenic kidney(s) will also degenerate and fail to connect with the bladder. Therefore, the means by which the fetus produces urine and transports it to the bladder for excretion into the amniotic sac has been severely compromised (in the cases of URA), or completely eliminated (in the cases of BRA). The decreased volume of amniotic fluid causes the growing fetus to become compressed by the mothers uterus. This compression can cause many physical deformities of the fetus, most common of which is Potter facies. Lower extremity anomalies are frequent in these cases, which often presents with clubbed feet and/or bowing of the legs..Sirenomelia, or "Mermaid syndrome" (which occurs approximately in 1:45,000 births) can also present. In fact, nearly all reported cases of sirenomelia also present with BRA.It is associated with childhood polycystic kidney disease which is autosomal recessive in origin Other anomalies of the classic Potter sequence infant include a parrot beak nose, redundant skin, and the most common characteristic of infants with BRA which is a skin fold of tissue extending from the medial canthus across the cheek. The ears are slightly low and pressed against the head making them appear large. The adrenal glands often appear as small oval discs pressed against the posterior abdomen due to the absence of upward renal pressure. The bladder is often small, nondistensible and may be filled with a minute amount of fluid. In males the vas deferens and seminal vesicles may be absent, while in females the uterus and upper vagina may be absent. Other abnormalities include anal atresia, absence of the rectum and sigmoid colon, esophageal and duodenal atresia, and a single umbilical artery. Presence of a diaphragmatic hernia is also common in these fetuses/infants. Additionally, the alveolar sacs of the lungs fail to properly develop as a result of the reduced volume of amniotic fluid. Labor is often induced between 22 and 36 weeks of gestation (however, some of these pregnancies may go to term) and unaborted infants typically survive for only a few minutes to a few hours. These infants will eventually die as either a result of pulmonary hypoplasia or renal failure. Causes The Potter sequence is due to restricted ability for certain organs to grow due to severe oligohydramnios. In one study, the causes leading to Potter sequence were bilateral renal agenesis in 21.25% of cases; cystic dysplasia in 47.5%; obstructive uropathy in 25%; and others in 5.25%. Bilateral renal agenesis Bilateral renal agenesis has been estimated to occur at a frequency of approximately 1:4000 to 1:8000 fetuses and neonates. However, recent analysis has estimated that the condition may occur at a much greater frequency. The condition has been reported to occur twice as commonly in males as in females, suggesting that certain genes of the Y chromosome may act as modifiers. However, no candidate genes on the Y chromosome have yet been identified.BRA appears to have a predominantly genetic etiology and many cases represent the most severe manifestation of an autosomal dominant condition with incomplete penetrance and variable expressivity. There are several genetic pathways that could result in this condition. In 2017 researchers identified heritable autosomal dominant mutations in the gene GREB1L in two unrelated families as being the cause of both BRA and URA utilizing Exome Sequencing and direct sequence analysis. This is the first reported genetic lesion implicated in the activation of Retinoic Acid Receptor (RAR) Targets that has been associated with renal agenesis in humans. The majority of other possible candidate genetic pathways are autosomal recessive in nature and do not coincide with the frequency or penetrance at which BRA typically occurs in the human population. Additionally, candidate genetic pathways would be expected to involve genes expressed in the developing urogenital system (UGS). Often, these same genes and/or pathways of interacting genes are also expressed in the developing UGS as well as the central nervous system (CNS), gut, lung, limbs, and eyes. Pathogenesis Development of the mature kidney begins between weeks 5 and 7 of gestation. Fetal urine production begins in early gestation and comprises the majority of the amniotic fluid in the second and third trimesters of pregnancy. The fetus continuously swallows amniotic fluid, which is reabsorbed by the gastrointestinal tract and then reintroduced into the amniotic cavity by the kidneys via urination. Oligohydramnios occurs if the volume of amniotic fluid is less than normal for the corresponding period of gestation. The fetal urine is critical to the proper development of the lungs by aiding in the expansion of the airways - alveoli, by means of hydrodynamic pressure and by also supplying proline which is a critical amino acid for lung development. Alveoli are the small sacs in the lungs that exchange oxygen with the blood. If the alveoli, and thereby the lungs, are underdeveloped at the time of birth the infant will not be able to breathe air properly and will go into respiratory distress shortly after birth due to pulmonary hypoplasia (underdeveloped lungs). This is the primary cause of death to Potter sequence infants secondary to renal failure. The fetal urine also serves to cushion the fetus from being compressed by the mothers uterus as it grows. Prognosis The outcome of Potters Sequence is poor. A series of 23 patients in 2007 recorded 7 deaths, 4 in the neonatal period. All 16 survivors have chronic kidney disease, with half developing end stage renal failure (median age 0.3 years, range 2 days to 8.3 years). Survivors had growth impairment (44%) and cognitive and motor development delay (25%)The first child to survive Bilateral Renal Agenesis (BRA), Abigail Rose Herrera Beutler, was born in July 2013 to US Congresswoman Jaime Herrera Beutler. A few weeks before she was born, Dr. Jessica Bienstock, a professor of maternal-fetal medicine at Johns Hopkins Hospital, administered a series of saline solution injections into the mothers womb to help the babys lungs to develop. After Abigail was born, the procedure was considered a success. The infant did not need artificial respiration and could breathe on her own. Her parents kept her on kidney dialysis at home until old enough for a kidney transplant. On February 8, 2016, at the age of two, Abigail received a kidney from her father at the Lucile Packard Childrens Hospital Stanford in California. History Bilateral renal agenesis (BRA) was first recognized as a defect of human fetal development in 1671 by Wolfstrigel.In 1946, Edith Potter (1901–1993) described a series of 20 cases with absent kidneys, noting the characteristic appearance of the head and lungs. Up until this time, the condition itself was considered to be extremely rare. However, in part to Potters work, it has come to light that the condition presents far more frequently than previously reported. Potter analyzed approximately 5000 autopsy cases performed on fetuses and newborn infants over a period of ten years and found that 20 of these infants presented with BRA, all of which had distinctive facial characteristics which did not appear to them to have any specific embryologic correlation with the renal anomaly. It was only much later when she and others attributed the multiple congenital deformities, including the features of Potters facies and also pulmonary hypoplasia, to have been caused by the prolonged severe lack of amniotic fluid. These facial characteristics have subsequently been termed as being known as Potter facies. From her analysis, she was able to deduce the sequence of events that leads to what is now known as Potter sequence.Potter went on to become a pioneer in the field of human renal development and her contributions are still employed and appreciated by clinicians and researchers to this day. Terminology Potter syndrome is not technically a syndrome as it does not collectively present with the same telltale characteristics and symptoms in each and every case. It is more accurately described as a "sequence" or chain of events that may have different beginnings (absent kidneys, cystic kidneys, obstructed ureters or other causes), but which all end with the same conclusion (absent or reduced volume of amniotic fluid). This is why Potter syndrome is often called Potter sequence or oligohydramnios sequence by some clinicians and researchers. The term Potter syndrome is most frequently associated with the condition of oligohydramnios sequence regardless of the root cause of the absence or reduced volume of amniotic fluid. However, as noted in this article, the term Potter syndrome was initially coined in order to refer to fetuses and infants with BRA. It was not until later that the term became more encompassing as it was noted that other causes of failed fetal urine production also resulted in similar physical characteristics and prognoses of the fetuses and infants with BRA (that which Potter originally described in 1946). Since then, the term Potter syndrome has become a misnomer and experts have attempted not to eliminate the terminology, but to modify it in a way so as to be able to determine the different root causes by creating a nomenclature system. However, this classification system has not caught on in the clinical and research fields. See also Kidney development References External links 00350 at CHORUS
Chemical pneumonitis	Chemical pneumonitis is inflammation of the lung caused by aspirating or inhaling irritants. It is sometimes called a "chemical pneumonia", though it is not infectious. There are two general types of chemical pneumonitis: acute and chronic. Irritants capable of causing chemical pneumonitis include vomitus, barium used in gastro-intestinal imaging, chlorine gas (among other pulmonary agents), ingested gasoline or other petroleum distillates, ingested or skin absorbed pesticides, gases from electroplating, smoke and others. It may also be caused by the use of inhalants. Mendelsons syndrome is a type of chemical pneumonitis. Mineral oil should not be given internally to young children, pets, or anyone with a cough, hiatal hernia, or nocturnal reflux, because it can cause complications such as lipoid pneumonia. Due to its low density, it is easily aspirated into the lungs, where it cannot be removed by the body. In children, if aspirated, the oil can work to prevent normal breathing, resulting in death of brain cells and permanent paralysis and/or brain damage. Signs and symptoms Acute: Cough Difficulty Breathing Abnormal lung sounds (wet or gurgling sounds when breathing) Chest pain, tightness or burning sensationChronic: Persistent cough Shortness of breath Increased susceptibility to respiratory illnessSymptoms of chronic chemical pneumonitis may or may not be present, and can take months or years to develop to the point of noticeability. Diagnosis The pragmatic challenge is to distinguish from aspiration pneumonia with an infectious component because the former does not require antibiotics while the latter does. While some issues, such as a recent history of exposure to substantive toxins, can foretell the diagnosis, for a patient with dyphagia the diagnosis may be less obvious, as the dyphagic patient may have caustic gastric contents damaging the lungs which may or may not have progressed to bacterial infection. The following tests help determine how severely the lungs are affected: Blood gases (measurement of how much oxygen and carbon dioxide are in your blood) CT scan of chest Lung function studies (tests to measure breathing and how well the lungs are functioning) X-ray of the chest Swallowing studies to check if stomach acid is the cause of pneumonitis Treatment Treatment is focused on reversing the cause of inflammation and reducing symptoms. Corticosteroids may be given to reduce inflammation, often before long-term scarring occurs. Antibiotics are usually not helpful or needed, unless there is a secondary infection. Oxygen therapy may be helpful. References == External links ==
Barotrauma	Barotrauma is physical damage to body tissues caused by a difference in pressure between a gas space inside, or in contact with, the body, and the surrounding gas or fluid. The initial damage is usually due to over-stretching the tissues in tension or shear, either directly by expansion of the gas in the closed space or by pressure difference hydrostatically transmitted through the tissue. Tissue rupture may be complicated by the introduction of gas into the local tissue or circulation through the initial trauma site, which can cause blockage of circulation at distant sites or interfere with normal function of an organ by its presence. Barotrauma generally manifests as sinus or middle ear effects, lung overpressure injuries and injuries resulting from external squeezes. Decompression sickness is indirectly caused by ambient pressure reduction, and the tissue damage is caused directly and indirectly by gas bubbles, but these bubbles form out of supersaturated solution from dissolved gases, and are not generally considered barotrauma. Decompression illness is a term which includes decompression sickness and arterial gas embolism caused by lung overexpansion barotrauma. It is also classified under the broader term of Dysbarism, which covers all medical conditions resulting from changes of ambient pressure.Barotrauma typically occurs when the organism is exposed to a significant change in ambient pressure, such as when a scuba diver, a free-diver or an airplane passenger ascends or descends or during uncontrolled decompression of a pressure vessel such as a diving chamber or pressurised aircraft, but can also be caused by a shock wave. Ventilator-induced lung injury (VILI) is a condition caused by over-expansion of the lungs by mechanical ventilation used when the body is unable to breathe for itself and is associated with relatively large tidal volumes and relatively high peak pressures. Barotrauma due to overexpansion of an internal gas-filled space may also be termed volutrauma. Bats can be killed by lung barotrauma when flying in low-pressure regions close to operating wind-turbine blades, and fish with sealed swim bladders experience barotrauma when pulled up from the depths. Presentation Examples of organs or tissues easily damaged by barotrauma are: Middle ear and inner ear (barotitis or aerotitis) Paranasal sinuses (causing aerosinusitis) Lungs Eyes (the under-pressure air space is inside the diving mask) Skin (when wearing a diving suit which creates an air space) Brain and cranium (temporal lobe injury secondary to temporal bone rupture) Teeth (causing barodontalgia, i.e., barometric pressure related dental pain, or dental fractures) Genital squeeze and associated urinary complications of P-valve use. Causes Any cause of sufficiently large and rapid environmental pressure change can potentially cause barotrauma. Several commonly recognised examples are listed below. Pressure differences while diving When diving, the pressure differences which cause the barotrauma are changes in hydrostatic pressure: There are two components to the surrounding pressure acting on the diver: the atmospheric pressure and the water pressure. A descent of 10 metres (33 feet) in water increases the ambient pressure by an amount approximately equal to the pressure of the atmosphere at sea level. So, a descent from the surface to 10 metres (33 feet) underwater results in a doubling of the pressure on the diver. This pressure change will reduce the volume of a flexible gas-filled space by half. Boyles law describes the relationship between the volume of the gas space and the pressure in the gas.Barotraumas of descent are caused by preventing the free change of volume of the gas in a closed space in contact with the diver, resulting in a pressure difference between the tissues and the gas space, and the unbalanced force due to this pressure difference causes deformation of the tissues resulting in cell rupture.Barotraumas of ascent are also caused when the free change of volume of the gas in a closed space in contact with the diver is prevented. In this case the pressure difference causes a resultant tension in the surrounding tissues which exceeds their tensile strength. Use of a hyperbaric chamber Patients undergoing hyperbaric oxygen therapy must equalize their ears to avoid barotrauma. High risk of otic barotrauma is associated with unconscious patients. Rapid decompression of a pressurised artificial environment Explosive decompression of a hyperbaric environment can produce severe barotrauma, followed by severe decompression bubble formation and other related injury. The Byford Dolphin incident is an example. Rapid uncontrolled decomression from caissons, airlocks, pressurised aircraft, spacecraft, and pressure suits can have similar effects of decompression barotrauma. Rapid pressurisation of an artificial environment Collapse of a pressure resistant structure such as a submarine, submersible, or atmospheric diving suit can cause rapid compression barotrauma. Rapid change of altitude A rapid change of altitude can cause barotrauma when internal air spaces cannot be equalised. Self inflicted barotrauma Excessively strenuous efforts to equalise the ears using the Valsalva manoeuvre can overpressurise the middle ear, and can cause middle ear and/or inner ear barotrauma. Blast-induced barotrauma An explosive blast and explosive decompression create a pressure wave that can induce barotrauma. The difference in pressure between internal organs and the outer surface of the body causes injuries to internal organs that contain gas, such as the lungs, gastrointestinal tract, and ear.Lung injuries can also occur during rapid decompression, although the risk of injury is lower than with explosive decompression. Ventilator-induced barotrauma Mechanical ventilation can lead to barotrauma of the lungs. This can be due to either: absolute pressures used in order to ventilate non-compliant lungs. shearing forces, particularly associated with rapid changes in gas velocity.The resultant alveolar rupture can lead to pneumothorax, pulmonary interstitial emphysema (PIE) and pneumomediastinum.Barotrauma is a recognised complication of mechanical ventilation that can occur in any patient receiving mechanical ventilation, but is most commonly associated with acute respiratory distress syndrome. It used to be the most common complication of mechanical ventilation but can usually be avoided by limiting tidal volume and plateau pressure to less than 30 to 50 cm water column (30 to 50 mb). As an indicator of transalveolar pressure, which predicts alveolar distention, plateau pressure or peak airway pressure (PAP) may be the most effective predictor of risk, but there is no generally accepted safe pressure at which there is no risk. Risk also appears to be increased by aspiration of stomach contents and pre-existing disease such as necrotising pneumonia and chronic lung disease. Status asthmaticus is a particular problem as it requires relatively high pressures to overcome bronchial obstruction.When lung tissues are damaged by alveolar over-distension, the injury may be termed volutrauma, but volume and transpulmonary pressure are closely related. Ventilator induced lung injury is often associated with high tidal volumes (Vt). Pathophysiology Lung overpressure injury A free-diver can dive and safely ascend without exhaling, because the gas in the lungs had been inhaled at atmospheric pressure, is compressed during the descent, and expands back to the original volume during ascent. A scuba or surface-supplied diver breathing gas at depth from underwater breathing apparatus fills their lungs with gas at a ambient pressure greater than atmospheric pressure. At 10 metres the lungs contain twice the amount of gas that they would contain at atmospheric pressure, and if they ascend without exhaling the gas will expand to match the decreasing pressure until the lungs reach their elastic limit, and begin to tear, and is very likely to sustain life-threatening lung damage. Besides tissue rupture, the overpressure may cause ingress of gases into the tissues through the ruptures, and further afield through the circulatory system. Pulmonary barotrauma (PBt) of ascent is also known as pulmonary over-inflation syndrome (POIS), lung over-pressure injury (LOP) and burst lung. Consequent injuries may include arterial gas embolism, pneumothorax, mediastinal, interstitial and subcutaneous emphysemas, depending on where the gas ends up, not usually all at the same time. Arterial gas embolism Gas in the arterial system can be carried to the blood vessels of the brain and other vital organs. It typically causes transient embolism similar to thromboembolism but of shorter duration. Where damage occurs to the endothelium inflammation develops and symptoms resembling stroke may follow. The bubbles are generally distributed and of various sizes, and usually affect several areas, resulting in an unpredictable variety of neurological deficits. Unconsciousness or other major changes to the state of consciousness within about 10 minutes of surfacing are generally assumed to be gas embolism until proven otherwise. The belief that the gas bubbles themselves formed static emboli which remain in place until recompression has been superseded by the knowledge that the gas emboli are normally transient, and the damage is due to inflammation following endothelial damage and secondary injury from inflammatory mediator upregulation.Hyperbaric oxygen can cause downregulation of the inflammatory response and resolution of oedema by causing hyperoxic arterial vasoconstriction of the supply to capillary beds. High concentration normobaric oxygen is appropriate as first aid but is not considered definitive treatment even when the symptoms appear to resolve. Relapses are common after discontinuing oxygen without recompression. Pneumothorax A pneumothorax is an abnormal collection of air in the pleural space between the lung and the chest wall. Symptoms typically include sudden onset of sharp, one-sided chest pain and shortness of breath. In a minority of cases, a one-way valve is formed by an area of damaged tissue, and the amount of air in the space between chest wall and lungs increases; this is called a tension pneumothorax. This can cause a steadily worsening oxygen shortage and low blood pressure. This leads to a type of shock called obstructive shock, which can be fatal unless reversed. Very rarely, both lungs may be affected by a pneumothorax. It is often called a "collapsed lung", although that term may also refer to atelectasis.Divers who breathe from an underwater apparatus are supplied with breathing gas at ambient pressure, which results in their lungs containing gas at higher than atmospheric pressure. Divers breathing compressed air (such as when scuba diving) may develop a pneumothorax as a result of barotrauma from ascending just 1 metre (3 ft) while breath-holding with their lungs fully inflated. An additional problem in these cases is that those with other features of decompression sickness are typically treated in a diving chamber with hyperbaric therapy; this can lead to a small pneumothorax rapidly enlarging and causing features of tension.Diagnosis of a pneumothorax by physical examination alone can be difficult (particularly in smaller pneumothoraces). A chest X-ray, computed tomography (CT) scan, or ultrasound is usually used to confirm its presence. Other conditions that can result in similar symptoms include a hemothorax (buildup of blood in the pleural space), pulmonary embolism, and heart attack. A large bulla may look similar on a chest X-ray. Pneumomediastinum Also known as mediastinal emphysema to divers, pneumomediastinum is a volume of gas inside the mediastinum, the central cavity in the chest between the lungs and surrounding the heart and central blood vessels, usually formed by gas escaping from the lungs as a result of lung rupture.Gas bubbles escaping from a ruptured lung can travel along the outside of bronchioles and blood vessels until they reach the mediastinal cavity round the heart, major blood vessels, oesophagus and trachea. Gas trapped in the mediastinum expands as the diver continues to rise. The pressure of the trapped gas may cause intense pain inside the rib cage and in the shoulders, and the gas may compress the respiratory passageways, making breathing difficult, and collapse blood vessels. Symptoms range from pain under the sternum, shock, shallow breathing, unconsciousness, respiratory failure, and associated cyanosis. The gas will usually be absorbed by the body over time, and when the symptoms are mild, no treatment may be necessary. Otherwise it may be vented through a hypodermic needle inserted into the mediastinum. Recompression is not usually indicated. Diagnosis Diagnosis of barotrauma generally involves a history of exposure to a source of pressure which could cause the injury suggested by the symptoms. This can vary from the immediately obvious if exposed to explosive blast, or mask squeeze, to rather complex discrimination between possibilities of inner ear decompression sickness and inner ear barotrauma, which may have nearly identical symptoms but different causative mechanism and mutually incompatible treatments. The detailed dive history may be necessary in these cases.In terms of barotrauma the diagnostic workup for the affected individual could include the following: Laboratory: Creatine kinase (CPK) level: Increases in CPK levels indicate tissue damage associated with decompression sickness. Complete blood count (CBC) Arterial blood gas (ABG) determinationImaging: Chest radiography can show pneumothorax, and is indicated if there is chest discomfort or breathing difficulty Computed tomography (CT) scans and magnetic resonance imaging (MRI) may be indicated when there is severe headache or severe back pain after diving. CT is the most sensitive method to evaluate for pneumothorax. It can be used where barotrauma-related pneumothorax is suspected and chest radiograph findings are negative. Echocardiography can be used to detect the number and size of gas bubbles in the right side of the heart. Ear barotrauma Barotrauma can affect the external, middle, or inner ear. Middle ear barotrauma (MEBT) is the most common diving injury, being experienced by between 10% and 30% of divers and is due to insufficient equilibration of the middle ear. External ear barotrauma may occur if air is trapped in the external auditory canal. Diagnosis of middle and external ear barotraume is relatively simple, as the damage is usually visible if severe enough to require intervention. External auditory canal Barotrauma can occur in the external auditory canal if it is blocked by cerumen, exostoses, a tight-fitting diving suit hood or earplugs, which create an airtight, air-filled space between the eardrum and the blockage. On descent, a preeure differential develops between the ambient water and the interior of this space, and this can cause swelling and haemorrhagic blistering of the canal. Treatment is usually analgesics and topical steroid eardrops. Complications may include local infection. This form of barotrauma is usually easily avoided. Middle ear Middle ear barotrauma (MEBT) is an injury caused by a difference in pressure between the external ear canal and the middle ear. It is common in underwater divers and usually occurs when the diver does not equalise sufficiently during descent or, less commonly, on ascent. Failure to equalise may be due to inexperience or eustachian tube dysfunction, which can have many possible causes. Unequalised ambient pressure increase during descent causes a pressure imbalance between the middle ear air space and the external auiditory canal over the eardrum, referred to by divers as ear squeeze, causing inward stretching, serous effusion and haemorrhage, and eventual rupture. During ascent internal over-pressure is normally passively released through the eustachian tube, but if this does not happen the volume expansion of middle ear gas will cause outward bulging, stretching and eventual rupture of the eardrum known to divers as reverse ear squeeze. This damage causes local pain and hearing loss. Tympanic rupture during a dive can allow water into the middle ear, which can cause severe vertigo from caloric stimulation. This may cause nausea and vomiting underwater, which has a high risk of aspiration of vomit or water, with possible fatal consequences. Inner ear Inner ear barotrauma (IEBt), though much less common than MEBT, shares a similar external cause. Mechanical trauma to the inner ear can lead to varying degrees of conductive and sensorineural hearing loss as well as vertigo. It is also common for conditions affecting the inner ear to result in auditory hypersensitivity. Two possible mechanisms are associated with forced Valsalva manoeuvre. In the one, the Eustachian tube opens in response to the pressure, and a sudden rush of high pressure air into the middle ear causes stapes footplate dislocation and inward rupture of the oval or round window. In the other, the tube remains closed and increased cerebrospinal fluit pressure is transmitted through the cochlea and causes outward rupture of the round window.Inner ear barotrauma can be difficult to distinguish from Inner ear decompression sickness. Both conditions manifest as cochleovestibular symptoms. The similarity of symptoms makes differential diagnosis difficult, which can delay appropriate treatment or lead to inappropriate treatment.Nitrogen narcosis, oxygen toxicity, hypercarbia, and hypoxia can cause disturbances in balance or vertigo, but these appear to be central nervous system effects, not directly related to effects on the vestibular organs. High-pressure nervous syndrome during heliox compression is also a central nervous system dysfunction. Inner ear injuries with lasting effects are usually due to round window ruptures, often associated with Valsalva maneuver or inadequate middle ear equalisation. Inner ear barotraume is often concurrent with middle ear barotrama as the external causes are generally the same. A variety of injuries may be present, which may include inner ear haemorrhage, intralabyrinthine membrane tear, perilymph fistula, and other pathologies.Divers who develop cochlear and/or vestibular symptoms during descent to any depth, or during shallow diving in which decompression sickness is unlikely, should be treated with bed rest with head elevation, and should avoid any activity which could cause raised cerebrospinal fluid and intralabyrinthine pressure. If there is no improvement in symptoms after 48 hours, exploratory tympanotomy may be considered to investigate possible repair of a labyrinthine window fistula. Recompression therapy is contraindicated in these cases, but is the definitive treatment for inner ear decompression sickness, making an early and accurate differential diagnosis important for deciding on appropriate treatment. IEBt in divers may be difficult to distinguish from inner ear decompression sickness (IEDCS), and as a dive profile alone cannot always eliminate either of the possibilities, the detailed dive history may be necessary to diagnose the more likely injury. It is also possible for both to occur at the same time, and IEDCS is more likely to affect the semicircular canals, causing severe vertigo, while IEBt is more likely to affect the cochlea, causing hearing loss, but these are just statistical probabilities, and in reality it can go either way or both. It is accepted practice to assume that if any symptom typical of DCS is present, that the diver has DCS and will be treated accordingly with recompression. Limited case data suggest that recompression does not usually cause harm if the differential diagnosis between IEBt vs IEDCS is doubtful. Barosinusitis The sinuses, like other air-filled cavities, are susceptible to barotrauma if their openings become obstructed. This can result in pain as well as epistaxis (nosebleed). Diagnosis is usually simple provided the history of pressure exposure is mentioned. Barosinusitis, is also called aerosinusitis, sinus squeeze or sinus barotrauma. Sinus barotrauma can be caused by external or internal overpressure. External over-pressure is called sinus squeeze by divers, while internal over-pressure is usually referred to as reverse block or reverse squeeze. Mask squeeze If a divers mask is not equalized during descent the relative negative internal pressure can produce petechial hemorrhages in the area covered by the mask along with subconjunctival hemorrhages. Helmet squeeze A problem mostly of historical interest, but still relevant to surface supplied divers who dive with the helmet sealed to the dry suit. If the air supply hose is ruptured near or above the surface, the pressure difference between the water around the diver and the air in the hose can be several bar. The non-return valve at the connection to the helmet will prevent backflow if it is working correctly, but if absent, as in the early days of helmet diving, or if it fails, the pressure difference will tend to squeeze the diver into the rigid helmet, which can result in severe trauma. The same effect can result from a large and rapid increase in depth if the air supply is insufficient to keep up with the increase in ambient pressure. On a helmet with a neck dam, the neck dam will allow water to flood the helmet before serious barotrauma can occur. This can happen with helium reclaim helmets if the reclaim regulator system fails, so there is a manual bypass valve, which allows the helmet to be purged so breathing can continue on open circuit. Pulmonary barotrauma Lung over-pressure injury in ambient pressure divers using underwater breathing apparatus is usually caused by breath-holding on ascent. The compressed gas in the lungs expands as the ambient pressure decreases causing the lungs to over-expand and rupture unless the diver allows the gas to escape by maintaining an open airway, as in normal breathing. The lungs do not sense pain when over-expanded giving the diver little warning to prevent the injury. This does not affect breath-hold divers as they bring a lungful of air with them from the surface, which merely re-expands safely to near its original volume on ascent. The problem only arises if a breath of ambient pressure gas is taken at depth, which may then expand on ascent to more than the lung volume. Pulmonary barotrauma may also be caused by explosive decompression of a pressurised aircraft, as occurred on 1 February 2003 to the crew in the Space Shuttle Columbia disaster. Prevention In divers Barotrauma may be caused when diving, either from being crushed, or squeezed, on descent or by stretching and bursting on ascent; both can be avoided by equalising the pressures. A negative, unbalanced pressure is known as a squeeze, crushing eardrums, dry suit, lungs or mask inwards and can be equalised by putting air into the squeezed space. A positive unbalanced pressure expands internal spaces rupturing tissue and can be equalised by letting air out, for example by exhaling. Both may cause barotrauma. There are a variety of techniques depending on the affected area and whether the pressure inequality is a squeeze or an expansion: Ears and sinuses: There is a risk of stretched or burst eardrums, usually crushed inwards during descent but sometimes stretched outwards on ascent. The diver can use a variety of methods to let air into or out of the middle ears via the Eustachian tubes. Sometimes swallowing will open the Eustachian tubes and equalise the ears. Lungs: There is a risk of pneumothorax, arterial gas embolism, and mediastinal and subcutaneous emphysema during ascent, which are commonly called burst lung or lung overpressure injury by divers. To equalise the lungs, all that is necessary is not to hold the breath during ascent. This risk does not occur when breath-hold diving from the surface, unless the diver breathes from an ambient pressure gas source underwater; breath-hold divers do suffer squeezed lungs on descent, crushing in the chest cavity, but, while uncomfortable, this rarely causes lung injury and returns to normal at the surface. Some people have pathology of the lung which prevent rapid flow of excess air through the passages, which can lead to lung barotrauma even if the breath is not held during rapid depressurisation. These people should not dive as the risk is unacceptably high. Most commercial or military diving medical examinations will look specifically for signs of this pathology. Diving mask squeeze enclosing the eyes and nose: The main risk is rupture of the capillaries of the eyes and facial skin because of the negative pressure difference between the gas space and blood pressure, or orbital emphysema from higher pressures. This can be avoided by breathing air into the mask through the nose. Goggles covering only the eyes are not suitable for deep diving as they cannot be equalised. Dry suit squeeze. The main risk is skin getting pinched and bruised by folds of the dry suit when squeezed on descent. Most dry suits can be equalised against squeeze via a manually operated valve fed from a low pressure gas supply. Air must be manually injected during the descent to avoid squeeze and is manually or automatically vented on the ascent to maintain buoyancy control. Diving helmet squeeze: Helmet squeeze will occur if the gas supply hose is severed above the diver and the non-return valve at the helmet gas inlet fails or is not fitted. Severity will depend on the hydrostatic pressure difference. A very rapid descent, usually by accident, may exceed the rate at which the breathing gas supply can equalise the pressure causing a temporary squeeze. The introduction of the non-return valve and high maximum gas supply flow rates have all but eliminated both these risks. In helmets fitted with a neck dam, the dam will admit water into the helmet if the internal pressure gets too low; this is less of a problem than helmet squeeze but the diver may drown if the gas supply is not reinstated quickly.: 90 This form of barotrauma is avoidable by controlled descent rate, which is standard practice for commercial divers, who will use shotlines, diving stages and wet bells to control descent and ascent rates. Medical screening Professional divers are screened for risk factors during initial and periodical medical examination for fitness to dive. In most cases recreational divers are not medically screened, but are required to provide a medical statement before acceptance for training in which the most common and easy to identify risk factors must be declared. If these factors are declared, the diver may be required to be examined by a medical practitioner, and may be disqualified from diving if the conditions indicate.Asthma, Marfan syndrome, and COPD pose a very high risk of pneumothorax. In some countries these may be considered absolute contraindications, while in others the severity may be taken into consideration. Asthmatics with a mild and well controlled condition may be permitted to dive under restricted circumstances. Training A significant part of entry level diver training is focused on understanding the risks and procedural avoidance of barotrauma. Professional divers and recreational divers with rescue training are trained in the basic skills of recognizing and first aid management of diving barotrauma. In mechanical ventilation Isolated mechanical forces may not adequately explain ventilator induced lung injury (VILI). The damage is affected by the interaction of these forces and the pre-existing state of the lung tissues, and dynamic changes in alveolar structure may be involved. Factors such as plateau pressure and positive end-expiratory pressure (PEEP) alone do not adequately predict injury. Cyclic deformation of lung tissue may play a large part in the cause of VILI, and contributory factors probably include tidal volume, positive end-expiratory pressure and respiratory rate. There is no protocol guaranteed to avoid all risk in all applications. Treatment Treatment of diving barotrauma depends on the symptoms, which depend on the affected tissues. Lung over-pressure injury may require a chest drain to remove air from the pleura or mediastinum. Recompression with hyperbaric oxygen therapy is the definitive treatment for arterial gas embolism, as the raised pressure reduces bubble size, the reduced blood inert gas concentration may accelerate inert gas solution, and high oxygen partial pressure helps oxygenate tissues compromised by the emboli. Care must be taken when recompressing to avoid a tension pneumothorax. Barotraumas that do not involve gas in the tissues are generally treated according to severity and symptoms for similar trauma from other causes. First aid Pre-hospital care for lung barotrauma includes basic life support of maintaining adequate oxygenation and perfusion, assessment of airway, breathing and circulation, neurological assessment, and managing any immediate life-threatening conditions. High-flow oxygen up to 100% is considered appropriate for diving accidents. Large-bore venous access with isotonic fluid infusion is recommended to maintain blood pressure and pulse. Emergency treatment Pulmonary barotrauma: Endotracheal intubation may be required if the airway is unstable or hypoxia persists when breathing 100% oxygen. Needle decompression or tube thoracostomy may be necessary to drain a pneumothorax or ha
Barotrauma	emothorax Foley catheterization may be necessary for spinal cord AGE if the person is unable to urinate. Intravenous hydration may be required to maintain adequate blood pressure. Therapeutic recompression is indicated for severe AGE. The diving medical practitioner will need to know the vital signs and relevant symptoms, along with the recent pressure exposure and breathing gas history of the patient. Air transport should be below 1,000 feet (300 m) if possible, or in a pressurized aircraft which should be pressurised to as low an altitude as reasonably possible.Sinus squeeze and middle ear squeeze are generally treated with decongestants to reduce the pressure differential, with anti-inflammatory medications to treat the pain. For severe pain, narcotic analgesics may be appropriate.Suit, helmet and mask squeeze are treated as trauma according to symptoms and severity. Medication The primary medications for lung barotrauma are hyperbaric and normobaric oxygen, hyperbaric heliox or nitrox, isotonic fluids, anti-inflammatory medications, decongestants, and analgesics. Outcomes Following barotrauma of the ears or lungs from diving the diver should not dive again until cleared by a diving doctor. After ear injury examination will include a hearing test and a demonstration that the middle ear can be autoinflated. Recovery can take weeks to months. Epidemiology An estimate of in the order of 1000 dive injuries per year occur in the United States and Canada. Many of these involve barotrauma, with nearly 50% of reported injuries involving middle ear barotrauma. Diving injuries tend to correlate with trait anxiety and a tendency to panic, lack of experience, advancing age and reduction in fitness, alcohol usage, obesity, asthma, chronic sinusitis and otitis. Barotrauma in other animals Whales and dolphins develop severely disabling barotrauma when exposed to excessive pressure changes induced by navy sonar, oil industry airguns, explosives, undersea earthquakes and volcanic eruptions.Injury and mortality of fish, marine mammals, including sea otters, seals, dolphins and whales, and birds by underwater explosions has been recorded in several studies. Bats can suffer fatal barotrauma in the low pressure zones behind the blades of wind turbines due to their more fragile mammalian lung structure in comparison with the more robust avian lungs, which are less affected by pressure change. Swim bladder overexpansion Fish with isolated swim bladders are susceptible to barotrauma of ascent when brought to the surface by fishing. The swim bladder is an organ of buoyancy control which is filled with gas extracted from solution in the blood, and which is normally removed by the reverse process. If the fish is brought upwards in the water column faster than the gas can be resorbed, the gas will expand until the bladder is stretched to its elastic limit, and may rupture. Barotrauma can be directly fatal or disable the fish rendering it vulnerable to predation, but rockfish are able to recover if they are returned to depths similar to those they were pulled up from, shortly after surfacing. Scientists at NOAA developed the Seaqualizer to quickly return rockfish to depth. The device could increase survival in caught-and-released rockfish. See also References == External links ==
Monoplegia	Monoplegia is paralysis of a single limb, usually an arm. Common symptoms associated with monoplegic patients are weakness, numbness, and pain in the affected limb. Monoplegia is a type of paralysis that falls under hemiplegia. While hemiplegia is paralysis of half of the body, monoplegia is localized to a single limb or to a specific region of the body. Monoplegia of the upper limb is sometimes referred to as brachial monoplegia, and that of the lower limb is called crural monoplegia. Monoplegia in the lower extremities is not as common of an occurrence as in the upper extremities. Monoparesis is a similar, but less severe, condition because one limb is very weak, not paralyzed. For more information, see paresis. Many conditions that cause paraplegia or quadriplegia begin as monoplegia. Thus, the diagnosis of spinal paraplegia must also be consulted. In addition, multiple cerebral disorders that cause hemiplegia may begin as monoplegia. Monoplegia is also frequently associated with, and considered to be the mildest form of, cerebral palsy. Signs and symptoms There are a number of symptoms associated with monoplegia. Curling of the hands or stiffness of the feet, weakness, spasticity, numbness, paralysis, pain in the affected limb, headaches, and shoulder pain are all considered to be symptoms of monoplegia. Patients of monoplegia typically feel symptoms of weakness and loss of sensation in the affected extremity, usually an arm. Despite these symptoms, the extremity with paralysis continues to maintain a strong pulse. While chronic progressive brachial monoplegia is uncommon, syringomyelia and tumors of the cervical cord or brachial plexus may be the cause. The onset of brachial plexus paralysis is usually explosive where pain is the initial feature. Pain localizes to the shoulder but may be more diffuse, or could be limited to the lower arm. Pain is severe and often described as sharp, stabbing, throbbing, or aching. The duration of pain, which is constant, varies from a span of several hours to 3 weeks. As the pain subsides, weakness usually appears. In addition, chronicle progressive weakness of one leg suggests a tumor of the spinal cord of the lumbar plexus. Fever is often the first symptom of lumbar plexus paralysis, followed by pain in one or both legs. The pain has an abrupt onset and may occur in a femoral or sciatic distribution. Weakness may develop concurrently with pain or be delayed for as long as 3 weeks. Furthermore, a monomeric form of spinal muscular atrophy, affecting only one leg or arm, should be considered when progressive weakness is not accompanied by sensory loss. Causes Some potential causes of monoplegia are listed below. Cerebral palsy Direct physical trauma to the affected limb Central nervous mass lesion, including tumor, hematoma, or abscess Complicated migraine Epilepsy Head or spinal trauma Hereditary brachial neuritis Hereditary neuropathy with liability to pressure palsy Neonatal brachial plexus paralysis Neuropathy Plexopathy Traumatic peroneal neuropathy Vaccine-associated paralytic poliomyelitis Hemiparetic seizures Monomeric spinal muscular atrophy StrokeSpecifically, monoplegia in the lower extremities is typically caused by Brown Sequard syndrome and hematomas in the frontoparietal cortex near the middle that could produce a deficit such as this, but this is a very uncommon occurrence. Mechanism In monoplegia, the spine and the proximal portion of nerves are usually the abnormal sites of limb weakness. Monoplegia resulting from upper extremity impairments following a stroke occurs due to direct damage to the primary motor cortex, primary somatosensory cortex, secondary sensorimotor cortex, sensorimotor cortical areas, subcortical structures, and/or the corticospinal tract. It is often found that impairments following stroke are either caused by damage to the same or adjacent neurological structures. A combination of these impairments is more likely than just one in isolation. Damage to the corticospinal system results in an inability to activate muscles with enough force or in a coordinated manner, which can lead to paresis, loss of fractional movement, and abnormal muscle tone. Damage to the somatosensory cortical areas causes loss of somatosensation which results in an impaired ability to monitor movement.Considering monoplegia as it relates to cerebral palsy, in premature infants, the most common cause of cerebral palsy is periventricular hemorrhagic infarction. In term infants, the underlying causes are often cerebral malformations, cerebral infarction, and intracerebral hemorrhage. Delayed crawling or walking are the usual concerns that arise in infants with paralysis of the limb. In these cases, abnormalities of the legs are the main focus of the attention. Diagnosis Monoplegia is diagnosed by a physician after a physical examination and sometimes after further neurologic examination as well. As monoplegia is fairly rare, after physical examination of a patient complaining of monoplegia, sometimes weakness of an additional limb is also identified and the patient is diagnosed with hemiplegia or paraplegia instead. After neurologic examination of the limb, a diagnosis of a monoplegic limb can be given if the patient receives a Medical Research Council power grade of 0, which is a measurement of the patients limb strength. Needle Electromyography is often used to study all limbs, essentially showing the extent in each limb involvement. Furthermore, magnetic resonance imaging (MRI) is the diagnostic modality of choice for investigating all forms of hemiplegia. It is especially informative to show migrational defects in hemiplegic cerebral palsy associated with seizures.An approach called single-pulse transcranial magnetic stimulation (spTMS) has also been used to help diagnose motor deficits such as monoplegia. This is done by evaluating the functional level of the corticospinal tract through stimulation of the corticospinal lesions in order to obtain neurophysiologic evidence on the integrity of the corticospinal tracts. Single-pulse transcranial magnetic stimulation provides neuropsychological feedback such as motor-evoked potentials (MEPs) and central motor conduction time (CMCT). This feedback can then be compared to the normal limits of patients who do not show evidence of deficits in the corticospinal tracts. Treatment There is no cure for monoplegia, but treatments typically include physical therapy and counseling to help recover muscle tone and function. Recovery will vary depending on diagnosis of temporary, partial or complete paralysis. Much of the therapies focus on the upper limb due to the fact that monoplegia in the upper limbs is much more common than in the lower limbs. It has been found that intense activity-based and goal-directed therapy, such as constraint-induced movement therapy and bimanual therapy, are more effective than standard care. Studies suggest the less affected hand could provide a template for improving motor performance of the more affected hand, and provides a strong rationale for the development of bimanual training approaches. In addition to that, there is strong evidence to support that occupational therapy home programs that are goal-directed could be used to supplement hands-on direct therapy.Constraint-induced movement therapy (CIMT) is specifically targeted at upper limb monoplegia as a result of a stroke. In CIMT the unaffected arm is restrained, forcing the use and frequent practice of the affected arm. This approach to therapy is carried out during ordinary and daily activities by the affected person. It has been found that CIMT is more effective at specifically improving arm movement than a physiotherapy approach or no treatment at all. This type of therapy has proved to provide an only moderate improvement in patients with monoplegia. More research needs to be conducted in order to establish the lasting benefit of constraint-induced movement therapy. Brain computer interface (BCI) systems have been proposed as a tool for rehabilitation of monoplegia, specifically in the upper limb after a stroke. BCI systems provide sensory feedback in the brain via functional electrical stimulation, virtual reality environments, or robotic systems, which allows for the use of brain signals. This is extremely crucial because the networking in the brain is often compromised after a stroke, leading to impaired movement or paralysis. BCI systems allow for detection of intention to move through the primary motor cortex, then provide the matched sensory stimulation according to feedback that is provided. This leads to activity-dependent plasticity within the user, requiring them to pay careful attention to tasks that require the activation or deactivation of specific brain areas. BCI systems utilize different sources of information for feedback, including electroencephalography (EEG), magnetoencephalography, functional magnetic resonance imaging, near-infrared spectroscopy, or electrocorticography. Among all of these, the EEG signals are the most useful for this type of rehabilitation because they are highly accurate and stable.Another form of treatment for monoplegia is functional electrical stimulation (FES). It is targeted at patients who acquired monoplegia through incidents such as a spinal cord injury, stroke, multiple sclerosis, or cerebral palsy and utilizes electrical stimulation in order to cause the remaining motor units in the paralyzed muscles to contract. As in traditional muscular training, FES improves the force with which the unaffected muscles contract. For less severely affected patients, FES allows for greater improvement in range of motion than traditional physical therapy. References == External links ==
Rh deficiency syndrome	Rh deficiency syndrome is a type of hemolytic anemia that involves erythrocytes whom membranes are deficient in Rh antigens. It is considered a rare condition. See also List of hematologic conditions RHAG References == External links ==
Familial hypertriglyceridemia	Familial hypertriglyceridemia (type IV familial dyslipidemia) is a genetic disorder characterized by the liver overproducing very-low-density lipoproteins (VLDL). As a result, an affected individual will have an excessive number of VLDL and triglycerides on a lipid profile. This genetic disorder usually follows an autosomal dominant inheritance pattern. The disorder presents clinically in patients with mild to moderate elevations in triglyceride levels. Familial hypertriglyceridemia is typically associated with other co-morbid conditions such as hypertension, obesity, and hyperglycemia. Individuals with the disorder are mostly heterozygous in an inactivating mutation of the gene encoding for lipoprotein lipase (LPL). This sole mutation can markedly elevate serum triglyceride levels. However, when combined with other medications or pathologies it can further elevate serum triglyceride levels to pathologic levels. Substantial increases in serum triglyceride levels can lead to certain clinical signs and the development of acute pancreatitis. Familial hypertriglyceridemia falls in the Fredrickson-Levy and Lees (FLL) phenotypes. The phenotypes include types I, IIa, IIb, III, IV, and V dyslipidemias. Familial hypertriglyceridemia is considered a type IV familial dyslipidemia it is distinguished from other dyslipidemias based on the individuals lipid profile. Familial hypertriglyceridemia separates itself from other dyslipidemias with significantly high triglycerides and low HDL levels. It is important to recognize that co-morbid conditions that often concomitantly exist with the disorder can further alter the lipid panel. Etiology Familial hypertriglyceridemia is considered to be inherited in an autosomal dominant manner. However, it is important to recognize that most cases have a polygenic inheritance distancing themselves from traditional Mendelian inheritance patterns. One of the most common mutations implicated in the development of familial hypertriglyceridemia is a heterozygous inactivating mutation of the LPL gene. Inactivation of this gene leads to an individuals inability to hydrolyze the triglycerides within the VLDL core. This inactivation of function leads to a considerable accumulation of triglycerides and VLDL in the bloodstream, which then contributes to several avenues of pathology. Individuals with insulin resistance can have even further elevated levels of hypertriglyceridemia due to the fact that insulin is a potent activator of LPL. Therefore, an individual who is resistant to the bioactivity of insulin will have decreased LPL activity and will therefore lead to further hypertriglyceridemia, helping push serum triglycerides to pathologic levels. Beyond the classic understanding of single-gene mutation leading to disease, hypertriglyceridemia is also linked to several different genetic loci permitting additional aberrant changes to other lipid levels in the body. Epidemiology Familial hypertriglyceridemia can follow an autosomal dominant monogenic inheritance pattern. The frequency of heterozygous carriers of certain pathologic mutations in the LPL gene can range from 0.06% to 20%. It is important to note that dissimilar mutations can confer varying degrees of underlying pathology. However, most cases of familial hypertriglyceridemia follow a polygenic inheritance pattern involving mutations in multiple genetic foci. Pathophysiology Inactivity of lipoprotein lipase (LPL) plays the predominant role in the development of familial hypertriglyceridemia. LPL plays a role in the metabolism of triglycerides within VLDL molecules. Inactivation mutations in LPL will create an environment with an increased concentration of VLDL molecules and therefore, triglycerides. The elevation of baseline triglyceride levels begins the cascade into other pathologies.The most common acute manifestation of hypertriglyceridemia is the occurrence of pancreatitis. Pancreatitis is caused by the premature activation of exocrine pancreatic enzymes. Secreted zymogens are cleaved to active trypsin and play a central role in digestion of food in the duodenum. If there is premature activation of trypsin within the pancreatic tissues, there is an induction of autodigestion of local tissue which leads to the initial presentation of pancreatitis. Autodigestion of local tissues also leads to disruptions in pancreatic microvascular tissue which can cause an ischemia-reperfusion event at the pancreatic level. There are other varying secondary causes of pancreatitis that can further contribute to the primary scenario of pancreatitis related to familial hypertriglyceridemia. Treatment Treatment for familial hypertriglyceridemia should focus primarily on reducing serum triglyceride levels. If an individual has co-morbid conditions, ensuring that they are adequately addressed will aid in obtaining a more normal baseline lipid panel. Current guidelines suggest that when evaluating individuals with familial hypertriglyceridemia there should be special attention paid to their risk of developing cardiovascular disease in individuals with mild to moderate hypertriglyceridemia. Individuals with severe hypertriglyceridemia should be promptly evaluated for the possibility of developing pancreatitis. The initial treatment for severe hypertriglyceridemia consists of beginning an individual on fibrate therapy in an attempt to normalize triglyceride levels. Fibrates such as fenofibrate or gemfibrozil are considered first-line therapy for the disease. Adjunctive niacin therapy can be used for individuals who are unable to decrease triglyceride levels through fibrate monotherapy. Niacin is especially useful for individuals who have a high risk of getting pancreatitis. Fish oil supplement can also be used as it has been shown to incur a significant reduction to both triglyceride and VLDL levels. If properly managed, individuals with familial hypertriglyceridemia have a fairly good prognosis. If therapy is successful, these individuals do not have uncontrolled severe triglycerides and VLDL. It is important to educate individuals on possible secondary causes of elevated lipid profiles. Proper management of the secondary causes provides a good prognosis for overall individual health. See also Primary hyperlipoproteinemia Familial apoprotein CII deficiency Skin lesion References == External links ==
Local anesthetic	A local anesthetic (LA) is a medication that causes absence of pain sensation. In the context of surgery, a local anesthetic creates an absence of pain in a specific location of the body without a loss of consciousness, as opposed to a general anesthetic. When it is used on specific nerve pathways (local anesthetic nerve block), paralysis (loss of muscle power) also can be achieved. Examples Short Duration & Low Potency Procaine Chloroprocaine Medium Duration & Potency Lidocaine Prilocaine High Duration & Potency Tetracaine Bupivacaine Cinchocaine Ropivacaine Clinical LAs belong to one of two classes: aminoamide and aminoester local anesthetics. Synthetic LAs are structurally related to cocaine. They differ from cocaine mainly in that they have a very low abuse potential and do not produce hypertension or (with few exceptions) vasoconstriction. They are used in various techniques of local anesthesia such as: Topical anesthesia (surface) Topical administration of cream, gel, ointment, liquid, or spray of anaesthetic dissolved in DMSO or other solvents/carriers for deeper absorption Infiltration Brachial plexus block Epidural (extradural) block Spinal anesthesia (subarachnoid block) IontophoresisThe suffix "-caine" at the ends of these medication names was extracted from the word "cocaine", because cocaine was formerly used as a local anesthetic. Medical uses Acute pain Acute pain may occur due to trauma, surgery, infection, disruption of blood circulation, or many other conditions in which tissue injury occurs. In a medical setting, pain alleviation is desired when its warning function is no longer needed. Besides improving patient comfort, pain therapy can also reduce harmful physiological consequences of untreated pain.Acute pain can often be managed using analgesics. However, conduction anesthesia may be preferable because of superior pain control and fewer side effects. For purposes of pain therapy, LA drugs are often given by repeated injection or continuous infusion through a catheter. LA drugs are also often combined with other agents such as opioids for synergistic analgesic action. Low doses of LA drugs can be sufficient so that muscle weakness does not occur and patients may be mobilized.Some typical uses of conduction anesthesia for acute pain are: Labor pain (epidural anesthesia, pudendal nerve blocks) Postoperative pain (peripheral nerve blocks, epidural anesthesia) Trauma (peripheral nerve blocks, intravenous regional anesthesia, epidural anesthesia) Chronic pain Chronic pain is a complex and often serious condition that requires diagnosis and treatment by an expert in pain medicine. LAs can be applied repeatedly or continuously for prolonged periods to relieve chronic pain, usually in combination with medication such as opioids, NSAIDs, and anticonvulsants. Though it can be easily performed, repeated local anaesthetic blocks in chronic pain conditions are not recommended as there is no evidence of long-term benefits. Surgery Virtually every part of the body can be anesthetized using conduction anesthesia. However, only a limited number of techniques are in common clinical use. Sometimes, conduction anesthesia is combined with general anesthesia or sedation for the patients comfort and ease of surgery. However, many anaesthetists, surgeons, patients and nurses believe that it is safer to perform major surgeries under local anesthesia than general anesthesia. Typical operations performed under conduction anesthesia include: Dentistry (surface anesthesia, infiltration anesthesia or intraligamentary anesthesia during restorative operations such as fillings, crowns, and root canals, or extractions, and regional nerve blocks during extractions and surgeries) Podiatry (cutaneous, nail avulsions, matricectomy, bunionectomy, hammertoe repair and various other podiatric procedures) Eye surgery (surface anesthesia with topical anesthetics or retrobulbar block during cataract removal or other ophthalmic procedures) ENT operations, head and neck surgery (infiltration anesthesia, field blocks, or peripheral nerve blocks, plexus anesthesia) Shoulder and arm surgery (plexus anesthesia or intravenous regional anesthesia) Heart and lung surgery (epidural anesthesia combined with general anesthesia) Abdominal surgery (epidural anesthesia/spinal anesthesia, often combined with general anesthesia during inguinal hernia repair or other abdominal surgery ) Gynecological, obstetrical, and urological operations (spinal/epidural anesthesia) Bone and joint surgery of the pelvis, hip, and leg (spinal/epidural anesthesia, peripheral nerve blocks, or intravenous regional anesthesia) Surgery of skin and peripheral blood vessels (topical anesthesia, field blocks, peripheral nerve blocks, or spinal/epidural anesthesia) Diagnostic tests Diagnostic tests such as bone marrow aspiration, lumbar puncture (spinal tap) and aspiration of cysts or other structures are made to be less painful upon administration of local anesthetic before insertion of larger needles. Other uses Local anesthesia is also used during insertion of IV devices, such as pacemakers and implantable defibrillators, ports used for giving chemotherapy medications and hemodialysis access catheters.Topical anesthesia, in the form of lidocaine/prilocaine (EMLA) is most commonly used to enable relatively painless venipuncture (blood collection) and placement of intravenous cannulae. It may also be suitable for other kinds of punctures such as ascites drainage and amniocentesis. Surface anesthesia also facilitates some endoscopic procedures such as bronchoscopy (visualization of the lower airways) or cystoscopy (visualization of the inner surface of the bladder) Side effects Localized side effects Edema of tongue, pharynx and larynx may develop as a side effect of local anaesthesia. This could be caused by a variety of reasons including trauma during injection, infection, an allergic reaction, haematoma or injection of irritating solutions such as cold-sterilisation solutions. Usually there is tissue swelling at the point of injection. This is due to puncturing of the vein which allows the blood to flow into loose tissues in the surrounding area. Blanching of the tissues in the area where the local anaesthetic is deposited is also common. This gives the area a white appearance as the blood flow is prevented due to vasoconstriction of arteries in the area. The vasoconstriction stimulus gradually wears off and subsequently the tissue returns to normal in less than 2 hours.The side effects of inferior alveolar nerve block include feeling tense, clenching of the fists and moaning.The duration of soft tissue anaesthesia is longer than pulpal anaesthesia and is often associated with difficulty eating, drinking and speaking. Risks The risk of temporary or permanent nerve damage varies between different locations and types of nerve blocks.There is risk of accidental damage to local blood vessels during injection of the local anaesthetic solution. This is referred to as Haematoma and could result in pain, trismus, swelling and/or discolouration of the region. The density of tissues surrounding the injured vessels is an important factor for Haematoma. There is greatest chance of this occurring in a posterior superior alveolar nerve block or in a pterygomandibular block.Giving local anaesthesia to patients with liver disease can have significant consequences. Thorough evaluation of the disease should be carried out to assess potential risk to the patient as in significant liver dysfunction, the half-life of amide local anaesthetic agents may be drastically increased thus increasing the risk of overdose. Local anaesthetics and vasoconstrictors may be administered to pregnant patients however it is very important to be extra cautious when giving a pregnant patient any type of drug. Lidocaine can be safely used but bupivacaine and mepivacaine should be avoided. Consultation with the obstetrician is vital before administrating any type of local anaesthetic to a pregnant patient. Recovery Permanent nerve damage after a peripheral nerve block is rare. Symptoms are likely to resolve within a few weeks. The vast majority of those affected (92%–97%) recover within four to six weeks; 99% of these people have recovered within a year. An estimated one in 5,000 to 30,000 nerve blocks results in some degree of permanent persistent nerve damage.Symptoms may continue to improve for up to 18 months following injury. Potential side effects General systemic adverse effects are due to the pharmacological effects of the anesthetic agents used. The conduction of electric impulses follows a similar mechanism in peripheral nerves, the central nervous system, and the heart. The effects of local anesthetics are, therefore, not specific for the signal conduction in peripheral nerves. Side effects on the central nervous system and the heart may be severe and potentially fatal. However, toxicity usually occurs only at plasma levels which are rarely reached if proper anesthetic techniques are adhered to. High plasma levels might arise, for example, when doses intended for epidural or intrasupport tissue administration are accidentally delivered as intravascular injection. Emotional reactions When patients are emotionally affected in the form of nervousness or fear, it can lead to vasovagal collapse. This is the anticipation of pain during administration that activates the parasympathetic nervous system while inhibiting the orthosympathetic nervous system. What results is a dilation of arteries in muscles which can lead to a reduction in circulating blood volume inducing a temporary shortness of blood flow to the brain. Notable symptoms include restlessness, visibly looking pale, perspiration and possible loss of consciousness. In severe cases, clonic cramps resembling an epileptic insult may occur.On the other hand, fear of administration can also result in accelerated, shallow breathing, or hyperventilation. The patient may feel a tingling sensation in hands and feet or a sense of light-headedness and increased chest pressure.Hence, it is crucial for the medical professional administrating the local anaesthesia, especially in the form of an injection, to ensure that the patient is in a comfortable setting and has any potential fears alleviated in order to avoid these possible complications. Central nervous system Depending on local tissue concentrations of local anesthetics, excitatory or depressant effects on the central nervous system may occur. Initial symptoms of systemic toxicity include ringing in the ears (tinnitus), a metallic taste in the mouth, tingling or numbness of the mouth, dizziness and/or disorientation. At higher concentrations, a relatively selective depression of inhibitory neurons results in cerebral excitation, which may lead to more advanced symptoms include motor twitching in the periphery followed by grand mal seizures. It is reported that seizures are more likely to occur when bupivacaine is used, particularly in combination with chloroprocaine.A profound depression of brain functions may occur at even higher concentrations which may lead to coma, respiratory arrest, and death. Such tissue concentrations may be due to very high plasma levels after intravenous injection of a large dose. Another possibility is direct exposure of the central nervous system through the cerebrospinal fluid, i.e., overdose in spinal anesthesia or accidental injection into the subarachnoid space in epidural anesthesia. Cardiovascular system Cardiac toxicity can result from improper injection of agent into a vessel. Even with proper administration, it is inevitable for some diffusion of agent into the body from the site of application due to unforeseeable anatomical idiosyncrasies of the patient. This may affect the nervous system or cause the agent to enter into general circulation. However, infections are very seldom transmitted. Cardiac toxicity associated with overdose of intravascular injection of local anesthetic is characterized by hypotension, atrioventricular conduction delay, idioventricular rhythms, and eventual cardiovascular collapse. Although all local anesthetics potentially shorten the myocardial refractory period, bupivacaine blocks the cardiac sodium channels, thereby making it most likely to precipitate malignant arrhythmias. Even levobupivacaine and ropivacaine (single-enantiomer derivatives), developed to ameliorate cardiovascular side effects, still harbor the potential to disrupt cardiac function. Toxicity from anesthetic combinations is additive. Endocrine Endocrine and metabolic systems only have slightly adverse effects with most cases being without clinical repercussions. Immunologic allergy Adverse reactions to local anesthetics (especially the esters) are not uncommon, but legitimate allergies are very rare. Allergic reactions to the esters is usually due to a sensitivity to their metabolite, para-aminobenzoic acid, and does not result in cross-allergy to amides. Therefore, amides can be used as alternatives in those patients. Nonallergic reactions may resemble allergy in their manifestations. In some cases, skin tests and provocative challenge may be necessary to establish a diagnosis of allergy. Also cases of allergy to paraben derivatives occur, which are often added as preservatives to local anesthetic solutions. Methemoglobinemia Methemoglobinemia is a process where iron in hemoglobin is altered, reducing its oxygen-carrying capability, which produces cyanosis and symptoms of hypoxia. Exposure to aniline group chemicals such as benzocaine, lidocaine, and prilocaine can produce this effect, especially benzocaine. The systemic toxicity of prilocaine is comparatively low, but its metabolite, o-toluidine, is known to cause methemoglobinemia. Second-generation effects Application of local anesthetics during oocyte removal during in vitro fertilisation has been up to debate. Pharmacological concentrations of anesthetic agents have been found in follicular fluid. Clinical trials have not concluded any effects on pregnant women. However, there is some concern with the behavioral effects of lidocaine on offspring in rats.During pregnancy, it is not common for local anesthetics to have any adverse effect on the fetus. Despite this, risks of toxicity may be higher in pregnancy due to an increase in unbound fraction of local anesthetic and physiological changes increase the transfer of local anesthetic into the central nervous system. Hence, it is recommended that pregnant women use a lower dose of local anesthetic to reduce any potential complications. Treatment of overdose: "Lipid rescue" This method of toxicity treatment was invented by Dr. Guy Weinberg in 1998, and was not widely used until after the first published successful rescue in 2006. Evidence indicates Intralipid, a commonly available intravenous lipid emulsion, can be effective in treating severe cardiotoxicity secondary to local anesthetic overdose, including human case reports of successful use in this way (lipid rescue). However, the evidence at this point is still limited.Though most reports to date have used Intralipid, a commonly available intravenous lipid emulsion, other emulsions, such as Liposyn and Medialipid, have also been shown effective. Ample supporting animal evidence and human case reports show successful use in this way. In the UK, efforts have been made to publicise this use more widely and lipid rescue has now been officially promoted as a treatment by the Association of Anaesthetists of Great Britain and Ireland. One published case has been reported of successful treatment of refractory cardiac arrest in bupropion and lamotrigine overdose using lipid emulsion.The design of a homemade lipid rescue kit has been described.Although lipid rescue mechanism of action is not completely understood, the added lipid in the blood stream may act as a sink, allowing for the removal of lipophilic toxins from affected tissues. This theory is compatible with two studies on lipid rescue for clomipramine toxicity in rabbits and with a clinical report on the use of lipid rescue in veterinary medicine to treat a puppy with moxidectin toxicosis. Mechanism of action All LAs are membrane-stabilizing drugs; they reversibly decrease the rate of depolarization and repolarization of excitable membranes (like nociceptors). Though many other drugs also have membrane-stabilizing properties, not all are used as LAs (propranolol, for example, though it has LA properties). LA drugs act mainly by inhibiting sodium influx through sodium-specific ion channels in the neuronal cell membrane, in particular the so-called voltage-gated sodium channels. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is inhibited. The receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium channel. Local anesthetic drugs bind more readily to sodium channels in an activated state, thus onset of neuronal blockade is faster in rapidly firing neurons. This is referred to as state-dependent blockade. LAs are weak bases and are usually formulated as the hydrochloride salt to render them water-soluble. At a pH equal to the protonated bases pKa, the protonated (ionized) and unprotonated (unionized) forms of the molecule exist in equimolar amounts, but only the unprotonated base diffuses readily across cell membranes. Once inside the cell, the local anesthetic will be in equilibrium, with the formation of the protonated (ionized) form, which does not readily pass back out of the cell. This is referred to as "ion-trapping". In the protonated form, the molecule binds to the LA binding site on the inside of the ion channel near the cytoplasmic end. Most LAs work on the internal surface of the membrane - the drug has to penetrate the cell membrane, which is achieved best in the nonionised form. This is exemplified by the permanently ionised LA RAC 421-II which cannot diffuse across the cell membrane but, if injected into the cytosol of a nerve fibre, can induce NaKATPase blockage and anaesthetic effects. Acidosis such as caused by inflammation at a wound partly reduces the action of LAs. This is partly because most of the anesthetic is ionized and therefore unable to cross the cell membrane to reach its cytoplasmic-facing site of action on the sodium channel. All nerve fibers are sensitive to LAs, but due to a combination of diameter and myelination, fibers have different sensitivities to LA blockade, termed differential blockade. Type B fibers (sympathetic tone) are the most sensitive followed by type C (pain), type A delta (temperature), type A gamma (proprioception), type A beta (sensory touch and pressure), and type A alpha (motor). Although type B fibers are thicker than type C fibers, they are myelinated, thus are blocked before the unmyelinated, thin C fiber. Techniques Local anesthetics can block almost every nerve between the peripheral nerve endings and the central nervous system. The most peripheral technique is topical anesthesia to the skin or other body surface. Small and large peripheral nerves can be anesthetized individually (peripheral nerve block) or in anatomic nerve bundles (plexus anesthesia). Spinal anesthesia and epidural anesthesia merge into the central nervous system. Injection of LAs is often painful. A number of methods can be used to decrease this pain, including buffering of the solution with bicarbonate and warming.Clinical techniques include: Surface anesthesia is the application of an LA spray, solution, or cream to the skin or a mucous membrane; the effect is short lasting and is limited to the area of contact. Infiltration anesthesia is infiltration of LA into the tissue to be anesthetized; surface and infiltration anesthesia are collectively topical anesthesia Field block is subcutaneous injection of an LA in an area bordering on the field to be anesthetized. Peripheral nerve block is injection of LA in the vicinity of a peripheral nerve to anesthetize that nerves area of innervation. Plexus anesthesia is injection of LA in the vicinity of a nerve plexus, often inside a tissue compartment that limits the diffusion of the drug away from the intended site of action. The anesthetic effect extends to the innervation areas of several or all nerves stemming from the plexus. Epidural anesthesia is an LA injected into the epidural space, where it acts primarily on the spinal nerve roots; depending on the site of injection and the volume injected, the anesthetized area varies from limited areas of the abdomen or chest to large regions of the body. Spinal anesthesia is an LA injected into the cerebrospinal fluid, usually at the lumbar spine (in the lower back), where it acts on spinal nerve roots and part of the spinal cord; the resulting anesthesia usually extends from the legs to the abdomen or chest. Intravenous regional anesthesia (Biers block) is when blood circulation of a limb is interrupted using a tourniquet (a device similar to a blood-pressure cuff), then a large volume of LA is injected into a peripheral vein. The drug fills the limbs venous system and diffuses into tissues, where peripheral nerves and nerve endings are anesthetized. The anesthetic effect is limited to the area that is excluded from blood circulation and resolves quickly once circulation is restored. Local anesthesia of body cavities includes intrapleural anesthesia and intra-articular anesthesia. Transincision (or transwound) catheter anesthesia uses a multilumen catheter inserted through an incision or wound and aligned across it on the inside as the incision or wound is closed, providing continuous administration of local anesthetic along the incision or woundsDental-specific techniques include: Vazirani-Alkinosi Technique The Vazirani-alkinosi technique is also known as the closed-mouth mandibular nerve block. It is mostly used in patients who have limited opening of the mandible or in those that have trismus; spasm of the muscles of mastication. The nerves which are anesthetised in this technique are the inferior alveolar, incisive, mental, lingual and mylohyoid nerves. Dental needles are available in 2 lengths; short and long. As Vazirani-akinosi is a local anaesthetic technique which requires penetration of a significant thickness of soft tissues, a long needle is used. The needle is inserted into the soft tissue which covers the medial border of the mandibular ramus, in region of the inferior alveolar, lingual and mylohyoid nerves. The positioning of the bevel of the needle is very important as it must be positioned away from the bone of the mandibular ramus and instead towards the midline. Intraligamentary Infiltration Intraligamentary infiltration, also known as periodontal ligament injection or intraligamentary injection (ILIs), is known as "the most universal of the supplemental injections". ILIs are usually administered when inferior alveolar nerve block techniques are inadequate or ineffective. ILIs are purposed for: 1. Single-tooth anesthesia 2. Low anesthetic dose 3. Contraindication for systemic anesthesia 4. Presence of systemic health problemsILI utilization is expected to increase because dental patients prefer fewer soft tissue anesthesia and dentists aim to reduce administration of traditional inferior alveolar nerve block (INAB) for routine restorative procedures.Injection methodology: The periodontal ligament space provides an accessible route to the cancellous alveolar bone, and the anesthetic reaches the pulpal nerve via natural perforation of intraoral bone tissue.Advantages of ILI over INAB: rapid onset (within 30 seconds), small dosage required (0.2-1.0 mL), limited area of numbness, lower intrinsic risks such as neuropathy, hematoma, trismus/jaw sprain and self-inflicted periodontal tissue injury, as well as decreased cardiovascular disturbances. Its usage as a secondary or supplementary anesthesia on the mandible has reported a high success rate of above 90%.Disadvantages: Risk of temporary periodontal tissue damage, likelihood of bacteriemia and endocarditis for at-risk populations, appropriate pressure and correct needle placement are imperative for anesthetic success, short duration of pulpal anesthesia limits the use of ILIs for several restorative procedures that require longer duration, postoperative discomfort, and injury on unerupted teeth such as enamel hypoplasia and defects. Technique description: All plaque and calculus to be eradicated, optimally before the operative visit to assist gingival tissue healing. Before injection, disinfect gingival sulcus with 0.2% chlorhexidine solution. Administration of soft tissue anesthesia is recommended prior to ILI administration. This helps to enhance patient comfort. Needle gauges of sizes 27-gauge short or 30-gauge ultra-short needle are usually utilized. The needle is inserted along the long axis, at a 30-degree angle, of the mesial or distal root for single rooted teeth and on the mesial and distal roots of multi-rooted teeth. Bevel orientation toward the root provides easier advancement of the needle apically. When the needle reaches between the root and crestal bone, significant resistance is experience. Anesthetic deposition is recommended at 0.2 mL, per root or site, over minimally 20 seconds. For its success, the anesthetic must be administered under pressure. It must not leak out of the sulcus into the mouth. Withdraw needle for minimally 10–15 seconds to permit complete deposition of solution. This can be slower than other injections as there is pressure build-up from the anesthetic administration. Blanching of the tissue is observed and may be more evident when vasoconstrictors are used. It is caused by a temporary obstruction of blood flow to the tissue.Syringes: Standard syringes can be used. The intraligamentary syringe offers mechanical advantage by using a trigger-grasp or click apparatus to employ a gear or lever that improves control and results in increased force to push the anesthetic cartridges rubber stopper forward for medication deposition with greater ease. C-CLADs (computer controlled local anesthetic delivery devices) can be used. Its usage of computer microprocessors allows for control of fluid dynamics and anesthetic deposition. This minimizes subjective flow rates and variability in pressure. This thereby results in enhanced hydrodynamic diffusion of solution into bone or the target area of deposition, thus permitting larger amounts of anesthetic solution to be delivered during ILIs without increased tissue damage.Things to note: ILIs are not recommended for patients with active periodontal inflammation. ILIs should not be administered at tooth sites with 5mm or more of periodontal attachment loss. Gow-Gates Technique Gow-Gates technique is used to provide anesthetics to the mandible of the patients mouth. With the aid of extra and intraoral landmarks, the needle is injected into the intraoral latero-anterior surface of the condyle, steering clear below the insertion of the lateral pterygoid muscle. The extraoral landmarks used for this technique are the lower border of the ear tragus, corners of the mouth and the angulation of the tragus on the side of the face.Biophysical forces (pulsation of the maxillary artery, muscular function of jaw movement) and gravity will aid with the diffusion of anesthetic to fill the whole pterygomandibular space. All three oral sensory parts of the mandibular branch of the trigeminal nerve and other sensory nerves in the region will come in contact with the anesthetic and this reduces the need to anesthetise supplementary innervation.In comparison to other regional block methods of anestheising the lower jaw, the Gow-Gates technique has a higher success rate in fully anesthetising the lower jaw. One study found that out of 1,200 patients receiving injections through the Gow-Gate technique, only 2 of them did not obtain complete anesthesia. Types Local anesthetic solutions for injection typically consist of: The local anesthetic agent itself A vehicle, which is usually water-based or just sterile water Vasoconstrictor possibly (see below) Reducing agent (antioxidant), e.g. if epinephrine is used, then sodium metabisulfite is used as a reducing agent Preservative, e.g. methylparaben BufferEsters are prone to producing allergic reactions, which may necessitate the use of an amide. The names of each locally clinical anesthetic have the suffix "-caine". Most ester LAs are metabolized by pseudocholinesterase, while amide LAs are metabolized in the liver. This can be a factor in choosing an agent in patients with liver failure, although since cholinesterases are produced in the liver, physiologically (e.g. very young or very old individual) or pathologically (e.g. cirrhosis) impaired hepatic metabolism is also a consideration when using esters. Sometimes, LAs are combined, e.g.: Lidocaine/prilocaine (EMLA, eutectic
Local anesthetic	mixture of local anesthetic) Lidocaine/tetracaine (Rapydan) TACLA solutions for injection are sometimes mixed with vasoconstrictors (combination drug) to increase the duration of local anesthesia by constricting the blood vessels, thereby safely concentrating the anesthetic agent for an extended duration, as well as reducing hemorrhage. Because the vasoconstrictor temporarily reduces the rate at which the systemic circulation removes the local anesthetic from the area of the injection, the maximum doses of LAs when combined with a vasoconstrictor is higher compared to the same LA without any vasoconstrictor. Occasionally, cocaine is administered for this purpose. Examples include: Prilocaine hydrochloride and epinephrine (trade name Citanest Forte) Lidocaine, bupivacaine, and epinephrine (recommended final concentrations of 0.5, 0.25, and 0.5%, respectively) Iontocaine, consisting of lidocaine and epinephrine Septocaine (trade name Septodont), a combination of articaine and epinephrineOne combination product of this type is used topically for surface anaesthesia, TAC (5-12% tetracaine,1/2000 (0.05%, 500 ppm, 1⁄2 per mille) adrenaline, 4 or 10% cocaine). Using LA with vasoconstrictor is safe in regions supplied by end arteries. The commonly held belief that LA with vasoconstrictor can cause necrosis in extremities such as the nose, ears, fingers, and toes (due to constriction of end arteries), is invalidated, since no case of necrosis has been reported since the introduction of commercial lidocaine with epinephrine in 1948. Ester group Benzocaine Chloroprocaine Cocaine Cyclomethycaine Dimethocaine (Larocaine) Piperocaine Propoxycaine Procaine (Novocaine) Proparacaine Tetracaine (Amethocaine) Amide group Articaine Bupivacaine Cinchocaine (Dibucaine) Etidocaine Levobupivacaine Lidocaine (Lignocaine) Mepivacaine Prilocaine Ropivacaine Trimecaine Naturally derived Saxitoxin Neosaxitoxin Tetrodotoxin Menthol Eugenol Cocaine SpilantholMost naturally occurring local anesthetics with the exceptions of menthol, eugenol and cocaine are neurotoxins, and have the suffix -toxin in their names. Cocaine binds the intracellular side of the channels while saxitoxin, neosaxitoxin and tetrodotoxin bind to the extracellular side of sodium channels. History In Peru, the ancient Incas are believed to have used the leaves of the coca plant as a local anaesthetic in addition to its stimulant properties. It was also used for slave payment and is thought to play a role in the subsequent destruction of Incas culture when Spaniards realized the effects of chewing the coca leaves and took advantage of it. Cocaine was first used as a local anesthetic in 1884. The search for a less toxic and less addictive substitute led to the development of the aminoester local anesthetics stovaine in 1903 and procaine in 1904. Since then, several synthetic local anesthetic drugs have been developed and put into clinical use, notably lidocaine in 1943, bupivacaine in 1957, and prilocaine in 1959. The invention of clinical use of local anaesthesia is credited to the Vienna School which included Sigmund Freud (1856-1939), Carl Koller (1857-1944) and Leopold Konigstein (1850-1942). They introduced local anaesthesia, using cocaine, through self-experimation on their oral mucosa before introducing it to animal or human experimentation. The Vienna school first started using cocaine as local anaesthesia in ophthalmology and it was later incorporated into ophthalmologic practice. Dr. Halsted and Dr. Hall, in the United States in 1885 described an intraoral anaesthetic technique of blocking the inferior alveolar nerve and the antero-superior dental nerve using 4% cocaine.{Shortly after the first use of cocaine for topical anesthesia, blocks on peripheral nerves were described. Brachial plexus anesthesia by percutaneous injection through axillary and supraclavicular approaches was developed in the early 20th century. The search for the most effective and least traumatic approach for plexus anesthesia and peripheral nerve blocks continues to this day. In recent decades, continuous regional anesthesia using catheters and automatic pumps has evolved as a method of pain therapy. Intravenous regional anesthesia was first described by August Bier in 1908. This technique is still in use and is remarkably safe when drugs of low systemic toxicity such as prilocaine are used. Spinal anesthesia was first used in 1885, but not introduced into clinical practice until 1899, when August Bier subjected himself to a clinical experiment in which he observed the anesthetic effect, but also the typical side effect of postpunctural headache. Within a few years, spinal anesthesia became widely used for surgical anesthesia and was accepted as a safe and effective technique. Although atraumatic (noncutting-tip) cannulae and modern drugs are used today, the technique has otherwise changed very little over many decades. Epidural anesthesia by a caudal approach had been known in the early 20th century, but a well-defined technique using lumbar injection was not developed until 1921, when Fidel Pagés published his article "Anestesia Metamérica". This technique was popularized in the 1930s and 1940s by Achile Mario Dogliotti. With the advent of thin, flexible catheters, continuous infusion and repeated injections have become possible, making epidural anesthesia still a highly successful technique. Besides its many uses for surgery, epidural anesthesia is particularly popular in obstetrics for the treatment of labor pain. See also Amylocaine Anesthetic General anesthetic List of cocaine analogues List of local anesthetics References External links The American Society of Regional Anesthesia Regional Anesthesia and Pain & Medicine
Dysosteosclerosis	Dysosteosclerosis (DSS), also known as autosomal recessive dysosteosclerosis or X-linked recessive dysosteosclerosis, is a rare osteoclast-poor form of osteosclerosis that is presented during infancy and early childhood, characterized by progressive osteosclerosis and platyspondyly. Platyspondyly and other skeletal abnormalities are radiographic features of the disease which distinguish DSS from other osteosclerotic disorders. Patients usually experience neurological and psychological deterioration, therefore patients are commonly associated with delayed milestones. The cause of DSS is unclear. Different genetic mutations are observed in patients, therefore it is suggested that the cause is genetically heterogeneous. Genetic mutations responsible include, but are not limited to, TCIRG1, TNFRSF11A , and SLC29A3. It is congenital and inherited as an autosomal recessive disorder, however, an X-linked recessive inheritance is outlined in some families. There is no cure for DSS. Supportive care includes orthopaedic care. Symptomatic treatment involves the reduction in calcium intake in diet. Less than 30 cases of DSS have been reported in literature to date. Symptoms and Signs The main signs and symptoms of DSS includes: Skeletal abnormalities: platyspondyly, sclerosis Physical abnormalities: short stature, macrocephaly Neurological abnormalities: delayed development, mental retardation Skeletal abnormalities In general, patients with DSS develop osteopenia and bone fragility. DSS also affects specific areas of the human skeleton, such as the spine, skull, pelvis, and limbs. The most common sign of DSS is platyspondyly, which is the flattening of vertebral bodies of the axial skeleton, present in 80-99% of individuals with DSS. Other spinal abnormalities associated with DSS include widened intervertebral disks, small, dense vertebral bodies, irregular vertebral endplates, hypoplastic vertebral bodies, and pronounced vertebral anterior notches.More than 80% of patients also reported abnormalities of the skull. Common symptoms include craniofacial hyperostosis, which is the excessive growth of bone in the skull and face. Skull base sclerosis, periorbital sclerosis, hypoplastic mandibular condyle, and absent paranasal or frontal sinuses are present in rare cases.It is also reported that individuals may also have pelvic abnormalities. This includes the development of narrow iliac wings, as well as widened femoral necks. However, incidence of both symptoms are rare in patients with DSS, occurring in less than 30% of cases.The occurrence of DSS also leads to deformities of the limbs. 80% of patients reported with abnormalities of the metaphysis such as metaphyseal flaring, radiolucent metaphyses, abnormal metaphyseal trabeculation, which is abnormal trabecula patterns in the metaphyseal region, and epimetaphyseal sclerosis. Other limbic abnormalities include progressive bowing of long bones, which is present in rare cases. Physical abnormalities In general, patients appear to be short statured. In addition, as a result of sclerosis of the frontal and parietal region of the calvarium, macrocephaly and square shaped heads are reported in more than 80% of patients.Abnormal skin conditions of red-violet macular mottled skins over the entire body are occasionally observed in patients. However it is unclear whether this clinical feature is relevant to diagnosis of DSS. Neurological abnormalities Visual problems are often found in people with DSS. Patients experience optic atrophy due to progressive cranial nerve compression, which may lead to nystagmus or even blindness in severe cases.Other neurological abnormalities include intellectual disability, speech and psychological deterioration. Convulsions and status epilepticus are also present in patients, however the mechanisms for the development of these features are unknown. Patients also experience cranial nerve damage resulting from progressive cranial pressure. Pathogenesis DSS is classified as an autosomal recessive disease(OMIM 224300), but it is also identified as an X-linked recessive inheritance in certain families. The total number of genes that are responsible for causing the disease and the correlation between genotype and phenotype remains unclear. Multiple gene mutations were identified in different patients via whole genome sequencing, therefore it is presumed that DSS is genetically heterogeneous. TCIRG1 mutation The TCIRG1 gene is present in chromosome locus 11q13, which encodes for the a3 subunit of vacuolar H+ ATPase (V-ATPase) that is unique to osteoclasts. The a3 subunit is responsible in anchoring the vacuolar proton pump to the ruffled membrane of osteoclasts. The V-ATPase is important in mediating the transport of hydrogen ions into the resorption lacunae, which is a pit on the bone surface enclosed by the osteoclast for bone resorption. The accumulation of ions in the lacuna facilitates the decomposition of hydroxyapatite crystals by creating an acidic environment, resulting in bone resorption. Mutation of the gene results in osteoclast-rich osteopetrosis due to poor translation and altered structure of proton pump structure, which is normally involved in large amounts of osteoclast activity leading to absorption of bone tissue. Mutation of TCIRG1 gene may arise from deletion or gene splicing defects, leading to frame-shifts of the nucleotides of the gene.TCIRG1 mutations illustrate the heterogeneity of DSS through a case study where DSS occurred due to a frameshift mutation, in conjunction with a mutation at an intron located in the gene in one of the alleles of chromosome 11 resulting in a splice site mutation. Despite a frameshift mutation altering the C-terminal of the proton pump, due to increased remnant expression of the wild type transcript, it only resulted in intermediate autosomal recessive DSS due to the partial retainment of vacuolar proton pump function. TNFRSF11A mutation The TNFRSF11A gene is present in chromosome locus 18q21.33, which encodes for the receptor activator of NF-κB (RANK). RANK is expressed in immature osteoclasts, which facilitates osteoclasts maturation upon binding of RANK ligand (RANKL). Binding of RANK ligand mediates the RANK/RANKL/OPG signalling pathway. The pathway mediates osteoclast differentiation and activation by promoting differentiation of precursors into multinucleated osteoclasts, and activating osteoclasts, thereby contributing to bone resorption and remodelling. Health conditions related to genetic changes in TNFRSF11A includes osteopetrosis, osteolysis, and Pagets disease of bone.Multiple reports of gene mutations exists underlining the mutation of the exons and introns leading to aberrant splicing. There are five variants to the TNFRSF11A gene which produces five unique protein iso-forms. The effects of alternative splicing on each variants are unclear. However, it is suggested that such changes lead to different expression patterns of the gene in both space and time. Some mutant splicing variants would undergo nonsense-mediated mRNA decay (NMD), while others would not be subjected to NMD, and instead produce a truncated isoform of the RANK protein. The mutated protein has structural defects hence hinders normal function in the signalling pathway, contributing to development of the disease. SLC29A3 mutation The SLC29A3 gene is present in chromosome locus10q22.1, which encodes for the equilibrative nucleoside transporter 3 (ENT3), a nucleoside transporter that is present in membranes of mitochondria and lysosomes. ENT3 is responsible for the trafficking of nucleoside, free purines and pyrimidines into the mitochondria and out of lysosomes. Mutations in the gene is often accompanied by histiocytosis-lymphadenopathy plus syndrome, which is characterised by the accumulation of histiocytes leading to lymphadenopathy and other symptoms.Insertion in the coding region was reported in a patient but no records were found in any genetic databanks. Missense mutation was reported to be present in multiple patients and ranked disease-causing by MutationTaster. This insertion mutation is located in the loop within transmembrane helices 1 and 2, while the missense mutations is located in the loop within transmembrane helix 6, 9, and 11.Mutation leads to impaired ENT3 transportation activity, accumulation of nucleotides and nucleoside in lysosomes. As osteoclasts express the SLC29A3 gene, mutation results in incapacitated differentiated osteoclasts ability in demineralising calcium phosphate crystal surfaces, disrupted osteoclastic differentiation, and diminished osteoclast counts. The reduced osteoclast differentiation and activity results in decreased demineralisation and reabsorption of bone structures. Radiographic features Whilst some symptoms of DSS can be visually identified, many key symptoms of DSS cannot be identified as such. Therefore, radiographic techniques are required to reach a correct diagnosis for DSS. Abnormal features of the axial skeleton Skull In the skull, sclerosis is predominantly observed in the cranial vault and skull base. Other symptoms displayed in the skull include dental anomalies such as abnormal dentition, hypodontia and impaired tooth calcification; intracranial calcifications, which is the calcification of the brain parenchyma; narrow optic canal and other cranial foramina. Abnormal features of the appendicular skeleton Chest The ribs are sclerotic, truncated, expanded, and featureless. Sclerosis is also present in the sternum, clavicles and scapulae. Pectus carinatum, a chest deformity, is also characteristic of the disease. Long bones Sclerosis of epiphyses, diaphyses, and metaphyses with increased radiolucency are key characteristics of the disease. In addition, mottled metaphyseal sclerosis and widening are also present in patients. Development of irregular patchy sclerosis along the bone can also be identified, as well as metaphyseal flaring evolve towards Erlenmeyer flask deformity with nonuniform patches of sclerosis, which are especially prevalent in older patients.The metadiaphyses, a portmanteau of the metaphysis and diaphysis, are bulbous and expanded with bowing and relative radiolucency. The expanded regions are also sclerotic and gives the characteristic bone-in-bone appearance. Spine Platyspondyly is the development of flattened vertebral bodies, which is one of the most notable symptoms as it distinguishes DSS from other similar diseases such as osteosclerosis. It is observed to be most significant in the thoracic region with increased intervertebral spaces. Platyspondyly development begins with generalised osteosclerosis, then subsequent interspersing sclerotic bands develop within vertebral bodies with normal bone density, showing radiolucency. Diagnosis Medical diagnosis of DSS involves various examinations and evaluations. This usually includes physical examinations, medical history evaluations, assessment of signs and symptoms, laboratory tests and image studies. Biopsy may also be required if necessary.Signs and symptoms of DSS show similarities with multifarious disorders and diseases such as osteosclerosis, H syndrome and Pyle disease. As such, it is likely that DSS is consequently incorrectly identified as osteopertrosis. Therefore, additional tests may be performed in order to arrive at a definitive diagnosis. Prognosis and management Overall the disease has a poor prognosis, with treatment mainly focusing on palliation and comfort care.As the mechanism and clinical course of DSS remains unclear, definitive treatment is not available for patients. Bone marrow transplant may improve skeletal abnormalities, however it is improbable the transplant will ameliorate the unexplained neurological deteriorations. In addition, the surgery may not be suitable for every patients as the underlying genetic cause of the disease varies amongst patients. Advice of control and reduction in excessive calcium intake may be recommended by physicians to ensure circulating levels of parathyroid hormones are normal to induce and maintain bone resorption. == References ==
Polycoria	Polycoria is a pathological condition of the eye characterized by more than one pupillary opening in the iris. It may be congenital or result from a disease affecting the iris. It results in decreased function of iris and pupil, affecting the physical eye and visualization. In the early history of China, double pupils were seen as a sign that a child would become a great king or sage. Epidemiology Polycoria is extremely rare, and other conditions are frequently mistaken for it. Polycoria is often congenital, however not diagnosed until adulthood. The general cause of polycoria is unknown, but there are some other eye conditions that are in association with polycoria. These include (although not often) polar cataracts, glaucoma, abnormally long eyelashes, abnormal eye development, and poor vision.There have been cases diagnosed from age 3 to adulthood. The prevalence of true polycoria is minimal. The two kinds of polycoria are true polycoria and false pseudopolycoria. There are no known or proposed trends in the occurrences of polycoria based on geographical location, age, gender, or season. True polycoria In cases of true polycoria, there is an extra pupil that tends to be reactive to light and medication. To be considered true polycoria the extra pupil and the principal pupil must dilate and contract simultaneously with triggers such as light and administered drugs. The extraneous pupil is c. 2.5mm away from the principal pupil. In cases of true polycoria there is an intact sphincter muscle, which contracts and dilates the pupils. In an eye without polycoria, the sphincter muscle is a part of the iris that functions to constrict and dilate the pupil. A patient with true polycoria experiences handicapped vision as well as stimulation of the retina in response to bright lights.It is said that the term "true polycoria" is overused, and used correctly when addressing congenital deformations of the iris. Often "true polycoria" is used when it in fact is a case of pseudopolycoria. Pseudopolycoria Although less rare than true polycoria, pseudopolycoria is still very uncommon. In cases of pseudopolycoria there is a "passive constriction" that differentiates the extra pupil from the true pupil during constriction and dilation. The extra pupil in pseudopolycoria is different than the extra pupil in true polycoria because it shows defects that are independent of the sphincter muscles. Pseudopolycoria is often associated with Seckel syndrome, posterior polymorphous dystrophy, and juvenile glaucoma.Pseudopolycoria consists of splitting of the iris that are not contingent with the sphincter muscles at the root of the iris. Symptoms and diagnosis When a patient is diagnosed with polycoria, the signs and symptoms shown are associated with ocular and adnexal growth abnormalities. The iris and the pupil become less effective. Signs can be present as a child; however, the patient may be diagnosed later in their life. This condition results in abnormal eye development affecting both eyes or just one.Upon gross examination the patient will typically have excessively long eyelashes. The iris becomes hypoplastic, making abnormally shaped pupils with prominent crypts. The crypts are little squiggly lines that radiate out around the pupil; with this condition, thick round or oval openings can be seen.On diagnosis, signs lead to symptoms where there is more than one set of iris muscles, which controls the amount of light being brought into the eye. When the iris becomes deformed, it will disarrange the control of light coming in leading to blurred vision and finding it hard to visually focus. Polar cataracts will also be present in this condition where a round, opaque malformation of distorted lens fibers is located in the central posterior part of the lens showing disformality. Blindness may also be caused due to damage of the optic nerve from glaucoma. Treatment Polycoria has been linked to hereditary genetics, and also associated with polar cataracts, glaucoma, and retinal detachment. Not all cases are treated for this iris abnormality, but when cases are treated the only treatment is surgical procedure and life-long ocular monitoring that is highly recommended. Considerations for surgery are surgical correction, intraocular surgery, and/or reapproximation, as if it was being treated for glaucoma or retinal detachment. Children under the age of 3, who do not seek surgical surgery, have responded well with miotic drops that contained mydriatic/cycloplegic, allowing the separate eye sphincters to dilate and constrict together. This allows improved balance of uncorrected visual acuity. A 1-mm limbal incisions would be made, a spatula is inserted through the side to elevate the two pupils (avoiding contact with the lens), and the iris tissue would be cut using viscoelastic material. Finally, the limbal incisions were closed with stromal hydration, and intracameral cefuroxime is applied. Surgical technique There have been cases where there are various techniques for surgical procedures and can be performed on children and adults. One of the techniques for repair is by using a double armed polypropylene suture, where the suture is left externally on the sclera with a knot buried in the scleral flap. This technique allows posterior fixation of intraocular lens implants in the absence of capsular support. Another technique for surgery is called pupilloplasty, where the patient would be placed under retrobulbar anesthesia with the pupils being dilated with 1% tropicamide. Prognosis Postoperative care Hypertonic saline solution used as eye drops may be used to reduce the corneal edema, the use of anti-glaucomatous topicals to help improve corneal edema, and aqueous suppressants that are accompanied by miotics, include topical beta blockers, alpha antagonists, and carbonic anhydrase inhibitors. Antibiotics and steroid drops for 4 weeks post surgery. Complications and benefits Complications of surgical procedures are possible suture erosion through the sclera, conjunctiva, or both. Minor intraocular inflammation during and after surgery. Improved distant and near visual acuity, little defects surrounding sphincter muscles, and normal pupillary margins. Prevention There are no known preventive measures for polycoria, however genetic testing may be able to reveal genetic patterns of the disorder. Conditions such as reduced corneal thickness, are observed in people with cases of polycoria, as well as keratoconus (keratoconus is a corneal disease has the possibility of leading to blindness and/or astigmatism). However, there are some proposals that it is caused by a dissociation of the pupil margins, a partial coloboma which is a hole in the eye, or abnormal eye tissue composition. Causes There is not any known direct mechanisms involved in the development of true polycoria or pseudopolycoria. There are some proposed ideas, one being that after the sphincter muscle is fully formed and developed in the eye there is a severing of the pupillary margins leading to the distinction of the extra pupil and the principal pupil. Polycoria can also be caused any hole in ones iris to develop a sphincter muscle development. Another proposed theory about the cause of polycoria is intrauterine trauma, or postpartum iris trauma.If the development of the iris is hindered, the ectoderm of the eye (which forms the lens and corneal epithelium) may split, which could lead to pseudopolycoria. Genetics The gene that is the cause of this disorder is the PRDM5 gene. The PRDM5 gene has also been linked to Brittle Cornea syndrome, which is a tissue disorder of the eye, as well as Axenfeld syndome. PRDM5 plays crucial roles in the molecular composition of the eye, as well as the tissue thickness. Axenfeld syndrome occurs in the patient in a case of the mutation of the FOXC1 gene, which is a heterozygous mutation. History Since true polycoria and pseudopolycoria are so rare, there is not much history on the disorders in the tradition of modern western medicine. According to an article published in 2002, there have only been 2 cases of true polycoria since 1966.Early Chinese history names multiple legendary figures as having double pupils, which as a result was led to a beliefs that a child born two double pupils were destined to be a great king or sage. Xiang Yu, Hegemon of Chu, blood brother and later arch nemesis of Liu Bang, the founding emperor of the Han dynasty, was given great esteem due to his prowess in combat and auspicious double pupil. After overthrowing the Qin dynasty together, he was named Hegemon of the loose series of kingdoms he created in its wake, while he gave Liu Bang the remote province of Han. The Civil War that followed called the Chu-Han contention, ending with a Han victory and a legendary last stand by the Hegemon. See also Eye injury Iridodialysis Monocular diplopia Coloboma == References ==
Entomophthoramycosis	Entomophthoramycosis (or Entomophthoromycosis) is a mycosis caused by Entomophthorales.Examples include basidiobolomycosis and conidiobolomycosis. Diagnosis A culture of the infected tissue of the individual suspected of having Entomophthoramycosis Treatment Treatment for phycomycosis is very difficult and includes surgery when possible. Postoperative recurrence is common. Antifungal drugs show only limited effect on the disease, but itraconazole and terbinafine hydrochloride are often used for two to three months following surgery. Humans with Basidiobolus infections have been treated with amphotericin B and potassium iodide. For pythiosis and lagenidiosis, a new drug targeting water moulds called caspofungin is available, but it is very expensive. Immunotherapy has been used successfully in humans and horses with pythiosis. Treatment for skin lesions is traditionally with potassium iodide, but itraconazole has also been used successfully. References == External links ==
Alpha-1 antitrypsin deficiency	Alpha-1 antitrypsin deficiency (A1AD or AATD) is a genetic disorder that may result in lung disease or liver disease. Onset of lung problems is typically between 20 and 50 years of age. This may result in shortness of breath, wheezing, or an increased risk of lung infections. Complications may include chronic obstructive pulmonary disease (COPD), cirrhosis, neonatal jaundice, or panniculitis.A1AD is due to a mutation in the SERPINA1 gene that results in not enough alpha-1 antitrypsin (A1AT). Risk factors for lung disease include tobacco smoking and environmental dust. The underlying mechanism involves unblocked neutrophil elastase and buildup of abnormal A1AT in the liver. It is autosomal co-dominant, meaning that one defective allele tends to result in milder disease than two defective alleles. The diagnosis is suspected based on symptoms and confirmed by blood tests or genetic tests.Treatment of lung disease may include bronchodilators, inhaled steroids, and, when infections occur, antibiotics. Intravenous infusions of the A1AT protein or in severe disease lung transplantation may also be recommended. In those with severe liver disease liver transplantation may be an option. Avoiding smoking is recommended. Vaccination for influenza, pneumococcus, and hepatitis is also recommended. Life expectancy among those who smoke is 50 years while among those who do not smoke it is almost normal.The condition affects about 1 in 2,500 people of European descent. Severe deficiency occurs in about 1 in 5,000. In Asians it is uncommon. About 3% of people with COPD are believed to have the condition. Alpha-1 antitrypsin deficiency was first described in the 1960s. Signs and symptoms Individuals with A1AD may develop chronic obstructive pulmonary disease (emphysema) during their thirties or forties even without a history of smoking, though smoking greatly increases the risk. Symptoms may include shortness of breath (on exertion and later at rest), wheezing, and sputum production. Symptoms may resemble recurrent respiratory infections or asthma.A1AD may cause several manifestations associated with liver disease, which include impaired liver function and cirrhosis. In newborns, alpha-1 antitrypsin deficiency can result in early onset jaundice followed by prolonged jaundice. Between 3% and 5% of children with ZZ mutations develop life-threatening liver disease, including liver failure. A1AD is a leading reason for liver transplantation in newborns. In newborns and children, A1AD may cause jaundice, poor feeding, poor weight gain, hepatomegaly and splenomegaly. Apart from COPD and chronic liver disease, α1-antitrypsin deficiency has been associated with necrotizing panniculitis (a skin condition) and with granulomatosis with polyangiitis in which inflammation of the blood vessels may affect a number of organs but predominantly the lungs and the kidneys. Genetics Serpin peptidase inhibitor, clade A, member 1 (SERPINA1) is the gene that encodes the protein alpha-1 antitrypsin. SERPINA1 has been localized to chromosome 14q32. Over 75 mutations of the SERPINA1 gene have been identified, many with clinically significant effects. The most common cause of severe deficiency, PiZ, is a single base-pair substitution leading to a glutamic acid to lysine mutation at position 342 (dbSNP: rs28929474), while PiS is caused by a glutamic acid to valine mutation at position 264 (dbSNP: rs17580). Other rarer forms have been described. Pathophysiology A1AT is a glycoprotein mainly produced in the liver by hepatocytes, and, in some quantity, by enterocytes, monocytes, and macrophages. In a healthy lung, it functions as an inhibitor against neutrophil elastase, a neutral serine protease that controls lung elastolytic activity which stimulates mucus secretion and CXCL8 release from epithelial cells that perpetuate the inflammatory state. With A1AT deficiency, neutrophil elastase can disrupt elastin and components of the alveolar wall of the lung that may lead to emphysema, and hypersecretion of mucus can develop chronic bronchitis. Both conditions are the makeup of chronic obstructive pulmonary disease (COPD).Normal blood levels of alpha-1 antitrypsin may vary with analytical method but are typically around 1.0-2.7 g/L. In individuals with PiSS, PiMZ and PiSZ genotypes, blood levels of A1AT are reduced to between 40 and 60% of normal levels; this is usually sufficient to protect the lungs from the effects of elastase in people who do not smoke. However, in individuals with the PiZZ genotype, A1AT levels are less than 15% of normal, and they are likely to develop panlobular emphysema at a young age. Cigarette smoke is especially harmful to individuals with A1AD. In addition to increasing the inflammatory reaction in the airways, cigarette smoke directly inactivates alpha-1 antitrypsin by oxidizing essential methionine residues to sulfoxide forms, decreasing the enzyme activity by a factor of 2,000.With A1AT deficiency, the pathogenesis of the lung disease is different from that of the liver disease, which is caused by the accumulation of abnormal A1AT proteins in the liver, resulting in liver damage. As such, lung disease and liver disease of A1AT deficiency appear unrelated, and the presence of one does not appear to predict the presence of the other. Between 10 and 15% of people with the PiZZ genotype will develop liver fibrosis or liver cirrhosis, because the A1AT is not secreted properly and therefore accumulates in the liver. The mutant Z form of A1AT protein undergoes inefficient protein folding (a physical process where a protein chain achieves its final conformation). 85 percent of the mutant Z form are unable to be secreted and remain in the hepatocyte. Nearly all liver disease caused by A1AT is due to the PiZZ genotype, although other genotypes involving different combinations of mutated alleles (compound heterozygotes) may also result in liver disease. A liver biopsy in such cases will reveal PAS-positive, diastase-resistant inclusions within hepatocytes. Unlike glycogen and other mucins which are diastase sensitive (i.e., diastase treatment disables PAS staining), A1AT deficient hepatocytes will stain with PAS even after diastase treatment - a state thus referred to as "diastase resistant". The accumulation of these inclusions or globules is the main cause of liver injury in A1AT deficiency. However, not all individuals with PiZZ genotype develop liver disease (incomplete penetrance), despite the presence of accumulated mutated protein in the liver. Therefore, additional factors (environmental, genetic, etc.) likely influence whether liver disease develops. Diagnosis The gold standard of diagnosis for A1AD consists of blood tests to determine the phenotype of the AAT protein or genotype analysis of DNA. Liver biopsy is the gold standard for determining the extent of hepatic fibrosis and assessing for the presence of cirrhosis.A1AT deficiency remains undiagnosed in many patients. Patients are usually labeled as having COPD without an underlying cause. It is estimated that about 1% of all COPD patients actually have an A1AT deficiency. Testing is recommended in those with COPD, unexplained liver disease, unexplained bronchiectasis, granulomatosis with polyangiitis or necrotizing panniculitis. American guidelines recommend that all people with COPD are tested, whereas British guidelines recommend this only in people who develop COPD at a young age with a limited smoking history or with a family history. The initial test performed is serum A1AT level. A low level of A1AT confirms the diagnosis and further assessment with A1AT protein phenotyping and A1AT genotyping should be carried out subsequently.As protein electrophoresis does not completely distinguish between A1AT and other minor proteins at the alpha-1 position (agarose gel), antitrypsin can be more directly and specifically measured using a nephelometric or immunoturbidimetric method. Thus, protein electrophoresis is useful for screening and identifying individuals likely to have a deficiency. A1AT is further analyzed by isoelectric focusing (IEF) in the pH range 4.5-5.5, where the protein migrates in a gel according to its isoelectric point or charge in a pH gradient. Normal A1AT is termed M, as it migrates toward the center of such an IEF gel. Other variants are less functional and are termed A-L and N-Z, dependent on whether they run proximal or distal to the M band. The presence of deviant bands on IEF can signify the presence of alpha-1 antitrypsin deficiency. Since the number of identified mutations has exceeded the number of letters in the alphabet, subscripts have been added to most recent discoveries in this area, as in the Pittsburgh mutation described above. As every person has two copies of the A1AT gene, a heterozygote with two different copies of the gene may have two different bands showing on electrofocusing, although a heterozygote with one null mutant that abolishes expression of the gene will only show one band. In blood test results, the IEF results are notated as, e.g., PiMM, where Pi stands for protease inhibitor and "MM" is the banding pattern of that person.Other detection methods include use of enzyme-linked-immuno-sorbent-assays in vitro and radial immunodiffusion. Alpha-1 antitrypsin levels in the blood depend on the genotype. Some mutant forms fail to fold properly and are, thus, targeted for destruction in the proteasome, whereas others have a tendency to polymerize, thereafter being retained in the endoplasmic reticulum. The serum levels of some of the common genotypes are: PiMM: 100% (normal) PiMS: 80% of normal serum level of A1AT PiSS: 60% of normal serum level of A1AT PiMZ: 60% of normal serum level of A1AT PiSZ: 40% of normal serum level of A1AT PiZZ: 10–15% (severe alpha-1 antitrypsin deficiency) Treatment Treatment of lung disease may include bronchodilators, inhaled steroids, and, when infections occur, antibiotics. Intravenous infusions of the A1AT protein or in severe disease lung transplantation may also be recommended. In those with severe liver disease liver transplantation may be an option. Avoiding smoking and getting vaccinated for influenza, pneumococcus, and hepatitis is also recommended.People with lung disease due to A1AD may receive intravenous infusions of alpha-1 antitrypsin, derived from donated human plasma. This augmentation therapy is thought to arrest the course of the disease and halt any further damage to the lungs. Long-term studies of the effectiveness of A1AT replacement therapy are not available. It is currently recommended that patients begin augmentation therapy only after the onset of emphysema symptoms. As of 2015 there were four IV augmentation therapy manufacturers in the United States, Canada, and several European countries. IV therapies are the standard mode of augmentation therapy delivery.Liver disease due to A1AD does not include any specific treatment, beyond routine care for chronic liver disease. However, the presence of cirrhosis affects treatment is several ways. Individuals with cirrhosis and portal hypertension should avoid contact sports to minimize the risk of splenic injury. All people with A1AD and cirrhosis should be screened for esophageal varices, and should avoid all alcohol consumption. Nonsteroidal antiinflammatory drugs (NSAIDs) should also be avoided, as these medications may worsen liver disease in general, and may particularly accelerate the liver injury associated with A1AD. Augmentation therapy is not appropriate for people with liver disease. If progressive liver failure or decompensated cirrhosis develop, then liver transplantation may be necessary. Epidemiology People of Northern European and Iberian ancestry are at the highest risk for A1AD. Four percent of them carry the PiZ allele; between 1 in 625 and 1 in 2000 are homozygous.Another study detected a frequency of 1 in 1550 individuals. The highest prevalence of the PiZZ variant was recorded in the northern and western European countries with mean gene frequency of 0.0140. Worldwide, an estimated 1.1 million people have A1AT deficiency and roughly 116 million are carriers of mutations.A1AD is one of the most common genetic diseases worldwide and the second most common metabolic disease affecting the liver. History A1AD was discovered in 1963 by Carl-Bertil Laurell (1919–2001), at the University of Lund in Sweden. Laurell, along with a medical resident, Sten Eriksson, made the discovery after noting the absence of the α1 band on protein electrophoresis in five of 1500 samples; three of the five patients were found to have developed emphysema at a young age.The link with liver disease was made six years later, when Harvey Sharp et al. described A1AD in the context of liver disease. Research Recombinant and inhaled forms of A1AT are being studied. References External links Alpha-1-antitrypsin deficiency on Orphanet
Taurodontism	Taurodontism is defined as the enlargement of pulp chambers with the furcation area being displaced toward the apex of the root. It cannot be diagnosed clinically and requires radiographic visualization since the crown of a taurodontic tooth appears normal and its distinguishing features are present below the alveolar margin. Taurodontism can present in deciduous or permanent dentition, unilaterally or bilaterally, but is most common in the permanent molar teeth of humans. The underlying mechanism of taurodontism is the failure or late invagination of Hertwigs epithelial root sheath, which leads an apical shift of the root furcation. Classification The term was coined by Sir Arthur Keith. It comes from the Latin taurus meaning "bull" and the Greek ὀδούς (odous), genitive singular ὀδόντος (odontos) meaning "tooth", to indicate the similarity of these teeth to those of hoofed/ungulates, or cud-chewing animals.Radiographic characteristics of taurodontism include: lack of pulp chamber constriction at the cementoenamel junction (CEJ); an enlarged pulp chamber that appears rectangular in shape; and displacement of the pulp chamber floor toward the root apex, shortening the roots and root canals.Earlier classification systems considered only the apical displacement of the pulp chamber floor; whereas, later systems additionally consider the position of the pulp chamber in relation to the cemento-enamel junction and alveolar margin. Shaw 1928 One of the first attempts to classify taurodontism was made by C.J.Shaw. He used the apical displacement of the pulp chamber floor to classify taurodontism into four distinct categories: cynodont (normal), hypotaurodont, hypertaurodont, and mesotaurodont. Shifman & Chanannel 1978 Later, Shifman & Chanannel quantified the degree of taurodontism based on a mathematical formula relating the anatomical landmarks as shown in the figure above. The anatomical landmark ratio is calculated as shown below: Landmark ratio Landmark ratio = distance from A to B distance from B to C {\displaystyle {\text{Landmark ratio}}={\frac {\text{distance from A to B}}{\text{distance from B to C}}}} Where, A = the lowest point of the pulp chamber roof, B = the highest point of the pulp chamber floor, and C = the longest root’s apex. Using this formula, a tooth is a taurodont if the landmark ratio is ≥ 0.2 and the distance from the highest point of the pulp chamber floor (B) to the cemento-enamel junction (D) is ≥ 2.5 mm. The full classification system based on this formula are displayed in the table below: It is important to note that historically, there has been professional debate regarding the taurodont classification systems as to: 1) how much displacement and/or morphologic change constitutes taurodontism, 2) whether classification should be indexed stepwise or on a continuum, and 3) whether to include certain teeth in the occurrence of taurodontism. For example, as premolars are narrow mesio-distally, taurodontism is hard to identify radiographically on premolars. Therefore, some researchers exclude premolars from their classification systems. Additionally, there has been criticism over the use of landmarks that undergo changes. For example, due to trauma or wear, tertiary dentin can be deposited which can then alter some measurements; thus, caution should be employed when diagnosing taurodontism in this case. Finally, as these measurements are dimensionally quite small, they are also subject to large relative error. Clinical Considerations The altered morphology of taurodont teeth can present challenges during dental treatment. Most notably, endodontists will have difficulty in not only removing the voluminous pulp, but also filling the large pulp chamber and complex root canal system. Prosthodontists and orthodontists should also exercise caution in using taurodont teeth as sites for dental anchorage. Due to the apical displacement of the furcation area, the taurodont tooth is not held as securely in the alveolar socket. Conversely, this may make taurodont teeth easier to extract. Finally, taurodont teeth may have favorable prognosis from a periodontal point of view, as the furcation area is apical and thus less susceptible to periodontal damage. Anthropology Taurodontism is still a condition of anthropological importance as it was seen in Neanderthals.The trait "is common among extant New World monkeys, apes, and fossil hominins". Related conditions Although taurodontism is frequently an isolated anomaly, it may be found in association with several other conditions such as: amelogenesis imperfecta, Down syndrome, Klinefelter syndrome, Mohr syndrome, Wolf-Hirschhorn syndrome, Lowe syndrome, ectodermal dysplasia and tricho-dento-osseous syndrome.Taurodontism may be related to: A retrograde character A primitive pattern An autosomal dominant trait Atavistic feature An X-linked trait A mutation References == External links ==
Sinus pericranii	Sinus pericranii (SP) is a rare disorder characterized by a congenital (or occasionally, acquired) epicranial venous malformation of the scalp. Sinus pericranii is an abnormal communication between the intracranial and extracranial venous drainage pathways. Treatment of this condition has mainly been recommended for aesthetic reasons and prevention of bleeding. Signs and symptoms Sinus pericranii typically present as soft palpable masses along midline skull, which may fluctuate in size depending on body positioning. Classically, these lesions are not associated with color change of the overlying skin, such as with other vascular lesions such as hemangioma. Cause The nature of this malformation remains unclear. Congenital, spontaneous, and acquired origins are accepted. The hypothesis of a spontaneous origin in the current case of SP is supported by no evidence of associated anomalies, such as cerebral aneurysmal venous malformations, systemic angiomas, venous angioma dural malformation, internal cerebral vein aneurysm, and cavernous hemangiomas. Mechanism Sinus pericranii is a venous anomaly where a communication between the intracranial dural sinuses and dilated epicranial venous structures exists. That venous anomaly is a collection of nonmuscular venous blood vessels adhering tightly to the outer surface of the skull and directly communicating with intracranial venous sinuses through diploic veins. The venous collections receive blood from and drain into the intracranial venous sinuses. The varicosities are intimately associated with the periosteum, are distensible, and vary in size when changes in intracranial pressure occur. Diagnosis Treatment The surgical treatment involves the resection of the extracranial venous package and ligation of the emissary communicating vein. In some cases of SP, surgical excision is performed for cosmetic reasons. The endovascular technique has been described by transvenous approach combined with direct puncture and the recently endovascular embolization with Onyx. See also Mondors disease List of cutaneous conditions == References ==
Inhalant	Inhalants are a broad range of household and industrial chemicals whose volatile vapors or pressurized gases can be concentrated and breathed in via the nose or mouth to produce intoxication, in a manner not intended by the manufacturer. They are inhaled at room temperature through volatilization (in the case of gasoline or acetone) or from a pressurized container (e.g., nitrous oxide or butane), and do not include drugs that are sniffed after burning or heating. For example, amyl nitrite (poppers), nitrous oxide and toluene – a solvent widely used in contact cement, permanent markers, and certain types of glue – are considered inhalants, but smoking tobacco, cannabis, and crack are not, even though these drugs are inhaled as smoke or vapor.While a few inhalants are prescribed by medical professionals and used for medical purposes, as in the case of inhaled anesthetics and nitrous oxide (an anxiolytic and pain relief agent prescribed by dentists), this article focuses on inhalant use of household and industrial propellants, glues, fuels, and other products in a manner not intended by the manufacturer, to produce intoxication or other psychoactive effects. These products are used as recreational drugs for their intoxicating effect. According to a 1995 report by the National Institute on Drug Abuse, the most serious inhalant use occurs among homeless children and teenagers who "... live on the streets completely without family ties." Inhalants are the only substance used more by younger teenagers than by older teenagers. Inhalant users inhale vapor or aerosol propellant gases using plastic bags held over the mouth or by breathing from a solvent-soaked rag or an open container. The practices are known colloquially as "sniffing", "huffing" or "bagging". The effects of inhalants range from an alcohol-like intoxication and intense euphoria to vivid hallucinations, depending on the substance and the dose. Some inhalant users are injured due to the harmful effects of the solvents or gases or due to other chemicals used in the products that they are inhaling. As with any recreational drug, users can be injured due to dangerous behavior while they are intoxicated, such as driving under the influence. In some cases, users have died from hypoxia (lack of oxygen), pneumonia, heart failure or arrest, or aspiration of vomit. Brain damage is typically seen with chronic long-term use of solvents as opposed to short-term exposure.Even though many inhalants are legal, there have been legal actions taken in some jurisdictions to limit access by minors. While solvent glue is normally a legal product, a Scottish court has ruled that supplying glue to children is illegal if the store knows the children intend to inhale the glue. In the US, thirty-eight of 50 states have enacted laws making various inhalants unavailable to those under the age of 18 or making inhalant use illegal. Classification Inhalants can be classified by the intended function. Most inhalant drugs that are used non-medically are ingredients in household or industrial chemical products that are not intended to be concentrated and inhaled. A small number of recreational inhalant drugs are pharmaceutical products that are used illicitly. Product category Another way to categorize inhalants is by their product category. There are three main product categories: solvents; gases; and medical drugs which are used illicitly. Solvents A wide range of volatile solvents intended for household or industrial use are inhaled as recreational drugs. This includes petroleum products (gasoline and kerosene), toluene (used in paint thinner, permanent markers, contact cement and model glue), and acetone (used in nail polish remover). These solvents vaporize at room temperature. Ethanol (the alcohol which is normally drunk) is sometimes inhaled, but this cannot be done at room temperature. The ethanol must be converted from liquid into gaseous state (vapor) or aerosol (mist), in some cases using a nebulizer, a machine that agitates the liquid into an aerosol. The sale of nebulizers for inhaling ethanol was banned in some US states due to safety concerns. Gases A number of gases intended for household or industrial use are inhaled as recreational drugs. This includes chlorofluorocarbons used in aerosols and propellants (e.g., aerosol hair spray, aerosol deodorant). A gas used as a propellant in whipped cream aerosol containers, nitrous oxide, is used as a recreational drug. Pressurized canisters of propane and butane gas, both of which are intended for use as fuels, are used as inhalants. Medical anesthetics Several medical anesthetics are used as recreational drugs, including diethyl ether (a drug that is no longer used medically, due to its high flammability and the development of safer alternatives) and nitrous oxide, which is widely used in the 2010s by dentists as an anti-anxiety drug during dental procedures. Diethyl ether has a long history of use as a recreational drug. The effects of ether intoxication are similar to those of alcohol intoxication, but more potent. Also, due to NMDA antagonism, the user may experience all the psychedelic effects present in classical dissociatives such as ketamine in forms of thought loops and the feeling of the mind being disconnected from ones body. Nitrous oxide is a dental anesthetic that is used as a recreational drug, either by users who have access to medical-grade gas canisters (e.g., dental hygienists or dentists) or by using the gas contained in whipped cream aerosol containers. Nitrous oxide inhalation can cause pain relief, depersonalisation, derealisation, dizziness, euphoria, and some sound distortion. Classification by effect It is also possible to classify inhalants by the effect they have on the body. Some solvents act as depressants, causing users to feel relaxed or drowsy while others act as stimulants. Many inhalants act primarily as asphyxiant gases, with their primary effect due to oxygen deprivation. Nitrous oxide can be categorized as a dissociative drug, as it can cause visual and auditory hallucinations. Other agents may have more direct effects at receptors, as inhalants exhibit a variety of mechanisms of action. The mechanisms of action of many non-medical inhalants have not been well elucidated. Anesthetic gases used for surgery, such as nitrous oxide or enflurane, are believed to induce anesthesia primarily by acting as NMDA receptor antagonists, open-channel blockers that bind to the inside of the calcium channels on the outer surface of the neuron, and provide high levels of NMDA receptor blockade for a short period of time. This makes inhaled anesthetic gases different from other NMDA antagonists, such as ketamine, which bind to a regulatory site on the NMDA-sensitive calcium transporter complex and provide slightly lower levels of NMDA blockade, but for a longer and much more predictable duration. This makes a deeper level of anesthesia achievable more easily using anesthetic gases but can also make them more dangerous than other drugs used for this purpose. Chemical structure Inhalants can also be classified by chemical structure. Classes include: Administration and effects Inhalant users inhale vapors or aerosol propellant gases using plastic bags held over the mouth or by breathing from an open container of solvents, such as gasoline or paint thinner. Nitrous oxide gases from whipped cream aerosol cans, aerosol hairspray or non-stick frying spray are sprayed into plastic bags. Some nitrous oxide users spray the gas into balloons. When inhaling non-stick cooking spray or other aerosol products, some users may filter the aerosolized particles out with a rag. Some gases, such as propane and butane gases, are inhaled directly from the canister. Once these solvents or gases are inhaled, the extensive capillary surface of the lungs rapidly absorb the solvent or gas, and blood levels peak rapidly. The intoxication effects occur so quickly that the effects of inhalation can resemble the intensity of effects produced by intravenous injection of other psychoactive drugs.Ethanol is also inhaled, either by vaporizing it by pouring it over dry ice in a narrow container and inhaling with a straw or by pouring alcohol in a corked bottle with a pipe, and then using a bicycle pump to make a spray. Alcohol can be vaporized using a simple container and open-flame heater. Medical devices such as asthma nebulizers and inhalers were also reported as means of application. The practice gained popularity in 2004, with the marketing of the device dubbed AWOL (Alcohol without liquid), a play on the military term AWOL (Absent Without Leave). AWOL, created by British businessman Dominic Simler, was first introduced in Asia and Europe, and then in the United States in August 2004. AWOL was used by nightclubs, at gatherings and parties, and it garnered attraction as a novelty, as people enjoyed passing it around in a group. AWOL uses a nebulizer, a machine that agitates the liquid into an aerosol. AWOLs official website states that "AWOL and AWOL 1 are powered by Electrical Air Compressors while AWOL 2 and AWOL 3 are powered by electrical oxygen generators", which refer to a couple of mechanisms used by the nebulizer drug delivery device for inhalation. Although the AWOL machine is marketed as having no downsides, such as the lack of calories or hangovers, Amanda Shaffer of Slate describes these claims as "dubious at best". Although inhaled alcohol does reduce the caloric content, the savings are minimal. After expressed safety and health concerns, sale or use of AWOL machines was banned in a number of American states.The effects of solvent intoxication can vary widely depending on the dose and what type of solvent or gas is inhaled. A person who has inhaled a small amount of rubber cement or paint thinner vapor may be impaired in a manner resembling alcohol inebriation. A person who has inhaled a larger quantity of solvents or gases, or a stronger chemical, may experience stronger effects such as distortion in perceptions of time and space, hallucinations, and emotional disturbances. The effects of inhalant use are also modified by the combined use of inhalants and alcohol or other drugs. In the short term, many users experience headaches, nausea and vomiting, slurred speech, loss of motor coordination, and wheezing. A characteristic "glue sniffers rash" around the nose and mouth is sometimes seen after prolonged use. An odor of paint or solvents on clothes, skin, and breath is sometimes a sign of inhalant abuse, and paint or solvent residues can sometimes emerge in sweat.According to NIH, even a single session of inhalant use "can disrupt heart rhythms and lower oxygen levels", which can lead to death. "Regular abuse can result in serious harm to the brain, heart, kidneys, and liver." Dangers and health problems Statistics on deaths caused by heavy inhalant use are difficult to determine. It may be severely under-reported because death is often attributed to a discrete event such as a stroke or a heart attack, even if the event happened because of inhalant use. Inhalant use was mentioned on 144 death certificates in Texas during the period 1988–1998 and was reported in 39 deaths in Virginia between 1987 and 1996 from acute voluntary exposure to used inhalants. General risks Regardless of which inhalant is used, inhaling vapors or gases can lead to injury or death. One major risk is hypoxia (lack of oxygen), which can occur due to inhaling fumes from a plastic bag, or from using proper inhalation mask equipment (e.g., a medical mask for nitrous oxide) but not adding oxygen or room air. Another danger is freezing the throat. When a gas that was stored under high pressure is released, it cools abruptly and can cause frostbite if it is inhaled directly from the container. This can occur, for example, with inhaling nitrous oxide. When nitrous oxide is used as an automotive power adder, its cooling effect is used to make the fuel-air charge denser. In a person, this effect is potentially lethal. Many inhalants are volatile organic chemicals and can catch fire or explode, especially when combined with smoking. As with many other drugs, users may also injure themselves due to loss of coordination or impaired judgment, especially if they attempt to operate machinery. Solvents have many potential risks in common, including pneumonia, cardiac failure or arrest, and aspiration of vomit. The inhaling of some solvents can cause hearing loss, limb spasms, and damage to the central nervous system and brain. Serious but potentially reversible effects include liver and kidney damage and blood-oxygen depletion. Death from inhalants is generally caused by a very high concentration of fumes. Deliberately inhaling solvents from an attached paper or plastic bag or in a closed area greatly increases the chances of suffocation. Brain damage is typically seen with chronic long-term use as opposed to short-term exposure. Parkinsonism (see: Signs and symptoms of Parkinsons disease) has been associated with huffing. Female inhalant users who are pregnant may have adverse effects on the fetus, and the baby may be smaller when it is born and may need additional health care (similar to those seen with alcohol – fetal alcohol syndrome). There is some evidence of birth defects and disabilities in babies born to women who sniffed solvents such as gasoline. In the short term, death from solvent use occurs most commonly from aspiration of vomit while unconscious or from a combination of respiratory depression and hypoxia, the second cause being especially a risk with heavier-than-air vapors such as butane or gasoline vapor. Deaths typically occur from complications related to excessive sedation and vomiting. Actual overdose from the drug does occur, however, and inhaled solvent use is statistically more likely to result in life-threatening respiratory depression than intravenous use of opioids such as heroin. Most deaths from solvent use could be prevented if individuals were resuscitated quickly when they stopped breathing and their airway cleared if they vomited. However, most inhalant use takes place when people inhale solvents by themselves or in groups of people who are intoxicated. Certain solvents are more hazardous than others, such as gasoline. In contrast, a few inhalants like amyl nitrate and diethyl ether have medical applications and are not toxic in the same sense as solvents, though they can still be dangerous when used recreationally. Nitrous oxide is thought to be particularly non-toxic, though heavy long-term use can lead to a variety of serious health problems linked to destruction of vitamin B12 and folic acid. Risks of specific agents The hypoxic effect of inhalants can cause damage to many organ systems (particularly the brain, which has a very low tolerance for oxygen deprivation), but there can also be additional toxicity resulting from either the physical properties of the compound itself or additional ingredients present in a product. Organochlorine solvents are particularly hazardous; many of these are now restricted in developed countries due to their environmental impact. Methylene chloride, after being metabolized, can cause carbon monoxide poisoning. Gasoline sniffing can cause lead poisoning, in locations where leaded gas is not banned. Ingestion of alkyl nitrites can cause methemoglobinemia, and by inhalation it has not been ruled out. Carbon tetrachloride can cause significant damage to multiple systems, but its association with liver damage is so strong that it is used in animal models to induce liver injury. Use of butane, propane, nitrous oxide and other inhalants can create a risk of freezing burns from contact with the extremely cold liquid (See aerosol burn). The risk of such contact is greatly increased by the impaired judgement and motor coordination brought on by inhalant intoxication. Benzene use can cause bone marrow depression. It is also a known carcinogen. Toluene can damage myelin.Toxicity may also result from the pharmacological properties of the drug; excess NMDA antagonism can completely block calcium influx into neurons and provoke cell death through apoptosis, although this is more likely to be a long-term result of chronic solvent use than a consequence of short-term use. Sudden sniffing death syndrome Sudden sniffing death syndrome is commonly known as SSDS. Inhaling butane gas can cause drowsiness, unconsciousness, asphyxia, and cardiac arrhythmia. Butane is the most commonly misused volatile solvent in the UK and caused 52% of solvent-related deaths in 2000. When butane is sprayed directly into the throat, the jet of fluid can cool rapidly to −20 °C by adiabatic expansion, causing prolonged laryngospasm.Some inhalants can also indirectly cause sudden death by cardiac arrest, in a syndrome known as "sudden sniffing death". The anaesthetic gases present in the inhalants appear to sensitize the user to adrenaline and, in this state, a sudden surge of adrenaline (e.g., from a frightening hallucination or run-in with aggressors), may cause fatal cardiac arrhythmia.Furthermore, the inhalation of any gas that is capable of displacing oxygen in the lungs (especially gases heavier than oxygen) carries the risk of hypoxia as a result of the very mechanism by which breathing is triggered. Since reflexive breathing is prompted by elevated carbon dioxide levels (rather than diminished blood oxygen levels), breathing a concentrated, relatively inert gas (such as computer-duster tetrafluoroethane or nitrous oxide) that removes carbon dioxide from the blood without replacing it with oxygen will produce no outward signs of suffocation even when the brain is experiencing hypoxia. Once full symptoms of hypoxia appear, it may be too late to breathe without assistance, especially if the gas is heavy enough to lodge in the lungs for extended periods. Even completely inert gases, such as argon, can have this effect if oxygen is largely excluded. Legal aspects Solvent glue Even though solvent glue is normally a legal product, there is a case where a court has ruled that supplying glue to children is illegal. Khaliq v HM Advocate was a Scottish criminal case decided by the High Court of Justiciary on appeal, in which it was decided that it was an offense at common law to supply glue-sniffing materials that were otherwise legal in the knowledge that they would be used recreationally by children. Two shopkeepers in Glasgow were arrested and charged with supplying to children "glue-sniffing kits" consisting of a quantity of petroleum-based glue in a plastic bag. They argued there was nothing illegal about the items that they had supplied. On appeal, the High Court took the view that, even though glue and plastic bags might be perfectly legal, everyday items, the two shopkeepers knew perfectly well that the children were going to use the articles as inhalants and the charge on the indictment should stand. When the case came to trial at Glasgow High Court the two were sentenced to three years imprisonment. "Thirty-eight of 50 [US] states have enacted laws making various inhalants unavailable to those under the age of 18. Other states prohibit the sale of these items to anyone without recognition of purpose for the purchase. Some states mandate laws against using these products for purposes of getting high, while some states have laws about possessing certain inhalants. Nearly every state imposes fines and jail terms for violation of their specific laws.""Connecticut law bans the unauthorized manufacture or compounding, possession, control, sale, delivery, or administration of any "restricted substance". It defines restricted substances as... specific volatile substances if they are sold, compounded, possessed or controlled, or delivered or administered to another person for breathing, inhaling, sniffing, or drinking to induce a stimulant, depressant, or hallucinogenic effect. Violators can be fined up to $100." As well, 24 states "ban the use, possession, or sale or other distribution of inhalants... like glue and solvents.""Louisiana prohibits the sale, transfer, or possession of model glue and inhalable toluene substances to minors. In Ohio, it is illegal to inhale certain compounds for intoxication—a common, general prohibition other states have enacted. Some states draw their prohibitions more narrowly... In Massachusetts, retailers must ask minors for identification before selling them glue or cement that contains a solvent that can release toxic vapors." Propellant gases "New Jersey... prohibits selling or offering to sell minors products containing chlorofluorocarbon that is used in refrigerant." Poppers The sale of alkyl nitrite-based poppers was banned in Canada in 2013. Although not considered a narcotic and not illegal to possess or use, they are considered a drug. Sales that are not authorized can now be punished with fines and prison. Since 2007, reformulated poppers containing isopropyl nitrite are sold in Europe because only isobutyl nitrite is prohibited. In France, the sale of products containing butyl nitrite, pentyl nitrite, or isomers thereof, has been prohibited since 1990 on grounds of danger to consumers. In 2007, the government extended this prohibition to all alkyl nitrites that were not authorized for sale as drugs. After litigation by sex shop owners, this extension was quashed by the Council of State on the grounds that the government had failed to justify such a blanket prohibition: according to the court, the risks cited, concerning rare accidents often following abnormal usage, rather justified compulsory warnings on the packaging.In the United Kingdom, poppers are widely available and frequently (legally) sold in gay clubs/bars, sex shops, drug paraphernalia head shops, over the Internet and on markets. It is illegal under Medicines Act 1968 to sell them advertised for human consumption, and to bypass this, they are usually sold as odorizers. In the U.S., originally marketed as a prescription drug in 1937, amyl nitrite remained so until 1960, when the Food and Drug Administration removed the prescription requirement due to its safety record. This requirement was reinstated in 1969, after observation of an increase in recreational use. Other alkyl nitrites were outlawed in the U.S. by Congress through the Anti-Drug Abuse Act of 1988. The law includes an exception for commercial purposes. The term commercial purpose is defined to mean any use other than for the production of consumer products containing volatile alkyl nitrites meant for inhaling or otherwise introducing volatile alkyl nitrites into the human body for euphoric or physical effects. The law came into effect in 1990. Visits to retail outlets selling these products reveal that some manufacturers have since reformulated their products to abide by the regulations, through the use of the legal cyclohexyl nitrite as the primary ingredient in their products, which are sold as video head cleaners, polish removers, or room odorants. Nitrous oxide In the United States, possession of nitrous oxide is legal under federal law and is not subject to DEA purview. It is, however, regulated by the Food and Drug Administration under the Food Drug and Cosmetics Act; prosecution is possible under its "misbranding" clauses, prohibiting the sale or distribution of nitrous oxide for the purpose of human consumption as a recreational drug. Many states have laws regulating the possession, sale, and distribution of nitrous oxide. Such laws usually ban distribution to minors or limit the amount of nitrous oxide that may be sold without a special license. For example, in the state of California, possession for recreational use is prohibited and qualifies as a misdemeanor. In New Zealand, the Ministry of Health has warned that nitrous oxide is a prescription medicine, and its sale or possession without a prescription is an offense under the Medicines Act. This statement would seemingly prohibit all non-medicinal uses of the chemical, though it is implied that only recreational use will be legally targeted. In India, for general anesthesia purposes, nitrous oxide is available as Nitrous Oxide IP. Indias gas cylinder rules (1985) permit the transfer of gas from one cylinder to another for breathing purposes. Because Indias Food & Drug Authority (FDA-India) rules state that transferring a drug from one container to another (refilling) is equivalent to manufacturing, anyone found doing so must possess a drug manufacturing license. Patterns of non-medical use Inhalant drugs are often used by children, teenagers, incarcerated or institutionalized people, and impoverished people, because these solvents and gases are ingredients in hundreds of legally available, inexpensive products, such as deodorant sprays, hair spray, contact cement and aerosol air fresheners. However, most users tend to be "... adolescents (between the ages of 12 and 17)." In some countries, chronic, heavy inhalant use is concentrated in marginalized, impoverished communities. Young people who become used to heavy amounts of inhalants chronically are also more likely to be those who are isolated from their families and community. The article "Epidemiology of Inhalant Abuse: An International Perspective" notes that "[t]he most serious form of obsession with inhalant use probably occurs in countries other than the United States where young children live on the streets completely without family ties. These groups almost always use inhalants at very high levels (Leal et al. 1978). This isolation can make it harder to keep in touch with the sniffer and encourage him or her to stop sniffing."The article also states that "... high [inhalant use] rates among barrio Hispanics almost undoubtedly are related to the poverty, lack of opportunity, and social dysfunction that occur in barrios" and states that the "... same general tendency appears for Native-American youth" because "... Indian reservations are among the most disadvantaged environments in the United States; there are high rates of unemployment, little opportunity, and high rates of alcoholism and other health problems." There are a wide range of social problems associated with inhalant use, such as feelings of distress, anxiety and grief for the community; violence and damage to property; violent crime; stresses on the juvenile justice system; and stresses on youth agencies and support services. Africa and Asia Glue and gasoline (petrol) sniffing is also a problem in parts of Africa, especially with street children. In India and South Asia, three of the most widely used inhalants are the Dendrite brand and other forms of contact adhesives and rubber cement manufactured in Kolkata, and toluenes in paint thinners. Genkem is a brand of glue, which had become the generic name for all the glues used by glue-sniffing children in Africa before the manufacturer replaced n-hexane in its ingredients in 2000.The United Nations Office on Drugs and Crime has reported that glue sniffing is at the core of "street culture" in Nairobi, Kenya, and that the majority of street children in the city are habitual solvent users. Research conducted by Cottrell-Boyce for the African Journal of Drug and Alcohol Studies found that glue sniffing amongst Kenyan street children was primarily functional – dulling the senses against the hardship of life on the street – but it also provided a link to the support structure of the "street family" as a potent symbol of shared experience.Similar incidents of glue sniffing among destitute youth in the Philippines have also been reported, most commonly from groups of street children and teenagers collectively known as "Rugby" boys, which were named after a brand of toluene-laden contact cement. Other toluene-containing substances have also been used, most notably the Vulca Seal brand of roof sealants. Bostik Philippines, which currently owns the Rugby and Vulca Seal brands, has since responded to the issue by adding bitterants such as mustard oil to their Rugby line, as well as reformulating it by replacing toluene with xylene. Several other manufacturers have also followed suit. Another very common inhalant is Erase-X, a correction fluid that contains toluene. It has become very common for school and college students to use it, because it is easily available in stationery shops in India. This fluid is also used by street and working children in Delhi. Europe and North America In the UK, marginalized youth use a number of inhalants, such as solvents and propellants. In Russia and Eastern Europe, gasoline sniffing became common on Russian ships following attempts to limit the supply of alcohol to ship crews in the 1980s. The documentary Children Underground depicts the huffing of a solvent called Aurolac (a product used in chroming) by Romanian homeless children. During the Interbellum the inhalation of ether (etheromania) was widespread in some regions of Poland, especially in Upper Silesia—tens of thousands of people were affected by this problem.In Canada, Native children in the isolated Northern Labrador community of Davis Inlet were the focus of national concern in 1993, when many were found to be sniffing gasoline.
Inhalant	The Canadian and provincial Newfoundland and Labrador governments intervened on a number of occasions, sending many children away for treatment. Despite being moved to the new community of Natuashish in 2002, serious inhalant use problems have continued. Similar problems were reported in Sheshatshiu in 2000 and also in Pikangikum First Nation. In 2012, the issue once again made the news media in Canada. In Mexico, the inhaling of a mixture of gasoline and industrial solvents, known locally as "Activo" or "Chemo", has risen in popularity among the homeless and among the street children of Mexico City in recent years. The mixture is poured onto a handkerchief and inhaled while held in ones fist. In the US, ether was used as a recreational drug during the 1930s Prohibition era, when alcohol was made illegal. Ether was either sniffed or drunk and, in some towns, replaced alcohol entirely. However, the risk of death from excessive sedation or overdose is greater than that with alcohol, and ether drinking is associated with damage to the stomach and gastrointestinal tract. Use of glue, paint and gasoline became more common after the 1950s. Model airplane glue-sniffing as problematic behavior among youth was first reported in 1959 and increased in the 1960s. Use of aerosol sprays became more common in the 1980s, as older propellants such as CFCs were phased out and replaced by more environmentally friendly compounds such as propane and butane. Most inhalant solvents and gases are not regulated under drug laws such as the United States Controlled Substances Act. However, many US states and Canadian cities have placed restrictions on the sale of some solvent-containing products to minors, particularly for products widely associated with sniffing, such as model cement. The practice of inhaling such substances is sometimes colloquially referred to as huffing, sniffing (or glue sniffing), dusting, or chroming. Australia Australia has long faced a petrol (gasoline) sniffing problem in isolated and impoverished aboriginal communities. Although some sources argue that sniffing was introduced by United States servicemen stationed in the nations Top End during World War II or through experimentation by 1940s-era Cobourg Peninsula sawmill workers, other sources claim that inhalant abuse (such as glue inhalation) emerged in Australia in the late 1960s. Chronic, heavy petrol sniffing appears to occur among remote, impoverished indigenous communities, where the ready accessibility of petrol has helped to make it a common addictive substance. In Australia, petrol sniffing now occurs widely throughout remote Aboriginal communities in the Northern Territory, Western Australia, northern parts of South Australia, and Queensland. The number of people sniffing petrol goes up and down over time as young people experiment or sniff occasionally. "Boss", or chronic, sniffers may move in and out of communities; they are often responsible for encouraging young people to take it up.A 1983 survey of 4,165 secondary students in New South Wales showed that solvents and aerosols ranked just after analgesics (e.g., codeine pills) and alcohol for drugs that were inappropriately used. This 1983 study did not find any common usage patterns or social class factors. The causes of death for inhalant users in Australia included pneumonia, cardiac failure/arrest, aspiration of vomit, and burns. In 1985, there were 14 communities in Central Australia reporting young people sniffing. In July 1997, it was estimated that there were around 200 young people sniffing petrol across 10 communities in Central Australia. Approximately 40 were classified as chronic sniffers. There have been reports of young Aboriginal people sniffing petrol in the urban areas around Darwin and Alice Springs. In 2005, the Government of Australia and BP Australia began the usage of opal fuel in remote areas prone to petrol sniffing. Opal is a non-sniffable fuel (which is much less likely to cause a high) and has made a difference in some indigenous communities. In popular culture Music and musical culture One of the early musical references to inhalant use occurs in the 1974 Elton John song "The Bitch Is Back", in the line "I get high in the evening sniffing pots of glue." Inhalant use, especially glue-sniffing, is widely associated with the late-1970s punk youth subculture in the UK and North America. Raymond Cochrane and Douglas Carroll claim that when glue sniffing became widespread in the late 1970s, it was "adopted by punks because public [negative] perceptions of sniffing fitted in with their self-image" as rebels against societal values. While punks at first used inhalants "experimentally and as a cheap high, adult disgust and hostility [to the practice] encouraged punks to use glue sniffing as a way of shocking society." As well, using inhalants was a way of expressing their anti-corporatist DIY (do it yourself) credo; by using inexpensive household products as inhalants, punks did not have to purchase industrially manufactured liquor or beer. One history of the punk subculture argues that "substance abuse was often referred to in the music and did become synonymous with the genre, glue-sniffing especially" because the youths "faith in the future had died and that the youth just didnt care anymore" due to the "awareness of the threat of nuclear war and a pervasive sense of doom." In a BBC interview with a person who was a punk in the late 1970s, they said that "there was a real fear of imminent nuclear war—people were sniffing glue knowing that it could kill them, but they didnt care because they believed that very soon everybody would be dead anyway." A number of 1970s punk rock and 1980s hardcore punk songs refer to inhalant use. The Ramones, an influential early US punk band, referred to inhalant use in several of their songs. The song "Now I Wanna Sniff Some Glue" describes adolescent boredom, and the song "Carbona not Glue" states, "My brain is stuck from shooting glue." An influential punk fanzine about the subculture and music took its name (Sniffin Glue) from the Ramones song. The 1980s punk band The Dead Milkmen wrote a song, "Life is Shit" from their album Beelzebubba, about two friends hallucinating after sniffing glue. Punk-band-turned-hip-hop group the Beastie Boys penned a song "Hold it Now – Hit It", which includes the line "cause Im beer drinkin, breath stinkin, sniffing glue." Their song "Shake Your Rump" includes the lines, "Should I have another sip no skip it/In the back of the ride and bust with the whippits". Pop punk band Sum 41 wrote a song, "Fat Lip", which refers to a character who does not "make sense from all the gas you be huffing..." The song Lança-perfume, written and performed by Brazilian pop star Rita Lee, became a national hit in 1980. The song is about chloroethane and its widespread recreational sale and use during the rise of Brazils carnivals. Inhalants are referred to by bands from other genres, including several grunge bands—an early 1990s genre that was influenced by punk rock. The 1990s grunge band Nirvana, which was influenced by punk music, penned a song, "Dumb", in which Kurt Cobain sings "my heart is broke / But I have some glue/help me inhale / And mend it with you". L7, an all-female grunge band, penned a song titled "Scrap" about a skinhead who inhales spray-paint fumes until his mind "starts to gel". Also in the 1990s, the Britpop band Suede had a UK hit with their song "Animal Nitrate" whose title is a thinly veiled reference to amyl nitrite. The Beck song "Fume" from his "Fresh Meat and Old Slabs" release is about inhaling nitrous oxide. Another Beck song, "Cold Ass Fashion", contains the line "O.G. – Original Gluesniffer!" Primuss 1998 song "Lacquer Head" is about adolescents who use inhalants to get high. Hip hop performer Eminem wrote a song, "Bad Meets Evil", which refers to breathing "... ether in three lethal amounts." The Brian Jonestown Massacre, a retro-rock band from the 1990s, has a song "Hyperventilation", which is about sniffing model-airplane cement. Frank Zappas song "Teenage Wind" from 1981 has a reference to glue sniffing: "Nothing left to do but get out the ol glue; Parents, parents; Sniff it good now..." Films A number of films have depicted or referred to the use of solvent inhalants. In the 1980 comedy film Airplane!, the character of McCroskey (Lloyd Bridges) refers to his inhalant use when he states, "I picked the wrong week to quit sniffing glue." In the 1996 film Citizen Ruth, the character Ruth (Laura Dern), a homeless drifter, is depicted inhaling patio sealant from a paper bag in an alleyway. In the tragicomedy Love Liza, the main character, played by Philip Seymour Hoffman, plays a man who takes up building remote-controlled airplanes as a hobby to give him an excuse to sniff the fuel in the wake of his wifes suicide. Harmony Korines 1997 Gummo depicts adolescent boys inhaling contact cement for a high. Edet Belzbergs 2001 documentary Children Underground chronicles the lives of Romanian street children addicted to inhaling paint. In The Basketball Diaries, a group of boys is huffing carbona cleaning liquid at 3 minutes and 27 seconds into the movie; further on, a boy is reading a diary describing the experience of sniffing the cleaning liquid. In the David Lynch film Blue Velvet, the bizarre and manipulative character played by Dennis Hopper uses a mask to inhale amyl nitrite. In Little Shop of Horrors, Steve Martins character dies from nitrous oxide inhalation. The 1999 independent film Boys Dont Cry depicts two young low-income women inhaling aerosol computer cleaner (compressed gas) for a buzz. In The Cider House Rules, Michael Caines character is addicted to inhaling ether vapors. In Thirteen, the main character, a teen, uses a can of aerosol computer cleaner to get high. In the action movie Shooter, an ex-serviceman on the run from the law (Mark Wahlberg) inhales nitrous oxide gas from a number of Whip-It! whipped cream canisters until he becomes unconscious. The South African film The Wooden Camera also depicts the use of inhalants by one of the main characters, a homeless teen, and their use in terms of socio-economic stratification. The title characters in Samson and Delilah sniff petrol; in Samsons case, possibly causing brain damage. In the 2004 film Taxi, Queen Latifah and Jimmy Fallon are trapped in a room with a burst tank containing nitrous oxide. Queen Latifahs character curses at Fallon while they both laugh hysterically. Fallons character asks if it is possible to die from nitrous oxide, to which Queen Latifahs character responds with "Its laughing gas, stupid!" Neither of them had any side effects other than their voices becoming much deeper while in the room. In the French horror film Them, (2006) a French couple living in Romania are pursued by a gang of street children who break into their home at night. Olivia Bonamys character is later tortured and forced to inhale aurolac from a silver-colored bag. During a flashback scene in the 2001 film Hannibal, Hannibal Lecter gets Mason Verger high on amyl nitrite poppers, then convinces Verger to cut off his own face and feed it to his dogs. Books The science fiction story "Waterspider" by Philip K. Dick (first published in January 1964 in If magazine) contains a scene in which characters from the future are discussing the culture of the early 1950s. One character says: "You mean he sniffed what they called airplane dope? He was a glue-sniffer?", to which another character replies: "Hardly. That was a mania among adolescents and did not become widespread in fact until a decade later. No, I am speaking about imbibing alcohol."The book Fear and Loathing in Las Vegas describes how the two main characters inhale diethyl ether and amyl nitrite. Television In the comedy series Newman and Baddiel in Pieces, Rob Newmans inhaling gas from a foghorn was a running joke in the series. One episode of the Jeremy Kyle Show featured a woman with a 20-year butane gas addiction. In the series Its Always Sunny in Philadelphia, Charlie Kelly has an addiction to huffing glue. Additionally, season nine episode 8 shows Dennis, Mac, and Dee getting a can of gasoline to use as a solvent, but instead end up taking turns huffing from the canister. A 2008 episode of the reality show Intervention (season 5, episode 9) featured Allison, who was addicted to huffing computer duster for the short-lived, psychoactive effects. Allison has since achieved a small but significant cult following among bloggers and YouTube users. Several remixes of scenes from Allisons episode can be found online. Since 2009, Allison has worked with drug and alcohol treatment centers in Los Angeles County. In the third episode of season 5 of American Dad!, titled "Home Adrone", Roger asks an airline stewardess to bring him industrial adhesive and a plastic bag. In the seventh episode of the fourteenth season of South Park, Towelie, an anthropomorphic towel, develops an addiction to inhaling computer duster. In the show Squidbilles, the main character Early Cuyler is often seen inhaling gas or other substances. See also Inhaler or puffer, a medical device used for delivering medication into the body via the lungs (often used in the treatment of asthma) Khaliq v HM Advocate, a Scottish criminal case in which the court ruled that it is an offense to supply materials that were used for sniffing Mt Theo Program, a successful petrol-sniffing prevention program run by the indigenous Warlpiri community in Central Australia Jenkem, a purported inhalant and hallucinogen supposedly created from fermented human waste List of medical inhalants References Notes Further reading Burk, Isabel (2001). Inhalant Prevention Resource Guide (PDF). VA Dpt Ed (2nd ed.). The Health Network. Chier, Ruth (2003) [1997]. Danger: Inhalants. The Drug Awareness Library. Powerkids Press. pp. 24. ISBN 9780823923403. Lobo, Ingrid A. (2004). Inhalants. Drugs: the Straight Facts. p. 112. ISBN 9780791076361. External links Inhalants at National Institute on Drug Abuse "NIDA for Teens: Inhalants" at National Institute on Drug Abuse "Inhalants – Facts and Figures". Office of National Drug Control Policy. Archived from the original on 27 October 2002. Alt URL
Cortical visual impairment	Cortical visual impairment (CVI) is a form of visual impairment that is caused by a brain problem rather than an eye problem. (The latter is sometimes termed "ocular visual impairment" when discussed in contrast to cortical visual impairment.) Some people have both CVI and a form of ocular visual impairment. CVI is also sometimes known as cortical blindness, although most people with CVI are not totally blind. The term neurological visual impairment (NVI) covers both CVI and total cortical blindness. Delayed visual maturation, another form of NVI, is similar to CVI, except the childs visual difficulties resolve in a few months. Though the vision of a person with CVI may change, it rarely if ever becomes totally normal. The major causes of CVI are as follows: asphyxia, hypoxia (a lack of sufficient oxygen in the bodys blood cells), or ischemia (not enough blood supply to the brain), all of which may occur during the birth process; developmental brain defects; head injury; hydrocephalus (when the cerebrospinal fluid does not circulate properly around the brain, and collects in the head, putting pressure on the brain); a stroke involving the occipital lobe; and infections of the central nervous system, such as meningitis and encephalitis. Visual and Behavioural Characteristics Visual and Behavioural Characteristics of CVI are individual and may include several (but not necessarily all) of the following: The person with CVI may exhibit what at first appears to be frequent variable changes in vision. However, it is the environment that impacts their visual function rather than their neurology or capacity for vision at that moment. A persons change in visual function when processing visual information in a complex environment, or trying to process a certain complex or unfamiliar visual target likely accounts for what looks like their visual ability changing from one day to the next, or from minute to minute. Feeling tired or unwell may also compound this challenge. For some people with CVI the complexity of the environment, including variables like the complexity and familiarity of the visual input, or processing various forms of secondary sensory input (for instance, sound or touch) may cause them to have difficulty using their vision to their full potential. The amount of sensory input an individual can tolerate without impacting function significantly may change throughout development and person to person. Managing fatigue may reduce fluctuations but does not eliminate them, however utilizing breaks and being well rested may help to increase resilience during these times. Addressing these changes may mean adapting strategies that work for the individual person. For example, When undertaking critical activities, people with CVI should be prepared for their vision to fluctuate, by taking precautions such as always carrying a white cane, if they use one, even if they dont always use it to the fullest. Another example is having very large print available, just in case its needed (For example, consider the consequences of losing vision while giving a public speech). Other potential adaptations to improve visual function in higher environmental complexity may include strategies like clearing away excess clutter from a work spaces, or providing a plain background to view objects against, reducing noise levels, or other methods of monitoring and adapting for environmental complexity. One eye may perform significantly worse than the other, and depth perception can be very limited (although not necessarily zero). The field of view may be severely limited. The best vision might be in the centre (like tunnel vision) but more often it is at some other point, and it is difficult to tell what the person is really looking at. Note that if the person also has a common ocular visual impairment such as nystagmus then this can also affect which part(s) of the visual field are best. (Sometimes there exists a certain gaze direction which minimises the nystagmus, called a "null point.") Even though the field of view may be very narrow indeed, it is often possible for the person to detect and track movement. Movement is handled by the V5 part of the visual cortex, which may have escaped the damage. Sometimes a moving object can be seen better than a stationary one; at other times the person can sense movement but cannot identify what is moving. (This can be annoying if the movement is prolonged, and to escape the annoyance the person may have to either gaze right at the movement or else obscure it.) Sometimes it is possible for a person with CVI to see things while moving their gaze around that they didnt detect when stationary. However, movement that is too fast can be hard to track; some people find that fast-moving objects "disappear." Materials with reflective properties, which can simulate movement, may be easier for a person with CVI to see. However, too many reflections can be confusing (see cognitive overload). Some objects may be easier to see than others. For example, the person may have difficulty recognising faces or facial expressions but have fewer problems with written materials. This is presumably due to the different way that the brain processes different things. Colour and contrast are important. The brains colour processing is distributed in such a way that it is more difficult to damage, so people with CVI usually retain full perception of colour. This can be used to advantage by colour-coding objects that might be hard to identify otherwise. Sometimes yellow and red objects are easier to see, as long as this does not result in poor contrast between the object and the background. People with CVI strongly prefer a simplified view. When dealing with text, for example, the person might prefer to see only a small amount of it at once. People with CVI frequently hold text close to their eyes, both to make the text appear larger and to minimise the amount they must look at. This also ensures that important things such as letters are not completely hidden behind any scotomas (small defects in parts of the functioning visual field), and reduces the chances of getting lost in the text. However, the simplification of the view should not be done in such a way that it requires too rapid a movement to navigate around a large document, since too much motion can cause other problems (see above). In viewing an array of objects, people with CVI can more easily see them if they only have to look at one or two at a time. People with CVI also see familiar objects more easily than new ones. Placing objects against a plain background also makes them easier for the person with CVI to see. For the same reason (simplified view), the person may also dislike crowded rooms and other situations where their functioning is dependent on making sense of a lot of visual clutter. Visual processing can take a lot of effort. Often the person has to make a conscious choice about how to divide mental effort between making sense of visual data and performing other tasks. For some people, maintaining eye contact is difficult, which can create problems in Western culture (for example, bonding can be difficult for some parents who have an infant with CVI, and lack of contact in an older child can cause others to regard him or her with suspicion). It can also be difficult for some people with CVI to look at an object and reach for it at the same time. Looking and reaching are sometimes accomplished as two separate acts: look, then look away and reach. People with CVI can sometimes benefit from a form of blindsight, which manifests itself as a kind of awareness of ones surroundings that cannot consciously be explained (for example, the person correctly guesses what they should do in order to avoid an obstacle but does not actually see that obstacle). However, this cannot be relied on to work all the time. In contrast, some people with CVI exhibit spatial difficulties and may have trouble moving about in their environment. Approximately one third of people with CVI have some photophobia. It can take longer than usual to adjust to large changes in light level, and flash photography can be painful. On the other hand, CVI can also in some cases cause a desire to gaze compulsively at light sources, including such things as candle flames and fluorescent overhead lights. The use of good task lighting (especially low-temperature lamps which can be placed at very close range) is often beneficial. Although people (with or without CVI) generally assume that they see things as they really are, in reality the brain may be doing a certain amount of guessing and "filling in", which is why people sometimes think they see things that turn out on closer inspection not to be what they seemed. This can occur more frequently when a person has CVI. Hence, a person with CVI can look at an optical illusion or abstract picture and perceive something that is significantly different from what a person without CVI will perceive.The presence of CVI does not necessarily mean that the persons brain is damaged in any other way, but it can often be accompanied by other neurological problems, the most common being epilepsy. Diagnosis Diagnosing CVI is difficult. A diagnosis is usually made when visual performance is poor but it is not possible to explain this from an eye examination. Before CVI was widely known among professionals, some would conclude that the patient was faking their problems or had for some reason engaged in self-deception. However, there are now testing techniques that do not depend on the patients words and actions, such as fMRI scanning, or the use of electrodes to detect responses to stimuli in both the retina and the brain. These can be used to verify that the problem is indeed due to a malfunction of the visual cortex and/or the posterior visual pathway. See also Cortical blindness References Further reading Tallent, Aubri & Tallent, Andrei (2012). Little Bear Sees: How Children with Cortical Visual Impairment Can Learn to See. Little Bear Sees Publishing, of Wyatt-MacKenzie. p. 156. ISBN 978-1936214822. OCLC 1936214822. Roman-Lantzy, Christine (2019). Cortical Visual Impairment: Advanced Principles. New York: AFB Press. ISBN 978-1616480073. OCLC 1055566701. Roman-Lantzy, Christine (2017). Cortical Visual Impairment: An Approach to Assessment and Intervention 2nd Ed. New York: AFB Press. ISBN 978-0891286882. Dutton GN, Lueck, AH (2015). Vision and the Brain: Understanding Cerebral Visual Impairment in Children. New York: AFB Press. ISBN 978-0891286394. OCLC 904801331. Dutton, Gordon N (2006). "Cerebral Visual Impairment: Working within and around the Limitations of Vision". In Lueck, Amanda Hall; Dennison, Elizabeth; American Foundation for the Blind (eds.). Proceedings of the Summit on Cerebral/Cortical Visual Impairment: educational, family, and medical perspectives. New York: AFB Press. ISBN 0-89128-817-1. OCLC 68133091. Dutton GN, Jacobson LK (2001). "Cerebral visual impairment in children". Seminars in Neonatology. 6 (6): 477–85. doi:10.1053/siny.2001.0078. PMID 12014888. "Fact Sheet: Cortical Visual Impairment" by Mary Ann Demchak, Charmaine Rickard and Marty Elquist, published by The University of Nevada, Reno in the Nevada Dual Sensory Impairment Project 2002. External links CVI Now A CVI resource hub associated with Perkins School For the Blind Little Bear Sees A foundation providing families with information, tools and research which improves the lives of children with CVI PCVIS The Pediatric Cortical Visual Impairment Society is a nonprofit promoting research related to the improvement of vision care for children with CVI
Idiopathic guttate hypomelanosis	Idiopathic guttate hypomelanosis is characterised by multiple small whitish flat spots. They are typically irregular, well defined and frequently appear on the arms, legs and face of older people.It occurs in up to 80% of over 70-year olds. Females may notice them at a younger age than males. See also List of cutaneous conditions Skin lesion == References ==
Fetal-maternal haemorrhage	Fetal-maternal haemorrhage is the loss of fetal blood cells into the maternal circulation. It takes place in normal pregnancies as well as when there are obstetric or trauma related complications to pregnancy. Normally the maternal circulation and the fetal circulation are kept from direct contact with each other, with gas and nutrient exchange taking place across a membrane in the placenta made of two layers, the syncytiotrophoblast and the cytotrophoblast. Fetal-maternal haemorrhage occurs when this membrane ceases to function as a barrier and fetal cells may come in contact with and enter the maternal vessels in the decidua/endometrium. Description Normal pregnancy It is estimated that less than 1ml of fetal blood is lost to the maternal circulation during normal labour in around 96% of normal deliveries. The loss of this small amount of blood may however be a sensitising event and stimulate antibody production to the foetal red blood cells, an example of which is Rhesus disease of the newborn. Abnormal pregnancy Causes of increased foetal-maternal haemorrhage are seen as a result of trauma, placental abruption or may be spontaneous with no cause found. Up to 30ml of foetal-maternal transfusion may take place with no significant signs or symptoms seen in either mother or foetus. Loss in excess of this may result in significant morbidity and mortality to the fetus. Fetal-maternal haemorrhage is one cause of intrauterine death (IUD). Diagnosis The Kleihauer–Betke test is a blood test used to measure the amount of foetal hemoglobin transferred from a foetus to its mothers bloodstream. It takes advantage of the differential resistance of foetal hemoglobin to acid. A standard blood smear is prepared from the mothers blood, and exposed to an acid bath. This removes adult hemoglobin, but not foetal hemoglobin, from the red blood cells. Subsequent staining, using Shepards method, makes fetal cells (containing foetal hemoglobin) appear rose-pink in color, while adult red blood cells are only seen as "ghosts". 2000 cells are counted under the microscope and a percentage of foetal to maternal cells is calculated. Fetal-maternal haemorrhage can also be diagnosed by flow cytometry, using anti-foetal hemoglobin antibodies (anti-HbF). Treatment If ongoing and rapid haemorrhage is occurring then immediate delivery of the foetus may be indicated if the fetus is sufficiently developed. If the haemorrhage has already occurred and now stopped, an inutero transfusion of red cells to the foetus may be recommended. References == External links ==
Emanuel syndrome	Emanuel syndrome, also known as derivative 22 syndrome, or der(22) syndrome, is a rare disorder associated with multiple congenital anomalies, including profound intellectual disability, preauricular skin tags or pits, and conotruncal heart defects. It can occur in offspring of carriers of the constitutional chromosomal translocation t(11;22)(q23;q11), owing to a 3:1 meiotic malsegregation event resulting in partial trisomy of chromosomes 11 and 22. An unbalanced translocation between chromosomes 11 and 22 is described as Emanuel syndrome. It was first described in 1980 by American medical researchers Beverly S. Emanuel and Elaine H. Zackai, and a consortium of European scientists the same year. Sign and symptoms Infants with Emanuel syndrome have weak muscle tone (hypotonia) and fail to gain weight and grow at the expected rate (failure to thrive). Their development is significantly delayed, and most affected individuals have severe to profound intellectual disability. Other features of Emanuel syndrome include an unusually small head (microcephaly), distinctive facial features, and a small lower jaw (micrognathia). Ear abnormalities are common, including small holes in the skin just in front of the ears (preauricular pits, or sinuses). About half of all affected infants are born with an opening in the roof of the mouth (cleft palate) or a high arched palate. Males with Emanuel syndrome often have genital abnormalities. Additional signs of this condition can include heart defects and absent or unusually small (hypoplastic) kidneys; these problems can be life-threatening in infancy or childhood. Causes Emanuel syndrome is an inherited chromosome abnormality. It is caused by the presence of extra genetic material from chromosome 11 and chromosome 22 in each cell. In addition to the usual 46 chromosomes, people with Emanuel syndrome have an extra (supernumerary) chromosome consisting of a piece of chromosome 11 attached to a piece of chromosome 22. The extra chromosome is known as a derivative 22, or der(22), chromosome. Genetics People with Emanuel syndrome typically inherit the der(22) chromosome from an unaffected parent. The parent carries a chromosomal rearrangement between chromosomes 11 and 22 called a balanced translocation. No genetic material is gained or lost in a balanced translocation, so these chromosomal changes usually do not cause any health problems. As this translocation is passed to the next generation, it can become unbalanced. Individuals with Emanuel syndrome inherit an unbalanced translocation between chromosomes 11 and 22 in the form of a der(22) chromosome. (This der(22) chromosome is classified as one of the small supernumerary marker chromosomes.) These individuals have two normal copies of chromosome 11, two normal copies of chromosome 22 and extra genetic material from the der(22) chromosome. As a result of the extra chromosome, people with Emanuel syndrome have three copies of some genes in each cell instead of the usual two copies. The excess genetic material disrupts the normal course of development, leading to intellectual disability and birth defects. Researchers are working to determine which genes are included on the der(22) chromosome and what role these genes play in development. Diagnosis Emanuel syndrome can be diagnosed with a karyotype, fluorescence in situ hybridization or a chromosomal microarray analysis. Treatment Emanuel syndrome has no known cure, but individual symptoms may be treated. Assessments of individual systems, such as the cardiovascular, gastrointestinal, orthopedic, and neurological, may be necessary to determine the extent of impairment and options for treatment. See also The small supernumerary marker chromosome in the Emanuel syndrome References Further reading "Chromosome 11". Genetics Home Reference. U.S. National Library of Medicine. 2016. == External links ==
Hives	Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasting skin change. Fewer than 5% of cases last for more than six weeks. The condition frequently recurs.Hives frequently occur following an infection or as a result of an allergic reaction such as to medication, insect bites, or food. Psychological stress, cold temperature, or vibration may also be a trigger. In half of cases the cause remains unknown. Risk factors include having conditions such as hay fever or asthma. Diagnosis is typically based on the appearance. Patch testing may be useful to determine the allergy.Prevention is by avoiding whatever it is that causes the condition. Treatment is typically with antihistamines such as diphenhydramine and ranitidine. In severe cases, corticosteroids or leukotriene inhibitors may also be used. Keeping the environmental temperature cool is also useful. For cases that last more than six weeks immunosuppressants such as ciclosporin may be used.About 20% of people are affected. Cases of short duration occur equally in males and females while cases of long duration are more common in females. Cases of short duration are more common among children while cases of long duration are more common among those who are middle aged. Hives have been described at least since the time of Hippocrates. The term urticaria is from the Latin urtica meaning "nettle". Signs and symptoms Hives, or urticaria, is a form of skin rash with red, raised, itchy bumps. They may also burn or sting. Welts (raised areas surrounded by a red base) from hives can appear anywhere on the surface of the skin. Whether the trigger is allergic or not, a complex release of inflammatory mediators, including histamine from cutaneous mast cells, results in fluid leakage from superficial blood vessels. Welts may be pinpoint in size or several inches in diameter. Often the patches of rash move around.About 20% of people are affected. Cases of short duration occur equally in males and females, lasting a few days and without leaving any long-lasting skin changes. Cases of long duration are more common in females. Cases of short duration are more common among children while cases of long duration are more common among those who are middle aged. Fewer than 5% of cases last for more than six weeks. The condition frequently recurs. In half of cases of hives, the cause remains unknown.Angioedema is a related condition (also from allergic and nonallergic causes), though fluid leakage is from much deeper blood vessels in the subcutaneous or submucosal layers. Individual hives that are painful, last more than 24 hours, or leave a bruise as they heal are more likely to be a more serious condition called urticarial vasculitis. Hives caused by stroking the skin (often linear in appearance) are due to a benign condition called dermatographic urticaria. Cause Hives can also be classified by the purported causative agent. Many different substances in the environment may cause hives, including medications, food and physical agents. In perhaps more than 50% of people with chronic hives of unknown cause, it is due to an autoimmune reaction. Risk factors include having conditions such as hay fever or asthma. Medications Drugs that have caused allergic reactions evidenced as hives include codeine, sulphate of morphia, dextroamphetamine, aspirin, ibuprofen, penicillin, clotrimazole, trichazole, sulfonamides, anticonvulsants, cefaclor, piracetam, vaccines, and antidiabetic drugs. The antidiabetic sulphonylurea glimepiride, in particular, has been documented to induce allergic reactions manifesting as hives. Food The most common food allergies in adults are shellfish and nuts. The most common food allergies in children are shellfish, nuts, eggs, wheat, and soy. One study showed Balsam of Peru, which is in many processed foods, to be the most common cause of immediate contact urticaria. Another food allergy that can cause hives is alpha-gal allergy, which may cause sensitivity to milk and red meat. A less common cause is exposure to certain bacteria, such as Streptococcus species or possibly Helicobacter pylori. Infection or environmental agent Hives including chronic spontaneous hives can be a complication and symptom of a parasitic infection, such as blastocystosis and strongyloidiasis among others.The rash that develops from poison ivy, poison oak, and poison sumac contact is commonly mistaken for urticaria. This rash is caused by contact with urushiol and results in a form of contact dermatitis called urushiol-induced contact dermatitis. Urushiol is spread by contact but can be washed off with a strong grease- or oil-dissolving detergent and cool water and rubbing ointments. Dermatographic urticaria Dermatographic urticaria (also known as dermatographism or "skin writing") is marked by the appearance of weals or welts on the skin as a result of scratching or firm stroking of the skin. Seen in 4–5% of the population, it is one of the most common types of urticaria, in which the skin becomes raised and inflamed when stroked, scratched, rubbed, and sometimes even slapped.The skin reaction usually becomes evident soon after the scratching and disappears within 30 minutes. Dermatographism is the most common form of a subset of chronic hives, acknowledged as "physical hives".It stands in contrast to the linear reddening that does not itch seen in healthy people who are scratched. In most cases, the cause is unknown, although it may be preceded by a viral infection, antibiotic therapy, or emotional upset. Dermatographism is diagnosed by applying pressure by stroking or scratching the skin. The hives should develop within a few minutes. Unless the skin is highly sensitive and reacts continually, treatment is not needed. Taking antihistamines can reduce the response in cases that are annoying to the person. Pressure or delayed pressure This type of hives can occur right away, precisely after a pressure stimulus or as a deferred response to sustained pressure being enforced to the skin. In the deferred form, the hives only appear after about six hours from the initial application of pressure to the skin. Under normal circumstances, these hives are not the same as those witnessed with most urticariae. Instead, the protrusion in the affected areas is typically more spread out. The hives may last from eight hours to three days. The source of the pressure on the skin can happen from tight fitted clothing, belts, clothing with tough straps, walking, leaning against an object, standing, sitting on a hard surface, etc. The areas of the body most commonly affected are the hands, feet, trunk, abdomen, buttocks, legs and face. Although this appears to be very similar to dermatographism, the cardinal difference is that the swelled skin areas do not become visible quickly and tend to last much longer. This form of the skin disease is, however, rare. Cholinergic or stress Cholinergic urticaria (CU) is one of the physical urticaria which is provoked during sweating events such as exercise, bathing, staying in a heated environment, or emotional stress. The hives produced are typically smaller than classic hives and are generally shorter-lasting.Multiple subtypes have been elucidated, each of which require distinct treatment. Cold-induced The cold type of urticaria is caused by exposure of the skin to extreme cold, damp and windy conditions; it occurs in two forms. The rare form is hereditary and becomes evident as hives all over the body 9 to 18 hours after cold exposure. The common form of cold urticaria demonstrates itself with the rapid onset of hives on the face, neck, or hands after exposure to cold. Cold urticaria is common and lasts for an average of five to six years. The population most affected is young adults, between 18 and 25 years old. Many people with the condition also have dermographism and cholinergic hives.Severe reactions can be seen with exposure to cold water; swimming in cold water is the most common cause of a severe reaction. This can cause a massive discharge of histamine, resulting in low blood pressure, fainting, shock and even loss of life. Cold urticaria is diagnosed by dabbing an ice cube against the skin of the forearm for 1 to 5 minutes. A distinct hive should develop if a person has cold urticaria. This is different from the normal redness that can be seen in people without cold urticaria. People with cold urticaria need to learn to protect themselves from a hasty drop in body temperature. Regular antihistamines are not generally efficacious. One particular antihistamine, cyproheptadine (Periactin), has been found to be useful. The tricyclic antidepressant doxepin has been found to be effective blocking agents of histamine. Finally, a medication named ketotifen, which keeps mast cells from discharging histamine, has also been employed with widespread success. Solar urticaria This form of the disease occurs on areas of the skin exposed to the sun; the condition becomes evident within minutes of exposure. Water-induced This type of urticaria is also termed rare and occurs upon contact with water. The response is not temperature-dependent and the skin appears similar to the cholinergic form of the disease. The appearance of hives is within one to 15 minutes of contact with the water and can last from 10 minutes to two hours. This kind of hives does not seem to be stimulated by histamine discharge like the other physical hives. Most researchers believe this condition is actually skin sensitivity to additives in the water, such as chlorine. Water urticaria is diagnosed by dabbing tap water and distilled water to the skin and observing the gradual response. Aquagenic urticaria is treated with capsaicin (Zostrix) administered to the chafed skin. This is the same treatment used for shingles. Antihistamines are of questionable benefit in this instance since histamine is not the causative factor. Exercise The condition was first distinguished in 1980. People with exercise urticaria (EU) experience hives, itchiness, shortness of breath and low blood pressure five to 30 minutes after beginning exercise. These symptoms can progress to shock and even sudden death. Jogging is the most common exercise to cause EU, but it is not induced by a hot shower, fever, or with fretfulness. This differentiates EU from cholinergic urticaria.EU sometimes occurs only when someone exercises within 30 minutes of eating particular foods, such as wheat or shellfish. For these individuals, exercising alone or eating the injuring food without exercising produces no symptoms. EU can be diagnosed by having the person exercise and then observing the symptoms. This method must be used with caution and only with the appropriate resuscitative measures at hand. EU can be differentiated from cholinergic urticaria by the hot water immersion test. In this test, the person is immersed in water at 43 °C (109.4 °F). Someone with EU will not develop hives, while a person with cholinergic urticaria will develop the characteristic small hives, especially on the neck and chest.The immediate symptoms of this type are treated with antihistamines, epinephrine and airway support. Taking antihistamines prior to exercise may be effective. Ketotifen is acknowledged to stabilise mast cells and prevent histamine release, and has been effective in treating this hives disorder. Avoiding exercise or foods that cause the mentioned symptoms is very important. In particular circumstances, tolerance can be brought on by regular exercise, but this must be under medical supervision. Pathophysiology The skin lesions of urticarial disease are caused by an inflammatory reaction in the skin, causing leakage of capillaries in the dermis, and resulting in an edema which persists until the interstitial fluid is absorbed into the surrounding cells.Hives are caused by the release of histamine and other mediators of inflammation (cytokines) from cells in the skin. This process can be the result of an allergic or nonallergic reaction, differing in the eliciting mechanism of histamine release. Allergic hives Histamine and other proinflammatory substances are released from mast cells in the skin and tissues in response to the binding of allergen-bound IgE antibodies to high-affinity cell surface receptors. Basophils and other inflammatory cells are also seen to release histamine and other mediators, and are thought to play an important role, especially in chronic urticarial diseases. Autoimmune hives Over half of all cases of chronic idiopathic hives are the result of an autoimmune trigger. Roughly 50% of people with chronic urticaria spontaneously develop autoantibodies directed at the receptor FcεRI located on skin mast cells. Chronic stimulation of this receptor leads to chronic hives. People with hives often have other autoimmune conditions, such as autoimmune thyroiditis, celiac disease, type 1 diabetes, rheumatoid arthritis, Sjögrens syndrome or systemic lupus erythematosus. Infections Hive-like rashes commonly accompany viral illnesses, such as the common cold. They usually appear three to five days after the cold has started, and may even appear a few days after the cold has resolved. Nonallergic hives Mechanisms other than allergen-antibody interactions are known to cause histamine release from mast cells. Many drugs, for example morphine, can induce direct histamine release not involving any immunoglobulin molecule. Also, a diverse group of signaling substances called neuropeptides, have been found to be involved in emotionally induced hives. Dominantly inherited cutaneous and neurocutaneous porphyrias (porphyria cutanea tarda, hereditary coproporphyria, variegate porphyria and erythropoietic protoporphyria) have been associated with solar urticaria. The occurrence of drug-induced solar urticaria may be associated with porphyrias. This may be caused by IgG binding, not IgE. Dietary histamine poisoning This is termed scombroid food poisoning. Ingestion of free histamine released by bacterial decay in fish flesh may result in a rapid-onset, allergic-type symptom complex which includes hives. However, the hives produced by scombroid is reported not to include wheals. Stress and chronic idiopathic hives Chronic idiopathic hives has been anecdotally linked to stress since the 1940s. A large body of evidence demonstrates an association between this condition and both poor emotional well-being and reduced health-related quality of life. A link between stress and this condition has also been shown. A recent study has demonstrated an association between stressful life events (e.g. bereavement, divorce, etc.) and chronic idiopathic urticaria and also an association between post-traumatic stress and chronic idiopathic hives. Diagnosis Diagnosis is typically based on the appearance. The cause of chronic hives can rarely be determined. Patch testing may be useful to determine the allergy. In some cases regular extensive allergy testing over a long period of time is requested in hopes of getting new insight. No evidence shows regular allergy testing results in identification of a problem or relief for people with chronic hives. Regular allergy testing for people with chronic hives is not recommended. Acute versus chronic Acute urticaria is defined as the presence of evanescent wheals which completely resolve within six weeks. Acute urticaria becomes evident a few minutes after the person has been exposed to an allergen. The outbreak may last several weeks, but usually the hives are gone in six weeks. Typically, the hives are a reaction to food, but in about half the cases, the trigger is unknown. Common foods may be the cause, as well as bee or wasp stings, or skin contact with certain fragrances. Acute viral infection is another common cause of acute urticaria (viral exanthem). Less common causes of hives include friction, pressure, temperature extremes, exercise, and sunlight. Chronic urticaria (ordinary urticaria) is defined as the presence of evanescent wheals which persist for greater than six weeks. Some of the more severe chronic cases have lasted more than 20 years. A survey indicated chronic urticaria lasted a year or more in more than 50% of those affected and 20 years or more in 20% of them.Acute and chronic hives are visually indistinguishable. Related conditions Angioedema Angioedema is similar to hives, but in angioedema, the swelling occurs in a lower layer of the dermis than in hives, as well as in the subcutis. This swelling can occur around the mouth, eyes, in the throat, in the abdomen, or in other locations. Hives and angioedema sometimes occur together in response to an allergen, and is a concern in severe cases, as angioedema of the throat can be fatal. Vibratory angioedema This very rare form of angioedema develops in response to contact with vibration. In vibratory angioedema, symptoms develop within two to five minutes after contact with a vibrating object and abate after about an hour. People with this disorder do not experience dermographism or pressure urticaria. Vibratory angioedema is diagnosed by holding a vibrating device such as a laboratory vortex machine against the forearm for four minutes. Speedy swelling of the whole forearm extending into the upper arm is also noted later. The principal treatment is avoidance of vibratory stimulants. Antihistamines have also been proven helpful. Management The mainstay of therapy for both acute and chronic hives is education, avoiding triggers and using antihistamines. Chronic hives can be difficult to treat and lead to significant disability. Unlike the acute form, 50–80% of people with chronic hives have no identifiable triggers. But 50% of people with chronic hives will experience remission within 1 year. Overall, treatment is geared towards symptomatic management. Individuals with chronic hives may need other medications in addition to antihistamines to control symptoms. People who experience hives with angioedema require emergency treatment as this is a life-threatening condition. Treatment guidelines for the management of chronic hives have been published. According to the 2014 American practice parameters, treatment involves a stepwise approach. Step 1 consists of second generation, H1 receptor blocking antihistamines. Systemic glucocorticoids can also be used for episodes of severe disease but should not be used for long term due to their long list of side effects. Step 2 consists of increasing the dose of the current antihistamine, adding other antihistamines, or adding a leukotriene receptor antagonist such as montelukast. Step 3 consists of adding or replacing the current treatment with hydroxyzine or doxepin. If the individual doesnt respond to steps 1–3 then they are considered to have refractory symptoms. At this point, anti-inflammatory medications (dapsone, sulfasalazine), immunosuppressants (cyclosporin, sirolimus) or other medications like omalizumab can be used. These options are explained in more detail below. Antihistamines Non-sedating antihistamines that block histamine H1 receptors are the first line of therapy. First-generation antihistamines, such as diphenhydramine or hydroxyzine, block both brain and peripheral H1 receptors, and cause sedation. Second-generation antihistamines, such as loratadine, cetirizine or desloratadine, selectively antagonize peripheral H1 receptors, and are less sedating, less anticholinergic, and generally preferred over the first-generation antihistamines. Fexofenadine, a new-generation antihistamine that blocks histamine H1 receptors, may be less sedating than some second-generation antihistamines.People who do not respond to the maximum dose of H1 antihistamines may benefit from increasing the dose, then to switching to another non-sedating antihistamine, then to adding a leukotriene antagonist, then to using an older antihistamine, then to using systemic steroids and finally to using ciclosporin or omalizumab.H2-receptor antagonists are sometimes used in addition to H1-antagonists to treat urticaria, but there is limited evidence for their efficacy. Systemic steroids Oral glucocorticoids are effective in controlling symptoms of chronic hives however they have an extensive list of adverse effects such as adrenal suppression, weight gain, osteoporosis, hyperglycemia, etc. Therefore, their use should be limited to a couple of weeks. In addition, one study found that systemic glucocorticoids combined with antihistamines did not hasten the time to symptom control compared with antihistamines alone. Leukotriene-receptor antagonists Leukotrienes are released from mast cells along with histamine. The medications, montelukast and zafirlukast block leukotriene receptors and can be used as add on treatment or in isolation for people with CU. It is important to note that these medications may be more beneficial for people with NSAID induced CU. Other Other options for refractory symptoms of chronic hives include anti-inflammatory medications, omalizumab, and immunosuppressants. Potential anti-inflammatory agents include dapsone, sulfasalazine, and hydroxychloroquine. Dapsone is a sulfone antimicrobial agent and is thought to suppress prostaglandin and leukotriene activity. It is helpful in therapy-refractory cases and is contraindicated in people with G6PD deficiency. Sulfasalazine, a 5-ASA derivative, is thought to alter adenosine release and inhibit IgE mediated mast cell degranulation, Sulfasalazine is a good option for people with anemia who cannot take dapsone. Hydroxychloroquine is an antimalarial agent that suppresses T lymphocytes. It has a low cost however it takes longer than dapsone or sulfasalazine to work. Omalizumab was approved by the FDA in 2014 for people with hives 12 years old and above with chronic hives. It is a monoclonal antibody directed against IgE. Significant improvement in pruritus and quality of life was observed in a phase III, multicenter, randomized control trial.Immunosuppressants used for CU include cyclosporine, tacrolimus, sirolimus, and mycophenolate. Calcineurin inhibitors, such as cyclosporine and tacrolimus, inhibit cell responsiveness to mast cell products and inhibit T cell activity. They are preferred by some experts to treat severe symptoms. Sirolimus and mycophenolate have less evidence for their use in the treatment of chronic hives but reports have shown them to be efficacious. Immunosuppressants are generally reserved as the last line of therapy for severe cases due to their potential for serious adverse effects. Research Afamelanotide is being studied as a hives treatment.Opioid antagonists such as naltrexone have tentative evidence to support their use. History The term urticaria was first used by the Scottish physician William Cullen in 1769. It originates from the Latin word urtica, meaning stinging hair or nettle, as the classical presentation follows the contact with a perennial flowering plant Urtica dioica. The history of urticaria dates back to 1000–2000 BC with its reference as a wind-type concealed rash in the book The Yellow Emperors Inner Classic from Huangdi Neijing. Hippocrates in the 4th century first described urticaria as "knidosis" after the Greek word knido for nettle. The discovery of mast cells by Paul Ehrlich in 1879 brought urticaria and similar conditions under a comprehensive idea of allergic conditions. See also Urticarial vasculitis Dermatitis References External links Urticaria photo library at Dermnet
Re-entry ventricular arrhythmia	Re-entry ventricular arrhythmia is a type of paroxysmal tachycardia occurring in the ventricle where the cause of the arrhythmia is due to the electric signal not completing the normal circuit, but rather an alternative circuit looping back upon itself. There develops a self-perpetuating rapid and abnormal activation. ("Circus Movement" is another term for this.) Conditions necessary for re-entry include a combination of unidirectional block and slowed conduction. Circus movement may also occur on a smaller scale within the AV node (dual AV nodal physiology), a large bypass tract is not necessary.Re-entry is divided into two major types: [Anatomically Defined] re-entry and [Functionally Defined] re-entry. The circus movement can occur around an anatomical or functional core. Either type may occur alone, or together.Anatomically defined re-entry has a fixed anatomic pathway. Anomalous conduction via accessory pathways (APs) creates the re-entry circuit (which are also called bypass tracts), that exists between the atria and ventricles. Wolff–Parkinson–White syndrome (WPW) is an example of anatomically defined re-entry. WPW syndrome is an atrioventricular re-entrant tachycardia (AVRT), secondary to an accessory pathway that connects the epicardial surfaces of the atrium and ventricle along the AV groove. The majority of time symptomatic WPW fits the definition of AVRT (Supraventricular tachycardia) however AVNRT (dual AV nodal physiology) exist in ~10% of patients with WPW syndrome creating the possibility of spontaneous atrial fibrillation degenerating into ventricular fibrillation (VF). The fact that WPW patients are young and do not have structural heart disease, lead to using catheter ablation of the APs with the elimination of the atrial fibrillation as well as the episodes of re-entrant ventricular tachycardia. This elimination of the atrial fibrillation with ablation implies APs have some pathophysiologic role in the development of a-fib in the WPW patient.Functionally defined re-entry does not require the alternative anatomically defined circuit accessory pathways and it may not reside in just one location. Ventricular fibrillation (VF) following ventricular tachycardia (VT) may be described as a functionally defined re-entry problem caused by multiple mini re-entrant circuits spontaneously created within the ventricular myocardium. The original re-entrant circuit breaks down into multiple mini reentrant circuits. (VF becoming the grand finale of a single prolonged VT larger circus movement, propagating change in the "functional core" of the ventricular myocardium, dissipating mini reentrant circuits, exhibited as ventricular fibrillation.) Ischemia, electrolyte, pH abnormalities, or bradycardia are potential causes of functionally defined re-entry due to changes in the properties of the cardiac tissues functional core. (No accessory pathway required). For reentry to occur, the path length of circuit should be greater than the wave length (ERP × conduction velocity) of impulse. See also AV reentrant tachycardia AV nodal reentrant tachycardia References == External links ==
Ectodermal dysplasia	Ectodermal dysplasia (ED) is a group of genetic syndromes all deriving from abnormalities of the ectodermal structures.: 570 More than 150 different syndromes have been identified.Despite some of the syndromes having different genetic causes, the symptoms are sometimes very similar. Diagnosis is usually by clinical observation, often with the assistance of family medical histories so that it can be determined whether transmission is autosomal dominant or recessive. Ectodermal dysplasias are described as "heritable conditions in which there are abnormalities of two or more ectodermal structures such as the hair, teeth, nails, sweat glands, salivary glands, cranial-facial structure, digits and other parts of the body." Presentation Hair Individuals affected by an ED syndrome frequently have abnormalities of the hair follicles. Scalp and body hair may be thin, sparse, and very light in color, even though beard growth in affected males may be normal. The hair may grow very slowly or sporadically and it may be excessively fragile, curly, or even twisted. Kinky hair is also a possibility. Nails Fingernails and toenails may be thick, abnormally shaped, discolored, ridged, slow-growing, or brittle. The cuticles may be prone to infections. Skin The skin may be lightly pigmented. Skin sustaining injury may grow back permanently hypo-pigmented. In some cases, red or brown pigmentation may be present. Skin can be prone to rashes or infections and can be thick over the palms and soles. Care must be taken to prevent cracking, bleeding, and infection. Sweat glands Individuals affected by certain ED syndromes cannot perspire. Their sweat glands may function abnormally or may not have developed at all because of inactive proteins in the sweat glands. Without normal sweat production, the body cannot regulate temperature properly. Therefore, overheating is a common problem, especially during hot weather. Access to cool environments is important. Salivary glands Several studies have examined salivary flow rate in individuals and found parotid and submandibular salivary flow ranging from 5 to 15 times lower than average. This is consistent with the salivary glands being of ectodermal origin, although some findings have suggested that there is also mesodermal input. Teeth The development of tooth buds frequently results in congenitally absent teeth (in many cases a lack of a permanent set) and/or in the growth of teeth that are peg-shaped or pointed. The enamel may also be defective. Cosmetic dental treatment is almost always necessary and children may need dentures as early as two years of age. Multiple denture replacements are often needed as the child grows, and dental implants may be an option in adolescence, once the jaw is fully grown. Nowadays the option of extracting the teeth and substituting them with dental implants is quite common. In other cases, teeth can be crowned. Orthodontic treatment also may be necessary. Because dental treatment is complex, a multi-disciplinary approach is best. Other features People with ED often have certain cranial-facial features which can be distinctive: frontal bossing is common, longer or more pronounced chins are frequent, broader noses are also very common. In some types of ED, abnormal development of parts of the eye can result in dryness of the eye, cataracts, and vision defects. Professional eye care can help minimize the effects of ED on vision. Similarly, abnormalities in the development of the ear may cause hearing problems. Respiratory infections can be more common because the normal protective secretions of the mouth and nose are not present. Precautions must be taken to limit infections. Genetics ED can be classified by inheritance (autosomal dominant, autosomal recessive and X-linked) or by which structures are involved (hair, teeth, nails and/or sweat glands). There are several different types with distinct genetic causes: Hay–Wells syndrome (Rapp–Hodgkin syndrome) and EEC syndrome are all associated with TP63. Hypohidrotic ectodermal dysplasia can be associated with EDA, EDAR and EDARADD. Margarita Island ectodermal dysplasia is associated with PVRL1. Ectodermal dysplasia with skin fragility is associated with PKP1. Cloustons hidrotic ectodermal dysplasia is associated with GJB6. Naegeli syndrome/Dermatopathia pigmentosa reticulariss is associated with KRT14. Pachyonychia congenita is caused by multiple keratins. Focal dermal hypoplasia is associated with PORCN. Ellis–van Creveld syndrome is associated with EVC. Palmoplantar ectodermal dysplasia refers to several different conditions selectively affecting the hands and feet. Diagnosis In terms of the clinical evaluation, clinical features are the classification method Treatment Management for this condition is symptom specific Society and culture Notable cases Michael Berryman, American actor with hypohidrotic ectodermal dysplasia Levi Hawken, New Zealand skateboarder and artist who became well known in 2011 in New Zealand for the "Nek minnit" viral video on YouTube See also List of cutaneous conditions List of cutaneous conditions caused by mutations in keratins References == External links ==
Hypertensive heart disease	Hypertensive heart disease includes a number of complications of high blood pressure that affect the heart. While there are several definitions of hypertensive heart disease in the medical literature, the term is most widely used in the context of the International Classification of Diseases (ICD) coding categories. The definition includes heart failure and other cardiac complications of hypertension when a causal relationship between the heart disease and hypertension is stated or implied on the death certificate. In 2013 hypertensive heart disease resulted in 1.07 million deaths as compared with 630,000 deaths in 1990.According to ICD-10, hypertensive heart disease (I11), and its subcategories: hypertensive heart disease with heart failure (I11.0) and hypertensive heart disease without heart failure (I11.9) are distinguished from chronic rheumatic heart diseases (I05-I09), other forms of heart disease (I30-I52) and ischemic heart diseases (I20-I25). However, since high blood pressure is a risk factor for atherosclerosis and ischemic heart disease, death rates from hypertensive heart disease provide an incomplete measure of the burden of disease due to high blood pressure. Signs and symptoms The symptoms and signs of hypertensive heart disease will depend on whether or not it is accompanied by heart failure. In the absence of heart failure, hypertension, with or without enlargement of the heart (left ventricular hypertrophy) is usually symptomless.Symptoms, signs and consequences of congestive heart failure can include: Fatigue Irregular pulse or palpitations Swelling of feet and ankles Weight gain Nausea Shortness of breath Difficulty sleeping flat in bed (orthopnea) Bloating and abdominal pain Greater need to urinate at night An enlarged heart (cardiomegaly) Left ventricular hypertrophy and left ventricular remodeling Diminished coronary flow reserve and silent myocardial ischemia Coronary heart disease and accelerated atherosclerosis Heart failure with normal left ventricular ejection fraction (HFNEF), often termed diastolic heart failure Atrial fibrillation, other cardiac arrhythmias, or sudden cardiac deathHeart failure can develop insidiously over time or patients can present acutely with acute heart failure or acute decompensated heart failure and pulmonary edema due to sudden failure of pump function of the heart. Sudden failure can be precipitated by a variety of causes, including myocardial ischemia, marked increases in blood pressure, or cardiac arrhythmias. Diagnosis Differential diagnosis Other conditions can share features with hypertensive heart disease and need to be considered in the differential diagnosis. For example: Coronary artery disease or ischemic heart diseases due to atherosclerosis Hypertrophic cardiomyopathy Left ventricular hypertrophy in athletes Congestive heart failure or heart failure with normal ejection fraction due to other causes Atrial fibrillation or other disorders of cardiac rhythm due to other causes Sleep apnea Prevention Because there are no symptoms with high blood pressure, people can have the condition without knowing it. Diagnosing high blood pressure early can help prevent heart disease, stroke, eye problems, and chronic kidney disease.The risk of cardiovascular disease and death can be reduced by lifestyle modifications, including dietary advice, promotion of weight loss and regular aerobic exercise, moderation of alcohol intake and cessation of smoking. Drug treatment may also be needed to control the hypertension and reduce the risk of cardiovascular disease, manage the heart failure, or control cardiac arrhythmias. Patients with hypertensive heart disease should avoid taking over the counter nonsteroidal anti-inflammatory drugs (NSAIDs), or cough suppressants, and decongestants containing sympathomimetics, unless otherwise advised by their physician as these can exacerbate hypertension and heart failure. Blood pressure goals According to JNC 7, BP goals should be as follows: Less than 140/90mm Hg in patients with uncomplicated hypertension Less than 130/85mm Hg in patients with diabetes and those with renal disease with less than 1g/24-hour proteinuria Less than 125/75mm Hg in patients with renal disease and more than 1 g/24-hour proteinuria Treatment The medical care of patients with hypertensive heart disease falls under 2 categories— Treatment of hypertension Prevention (and, if present, treatment) of heart failure or other cardiovascular disease Epidemiology Hypertension or high blood pressure affects at least 26.4% of the worlds population. Hypertensive heart disease is only one of several diseases attributable to high blood pressure. Other diseases caused by high blood pressure include ischemic heart disease, cancer, stroke, peripheral arterial disease, aneurysms and kidney disease. Hypertension increases the risk of heart failure by two or three-fold and probably accounts for about 25% of all cases of heart failure. In addition, hypertension precedes heart failure in 90% of cases, and the majority of heart failure in the elderly may be attributable to hypertension. Hypertensive heart disease was estimated to be responsible for 1.0 million deaths worldwide in 2004 (or approximately 1.7% of all deaths globally), and was ranked 13th in the leading global causes of death for all ages. A world map shows the estimated disability-adjusted life years per 100,000 inhabitants lost due to hypertensive heart disease in 2004. Sex differences There are more women than men with hypertension, and, although men develop hypertension earlier in life, hypertension in women is less well controlled. The consequences of high blood pressure in women are a major public health problem and hypertension is a more important contributory factor in heart attacks in women than men. Until recently women have been under-represented in clinical trials in hypertension and heart failure. Nevertheless, there is some evidence that the effectiveness of antihypertensive drugs differs between men and women and that treatment for heart failure may be less effective in women. Ethnic differences Studies in the US indicate that a disproportionate number of African Americans have hypertension compared with non-Hispanic whites and Mexican Americans, and that they have a greater burden of hypertensive heart disease. Heart failure is more common in people of African American ethnicity, mortality from heart failure is also consistently higher than in white patients, and it develops at an earlier age. Recent data suggests that rates of hypertension are increasing more rapidly in African Americans than other ethnic groups. The excess of high blood pressure and its consequences in African Americans is likely to contribute to their shorter life expectancy compared with white Americans. References == External links ==
Drug-induced autoimmune hemolytic anemia	Drug-induced autoimmune hemolytic anemia is a form of hemolytic anemia. In some cases, a drug can cause the immune system to mistakenly think the bodys own red blood cells are dangerous, foreign substances. Antibodies then develop against the red blood cells. The antibodies attach to red blood cells and cause them to break down too early. It is known that more than 150 drugs can cause this type of hemolytic anemia. The list includes : Cephalosporins (a class of antibiotics) Dapsone Levodopa Levofloxacin Methyldopa Nitrofurantoin Nonsteroidal anti-inflammatory drugs (NSAIDs) - among them, the commonly used Diclofenac and Ibuprofen Phenazopyridine (pyridium) QuinidinePenicillin in high doses can induce immune mediated hemolysis via the hapten mechanism in which antibodies are targeted against the combination of penicillin in association with red blood cells. Complement is activated by the attached antibody leading to the removal of red blood cells by the spleen.The drug itself can be targeted by the immune system, e.g. by IgE in a Type I hypersensitivity reaction to penicillin, rarely leading to anaphylaxis. See also List of circulatory system conditions List of hematologic conditions References == External links ==
Enophthalmos	Enophthalmos is a posterior displacement of the eyeball within the orbit. It is due to either enlargement of the bony orbit and/or reduction of the orbital content, this in relation to each other.It should not be confused with its opposite, exophthalmos, which is the anterior displacement of the eye. It may be a congenital anomaly, or be acquired as a result of trauma (such as in a blowout fracture of the orbit), Horners syndrome (apparent enophthalmos due to ptosis), Marfan syndrome, Duanes syndrome, silent sinus syndrome or phthisis bulbi. References Further reading Cline RA, Rootman J (1984). "Enophthalmos: a clinical review". Ophthalmology. 91 (3): 229–37. doi:10.1016/s0161-6420(84)34299-3. PMID 6717910. == External links ==
Respiratory arrest	Respiratory arrest is a sickness caused by apnea (cessation of breathing) or respiratory dysfunction severe enough it will not sustain the body (such as agonal breathing). Prolonged apnea refers to a patient who has stopped breathing for a long period of time. If the heart muscle contraction is intact, the condition is known as respiratory arrest. An abrupt stop of pulmonary gas exchange lasting for more than five minutes may damage vital organs especially the brain, possibly permanently. Lack of oxygen to the brain causes loss of consciousness. Brain injury is likely if respiratory arrest goes untreated for more than three minutes, and death is almost certain if more than five minutes. Damage may be reversible if treated early enough. Respiratory arrest is a life-threatening medical emergency that requires immediate medical attention and management. To save a patient in respiratory arrest, the goal is to restore adequate ventilation and prevent further damage. Management interventions include supplying oxygen, opening the airway, and means of artificial ventilation. In some instances, an impending respiratory arrest could be predetermined by signs the patient is showing, such as the increased work of breathing. Respiratory arrest will ensue once the patient depletes their oxygen reserves and loses the effort to breathe. Respiratory arrest should be distinguished from respiratory failure. The former refers to the complete cessation of breathing, while respiratory failure is the inability to provide adequate ventilation for the bodys requirements. Without intervention, both may lead to decreased oxygen in the blood (hypoxemia), elevated carbon dioxide level in the blood (hypercapnia), inadequate oxygen perfusion to tissue (hypoxia), and may be fatal. Respiratory arrest is also different from cardiac arrest, the failure of heart muscle contraction. If untreated, one may lead to the other. Signs and symptoms One common symptom of respiratory arrest is cyanosis, a bluish discoloration of the skin resulting from an inadequate amount of oxygen in the blood. If respiratory arrest remains without any treatment, cardiac arrest will occur within minutes of hypoxemia, hypercapnia or both. At this point, patients will be unconscious or about to become unconscious.Symptoms of respiratory compromise can differ with each patient. Complications from respiratory compromise are increasing rapidly across the clinical spectrum, partly due to expanded use of opioids combined with the lack of standardized guidelines among medical specialties. While respiratory compromise creates problems that are often serious and potentially life-threatening, they may be prevented with the proper tools and approach. Appropriate patient monitoring and therapeutic strategies are necessary for early recognition, intervention and treatment. Causes Airway obstruction: Obstruction may occur in the upper and lower airway. Upper airway: Obstruction of the upper airway is common in infants less than 3 months old because they are nose breathers. Nasal blockage may easily lead to upper airway obstruction in infants. For other ages, upper airway obstruction may occur from a foreign body or edema of the pharynx, larynx, or trachea. In cases of decreased or total loss of consciousness, the tongue can lose muscle tone and obstruct the upper airway. Other potential causes of obstruction include tumors of the upper respiratory tract (oral cavity, pharynx, larynx), bodily fluids (blood, mucus, vomit), and trauma to the upper airway. The most common type of tumor of upper respiratory tract is squamous cell carcinoma, with the greatest risk factors for this condition being alcohol and tobacco use, with HPV (genotype 16) being another important risk factor. An epidemiological study of over 5 million cases of head and neck trauma in the United States resulting in visits to the emergency department found that the majority occur due to falls or blunt force, with foreign body injuries being more common in the pediatric population. Lower airway: may occur from bronchospasm, drowning, or airspace filling disorders (e.g. pneumonia, pulmonary edema, pulmonary hemorrhage). Obstructive conditions of the lower airway, including severe asthma or COPD episodes, can also lead to respiratory arrest. During these episodes, known as exacerbations, airway resistance is increased due to inflammatory changes in the lungs. This leads to increased work of breathing and decreased oxygen delivery to tissue. In asthma, this involves bronchiolar constriction whereas in COPD this involves small airway collapse during expiration and subsequent air-trapping. One of the ways the body attempts to compensate for these increased respiratory demands is by increasing respiratory rate, which in turn worsens respiratory muscle fatigue of the diaphragm and can eventually lead to respiratory arrest and death without timely medical intervention. Decreased respiratory effort: Central nervous system impairment leads to decreased respiratory effort. The respiratory center of the brain is located in the pons and medulla and is primarily driven by elevated carbon dioxide levels in the blood (hypercapnia) with decreased oxygen levels (hypoxemia) serving as a less potent stimulus. Central nervous system disorders, such as stroke and tumors, may cause hypoventilation. Drugs may decrease respiratory effort as well, such as opioids, sedative-hypnotics, and alcohol. These lower respiratory drive by blunting the response of the respiratory center of the brain to hypercapnia. Metabolic disorders could also decrease respiratory effort. Hypoglycemia and hypotension depress the central nervous system and compromise the respiratory system. Respiratory muscle weakness: Neuromuscular disorders may lead to respiratory muscle weakness, such as spinal cord injury, neuromuscular diseases, and neuromuscular blocking drugs. Respiratory muscle fatigue can also lead to respiratory muscle weakness if patients breathe over 70% of their maximum voluntary ventilation. Breathing over an extended period of time near maximum capacity can cause metabolic acidosis or hypoxemia, ultimately leading to respiratory muscle weakness. Diagnosis Diagnosis requires clinical evaluation, as detailed below. Initial assessment After determining the scene is safe, approach the patient and attempt to converse with him or her. If the patient responds verbally, you have established that there is at least a partially patent airway and that the patient is breathing (therefore not currently in respiratory arrest). If the patient is unresponsive, look for chest rise, which is an indicator of active breathing. A sternal rub is sometimes used to further assess for responsiveness. Initial assessment also involves checking for a pulse, by placing two fingers against the carotid artery, radial artery, or femoral artery to ensure this is purely respiratory arrest and not cardiopulmonary arrest. Checking a pulse after encountering an unresponsive patient is no longer recommended for non-medically trained personnel. Once one has determined that the patient is in respiratory arrest, the steps below can help to further identify the cause of the arrest. Clearing and opening the upper airway The first step to determining the cause of arrest is to clear and open the upper airway with correct head and neck positioning. The practitioner must lengthen and elevate the patients neck until the external auditory meatus is in the same plane as the sternum. The face should be facing the ceiling. The mandible should be positioned upwards by lifting the lower jaw and pushing the mandible upward. These steps are known as head tilt, chin lift, and jaw thrust, respectively. If a neck or spinal injury is suspected, the provider should avoid performing this maneuver as further nervous system damage may occur. The cervical spine should be stabilized, if possible, by using either manual stabilization of the head and neck by a provider or applying a C-collar. The C-collar can make ventilatory support more challenging and can increase intracranial pressure, therefore is less preferable than manual stabilization. If a foreign body can be detected, the practitioner may remove it with a finger sweep of the oropharynx and suction. It is important that the practitioner does not cause the foreign body to be lodged even deeper into the patients body. Foreign bodies that are deeper into the patients body can be removed with Magill forceps or by suction. A Heimlich maneuver can also be used to dislodge the foreign body. The Heimlich maneuver consists of manual thrusts to the upper abdomen until the airway is clear. In conscious adults, the practitioner will stand behind the patient with arms around the patients midsection. One fist will be in a clenched formation while the other hand grabs the fist. Together, both hands will thrust inward and upward by pulling up with both arms. Treatment Treatment varies depending on the cause of respiratory arrest. In many cases, it is necessary to establish an alternate airway and providing artificial ventilation that can include modes of mechanical ventilation. There are many ways to provide an airway and to deliver breathing support. The list below includes several options. Opioid-overdose Opioid overdose remains a major cause of death with an increase in rate of death by 12% in the United States from 2016 to 2017. In cases of overdose leading to respiratory arrest, the recommended treatment according to the 2015 American Heart Association guidelines is to administer intramuscular or intranasal naloxone at an initial dose of 0.04-0.4 mg. Dosing may be repeated up to 2 mg if initial dose is ineffective. Special consideration must be taken in individuals with opioid dependency as naloxone administration can induce severe opioid withdrawal, hence the recommended starting doses above. Goal of naloxone therapy is to restore respiratory drive in the individual, however mechanical ventilation may still be necessary during initial resuscitation. Bag-valve-mask (BVM) ventilation devices Resistance to bag valve mask may suggest presence of a foreign body that is obstructing airways and commonly used as a diagnostic tool and treatment for respiratory arrest. The bag-valve-mask device has a self-inflating bag with a soft mask that rests on the face. When the bag is connected to an oxygen supply, the patient will receive 60 to 100% of inspired oxygen. The purpose of bag-valve-mask is to provide adequate temporary ventilation and allow the body to achieve airway control by itself. However, if the bag-valve-mask is left on for more than five minutes, air may be introduced into the stomach. At that point, a nasogastric tube should be inserted to take the accumulated air out. During this process, practitioners must carefully position and maneuver the bag-valve-mask in order to keep airways open. To ensure an adequate seal when using the bag valve mask to ventilate, specific hand positioning is typically used. The provider places his or her thumb and index finger in a C shape on top of the mask and grips the jaw under the mask with the other three fingers, creating an E shape. The thumb and index finger provide downward pressure on the mask while the remaining fingers maintain head tilt and jaw thrust. The free hand can then be used to provide ventilation via the bag. For children, pediatric bags can be used. Pediatric bags have a valve that limits peak airway pressures to around 35–40 cm of water. Practitioners must tweak valve settings to accurately determine each of their patients to avoid hypoventilation or hyperventilation. When applying ventilation with the bag valve mask, the provider should apply just enough pressure to bag to see a chest rise. Providing excessive bag pressure can actually impair the blood flow to the heart and brain, so during CPR extra caution should be taken to limit size of tidal volume. The rate of manual ventilation should not exceed 12 times per minute, or one ventilation every 5 seconds as to avoid hyperventilation. Airway patency devices An oropharyngeal or nasopharyngeal airway is used during bag-valve-mask ventilation to prevent soft tissues from blocking the airway. An oropharyngeal airway may cause gagging and vomiting. Therefore, an oropharyngeal airway must be sized appropriately. An airway that is incorrectly sized can worsen the airway obstruction. The distance measured should be from the corner of the patients mouth to the angle of the jaw or earlobe. Laryngeal mask airways The laryngeal mask airway (LMA) is a tube with an inflatable cuff. A laryngeal mask airway can be positioned in the lower oropharynx to prevent airway obstruction by soft tissues and to create a safe channel for ventilation. The laryngeal mask airway is the standard rescue ventilation when endotracheal intubation cannot be accomplished. To insert the laryngeal mask airway into the patient, the deflated mask should be pressed against the hard palate, rotated past the base of the tongue, and reaching the pharynx. Once the mask has been placed in the correct position, the mask can be inflated. Some benefits of the laryngeal mask airway include minimization of gastric inflation and protection against regurgitation. A potential problem the laryngeal mask airway poses is that over inflation will make the mask more rigid and less able to adapt to the patients anatomy, compressing the tongue and causing tongue edema. In that case, the mask pressure should be lowered or a larger mask size should be used. If non-comatose patients are given muscle relaxants before the insertion of the laryngeal mask airway, they may gag and aspirate when the drugs are worn off. At that point, the laryngeal mask airway should be removed immediately to eliminate the gag response and buy time to start at new alternative intubation technique. Endotracheal intubation A tracheal tube is inserted into the trachea through the mouth or nose. Endotracheal tubes contain high-volume, low-pressure balloon cuffs to minimize air leakage and the risk of aspiration. Cuffed tubes were made originally for adults and children over 8 years old, but cuffed tubes have been used in infants and younger children to prevent air leakage. Cuffed tubes can be inflated to the extent needed to prevent air leakage. The endotracheal tube is a guaranteed mechanism to secure a compromised airway, limit aspiration, and bring about mechanical ventilation in comatose patients. The endotracheal tube is a great method for patients who are comatose, have an obstructed airway, or need mechanical ventilation. The endotracheal tube also allows suctioning of the lower respiratory tract. Drugs that can be inserted through the endotracheal tube during cardiac arrest are discouraged. Before intubation, patients need correct patient positioning and ventilation with 100% oxygen. The purpose of ventilation with 100% oxygen is to denitrogenate healthy patients and prolong the safe apneic time. Tubes with an internal diameter of over 8mm are acceptable for most adults. Insertion technique includes visualizing the epiglottis, the posterior laryngeal structure, and not passing the tube unless tracheal insertion is ensured. Surgical airway Surgical entry is required when the upper airway is obstructed by a foreign body, massive trauma has occurred, or if ventilation cannot be accomplished by any of the aforementioned methods. The requirement of the surgical airway is commonly known as the response to failed intubation. In comparison, surgical airways require 100 seconds to complete from incision to ventilation compared to laryngeal mask airways and other devices. During emergency cricothyrotomy, the patient lies on his back with neck extended and shoulders backward. The larynx is held in one hand by the practitioner while the other hand is holding a blade to incise the skin through the subcutaneous tissue and into the midline of the cricothyroid membrane to access the trachea. A hollow tube is used inserted into the trachea to keep the airway open. A tracheal hook is used to keep the space open and prevent retraction. Complications may include hemorrhage, subcutaneous emphysema, pneumomediastinum, and pneumothorax. Cricothyrotomy is used as emergency surgical access due to being fast and simple. Another surgical airway method is called tracheostomy. Tracheostomy is done in the operating room by a surgeon. This is the preferred method for patients requiring long-term ventilation. Tracheostomy uses skin puncture and dilators to insert the tracheostomy tube. Drugs to aid intubation Patients with respiratory arrest can be intubated without drugs. However, patients can be given sedating and paralytic drugs to minimize discomfort and help out with intubation. Pretreatment includes 100% oxygen, lidocaine, and atropine. 100% oxygen should be administered for 3 to 5 minutes. The time depends on pulse rate, pulmonary function, RBC count, and other metabolic factors. Lidocaine can be given in 1.5 mg/kg IV a few minutes before sedation and paralysis. The purpose of administering lidocaine is to blunt the sympathetic response of an increased heart rate, blood pressure, and intracranial pressure caused by laryngoscopy. Atropine can be given when children produce a vagal response, evidenced by bradycardia, in response to intubation. Some physicians even give out vecuronium, which is a neuromuscular blocker to prevent muscle fasciculations in patients over 4 years old. Fasciculations may result in muscle pain on awakening. Laryngoscopy and intubation are uncomfortable procedures, so etomidate may be delivered. Etomidate is a short-acting IV drug with sedative analgesic properties. The drug works well and does not cause cardiovascular depression. Ketamine is an anesthetic that may be used as well, but it may cause hallucinations or bizarre behavior upon awakening. Thiopental and methohexital may be used as well to provide sedation, but they tend to cause hypotension. Volume-cycled ventilation The purpose of mechanical ventilators is to deliver a constant volume, constant pressure, or a combination of both with each breath. Any given volume will correspond to a specific pressure on the pressure-volume curve and vice versa in any case. Settings on each mechanical ventilator may include respiratory rate, tidal volume, trigger sensitivity, flow rate, waveform, and inspiratory/expiratory ratio. The volume-cycled ventilation includes the volume-control function and delivers a set tidal volume. The pressure is not a fixed number but it varies with resistance and capacitance of the respiratory system. The volume-cycled ventilation is the simplest and most efficient of providing ventilation to a patients airway compared to other methods of mechanical ventilation. Each inspiratory effort that is beyond the set sensitivity threshold will be accounted for and fixed to the delivery of the corresponding tidal volume. If the patient does not breathe enough, then the volume-cycled ventilation will initiate a breath for the patient to bring up the breathing rate to the minimum respiratory rate. The synchronized intermittent mandatory ventilation (SIMV) is a similar method of mechanical ventilation that also delivers breaths at a fixed rate and volume that corresponds to the patients breathing. Unlike the Volume-Cycled Ventilation, patient efforts above the fixed rate are unassisted in the synchronized intermittent mandatory ventilation (SIMV). Pressure-cycled ventilation The pressure-cycled ventilation includes pressure control ventilation and pressure support ventilation. Both methods offer a set inspiratory pressure. The tidal volume varies depending on the resistance and elastance of the respiratory system. Pressure-cycled ventilation can help alleviate symptoms in patients with acute respiratory distress syndrome by limiting the distending pressure of the lungs. The pressure control ventilation is specifically a pressure-cycled form of assist-control ventilators. Assist-control ventilators describe a mode of ventilation that maintains a minimum respiratory rate regardless of whether or not the patient initiates a spontaneous breath. Each inspiratory effort that is beyond the sensitivity threshold delivers full pressures support for a fixed inspiratory time. There is maintenance of a minimum respiratory rate. In the pressure support ventilation, the minimum rate is not set. Instead, all breaths are triggered by the patient. The way that the pressure support ventilation works is by assisting the patient with a constant pressure until the patients inspiratory flow falls below a threshold. The longer, deeper inspiratory flows by the patient will result in a larger tidal volume. This method of mechanical ventilation will help patients assume more work of breathing. Noninvasive positive pressure ventilation (NIPPV) Noninvasive positive pressure ventilation is the delivery of positive pressure ventilation through a tight-fitting mask that covers the nose and mouth. It assists patients who can spontaneously breathe. Noninvasive positive pressure ventilation delivers end-expiratory pressure with a volume control setting. There are two ways that noninvasive positive pressure ventilation can be delivered: continuous positive airway pressure or bilevel positive airway pressure. In continuous positive airway pressure, constant pressure is maintained throughout cycles of respiration with no additional inspiratory support. In bilevel positive airway pressure, both expiratory positive airway pressure and inspiratory positive airway pressure are set by the physician. Noninvasive positive pressure ventilation should not be administered to people who are hemodynamically unstable, gastric emptying impaired, bowel obstructed or pregnant. In these circumstances, swallowing large amounts of air will result in vomiting and possibly death. If frequent arrhythmias, myocardial ischemia and shock arrhythmias occur, practitioners should change delivery to endotracheal intubation or conventional mechanical ventilation. People who should not use noninvasive positive pressure ventilation include obtunded patients or ones with secretions. Noninvasive positive pressure ventilation can be used in an outpatient setting for patients with obstructive sleep apnea. See also Crash cart Respiratory failure References == External links ==
Paranoid personality disorder	Paranoid personality disorder (PPD) is a mental illness characterized by paranoid delusions, and a pervasive, long-standing suspiciousness and generalized mistrust of others. People with this personality disorder may be hypersensitive, easily insulted, and habitually relate to the world by vigilant scanning of the environment for clues or suggestions that may validate their fears or biases. They are eager observers. They think they are in danger and look for signs and threats of that danger, potentially not appreciating other interpretations or evidence.They tend to be guarded and suspicious and have quite constricted emotional lives. Their reduced capacity for meaningful emotional involvement and the general pattern of isolated withdrawal often lend a quality of schizoid isolation to their life experience. People with PPD may have a tendency to bear grudges, suspiciousness, tendency to interpret others actions as hostile, persistent tendency to self-reference, or a tenacious sense of personal right. Patients with this disorder can also have significant comorbidity with other personality disorders, such as schizotypal, schizoid, narcissistic, avoidant and borderline. Causes A genetic contribution to paranoid traits and a possible genetic link between this personality disorder and schizophrenia exist. A large long-term Norwegian twin study found paranoid personality disorder to be modestly heritable and to share a portion of its genetic and environmental risk factors with the other cluster A personality disorders, schizoid and schizotypal.Psychosocial theories implicate projection of negative internal feelings and parental modeling. Cognitive theorists believe the disorder to be a result of an underlying belief that other people are unfriendly in combination with a lack of self-awareness. Diagnosis ICD-10 The World Health Organizations ICD-10 lists paranoid personality disorder under (F60.0). It is a requirement of ICD-10 that a diagnosis of any specific personality disorder also satisfies a set of general personality disorder criteria. It is also pointed out that for different cultures it may be necessary to develop specific sets of criteria with regard to social norms, rules and other obligations.PPD is characterized by at least three of the following symptoms: excessive sensitivity to setbacks and rebuffs; tendency to bear grudges persistently (i.e. refusal to forgive insults and injuries or slights); suspiciousness and a pervasive tendency to distort experience by misconstruing the neutral or friendly actions of others as hostile or contemptuous; a combative and tenacious sense of self-righteousness out of keeping with the actual situation; recurrent suspicions, without justification, regarding sexual fidelity of spouse or sexual partner; tendency to experience excessive self-aggrandizing, manifest in a persistent self-referential attitude; preoccupation with unsubstantiated "conspiratorial" explanations of events both immediate to the patient and in the world at large.Includes: expansive paranoid, fanatic, querulant and sensitive paranoid personality disorder. Excludes: delusional disorder and schizophrenia. DSM-5 The American Psychiatric Associations DSM-5 has similar criteria for paranoid personality disorder. They require in general the presence of lasting distrust and suspicion of others, interpreting their motives as malevolent, from an early adult age, occurring in a range of situations. Four of seven specific issues must be present, which include different types of suspicions or doubt (such as of being exploited, or that remarks have a subtle threatening meaning), in some cases regarding others in general or specifically friends or partners, and in some cases referring to a response of holding grudges or reacting angrily.PPD is characterized by a pervasive distrust and suspiciousness of others such that their motives are interpreted as malevolent, beginning by early adulthood and present in a variety of contexts. To qualify for a diagnosis, the patient must meet at least four out of the following criteria: Suspects, without sufficient basis, that others are exploiting, harming, or deceiving them. Is preoccupied with unjustified doubts about the loyalty or trustworthiness of friends or associates. Is reluctant to confide in others because of unwarranted fear that the information will be used maliciously against them. Reads hidden demeaning or threatening meanings into benign remarks or events. Persistently bears grudges (i.e., is unforgiving of insults, injuries, or slights). Perceives attacks on their character or reputation that are not apparent to others and is quick to react angrily or to counterattack. Has recurrent suspicions, without justification, regarding fidelity of spouse or sexual partner.The DSM-5 lists paranoid personality disorder essentially unchanged from the DSM-IV-TR version and lists associated features that describe it in a more quotidian way. These features include suspiciousness, intimacy avoidance, hostility and unusual beliefs/experiences. Other Various researchers and clinicians may propose varieties and subsets or dimensions of personality related to the official diagnoses. Psychologist Theodore Millon has proposed five subtypes of paranoid personality: Differential diagnosis Paranoid personality disorder can involve, in response to stress, very brief psychotic episodes (lasting minutes to hours). The paranoid may also be at greater than average risk of experiencing major depressive disorder, agoraphobia, social anxiety disorder, obsessive-compulsive disorder and substance-related disorders. Criteria for other personality disorder diagnoses are commonly also met, such as: schizoid, schizotypal, narcissistic, avoidant, borderline and negativistic personality disorder. Treatment Because of reduced levels of trust, there can be challenges in treating PPD. However, psychotherapy, antidepressants, antipsychotics and anti-anxiety medications can play a role when a person is receptive to intervention. Epidemiology PPD occurs in about 0.5–4.4% of the general population. It is seen in 2–10% of psychiatric outpatients. In clinical samples men have higher rates, whereas epidemiologically there is a reported higher rate of women. History Paranoid personality disorder is listed in DSM-V and was included in all previous versions of the DSM. One of the earliest descriptions of the paranoid personality comes from the French psychiatrist Valentin Magnan who described a "fragile personality" that showed idiosyncratic thinking, hypochondriasis, undue sensitivity, referential thinking and suspiciousness.Closely related to this description is Emil Kraepelins description from 1905 of a pseudo-querulous personality who is "always on the alert to find grievance, but without delusions", vain, self-absorbed, sensitive, irritable, litigious, obstinate, and living at strife with the world. In 1921, he renamed the condition paranoid personality and described these people as distrustful, feeling unjustly treated and feeling subjected to hostility, interference and oppression. He also observed a contradiction in these personalities: on the one hand, they stubbornly hold on to their unusual ideas, on the other hand, they often accept every piece of gossip as the truth. Kraepelin also noted that paranoid personalities were often present in people who later developed paranoid psychosis. Subsequent writers also considered traits like suspiciousness and hostility to predispose people to developing delusional illnesses, particularly "late paraphrenias" of old age.Following Kraepelin, Eugen Bleuler described "contentious psychopathy" or "paranoid constitution" as displaying the characteristic triad of suspiciousness, grandiosity and feelings of persecution. He also emphasized that these peoples false assumptions do not attain the form of real delusion.Ernst Kretschmer emphasized the sensitive inner core of the paranoia-prone personality: they feel shy and inadequate but at the same time they have an attitude of entitlement. They attribute their failures to the machinations of others but secretly to their own inadequacy. They experience constant tension between feelings of self-importance and experiencing the environment as unappreciative and humiliating.Karl Jaspers, a German phenomenologist, described "self-insecure" personalities who resemble the paranoid personality. According to Jaspers, such people experience inner humiliation, brought about by outside experiences and their interpretations of them. They have an urge to get external confirmation to their self-deprecation and that makes them see insults in the behavior of other people. They suffer from every slight because they seek the real reason for them in themselves. This kind of insecurity leads to overcompensation: compulsive formality, strict social observances and exaggerated displays of assurance.In 1950, Kurt Schneider described the "fanatic psychopaths" and divided them into two categories: the combative type that is very insistent about his false notions and actively quarrelsome, and the eccentric type that is passive, secretive, vulnerable to esoteric sects but nonetheless suspicious about others.The descriptions of Leonhard and Sheperd from the sixties describe paranoid people as overvaluing their abilities and attributing their failure to the ill-will of others; they also mention that their interpersonal relations are disturbed and they are in constant conflict with others.In 1975, Polatin described the paranoid personality as rigid, suspicious, watchful, self-centered and selfish, inwardly hypersensitive but emotionally undemonstrative. However, when there is a difference of opinion, the underlying mistrust, authoritarianism and rage burst through.In the 1980s, paranoid personality disorder received little attention, and when it did receive it, the focus was on its potential relationship to paranoid schizophrenia. The most significant contribution of this decade comes from Theodore Millon who divided the features of paranoid personality disorder to four categories:1) behavioral characteristics of vigilance, abrasive irritability and counterattack, 2) complaints indicating oversensitivity, social isolation and mistrust, 3) the dynamics of denying personal insecurities, attributing these to others and self-inflation through grandiose fantasies 4) coping style of detesting dependence and hostile distancing of oneself from others. Controversy Due to repeated concerns of the validity of PPD and poor empirical evidence, it has been suggested that PPD be removed from the DSM. This is also believed to contribute to low research output on PPD. See also References External links National Personality Disorder website for England Articles about Personality Disorders in Web4health web site
Diffuse infiltrative lymphocytosis syndrome	Diffuse infiltrative lymphocytosis syndrome occurs in HIV positive patients with low CD4 counts.It is similar to Sjögrens syndrome, with painless parotid and submandibular swelling, and sicca symptoms. The syndrome typically improves with HAART. == References ==
Skull bossing	Skull bossing is a descriptive term in medical physical examination indicating a protuberance of the skull, most often in the frontal bones of the forehead ("frontal bossing"). Although prominence of the skull bones may be normal, skull bossing may be associated with certain medical conditions, including nutritional, metabolic, hormonal, and hematologic disorders. Frontal bossing Frontal bossing is the development of an unusually pronounced forehead which may also be associated with a heavier than normal brow ridge. It is caused by enlargement of the frontal bone, often in conjunction with abnormal enlargement of other facial bones, skull, mandible, and bones of the hands and feet. Frontal bossing may be seen in a few rare medical syndromes such as acromegaly – a chronic medical disorder in which the anterior pituitary gland produces excess growth hormone (GH). Frontal bossing may also occur in diseases resulting in chronic anemia, where there is increased hematopoiesis and enlargement of the medullary cavities of the skull. Associated medical disorders Rickets Achondroplasia Acromegaly Basal cell nevus syndrome Congenital syphilis Cleidocranial dysostosis Crouzon syndrome Cryopyrin-Associated Periodic Syndrome (CAPS – PFS) Ectodermal dysplasia Extramedullary hematopoiesis Fragile X syndrome Hurler syndrome Osteopathia Striata with Cranial Sclerosis Pfeiffer syndrome Rubinstein-Taybi syndrome Russell-Silver syndrome (Russell-Silver dwarf) Thanatophoric dysplasia Talfan syndrome Trimethadione (antiseizure drug) use during pregnancy Beta-thalassemia (due to expansion of bone marrow secondary to increased hematopoiesis; see Extramedullary hematopoiesis) Hallermann-Streiff syndrome == References ==
Congenital diaphragmatic hernia	Congenital diaphragmatic hernia (CDH) is a birth defect of the diaphragm. The most common type of CDH is a Bochdalek hernia; other types include Morgagni hernia, diaphragm eventration and central tendon defects of the diaphragm. Malformation of the diaphragm allows the abdominal organs to push into the chest cavity, hindering proper lung formation.CDH is a life-threatening pathology in infants and a major cause of death due to two complications: pulmonary hypoplasia and pulmonary hypertension. Experts disagree on the relative importance of these two conditions, with some focusing on hypoplasia, others on hypertension. Newborns with CDH often have severe respiratory distress which can be life-threatening unless treated appropriately. Classification Bochdalek hernia The Bochdalek hernia, also known as a postero-lateral diaphragmatic hernia, is the most common manifestation of CDH, accounting for more than 95% of cases. In this instance the diaphragm abnormality is characterized by a hole in the postero-lateral corner of the diaphragm which allows passage of the abdominal viscera into the chest cavity. The majority of Bochdalek hernias (80–85%) occur on the left side of the diaphragm, a large proportion of the remaining cases occur on the right side. To date, it carries a high mortality and is an active area of clinical research. Morgagni hernia This rare anterior defect of the diaphragm is variably referred to as a Morgagni, retrosternal, or parasternal hernia. Accounting for approximately 2% of all CDH cases, it is characterized by herniation through the foramina of Morgagni which are located immediately adjacent and posterior to the xiphoid process of the sternum. Diaphragm eventration The diagnosis of congenital diaphragmatic eventration is used when there is abnormal displacement (i.e. elevation) of part or all of an otherwise intact diaphragm into the chest cavity. This rare type of CDH occurs because in the region of eventration the diaphragm is thinner, allowing the abdominal viscera to protrude upwards. Pathophysiology There are genetic causes of CDH including aneuploidies, chromosome copy number variants, and single gene mutations. Research implicates a few gene mutations including LONP1 and MYRF. It involves three major defects: A failure of the diaphragm to completely close during development Herniation of the abdominal contents into the chest Pulmonary hypoplasia Diagnosis This condition can often be diagnosed before birth and fetal intervention can sometimes help, depending on the severity of the condition. Infants born with diaphragmatic hernia experience respiratory failure due to both pulmonary hypertension and pulmonary hypoplasia. The first condition is a restriction of blood flow through the lungs thought to be caused by defects in the lung. Pulmonary hypoplasia or decreased lung volume is directly related to the abdominal organs presence in the chest cavity which causes the lungs to be severely undersized, especially on the side of the hernia.Survival rates for infants with this condition vary, but have generally been increasing through advances in neonatal medicine. Work has been done to correlate survival rates to ultrasound measurements of the lung volume as compared to the babys head circumference. This figure known as the lung-to-head ratio (LHR). Still, LHR remains an inconsistent measure of survival. Outcomes of CDH are largely dependent on the severity of the defect and the appropriate timing of treatment. A small percentage of cases go unrecognized into adulthood. Treatment The first step in management is orogastric tube placement and securing the airway (intubation). Ideally, the baby will never take a breath, to avoid air going into the intestines and compressing the lungs and heart. The baby will then be immediately placed on a ventilator. Extracorporeal membrane oxygenation (ECMO) has been used as part of the treatment strategy at some hospitals. ECMO acts as a heart-lung bypass. Diaphragm eventration is typically repaired thoracoscopically, by a technique called plication of the diaphragm. Plication basically involves a folding of the eventrated diaphragm which is then sutured in order to “take up the slack” of the excess diaphragm tissue. Prognosis Congenital diaphragmatic hernia has a mortality rate of 40–62%, with outcomes being more favorable in the absence of other congenital abnormalities. Individual rates vary greatly dependent upon multiple factors: size of hernia, organs involved, additional birth defects and/or genetic problems, amount of lung growth, age and size at birth, type of treatments, timing of treatments, complications (such as infections) and lack of lung function. See also Diaphragmatic rupture References External links Congenital Diaphragmatic Hernia Study Group under University of Texas Health Science Center at Houston DHREAMS (Diaphragmatic Hernia Research & Exploration; Advancing Molecular Science) Project coordinated at Columbia University Medical Center CDH International – A global initiative to stop Congenital Diaphragmatic Hernia
Neurofibroma	A neurofibroma is a benign nerve-sheath tumor in the peripheral nervous system. In 90% of cases, they are found as stand-alone tumors (solitary neurofibroma, solitary nerve sheath tumor or sporadic neurofibroma), while the remainder are found in persons with neurofibromatosis type I (NF1), an autosomal-dominant genetically inherited disease. They can result in a range of symptoms from physical disfiguration and pain to cognitive disability. Neurofibromas arise from nonmyelinating-type Schwann cells that exhibit biallelic inactivation of the NF1 gene that codes for the protein neurofibromin. This protein is responsible for regulating the RAS-mediated cell growth signaling pathway. In contrast to schwannomas, another type of tumor arising from Schwann cells, neurofibromas incorporate many additional types of cells and structural elements in addition to Schwann cells, making it difficult to identify and understand all the mechanisms through which they originate and develop. Types Neurofibromas have been subdivided into two broad categories: dermal and plexiform. Dermal neurofibromas are associated with a single peripheral nerve, while plexiform neurofibromas are associated with multiple nerve bundles. According to the World Health Organization classification system, dermal and plexiform neurofibromas are grade I tumors. Plexiform neurofibroma are more difficult to treat and can transform into malignant tumors. Dermal neurofibroma do not become malignant. Dermal neurofibroma Anatomy Dermal neurofibromas (sometimes referred to as cutaneous neurofibromas) originate in nerves in the skin. Three kinds are distinguished: Discrete cutaneous neurofibromas: Sessile or pedunculated masses on the skin, which are fleshy and non-tender, and can vary in size. Discrete subcutaneous neurofibromas: Lie below and look like bumps on the skin, which can sometimes be tender. Deep nodular neurofibromas: Involving tissues and organs underneath the dermis, but otherwise resembling cutaneous and subcutaneous neurofibromas. Age of onset Dermal neurofibromas typically arise in the teenage years and are often associated with the onset of puberty. In people with Neurofibromatosis Type I, they tend to continue to increase in number and size throughout adulthood, although limits exist as to how big they get, and cases progress at highly variable rates. Medical complications Dermal neurofibromas can lead to stinging, itching, pain, and disfigurement. No evidence of malignant transformation has been found. Plexiform neurofibroma Anatomy Plexiform neurofibromas can grow from nerves in the skin or from more internal nerve bundles, and can be very large. Internal plexiform neurofibromas are very difficult to remove completely because they extend through multiple layers of tissue and the attempt would damage healthy tissue or organs. Age of onset Plexiform neurofibromas occur earlier in life and are thought to be congenital defects. Medical complications Plexiform neurofibroma can cause disfigurement, neurological, and other clinical deficits. Plexiform neurofibromas have the potential to cause severe clinical complications if they occur in certain areas.About 10% of plexiform neurofibromas undergo transformation into a malignant peripheral nerve sheath tumor. Plexiform neurofibroma is a known precursor for MPNST in NF1 patients. The formation of malignant cancers from neurofibromas is associated with the loss of expression of the CDKN2A or TP53 gene in nonmyelinating Schwann cells that also exhibit biallelic inactivation of the NF1 gene. Cause This section discusses the tumorigenesis of neurofibroma in terms of genetics, cell signaling, histology and the cell cycle. Neurofibromin 1 gene The NF1 gene is composed of 60 exons spanning 350kb of genomic data, and maps to chromosomal region 17qll.2. This gene codes for neurofibromin which is a large 220-250 KDa cytoplasmic protein that is composed of 2,818 amino acids with three alternatively spliced exons (9a, 23a and 48a) in the encoding gene. The functional part of neurofibromin is a GAP, or GTPase-activating protein. GAP accelerates the conversion of the active GTP-bound RAS to its inactive GDP-bound form, inactivating RAS and reducing RAS-mediated growth signaling. Loss of RAS control leads to increased activity of other signaling pathways including RAF, ERK1/2, PI3K, PAK and mTOR-S6 kinase. This increased activity of downstream RAS pathways might work together to increase cell growth and survival. Genes that code for proteins that regulate cell growth, such as NF1 and TP53, are referred to as tumor suppressor genes. Neurofibromin has other growth-regulatory properties besides its ability to regulate RAS activity, but these other functions are poorly understood at this time. Schwann cells There are two kinds of Schwann cells, myelinating and nonmyelinating. While myelinating Schwann cells cover large diameter (>1 micrometer) peripheral nervous system (PNS) axons with myelin, nonmyelinating Schwann cells encapsulate small diameter PNS axons with their cytoplasmic processes. Nonmyelinating Schwann cells are the neoplastic element in neurofibromas. This conglomeration of nonmyelinating Schwann cells and axons is called a Remak bundle. While nonmyelinating Schwann cells are the origin of neurofibromas, the mutations that make them susceptible to this transformation occur in Schwann cell precursors during early nerve development. Mutated nonmyelinating Schwann cells do not form normal Remak bundles. Instead, they fail to properly surround and segregate target axons. It is unknown at this time why, if both types of Schwann cells exhibit bilallelic inactivation of the NF1 gene, only the nonmyelinating variety give rise to neurofibromas. Loss of tumor suppressor function Neurofibromas arise from nonmyelinating Schwann cells that only express the inactive version of the NF1 gene, which leads to a complete loss of expression of functional neurofibromin. While one defective allele may be inherited, loss of heterozygosity (LOH) must occur before a neurofibroma can form; this is called the two-hit hypothesis. This LOH happens by the same mechanisms, such as oxidative DNA damage, that causes mutations in other cells. Once a nonmyelinating Schwann cell has suffered inactivation of its NF1 genes, it begins to proliferate rapidly. This condition is called hyperplasia, which is cell growth beyond what is normally seen. However, despite increased numbers of nonmyelinating Schwann cells, there is no neurofibroma yet. In order for the neurofibroma to develop, cells that are heterozygous for the NF1 gene must be recruited to the site. It has been hypothesized that the proliferating nonmyelinating Schwann cells secrete chemoattractants such as the KIT ligand, and angiogenic factors such as the heparin-binding growth factor midkine. These chemicals promote the migration of different kinds of cells that are heterozygous for the NF1 gene into the hyperplastic lesions created by the nonmyelinating Schwann cells. These cell types include fibroblasts, perineurial cells, endothelial cells, and mast cells. The mast cells then secrete mitogens or survival factors that alter the developing tumor microenvironment and result in neurofibroma formation. Dermal and plexiform neurofibromas differ in later development stages, but the details are unclear at this point. Diagnosis Dermal neurofibromas may be 2 to 20 mm in diameter, is soft, flaccid, and pinkish-white, and frequently this soft small tumor can be invaginated, as if through a ring in the skin by pressure with the finger, a maneuver called "button-holing".: 619 A blood test for protein melanoma inhibitory activity may be used to detect the presence of neurofibromas.A biopsy can be used for histopathology diagnosis. Treatments Dermal neurofibroma Dermal neurofibromas are not usually surgically removed unless they are painful or disfiguring, because there are generally so many of them and they are not dangerous. CO2 lasers have been used to remove dermal neurofibromas. In a paper titled Hypertrophic Scars After Therapy with CO2 Laser for Treatment of Multiple Cutaneous Neurofibromas Ostertag et al. said this about treatment by laser: "The cosmetic disfigurement is the most important issue in the decision to treat cutaneous symptoms of neurofibromatosis. Treating patients with extensive neurofibromas with [a] CO2 laser is still the best choice. However, it is strongly advised that a test treatment be performed to judge the effectiveness of the procedure and whether the developed scar is an acceptable trade-off." Plexiform neurofibroma Surgery As of 2002, the primary treatment option for plexiform neurofibroma was surgery.Removal of plexiform neurofibromas is difficult because they can be large and cross tissue boundaries. However, besides pain, plexiform neurofibromas are sometimes removed due to the possibility of malignant transformation. The following examples show that plexiform neurofibromas can form anywhere and can make surgical resection difficult: A large plexiform neurofibroma in the leg of a 6-year-old male. The authors state: "Our case was operated, as both the cutaneous and deep branches of the peroneal nerve were involved causing pain and numbness in the leg, and because there was a possibility for malignant transformation, as growth in the mass was realized by the family members of the patient." The authors also note, "However, complete resection is L quite difficult O due to invasion H of the tumor into the surrounding soft tissues." A neurofibroma on the left ventricle. The neurofibroma was removed and the patients mitral valve had to be replaced. A 14-year-old girl with NF1 was diagnosed with a neurofibroma involving her bladder, a rare location. Radiation Once a plexiform neurofibroma has undergone malignant transformation, radiation and chemotherapy can be used as treatment. However, radiation is generally not used as a treatment for plexiform neurofibromas because of concerns that this could actually promote malignant transformation. There has even been a documented case of a Schwannoma being induced from a neurofibroma due to radiation therapy. Medications ACE inhibitors have been proposed as a novel treatment of neurofibromas. ACE inhibitors are currently used to treat hypertension and congestive heart failure, to avert remodeling and reinfarction after myocardial infarction, and to ameliorate diabetic nephropathy and other renal diseases. ACE inhibitors work by indirectly down regulating TGF-beta, which is a growth factor that has been shown to influence the development of tumors. No effect Pirfenidone inhibits fibroblast growth. Studies showed no improvement over controls. Tipifarnib (also known as drug R115777) inhibits the activation of RAS. This drug is a Farnesyltransferase inhibitor which inhibits the Ras kinase in a post translational modification step before the kinase pathway becomes hyperactive. It successfully passed phase one clinical trials but was suspended (NCT00029354) in phase two after showing no improvement over controls. Research The many drug therapies under study for neurofibromas are in various stages of research; more time will be required to determine if these are viable options for the treatment of neurofibromas. Sirolimus, a compound that inhibits mTOR signalling, is being studied to treat plexiform neurofibromas.The combination of erlotinib with sirolimus was studied to treat low-grade gliomas.Early research has shown potential for using the c-kit tyrosine kinase blocking properties of imatinib to treat plexiform neurofibromas.Peginterferon alfa-2b is being studied to treat plexiform neurofibromas.Sorafenib is being studied for treatment of unresectable plexiform neurofibroma and low-grade astrocytomas.In vitro, tranilast, inhibits growth of neurofibroma cells.Gene therapy for the neurofibromin 1 gene represents the ultimate solution to preventing the cluster of maladies which are enabled by the mutation. As of 2006, therapy for NF1 tumors had not been tested due to the lack of an appropriate NF1 tumor model. See also Malignant peripheral nerve sheath tumor Neurofibromatosis Neurofibromin Genetic disorder Watson syndrome Proteus syndrome RASopathy Palisaded encapsulated neuroma Skin lesion List of cutaneous conditions References External links DermAtlas 67 "Neurofibroma" at Dorlands Medical Dictionary Ferner RE, ODoherty MJ (December 2002). "Neurofibroma and schwannoma". Current Opinion in Neurology. 15 (6): 679–684. doi:10.1097/00019052-200212000-00004. PMID 12447105. S2CID 23782923.
Diffuse intrinsic pontine glioma	A diffuse intrinsic pontine glioma (DIPG) is a tumour located in the pons (middle) of the brain stem. Glioma is a general name for any tumour that arises from the supportive tissue called glia, which help keep the neurons in place and functioning well. DIPG is a brainstem glioma. The brain stem is the bottommost portion of the brain, connecting the cerebrum with the spinal cord. The majority of brain stem tumours occur in the pons and are diffusely infiltrating (they grow amidst the nerves), and therefore cannot be surgically removed. The brain stem contains all of the incoming neurons within the spinal cord, as well as important structures involved in eye movements and in face and throat muscle control and sensation. Diagnosis Like most brainstem tumors, diagnosing diffuse intrinsic pontine glioma usually involves non-invasive brain imaging like MRI, in addition to neurologic physical exam. Biopsies and other procedures are very uncommon. Similar to DIPG, diffuse midline gliomas (DMG) often fall into similar categories for both diagnosis and treatment as DIPG and are often categorized together. More recently, biopsies are performed so that the best option for clinical trials can be chosen.In studies resulting from the DIPG/DMG Registry and in connection with the DIPG/DMG Collaborative, statistics reveal that approximately 150–300 patients are diagnosed with DIPG in the USA per year, the median age of patients with DIPG is approximately 6–7 years old and the male/female ratio of DIPG patients is 1:1. Treatment The standard treatment for DIPG is 6 weeks of radiation therapy, which often dramatically improves symptoms. However, symptoms usually recur after 6 to 9 months and progress rapidly. Neurosurgery Surgery to attempt tumour removal is usually not possible or advisable for DIPG. By nature, these tumors 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. A neurosurgically performed brain-stem biopsy for immunotyping of diffuse intrinsic pontine glioma has served a limited recent role in experimental clinical studies and treatment trials. This, however, is not the current standard of care, as it presents considerable risk given the biopsy location, and thus is appropriately performed only in the context of participation in an ongoing clinical treatment trial. Pontine biopsy is in no way a therapeutic or curative surgery, and the risks (potentially catastrophic and fatal) are only outweighed when the diagnosis is uncertain (extremely unusual) or the patient is enrolled in an approved clinical trial. Radiotherapy Conventional radiotherapy, limited to the involved area of tumour, is the mainstay of treatment for DIPG. A total radiation dosage ranging from 5400 to 6000 cGy, administered in daily fractions of 150 to 200 cGy over 6 weeks, is standard. Hyperfractionated (twice-daily) radiotherapy was used previously to deliver higher radiation dosages, but did not lead to improved survival. Radiosurgery (e.g., gamma knife or cyberknife) has a role in the treatment of DIPG and may be considered in selected cases. Chemotherapy and other drug therapies The role of chemotherapy in DIPG remains unclear. Studies have shown little improvement in survival, although efforts (see below) through the Childrens Oncology Group (COG), Paediatric Brain Tumour Consortium (PBTC), and others are underway to explore further the use of chemotherapy and other drugs. Drugs that increase the effect of radiotherapy (radiosensitizers) have shown no added benefit, but promising new agents are under investigation. Immunotherapy with beta-interferon and other drugs has also had little effect in trials. Intensive or high-dose chemotherapy with autologous bone marrow transplantation or peripheral blood stem cell rescue has not demonstrated any effectiveness in brain stem gliomas. Future clinical trials may involve medicines designed to interfere with cellular pathways (signal transfer inhibitors), or other approaches that alter the tumor or its environment. Prognosis DIPG is a terminal illness, since it has a 5-year survival rate of <1%. The median overall survival of children diagnosed with DIPG is approximately 9 months. The 1- and 2-year survival rates are approximately 30% and less than 10%, respectively. These statistics make DIPG one of the most devastating pediatric cancers. Although 75–85% of patients show some improvement in their symptoms after radiation therapy, DIPGs almost always begin to grow again (called recurrence, relapse, or progression). Clinical trials have reported that the median time between radiation therapy and progression is 5–8.8 months. Patients whose tumors begin to grow again may be eligible for experimental treatment through clinical trials to try to slow or stop the growth of the tumor. However, clinical trials have not shown any significant benefit from experimental DIPG therapies so far.DIPGs that progress usually grow quickly and affect important parts of the brain. The median time from tumor progression to death is usually very short, between 1 and 4.5 months. During this time, doctors focus on palliative care: controlling symptoms and making the patient as comfortable as possible. Research As is the case with most brain tumors, a major difficulty in treating DIPG is overcoming the blood–brain barrier.In the brain – unlike in other areas of the body, where substances can pass freely from the blood into the tissue – there is very little space between the cells lining the blood vessels. Thus, the movement of substances into the brain is significantly limited. This barrier is formed by the lining cells of the vessels as well as by projections from nearby astrocytes. These two types of cells are knitted together by proteins to form what are called "tight junctions". The entire structure is called the blood–brain barrier (BBB). It prevents chemicals, toxins, bacteria, and other substances from getting into the brain, and thus serves a continuous protective function. However, with diseases such as brain tumors, the BBB can also prevent diagnostic and therapeutic agents from reaching their target. Researchers and clinicians have tried several methods to overcome the blood–brain barrier: Intrathecal/intraventricular administration: Chemotherapy is injected directly into the cerebrospinal fluid, either through a lumbar puncture or a surgically implanted catheter. Intracerebral implants: A neurosurgeon creates a cavity within a tumor to allow the placement of dime-sized chemotherapy wafers, such as Gliadel wafers. Several of these wafers can be placed at the time of surgery and will release the chemotherapy agent carmustine slowly over time. This provides a much higher concentration of chemotherapy in the brain than can be obtained with intravenous administration, and it causes fewer systemic side effects. However, it is an option only for patients with surgically resectable tumours; it cannot be used to treat DIPG. Osmotic blood–brain barrier disruption (BBBD): The cells of the blood–brain barrier are shrunk by a concentrated sugar solution (mannitol). This opens the barrier and allows 10 to 100 times more chemotherapy to enter the brain. A catheter is placed into a large artery (usually the one in the groin called the femoral artery) and threaded up to the carotid or vertebral artery. The hypertonic mannitol is injected, followed by a chemotherapeutic agent. Patients spend a few days in the hospital for each administration. This has been attempted with DIPG tumours. Convection-enhanced delivery: Chemotherapy is delivered to the tumour by a surgically implanted catheter under a pressure gradient to achieve more distribution than with diffusion alone. Limited experiments have been conducted with brain tumors, including one with a DIPG. Drug carriers: Carriers such as "Trojan horse" molecules, liposomes, and nanoparticles might theoretically allow a therapeutic drug to enter the brain. Such tactics are mostly in the investigatory stages and are not yet clinically relevant to brain tumour treatment. Prominent patients Karen Armstrong (1959–1962), daughter of American astronaut Neil Armstrong and his first wife, Janet Elizabeth Shearon. Elena Desserich (2000–2007), daughter of Brooke and Keith Desserich. After her passing her parents founded The Cure Starts Now Foundation, the first international DIPG/DMG charity that today has funded over $12 million in research at 114 hospitals. Her story was also chronicled in Notes Left Behind and became a New York Times bestselling book on November 12, 2009. Gabriella Miller (2003–2013), American childhood cancer awareness advocate who raised thousands of dollars for childhood cancer charities and founded Smashing Walnuts Foundation. The Gabriella Miller Kids First Research Act, signed into US law in 2014, was named after her. Lauren Hill (1995–2015), American freshman basketball player of Mount St. Joseph University, Cincinnati. To fulfil her wish of playing basketball for the college team for one game, the 2014 Hiram vs. Mount St. Joseph womens basketball game was scheduled 13 days earlier than the initially planned date and carried a brain cancer awareness message. Her efforts resulted in over $2.2 million raised for DIPG research through The Cure Starts Now Foundation. Nathaniel Kayne Finley (1999-2017), born to Curtis Lee, a former member of the U.S. Armed Forces and Kirsten Darlene Finley. Finley was a member of USA Swimming through Northern Kentucky Clippers and Daytona Beach Speed swimming clubs. Despite being diagnosed with DIPG in late 2016, Finley choose to attend LSU as a freshman in fall 2017, majoring in the College of Agriculture, Animal Sciences with aspirations of becoming a veterinarian. Prior to his death, Finley signed an advance directive, ensuring that his tumor could be donated for scientific research, the same year, he established Cannonballs for Kayne, a DIPG research foundation, committed to families, education and funding research for a cure. In popular culture Notes Left Behind, a non-fictional book published in 2009, is about a girl named Elena Desserich who left hundreds of notes to her family before she died of DIPG at age 6. == References ==
Cervical artery dissection	Cervical artery dissection is dissection of one of the layers that compose the carotid and vertebral artery in the neck (cervix). They include: Carotid artery dissection, a separation of the layers of the artery wall supplying oxygen-bearing blood to the head and brain. Vertebral artery dissection, a flap-like tear of the inner lining of the vertebral artery that supply blood to the brain and spinal cord.Cervical dissections can be broadly classified as either "spontaneous" or traumatic. Cervical artery dissections are a significant cause of strokes in young adults.A dissection typically results in a tear in one of the layers of the arterial wall. The result of this tear is often an intramural hematoma and/or aneurysmal dilation in the arteries leading to the intracranial area.Signs and symptoms of a cervical artery dissection are often non-specific and can be localized or generalized. There is no specific treatment, although most patients are either given an anti-platelet or anti-coagulation agent to prevent or treat strokes. Epidemiology Cervical artery dissection has been noted to be a common cause of young adult strokes, with some sources indicating a prevalence of up to 20% in this young adult population with annual incidence rates between 2.6 and 2.9 per 100,000, although these incidences may be misleading with true incidences being higher because clinical presentations can vary, many being minor or self-limited, and thus these dissections can go undiagnosed. In population-based studies, the peak age of presentation is approximately 45 years with a slight gender predisposition towards males (53-57%).Cervical arteries, as mentioned above, consist of two pairs of arteries: vertebral and carotid. As such, cervical artery dissection can be further categorized based on the involvement of artery: carotid vs. vertebral, and the location of the dissection: intracranial vs. extracranial. Causes The two main causes of cervical artery dissection can be broadly categorized as either spontaneous or traumatic. Arterial walls are composed of three layers: an intima (the innermost layer), media (the middle muscular layer), and adventitia (the outermost layer). A tear in one of the layers of the arterial walls can result in blood collecting within a pocket between the layers of the artery, which can result in an intramural hematoma and/or aneursymal dilation. At the moment, there is no definitive location for the dissection, with some believing dissection initially occurs within the connective tissue and vasa vasorum of the media while others believe dissection begins with an intimal tear. Spontaneous Spontaneous cervical artery dissections are dissections that occur without any trauma to the neck. More specifically, this can include potential causes such as hereditary connective tissue diseases, family history of strokes, infections and other miscellaneous causes such as smoking, hypertension, migraines and contraceptive use. Hereditary connective tissue diseases include autosomal polycystic kidney disease, Ehlers-Danlos syndrome, Marfan syndrome, fibromuscular dysplasia, and osteogenesis imperfecta type 1 although studies have shown that the link between hereditary connective tissue diseases and cervical artery dissection is low, ranging from 0-0.6% in one study and 5-18% in another study. Traumatic Traumatic cervical artery dissections are dissections that occur after any sort of trauma to the neck, ranging from minor trauma such as nose-blowing or sneezing to severe trauma such as roadside accidents. Most traumatic dissections are secondary to some form of rapid decelerations injuries resulting in hyperextension or hyperflexion with rotational injury of the neck. Pathophysiology Cervical artery dissections begin initially with a small tear in the innermost layer of the arterial wall, the tunica intima, or rupture of the vasa vasorum with bleeding within the media. As the arterial wall begins to tear, blood begins to enter this newly formed false lumen and the resulting hematoma formation can either narrow (stenosis) or occlude the artery, decreasing or completely blocking blood flow through the artery. A complete occlusion of the artery can result in cerebral ischemia as the brain is depleted of oxygen-rich blood. Because the brain has a pair of carotid and vertebral arteries on each side of the neck, a unilateral occlusion can be asymptomatic, as the bilateral circulation continues perfusing the brain. Thrombus formation is the natural physiologic response to the vascular injury to prevent significant blood loss. However, parts of the thrombus can break apart and result in emboli that can lodge themselves in distal cerebral arteries causing ischemic stroke, otherwise known as a cerebral infarction. Signs and Symptoms The signs and symptoms of cervical artery dissection are often non-specific or generalized and can either develop acutely or over several days. Headache Visual disturbances (i.e. diplopia, ptosis) Tinnitus Neck and face pain Horner syndrome (often partial) Loss of taste Anosmia Unilateral weakness Stroke Imaging Various imaging modalities can be used for the diagnosis of cervical artery dissection. The diagnosis of cervical artery dissection can be confirmed with the presence of a mural hematoma on ultrasound (US) or magnetic resonance imaging (MRI) and will also guide therapeutic decision making. MRI, with a fat-suppressed T1 sequence, is often first-line imaging. However, other modalities exist with helical computed topographic angiography (CTA) becoming the new gold-standard. Magnetic resonance angiography (MRA) and doppler US can also be utilized as additional non-invasive imaging techniques. The purpose of these imaging techniques is often multi-functional. These imaging modalities can detect the direction and changes of blood flow within the arteries and whether the dissection has resulted in any damage to brain tissue. Treatment The primary goal of treatment in cervical artery dissection is preventing or treating a stroke. Treatment guidelines also depend on the presence of underlying connective tissue disorders, dissection secondary to trauma, and underlying medical conditions. Management is often using either antiplatelet agents (i.e. aspirin) or anti-coagulation to prevent development of thrombus. Antiplatelet drugs can be given as individual drugs, or in combination (i.e. aspirin alone, or aspiring and clopidogrel). Anticoagulation such as heparin, intravenously (IV) or injectable (shot) can be given while inpatient and followed by heparin. A recent trial in 2015, the Cervical Artery Dissection in Stroke Study (CADISS), examined the efficacy of antiplatelet and anticoagulation treatment with the primary endpoint of ipsilateral stroke or death in individuals with symptomatic dissections. The CADISS trial revealed no significant difference in efficacy of antiplatelet and anticoagulant drugs in preventing strokes or death, but did note that strokes were rare in either group, and rarer than what has been reported in observational studies. == References ==
Chondrocalcinosis	Chondrocalcinosis or cartilage calcification is calcification (accumulation of calcium salts) in hyaline cartilage and/or fibrocartilage. It can be seen on radiography. Causes Buildup of calcium phosphate in the ankle joints has been found in about 50% of the general population, and may be associated with osteoarthritis.Another common cause of chondrocalcinosis is calcium pyrophosphate dihydrate crystal deposition disease (CPPD). CPPD is estimated to affect 4% to 7% of the adult populations of Europe and the United States. Previous studies have overestimated the prevalence by simply estimating the prevalence of chondrocalcinosis regardless of cause.A magnesium deficiency may cause chondrocalcinosis, and magnesium supplementation may reduce or alleviate symptoms. In some cases, arthritis from injury can cause chondrocalcinosis. Other causes of chondrocalcinosis include: Hypercalcaemia, especially when caused by hyperparathyroidism Arthritis Pseudogout Wilson disease Hemochromatosis Ochronosis Hypophosphatasia Hypothyroidism Hyperoxalemia Acromegaly Gitelman syndrome Diagnosis Chondrocalcinosis can be visualized on projectional radiography, CT scan, MRI, US, and nuclear medicine. CT scans and MRIs show calcific masses (usually within the ligamentum flavum or joint capsule), however radiography is more successful. At ultrasound, chondrocalcinosis may be depicted as echogenic foci with no acoustic shadow within the hyaline cartilage. As with most conditions, chondrocalcinosis can present with similarity to other diseases such as ankylosing spondylitis and gout. == References ==
Myasthenia gravis	Myasthenia gravis (MG) is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision, drooping eyelids, trouble talking, and trouble walking. Onset can be sudden. Those affected often have a large thymus or develop a thymoma.Myasthenia gravis is an autoimmune disease of the neuro-muscular junction which results from antibodies that block or destroy nicotinic acetylcholine receptors (AChR) at the junction between the nerve and muscle. This prevents nerve impulses from triggering muscle contractions. Most cases are due to immunoglobulin G1 (IgG1) and IgG3 antibodies that attack AChR in the postsynaptic membrane, causing complement-mediated damage and muscle weakness. Rarely, an inherited genetic defect in the neuromuscular junction results in a similar condition known as congenital myasthenia. Babies of mothers with myasthenia may have symptoms during their first few months of life, known as neonatal myasthenia. Diagnosis can be supported by blood tests for specific antibodies, the edrophonium test, or a nerve conduction study.MG is generally treated with medications known as acetylcholinesterase inhibitors, such as neostigmine and pyridostigmine. Immunosuppressants, such as prednisone or azathioprine, may also be used. The surgical removal of the thymus may improve symptoms in certain cases. Plasmapheresis and high-dose intravenous immunoglobulin may be used during sudden flares of the condition. If the breathing muscles become significantly weak, mechanical ventilation may be required. Once intubated acetylcholinesterase inhibitors may be temporarily held to reduce airway secretions.MG affects 50 to 200 per million people. It is newly diagnosed in three to 30 per million people each year. Diagnosis has become more common due to increased awareness. MG most commonly occurs in women under the age of 40 and in men over the age of 60. It is uncommon in children. With treatment, most of those affected lead relatively normal lives and have a normal life expectancy. The word is from the Greek mys, "muscle" and astheneia "weakness", and the Latin gravis, "serious". Signs and symptoms The initial, main symptom in MG is painless weakness of specific muscles, not fatigue. The muscle weakness becomes progressively worse during periods of physical activity and improves after periods of rest. Typically, the weakness and fatigue are worse toward the end of the day. MG generally starts with ocular (eye) weakness; it might then progress to a more severe generalized form, characterized by weakness in the extremities or in muscles that govern basic life functions. Eyes In about two-thirds of individuals, the initial symptom of MG is related to the muscles around the eye. Eyelid drooping (ptosis may occur due to weakness of m. levator palpebrae superioris) and double vision (diplopia, due to weakness of the extraocular muscles). Eye symptoms tend to get worse when watching television, reading, or driving, particularly in bright conditions. Consequently, some affected individuals choose to wear sunglasses. The term "ocular myasthenia gravis" describes a subtype of MG where muscle weakness is confined to the eyes, i.e. extraocular muscles, m. levator palpebrae superioris, and m. orbicularis oculi. Typically, this subtype evolves into generalized MG, usually after a few years. Eating The weakness of the muscles involved in swallowing may lead to swallowing difficulty (dysphagia). Typically, this means that some food may be left in the mouth after an attempt to swallow, or food and liquids may regurgitate into the nose rather than go down the throat (velopharyngeal insufficiency). Weakness of the muscles that move the jaw (muscles of mastication) may cause difficulty chewing. In individuals with MG, chewing tends to become more tiring when chewing tough, fibrous foods. Difficulty in swallowing, chewing, and speaking is the first symptom in about one-sixth of individuals. Speaking Weakness of the muscles involved in speaking may lead to dysarthria and hypophonia. Speech may be slow and slurred, or have a nasal quality. In some cases, a singing hobby or profession must be abandoned. Head and neck Due to weakness of the muscles of facial expression and muscles of mastication, facial weakness may manifest as the inability to hold the mouth closed (the "hanging jaw sign") and as a snarling expression when attempting to smile. With drooping eyelids, facial weakness may make the individual appear sleepy or sad. Difficulty in holding the head upright may occur. Other The muscles that control breathing and limb movements can also be affected; rarely do these present as the first symptoms of MG, but develop over months to years. In a myasthenic crisis, a paralysis of the respiratory muscles occurs, necessitating assisted ventilation to sustain life. Crises may be triggered by various biological stressors such as infection, fever, an adverse reaction to medication, or emotional stress. Pathophysiology MG is an autoimmune synaptopathy. The disorder occurs when the immune system malfunctions and generates antibodies that attack the bodys tissues. The antibodies in MG attack a normal human protein, the nicotinic acetylcholine receptor, or a related protein called MuSK, a muscle-specific kinase. Other, less frequent antibodies are found against LRP4, agrin, and titin proteins.Human leukocyte antigen haplotypes are associated with increased susceptibility to myasthenia gravis and other autoimmune disorders. Relatives of people with myasthenia gravis have a higher percentage of other immune disorders.The thymus gland cells form part of the bodys immune system. In those with myasthenia gravis, the thymus gland is large and abnormal. It sometimes contains clusters of immune cells that indicate lymphoid hyperplasia, and the thymus gland may give wrong instructions to immune cells. In pregnancy For women who are pregnant and already have MG, in a third of cases, they have been known to experience an exacerbation of their symptoms, and in those cases, it usually occurs in the first trimester of pregnancy. Signs and symptoms in pregnant mothers tend to improve during the second and third trimesters. Complete remission can occur in some mothers. Immunosuppressive therapy should be maintained throughout pregnancy, as this reduces the chance of neonatal muscle weakness, and controls the mothers myasthenia.About 10–20% of infants with mothers affected by the condition are born with transient neonatal myasthenia (TNM), which generally produces feeding and respiratory difficulties that develop about 12 hours to several days after birth. A child with TNM typically responds very well to acetylcholinesterase inhibitors, and the condition generally resolves over a period of three weeks, as the antibodies diminish, and generally does not result in any complications. Very rarely, an infant can be born with arthrogryposis multiplex congenita, secondary to profound intrauterine weakness. This is due to maternal antibodies that target an infants acetylcholine receptors. In some cases, the mother remains asymptomatic. Diagnosis MG can be difficult to diagnose, as the symptoms can be subtle and hard to distinguish from both normal variants and other neurological disorders.Three types of myasthenic symptoms in children can be distinguished: Transient neonatal myasthenia occurs in 10 to 15% of babies born to mothers afflicted with the disorder, and disappears after a few weeks. Congenital myasthenia, the rarest form, occurs when genes are present from both parents. Juvenile myasthenia gravis is most common in females.Congenital myasthenias cause muscle weakness and fatigability similar to those of MG. The signs of congenital myasthenia usually are present in the first years of childhood, although they may not be recognized until adulthood. Classification When diagnosed with MG, a person is assessed for his or her neurological status and the level of illness is established. This is usually done using the accepted Myasthenia Gravis Foundation of America Clinical Classification scale. Physical examination During a physical examination to check for MG, a doctor might ask the person to perform repetitive movements. For instance, the doctor may ask one to look at a fixed point for 30 seconds and to relax the muscles of the forehead, because a person with MG and ptosis of the eyes might be involuntarily using the forehead muscles to compensate for the weakness in the eyelids. The clinical examiner might also try to elicit the "curtain sign" in a person by holding one of the persons eyes open, which in the case of MG will lead the other eye to close. Blood tests If the diagnosis is suspected, serology can be performed: One test is for antibodies against the acetylcholine receptor; the test has a reasonable sensitivity of 80–96%, but in ocular myasthenia, the sensitivity falls to 50%. A proportion of the people without antibodies against the acetylcholine receptor have antibodies against the MuSK protein. In specific situations, testing is performed for Lambert-Eaton syndrome. Electrodiagnostics Muscle fibers of people with MG are easily fatigued, which the repetitive nerve stimulation test can help diagnose. In single-fiber electromyography, which is considered to be the most sensitive (although not the most specific) test for MG, a thin needle electrode is inserted into different areas of a particular muscle to record the action potentials from several samplings of different individual muscle fibers. Two muscle fibers belonging to the same motor unit are identified, and the temporal variability in their firing patterns is measured. Frequency and proportion of particular abnormal action potential patterns, called "jitter" and "blocking", are diagnostic. Jitter refers to the abnormal variation in the time interval between action potentials of adjacent muscle fibers in the same motor unit. Blocking refers to the failure of nerve impulses to elicit action potentials in adjacent muscle fibers of the same motor unit. Ice test Applying ice for 2–5 minutes to the muscles reportedly has a sensitivity and specificity of 76.9% and 98.3%, respectively, for the identification of MG. Acetylcholinesterase is thought to be inhibited at the lower temperature, which is the basis for this diagnostic test. This generally is performed on the eyelids when ptosis is present and is deemed positive if a ≥2-mm rise in the eyelid occurs after the ice is removed. Edrophonium test This test requires the intravenous administration of edrophonium chloride or neostigmine, drugs that block the breakdown of acetylcholine by cholinesterase (acetylcholinesterase inhibitors). This test is no longer typically performed, as its use can lead to life-threatening bradycardia (slow heart rate) which requires immediate emergency attention. Production of edrophonium was discontinued in 2008. Imaging A chest X-ray may identify widening of the mediastinum suggestive of thymoma, but computed tomography or magnetic resonance imaging (MRI) are more sensitive ways to identify thymomas and are generally done for this reason. MRI of the cranium and orbits may also be performed to exclude compressive and inflammatory lesions of the cranial nerves and ocular muscles. Pulmonary function test The forced vital capacity may be monitored at intervals to detect increasing muscular weakness. Acutely, negative inspiratory force may be used to determine adequacy of ventilation; it is performed on those individuals with MG. Management Treatment is by medication and/or surgery. Medication consists mainly of acetylcholinesterase inhibitors to directly improve muscle function and immunosuppressant drugs to reduce the autoimmune process. Thymectomy is a surgical method to treat MG. Medication Worsening may occur with medication such as fluoroquinolones, aminoglycosides, and magnesium. About 10% of people with generalized MG are considered treatment-refractory. Autologous hematopoietic stem cell transplantation (HSCT) is sometimes used in severe, treatment-refractory MG. Available data provide preliminary evidence that HSCT can be an effective therapeutic option in carefully selected cases.Efgartigimod alfa was approved for medical use in the United States in December 2021. Acetylcholinesterase inhibitors Acetylcholinesterase inhibitors can provide symptomatic benefit and may not fully remove a persons weakness from MG. While they might not fully remove all symptoms of MG, they still may allow a person the ability to perform normal daily activities. Usually, acetylcholinesterase inhibitors are started at a low dose and increased until the desired result is achieved. If taken 30 minutes before a meal, symptoms will be mild during eating, which is helpful for those who have difficulty swallowing due to their illness. Another medication used for MG, atropine, can reduce the muscarinic side effects of acetylcholinesterase inhibitors. Pyridostigmine is a relatively long-acting drug (when compared to other cholinergic agonists), with a half-life around four hours with relatively few side effects. Generally, it is discontinued in those who are being mechanically ventilated, as it is known to increase the amount of salivary secretions. A few high-quality studies have directly compared cholinesterase inhibitors with other treatments (or placebo); their practical benefit may be such that conducting studies in which they would be withheld from some people would be difficult. Immune suppressants The steroid prednisone might also be used to achieve a better result, but it can lead to the worsening of symptoms for 14 days and takes 6–8 weeks to achieve its maximal effectiveness. Due to the myriad symptoms that steroid treatments can cause, it is not the preferred method of treatment. Other immune suppressing medications may also be used including rituximab. Plasmapheresis and IVIG If the myasthenia is serious (myasthenic crisis), plasmapheresis can be used to remove the putative antibodies from the circulation. Also, intravenous immunoglobulins (IVIGs) can be used to bind the circulating antibodies. Both of these treatments have relatively short-lived benefits, typically measured in weeks, and often are associated with high costs, which make them prohibitive; they are generally reserved for when MG requires hospitalization. Surgery As thymomas are seen in 10% of all people with the MG, they are often given a chest X-ray and CT scan to evaluate their need for surgical removal of their thymus glands and any cancerous tissue that may be present. Even if surgery is performed to remove a thymoma, it generally does not lead to the remission of MG. Surgery in the case of MG involves the removal of the thymus, although in 2013, no clear benefit was indicated except in the presence of a thymoma. A 2016 randomized, controlled trial, however, found some benefits. Physical measures People with MG should be educated regarding the fluctuating nature of their symptoms, including weakness and exercise-induced fatigue. Exercise participation should be encouraged with frequent rest. In people with generalized MG, some evidence indicates a partial home program including training in diaphragmatic breathing, pursed-lip breathing, and interval-based muscle therapy may improve respiratory muscle strength, chest wall mobility, respiratory pattern, and respiratory endurance. Medical imaging In people with myasthenia gravis, older forms of iodinated contrast used for medical imaging have caused an increased risk of exacerbation of the disease, but modern forms have no immediate increased risk. Prognosis The prognosis of people with MG is generally good, as is quality of life, given very good treatment. Monitoring of a person with MG is very important, as at least 20% of people diagnosed with it will experience a myasthenic crisis within two years of their diagnosis, requiring rapid medical intervention. Generally, the most disabling period of MG might be years after the initial diagnosis. In the early 1900s, 70% of detected cases died from lung problems; now, that number is estimated to be around 3–5%, which is attributed to increased awareness and medications to manage symptoms. Epidemiology MG occurs in all ethnic groups and both sexes. It most commonly affects women under 40 and people from 50 to 70 years old of either sex, but it has been known to occur at any age. Younger people rarely have thymoma. Prevalence in the United States is estimated at between 0.5 and 20.4 cases per 100,000, with an estimated 60,000 Americans affected. Within the United Kingdom, an estimated 15 cases of MG occur per 100,000 people. History The first to write about MG were Thomas Willis, Samuel Wilks, Erb, and Goldflam. The term "myasthenia gravis pseudo-paralytica" was proposed in 1895 by Jolly, a German physician. Mary Walker treated a person with MG with physostigmine in 1934. Simpson and Nastuck detailed the autoimmune nature of the condition. In 1973, Patrick and Lindstrom used rabbits to show that immunization with purified muscle-like acetylcholine receptors caused the development of MG-like symptoms. Research Immunomodulating substances, such as drugs that prevent acetylcholine receptor modulation by the immune system, are currently being researched. Some research recently has been on anti-c5 inhibitors for treatment research as they are safe and used in the treatment of other diseases. Ephedrine seems to benefit some people more than other medications, but it has not been properly studied as of 2014. In the laboratory, MG is mostly studied in model organisms, such as rodents. In addition, in 2015, scientists developed an in vitro functional, all-human, neuromuscular junction assay from human embryonic stem cells and somatic-muscle stem cells. After the addition of pathogenic antibodies against the acetylcholine receptor and activation of the complement system, the neuromuscular co-culture shows symptoms such as weaker muscle contractions. References Further reading Zhang Z, Guo J, Su G, Li J, Wu H, Xie X (17 November 2014). "Evaluation of the quality of guidelines for myasthenia gravis with the AGREE II instrument". PLOS ONE. 9 (11): e111796. Bibcode:2014PLoSO...9k1796Z. doi:10.1371/journal.pone.0111796. PMC 4234220. PMID 25402504. "NCBI – Diagnostic". www.ncbi.nlm.nih.gov. Retrieved 11 July 2015.
Arteriovenous malformation	Arteriovenous malformation is an abnormal connection between arteries and veins, bypassing the capillary system. This vascular anomaly is widely known because of its occurrence in the central nervous system (usually cerebral AVM), but can appear in any location. Although many AVMs are asymptomatic, they can cause intense pain or bleeding or lead to other serious medical problems.AVMs are usually congenital and belong to the RASopathies. The genetic transmission patterns of AVMs are incomplete, but there are known genetic mutations (for instance in the epithelial line, tumor suppressor PTEN gene) which can lead to an increased occurrence throughout the body. Signs and symptoms Symptoms of AVM vary according to the location of the malformation. Roughly 88% of people with an AVM are asymptomatic; often the malformation is discovered as part of an autopsy or during treatment of an unrelated disorder (called in medicine an "incidental finding"); in rare cases, its expansion or a micro-bleed from an AVM in the brain can cause epilepsy, neurological deficit, or pain.The most general symptoms of a cerebral AVM include headaches and epileptic seizures, with more specific symptoms occurring that normally depend on the location of the malformation and the individual. Such possible symptoms include: Difficulties with movement coordination, including muscle weakness and even paralysis; Vertigo (dizziness); Difficulties of speech (dysarthria) and communication, such as aphasia; Difficulties with everyday activities, such as apraxia; Abnormal sensations (numbness, tingling, or spontaneous pain); Memory and thought-related problems, such as confusion, dementia or hallucinations.Cerebral AVMs may present themselves in a number of different ways: Bleeding (45% of cases) Acute onset of severe headache. May be described as the worst headache of the patients life. Depending on the location of bleeding, may be associated with new fixed neurologic deficit. In unruptured brain AVMs, the risk of spontaneous bleeding may be as low as 1% per year. After a first rupture, the annual bleeding risk may increase to more than 5%. Seizure or brain seizure (46%) Depending on the place of the AVM, it can cause loss of vision in one place. Headache (34%) Progressive neurologic deficit (21%) May be caused by mass effect or venous dilatations. Presence and nature of the deficit depend on location of lesion and the draining veins. Pediatric patients Heart failure Macrocephaly Prominent scalp veins Pulmonary arteriovenous malformations Pulmonary arteriovenous malformations are abnormal communications between the veins and arteries of the pulmonary circulation, leading to a right-to-left blood shunt. They have no symptoms in up to 29% of all cases, however they can give rise to serious complications including hemorrhage, and infection. They are most commonly associated with hereditary hemorrhagic telangiectasia. Genetics Can occur due to autosomal dominant diseases, such as hereditary hemorrhagic telangiectasia. Pathophysiology Arteries and veins are part of the vascular system. Arteries carry blood away from the heart to the lungs or the rest of the body, where the blood passes through capillaries, and veins return the blood to the heart. An AVM interferes with this process by forming a direct connection of the arteries and veins. AVMs can cause intense pain and lead to serious medical problems. Although AVMs are often associated with the brain and spinal cord, they can develop in other parts of the body.Normally, the arteries in the vascular system carry oxygen-rich blood, except in the case of the pulmonary artery. Structurally, arteries divide and sub-divide repeatedly, eventually forming a sponge-like capillary bed. Blood moves through the capillaries, giving up oxygen and taking up waste products, including CO2, from the surrounding cells. Capillaries in turn successively join to form veins that carry blood away. The heart acts to pump blood through arteries and uptake the venous blood.As an AVM lacks the dampening effect of capillaries on the blood flow, the AVM can get progressively larger over time as the amount of blood flowing through it increases, forcing the heart to work harder to keep up with the extra blood flow. It also causes the surrounding area to be deprived of the functions of the capillaries—removal of CO2 and delivery of nutrients to the cells. The resulting tangle of blood vessels, often called a nidus (Latin for "nest"), has no capillaries. It can be extremely fragile and prone to bleeding because of the abnormally direct connections between high-pressure arteries and low-pressure veins. The resultant sign, audible via stethoscope, is a rhythmic, whooshing sound caused by excessively rapid blood flow through the arteries and veins. It has been given the term "bruit", French for noise. On some occasions, a patient with a brain AVM may become aware of the noise, which can compromise hearing and interfere with sleep in addition to causing psychological distress. Diagnosis AVMs are diagnosed primarily by the following imaging methods: Computerized tomography (CT) scan is a noninvasive X-ray to view the anatomical structures within the brain to detect blood in or around the brain. A newer technology called CT angiography involves the injection of contrast into the blood stream to view the arteries of the brain. This type of test provides the best pictures of blood vessels through angiography and soft tissues through CT. Magnetic resonance imaging (MRI) scan is a noninvasive test, which uses a magnetic field and radio-frequency waves to give a detailed view of the soft tissues of the brain. Magnetic resonance angiography (MRA) – scans created using magnetic resonance imaging to specifically image the blood vessels and structures of the brain. A magnetic resonance angiogram can be an invasive procedure, involving the introduction of contrast dyes (e.g., gadolinium MR contrast agents) into the vasculature of a patient using a catheter inserted into an artery and passed through the blood vessels to the brain. Once the catheter is in place, the contrast dye is injected into the bloodstream and the MR images are taken. Additionally or alternatively, flow-dependent or other contrast-free magnetic resonance imaging techniques can be used to determine the location and other properties of the vasculature.AVMs can occur in various parts of the body: brain (cerebral AV malformation) spleen lung kidney spinal cord liver intercostal space iris spermatic cord extremities – arm, shoulder, etc.AVMs may occur in isolation or as a part of another disease (for example, Von Hippel-Lindau disease or hereditary hemorrhagic telangiectasia).AVMs have been shown to be associated with aortic stenosis.Bleeding from an AVM can be relatively mild or devastating. It can cause severe and less often fatal strokes. If a cerebral AVM is detected before a stroke occurs, usually the arteries feeding blood into the nidus can be closed off to avert the danger. However, interventional therapy may also be relatively risky. Treatment Treatment for brain AVMs can be symptomatic, and patients should be followed by a neurologist for any seizures, headaches, or focal neurologic deficits. AVM-specific treatment may also involve endovascular embolization, neurosurgery or radiosurgery. Embolization, that is, cutting off the blood supply to the AVM with coils, particles, acrylates, or polymers introduced by a radiographically guided catheter, may be used in addition to neurosurgery or radiosurgery, but is rarely successful in isolation except in smaller AVMs. Gamma knife may also be used.Treatment of lung AVMs is typically performed with endovascular embolization alone, which is considered the standard of care. Epidemiology The estimated detection rate of AVM in the US general population is 1.4/100,000 per year. This is approximately one fifth to one seventh the incidence of intracranial aneurysms. An estimated 300,000 Americans have AVMs, of whom 12% (approximately 36,000) will exhibit symptoms of greatly varying severity. History Luschka (1820–1875) and Virchow (1821–1902) first described arteriovenous malformations in the mid-1800s. Olivecrona (1891–1980) performed the first surgical excision of an intracranial AVM in 1932. Society and culture Notable cases Indonesian actress Egidia Savitri died from complications of AVM on November 29, 2013. Phoenix Suns point guard AJ Price nearly died from AVM in 2004 while a student at the University of Connecticut. On December 13, 2006, Senator Tim Johnson of South Dakota was diagnosed with AVM and treated at George Washington University Hospital. On August 3, 2011, Mike Patterson of the Philadelphia Eagles collapsed on the field and had a seizure during a practice, leading to him being diagnosed with AVM. Actor Ricardo Montalbán was born with spinal AVM. During the filming of the 1951 film Across the Wide Missouri, Montalbán was thrown from his horse, knocked unconscious, and trampled by another horse which aggravated his AVM and resulted in a painful back injury that never healed. The pain increased as he aged, and in 1993, Montalbán underwent 9+1⁄2 hours of spinal surgery which left him paralyzed below the waist and using a wheelchair. Actor/comedian T. J. Miller was diagnosed with AVM after filming Yogi Bear in New Zealand in 2010; Miller described his experience with the disease on the Pete Holmes podcast You Made It Weird on October 28, 2011, shedding his comedian side for a moment and becoming more philosophical, narrating his behaviors and inability to sleep during that time. He had a seizure upon return to Los Angeles and successfully underwent surgery that had a mortality rate of ten percent. Jazz guitarist Pat Martino experienced an AVM and subsequently developed amnesia and manic depression. He eventually re-learned to play the guitar by listening to his own recordings from before the aneurysm. YouTube vlogger Nikki Lilly (Nikki Christou), winner of the 2016 season of Junior Bake Off was born with AVM, which has resulted in some facial disfigurement. Composer and lyricist William Finn was diagnosed with AVM and underwent Gamma Knife surgery in September 1992, soon after he won the 1992 Tony Award for best musical, awarded to "Falsettos". Finn wrote the 1998 Off-Broadway musical A New Brain about the experience. Former Florida Gators and Oakland Raiders linebacker Neiron Ball was diagnosed with AVM in 2011 while playing for Florida, but recovered and was cleared to play. On September 16, 2018, Ball was placed in a medically induced coma due to complications of the disease, which lasted until his death on September 10, 2019. Country music singer Drake White was diagnosed with AVM in January 2019, and is undergoing treatment. Cultural Depictions In the HBO series Six Feet Under (TV series), main character Nate Fisher discovers he has an AVM after being in a car accident and getting a precautionary cat scan at the hospital during Season 1. His AVM becomes a key focus during Season 2 and again in Season 5. Research Despite many years of research, the central question of whether to treat AVMs has not been answered. All treatments, whether involving surgery, radiation, or drugs, have risks and side-effects. Therefore, it might be better in some cases to avoid treatment altogether and simply accept a small risk of coming to harm from the AVM itself. This question is currently being addressed in clinical trials. See also Foix–Alajouanine syndrome Haemangioma Klippel–Trénaunay syndrome Parkes Weber syndrome == References ==
Soft tissue injury	A soft tissue injury is the damage of muscles, ligaments and tendons throughout the body. Common soft tissue injuries usually occur from a sprain, strain, a one-off blow resulting in a contusion or overuse of a particular part of the body. Soft tissue injuries can result in pain, swelling, bruising and loss of function. Signs and symptoms Sprains A sprain is a type of acute injury which results from the stretching or tearing of a ligament. Depending on the severity of the sprain, the movement on the joint can be compromised since ligaments aid in the stability and support of joints. Sprains are commonly seen in vulnerable areas such as the wrists, knees and ankles. They can occur from movements such as falling on an outstretched hand or a twisting of the ankle or foot.The severity of a sprain can be classified: Grade 1: Only some of the fibers in the ligament are torn, and the injured site is moderately painful and swollen. Function in the joint will be unaffected for the most part. Grade 2: Many of the ligament fibers are torn, and pain and swelling is moderate. The functionality of the joint is compromised. Grade 3: The soft tissue is completely torn, and functionality and strength on the joint is completely compromised. In most cases, surgery is needed to repair the damage. Strains A strain is a type of acute injury that occurs to the muscle or tendon. Similar to sprains, it can vary in severity, from a stretching of the muscle or tendon to a complete tear of the tendon from the muscle. Some of the most common places that strains occur are in the foot, back of the leg (hamstring), or back. Bruising (contusion) A contusion is the discoloration of the skin, which results from underlying muscle fibers and connective tissue being crushed. This can happen in a variety of ways such as a direct blow to the skin, or a fall taken against a hard surface. The discoloration in the skin is present when blood begins to pool around the injury. Tendinitis Tendinitis is a type of overuse injury to the tendons, which demonstrates signs of inflammation of tendons around a joint. Tendinitis is the most common cause of shoulder pain and also leg pain . Tendinitis occurs when there is repetitive stress on the subacromial bursa, which causes the bones to make contact with the tendons and irritate them. Diagnosis Classifications Acute injuries Any type of injury that occurs to the body through sudden trauma, such as a fall, twist or blow to the body. A few examples of this type of injury would be sprains, strains and contusions. Overuse injuries An overuse injury occurs when a certain activity is repeated frequently and the body does not have enough time to recover between occurrences. Examples include bursitis and tendinitis. Commonly injured tissues With examples of each. Parentheses indicate location in body LigamentsAnterior cruciate ligament (knee), medial collateral ligament (knee), ulnar collateral ligaments (wrist/hand), interspinous ligaments (vertebrae)MusclesBiceps brachii (upper arm), rectus femoris (thigh), transverse abdominis (abdominals)TendonsPatellar tendon (knee), calcaneal/Achilles tendon (foot/lower leg), biceps tendon (shoulder/elbow)NervesBrachial plexus (shoulder), ulnar nerve (elbow/hand), peroneal nerve (ankle/foot), cranial nerves I-XII(head)BonesFemur (leg), humerus (arm), ribs (torso), metatarsals I-VI (foot), metacarpals I-VI (hand)CartilageMenisci (knee), intervertebral discs (spine), acetabulum (hip) Management RICE method The RICE method is an effective procedure used in the initial treatment of a soft tissue injury. Rest It is suggested that the patient take a break from the activity that caused the injury in order to give the injury time to heal. Ice The injury should be iced on and off in 20 minute intervals, avoiding direct contact of the ice with the skin. Compression Bandaging the injury will compress it, and prevent any further bleeding or swelling from occurring. Elevation Elevating the injury above the heart while resting will aid in the reduction of swelling. No HARM protocol This mnemonic indicates what not to do within the first 48–72 hours after the injury in order to speed up the recovery process. Heat Applying heat to the injured area can cause blood flow and swelling to increase. Alcohol Alcohol can inhibit the ability to feel if the injury is becoming more aggravated, as well as increasing blood flow and swelling. Re-injury Avoid any activities that could aggravate the injury and cause further damage. Massage Massaging an injured area can promote blood flow and swelling, and potentially cause more damage if done too early. Treatment If severe pain persists after the first 24hours it is recommended that an individual consult with a professional who can make a diagnosis and implement a treatment plan so the patient can return to everyday activities. To make a full diagnosis, a professional may use nerve conduction studies to localize nerve dysfunction (e.g. carpal tunnel syndrome), assess severity, and help with prognosis. Electrodiagnosis also helps differentiate between myopathy and neuropathy. Using the RICE method can somewhat be controversial as the science behind using ice is not necessarily very clear. On one hand, ice diminishes pain, metabolism, and muscle spasms. It also minimizes the inflammatory process and edema, which helps one recover from a soft-tissue injury. However, creatine kinase-MB isoform and myoglobin levels circulating in the blood increased after exercising. Ice impedes the recovery process by keeping the Creatine kinase-MB isoform and myoglobin levels increased 2–3 days post exercise. It is therefore important to weigh the pros and cons before applying any treatment, including the use of ice. Ultimately, the best method of imaging soft tissue is magnetic resonance imaging (MRI), though it is cost-prohibitive and carries a high false positive rate. References Sources Flegel, Melinda J. (2004). Sport first aid: A coach’s guide to preventing and responding to injuries. Hong Kong, Japan: Human Kinetics. Lindsay, R., Watson, G., Hickmont, D., Broadfoot, A., & Bruynel, L. (1994). Treat your own strains sprains and bruises. New Zealand: Spinal Publications. Lovering, R.M. (2008). "Physical therapy and related interventions". In P.M. Tiidus (ed.), Skeletal muscle damage and repair (pp. 219–230). United States of America: Human Kinetics. Prentice, William E. "Tissue Response to Injury", Principles of Athletic Training: A Competency Based Approach. 14th ed. New York: McGraw Hill Companies, 2011. 260–277. Subotnick, Steven (1991). Sports and Exercise Injuries: Conventional, Homeopathic and Alternative Treatments. California, United States of America: North Atlantic Books.
Venezuelan hemorrhagic fever	Venezuelan hemorrhagic fever (VHF) is a zoonotic human illness first identified in 1989. The disease is most prevalent in several rural areas of central Venezuela and is caused by Guanarito mammarenavirus (GTOV) which belongs to the Arenaviridae family. The short-tailed cane mouse (Zygodontomys brevicauda) is the main host for GTOV which is spread mostly by inhalation of aerosolized droplets of saliva, respiratory secretions, urine, or blood from infected rodents. Person-to-person spread is possible, but uncommon. Presentation VHF has many similarities to Lassa fever and to the arenavirus hemorrhagic fevers that occur in Argentina and Bolivia. It causes fever and malaise followed by hemorrhagic manifestations and convulsions. Some presentations of the virus are also characterized by vascular damage, bleeding diathesis, fever, and multiple organ involvement. Clinical diagnosis of VHF has proven to be difficult based on the nonspecific symptoms. The disease is fatal in 30% of cases and is endemic to Portuguesa state and Barinas state in Venezuela. Treatment and prevention for the VHF virus are limited and there are currently no licensed vaccines available that can act to prevent the disease. However, once infected, ribavirin, an anti-viral drug given intravenously, is one way to treat VHF. Virus Arenaviruses are enveloped, single-stranded, bisegmented RNA viruses with antisense genomes. Based on their antigenic properties, arenaviruses have been classified into two major groups: the Old World arenaviruses, and the New World arenaviruses. Old World arenaviruses include lymphocytic choriomeningitis virus and Lassa virus. New world arena viruses are further broken down into three clades, A, B, and C. The Guanarito arena virus belongs to clade B and is the cause of VHF. On the biosafety level scale of one to four, with four causing the most risk, the viruses causing hemorrhagic fevers have been assigned a four by the CDC. Host The short-tailed cane mouse, the main host of GTOV, is native to western Venezuela and resides in large numbers in tall grass, cultivated agricultural fields, human homes, and outbuildings. It is speculated that demographic and ecological changes in the rural areas increased the frequency of contact between humans and infected rodents such that VHF emerged. History From September 1989 through December 2006, the State of Portuguesa recorded 618 cases of VHF. Nearly all of the cases were individuals who worked or lived in Guanarito during the time they became infected. The case fatality rate was 23.1%.Because the virus is contracted by aerosol dissemination, concern arose shortly after the first cases emerged in 1989 due to fear of biological warfare. Potential biological terrorism agents were identified and categorized in 1999 by the Centers for Disease Control and Prevention (CDC) as part of the Congressional initiative to further response capabilities to biological weapons. Arenaviruses causing hemorrhagic fevers, along with a genus of virus called filoviruses, were categorized in Category A; these are pathogens with the highest potential impact on public health safety. A notable event in the timeline of this virus scientific knowledge was the unexplained disappearance of a vial of the virus at the University of Texas Medical Branch Galveston National Laboratory, announced 2013 March 24. References == External links ==
Retinoschisis	Retinoschisis is an eye disease characterized by the abnormal splitting of the retinas neurosensory layers, usually in the outer plexiform layer. Retinoschisis can be divided into degenerative forms which are very common and almost exclusively involve the peripheral retina and hereditary forms which are rare and involve the central retina and sometimes the peripheral retina. The degenerative forms are asymptomatic and involve the peripheral retina only and do not affect the visual acuity. Some rarer forms result in a loss of vision in the corresponding visual field.Almost all cases are X-linked recessive and caused by a mutation in the retinoschisin gene (RS1). Classification Hereditary X linked juvenile retinoschisis Familial foveal retinoschisis Tractional Exudative Secondary to Optic disc pit Degenerative Typical Reticular Degenerative retinoschisis This type of retinoschisis is very common with a prevalence of up to 7 percent in normal persons. Its cause is unknown. It can easily be confused with retinal detachment by the non-expert observer and in difficult cases even the expert may have difficulty differentiating the two. Such differentiation is important since retinal detachment almost always requires treatment while retinoschisis never itself requires treatment and leads to retinal detachment (and hence to visual loss) only occasionally. Unfortunately one still sees cases of uncomplicated retinoschisis treated by laser retinopexy or cryopexy in an attempt to stop its progression towards the macula. Such treatments are not only ineffective but unnecessarily risk complications. There is no documented case in the literature of degenerative retinoschisis itself (as opposed to the occasional situation of retinal detachment complicating retinoschisis) in which the splitting of the retina has progressed through the fovea. There is no clinical utility in differentiating between typical and reticular retinoschisis. Degenerative retinoschisis is not known to be a genetically inherited condition. There is always vision loss in the region of the schisis as the sensory retina is separated from the ganglion layer. But as the loss is in the periphery, it goes unnoticed. It is the very rare schisis that encroaches on the macula where retinopexy is then properly used. Hereditary retinoschisis Hereditary retinoschisis is derived from a defective retinoschisin protein, which is due to an X-linked genetic defect. The genetic form of this disease usually starts during childhood and is called X-linked Juvenile Retinoschisis (XLRS) or Congenital Retinoschisis. Affected males are usually identified in grade school, but occasionally are identified as young infants. It is estimated that this much less common form of retinoschisis affects one in 5,000 to 25,000 individuals, primarily young males. Schisis is derived from the Greek word meaning splitting, describing the splitting of the retinal layers from each other. However, schisis is a word fragment, and the term retinoschisis should be used, as should the term iridoschisis when describing splitting of the iris. If the retinoschisis involves the macula, then the high-resolution central area of vision used to view detail is lost, and this is one form of macular disease. Although it might be described by some as a "degeneration", the term macular degeneration should be reserved for the specific disease "age-related macular degeneration". Very few affected individuals go completely blind from retinoschisis, but some sufferers have very limited reading vision and are "legally blind". Visual acuity can be reduced to less than 20/200 in both eyes. Individuals affected by XLRS are at an increased risk for retinal detachment and eye hemorrhage, among other potential complications. Retinoschisis causes acuity loss in the center of the visual field through the formation of tiny cysts in the retina, often forming a "spoke-wheel" pattern that can be very subtle. The cysts are usually only detectable by a trained clinician. In some cases vision cannot be improved by glasses, as the nerve tissue itself is damaged by these cysts. The National Eye Institute (NEI) of the National Institutes of Health (NIH) is conducting clinical and genetic studies of X-Linked Juvenile Retinoschisis. This study began in 2003 and as of 2018 is continuing to recruit patients. A better understanding of why and how XLRS develops might lead to improved treatments. Males diagnosed with X-linked juvenile retinoschisis and females who are suspected carriers may be eligible to participate. In addition to giving a medical history and submitting medical records, participants submit a blood sample and the NEI will perform a genetic analysis. There is no cost to participate in this study. Tractional retinoschisis This may be present in conditions causing traction on the retina especially at the macula. This may occur in: a) The vitreomacular traction syndrome; b) Proliferative diabetic retinopathy with vitreoretinal traction; c) Atypical cases of impending macular hole. Exudative retinoschisis Retinoschisis involving the central part of the retina secondary to an optic disc pit was erroneously considered to be a serous retinal detachment until correctly described by Lincoff as retinoschisis. Significant visual loss may occur and following a period of observation for spontaneous resolution, treatment with temporal peripapillary laser photocoagulation followed by vitrectomy and gas injection followed by face-down positioning is very effective in treating this condition. Diagnosis The diagnosis of the disease is usually made during an examination of the back of the eye (fundus) where any splits, tears or rips may be seen. One diagnostic tool is optical coherence tomography (OCT), which that uses light waves to create images of the retina and based on ophthalmoscopy with scleral depression and contact lens examination. The fellow eye should also be examined. Treatment Retinoschisis usually doesn’t require treatment aside from glasses to improve vision. However, some children with X-linked retinoschisis may have bleeding in their eye. This can be treated with either laser therapy or cryosurgery. In rare cases, children may need surgery to stop the bleeding. As of 2022, a clinical trial of gene therapy to treat XLRS was ongoing. After 1 year, the paper concluded that the therapy "was generally safe and well tolerated but failed to demonstrate a measurable treatment effect". References External links GeneReview/NCBI/NIH/UW entry on X-Linked Juvenile Retinoschisis X-linked juvenile retinoschisis on Genetics Home Reference NCBI Genetic Testing Registry
Cervical pregnancy	A cervical pregnancy is an ectopic pregnancy that has implanted in the uterine endocervix. Such a pregnancy typically aborts within the first trimester, however, if it is implanted closer to the uterine cavity – a so-called cervico-isthmic pregnancy – it may continue longer. Placental removal in a cervical pregnancy may result in major hemorrhage. Diagnosis The diagnosis is made in asymptomatic pregnant women either by inspection seeing a bluish discolored cervix or, more commonly, by obstetric ultrasonography. A typical non-specific symptom is vaginal bleeding during pregnancy. Ultrasound will show the location of the gestational sac in the cervix, while the uterine cavity is "empty". Cervical pregnancy can be confused with a miscarriage when pregnancy tissue is passing through the cervix. Histologically the diagnosis has been made by Rubins criteria on the surgical specimen: cervical glands are opposite the trophoblastic tissue, the trophoblastic attachment is below the entrance of the uterine vessels to the uterus or the anterior peritoneal reflection, and fetal elements are absent from the uterine corpus. As many pregnancies today are diagnosed early and no hysterectomy is performed, Rubins criteria can often not be applied. Management True cervical pregnancies tend to abort; if, however, the pregnancy is located higher in the canal and the placenta finds support in the uterine cavity, it can go past the first trimester. With the placenta being implanted abnormally, extensive vaginal bleeding can be expected at time of delivery and placental removal. While early cervical pregnancies may abort spontaneously or can be managed with excision, D&C, suturing, electrocautery, and tamponading, by medication such as methotrexate, and/or by uterine artery embolization, a more advanced pregnancy may require a hysterectomy to control bleeding. The more advanced the pregnancy, the higher the risk for major bleeding necessitating a hysterectomy.On very rare occasions, a cervical pregnancy results in the birth of a live baby; typically, the pregnancy is in the upper part of the cervical canal and manages to extend into the lower part of the uterine cavity. A cervical pregnancy can develop together with a normal intrauterine pregnancy; such a heterotopic pregnancy will call for expert management as to not to endanger the intrauterine pregnancy. Epidemiology The incidence has been reported to be about 1:1,000 to 1:16,000 pregnancies.Pregnancies involving the isthmus – the segment of the uterus between the cervix and the fundus – are more common than true cervical pregnancies. While in many situations the cause of the abnormal implantation remains unclear, there is evidence to link the development of cervical pregnancy to uterine instrumentation, specifically repeated D&Cs (dilatation and curettage). Cervical pregnancies are to be distinguished from pregnancies that start from an implantation in a scar of a previous cesarean section, so-called scar pregnancies. References == External links ==
Vaginal atresia	Vaginal atresia is a condition in which the vagina is abnormally closed or absent. The main causes can either be complete vaginal hypoplasia, or a vaginal obstruction, often caused by an imperforate hymen or, less commonly, a transverse vaginal septum. It results in uterovaginal outflow tract obstruction. This condition does not usually occur by itself within an individual, but coupled with other developmental disorders within the female. The disorders that are usually coupled with a female who has vaginal atresia are Mayer-Rokitansky-Küster-Hauser syndrome, Bardet-Biedl syndrome, or Fraser syndrome. One out of every 5,000 women have this abnormality. Symptoms and signs Symptoms and signs in the newborn can be sepsis, abdominal mass, and respiratory distress. Other abdominopelvic or perineal congenital anomalies frequently prompt radiographic evaluation in the newborn, resulting in a diagnosis of coincident vaginal atresia. Symptoms for vaginal atresia include cyclical abdominal pain, the inability to start having menstrual cycles, a small pouch or dimple where a vaginal opening should be, and pelvic mass when the upper vagina becomes filled with menstrual blood. Signs and symptoms of vaginal atresia or vaginal agenesis can often go unnoticed in females until they reach the age of menstruation. Women may also experience some form of abdominal pain or cramping. Causes The cause for vaginal atresia is unknown. Typically, the creation of the vaginal canal is completed within the fetus by the 20th week of gestation. Researchers believe in patients with vaginal atresia, tubes known as the Müllerian ducts do not develop correctly within the first 20 weeks of gestation/pregnancy. Typically, one of these ducts develops in the fallopian tubes while the other ducts develop into the vagina and uterus. Vaginal atresia is found to occur when the urogenital sinus does not contribute to the formation of the lower portion of the vagina. As previously mentioned, there are other disorders or syndromes that are found in conjunction with individuals living with vaginal atresia. These disorders are: Rokitansky-Mayer-Küster-Hauser syndrome Rokitansky-Mayer-Küster-Hauser syndrome is a disorder in females that causes the uterus and vagina to be absent or underdeveloped. Those born with this disorder are considered to be genetic female and have a 46XX chromosomes. Kidney anomalies often accompany this disorder as well. Also referred to as Müllerian agenesis, vaginal agenesis, or Müllerian aplasia, this disorder affects 1 in every 4,000-5,000 females. A cloacal malformation often accompanies this disorder, which is the surgical treatment that incorporates several vaginal replacement techniques. This disorder is caused by an implication in the WNT4 protein coding gene, which is found on the short arm (p) of chromosome 1. A genetic mutation occurs causing a substitution of leucine to proline residue at position 12 on the amino acid in the WNT4 protein. Essentially, this will cause a reduction in the intranuclear levels of β catenin. Additionally, steroidogenic enzymes such as 17α-hydroxylase and 3β-hydroxysteriod dehydrogenase are inhibited because of this mutation, which leads to an excess amount to androgen in the system. As the WNT4 gene is essential for developing a protein that is essential for female sex development, the Müllerian duct is either absent or deformed when this gene is not present. The development of the female reproductive system may be disrupted in the absence of the WNT4 proteins regulation. Abnormal androgen production is also induced, eventually leading to hyperandrogenism and Müllerian aplasia. Bardet-Biedl Syndrome Bardet-Biedl syndrome (BBS) is a ciliopathic human genetic disorder that can affect various parts of the body. Parts of the urogenital system where the effects of BBS are seen include: ectopic urethra, kidney failure, uterus duplex, hypogonadism, septate vagina, and hypoplasia of the fallopian tubes, uterus, ovaries. Some of the common characteristics associated with this syndrome include intellectual disorders, loss of vision, kidney problems, and obesity.The mechanism that causes BBS is still remains unclear. Mutations in more than 20 genes can cause BBS and is an inherited recessive condition. Some of the gene mutations that occur in BBS are listed below: BBS1, BBS2, ARL6 (BBS3), BBS4, BBS5, MKKS (BBS6), BBS7, TTC8 (BBS8), BBS9, BBS10, TRIM32 (BBS11), BBS12, MKS1 (BBS13), CEP290 (BBS14), WDPCP (BBS15), SDCCAG8 (BBS16), LZTFL1 (BBS17), BBIP1 (BBS18), IFT27 (BBS19), IFT72 (BBS20), and C8ORF37(BBS21) The majority of the genes that are related to BBS encode proteins which are called cilia and basal bodies, which are related structures. Fraser Syndrome Fraser syndrome is a disorder that affects the development of the child prior to birth. Infants born with Fraser syndrome often have eyes that are malformed and completely covered by skin. Also the child is born with fingers and toes that are fused together along with abnormalities within the urine tract. As this disorder relates to vaginal atresia, infants born with Fraser syndrome are also born with malformations in their genitals. McKusick-Kaufman syndrome A female with McKusick-Kaufman syndrome has vaginal atresia that is often present with imperforate anus, heart defects, hydrometrocolpos, and/or polydactyly, The female will still develop secondary sexual characteristics. Mechanism The exact mechanism for vaginal atresia is not well known, as specific molecular mechanisms which lead to the closing or absence of the vagina are unclear. There are various pathways that may support or restrict regular vaginal development. Research has shown that changing factors may also include paracrine and autocrine signals and changes in the basis of developing organs. Specific patterns of genetic transmission have not been identified for this condition. Normal reproductive organ production requires timely coordination of the following systems: external genitalia, internal ductal system, and gonadal structure. The abnormal development of the vagina results in an incomplete unit (low, mid, high transverse septum), failure of epithelium degeneration (imperforate hymen), and vaginal atresia.According to a number of medical professionals, timely coordination of interdependent systems is required for normal reproductive organ development in both males and females. The description of vaginal atresia mechanism can be explained in several steps of development of the uterovaginal canal per the information provided by these medical professionals. These interdependent systems are external genitalia, gonadal structures, and internal ductal system. The absence of androgens, Müllerian-inhibiting substance (MIS), and testes causes the continuous differentiation of the Müllerian ducts with reversion of the wolffian ducts in the female embryo. The Müllerian duct will then elongate to reach the urogenital sinus within 9 weeks of gestation; this forms the uterovaginal canal. By 15–26 weeks of gestation, cephalic growth of the sinovaginal bulb is completed. The vaginal plate is also formed from the fusion of vaginal cord with the sinovaginal bulb. The formation of the uterovaginal canal is thought to occur from the caudal to the cephalic portion, all while the urogenital sinus is used to create the epithelial lining. Development of the vagina is completed by the fifth month of gestation. While the mesenchyme that surrounds the structures transitions into musculature of the genital tract, the fallopian tubes are formed via the cephalic remnants of the Müllerian duct. This developmental process attributes to the process of how proper vaginal development takes place. Failure of the septum to regress between the fused Müllerian ducts results in a septate uterus. The incomplete fusion of the Müllerian ducts attributes to the formation of arcuate, bicornuate, or didelphid uteri.Females who have both Rokitansky-Mayer-Küster-Hauser syndrome and uterovaginal atresia are theorized to have a failing caudal development within the Müllerian ducts. Variations of transverse vaginal septum might be described by the malfunctions at the level of the vaginal plate. Though the Müllerian and urogenital sinuses play a huge role in the derivation of the vagina, it is unclear how much of a role each of these play normal vaginal development. Diagnosis Vaginal atresia can sometimes be diagnosed by physical examination soon after birth. A child with vaginal atresia often has other congenital abnormalities and other tests such as X-ray and tests to evaluate the kidneys are done. Findings in adolescents may include abdominal pain, difficulty voiding, and backache, but most present with amenorrhea. Difficulties with sexual intercourse can suggest atresia. In the event that the condition is not caught shortly after birth, vaginal atresia becomes more evident when no menstrual cycle is occurs. If vaginal atresia is suspected by the doctor, a blood test may also be request for any of the previously mentioned syndromes, a magnetic resonance imaging (MRI) test, or an ultrasound. A regular evaluation of children born with an imperforate anus or anorectal malformation should be paired with the assessment of the results from these tests. Treatment There are several methods of treatment for individuals with vaginal atresia. The first method of treatment that is recommended would be self-dilation of the vagina. A doctor may first recommend that the patient first attempts to create a vagina themselves through the process self-dilation. The self dilation technique consists of using vaginal dilators, which are small round tubes that vary in size and are similar in size and shape to tampons. Vaginal dilators may be pressed alongside the vaginal area on a regular basis in order to further open the vaginal canal. Franks procedure is a technique that used a progressive series of vaginal dilators that are inserted into the dimple of the vagina while using pressure. This will widen any space that exists between the bladder and the rectum. Franks procedure can be performed directly by the patient, therefore requiring no surgery or anesthesia. The procedure/technique can take months to complete, with regular compliance necessary. The overall success rate for females who use Franks procedure is 80%. If this procedure does not work, then surgery would be the next method of treatment. Another alternative form of treatment would be surgery, or the creation of a new vagina. Prognosis The prognosis for vaginal atresia is one that is complicated. There are variations in patients anatomic findings as well as an absence in consistent surgical techniques which makes it difficult to give a prognosis for this condition. Along with other conditions that give rise to an abnormal perineum (i.e. ambiguous genitalia and other various abnormalities that range from cloaca to urogenital sinus), individuals with vaginal atresia often report reconstruction as an outcome of treatment. Due to this, it is difficult to compare outcomes between individuals with vaginal atresia. Rokitansky-Mayer-Küster-Hauser Syndrome Fertility options for girls and women with Rokitansky-Mayer-Küster-Hauser syndrome has a bit more information. Girls and women who are born without a complete vagina, but still have a regular sized uterus more than likely will be able to become pregnant and have a baby. However, if the female is born with a tiny uterus, or without a uterus, they will not be able to have a baby. As the ovaries may be normal in this case, the egg may be fertilized with a donors or partners sperm. In this case, surrogacy, would be an option where there will be a gestational carrier to carry the pregnancy for the couple. Adoption may also be an option for females with Rokitansky-Mayer-Küster-Hauser syndrome. Another possibility could be uterine transplants, however this a new and developing form of treatment. Fertility options are being researched daily, so there can always be a new method available.Any pain associated with Rokitansky-Mayer-Küster-Hauser syndrome comes from menstruation related cramping and can be treated with several ways. Individuals with this syndrome may be born with a uterine remnant (tiny uterus), which can become filled with blood in the pelvic cavity causing pain. A medical professional can assess the severity of having a uterine remnant within each patient to determine if removal of the uterus is necessary. Bardet-Biedl Syndrome There is no cure available for individuals with Bardet-Biedl Syndrome; however, there are methods of treatment for some of the signs and symptoms within each individual. Corrective surgery of malformation related to the disorder may be an option for treatment. Genetic counseling can also be beneficial to families with this disorder. == References ==
Congenital dermal sinus	Congenital dermal sinus is an uncommon form of cranial or spinal dysraphism. It occurs in 1 in 2500 live births. It occurs as a dermal indentation, found along the midline of the neuraxis and often presents alongside infection and neurological deficit. Congenital dermal sinus form due to a focal failure of dysjunction between the cutaneous ectoderm and neuroectoderm during the third to eight week of gestation. Typically observed in the lumbar and lumbosacral region, congenital dermal sinus can occur from the nasion and occiput region down.Early diagnosis and treatment is crucial for cases of congenital dermal sinus. It ensures that neurological condition does not degrade and prevents infection. Diagnosis can be confirmed through the use of advanced neuroimaging to observe the tract and associated lesions. Embryogenesis During normal development, cutaneous ectoderm separates from neuroectoderm to allow for the insertion of mesoderm. That is, the skin separates from the tissue of the spinal cord to allow proper formation of the vertebral column. In cases of congenital dermal sinus there is a failure in this process, resulting in formation of a persistent connection between the skin and neural tissue. This manifests as a tract extending from the surface of the skin to the spinal cord lined with stratified squamous epithelium, surrounded by dermal and neurological tissue. The tract may terminate in the deep fascia, or even make contact with neural elements. Congenital dermal sinus may form at any point along the midline of the neuraxis, however, the majority form in the lumbar and lumbosacral region (41% and 35% of cases respectively). Diagnosis Congenital dermal sinus is often diagnosed in infants and children. Early diagnosis is important in congenital dermal sinus, so that treatment can be provided early, to prevent progression of associated complications. Clinical features There three key hallmarks of congenital dermal sinus: cutaneous abnormalities, infection, and neurological deficits. Cutaneous abnormalities Congenital dermal sinus is a tract from the surface layer of the skin, through the deeper tissues into the cranial or spinal cavity. The skin findings of this tract can include: Pit along neuraxis Flat capillary hemangioma Hypertrichosis Skin tag Abnormal pigmentation Subcutaneous lipoma Signs of local infection Infection The stratified squamous epithelium of the congenital dermal sinus tract can extend to the spinal fascia of the dura mater or all the way to the spinal cord. Thus, the congenital dermal sinus forms a point of entry for infection, this can allow for the formation of an abscess, especially among children. Infection can then travel up the spinal cord to result in meningitis, which can be fatal if left untreated. Neurological deficit Congenital dermal sinus is often also associated with spinal fluid drainage, intradural cysts and spinal cord tethering; conveying neurological deficit. Neurological deficit can occur due to spinal cord compression from intradural dermoid cyst growth in the epidermis and dermis. Tethered spinal cord can result in gait difficulties and sphincter dysfunction, as well as compressing the spine. Neurological deficits are more likely to occur where diagnosis has not been timely, allowing cysts and or infection. Imaging Magnetic Resonance Imaging (MRI) is the preferred tool for diagnostic and preoperative imaging of congenital dermal sinus. MRI allows the neural structures to be observed, visualizing the tract and its anomalies and lesions. For example, exposing tethered cord, inclusion tumors or spinal cord malformations. Observation by X-ray is limited in diagnosis, especially due to immature calcification of infants less than 18 months. X-ray may be used in conjunction with MRI or sonogram images to assist preoperatively. Treatment Treatment of congenital dermal sinus involves complete resection of the tract as well as intradural exploration. Prophylactic surgical removal of the congenital dermal sinus tract is beneficial for the patient, allowing neurological and bladder function to be maintained. Early surgical intervention results decreases the risk of infection and/or tumour progression – factors typically associated with delayed presentation of congenital dermal sinus. ] Intradural exploration is necessary as excision of the entire tract, as well as any of its intradural connections, reduces need for further surgical intervention.The surgical technique involves ‘removing the cutaneous lesion in ellipse’. The tract of the congenital dermal sinus must then be explored and excised, with intradural lesions dissected. If not all epithelial tissue is removed, there is a possibility for the dermoid cyst to reoccur and require further operation. Further operations are limited by postoperative and post-infection scarring. History Prior to pervasive use and availability of advanced methods of neuroimaging, it is possible that the rate of incidence of congenital dermal sinus has been supplemented by the incidence of coccygeal pits. Coccygeal pits are distinct from congenital dermal sinus as they are found within the gluteal cleft, rather than above the gluteal cleft. The caudally orientated coccygeal pits are not associated with intradural pathology and do not need to be excised, unlike the cephalically oriented tracts of the congenital dermal sinus which confer great intradural pathology and require surgical intervention. While coccygeal pits occur in 4% of neonate population, congenital dermal sinus is only found in 1 in 2500 live births. == References ==
Limb–girdle muscular dystrophy	Limb–girdle muscular dystrophy (LGMD) is a genetically heterogeneous group of rare muscular dystrophies that share a set of clinical characteristics. It is characterised by progressive muscle wasting which affects predominantly hip and shoulder muscles. LGMD usually has an autosomal pattern of inheritance. It currently has no known cure or treatment. Signs and symptoms By definition, all limb girdle muscular dystrophies (LGMD) cause progressive proximal weakness, meaning weakness of the muscles on or close to the torso that worsens over time. Explicitly, LGMD preferentially affects muscles of the hip girdle, thigh, shoulder girdle, and/or upper arm. The muscle weakness is generally symmetric. Usually, the hip girdle is the first area to exhibit weakness, manifesting as difficulty walking, going up and/or down stairs, rising from a chair, bending at the waist, or squatting. Because of these difficulties, falling can occur frequently. Weakness of the shoulder girdle can make lifting objects, or even elevating the arms, difficult or impossible. Rate of progression varies between patients. Eventually, the abilities to run and walk can deteriorate. The disease commonly leads to dependence on a wheelchair within years of symptom onset, although some patients maintain mobility. Eventually the disease can affect other muscles such as the ones located in the face. By definition, LGMDs primarily affect skeletal muscles, although cardiac muscle can be affected to a lesser degree in select subtypes, which can cause palpitations There can be significant variability in disease features and severity between LGMD subtypes, and even within any given LGMD subtype. Additional possible presentations include: In most cases, pain is not present with LGMD, and mental function is not affected. LGMD can begin in childhood, adolescence, young adulthood or even later, the age of onset is usually between 10 and 30. Both genders are affected equally. When limb-girdle muscular dystrophy begins in childhood, the progression appears to be faster and the disease more disabling. When the disorder begins in adolescence or adulthood the disease is generally not as severe and progresses more slowly. There is no sensory neuropathy or autonomic or visceral dysfunction at presentation. Genetics LGMD is a genetic and heritable disorder, due to one of many genetic mutations of proteins involved in muscle function. All currently identified LGMDs have an inheritance pattern that is dominant or recessive, although the definition of LGMD allows for diseases with more complicated inheritance patterns to be classified as LGMD. Examples of proteins affected in LGMD are α, β, γ and δ sarcoglycans. Diagnosis The diagnosis of limb–girdle muscular dystrophy can be done via muscle biopsy, which will show the presence of muscular dystrophy, and genetic testing is used to determine which type of muscular dystrophy a patient has. Immunohistochemical dystrophin tests can indicate a decrease in dystrophin detected in sarcoglycanopathies. In terms of sarcoglycan deficiency there can be variance (if α-sarcoglycan and γ-sarcoglycan are not present then theres a mutation in LGMD2D).The 2014 Evidence-based guideline summary: Diagnosis and treatment of limb–girdle and distal dystrophies indicates that individuals suspected of having the inherited disorder should have genetic testing. Other tests/analysis are: High CK levels(x10-150 times normal) MRI can indicate different types of LGMD. EMG can confirm the myopathic characteristic of the disease. Electrocardiography (cardiac arrhythmias in LGMD1B can occur) Types The "LGMD D" family is autosomal dominant, and the "LGMD R" family is autosomal recessive. Limb–girdle muscular dystrophy is explained in terms of gene, locus, OMIM and type as follows: LGMD criteria For a disease entity to be classified as an LGMD, the following criteria must be met: genetic, with an identifiable inheritance pattern such as autosomal dominant, autosomal recessive, digenic, or polygenic. relatively selective to skeletal muscle predominantly proximal muscle involvement independent walking is achieved at one point in life elevated serum creatine kinase muscle fiber loss dystrophic changes in muscle histology degenerative changes on medical imaging end-stage pathology seen in the most affected muscles described in at least two unrelated families Differential Many diseases can manifest similarly to LGMD. Dystrophinopathies, including Duchenne muscular dystrophy, Becker muscular dystrophy, and manifesting dystrophinopathy in female carriers, can present similarly to LGMD. Facioscapulohumeral muscular dystrophy can appear similarly, especially when it spares the facial muscles. Also in the differential are Emery-Dreifuss muscular dystrophies, Pompe disease, later-onset congenital myasthenic syndromes, and proximal-predominant hereditary motor neuropathies. Treatment There are few studies corroborating the effectiveness of exercise for limb–girdle muscular dystrophy. However studies have shown that exercise can, in fact, damage muscles permanently due to intense muscle contraction. Physical therapy may be required to maintain as much muscle strength and joint flexibility as possible. Calipers may be used to maintain mobility and quality of life. Careful attention to lung and heart health is required, corticosteroids in LGMD 2C-F individuals, shows some improvement. Additionally individuals can follow management that follows: Occupational therapy Respiratory therapy Speech therapy Neutralizing antibody to myostatin should not be pursuedThe sarcoglycanopathies could be possibly amenable to gene therapy. Prognosis In terms of the prognosis of limb–girdle muscular dystrophy in its mildest form, affected individuals have near-normal muscle strength and function. LGMD isnt typically a fatal disease, though it may eventually weaken the heart and respiratory muscles, leading to illness or death due to secondary disorders. Epidemiology The minimum prevalence of limb–girdle muscular dystrophy, as a group, likely ranges from 2.27-10 per 100,000 (1:44,000 to 1:10,000). LGMD is the fourth most common muscular dystrophy, after the dystrophinopathies, myotonic dystrophies, and facioscapulohumeral muscular dystrophy. The prevalence of individual LGMDs, as studied in the United States, in descending order, are those due to mutation of 1) calpain, 2) dysferlin, 3) collagen VI, 4) sarcoglycans, 5) anoctamin 5, and 6) fukutin-related protein. It is difficult to calculate the worldwide prevalence of even the most common LGMD types, due to the founder effect causing varying prevalence by region. The less common types are very rare, often only described is limited regions of the world. History The term limb girdle muscular dystrophy was published in 1954, describing a group of heterogeneous conditions that clinicians noticed to be distinct from Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, and myotonic dystrophy. The genetics of LGMDs began to be understood in the late 1900s, which led the European Neuromuscular Centre (ENMC) to establish a consensus on classification of LGMDs in 1995. The classification scheme at that time denoted autosomal dominant LGMDs as LGMD1 and autosomal recessive LGMDs as LGMD2. A letter was appended to the names of LGMDs according to the order of discovery of the causal genetic mutation. As LGMD2Z was established, the question arose of what letter to assign the next discovered LGMD2. With this issue, among other motives, the ENMC established a new consensus on the classification and definition of LGMD in 2017. With the new definition, several diseases were removed from the LGMD category: Research There is a variety of research under way targeted at various forms of limb–girdle muscular dystrophy. Among the treatments thought to hold promise is gene therapy, which is the delivery of genetic material, often a copy of a healthy gene, into cells.According to a review by Bengtsson et al. some success with AAV-mediated gene therapies (for different disorders) have increased interest in researchers, with CRISPR/Cas9 and exon-skipping helping these therapeutic goals along. Limb–girdle muscular dystrophies have many different types which are due to different gene mutations. LGMD2D is caused by a mutation in the α-sarcoglycan gene. Future treatment could be had by gene therapy through recombinant adeno-associated vectors.According to a review by Straub, et al., there are several research issues that need to be addressed: the rareness of the disease, poor understanding of the mechanism of LGMD R, and absence of patient cohorts, all contributing to lack of biomarkers for LGMD. The review goes on to state that animal models for LGMD R have been used to analyze therapeutic medications. Also, although prednisone has been used and has had positive effects on affected LGMD2 individuals, there is still no evidence of its effectiveness in trials that are placebo-controlled. See also Muscle atrophy References Further reading Cotta, Ana; Carvalho, Elmano; da-Cunha-Júnior, Antonio Lopes; Paim, Júlia Filardi; Navarro, Monica M.; Valicek, Jaquelin; Menezes, Miriam Melo; Nunes, Simone Vilela; Xavier Neto, Rafael (2014). "Common recessive limb girdle muscular dystrophies differential diagnosis: why and how?". Arquivos de Neuro-Psiquiatria. 72 (9): 721–734. doi:10.1590/0004-282X20140110. ISSN 0004-282X. PMID 25252238. Liu, Jian; Harper, Scott Q. (2012-08-01). "RNAi-based Gene Therapy for Dominant Limb Girdle Muscular Dystrophies". Current Gene Therapy. 12 (4): 307–314. doi:10.2174/156652312802083585. ISSN 1566-5232. PMC 4120526. PMID 22856606. ANGELINI, CORRADO; TASCA, ELISABETTA; NASCIMBENI, ANNA CHIARA; FANIN, MARINA (2014-12-01). "Muscle fatigue, nNOS and muscle fiber atrophy in limb girdle muscular dystrophy". Acta Myologica. 33 (3): 119–126. ISSN 1128-2460. PMC 4369848. PMID 25873780. == External links ==
Erythrocyanosis crurum	Erythrocyanosis crurum is a skin condition, a variant of acrocyanosis caused by chronic exposure to cold. See also Chilblains List of cutaneous conditions References Otto Braun-Falco; G. Plewig; H. H. Wolff; Walter H. C. Burgdorf (2000). Dermatology. Springer Verlag. p. 889. ISBN 3-540-59452-3. James, William D.; Berger, Timothy G.; et al. (2006). Andrews Diseases of the Skin: Clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0. == External links ==
Aortoiliac occlusive disease	In medicine, aortoiliac occlusive disease is a form of central artery disease involving the blockage of the abdominal aorta as it transitions into the common iliac arteries. Signs and symptoms Classically, it is described in male patients as a triad of the following signs and symptoms: claudication of the buttocks and thighs absent or decreased femoral pulses erectile dysfunctionThis combination is known as Leriche syndrome. However, any number of symptoms may present, depending on the distribution and severity of the disease, such as muscle atrophy, slow wound healing in the legs, and critical limb ischemia. Diagnosis The physical examination usually shows weakened femoral pulses and a reduced ankle-brachial index. The diagnosis can be verified by color duplex scanning, which reveals either a peak systolic velocity ratio ≥2.5 at the site of stenosis and/or a monophasic waveform. MRA and multidetector CTA are often used to determine the extent and type of obstruction. Another technique is digital subtraction angiography which allows verification of the diagnosis and endovascular treatment in a single session. Angiography provides important information regarding the perfusion and patency of distal arteries (e.g. femoral artery). The presence of collateral arteries in the pelvic and groin area is important in maintaining crucial blood flow and lower limb viability. However, angiography should only be used if symptoms warrant surgical intervention. Treatment Treatment involves revascularization typically using either angioplasty or a type of vascular bypass Kissing balloon angioplasty +/- stent, so named because the two common iliac stents touch each other in the distal aorta. Aorto-iliac bypass graft Axillary-bi-femoral and femoral-femoral bypass (sometimes abbreviated "ax-fem fem-fem") History The condition was first described by Robert Graham in 1914, but the condition with its triad of symptoms was ascribed to René Leriche. Leriche, a French surgeon, linked the pathophysiology with the anatomy of the condition. John Hunters dissections of atherosclerotic aortic bifurcations from the late 18th century are preserved at the Hunterian Museum, but Leriche was first to publish on the subject based on a patient he treated with the condition at the age of 30. Following treatment the 30-year-old was able to walk without pain and maintain an erection. See also Claudication Peripheral arterial disease References == External links ==
Myopericarditis	Myopericarditis is a combination of both myocarditis and pericarditis appearing in a single individual, namely inflammation of both the pericardium and the heart muscle. It can involve the presence of fluid in the heart. Risk factors The appearance of myopericarditis is associated with infections such as acute tonsillitis, pneumonia, and gastroenteritis.Smallpox vaccination has been a known risk factor for myocarditis and pericarditis since the 1950s. In 1983, an incidence of myocarditis of 1 per 10 000 was reported among Finnish military personnel. Among US military service members vaccinated between December 2002 and March 2003 with Dryvax smallpox vaccine 18 cases of probable myopericarditis were reported, which was an incidence of 7.8 per 100 000 over 30 days.A meta-review from 2022 shows that the overall risk for myopericarditis after receiving a COVID-19 vaccine is low. In addition, the incidence of myopericarditis is significantly higher with a smallpox vaccination in comparison with a COVID-19 vaccination. The ACAM2000 smallpox vaccine has been known to cause myopericarditis in some people. Etymology When ventricular function is normal, the term myopericarditis is used. Cases with impaired function are labeled perimyocarditis, though the two terms are often used interchangeably. Both will be reflected on an ECG.In a different naming scheme, inflammation that is predominantly pericarditis with some myocardial involvement is called myopericarditis, while predominant myocarditis with some pericardial involvement is called perimyocarditis. == References ==
Pearly penile papules	Pearly penile papules (PPP) are benign small bumps on the human penis. They vary in size from 1–4 mm, are pearly or flesh-colored, smooth and dome-topped or filiform, and appear in one or several rows around the corona, the ridge of the head of the penis and sometimes on the penile shaft. They are painless, non-cancerous and not harmful. Symptoms and signs PPPs are small bumps on the human penis. They vary in size from 1–4 mm, are pearly or flesh-colored, smooth and dome-topped or filiform, and appear in one or several rows around the corona, the ridge of the glans and sometimes on the penile shaft. They are painless, non-cancerous and not harmful. Cause and mechanism PPPs are a type of angiofibroma. Their function is not well-understood. They are sometimes described as vestigial remnants of penile spines, sensitive features found in the same location in other primates. PPPs secrete oil that moistens the glans of the penis. They do not spread and often spontaneously regress. Along with Fordyce glands PPPs secrete oils to keep the skin of the head of penis in good condition. Smegma can accumulate if these oils are produced in excess or there is inadequate washing under the foreskin. Diagnosis Diagnosis is by visualisation. On dermoscopy, the white-pink papules appear in a cobblestone-like pattern and contain a central dotted or comma-shaped blood vessels. There is no scale. PPPs are sometimes mistaken for genital warts due to a perceived similarity in appearance. They can also appear similar to molluscum contagiosum, sebaceous hyperplasia and lichen nitidus. Histopathology shows dense connective tissue, fibroblasts and many blood vessels. Treatment Generally, reassurance is given and no treatment is needed. Laser or cryotherapy may be considered for men who find PPPs distressing to look at or feel excessive embarrassment.Carbon dioxide laser generally has good outcomes with skin healing within seven days. The procedure requires anaesthesia, may need to be performed more than once, and has a risk of bleeding, scarring and colour changes. Another procedure involves a hyfrecator. Epidemiology PPPs are common and occur in 14% to 48% of young males. They are more common in uncircumcised males. Social and cultural Some men find PPPs distressing to look at, owing to their resemblance to some sexually transmitted infections. Although it is not related to any disease, PPPs are occasionally mistaken for HPV warts. There are also home remedies for "curing" it, despite the fact that the papules are neither infectious nor detrimental to ones health and may have beneficial functions. Some of the "home remedies" found on the Internet and elsewhere use mild ointments or creams to soften the papules, but others are physically dangerous techniques for papule removal which can result in permanent genital mutilation.Rapini et al. advise that, since dermatologists have safe, effective ways to remove the papules if desired, home remedies involving corrosive substances or self-surgery should be avoided, since they can permanently damage sexual functioning. Rapini et al. further state that removal should only be performed by a physician using proven medical techniques. References == External links ==
Parapharyngeal abscess	A parapharyngeal abscess is a deep neck space abscess of the parapharyngeal space (or pharyngomaxillary space), which is lateral to the superior pharyngeal constrictor muscle and medial to the masseter muscle. This space is divided by the styloid process into anterior and posterior compartments. The posterior compartment contains the carotid artery, internal jugular vein, and many nerves. Signs and symptoms Symptoms include fever, sore throat, painful swallowing, and swelling in the neck. An anterior space abscess can cause lockjaw (spasm of jaw muscle), and hard mass formation along the angle of the mandible, with medial bulging of the tonsil and lateral pharyngeal wall. A posterior space abscess causes swelling in the posterior pharyngeal wall, and lockjaw is minimal. Other structures within the carotid sheath may be involved, causing rigors, high fever, bacteremia, neurologic deficit, or a massive haemorrhage caused by carotid artery rupture. Cause Infection can occur from: Pharynx: acute and chronic infection of tonsil and adenoids Teeth: dental infection occurs from lower last molar tooth Ear: Bezolds abscess and petrositis Other space: infection of parotid retropharyngeal space External trauma: penetrating injuries of neck, injection of local anaesthetic Epidemiology Parapharyngeal abscess is more common in male than the female gender. Any age group can develop a parapharyngeal abscess but it is most commonly seen in children and adolescents. Adults who are immunocompromised are also at high risk. == References ==
Romano–Ward syndrome	Romano–Ward syndrome is the most common form of congenital Long QT syndrome (LQTS), a genetic heart condition that affects the electrical properties of heart muscle cells. Those affected are at risk of abnormal heart rhythms which can lead to fainting, seizures, or sudden death. Romano–Ward syndrome can be distinguished clinically from other forms of inherited LQTS as it affects only the electrical properties of the heart, while other forms of LQTS can also affect other parts of the body. Romano–Ward syndrome is caused by abnormal variants in the genes responsible for producing certain proteins used to transport charged particles (ion channels) within the heart. These abnormalities interfere with the electrical signals that heart cells use to coordinate contractions, causing the heart to take longer to recharge in between beats. The condition is usually diagnosed using an electrocardiogram, but other tests sometimes used include Holter monitoring, exercise testing, and genetic testing. It may be treated using medications such as beta-blockers, an implantable cardioverter-defibrillator, or surgery to disrupt the sympathetic nervous system. Romano–Ward syndrome is estimated to affect 1 in every 7,000 people. Signs and symptoms Romano–Ward syndrome increases the risk of abnormal heart rhythms or arrhythmias. These are typically a form of ventricular tachycardia known as Torsades de pointes which can cause faints, seizures, or even sudden death. Less dangerous arrhythmias such as atrial fibrillation also occur, causing symptoms of heart racing or palpitations. However, many of those with Romano–Ward syndrome will remain free from arrhythmias and therefore free from symptoms. Certain situations are more likely to precipitate arrhythmias such as exercise or mental stress in the LQT1 subtype, sudden loud noise in the LQT2 subtype, and during sleep or immediately upon waking in the LQT3 subtype.Romano–Ward syndrome can be differentiated from other forms of long QT syndrome by Romano-Wards sole involvement of the heart. While other forms of long QT syndrome are associated with deafness (Jervell and Lange-Nielsen syndrome), intermittent weakness and bone abormailities (LQT7, Andersen–Tawil syndrome), and autism spectrum disorder (LQT8, Timothy syndrome), these extra-cardiac manifestations are not seen in Romano-Ward. Causes Romano–Ward syndrome is a descriptive term for a group of subtypes of long QT syndrome, specifically subtypes LQT1-6 and LQT9-16. Several subtypes of Romano–Ward syndrome have been described based on the underlying genetic variant. These subtypes differ in clinical presentation and their response to treatment. There is robust evidence that the genetic variants associated with the three most common subtypes (LQT1, LQT2 and LQT3) are truly causative of the syndrome. However, there is uncertainty as to whether some of the other rarer subtypes are truly disease-causing by themselves or instead make individuals more susceptible to QT prolongation in response to other factors such as medication or low blood potassium levels (hypokalaemia). LQT1 LQT1 is the most common subtype of Romano–Ward syndrome, responsible for 30 to 35% of all cases. The gene responsible, KCNQ1, has been isolated to chromosome 11p15.5 and encodes the alpha subunit of the KvLQT1 potassium channel. This subunit interacts with other proteins (in particular, the minK beta subunit) to create the channel, which carries the delayed potassium rectifier current IKs responsible for the repolarisation phase of the cardiac action potential.Variants in KCNQ1 cause the LQT1 subtype of Romano–Ward syndrome when a single copy of the variant is inherited (heterozygous, autosomal dominant inheritance). When two copies of the variant are inherited (homozygous, autosomal recessive inheritance) the more severe Jervell and Lange-Nielsen syndrome is found, associated with more marked QT prolongation, congenital sensorineural deafness, and a greater risk of arrhythmias.LQT1 is associated with a high risk of faints but lower risk of sudden death than LQT2.LQT1 may also affect glucose regulation. After ingesting glucose, those with LQT1 produce more insulin than would be expected, which is followed by a period of insulin resistance. When the resistance diminishes, abnormally low blood glucose levels (hypoglycaemia) are sometimes seen. LQT2 The LQT2 subtype is the second-most common form of Romano–Ward syndrome, responsible for 25 to 30% of all cases. This form of Romano–Ward syndrome is caused by variants in the KCNH2 gene on chromosome 7. KCNH2 (also known as hERG) encodes the potassium channel which carries the rapid inward rectifier current IKr. This current contributes to the terminal repolarisation phase of the cardiac action potential, and therefore the length of the QT interval. LQT3 The LQT3 subtype of Romano–Ward syndrome is caused by variants in the SCN5A gene located on chromosome 3p21-24. SCN5A encodes the alpha subunit of the cardiac sodium channel, NaV1.5, responsible for the sodium current INa which depolarises cardiac cells at the start of the action potential. Cardiac sodium channels normally inactivate rapidly, but the mutations involved in LQT3 slow their inactivation leading to a small sustained late sodium current. This continued inward current prolongs the action potential and thereby the QT interval.A large number of mutations have been characterized as leading to or predisposing to LQT3. Calcium has been suggested as a regulator of SCN5A protein, and the effects of calcium on SCN5A may begin to explain the mechanism by which some of these mutations cause LQT3. Furthermore, mutations in SCN5A can cause Brugada syndrome, cardiac conduction disease, and dilated cardiomyopathy. In rare situations, some individuals can have combinations of these diseases. Other subtypes LQT5 is caused by variants in the KCNE1 gene. This gene is responsible for the potassium channel beta subunit MinK which, in conjunction with the alpha subunit encoded by KCNQ1, is responsible for the potassium current IKs, and variants associated with prolonged QT intervals decrease this current. The same variants in KCNE1 can cause the more severe Jervell and Lange-Nielsen syndrome when two copies are inherited (homozygous inheritance) and the milder LQT5 subtype of Romano–Ward syndrome when a single copy of the variant is inherited (heterozygous inheritance).The LQT6 subtype is caused by variants in the KCNE2 gene. This gene is responsible for the potassium channel beta subunit MiRP1 which generates the potassium current IKr, and variant that decrease this current have been associated with prolongation of the QT interval. However, subsequent evidence such as the relatively common finding of variants in the gene in those without long QT syndrome, and the general need for a second stressor such as hypokalaemia to be present to reveal the QT prolongation, has suggested that this gene instead represents a modifier to susceptibility to QT prolongation. Some, therefore, dispute whether variants in the gene are sufficient to cause Romano–Ward syndrome by themselves.LQT9 is caused by variants in the membrane structural protein, caveolin-3. Caveolins form specific membrane domains called caveolae in which voltage-gated sodium channels sit. Similar to LQT3, these caveolin variants increase the late sustained sodium current, which impairs cellular repolarization.LQT10 is an extremely rare subtype, caused by variants in the SCN4B gene. The product of this gene is an auxiliary beta-subunit (NaVβ4) forming cardiac sodium channels, variants in which increase the late sustained sodium current. LQT13 is caused by variants in GIRK4, a protein involved in the parasympathetic modulation of the heart. Clinically, the patients are characterized by only modest QT prolongation, but an increased propensity for atrial arrhythmias. LQT14, LQT15 and LQT16 are caused by variants in the genes responsible for calmodulin (CALM1, CALM2, and CALM3 respectively). Calmodulin interacts with several ion channels and its roles include modulation of the L-type calcium current in response to calcium concentrations, and trafficking the proteins produced by KCNQ1 and thereby influencing potassium currents. The precise mechanisms by which means these genetic variants prolong the QT interval remain uncertain.Table of causative genes Mechanism In the Romano-Ward forms of Long QT syndrome, genetic mutations affect how positively-charged ions, such as potassium, sodium and calcium ions are transported in and out of heart cells. Many of these genes encode proteins which form or interact with ion channels. In cardiac muscle, these ion channels play critical roles in maintaining the hearts normal rhythm. Mutations in any of these genes alter the structure or function of channels, which changes the flow of ions between cells, a disruption in ion transport alters the way the heart beats, leading to abnormal heart rhythm characteristic of the syndrome.The protein made by the ANK2 gene ensures that other proteins, particularly ion channels, are inserted into the cell membrane appropriately. A mutation in the ANK2 gene likely alters the flow of ions between cells in the heart, which disrupts the hearts normal rhythm and results in the features of Romano–Ward syndrome. Diagnosis Romano–Ward syndrome is principally diagnosed by measuring the QT interval corrected for heart rate (QTc) on a 12-lead electrocardiogram (ECG). Romano–Ward syndrome is associated with a prolonged QTc, although in some genetically proven cases of Romano–Ward syndrome this prolongation can be hidden, known as concealed Long QT syndrome. The QTc is less than 450 ms in 95% of normal males, and less than 460 ms in 95% of normal females. Romano–Ward syndrome is suggested if the QTc is longer than these cutoffs. However, as 5% of normal people also fall into this category, some suggest cutoffs of 470 and 480 ms for males and females respectively, corresponding with the 99th centiles of normal values.The major subtypes of Romano–Ward syndrome are associated with specific ECG features. LQT1 is typically associated with broad-based T-waves, whereas the T-waves in LQT2 are notched and of lower amplitude, whilst in LQT3 the T-waves are often late onset, being preceded by a long isoelectric segment.Other factors beyond the QT interval should be taken into account when making a diagnosis, some of which have been incorporated into scoring systems such as the Schwartz score. These factors include a history of characteristic abnormal heart rhythms (Torsades de Pointes), unexplained blackouts (syncope), and a family history of confirmed LQT syndrome. Other investigations that may suggest a diagnosis of the LQT1 form of Romano–Ward syndrome include paradoxical lengthening of the QT interval in response to exercise (QTc >470 ms at 2–4 minutes of recovery) or during an artificial infusion of adrenaline (lengthening of the absolute QT interval >30 ms during low dose adrenaline). Treatment The treatment for Romano–Ward syndrome aims to reduce the risk of arrhythmias. Lifestyle measures include avoiding very strenuous or competitive exercise. Those with the LQT2 form of Romano–Ward syndrome should avoid sudden loud noises such as alarm clocks as these may trigger arrhythmias. Fevers should be treated promptly with paracetamol. Grapefruit juice should be avoided as it contains a chemical which decreases IKr and further prolongs the QT interval. Medications that further prolong the QT interval such as sotalol should be avoided, lists of which can be found in publicly accessible online databases.Beta blockers such as propranolol or nadolol blunt the effects of adrenaline on the heart and thereby reduce the risk of arrhythmias. Mexiletine, flecainide and ranolazine decrease the late sodium current and are of particular use in the LQT3 form of Romano–Ward syndrome, and mexiletine may also be of benefit in other subtypes. Potassium supplements may be used at times when potassium is being lost such as when experiencing diarrhoea or vomiting, but medications that encourage the retention of potassium such as spironolactone or amiloride may also be required.An implantable defibrillator, a small device that monitors the heart rhythm and can automatically deliver an electric shock to restart the heart, may be recommended. These devices are recommended for those with Romano–Ward syndrome who have experienced a cardiac arrest or a blackout whilst taking beta blockers. In those who experience recurrent arrhythmias despite medical therapy, a surgical procedure called sympathetic denervation can be used to interrupt the nerves that stimulate the heart. Epidemiology Romano–Ward syndrome is the most common form of inherited long QT syndrome, affecting an estimated 1 in 7,000 people worldwide. See also Long QT syndrome Jervell and Lange-Nielsen syndrome Andersen-Tawil syndrome Timothy syndrome References Further reading Kelly, Evelyn B. (2013-01-07). Encyclopedia of Human Genetics and Disease. ABC-CLIO. ISBN 9780313387135. retrieved 2017-04-07 Nakano, Yukiko; Shimizu, Wataru (2016-01-01). "Genetics of long-QT syndrome". Journal of Human Genetics. 61 (1): 51–55. doi:10.1038/jhg.2015.74. ISSN 1434-5161. PMID 26108145. S2CID 30987284. == External links ==
Erythema nodosum	Erythema nodosum (EN) is an inflammatory condition characterized by inflammation of the fat cells under the skin, resulting in tender red nodules or lumps that are usually seen on both shins. It can be caused by a variety of conditions, and typically resolves spontaneously within 30 days. It is common in young people aged 12–20 years. Signs and symptoms Pre-eruptive phase The first signs of erythema nodosum are often flu-like symptoms such as a fever, cough, malaise, and aching joints. Some people also experience stiffness or swelling in the joints and weight loss. Eruptive stage Erythema nodosum is characterised by 1–2-inch (25–51 mm) nodules (rounded lumps) below the skin surface, usually on the shins. These subcutaneous nodules can appear anywhere on the body, but the most common sites are the shins, arms, thighs, and torso. Each nodule typically disappears after around two weeks, though new ones may continue to form for up to six or eight weeks. A new nodule usually appears red and is hot and firm to the touch. The redness starts to fade and it gradually becomes softer and smaller until it disappears. Each nodule usually heals completely without scarring over the course of about two weeks. Joint pain and inflammation sometimes continue for several weeks or months after the nodules appear.Less common variants of erythema nodosum include: Ulcerating forms, seen in Crohns disease Erythema contusiforme, when a subcutaneous hemorrhage (bleeding under the skin) occurs with an erythema nodosum lesion, causing the lesion to look like a contusion (bruise) Erythema nodosum migrans (also known as subacute nodular migratory panniculitis), a rare form of chronic erythema nodosum characterized by asymmetrical nodules that are mildly tender and migrate over time. Causes EN is associated with a wide variety of conditions. Idiopathic About 30–50% of EN cases are idiopathic (of an unknown cause). Infection Infections associated with EN include: Streptococcal infection which, in children, is by far the most common precipitant Primary infection of tuberculosis Mycoplasma pneumoniae Histoplasma capsulatum Yersinia Lymphogranuloma venereum (LGV), caused by the bacteria Chlamydia trachomatis Epstein-Barr virus Coccidioides immitis (Valley fever) Cat scratch disease Autoimmune disorders Autoimmune disorders associated with EN include: Inflammatory bowel disease (IBD): about 15% of patients develop erythema nodosum. Behçets disease Sarcoidosis Pregnancy Pregnancy may be associated with EN. Medications Medications associated with EN include: Omeprazole Sulfonamides Penicillins Bromides Hepatitis B vaccination Cancer Cancers associated with EN include: Non-Hodgkins lymphoma (NHL) Carcinoid tumours Pancreatic cancerEN may also be due to excessive antibody production in lepromatous leprosy leading to deposition of immune complexes.There is an association with the HLA-B27 histocompatibility antigen, which is present in 65% of patients with erythema nodosum.A useful mnemonic for causes is SORE SHINS (Streptococci, OCP, Rickettsia, Eponymous (Behçet), Sulfonamides, Hansens Disease (Leprosy), IBD, NHL, Sarcoidosis. Pathophysiology Erythema nodosum is probably a delayed hypersensitivity reaction to a variety of antigens. Although circulating immune complexes have been demonstrated in patients with inflammatory bowel disease, they have not been found in idiopathic or uncomplicated cases. Diagnosis Erythema nodosum is diagnosed clinically. A biopsy can be taken and examined microscopically to confirm an uncertain diagnosis. Microscopic examination usually reveals a neutrophilic infiltrate surrounding capillaries that results in septal thickening, with fibrotic changes in the fat around blood vessels. A characteristic microscopic finding is radial granulomas, well-defined nodular aggregates of histiocytes surrounding a stellate cleft.Additional evaluation should be performed to determine the underlying cause of erythema nodosum. This may include a full blood count, erythrocyte sedimentation rate (ESR), antistreptolysin-O (ASO) titer and throat culture, urinalysis, intradermal tuberculin test, and a chest x-ray. The ESR is typically high, the C-reactive protein elevated, and the blood showing an increase in white blood cells.The ESR is initially very high and falls as the nodules of erythema nodosum. The ASO titer is high in cases associated with a streptococcal throat infection. A chest X-ray should be performed to rule out pulmonary diseases, in particular sarcoidosis and Löfgren syndrome. Treatment Erythema nodosum is self-limiting and usually resolves itself within 3–6 weeks. A recurring form does exist, and in children, it is attributed to repeated infections with streptococcus. Treatment should focus on the underlying cause. Symptoms can be treated with bed rest, leg elevation, compressive bandages, wet dressings, and nonsteroidal anti-inflammatory agents (NSAIDs). NSAIDs are usually more effective at the onset of EN versus with chronic disease.Potassium iodide can be used for persistent lesions whose cause remains unknown. Corticosteroids and colchicine can be used in severe refractory cases. Thalidomide has been used successfully in the treatment of Erythema nodosum leprosum, and it was approved by the U.S. FDA for this use in July 1998. According to a 2009 meta-analysis, there is some evidence of benefit for both thalidomide and clofazimine in the treatment of erythema nodosum leprosum. Epidemiology Erythema nodosum is the most common form of panniculitis. It is most common in the ages of 20–30, and affects women 3–6 times more than men. Eponym The term, Subacute Migratory Panniculitis of Vilanova and Piñol, was named after the two Catalan dermatologists who provided a brief description and explanation of the disease, Xavier Montiu Vilanova (1902–1965) and Joaquin Aguade Piñol (1918–1977), in 1954, and was named in 1956. References == External links ==
Ascites	Ascites is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdominal size, increased weight, abdominal discomfort, and shortness of breath. Complications can include spontaneous bacterial peritonitis.In the developed world, the most common cause is liver cirrhosis. Other causes include cancer, heart failure, tuberculosis, pancreatitis, and blockage of the hepatic vein. In cirrhosis, the underlying mechanism involves high blood pressure in the portal system and dysfunction of blood vessels. Diagnosis is typically based on an examination together with ultrasound or a CT scan. Testing the fluid can help in determining the underlying cause.Treatment often involves a low-salt diet, medication such as diuretics, and draining the fluid. A transjugular intrahepatic portosystemic shunt (TIPS) may be placed but is associated with complications. Attempts to treat the underlying cause, such as by a liver transplant may be considered. Of those with cirrhosis, more than half develop ascites in the ten years following diagnosis. Of those in this group who develop ascites, half will die within three years. The term is from the Greek askítes meaning "baglike". Signs and symptoms Mild ascites is hard to notice, but severe ascites leads to abdominal distension. People with ascites generally will complain of progressive abdominal heaviness and pressure as well as shortness of breath due to mechanical impingement on the diaphragm.Ascites is detected with physical examination of the abdomen by visible bulging of the flanks in the reclining person ("flank bulging"), "shifting dullness" (difference in percussion note in the flanks that shifts when the person is turned on the side), or in massive ascites, with a "fluid thrill" or "fluid wave" (tapping or pushing on one side will generate a wave-like effect through the fluid that can be felt in the opposite side of the abdomen). Other signs of ascites may be present due to its underlying cause. For instance, in portal hypertension (perhaps due to cirrhosis or fibrosis of the liver) people may also complain of leg swelling, bruising, gynecomastia, hematemesis, or mental changes due to encephalopathy. Those with ascites due to cancer (peritoneal carcinomatosis) may complain of chronic fatigue or weight loss. Those with ascites due to heart failure may also complain of shortness of breath as well as wheezing and exercise intolerance. Complications Complications may include spontaneous bacterial peritonitis, hepatorenal syndrome, and thrombosis. Portal vein thrombosis and splenic vein thrombosis involve clotting of blood affects the hepatic portal vein or varices associated with splenic vein. This can lead to portal hypertension and a reduction in blood flow. When a person with liver cirrhosis has thrombosis, it is not possible to perform a liver transplant, unless the thrombosis is very minor. In case of minor thrombosis, there are some chances of survival using cadaveric liver transplant. Causes Causes of high serum-ascites albumin gradient (SAAG or transudate) are Cirrhosis – 81% (alcoholic in 65%, viral in 10%, cryptogenic in 6%) Heart failure – 3% Hepatic venous occlusion: Budd–Chiari syndrome or veno-occlusive disease Constrictive pericarditis Kwashiorkor (childhood protein-energy malnutrition)Causes of low SAAG ("exudate") areCancer (metastasis and primary peritoneal carcinomatosis) – 10% Infection: Tuberculosis – 2% or spontaneous bacterial peritonitis Pancreatitis – 1% Serositis Nephrotic syndrome Hereditary angioedemaOther rare causesMeigs syndrome Vasculitis Hypothyroidism Renal dialysis Peritoneum mesothelioma Abdominal tuberculosis Mastocytosis Diagnosis Routine complete blood count (CBC), basic metabolic profile, liver enzymes, and coagulation should be performed. Most experts recommend a diagnostic paracentesis be performed if the ascites is new or if the person with ascites is being admitted to the hospital. The fluid is then reviewed for its gross appearance, protein level, albumin, and cell counts (red and white). Additional tests will be performed if indicated such as microbiological culture, Gram stain and cytopathology.The serum-ascites albumin gradient (SAAG) is probably a better discriminant than older measures (transudate versus exudate) for the causes of ascites. A high gradient (> 1.1 g/dL) indicates the ascites is due to portal hypertension. A low gradient (< 1.1 g/dL) indicates ascites of non-portal hypertensive as a cause.Ultrasound investigation is often performed prior to attempts to remove fluid from the abdomen. This may reveal the size and shape of the abdominal organs, and Doppler studies may show the direction of flow in the portal vein, as well as detecting Budd-Chiari syndrome (thrombosis of the hepatic vein) and portal vein thrombosis. Additionally, the sonographer can make an estimation of the amount of ascitic fluid, and difficult-to-drain ascites may be drained under ultrasound guidance. An abdominal CT scan is a more accurate alternate to reveal abdominal organ structure and morphology. Classification Ascites exists in three grades: Grade 1: mild, only visible on ultrasound and CT Grade 2: detectable with flank bulging and shifting dullness Grade 3: directly visible, confirmed with the fluid wave/thrill test Pathophysiology Ascitic fluid can accumulate as a transudate or an exudate. Amounts of up to 35 liters are possible. Roughly, transudates are a result of increased pressure in the hepatic portal vein (>8 mmHg, usually around 20 mmHg (e.g., due to cirrhosis), while exudates are actively secreted fluid due to inflammation or malignancy. As a result, exudates are high in protein and lactate dehydrogenase and have a low pH (<7.30), a low glucose level, and more white blood cells. Transudates have low protein (<30 g/L), low LDH, high pH, normal glucose, and fewer than 1 white cell per 1000 mm3. Clinically, the most useful measure is the difference between ascitic and serum albumin concentrations. A difference of less than 1 g/dl (10 g/L) implies an exudate.Portal hypertension plays an important role in the production of ascites by raising capillary hydrostatic pressure within the splanchnic bed. Regardless of the cause, sequestration of fluid within the abdomen leads to additional fluid retention by the kidneys due to stimulatory effect on blood pressure hormones, notably aldosterone. The sympathetic nervous system is also activated, and renin production is increased due to decreased perfusion of the kidney. Extreme disruption of the renal blood flow can lead to hepatorenal syndrome. Other complications of ascites include spontaneous bacterial peritonitis (SBP), due to decreased antibacterial factors in the ascitic fluid such as complement. Treatment Ascites is generally treated while an underlying cause is sought, in order to prevent complications, relieve symptoms, and prevent further progression. In people with mild ascites, therapy is usually as an outpatient. The goal is weight loss of no more than 1.0 kg/day for people with both ascites and peripheral edema and no more than 0.5 kg/day for people with ascites alone. In those with severe ascites causing a tense abdomen, hospitalization is generally necessary for paracentesis. High serum-ascites albumin gradient (transudative) ascites Diet Salt restriction is the initial treatment, which allows diuresis (production of urine) since the person now has more fluid than salt concentration. Salt restriction is effective in about 15% of these people. Water restriction is needed if serum sodium levels drop below 130 mmol L−1. Diuretics Since salt restriction is the basic concept in treatment, and aldosterone is one of the hormones that acts to increase salt retention, a medication that counteracts aldosterone should be sought. Spironolactone (or other distal-tubule diuretics such as triamterene or amiloride) is the drug of choice since they block the aldosterone receptor in the collecting tubule. This choice has been confirmed in a randomized controlled trial. Diuretics for ascites should be dosed once per day. Generally, the starting dose is oral spironolactone 100 mg/day (max 400 mg/day). 40% of people will respond to spironolactone. For nonresponders, a loop diuretic may also be added and generally, furosemide is added at a dose of 40 mg/day (max 160 mg/day), or alternatively (bumetanide or torasemide). The ratio of 100:40 reduces risks of potassium imbalance. Serum potassium level and renal function should be monitored closely while on these medications.Monitoring diuresis: Diuresis can be monitored by weighing the person daily. The goal is weight loss of no more than 1.0 kg/day for people with both ascites and peripheral edema and no more than 0.5 kg/day for people with ascites alone. If daily weights cannot be obtained, diuretics can also be guided by the urinary sodium concentration. Dosage is increased until a negative sodium balance occurs. A random urine sodium-to-potassium ratio of > 1 is 90% sensitivity in predicting negative balance (> 78-mmol/day sodium excretion).Diuretic resistance: Diuretic resistance can be predicted by giving 80 mg intravenous furosemide after 3 days without diuretics and on an 80 mEq sodium/day diet. The urinary sodium excretion over 8 hours < 50 mEq/8 hours predicts resistance.If the person exhibits a resistance or poor response to diuretic therapy, ultrafiltration or aquapheresis may be needed to achieve adequate control of fluid retention and congestion. The use of such mechanical methods of fluid removal can produce meaningful clinical benefits in people with diuretic resistance and may restore responsiveness to conventional doses of diuretics. Paracentesis In those with severe (tense) ascites, therapeutic paracentesis may be needed in addition to medical treatments listed above. As this may deplete serum albumin levels in the blood, albumin is generally administered intravenously in proportion to the amount of ascites removed. Surgery Ascites that is refractory to medical therapy is considered an indication for liver transplantation. In the United States, the MELD score (online calculator) is used to prioritize people for transplantation. In a minority of people with advanced cirrhosis that have recurrent ascites, shunts may be used. Typical shunts used are portacaval shunt, peritoneovenous shunt, and the transjugular intrahepatic portosystemic shunt (TIPS). However, none of these shunts has been shown to extend life expectancy, and are considered to be bridged to liver transplantation. A meta-analysis of randomized controlled trials by the international Cochrane Collaboration concluded that "TIPS was more effective at removing ascites as compared with paracentesis...however, people with TIPS develop hepatic encephalopathy significantly more often".Another potential treatment option for patients with refractory/malignant ascites is the alfapump, (automated low flow ascites pump) which is an implantable device that removes ascites out of the peritoneal cavity and transports it via the pump into the bladder, where it passed naturally from the body through urination. Low SAAG ("exudative") ascites Exudative ascites generally does not respond to manipulation of the salt balance or diuretic therapy. Repeated paracentesis and treatment of the underlying cause is the mainstay of treatment. Society and culture It has been suggested that ascites was seen as a punishment especially for oath-breakers among the Proto-Indo-Europeans. This proposal builds on the Hittite military oath as well as various Vedic hymns (RV 7.89, AVS 4.16.7). A similar curse dates to the Kassite dynasty (12th century BC). References == External links ==
Brazilian purpuric fever	Brazilian purpuric fever (BPF) is an illness of children caused by the bacterium Haemophilus influenzae biogroup aegyptius which is ultimately fatal due to sepsis. BPF was first recognized in the São Paulo state of Brazil in 1984. At this time, young children between the ages of 3 months and 10 years were contracting a strange illness which was characterized by high fever and purpuric lesions on the body. These cases were all fatal, and originally thought to be due to meningitis. It was not until the autopsies were conducted that the cause of these deaths was confirmed to be infection by H. influenzae aegyptius. Although BPF was thought to be confined to Brazil, other cases occurred in Australia and the United States during 1984–1990. Haemophilus species are non-spore-forming gram-negative coccobacilli . They lack motility and are aerobic or facultatively anaerobic. They require preformed growth factors that are present in blood, specifically hemin (X factor) and NAD or NADP (V factor). The bacterium grows best at 35–37 °C and has an optimal pH of 7.6. Haemophilus species are obligate parasites and are part of the normal flora of the human upper respiratory tract. Presentation In documented BPF cases, the symptoms include high fever (101.3 °F/38,5 °C or higher), nausea, vomiting, severe abdominal pain, septic shock, and ultimately death. A history of conjunctivitis 30 days prior to the onset of fever was also present in the documented BPF cases. The physical presentation of children infected with BPF include purpuric skin lesions affecting mainly the face and extremities, cyanosis, rapid necrosis of soft tissue, particularly the hands, feet, nose, and ears. Analysis of the fatalities due to BPF showed hemorrhage in the skin, lungs, and adrenal glands. Histopathology showed hemorrhage, intravascular microthrombi and necrosis in the upper dermis, renal glomeruli, lungs, and hepatic sinusoids. Risk factors The risk factors associated with BPF are not well known. However, it has been suggested that children under 5 years of age are more susceptible to BPF since they lack serum bactericidal activity against the infection. Older children and adults have much higher titers of bactericidal antibodies, which serve as a protective measure. Also children residing in warmer geographic areas have been associated with a higher risk of BPF infection. Transmission The eye gnat (Liohippelates) was thought to be the cause of the conjunctivitis epidemic which occurred in Mato Grosso do Sul in 1991. These gnats were extracted from the conjunctival secretions of the children who were infected with conjunctivitis. 19 of those children developed BPF following the conjunctivitis. Other modes of transmission include contact with the conjunctival discharges of infected people, ophthalmic instruments which have not been properly sterilized, sharing eye makeup applicators or multiple-dose eye medications. Pathogenesis The pathogenesis of BPF is not well established but it is thought that patients become pharyngeal or conjunctival carriers of H. aegyptius, which is followed by spreading to the bloodstream. This hypothesis is supported by the isolation of from both the conjunctiva and oropharynx of documented BPF cases with H. aegyptius bacteremia. Possible virulence factors of H. aegyptius include lipooligosaccharides (LOS), capsular polysaccharides, pilus proteins (mediates adhesion to mucosal membrane), immunoglobulin A1 (IgA1), membrane associated proteins, and extracellular proteins. In a study conducted by Barbosa et al., a 60 kilodalton hemagglutinating extracellular product was suggested to be the major pathogenic factor linked to the hemorrhagic manifestations of BPF. This molecule was found to be absorbable by human O-type erythrocytes. After the molecule had been injected into rabbits, they showed reactions similar to that of BPF patients. Further research is being conducted to determine the mechanisms involved with the other virulence factors of H. aegyptius. The overall pathogenesis of BPF probably involves multiple steps and a number of bacterial factors. Diagnosis A positive BPF diagnosis includes the clinical symptoms (mainly the fever, purpuric lesions, and rapid progression of the disease), isolation of Haemophilus Influenzae Biogroup aegyptius from blood, and negative laboratory tests for Neisseria meningitidis. The negative tests for Neisseria meningitidis rules out the possibility of the symptoms being caused by meningitis, since the clinical presentations of the two diseases are similar. Prevention The basic method for control of the conjunctivitis includes proper hygiene and care for the affected eye. If the conjunctivitis is found to be caused by H. aegyptius Biogroup III then prompt antibiotic treatment preferably with rifampin has been shown to prevent progression to BPF. If the infected person resides in Brazil, it is mandatory that the infection is reported to the health authority so that a proper investigation of the contacts can be completed. This investigation will help to determine the probable source of the infection. Treatment It is extremely difficult to successfully treat BPF, mainly because of the difficulty obtaining a proper diagnosis. Since the disease starts out with what seems to be a common case of conjunctivitis, H. aegyptius is not susceptible to the antibiotic eye drops that are being used to treat it. This treatment is ineffective because it treats only the local ocular infection, whereas if it progresses to BPF, systemic antibiotic treatment is required. Although BPF is susceptible to many commonly used antibiotics, including ampicillin, cefuroxime, cefotaxime, rifampin, and chloramphenicol, by the time it is diagnosed the disease has progressed too much to be effectively treated. However, with the fast rate of progression of BPF it is unlikely that it will be successfully treated. With antibiotic therapy, the mortality rate of BPF is around 70%. References Barbosa, S.F.C.; Hoshino-Shimizu, S.; das Gracas A. Alknin, M.; Goto, H. (2003). "Implications of Haemophilus influenzae Biogroup aegyptius Hemagglutinins in the Pathogenesis of Brazilian Purpuric Fever". Journal of Infectious Diseases. 188 (1): 74–80. doi:10.1086/375739. PMID 12825174. Harrison, L.H.; Da Silva, G.A.; Pittman, M.; Fleming, D.W.; Vranjac, A.; Broome, C.V. (1989). "Epidemiology and Clinical Spectrum of Brazilian Purpuric Fever". Journal of Clinical Microbiology. 27 (4): 599–604. doi:10.1128/JCM.27.4.599-604.1989. PMC 267380. PMID 2656737. Harrison, L.H.; Simonsen, V.; Waldman, E.A. (2008). "Emergence and Disappearance of a Virulent Clone of Haemophilus influenzae Biogroup aegyptius,cause of Brazilian Purpuric Fever". Clinical Microbiology Reviews. 21 (4): 599–605. doi:10.1128/CMR.00020-08. PMC 2570154. PMID 18854482. McGillivary, G.; Tomaras, A.P.; Rhodes, E.R.; Actis, L.A (2005). "Cloning and sequencing of a genomic island found in the Brazilian Purpuric Fever clone of Haemophilis influenzae Biogroup aegyptius". Infection and Immunity. 73 (4): 1927–1938. doi:10.1128/IAI.73.4.1927-1938.2005. PMC 1087403. PMID 15784532. Rubin, L.G.; St. Geme III, J.W. (1993). "Role of Lipooligosaccharide in Virulence of the Brazilian Purpuric Fever Clone of Haemophilus influenzaeBiogroup aegyptius for Infant Rats". Infection and Immunity. 61 (2): 650–655. doi:10.1128/IAI.61.2.650-655.1993. PMC 302776. PMID 8093694. External links CDC
Fluorine deficiency	Fluoride or fluorine deficiency is a disorder which may cause increased dental caries (or tooth decay, is the breakdown of dental tissues by the acidic products released by the "bacterial fermentation of dietary carbohydrates.") and possibly osteoporosis (a bone disorder which leads to a decrease in bone mass, and an increase in bone fragility), due to a lack of fluoride in the diet. Common dietary sources of fluoride include tea, grape juice, wine, raisins, some seafoods, coffee, and tap water that has been fluoridated. The extent to which the condition truly exists, and its relationship to fluoride poisoning has given rise to some controversy. Fluorine is not considered to be an essential nutrient, but the importance of fluorides for preventing tooth decay is well-recognized, although the effect is predominantly topical. Prior to 1981, the effect of fluorides was thought to be largely systemic and preeruptive, requiring ingestion. Fluoride is considered essential in the development and maintenance of teeth by the American Dental Hygienists Association. Fluoride is also essential as it incorporates into the teeth to form and harden teeth enamels so that the teeth are more acid resistant as well as more resistant to cavity forming bacteria. Caries-inhibiting effects of fluoride were first believed to have been seen in 1902 when fluoride in high concentrations was found to stain teeth and prevent tooth decay.Fluoride salts, particularly sodium fluoride (NaF), are used in the treatment and prevention of osteoporosis. Symptoms such as fractured hips in the elderly or brittle and weak bones are caused due to fluorine deficiency in the body. Fluoride stimulates bone formation and increases bone density, however bone with excess fluoride content has an abnormal structure resulting in increased fragility. Thus fluoride therapy results in large increases in bone mineral density but the effect on fracture rates, while positive, is small.Disputes over the essentiality of fluorine date back to the 19th century, when fluorine was observed in teeth and bones. In 1973 a trial found reduced reproduction in mice fed fluorine-deficient diets, but a subsequent investigation determined that this was due to reduced iron absorption. Role of fluoride Fluoride has proven to be an essential element with preventative and protective properties. Fluoride is capable of combating and working against tooth decay and increases resistance to the "demineralisation of tooth enamel during attack by acidic bacterias". While essential for all individuals, it is significant for children, as when ingested, the fluoride is incorporated into their developing enamel. This in turn causes their teeth to become less prone to decay. Therefore, a relationship can be formulated, in that the more fluoride entering the body, the overall decline in the rate of decay. Sources of fluoride Fluorine is the 13th most aboundant element in the Earths crust. The ionic form of fluorine is called fluoride. Fluoride is most commonly found as inorganic or organic fluorides such as naturally occurring calcium fluoride or synthetic sodium fluoride. There are a number of sources of fluoride, these include: Water In Australia fluoride occurs naturally within water supplies, at a concentration of approximately 0.1 mg/L. However, this number varies amongst different populations, as specific fluoridated communities exceed this amount, ranging from 0.6 to 1.0 mg/L of fluoride present. The process of incorporating more fluoride into water systems is an affordable mechanism that can provide many beneficial effects in the long term. Dentrifices Fluoride toothpaste came into production in the 1890s, after its benefits were investigated. This product has become available to most industrialised countries, and within Australia accounts for "90% of total toothpaste purchased". Fluoride supplements Fluoride supplements were first recognised and highly suggested by health professionals, in areas where the practice of fluoridating water was not accepted. This practice is recommended for individuals, primarily children (who are at a greater risk of caries) in low-fluoride areas. Dietary recommendations The U.S. Institute of Medicine (IOM) updated Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for some minerals in 1997. Where there was not sufficient information to establish EARs and RDAs, an estimate designated Adequate Intake (AI) was used instead. AIs are typically matched to actual average consumption, with the assumption that there appears to be a need, and that need is met by what people consume. The current AI for women 19 years and older is 3.0 mg/day (includes pregnancy and lactation). The AI for men is 4.0 mg/day. The AI for children ages 1–18 increases from 0.7 to 3.0 mg/day. As for safety, the IOM sets Tolerable upper intake levels (ULs) for vitamins and minerals when evidence is sufficient. In the case of fluoride the UL is 10 mg/day. Collectively the EARs, RDAs, AIs and ULs are referred to as Dietary Reference Intakes (DRIs).The European Food Safety Authority (EFSA) refers to the collective set of information as Dietary Reference Values, with Population Reference Intake (PRI) instead of RDA, and Average Requirement instead of EAR. AI and UL defined the same as in United States. For women ages 18 and older the AI is set at 2.9 mg/day (includes pregnancy and lactation). For men the value is 3.4 mg/day. For children ages 1–17 years the AIs increase with age from 0.6 to 3.2 mg/day. These AIs are comparable to the U.S. AIs. The EFSA reviewed safety evidence and set an adult UL at 7.0 mg/day (lower for children). See also Water fluoridation Public relations campaigns of Edward Bernays References == External links ==
Conduct disorder	Conduct disorder (CD) is a mental disorder diagnosed in childhood or adolescence that presents itself through a repetitive and persistent pattern of behavior that includes theft, lies, physical violence that may lead to destruction, and reckless breaking of rules, in which the basic rights of others or major age-appropriate norms are violated. These behaviors are often referred to as "antisocial behaviors." It is often seen as the precursor to antisocial personality disorder, which by definition cannot be diagnosed until the individual is 18 years old. Conduct disorder may result from parental rejection and neglect and can be treated with family therapy, as well as behavioral modifications and pharmacotherapy. Conduct disorder is estimated to affect 51.1 million people globally as of 2013. Signs and symptoms One of the symptoms of conduct disorder is a lower level of fear. Research performed on the impact of toddlers exposed to fear and distress shows that negative emotionality (fear) predicts toddlers empathy-related response to distress. The findings support that if a caregiver is able to respond to infant cues, the toddler has a better ability to respond to fear and distress. If a child does not learn how to handle fear or distress the child will be more likely to lash out at other children. If the caregiver is able to provide therapeutic intervention teaching children at risk better empathy skills, the child will have a lower incident level of conduct disorder.Increased instances of violent and antisocial behavior are also associated with the condition; examples may range from pushing, hitting and biting when the child is young, progressing towards beating and inflicted cruelty as the child becomes older.Conduct disorder can present with limited prosocial emotions, lack of remorse or guilt, lack of empathy, lack of concern for performance, and shallow or deficient affect. Symptoms vary by individual, but the four main groups of symptoms are described below. Aggression to people and animals Often bullies, threatens or intimidates others Often initiates physical fights Has used a weapon that can cause serious physical harm to others (e.g., a bat, brick, broken bottle, knife, gun) Has been physically cruel to people Has been physically cruel to animals Has stolen while confronting a victim (e.g., mugging, purse snatching, extortion, armed robbery) Has forced someone into sexual activity (rape or molestation) Feels no remorse or empathy towards the harm, fear, or pain they may have inflicted on others Destruction of property Has deliberately engaged in fire setting with the intention of causing serious damage Has deliberately destroyed others property (other than by fire setting) Deceitfulness or theft Has broken into someone elses house, building, or car Often lies to obtain goods or favors or to avoid obligations (i.e., "cons" others) Has stolen items of nontrivial value without confronting a victim (e.g., shoplifting, but without breaking and entering; forgery) Serious violations of rules Often stays out at night despite parental prohibitions, beginning before age 13 years Has run away from home overnight at least twice while living in parental or parental surrogate home (or once without returning for a lengthy period) Is often truant from school, beginning before age 13 yearsThe lack of empathy these individuals have and the aggression that accompanies this carelessness for the consequences is dangerous- not only for the individual but for those around them. Developmental course Currently, two possible developmental courses are thought to lead to conduct disorder. The first is known as the "childhood-onset type" and occurs when conduct disorder symptoms are present before the age of 10 years. This course is often linked to a more persistent life course and more pervasive behaviors. Specifically, children in this group have greater levels of ADHD symptoms, neuropsychological deficits, more academic problems, increased family dysfunction and higher likelihood of aggression and violence.There is debate among professionals regarding the validity and appropriateness of diagnosing young children with conduct disorder. The characteristics of the diagnosis are commonly seen in young children who are referred to mental health professionals. A premature diagnosis made in young children, and thus labeling and stigmatizing an individual, may be inappropriate. It is also argued that some children may not in fact have conduct disorder, but are engaging in developmentally appropriate disruptive behavior. The second developmental course is known as the "adolescent-onset type" and occurs when conduct disorder symptoms are present after the age of 10 years. Individuals with adolescent-onset conduct disorder exhibit less impairment than those with the childhood-onset type and are not characterized by similar psychopathology. At times, these individuals will remit in their deviant patterns before adulthood. Research has shown that there is a greater number of children with adolescent-onset conduct disorder than those with childhood-onset, suggesting that adolescent-onset conduct disorder is an exaggeration of developmental behaviors that are typically seen in adolescence, such as rebellion against authority figures and rejection of conventional values. However, this argument is not established and empirical research suggests that these subgroups are not as valid as once thought.In addition to these two courses that are recognized by the DSM-IV-TR, there appears to be a relationship among oppositional defiant disorder, conduct disorder, and antisocial personality disorder. Specifically, research has demonstrated continuity in the disorders such that conduct disorder is often diagnosed in children who have been previously diagnosed with oppositional defiant disorder, and most adults with antisocial personality disorder were previously diagnosed with conduct disorder. For example, some research has shown that 90% of children diagnosed with conduct disorder had a previous diagnosis of oppositional defiant disorder. Moreover, both disorders share relevant risk factors and disruptive behaviors, suggesting that oppositional defiant disorder is a developmental precursor and milder variant of conduct disorder. However, this is not to say that this trajectory occurs in all individuals. In fact, only about 25% of children with oppositional defiant disorder will receive a later diagnosis of conduct disorder. Correspondingly, there is an established link between conduct disorder and the diagnosis of antisocial personality disorder as an adult. In fact, the current diagnostic criteria for antisocial personality disorder require a conduct disorder diagnosis before the age of 15. However, again, only 25-40% of youths with conduct disorder will develop an antisocial personality disorder. Nonetheless, many of the individuals who do not meet full criteria for antisocial personality disorder still exhibit a pattern of social and personal impairments or antisocial behaviors. These developmental trajectories suggest the existence of antisocial pathways in certain individuals, which have important implications for both research and treatment. Associated conditions Children with conduct disorder have a high risk of developing other adjustment problems. Specifically, risk factors associated with conduct disorder and the effects of conduct disorder symptomatology on a childs psychosocial context have been linked to overlapping with other psychological disorders. In this way, there seems to be reciprocal effects of comorbidity with certain disorders, leading to increased overall risk for these youth. Attention deficit hyperactivity disorder ADHD is the condition most commonly associated with conduct disorders, with approximately 25-30% of boys and 50-55% of girls with conduct disorder having a comorbid ADHD diagnosis. While it is unlikely that ADHD alone is a risk factor for developing conduct disorder, children who exhibit hyperactivity and impulsivity along with aggression is associated with the early onset of conduct problems. Moreover, children with comorbid conduct disorder and ADHD show more severe aggression. Substance use disorders Conduct disorder is also highly associated with both substance use and abuse. Children with conduct disorder have an earlier onset of substance use, as compared to their peers, and also tend to use multiple substances. However, substance use disorders themselves can directly or indirectly cause conduct disorder like traits in about half of adolescents who have a substance use disorder. As mentioned above, it seems that there is a transactional relationship between substance use and conduct problems, such that aggressive behaviors increase substance use, which leads to increased aggressive behavior.Substance use in conduct disorder can lead to antisocial behavior in adulthood. Schizophrenia Conduct disorder is a precursor to schizophrenia in a minority of cases, with about 40% of men and 31% of women with schizophrenia meeting criteria for childhood conduct disorder. Cause While the cause of conduct disorder is complicated by an intricate interplay of biological and environmental factors, identifying underlying mechanisms is crucial for obtaining accurate assessment and implementing effective treatment. These mechanisms serve as the fundamental building blocks on which evidence-based treatments are developed. Despite the complexities, several domains have been implicated in the development of conduct disorder including cognitive variables, neurological factors, intraindividual factors, familial and peer influences, and wider contextual factors. These factors may also vary based on the age of onset, with different variables related to early (e.g., neurodevelopmental basis) and adolescent (e.g., social/peer relationships) onset. Risks The development of conduct disorder is not immutable or predetermined. A number of interactive risk and protective factors exist that can influence and change outcomes, and in most cases conduct disorder develops due to an interaction and gradual accumulation of risk factors. In addition to the risk factors identified under cause, several other variables place youth at increased risk for developing the disorder, including child physical abuse, in-utero alcohol exposure, and maternal smoking during pregnancy. Protective factors have also been identified, and most notably include high IQ, being female, positive social orientations, good coping skills, and supportive family and community relationships.However, a correlation between a particular risk factor and a later developmental outcome (such as conduct disorder) cannot be taken as definitive evidence for a causal link. Co-variation between two variables can arise, for instance, if they represent age-specific expressions of similar underlying genetic factors. There have been studies that found that, although smoking during pregnancy does contribute to increased levels of antisocial behaviour, in mother-fetus pairs that were not genetically related (by virtue of in-vitro fertilisation), no link between smoking during pregnancy and later conduct problems was found. Thus, the distinction between causality and correlation is an important consideration. Learning disabilities While language impairments are most common, approximately 20-25% of youth with conduct disorder have some type of learning disability. Although the relationship between the disorders is complex, it seems as if learning disabilities result from a combination of ADHD, a history of academic difficulty and failure, and long-standing socialization difficulties with family and peers. However, confounding variables, such as language deficits, SES disadvantage, or neurodevelopmental delay also need to be considered in this relationship, as they could help explain some of the association between conduct disorder and learning problems. Cognitive factors In terms of cognitive function, intelligence and cognitive deficits are common amongst youths with conduct disorder, particularly those with early-onset and have intelligence quotients (IQ) one standard deviation below the mean and severe deficits in verbal reasoning and executive function. Executive function difficulties may manifest in terms of ones ability to shift between tasks, plan as well as organize, and also inhibit a prepotent response. These findings hold true even after taking into account other variables such as socioeconomic status (SES), and education. However, IQ and executive function deficits are only one piece of the puzzle, and the magnitude of their influence is increased during transactional processes with environmental factors. Brain differences Beyond difficulties in executive function, neurological research on youth with conduct disorder also demonstrate differences in brain anatomy and function that reflect the behaviors and mental anomalies associated in conduct disorder. Compared to normal controls, youths with early and adolescent onset of conduct disorder displayed reduced responses in brain regions associated with social behavior (i.e., amygdala, ventromedial prefrontal cortex, insula, and orbitofrontal cortex). In addition, youths with conduct disorder also demonstrated less responsiveness in the orbitofrontal regions of the brain during a stimulus-reinforcement and reward task. This provides a neural explanation for why youths with conduct disorder may be more likely to repeat poor decision making patterns. Lastly, youths with conduct disorder display a reduction in grey matter volume in the amygdala, which may account for the fear conditioning deficits. This reduction has been linked to difficulty processing social emotional stimuli, regardless of the age of onset. Aside from the differences in neuroanatomy and activation patterns between youth with conduct disorder and controls, neurochemical profiles also vary between groups. Individuals with conduct disorder are characterized as having reduced serotonin and cortisol levels (e.g., reduced hypothalamic-pituitary-adrenal (HPA) axis), as well as reduced autonomic nervous system (ANS) functioning. These reductions are associated with the inability to regulate mood and impulsive behaviors, weakened signals of anxiety and fear, and decreased self-esteem. Taken together, these findings may account for some of the variance in the psychological and behavioral patterns of youth with conduct disorder. Intra-individual factors Aside from findings related to neurological and neurochemical profiles of youth with conduct disorder, intraindividual factors such as genetics may also be relevant. Having a sibling or parent with conduct disorder increases the likelihood of having the disorder, with a heritability rate of .53. There also tends to be a stronger genetic link for individuals with childhood-onset compared to adolescent onset. In addition, youth with conduct disorder also exhibit polymorphism in the monoamine oxidase A gene, low resting heart rates, and increased testosterone. Family and peer influences Elements of the family and social environment may also play a role in the development and maintenance of conduct disorder. For instance, antisocial behavior suggestive of conduct disorder is associated with single parent status, parental divorce, large family size, and the young age of mothers. However, these factors are difficult to tease apart from other demographic variables that are known to be linked with conduct disorder, including poverty and low socioeconomic status. Family functioning and parent-child interactions also play a substantial role in childhood aggression and conduct disorder, with low levels of parental involvement, inadequate supervision, and unpredictable discipline practices reinforcing youths defiant behaviors. Peer influences have also been related to the development of antisocial behavior in youth, particularly peer rejection in childhood and association with deviant peers. Peer rejection is not only a marker of a number of externalizing disorders, but also a contributing factor for the continuity of the disorders over time. Hinshaw and Lee (2003) also explain that association with deviant peers has been thought to influence the development of conduct disorder in two ways: 1) a “selection” process whereby youth with aggressive characteristics choose deviant friends, and 2) a “facilitation” process whereby deviant peer networks bolster patterns of antisocial behavior. In a separate study by Bonin and colleagues, parenting programs were shown to positively affect child behavior and reduce costs to the public sector. Wider contextual factors In addition to the individual and social factors associated with conduct disorder, research has highlighted the importance of environment and context in youth with antisocial behavior. However, it is important to note that these are not static factors, but rather transactional in nature (e.g., individuals are influenced by and also influence their environment). For instance, neighborhood safety and exposure to violence have been studied in conjunction with conduct disorder, but it is not simply the case that youth with aggressive tendencies reside in violent neighborhoods. Transactional models propose that youth may resort to violence more often as a result of exposure to community violence, but their predisposition towards violence also contributes to neighborhood climate. Diagnosis Conduct disorder is classified in the fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM). It is diagnosed based on a prolonged pattern of antisocial behaviour such as serious violation of laws and social norms and rules in people younger than the age of 18. Similar criteria are used in those over the age of 18 for the diagnosis of antisocial personality disorder. No proposed revisions for the main criteria of conduct disorder exist in the DSM-5; there is a recommendation by the work group to add an additional specifier for callous and unemotional traits. According to DSM-5 criteria for conduct disorder, there are four categories that could be present in the childs behavior: aggression to people and animals, destruction of property, deceitfulness or theft, and serious violation of rules.Almost all adolescents who have a substance use disorder have conduct disorder-like traits, but after successful treatment of the substance use disorder, about half of these adolescents no longer display conduct disorder-like symptoms. Therefore, it is important to exclude a substance-induced cause and instead address the substance use disorder prior to making a psychiatric diagnosis of conduct disorder. Treatment First-line treatment is psychotherapy based on behavior modification and problem-solving skills. This treatment seeks to integrate individual, school, and family settings. Parent-management training can also be helpful. No medications have been FDA approved for Conduct Disorder, but risperidone (a second-generation antipsychotic) has the most evidence to support its use for aggression in children who have not responded to behavioral and psychosocial interventions. Selective Serotonin Reuptake Inhibitors (SSRIs) are also sometimes used to treat irritability in these patients. Prognosis About 25-40% of youths diagnosed with conduct disorder qualify for a diagnosis of antisocial personality disorder when they reach adulthood. For those that do not develop ASPD, most still exhibit social dysfunction in adult life. Epidemiology Conduct disorder is estimated to affect 51.1 million people globally as of 2013. The percentage of children affected by conduct disorder is estimated to range from 1-10%. However, among incarcerated youth or youth in juvenile detention facilities, rates of conduct disorder are between 23% and 87%. Sex differences The majority of research on conduct disorder suggests that there are a significantly greater number of males than females with the diagnosis, with some reports demonstrating a threefold to fourfold difference in prevalence. However, this difference may be somewhat biased by the diagnostic criteria which focus on more overt behaviors, such as aggression and fighting, which are more often exhibited by males. Females are more likely to be characterized by covert behaviors, such as stealing or running away. Moreover, conduct disorder in females is linked to several negative outcomes, such as antisocial personality disorder and early pregnancy, suggesting that sex differences in disruptive behaviors need to be more fully understood. Females are more responsive to peer pressure including feelings of guilt than males. Racial differences Research on racial or cultural differences on the prevalence or presentation of conduct disorder is limited. However, according to studies on American youth, it appears that African-American youth are more often diagnosed with conduct disorder, while Asian-American youth are about one-third as likely to develop conduct disorder when compared to White American youth. It has been widely theorized for decades that this disparity is due to unconscious bias in those who give the diagnosis. References Citations Bibliography Bernstein, N. (2000). Treating the unmanageable adolescent: A guide to oppositional defiant and conduct disorder. New York: Jason Aronson, Inc. Decety J.; Moriguchi Y. (2007). "The empathic brain and its dysfunction in psychiatric populations: implications for intervention across different clinical conditions". BioPsychoSocial Medicine. 1: 22–65. doi:10.1186/1751-0759-1-22. PMC 2206036. PMID 18021398. Eddy, J. (2006). Conduct disorders: The latest assessment and treatment strategies (4th Edition). Kansas City, MO: Compact Clinicals. Eyberg S. M.; Nelson M. M.; Boggs S. R. (2008). "Evidence-based psychosocial treatments for child and adolescent with disruptive behavior". Journal of Clinical Child & Adolescent Psychology. 37 (1): 215–237. CiteSeerX 10.1.1.595.3142. doi:10.1080/15374410701820117. PMID 18444059. S2CID 53345. Hughes, T. (2010). Identifying, Assessing, and Treating Conduct Disorder at School (Development and Psychopathology at School). New York: Springer. Lahey, B.B., Moffitt, T.E.,& Caspi, A. (eds.). Causes of conduct disorder and juvenile delinquency. New York: Guilford Press. Matthys, W. (2010). Oppositional defiant disorder and conduct disorder in children. Malden, MA: Wiley-Blackwell. McIntosh, K., & Livingston, P. (2008). Youth with conduct disorder: In trouble with the world. New York: Mason Crest Publishers. Raine A (2002). "Biosocial Studies of Antisocial and Violent Behavior in Children and Adults: A Review". Journal of Abnormal Child Psychology. 30 (4): 311–326. doi:10.1023/A:1015754122318. PMID 12108763. S2CID 11608050. Van Goozen, S. H. M.; Fairchild, G. (2008). "How can the study of biological processes help design new interventions for children with severe antisocial behavior?" (PDF). Development and Psychopathology. 20 (3): 941–973. doi:10.1017/s095457940800045x. PMID 18606039. S2CID 12035572. External links Conduct Disorder Symptoms and Treatment Society of Clinical Child and Adolescent Psychology Bullying tendency wired in brain from the BBC News. Bullies may enjoy seeing others in pain National Science Foundation Diagnosing Conduct Disorder in Primary Care Conduct Disorder
Microvasculitis	Microvasculitis refers to a range of diseases or presentations associated with a disease, where there is inflammation of small blood vessels: Kawasaki disease Susac syndrome Nerve microvasculitis Non-systemic vasculitic neuropathy (NSVN) Hepatitis C-related cryoglobulinemia neuropathy (CRYOVASC) Hepatitis B-associated PAN Diabetic lumbosacral radiculoplexus neuropathy (DLRPN) Non-diabetic lumbosacral radiculoplexus neuropathy (LRPN) Diabetic cervical-radiculoplexus neuropathy (DCRPN) Diabetic Cranio-Cervico-Radiculoplexus Neuropathy Diabetic Cervical Neuropathy == References ==
Urofacial syndrome	Urofacial syndrome, or Ochoa syndrome, is an autosomal recessive congenital disorder characterized by an association of a lower urinary tract and bowel dysfunction with a typical facial expression: When attempting to smile, the patient seems to be crying or grimacing. It was first described by the Colombian physician Bernardo Ochoa in the early 1960s. The inverted facial expression presented by children with this syndrome allows for early detection of the syndrome, which is vital for establishing a better prognosis as urinary related problems associated with this disease can cause harm if left untreated. Incontinence is another easily detectable symptom of the syndrome that is due to detrusor-sphincter discoordination. It may be associated with HPSE2. Signs and symptoms Infants with the disorder exhibit an inverted smile; they appear to be crying when they are actually smiling, in conjunction with uropathy. They also may be affected by hydronephrosis. Symptoms of this disease can start at very young ages. Many people with this syndrome will die in their teens to early 20s because of the renal failure (uropathy) if not diagnosed and treated. Children with the syndrome have abnormal facial development that cause an inverted smile, nerve connections are however normal. When attempting to smile, the child will appear to cry. Urinary problems arise as a result of a neurogenic bladder. Most patients older than the age of toilet training, present with enuresis, urinary-tract infection, hydronephrosis, and a spectrum of radiological abnormalities typical of obstructive or neurogenic bladders. Radiological abnormalities include things such as: trabeculated bladder, vesicoureteral reflex, external sphincter spasm, pyelonephritis, hyperreflexic bladder, noninhibited detrusor contraction, etc. Urinary abnormalities might result in renal deterioration and failure. This can be prevented by taking proper measures to restore normal micturition and by taking antibiotics to prevent infections. In some cases, the affected patients become hypertensive and progress to end-stage renal disease, while others become uremic. Additionally, most patients suffer from constipation. Early detection of this syndrome is possible through the peculiar faces that children present. Cause Urofacial syndrome occurs due to either disruption or mutation of a gene on chromosome 10q23q24. The gene is located on a 1 centimorgan interval between D10S1433 and D10S603. Alteration of this gene leads to alteration of facial and urinary developmental fields. This gene is believed to be the HPSE2 gene. The HPSE2 gene is expressed in both the central nervous system as well as the bladder. Heparanase 2 is protein coded by exons 8 and 9 on the HPSE2 gene. This protein is believed to be altered in the case of this syndrome. Studies performed on mice indicate that HPSE2 has no enzymatic activity.Mutations in the HPSE2 gene on chromosome 10q23q24 have been observed to cause Ochoa Syndrome. This means the defective gene responsible for the disorder is located on an autosome (chromosome 10 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.The relationship between a defective HPSE2 gene and Ochoa syndrome is unclear. There is postulation that the genetic changes may lead to an abnormality in the brain region, evidence for this postulation is that the areas of the brain that control facial expression and urination are in close proximity of each other. Other hypotheses think that the defective heparanase 2 protein may lead to problems with development of the urinary tract or with muscle function in the face and bladder. Diagnosis Treatment The treatment varies based on the condition and extent of the uropathy. To empty the bladder regularly, clean intermittent catheterization (CIC) can be used. If the urodynamic study shows non-inhibited detrusor contractions, an anticholinergic drug should be given additionally. To prevent recurrent infections, especially in the case of vesicoureteral reflux, the treatment can also include an antibiotic prophylaxis. Epidemiology Urofacial (Ochoa) syndrome received the Ochoa name because of the first person to describe it in 1987, Bernardo Ochoa. References == External links ==
Cervical rib	A cervical rib in humans is an extra rib which arises from the seventh cervical vertebra. Their presence is a congenital abnormality located above the normal first rib. A cervical rib is estimated to occur in 0.2% to 0.5% (1 in 200 to 500) of the population. People may have a cervical rib on the right, left or both sides.Most cases of cervical ribs are not clinically relevant and do not have symptoms; cervical ribs are generally discovered incidentally, most often during x-rays and CT scans. However, they vary widely in size and shape, and in rare cases, they may cause problems such as contributing to thoracic outlet syndrome, because of pressure on the nerves that may be caused by the presence of the rib.A cervical rib represents a persistent ossification of the C7 lateral costal element. During early development, this ossified costal element typically becomes re-absorbed. Failure of this process results in a variably elongated transverse process or complete rib that can be anteriorly fused with the T1 first rib below. Diagnosis On imaging, cervical ribs can be distinguished because their transverse processes are directed inferolaterally, whereas those of the adjacent thoracic spine are directed anterolaterally. Associated conditions The presence of a cervical rib can cause a form of thoracic outlet syndrome due to compression of the lower trunk of the brachial plexus or subclavian artery. These structures become encroached upon by the cervical rib and scalene muscles. Compression of the brachial plexus may be identified by weakness of the muscles in the hand, near the base of the thumb. Compression of the subclavian artery is often diagnosed by finding a positive Adsons sign on examination, where the radial pulse in the arm is lost during abduction and external rotation of the shoulder. A positive Adsons sign is non-specific for the presence of a cervical rib however, as many individuals without a cervical rib will have a positive test. Compression of the sympathetic chain may cause Horners syndrome. Other animals Many vertebrates, especially reptiles, have cervical ribs as a normal part of their anatomy rather than a pathological condition. Some sauropods had exceptionally long cervical ribs; those of Mamenchisaurus hochuanensis were nearly 4 meters long. In birds, the cervical ribs are small and completely fused to the vertebrae. In mammals, the ventral parts of the transverse processes of the cervical vertebrae are the fused-on cervical ribs. Recent studies have also found a high percent of cervical ribs in woolly mammoths. It is believed that the decline in mammoth numbers may have forced inbreeding within the species which in turn had increased the number of mammoths being born with cervical ribs. Cervical ribs have been connected with leukaemia in human children, so it has given scientists new evidence to believe that the mammoths extinction was attributed to the condition. References == External links ==
Pneumopericardium	Pneumopericardium is a medical condition where air enters the pericardial cavity. This condition has been recognized in preterm neonates, in which it is associated with severe lung pathology, after vigorous resuscitation, or in the presence of assisted ventilation. This is a serious complication, which if untreated may lead to cardiac tamponade and death. Pneumomediastinum, which is the presence of air in the mediastinum, may mimic and also coexist with pneumopericardium. It can be congenital, or introduced by a wound. Presentation The symptomatic patient may present with dyspnea, cyanosis, chest pain, pulsus paradoxus, bradycardia or tachycardia. Pathophysiology The mechanism responsible for pneumopericardium is the ‘Macklin effect’ – There is initially an increased pressure gradient between the alveoli and the interstitial space. Increased pressure leads to alveolar rupture, resulting in air getting through to the pericapillary interstitial pulmonary space. This space is continuous with the peribronchial and pulmonary perivascular sheaths. From here, the air tracks to the hilum of the lung and then to the mediastinum. In case of a pericardial tear, this air enters the pericardial cavity and pneumopericardium develops. The condition may remain asymptomatic or may progress to life-threatening conditions like tension pneumopericardium or cardiac tamponade. Diagnosis On physical examination, the patient may have the classic “Beck’s triad” – hypotension, raised JVP and distant heart sounds, when complicated by cardiac tamponade. Extension of the mediastinal air to the subcutaneous tissues via the fascial planes may lead to subcutaneous emphysema. When air and fluid mix together in the pericardial sac, a tinkling sound superimposed over a succussion splash is heard. This is known as a “Bruit de Moulin”, which is French for “Mill–wheel” murmur. Air between the anterior parietal pericardium and the thoracic cage may also give rise to the “Hamman’s Sign” – which is a crunching sound typically heard on auscultation of the chest, but may sometimes be heard even with the unaided ear. Treatment See also Hammans sign References Further reading Karoui, Mehdi; Bucur, Petru Octav (2 October 2008). "Pneumopericardium". New England Journal of Medicine. 359 (14): e16. doi:10.1056/NEJMicm074422. Franklin, WJ; Arora, G; Ayres, NA (2003). "Pneumopericardium and pneumomediastinum in an adolescent after blunt chest trauma". Texas Heart Institute Journal. 30 (4): 338–9. PMC 307727. PMID 14677752. == External links ==
Pontiac fever	Pontiac fever is an acute, nonfatal respiratory disease caused by various species of Gram-negative bacteria in the genus Legionella. It causes a mild upper respiratory infection that resembles acute influenza. Pontiac fever resolves spontaneously and often goes undiagnosed. Both Pontiac fever and the more severe Legionnaires disease may be caused by the same bacteria, but Pontiac fever does not include pneumonia. Cause Species of Legionella known to cause Pontiac fever include Legionella pneumophila, Legionella longbeachae, Legionella feeleii, Legionella micdadei, and Legionella anisa. Sources of the causative agents are aquatic systems and potting soil. The first outbreak caused by inhalation of aerosolized potting soil was discovered in New Zealand in January 2007. A total of 10 workers at a nursery came down with Pontiac fever. It was the first identification of L. longbeachae. Pontiac fever does not spread from person to person. It is acquired through aerosolization of water droplets and/or potting soil containing Legionella bacteria. Diagnosis Epidemiology Pontiac fever is known to have a short incubation period of 1 to 3 days. No fatalities have been reported and cases resolve spontaneously without treatment. It is often not reported. Age, gender, and smoking do not seem to be risk factors. Pontiac fever seems to affect young people in the age medians of 29, 30, and 32. Pathogenesis of the Pontiac fever is poorly known. History Pontiac fever was named for Pontiac, Michigan, where the first case was recognized. In 1968, several workers at the countys department of health came down with a fever and mild flu symptoms, but not pneumonia. After the 1976 Legionnaires outbreak in Philadelphia, the Michigan health department re-examined blood samples and discovered the workers had been infected with the newly identified Legionella pneumophila. An outbreak caused by Legionella micdadei in early 1988 in the UK became known as Lochgoilhead fever. Since that time, other species of Legionella that cause Pontiac fever have been identified, most notably in New Zealand, in 2007 where Legionella longbeachae was discovered. The New Zealand outbreak also marked the first time Pontiac fever had been traced to potting soil. References External links Pontiac fever at Curlie
Revesz syndrome	Revesz syndrome is a fatal disease that causes exudative retinopathy and bone marrow failure. Other symptoms include severe aplastic anemia, intrauterine growth retardation, fine sparse hair, fine reticulate skin pigmentation, ataxia due to cerebellar hypoplasia, and cerebral calcifications. Its effects are similar to that of Hoyeraal-Hreidarsson syndrome. It is a variant of dyskeratosis congenita. Cause Revesz syndrome is a genetic disease thought to be caused by short telomeres. Patients with Revesz syndrome have presented with heterozygous mutations in TINF2 gene which is located on chromosome 14q12. There is no treatment for this disease yet. Diagnosis Epidemiology Revesz syndrome has so far been observed only in children. There is not much information about the disease because of its low frequency in general population and under reporting of cases. History The syndrome is named after the author of the original case published in 1992. The patient was a 6-month-old male from Sudan. At 7 months, the patient developed aplastic anemia, and subsequently died at 19 months. A second case was reported in 1994 in a young girl in Hungary. She had many of the same symptoms as the child in Sudan. A third case, reported in Calicut, India, was that of a 5-year-old girl who also had additional features of retinal detachment and retinitis pigmentosa, which are unreported in this syndrome. See also List of cutaneous conditions Footnotes References Online Mendelian Inheritance in Man (OMIM): 300240 Revesz T, Fletcher S, al-Gazali LI, DeBuse P (September 1992). "Bilateral retinopathy, aplastic anaemia, and central nervous system abnormalities: a new syndrome?". J. Med. Genet. 29 (9): 673–5. doi:10.1136/jmg.29.9.673. PMC 1016105. PMID 1404302. Kajtár P, Méhes K (February 1994). "Bilateral coats retinopathy associated with aplastic anaemia and mild dyskeratotic signs". Am. J. Med. Genet. 49 (4): 374–7. doi:10.1002/ajmg.1320490404. PMID 8160728. Riyaz A, Najeeba R (September 2007). "Revesz syndrome". Indian Journal of Pediatrics. 74 (9): 862–3. doi:10.1007/s12098-007-0155-2. PMID 17901676. S2CID 46076752. == External links ==
Horseshoe kidney	Horseshoe kidney, also known as ren arcuatus (in Latin), renal fusion or super kidney, is a congenital disorder affecting about 1 in 500 people that is more common in men, often asymptomatic, and usually diagnosed incidentally. In this disorder, the patients kidneys fuse to form a horseshoe-shape during development in the womb. The fused part is the isthmus of the horseshoe kidney. The abnormal anatomy can affect kidney drainage resulting in increased frequency of kidney stones and urinary tract infections as well as increase risk of certain renal cancers.Fusion abnormalities of the kidney can be categorized into two groups: horseshoe kidney and crossed fused ectopia. The horseshoe kidney is the most common renal fusion anomaly. Signs and symptoms Although often asymptomatic, the most common presenting symptom of patients with a horseshoe kidney is abdominal or flank pain. However, presentation is often non-specific. Approximately a third of patients with horseshoe kidneys remain asymptomatic throughout their entire life with over 50% of patients having no medical issues related to their renal fusion when followed for a 25-year period. As a result, it is estimated that approximately 25% of patients with horseshoe kidneys are diagnosed incidentally with ultrasound or CT imaging. Associated conditions Patients with a horseshoe kidney can develop sequelae related to the abnormal anatomy and present with symptoms related to them.The general categories a horseshoe kidney may increase the risk for fall under the following categories: Kidney obstruction – commonly causes ureteropelvic junction obstruction (UPJ) which is a blockage at the area where the ureter connects to the renal pelvis. This can lead to urinary stasis which can promote infection and stone formation. Kidney infections – associated with vesicoureteral reflux (present in approximately 50% of all patients with renal fusion) which is an abnormal reflux of urine back into the ureters that increases risk of urinary tract infections. Kidney stones – deviant orientation of kidneys combined with slow urine flow and kidney obstruction may increase the risk of developing kidney stones. Treatment is further complicated if patient possesses aberrant skeletal anatomy. It is estimated 36% of patients with horseshoe kidneys will develop kidney stones. Kidney cancer – increased frequency of certain renal cancers such as transitional cell tumors, Wilms tumors, and carcinoid tumors. Heart abnormalities – ventricular septal defect Neurological abnormalities - encephalocoele, myelomeningocoele, spina bifida Skeletal abnormalities - kyphosis, scoliosis, hemeivertebra, and micrognathia. Genitourinary abnormalities - septate vagina, bicornuate uterus, hypospadias, undescended testis, adult polycystic kidney disease, and more than two kidneys. Genetic abnormalities - Turner syndrome, Down syndrome, Patau syndrome, Edward syndrome, oro-cranial-digital syndrome Cause There have been several proposed factors that may contribute to the development of a horseshoe kidney. Different exposures to the developing fetus such as different teratogens (e.g. thalidomide, ethanol, ACE inhibitors, cocaine, gentamicin, corticosteroids, NSAIDs, and vitamin A) have been hypothesized. Impairment of a developing embryos nephrogenic cell migration or abnormal migration of the kidneys due to fetal structural abnormalities is another potential factor. However, no definitive genetic cause has been identified. Pathophysiology Kidneys are normally located in the retroperitoneal space between the T12 and L3 vertebrae after ascending from the pelvis during development to rest underneath the adrenal glands. In patients with this condition, the horseshoe kidney ascent is commonly arrested by the inferior mesenteric artery due to the central fusion of the kidneys. However, this is present in only 40% of cases, and, in 20% of cases, the fused kidney remains in the pelvis. Its ascension may also be restricted by its own renal artery. Additionally, during normal development, the kidneys undergo a 90 degree medial rotation while ascending. However, due to the renal fusion, this rotation is impaired resulting in abnormal placement of the ureters. This in turn can lead to urinary stasis and drainage issues. Furthermore, approximately 70% of kidneys in normal individuals are supplied by a single renal artery with the remaining 30% having embryonic collateral or accessory arteries. With horseshoe kidneys, the majority are supplied by derivatives of the abdominal aorta or common illiac arteries depending on the final position of the kidneys. Diagnosis Horseshoe kidneys are commonly diagnosed incidentally on abdominal imaging. The diagnosis can be made with many different imaging modalities such as ultrasound, intravenous pyelogram, CT, and MRI.Common features that can be found on imaging include: Midline symmetrical fusion (present in 90% of cases) or lateral asymmetric fusion (present in 10% of cases) of the lower poles Position of fused kidneys are lower than normal with incomplete medial rotation Renal pelvis and ureters are positioned more anteriorly and ventrally cross the isthmus Isthmus that may be positioned below the inferior mesenteric artery Variant arterial supply that can originate from the abdominal aorta or common illiac arteries Lower poles of kidney that extend ventromedially and may be poorly defined Treatment Symphysiotomy, which involves separating the fused isthmus in order to release the kidneys, used to be a recommended treatment for this condition but has fallen out of favor due to complications and minimal benefit. Furthermore, kidneys can remain in their original abnormal location after the surgery. Instead, management focuses on treating the sequelae should the patient become symptomatic.While treatment typically does not differ from that of patients with normal kidney anatomy, kidney stones can warrant a different approach. Extracorporeal shockwave lithotripsy, a possible treatment for kidney stones, can be less effective in patients with horseshoe kidneys due to the abnormal anatomy causing difficulties with localizing the energy to the stones. Also, due to the kidney obstruction that can commonly occur with this renal fusion, clearance of the resulting stone fragments can also be impaired. For this reason, prior to any treatment with shockwave lithotripsy, a UPJ obstruction must first be ruled out as it significantly impair successful treatment. For stones that are less than 1.5 cm, ureteroscopy and shockwave lithotripsy can be first utilized. For stones larger than 1.5 cm or when previous treatment has failed, the stones can instead be removed through a minimally invasive procedure known as percutaneous nephrolithotomy.Compared to patients with normal kidneys, patients with horseshoe kidneys who undergo treatment with percutaneous nephrolithotomy experience no difference in complications or stone clearance.Patients will also typically require imaging before any abdominal surgery as the vascular supply to the abnormal kidney can be highly variable between patients. Additionally, the horseshoe kidneys can have a close association with colon which can increase risk of bowel injury. Epidemiology There is an incidence of 1 in every 500 individuals within a normal population.Males are more likely to develop a horseshoe kidney with a preponderance of 2:1.Certain genetic diseases can predispose patients to developing a horseshoe kidney: Edwards Syndrome: 67% Turner Syndrome: 14-20% Down Syndrome: <1% Notable cases Mel Gibson is affected with this condition. Sam Kinison, an American comedian, also had this condition. Robert Rowan a member of the Anglican clergy was afflicted by the condition. References == External links ==
Tympanosclerosis	Tympanosclerosis is a condition caused by hyalinization and subsequent calcification of subepithelial connective tissue of the tympanic membrane and middle ear, sometimes resulting in a detrimental effect to hearing. Signs and symptoms Myringosclerosis rarely causes any symptoms. Tympanosclerosis, on the other hand, can cause significant hearing loss or chalky, white patches on the middle ear or tympanic membrane. Causes The aetiology for tympanosclerosis is not extensively understood. There are several probable factors which could result in the condition appearing, including: Long term otitis media (or glue ear) Insertion of a tympanostomy tube. If aspiration is performed as part of the insertion, the risk of tympanosclerosis occurring increases. Risk also increases if a larger tube is used, or if the procedure is repeated. Atherosclerosis There is ongoing research as to whether or not cholesteatoma is associated with tympanosclerosis. If there is an association, it is likely that the two conditions co-exist. Pathophysiology Increased fibroblast activity results in deposition of collagen. Calcium phosphate plaques then form in the lamina propria of the tympanic membrane. Diagnosis If lesions are typical, non-extensive and with no detriment to hearing, investigation into the condition is rarely required. Audiometry is used to determine the extent of hearing loss, if any. Tympanometry produces tympanograms which can be different when tympanosclerosis is present. Computerised tomography (CT) can be used to determine if disease is present in the middle ear. Whilst hearing loss is a common symptom in many diseases of the ear, for example in otosclerosis (abnormal bone growth in the ear), the white, chalky patches on the tympanic membrane are fairly characteristic of tympanosclerosis. Cholesteatoma is similar in appearance but the whiteness is behind the tympanic membrane, rather than inside. Classification Myringosclerosis refers to a calcification only within the tympanic membrane and is usually less extensive than intratympanic tympanosclerosis, which refers to any other location within the middle ear such as the ossicular chain, middle ear mucosa or, less frequently, the mastoid cavity. Treatment Hearing aids are a common treatment for hearing loss disorders. A more specific treatment is surgical, involving excision of the sclerotic areas and then further repair of the ossicular chain. There are several techniques, sometimes involving two surgeries; success rates are, however, variable. Damage to the inner ear as a result of surgical procedures is a possible and serious concern, as it can result in forms of sensorineural deafness. Prognosis In most cases, tympanosclerosis does not cause any recognisable hearing loss up to ten years after the initial disease onset. Sclerotic changes seem to stabilise, but not resolve or dissolve, after 3 years. Epidemiology Myringosclerosis seems to be more common than tympanosclerosis. Most research has not been conducted upon the general, healthy population, but rather those with otitis media or patients who have had tympanostomy tubes in prior procedures. Of the children studied who had glue ear, and who were treated with tympanostomy tubing, 23-40% of cases had tympanosclerosis. One study suggested that people with atherosclerosis were more likely to have tympanosclerosis than otherwise healthy individuals. References External links Tympanosclerosis - Image of tympanosclerosis as revealed by otoscopy.
Blastomycosis-like pyoderma	Blastomycosis-like pyoderma is a cutaneous condition characterized by large verrucous plaques with elevated borders and multiple pustules.: 255, 272 See also List of cutaneous conditions pyoderma blastomycosis References == External links ==
Mastoiditis	Mastoiditis is the result of an infection that extends to the air cells of the skull behind the ear. Specifically, it is an inflammation of the mucosal lining of the mastoid antrum and mastoid air cell system inside the mastoid process. The mastoid process is the portion of the temporal bone of the skull that is behind the ear. The mastoid process contains open, air-containing spaces. Mastoiditis is usually caused by untreated acute otitis media (middle ear infection) and used to be a leading cause of child mortality. With the development of antibiotics, however, mastoiditis has become quite rare in developed countries where surgical treatment is now much less frequent and more conservative, unlike former times.There is no evidence that the drop in antibiotic prescribing for otitis media has increased the incidence of mastoiditis, raising the possibility that the drop in reported cases is due to a confounding factor such as childhood immunizations against Haemophilus and Streptococcus. Untreated, the infection can spread to surrounding structures, including the brain, causing serious complications. While the use of antibiotics has reduced the incidence of mastoiditis, the risk of masked mastoiditis, a subclinical infection without the typical findings of mastoiditis has increased with the inappropriate use of antibiotics and the emergence of multidrug-resistant bacteria. Signs and symptoms Some common symptoms and signs of mastoiditis include pain, tenderness, and swelling in the mastoid region. There may be ear pain (otalgia), and the ear or mastoid region may be red (erythematous). Fever or headaches may also be present. Infants usually show nonspecific symptoms, including anorexia, diarrhea, or irritability. Drainage from the ear occurs in more serious cases, often manifest as brown discharge on the pillowcase upon waking. Pathophysiology The pathophysiology of mastoiditis is straightforward: bacteria spread from the middle ear to the mastoid air cells, where the inflammation causes damage to the bony structures. Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis are the most common organisms recovered in acute mastoiditis. Organisms that are rarely found are Pseudomonas aeruginosa and other Gram-negative aerobic bacilli, and anaerobic bacteria. P. aeruginosa, Enterobacteriaceae, S. aureus and anaerobic bacteria (Prevotella, Bacteroides, Fusobacterium, and Peptostreptococcus spp. ) are the most common isolates in chronic mastoiditis. Rarely, Mycobacterium species can also cause the infection. Some mastoiditis is caused by cholesteatoma, which is a sac of keratinizing squamous epithelium in the middle ear that usually results from repeated middle-ear infections. If left untreated, the cholesteatoma can erode into the mastoid process, producing mastoiditis, as well as other complications. Diagnosis The diagnosis of mastoiditis is clinical—based on the medical history and physical examination. Imaging studies provide additional information; The standard method of diagnosis is via MRI scan although a CT scan is a common alternative as it gives a clearer and more useful image to see how close the damage may have gotten to the brain and facial nerves. Planar (2-D) X-rays are not as useful. If there is drainage, it is often sent for culture, although this will often be negative if the patient has begun taking antibiotics. Exploratory surgery is often used as a last resort method of diagnosis to see the mastoid and surrounding areas. Treatment If ear infections are treated in a reasonable amount of time, the antibiotics will usually cure the infection and prevent its spread. For this reason, mastoiditis is rare in developed countries. Most ear infections occur in infants as the eustachian tubes are not fully developed and dont drain readily.In all developed countries with up-to-date modern healthcare the primary treatment for mastoiditis is administration of intravenous antibiotics. Initially, broad-spectrum antibiotics are given, such as ceftriaxone. As culture results become available, treatment can be switched to more specific antibiotics directed at the eradication of the recovered aerobic and anaerobic bacteria. Long-term antibiotics may be necessary to completely eradicate the infection. If the condition does not quickly improve with antibiotics, surgical procedures may be performed (while continuing the medication). The most common procedure is a myringotomy, a small incision in the tympanic membrane (eardrum), or the insertion of a tympanostomy tube into the eardrum. These serve to drain the pus from the middle ear, helping to treat the infection. The tube is extruded spontaneously after a few weeks to months, and the incision heals naturally. If there are complications, or the mastoiditis does not respond to the above treatments, it may be necessary to perform a mastoidectomy: a procedure in which a portion of the bone is removed and the infection drained. Prognosis With prompt treatment, it is possible to cure mastoiditis. Seeking medical care early is important. However, it is difficult for antibiotics to penetrate to the interior of the mastoid process and so it may not be easy to cure the infection; it also may recur. Mastoiditis has many possible complications, all connected to the infection spreading to surrounding structures. Hearing loss is likely, or inflammation of the labyrinth of the inner ear (labyrinthitis) may occur, producing vertigo and an ear ringing may develop along with the hearing loss, making it more difficult to communicate. The infection may also spread to the facial nerve (cranial nerve VII), causing facial-nerve palsy, producing weakness or paralysis of some muscles of facial expression, on the same side of the face. Other complications include Bezolds abscess, an abscess (a collection of pus surrounded by inflamed tissue) behind the sternocleidomastoid muscle in the neck, or a subperiosteal abscess, between the periosteum and mastoid bone (resulting in the typical appearance of a protruding ear). Serious complications result if the infection spreads to the brain. These include meningitis (inflammation of the protective membranes surrounding the brain), epidural abscess (abscess between the skull and outer membrane of the brain), dural venous thrombophlebitis (inflammation of the venous structures of the brain), or brain abscess. Epidemiology In the United States and other developed countries, the incidence of mastoiditis is quite low, around 0.004%, although it is higher in developing countries. The condition most commonly affects children aged from two to thirteen months, when ear infections most commonly occur. Males and females are equally affected. See also the case of Simon Guggenheims son Pete Browning References Further reading Durand, Marlene & Joseph, Michael. (2001). Infections of the Upper Respiratory Tract. In Eugene Braunwald, Anthony S. Fauci, Dennis L. Kasper, Stephen L. Hauser, Dan L. Longo, & J. Larry Jameson (Eds.), Harrisons Principles of Internal Medicine (15th Edition), p. 191. New York: McGraw-Hill Cummings CW, Flint PW, Haughey BH, et al. Otolaryngology: Head & Neck Surgery. 4th ed. St Louis, Mo; Mosby; 2005:3019–3020. Mastoiditis E Medicine == External links ==
Pneumothorax ex vacuo	Pneumothorax ex vacuo is a rare type of pneumothorax which forms adjacent to an atelectatic lobe. It is seen preferentially with atelectasis of the right upper lobe and is the result of rapid atelectasis producing an abrupt decrease in the intrapleural pressure with subsequent release of nitrogen from pleural capillaries. Treatment Treatment consists of bronchoscopy rather than chest tube drainage. Radiographically, pneumothorax ex vacuo is suggested when an atelectatic lobe or lung, particularly right upper lobe atelectasis, is surrounded by a focal pneumothorax. Related illness "Trapped lung" presents in the same way as pneumothorax ex vacuo and can occur in patients with visceral pleural thickening and following drainage of an effusion. == References ==
Amaurosis fugax	Amaurosis fugax (Greek amaurosis meaning darkening, dark, or obscure, Latin fugax meaning fleeting) is a painless temporary loss of vision in one or both eyes. Signs and symptoms The experience of amaurosis fugax is classically described as a temporary loss of vision in one or both eyes that appears as a "black curtain coming down vertically into the field of vision in one eye;" however, this altitudinal visual loss is relatively uncommon. In one study, only 23.8 percent of patients with transient monocular vision loss experienced the classic "curtain" or "shade" descending over their vision. Other descriptions of this experience include a monocular blindness, dimming, fogging, or blurring. Total or sectorial vision loss typically lasts only a few seconds, but may last minutes or even hours. Duration depends on the cause of the vision loss. Obscured vision due to papilledema may last only seconds, while a severely atherosclerotic carotid artery may be associated with a duration of one to ten minutes. Certainly, additional symptoms may be present with the amaurosis fugax, and those findings will depend on the cause of the transient monocular vision loss. Cause Prior to 1990, amaurosis fugax could, "clinically, be divided into four identifiable symptom complexes, each with its underlying pathoetiology: embolic, hypoperfusion, angiospasm, and unknown". In 1990, the causes of amaurosis fugax were better refined by the Amaurosis Fugax Study Group, which has defined five distinct classes of transient monocular blindness based on their supposed cause: embolic, hemodynamic, ocular, neurologic, and idiopathic (or "no cause identified"). Concerning the pathology underlying these causes (except idiopathic), "some of the more frequent causes include atheromatous disease of the internal carotid or ophthalmic artery, vasospasm, optic neuropathies, giant cell arteritis, angle-closure glaucoma, increased intracranial pressure, orbital compressive disease, a steal phenomenon, and blood hyperviscosity or hypercoagulability." Embolic and hemodynamic origin With respect to embolic and hemodynamic causes, this transient monocular visual loss ultimately occurs due to a temporary reduction in retinal artery, ophthalmic artery, or ciliary artery blood flow, leading to a decrease in retinal circulation which, in turn, causes retinal hypoxia. While, most commonly, emboli causing amaurosis fugax are described as coming from an atherosclerotic carotid artery, any emboli arising from vasculature preceding the retinal artery, ophthalmic artery, or ciliary arteries may cause this transient monocular blindness. Atherosclerotic carotid artery: Amaurosis fugax may present as a type of transient ischemic attack (TIA), during which an embolus unilaterally obstructs the lumen of the retinal artery or ophthalmic artery, causing a decrease in blood flow to the ipsilateral retina. The most common source of these athero-emboli is an atherosclerotic carotid artery. However, a severely atherosclerotic carotid artery may also cause amaurosis fugax due to its stenosis of blood flow, leading to ischemia when the retina is exposed to bright light. "Unilateral visual loss in bright light may indicate ipsilateral carotid artery occlusive disease and may reflect the inability of borderline circulation to sustain the increased retinal metabolic activity associated with exposure to bright light." Atherosclerotic ophthalmic artery: Will present similarly to an atherosclerotic internal carotid artery. Cardiac emboli: Thrombotic emboli arising from the heart may also cause luminal obstruction of the retinal, ophthalmic, and/or ciliary arteries, causing decreased blood flow to the ipsilateral retina; examples being those arising due to (1) atrial fibrillation, (2) valvular abnormalities including post-rheumatic valvular disease, mitral valve prolapse, and a bicuspid aortic valve, and (3) atrial myxomas. Temporary vasospasm leading to decreased blood flow can be a cause of amaurosis fugax. Generally, these episodes are brief, lasting no longer than five minutes, and have been associated with exercise. These vasospastic episodes are not restricted to young and healthy individuals. "Observations suggest that a systemic hemodynamic challenge provoke[s] the release of vasospastic substance in the retinal vasculature of one eye." Giant cell arteritis: Giant cell arteritis can result in granulomatous inflammation within the central retinal artery and posterior ciliary arteries of eye, resulting in partial or complete occlusion, leading to decreased blood flow manifesting as amaurosis fugax. Commonly, amaurosis fugax caused by giant cell arteritis may be associated with jaw claudication and headache. However, it is also not uncommon for these patients to have no other symptoms. One comprehensive review found a two to nineteen percent incidence of amaurosis fugax among these patients. Systemic lupus erythematosus Periarteritis nodosa Eosinophilic vasculitis Hyperviscosity syndromePolycythemia HypercoagulabilityProtein C deficiency Antiphospholipid antibodiesAnticardiolipin antibodies Lupus anticoagulant Thrombocytosis Subclavian steal syndrome Malignant hypertension can cause ischemia of the optic nerve head leading to transient monocular visual loss. Drug abuse-related intravascular emboli Iatrogenic: Amaurosis fugax can present as a complication following carotid endarterectomy, carotid angiography, cardiac catheterization, and cardiac bypass. Ocular origin Ocular causes include: Iritis Keratitis Blepharitis Optic disc drusen Posterior vitreous detachment Closed-angle glaucoma Transient elevation of intraocular pressure Intraocular hemorrhage Coloboma Myopia Orbital hemangioma Orbital osteoma Keratoconjunctivitis sicca testing Neurologic origin Neurological causes include: Optic neuritis Compressive optic neuropathies Papilledema: "The underlying mechanism for visual obscurations in all of these patients appear to be transient ischemia of the optic nerve head consequent to increased tissue pressure. Axonal swelling, intraneural masses, and increased influx of interstitial fluid may all contribute to increases in tissue pressure in the optic nerve head. The consequent reduction in perfusion pressure renders the small, low-pressure vessels that supply the optic nerve head vulnerable to compromise. Brief fluctuations in intracranial or systemic blood pressure may then result in transient loss of function in the eyes." Generally, this transient visual loss is also associated with a headache and optic disk swelling. Multiple sclerosis can cause amaurosis fugax due to a unilateral conduction block, which is a result of demyelination and inflammation of the optic nerve, and "...possibly by defects in synaptic transmission and putative circulating blocking factors." Migraine Idiopathic Intracranial Hypertension Intracranial tumor Psychogenic Diagnosis Despite the temporary nature of the vision loss, those experiencing amaurosis fugax are usually advised to consult a physician immediately as it is a symptom that may herald serious vascular events, including stroke. Restated, "because of the brief interval between the transient event and a stroke or blindness from temporal arteritis, the workup for transient monocular blindness should be undertaken without delay." If the patient has no history of giant cell arteritis, the probability of vision preservation is high; however, the chance of a stroke reaches that for a hemispheric TIA. Therefore, investigation of cardiac disease is justified.A diagnostic evaluation should begin with the patients history, followed by a physical exam, with particular importance being paid to the ophthalmic examination with regards to signs of ocular ischemia. When investigating amaurosis fugax, an ophthalmologic consultation is absolutely warranted if available. Several concomitant laboratory tests should also be ordered to investigate some of the more common, systemic causes listed above, including a complete blood count, erythrocyte sedimentation rate, lipid panel, and blood glucose level. If a particular cause is suspected based on the history and physical, additional relevant labs should be ordered.If laboratory tests are abnormal, a systemic disease process is likely, and, if the ophthalmologic examination is abnormal, ocular disease is likely. However, in the event that both of these routes of investigation yield normal findings or an inadequate explanation, noninvasive duplex ultrasound studies are recommended to identify carotid artery disease. Most episodes of amaurosis fugax are the result of stenosis of the ipsilateral carotid artery. With that being the case, researchers investigated how best to evaluate these episodes of vision loss, and concluded that for patients ranging from 36 to 74 years old, "...carotid artery duplex scanning should be performed...as this investigation is more likely to provide useful information than an extensive cardiac screening (ECG, Holter 24-hour monitoring, and precordial echocardiography)." Additionally, concomitant head CT or MRI imaging is also recommended to investigate the presence of a "clinically silent cerebral embolism."If the results of the ultrasound and intracranial imaging are normal, "renewed diagnostic efforts may be made," during which fluorescein angiography is an appropriate consideration. However, carotid angiography is not advisable in the presence of a normal ultrasound and CT. Treatment If the diagnostic workup reveals a systemic disease process, directed therapies to treat that underlying cause should be initiated. If the amaurosis fugax is caused by an atherosclerotic lesion, aspirin is indicated, and a carotid endarterectomy considered based on the location and grade of the stenosis. Generally, if the carotid artery is still patent, the greater the stenosis, the greater the indication for endarterectomy. "Amaurosis fugax appears to be a particularly favorable indication for carotid endarterectomy. Left untreated, this event carries a high risk of stroke; after carotid endarterectomy, which has a low operative risk, there is a very low postoperative stroke rate." However, the rate of subsequent stroke after amaurosis is significantly less than after a hemispheric TIA, therefore there remains debate as to the precise indications for which a carotid endarterectomy should be performed. If the full diagnostic workup is completely normal, patient observation is recommended. See also Ocular ischemic syndrome Amaurosis Hemianopsia References == External links ==
Cor triatriatum	Cor triatriatum (or triatrial heart) is a congenital heart defect where the left atrium (cor triatriatum sinistrum) or right atrium (cor triatriatum dextrum) is subdivided by a thin membrane, resulting in three atrial chambers (hence the name). Cor triatriatum represents 0.1% of all congenital cardiac malformations and may be associated with other cardiac defects in as many as 50% of cases. The membrane may be complete or may contain one or more fenestrations of varying size. Cor triatrium sinistrum is more common. In this defect there is typically a proximal chamber that receives the pulmonic veins and a distal (true) chamber located more anteriorly where it empties into the mitral valve. The membrane that separates the atrium into two parts varies significantly in size and shape. It may appear similar to a diaphragm or be funnel-shaped, bandlike, entirely intact (imperforate) or contain one or more openings (fenestrations) ranging from small, restrictive-type to large and widely open. In the pediatric population, this anomaly may be associated with major congenital cardiac lesions such as tetralogy of Fallot, double outlet right ventricle, coarctation of the aorta, partial anomalous pulmonary venous connection, persistent left superior vena cava with unroofed coronary sinus, ventricular septal defect, atrioventricular septal (endocardial cushion) defect, and common atrioventricular canal. Rarely, asplenia or polysplenia has been reported in these patients. In the adult, cor triatriatum is frequently an isolated finding. Cause Cor triatriatum dextrum is extremely rare and results from the complete persistence of the right sinus valve of the embryonic heart. The membrane divides the right atrium into a proximal (upper) and a distal (lower) chamber. The upper chamber receives the venous blood from both vena cavae and the lower chamber is in contact with the tricuspid valve and the right atrial appendage. Mechanism The natural history of this defect depends on the size of the communicating orifice between the upper and lower atrial chambers. If the communicating orifice is small, the patient is critically ill and may succumb at a young age (usually during infancy) to congestive heart failure and pulmonary edema. If the connection is larger, patients may present in childhood or young adulthood with a clinical picture similar to that of mitral stenosis. Cor triatriatum may also be an incidental finding when it is nonobstructive. Diagnosis by ECHO, possibly followed by MRI. Diagnosis Primarily diagnosed with imaging, such as echocardiogram, CT, and/or MRI. Treatment The disorder can be treated surgically by removing the membrane dividing the atrium. References Church WS. Congenital malformation of heart: abnormal septum in left auricle. Trans Path Soz. 1868;19:188-190.Griffith TW. Note on a Second Example of Division of the Cavity of the Left Auricle into Two Compartments by a Fibrous Band. J Anat Physiol. Apr 1903;37:255-7. [Medline].Anderson RH. Understanding the nature of congenital division of the atrial chambers. Br Heart J. Jul 1992;68(1):1-3. [Medline].Richardson JV, Doty DB, Siewers RD, et al. Cor triatriatum (subdivided left atrium). J Thorac Cardiovasc Surg. Feb 1981;81(2):232-8. [Medline].Trento A, Zuberbuhler JR, Anderson RH, et al. Divided right atrium (prominence of the eustachian and thebesian valves). J Thorac Cardiovasc Surg. Sep 1988;96(3):457-63. [Medline].Marin-Garcia J, Tandon R, Lucas RV Jr, et al. Cor triatriatum: study of 20 cases. Am J Cardiol. Jan 1975;35(1):59-66. [Medline].Niwayama G. Cor triatriatum. Am Heart J. Feb 1960;59:291-317. [Medline].Jennings RB Jr, Innes BJ. Subtotal cor triatriatum with left partial anomalous pulmonary venous return. Successful surgical repair in an infant. J Thorac Cardiovasc Surg. Sep 1977;74(3):461-6. [Medline].Tuccillo B, Stümper O, Hess J, et al. Transoesophageal echocardiographic evaluation of atrial morphology in children with congenital heart disease. Eur Heart J. Feb 1992;13(2):223-31. [Medline].Wolf WJ. Diagnostic features and pitfalls in the two-dimensional echocardiographic evaluation of a child with cor triatriatum. Pediatr Cardiol. 1986;6(4):211-3. [Medline].Beller B, Childers R, Eckner F, et al. Cor triatriatum in the adult. Complicated by mitral insufficiency and aortic dissection. Am J Cardiol. May 1967;19(5):749-54. [Medline]. External links long description at emedicine
Vibrio vulnificus	Vibrio vulnificus is a species of Gram-negative, motile, curved rod-shaped (bacillus), pathogenic bacteria of the genus Vibrio. Present in marine environments such as estuaries, brackish ponds, or coastal areas, V. vulnificus is related to V. cholerae, the causative agent of cholera. At least one strain of V. vulnificus is bioluminescent.Infection with V. vulnificus leads to rapidly expanding cellulitis or sepsis.: 279 It was first isolated as a source of disease in 1976. Signs and symptoms Vibrio vulnificus is an extremely virulent bacterium that can cause three types of infections: Acute gastroenteritis from eating raw or undercooked shellfish: V. vulnificus causes an infection often incurred after eating seafood, especially raw or undercooked oysters. It does not alter the appearance, taste, or odor of oysters. Symptoms include vomiting, diarrhea, and abdominal pain. Necrotizing wound infections can occur in injured skin exposed to contaminated marine water. V. vulnificus bacteria can enter the body through open wounds when swimming or wading in infected waters, or by puncture wounds from the spines of fishes such as stingrays. People may develop a blistering dermatitis sometimes mistaken for pemphigus or pemphigoid. Invasive sepsis can occur after eating raw or undercooked shellfish, especially oysters. V. vulnificus is 80 times more likely to spread into the bloodstream in people with compromised immune systems, especially those with chronic liver disease. When this happens, severe symptoms including blistering skin lesions and septic shock can sometimes lead to death. This severe infection may occur regardless of whether the infection began from contaminated food or an open wound.Among healthy people, ingestion of V. vulnificus can cause vomiting, diarrhea, and abdominal pain. In someone with a compromised immune system, particularly those with chronic liver disease, it can infect the bloodstream, causing a severe and life-threatening illness characterized by fever and chills, decreased blood pressure (septic shock), and blistering skin lesions. While men have been shown to be more at risk from this infection than women, co-morbidities such as alcoholic cirrhosis and diseases affecting the endocrine system (diabetes, rheumatoid arthritis, etc.) put a person far more at risk to develop infection from V. vulnificus. Pathogenesis Capsule: V. vulnificus has a capsule, made of polysaccharides, and is thought to protect against phagocytosis. The capsule also aids the bacteria in escaping opsonization. Different strains of the bacteria are capable of shifting through the unencapsulated and encapsulated forms. Mouse models have shown that the unencapsulated forms are avirulent. These same strains however, are shown to have a higher predisposition to shift to the virulent encapsulated form when taken up by oysters.Endotoxin: Like all gram negative bacteria, V. vulnificus has LPS (lipopolysaccharide as the major component of its outer membrane). However, the LPS the bacteria produces isnt as efficient at triggering the immune systems release of tumor necrosis factor (TNF) alpha and other cytokines that produce shock syndromes. The capsular proteins the bacteria express however, are capable of producing an immune response contributing to shock syndrome.Exotoxin: V. vulnificus produces a number of extracellular toxins such as metalloprotease VvpE, cytolysin/hemolysin VvhA, and the multifunctional autoprocessing repeats-in-toxins (MARTX) toxin. While the VvhA and MARTX toxin are factors in the bacterias virulence, in vivo studies in mice suggest that the MARTX toxin is more responsible for bacterial dissemination from the intestine to produce sepsis.Iron: Growth of V. vulnificus is dependent on the amount of iron that is accessible to the bacteria. The observed association of the infection with liver disease (associated with increased serum iron) might be due to the capability of more virulent strains to capture iron bound to transferrin. Strains The most harmful strains of V. vulnificus documented have been observed in three different forms. The first is in an anti-phagocytic polysaccharide capsule that protects the bacteria. By encapsulating the bacteria, phagocytosis and opsonization are not able to occur, thus allowing the bacteria to continue throughout the organism it is in. The second way that V. vulnificus has been most harmful is with some of the toxins that it creates. These toxins are not part of the infection that V. vulnificus causes but instead they are part of a secondary infection in the GI tract that most certainly will lead to systemic infection. Lastly, V. vulnificus has been seen to cause more harm in patients who have higher levels of iron. Treatment Vibrio vulnificus wound infections have a mortality rate around 25%. In people in whom the infection worsens into sepsis, typically following ingestion, the mortality rate rises to 50%. The majority of these people die within the first 48 hours of infection. The optimal treatment is not known, but in one retrospective study of 93 people in Taiwan, use of a third-generation cephalosporin and a tetracycline (e.g., ceftriaxone and doxycycline, respectively) was associated with an improved outcome. Prospective clinical trials are needed to confirm this finding, but in vitro data support the supposition that this combination is synergistic against V. vulnificus. Likewise, the American Medical Association and the Centers for Disease Control and Prevention (CDC) recommend treating the person with a quinolone or intravenous doxycycline with ceftazidime. The first successful documented treatment of fulminant V. vulnificus sepsis was in 1995. Treatment was ceftazidime and intravenous (IV) ciprofloxacin and IV doxycycline, which proved successful. Prevention of secondary infections from respiratory failure and acute renal failure is crucial. Key to the diagnosis and treatment were the early recognition of bullae in an immunocompromised person with liver cirrhosis and oyster ingestion within the previous 48 hours, and the request by the physician for STAT Gram staining and blood cultures for V. vulnificus.Vibrio vulnificus often causes large, disfiguring ulcers that require extensive debridement or even amputation. Prognosis Vibrio vulnificus may not be a commonly known bacteria, but it is, however, the most common cause of death due to seafood in the United States. Infection and mortality due to V. vulnificus causes over 95% of deaths in the United States that are known to have occurred due to ingested seafood. Surprisingly enough, while V. vulnificus claims 95% of seafood related deaths, if treatment with tetracycline or other cephalosporin antibiotics is initiated at the onset of symptoms and is managed appropriately, patients will experience no long term effects, provided they continue to take the full course of antibiotics—typically about two weeks.The worst prognosis is in those people arriving at hospital in a state of shock. Total mortality in treated people (ingestion and wound) is around 33%.People especially vulnerable are those with liver disease (especially cirrhosis and hepatitis) or immunocompromised states (some kinds of cancer, bone marrow suppression, HIV, diabetes, etc.). With these cases, V. vulnificus usually enters the bloodstream, where it may cause fever and chills, septic shock (with sharply decreased blood pressure), and blistering skin lesions. About half of those who contract blood infections die. Vibrio vulnificus infections also disproportionately affect males; 85% of those developing endotoxic shock from the bacteria are male. Females having had an oophorectomy experienced increased mortality rates, as estrogen has been shown experimentally to have a protective effect against V. vulnificus. Epidemiology Vibrio vulnificus is commonly found in the Gulf of Mexico, where more than a dozen people have died from the infection since 1990. Most deaths at that time were occurring due to fulminant sepsis, either in the area of oyster harvest and ingestion, or in tourists returning home. Lack of disease recognition, and also of the risk factors, presentation, and cause, were and are major obstacles to good outcome and recovery.After the successful treatment of the first person, the Florida Department of Health was able to trace the origin of the outbreak to Apalachicola Bay oysters and their harvesting in water prone to excessive growth of the organism. This contamination was due to warmth of the water and change in freshwater dilution because of a change in flow of the Chattahoochee River into the Apalachicola River, and in turn into Apalachicola Bay. A similar situation occurred after Hurricane Katrina in New Orleans. Further treatment research While the treatment for V. vulnificus can be as straightforward as making the rapid choice of appropriate antibiotics, there have been cases in which the genes mutated, thus rendering antibiotics ineffective. While looking for an answer to this problem, researchers found that one way to stop the infection from spreading is to again mutate the bacteria. This mutation happens on the flagellum of the bacteria. When injected with flgC and flgE (two genes in the flagella that cause the mutation), the flagellum no longer function properly. When unable to move normally, the bacteria is no longer able to spread toxins through the body, thus decreasing the effect that V. vulnificus has on the body systemically. History The pathogen was first isolated in 1976 from a series of blood culture samples submitted to the CDC in Atlanta. It was described as a "lactose-positive vibrio". It was subsequently given the name Beneckea vulnifica, and finally Vibrio vulnificus by Farmer in 1979.Increasing seasonal temperatures and decreasing coastal salinity levels seem to favor a greater concentration of Vibrio within filter-feeding shellfish of the US Atlantic seaboard and the Gulf of Mexico, especially oysters (Crassostrea virginica). Scientists have frequently demonstrated the presence of V. vulnificus in the gut of oysters and other shellfish and in the intestines of fish that inhabit oyster reefs. The vast majority of people who develop sepsis from V. vulnificus became ill after they ate raw oysters; most of these cases have been men.In 2005, health officials clearly identified strains of V. vulnificus infections among evacuees from New Orleans due to the flooding there caused by Hurricane Katrina.In 2015 in Florida, eight cases of V. vulnificus infection with two resulting in death were reported. Natural transformation Natural transformation is a bacterial adaptation for DNA transfer between individual cells. V. vulnificus was found to become naturally transformable during growth on chitin in the form of crab shells. The ability to now carry out transformation experiments in the laboratory should facilitate molecular genetic analysis of this opportunistic pathogen. References External links Large and detailed article on V. vulnificus at Todars Online Textbook of Bacteriology CNN video on vibrio vulnificus Type strain of Vibrio vulnificus at BacDive - the Bacterial Diversity Metadatabase
Posterior urethral valve	Posterior urethral valve (PUV) disorder is an obstructive developmental anomaly in the urethra and genitourinary system of male newborns. A posterior urethral valve is an obstructing membrane in the posterior male urethra as a result of abnormal in utero development. It is the most common cause of bladder outlet obstruction in male newborns. The disorder varies in degree, with mild cases presenting late due to milder symptoms. More severe cases can have renal and respiratory failure from lung underdevelopment as result of low amniotic fluid volumes, requiring intensive care and close monitoring. It occurs in about one in 8,000 babies. Presentation PUV can be diagnosed before birth, or even at birth when the ultrasound shows that the male baby has a hydronephrosis. Some babies may also have oligohydramnios due to the urinary obstruction. The later presentation can be a urinary tract infection, diurnal enuresis, or voiding pain. Complications Incontinence Urinary tract infection Renal failure Vesicoureteral reflux Chronic kidney disease Oligohydramnios Diagnosis Abdominal ultrasound is of some benefit, but not diagnostic. Features that suggest posterior urethral valves are bilateral hydronephrosis, a thickened bladder wall with thickened smooth muscle trabeculations, and bladder diverticula.Voiding cystourethrogram (VCUG) is more specific for the diagnosis. Normal plicae circularis are variable in appearance and often not seen on normal VCUGs. PUV on voiding cystourethrogram is characterized by an abrupt tapering of urethral caliber near the verumontanum, with the specific level depending on the developmental variant. Vesicoureteral reflux is also seen in over 50% of cases. Very often the posterior urethra maybe dilated thus making the abrupt narrowing more obvious. the bladder wall may show trabeculations or sacculations or even diverticuli.Diagnosis can also be made by cystoscopy, where a small camera is inserted into the urethra for direct visualization of the posteriorly positioned valve. A limitation of this technique is that posterior valve tissue is translucent and can be pushed against the wall of the urethra by inflowing irrigation fluid, making it difficult to visualize. Cystoscopy may also demonstrate the bladder changes.Centers in Europe and Japan have also had excellent results with cystosonography, although it has not been approved for use in the United States yet. Classification Posterior urethral obstruction was first classified by H. H. Young in 1919. The verumontanum, or mountain ridge, is a distinctive landmark in the prostatic urethra, important in the systemic division of posterior valve disorders:Type I - Most common type; due to anterior fusing of the plicae colliculi, mucosal fins extending from the bottom of the verumontanum distally along the prostatic and membranous urethra Type II - Least common variant; vertical or longitudinal folds between the verumontanum and proximal prostatic urethra and bladder neck Type III - Less common variant; a disc of tissue distal to verumontanum, also theorized to be a developmental anomaly of congenital urogenital remnants in the bulbar urethraDewan has suggested that obstruction in the posterior urethra is more appropriately termed congenital obstructions of the posterior urethral membrane (COPUMs), a concept that has come from an in-depth analysis of the historical papers, and evaluation of patients with a prenatal diagnosis that has facilitated video recording of the uninstrumented obstructed urethra. The congenital obstructive lesions in the bulbar urethra, named Type III Valves by Young in 1919, have been eponymously referred to as Cobbs collar or Moormans ring. For each of the COPUM (Posterior Urethra) and Cobbs (Bulbar Urethra) lesions, the degree of obstruction can be variable, consistent with a variable expression of the embryopathy. The now nearly one hundred year old nomenclature of posterior urethral valves was based on limited radiology and primitive endoscopy, thus a change COPUM or Cobbs has been appropriate. Treatment If suspected antenatally, a consultation with a paediatric surgeon/ paediatric urologist maybe indicated to evaluate the risk and consider treatment options.Treatment is by endoscopic valve ablation. Fetal surgery is a high risk procedure reserved for cases with severe oligohydramnios, to try to limit the associated lung underdevelopment, or pulmonary hypoplasia, that is seen at birth in these patients. The risks of fetal surgery are significant and include limb entrapment, abdominal injury, and fetal or maternal death. Specific procedures for in utero intervention include infusions of amniotic fluid, serial bladder aspiration, and creating a connection between the amniotic sac and the fetal bladder, or vesicoamniotic shunt.There are three specific endoscopic treatments of posterior urethral valves: Vesicostomy followed by valve ablation - a stoma, or hole, is made in the urinary bladder, also known as low diversion, after which the valve is ablated and the stoma is closed. Pyelostomy followed by valve ablation - stoma is made in the pelvis of the kidney as a slightly high diversion, after which the valve is ablated and the stoma is closed Primary (transurethral) valve ablation - the valve is removed through the urethra without creation of a stomaThe standard treatment is primary (transurethral) ablation of the valves. Urinary diversion is used in selected cases, and its benefit is disputed.Following surgery, the follow-up in patients with posterior urethral valve syndrome is long term, and often requires a multidisciplinary effort between paediatric surgeons/ paediatric urologists, paediatric nephrologists, pulmonologists, neonatologists, radiologists and the family of the patient. Care must be taken to promote proper bladder compliance and renal function, as well as to monitor and treat the significant lung underdevelopment that can accompany the disorder. Definitive treatment may also be indicated for the vesico-ureteral reflux. Female homolog The female homolog to the male verumontanum from which the valves originate is the hymen. References == External links ==
Fibroma of tendon sheath	Fibroma of tendon sheath is a benign tumor that presents as a small subcutaneous nodule that slowly increases in size. The tumors often have a multinodular growth pattern, with individual nodules being composed of bland, slender, spindle-shaped cells (myofibroblasts) in a dense, fibrous matrix.” A common microscopic finding is the presence of elongated, slit-like blood vessels. The lesions nearly always arise in the distal portions of the extremities. They often occur on the fingers, hands, toes, or feet. Although they are benign, they may recur in up to 40% of cases.Although they may be regarded as a tumor of the skin, the lesions arise from tendons and aponeuroses in superficial sites, and are therefore properly classified as in the category "soft tissue tumor." The World Health Organization, 2020, reclassified these tumors as a specific, benign tumor type in a broad category of soft tissue neoplasms termed fibroblastic and myofibroblastic tumors.The biological nature of Fibroma of tendon sheath is not known, but the category appears to comprise a number of different pathologic processes. It is considered that about one-third of the lesions in this category may be acral variants of the entity, nodular fasciitis. See also Giant cell tumor of the tendon sheath List of cutaneous conditions == References ==
Single umbilical artery	Occasionally, there is only the one single umbilical artery (SUA) present in the umbilical cord. This is sometimes also called a two-vessel umbilical cord, or two-vessel cord. Approximately, this affects between 1 in 100 and 1 in 500 pregnancies, making it the most common umbilical abnormality. Its cause is not known. Most cords have one vein and two arteries. The vein carries oxygenated blood from the placenta to the baby and the arteries carry deoxygenated blood from the baby to the placenta. In approximately 1% of pregnancies there are only two vessels —usually a single vein and single artery. In about 75% of those cases, the baby is entirely normal and healthy. One artery can support a pregnancy and does not necessarily indicate problems. For the other 25%, a 2-vessel cord is a sign that the baby has other abnormalities—sometimes life-threatening and sometimes not.Doctors and midwives often suggest parents take the added precaution of having regular growth scans near term to rule out intrauterine growth restriction, which can happen on occasion and warrant intervention. Yet the majority of growth restricted infants with the abnormality also have other defects. Finally, neonates with the finding may also have a higher occurrence of renal problems, therefore close examination of the infant may be warranted shortly after birth. Among SUA infants, there is a slightly elevated risk for post-natal urinary infections. Presentation Associations SUA does increase the risk of the baby having cardiac, skeletal, intestinal or renal problems. Babies with SUA may have a higher likelihood of having other congenital abnormalities, especially of the heart. However, additional testing (high level ultrasound scans) can rule out many of these abnormalities prior to birth and alleviate parental anxiety.It may be associated with Trisomy 18, also known as Edwards syndrome. Intrauterine growth restriction has been found to be associated. Diagnosis It can be detected in the first trimester of pregnancy with the use of 2D ultrasound. The sonographer is able to identify a 2 vessel cord in an image with the bladder and color Doppler, which will show only one artery going around one side of the bladder. In a normal fetus, there would be 2 arteries (one on each side of the bladder). Echocardiograms of the fetus may be advised to ensure the heart is functioning properly. Genetic counseling may be useful, too, especially when weighing the pros and cons of more invasive procedures such as chorionic villus sampling and amniocentesis. These invasive procedures are usually performed when there is a suspected chromosomal abnormality or genetic defect and will confirm a diagnosis. Prognosis Although the presence of an SUA is a risk factor for additional complications, most fetuses with the condition will not experience other problems, either in utero or after birth. Especially encouraging are cases in which no other soft markers for congenital abnormalities are visible via ultrasound. Given that, the vast majority of expectant mothers do not receive the kind of advanced ultrasound scanning required to confirm SUA in utero. Epidemiology It is slightly more common in multiple births, in infants with chromosome anomalies, and in girls than in boys. References == External links ==
Urinary tract obstruction	Urinary tract obstruction is a urologic disease consisting of a decrease in the free passage of urine through one or both ureters and/or the urethra. It is a cause of urinary retention. Complete obstruction of the urinary tract requires prompt treatment for renal preservation. Any sign of infection, such as fever and chills, in the context of obstruction to urine flow constitutes a urologic emergency. Causes Causes of urinary tract obstruction include: Bladder stone and renal stone Benign prostatic hyperplasia Obstruction as a congenital disorder. Congenital urinary tract obstruction Urinary tract obstruction as a congenital disorder results in oligohydramnios which in turn can lead to the Potter sequence of atypical physical appearance. Pulmonary hypoplasia is by far the main cause of death in the early neonatal period for children with congenital lower urinary tract obstruction.Fetal surgery of congenital lower urinary tract obstruction seems to improve survival, according to a randomized yet small study. Sitting voiding position A meta-analysis on the influence of voiding position on urodynamics in healthy males and males with LUTS showed that in the sitting position, the residual urine in the bladder was significantly reduced. The other parameters, namely the maximum urinary flow and the voiding time were increased and decreased respectively. For healthy males, no influence was found on these parameters, meaning that they can urinate in either position. Diagnosis Treatment Treatment depends on the underlying cause of the obstruction and the severity of the symptoms. References == External links ==
Evil eye	The evil eye (Turkish: Nazar boncuğu; Ancient Greek: ὀφθαλμὸς βάσκανος; Greek: μάτι; Hebrew: עַיִן הָרָע; Romanian: Deochi; Italian: malocchio; Spanish: mal de ojo; Arabic: عين الحسد, ayn al-hasad; Persian: چشم زخم, Cheshm Zakhm; Dari: چشم مهره Cheshem Mohra; Kazakh: Көз) is a supernatural belief in a curse, brought about by a malevolent glare, usually given to a person when one is unaware. The evil eye dates back about 5,000 years. This iconic symbol is present across various religions and cultures, but most importantly Witchcraft. The earliest known belief in the power of the evil eye predates ancient Roman and Greek times classical antiquity, there has been literature that mentions at 6th century BC it appeared on Chalcidian drinking vessels, known as eye-cups, as a type of apotropaic magic. It is found in many cultures in the Mediterranean region, with such cultures often believing that receiving the evil eye will cause misfortune or injury, while others believe it to be a kind of supernatural force that casts or reflects a malevolent gaze back-upon those who wish harm upon others (especially innocents). Older iterations of the symbol were often made of ceramic or clay; however, following the production of glass beads in the Mediterranean region in approximately 1500 BC, evil eye beads were popularised with the Phoenicians, Persians, Greeks, Romans and Ottomans.The idea expressed by the term causes many different cultures to pursue protective measures against it, with around 40% of the worlds population believing in the evil eye. The concept and its significance vary widely among different cultures, but it is especially prominent in the Balkans, Mediterranean and West Asia. The idea appears multiple times in Jewish rabbinic literature. Other popular amulets and talismans used to ward off the evil eye include the hamsa, while Italy (especially Southern Italy) employs a variety of other unique charms and gestures to defend against the evil eye, including the cornicello, the cimaruta, and the sign of the horns. While the Egyptian Eye of Horus is a similar symbol of protection and good health, the Greek evil eye talisman specifically protects against malevolent gazes. Similarly, the Eye-Idols (c. 8700–3500 BC) excavated at the Tell Brak Eye Temple are believed to have been figurines offered to the gods, and according to the Metropolitan Museum of Art, are unrelated to a belief in the evil eye. History Belief in the evil eye dates all the way back to at least Ancient Ugarit, as it is attested to in texts from this city (ruins in modern-day Syria). Given that the city was destroyed circa 1250BC, during the late Bronze Age collapse to never be rebuilt, the belief dates back at least to this point, and likely earlier. Later in Greek Classical antiquity, it is referenced by Hesiod, Callimachus, Plato, Diodorus Siculus, Theocritus, Plutarch, Heliodorus, Pliny the Elder, and Aulus Gellius. Peter Walcots Envy and the Greeks (1978) listed more than one hundred works by these and other authors mentioning the evil eye. Noting that Greeks are an ethnic group indigenous to Greece and the Levant, artefacts can be found from this region. Ancient authors frequently mention the ὀφθαλμὸς βάσκανος (evil eye). Classical authors attempted both to describe and to explain the function of the evil eye. Plutarch in his work entitle Symposium has a separate chapter describing such beliefs. In his scientific explanation stated that the eyes were the chief, if not sole, source of the deadly rays that were supposed to spring up like poisoned darts from the inner recesses of a person possessing the evil eye. Plutarch treated the phenomenon of the evil eye as something seemingly inexplicable that is a source of wonder and cause of incredulity. Pliny the Elder described the ability of certain African enchanters to have the "power of fascination with the eyes and can even kill those on whom they fix their gaze".The idea of the evil eye appears in the poetry of Virgil in a conversation between the shepherds Menalcas and Damoetas. In the passage, Menalcas is lamenting the poor health of his stock: "What eye is it that has fascinated my tender lambs?". Ancient Greeks and Romans believed that the evil eye could affect both humans and animals, for example cattles. Protection from the eye The belief in the evil eye during antiquity varied across different regions and periods. The evil eye was not feared with equal intensity in every corner of the Roman Empire. There were places in which people felt more conscious of the danger of the evil eye. In Roman times, not only were individuals considered to possess the power of the evil eye but whole tribes, especially those of Pontus and Scythia, were believed to be transmitters of the evil eye.Many different objects and charms were used for protection from fascination. The protective items referred by the Greeks with a variety of names such as apotropaia, probaskania, periammata, periapta and profylaktika.The phallic charm called fascinum in Latin, from the verb fascinare, "to cast a spell" (the origin of the English word "fascinate") is one example of an apotropaic object used against the evil eye. They have been found throughout Europe and into the Middle East from contexts dating from the first century BC to the fourth century AD. The phallic charms were often objects of personal adornment (such as pendants and finger rings), but also appeared as stone carvings on buildings, mosaics, and wind-chimes (tintinnabula). Examples of stone phallic carvings, such as from Leptis Magna, depict a disembodied phallus attacking an evil eye by ejaculating towards it. In describing their ability to deflect the evil eye, Ralph Merrifield described the Roman phallic charm as a "kind of lightning conductor for good luck".Peisistratus hung the figure of a kind of grasshopper before the Acropolis of Athens for protection.Another way for protection from fascination used by the ancient Greeks and Romans was by spitting into the folds of the clothes.Ancient Greeks also had an old custom of dressing boys as girls in order to avert the evil eye. Around the world Belief in the evil eye is strongest in West Asia, Latin America, East and West Africa, Central America, South Asia, Central Asia, and Europe, especially the Mediterranean region; it has also spread to areas, including northern Europe, particularly in the Celtic regions, and the Americas, where it was brought by European colonists and West Asian immigrants.Belief in the evil eye is found in the Islamic doctrine, based upon the statement of the Islamic prophet Muhammad, "The influence of an evil eye is a fact..." [Sahih Muslim, Book 26, Number 5427]. Authentic practices of warding off the evil eye are also commonly practiced by Muslims: rather than directly expressing appreciation of, for example, a childs beauty, it is customary to say MashaAllah, that is, "God has willed it", or invoking Gods blessings upon the object or person that is being admired.A number of beliefs about the evil eye are also found in folk religion, typically revolving around the use of amulets or talismans as a means of protection. In the Aegean Region and other areas where light-colored eyes are relatively rare, people with green eyes, and especially blue eyes, are thought to bestow the curse, intentionally or unintentionally. Thus, in Greece and Turkey amulets against the evil eye take the form of eyes looking back at someone, and in the painting by John Phillip, we witness the culture-clash experienced by a woman who suspects that the artists gaze implies that he is looking at her with the evil eye. Among those who do not take the evil eye literally, either by reason of the culture in which they were raised or because they simply do not believe it, the phrase, "to give someone the evil eye" usually means simply to glare at the person in anger or disgust. The term has entered into common usage within the English language. Within the broadcasting industry, it refers to when a presenter signals to the interviewee or co-presenter to stop talking due to a shortage of time. Protective talismans and cures Attempts to ward off the curse of the evil eye have resulted in a number of talismans in many cultures. As a class, they are called "apotropaic" (Greek for "prophylactic" / προφυλακτικός or "protective", literally: "turns away") talismans, meaning that they turn away or turn back harm. Disks or balls, consisting of concentric blue and white circles (usually, from inside to outside, dark blue, light blue, white, and dark blue) representing an evil eye are common apotropaic talismans in West Asia and the Balkans, found on the prows of boats and elsewhere; in some forms of the folklore, the staring eyes are supposed to bend the malicious gaze back to the sorcerer. Known as nazar (Turkish: nazar boncuğu or nazarlık), this talisman is most frequently seen in Turkey, found in or on houses and vehicles or worn as beads. The word hamsa, also spelled khamsa and hamesh, means "five" referring to the fingers of the hand. In Jewish culture, the hamsa is called the Hand of Miriam; in the Levantine Christian culture is called the Hand of Mary, in some Muslim and Balkan cultures, the Hand of Fatima. Though condemned as superstition by doctrinaire Muslims, it is almost exclusively among the Near East and Mediterranean that the belief in envious looks containing destructive power or the talismanic power of a nazar to defend against them. To adherents of other faiths in the region, the nazar is an attractive decoration. A variety of motifs to ward off the evil eye are commonly woven into tribal kilim rugs. Such motifs include a cross (Turkish: Haç) to divide the evil eye into four, a hook (Turkish: Çengel) to destroy the evil eye, or a human eye (Turkish: Göz) to avert the evil gaze. The shape of a lucky amulet (Turkish: Muska; often, a triangular package containing a sacred verse) is often woven into kilims for the same reason. By religion In Judaism The evil eye is mentioned several times in the classic Pirkei Avot (Ethics of Our Fathers). In Chapter II, five disciples of Rabbi Yochanan ben Zakai give advice on how to follow the good path in life and avoid the bad. Rabbi Eliezer says an evil eye is worse than a bad friend, a bad neighbor, or an evil heart. Talmudic exegete, Rashi, says in the wake of the words of Israels Sages that when the ten sons of Jacob went down into Egypt to buy provisions, they made themselves inconspicuous by each entering into a separate gate, so that they would not be gazed upon by the local Egyptians and, thereby, trigger a malevolent response (the Evil eye) by their onlookers, seeing that they were all handsome and of brave and manly dispositions.Some Jews believe that a "good eye" designates an attitude of goodwill and kindness towards others. Someone who has this attitude in life will rejoice when his fellow man prospers; he will wish everyone well. An "evil eye" denotes the opposite attitude. A man with "an evil eye" will not only feel no joy but experience actual distress when others prosper and will rejoice when others suffer. A person of this character represents a great danger to moral purity, according to some Jews.Rabbi Abraham Isaac Kook explained that the evil eye is "an example of how one soul may affect another through unseen connections between them. We are all influenced by our environment... The evil eye is the venomous impact from malignant feelings of jealousy and envy of those around us."Many observant Jews avoid talking about valuable items they own, good luck that has come to them and, in particular, their children. If any of these are mentioned, the speaker and/or listener will say bli ayin hara (Hebrew), meaning "without an evil eye", or kein eina hara (Yiddish; often shortened to kennahara), "no evil eye". Another way to ward off the evil eye is to spit three times (or pretend to). Romans call this custom "despuere malum," to spit at evil. It has also been suggested the 10th Commandment: "Do not covet anything that belongs to your neighbor" is a law against bestowing the evil eye on another person. In Christianity Christianitys beliefs of the evil eye can be located in some passages of the Bible. In Luke 11:34 Jesus referenced to the eye as the lamp of the body. If a persons eye is generous, then their whole body will be full of light. If their eye is evil, then their whole body will be full of darkness. Cross necklaces are worn by some Christians who believe the cross offers protection from Satan. A simple and instant way of protection in European Christian countries is to make the sign of the cross with your hand and point two fingers, the index finger and the middle finger, towards the supposed source of influence or supposed victim as described in the first chapter of Bram Stokers novel Dracula published in 1897:When we started, the crowd round the inn door, which had by this time swelled to a considerable size, all made the sign of the cross and pointed two fingers towards me. With some difficulty, I got a fellow passenger to tell me what they meant. He would not answer at first, but on learning that I was English, he explained that it was a charm or guard against the evil eye. In Islam In Islam, the evil eye, or al-’ayn العين, also عين الحسودة), is a common belief that individuals have the power to cause harm to people, animals or objects, by looking at them in a way that indicates jealousy. Although envy activates the evil eye, this happens (or usually happens) unconsciously, and the person who casts it is not responsible (or usually not responsible) for it. In addition to being looked at, astrology may play a part. Someone may become a victim of the evil eye by virtue of an "unfavorable celestial configuration" at the time of victims birth, "according to some scholars".Among the rituals to ward off the evil eye are to say "TabarakAllah" (تبارك الله) ("Blessings of God") or "MashaAllah" (ما شاء الله) ("God has willed it") if a compliment is to be made. By geographic region Caribbean/West Indies In Trinidad and Tobago, the evil eye is called maljo (from French mal yeux, meaning bad eye). The term is used in the infinitive (to maljo) and as a noun (to have/get maljo) referring to persons who have been afflicted. Maljo may be passed on inadvertently, but is believed to be more severe when coming from an envious person or one with bad intentions. It is thought to happen more readily when a person is stared at- especially while eating food. A person who has been taken by the ‘bad eye’ may experience unexplained illness or misfortune. In traditional rural legends, ‘The general belief is that doctors cannot cure maljo----only people who know prayers can "cut" the maljo and thus cure the victim.’There are several secular approaches to combatting maljo, but more extreme cases are usually referred to as spiritual rituals, with a particularly strong influence from the Hindu religion. In non-religious respects, there is a strong cultural association between the evil eye and the color blue. It is believed to ward off maljo when worn as clothing or accessories, so much so that some striking shades are referred to as ‘maljo blue’. Blue ornaments may be used to protect a household, and blue bottles from Milk of Magnesia have been hung on trees or placed in the yard surrounding a property.Blue soap and Albion Blue (an indigo dye referred to Trinbagonians simply as ‘blue’) are traditionally used for domestic washing, but are also considered to prevent maljo if used in bath water or to anoint the soles of the feet. Jumbie beads are the poisonous seeds of the Rosary Pea tree which are used to make jewelry that also wards off maljo and evil spirits. One superstition is that a pinch can reverse maljo following interpersonal interactions, especially if one is stared at or given a compliment. Some also believe that rubbing ones own saliva in their hair will counteract maljo in general, but particularly from envy of the hair texture and length. A bath in the sea is also thought to relieve an afflicted person. Maljo believers are particularly concerned with safeguarding babies and children, who are considered to be most vulnerable to its effects. It may be ‘caused by someone born with a "blight" in the eye when such a person looks admiringly at a child. It can also occur with a pat on the head, or with just a glance. Whether it is intended or not, compliments (...) can cause maljo. It can be caused by a stranger, a member of the childs immediate family, or by another relative.’ It may even be passed on by a parent who is obsessed with their own child. A baby with maljo ‘refuses to eat or drink, cries continually, and "pines away.". It may have an "attack of fever".’Bracelets made of jet beads are traditionally given to newborns to wear as a preventative measure, while elders also recommend securing a bag of blue (dye) to the babys clothes. This is because a newborn is viewed as most vulnerable. Following East Indian influence, a tikka is a black dot that is placed on a babys forehead- thought to distract the attention of the evil eye and protect the child as such. The most common maljo remedy comes in the form of a Hindu ritual called a jharay. It may be practiced at home (usually by parents or elders) or by a Pandit or spiritual practitioner. There are many variations to the ritual, and non-Hindu persons readily participate if they are considered to have been affected by maljo. The main implement in a jharay is either a peacock feather or a cocoyea broom- a traditional broom made using the midrib of the coconut palm leaf. Some also report a knife or machete being used. In some instances, the cocoyea broom is measured against a particular part of the body at the beginning of the ceremony, and it is believed to be confirmation of maljo if the recorded length has changed by the end of the session. The officiant will say a prayer while using the tool of choice to brush the person from head to toe. The prayer is conventionally said in Hindi, but may also be said in English. A jharay may focus on a specific point of affliction or pain (head, hair, back, feet and so on). It is not unusual for a jharay ceremony to be carried out on children and babies. ‘People believe that maljo can cause death. Two types were reported: the "dragging" kind, where the baby gets smaller and smaller and goes through all of the symptoms mentioned above, before withering and dying; the "Twenty-four hour" maljo, said to kill in just twenty-four hours if effective help is not obtained.’Another Hindu ritual called the oucchay is also employed to heal maljo- though this might also be interchangeably called a jharay. Ingredients such as onion skin, salt, cobweb, hot pepper or mustard seeds, piece of a cocoyea broom, a lock of the victims hair (in the case of children, it is a lock of the mothers hair) are wrapped in a tissue or newspaper. The officiant will circle the wrapped objects around the victims body before burning them all. It is believed that if the items create a large, crackling flame and a foul stench, it is an indication that the victim had a severe case of maljo. At the end of the ritual, the victim may be asked to walk away without looking back while the objects burn. In Afro-Caribbean Spiritual Baptist and Orisha tradition, a special piece of jewelry called a guard will be blessed by an elder, who invokes its protection on the wearer. It may be a waist bead, anklet, bracelet, or necklace. For babies, a large safety pin might be used as a guard. Greece The evil eye, known as μάτι (mati), "eye", as an apotropaic visual device, is known to have been a fixture in Greece dating back to at least the 6th century BC, when it commonly appeared on drinking vessels. In Greece, the evil eye is cast away through the process of xematiasma (ξεμάτιασμα), whereby the "healer" silently recites a secret prayer passed over from an older relative of the opposite sex, usually a grandparent. Such prayers are revealed only under specific circumstances, as according to their customs those who reveal them indiscriminately lose their ability to cast off the evil eye. There are several regional versions of the prayer in question, a common one being: "Holy Virgin, Our Lady, if [insert name of the victim] is suffering of the evil eye, release him/her of it." Evil repeated three times. According to custom, if one is indeed afflicted with the evil eye, both victim and "healer" then start yawning profusely. The "healer" then performs the sign of the cross three times, and emits spitting-like sounds in the air three times. Another "test" used to check if the evil eye was cast is that of the oil: under normal conditions, olive oil floats in water, as it is less dense than water. The test of the oil is performed by placing one drop of olive oil in a glass of water, typically holy water. If the drop floats, the test concludes there is no evil eye involved. If the drop sinks, then it is asserted that the evil eye is cast indeed. Another form of the test is to place two drops of olive oil into a glass of water. If the drops remain separated, the test concludes there is no evil eye, but if they merge, there is. There is also a third form where in a plate full of water the "healer" places three or nine drops of oil. If the oil drops become larger and eventually dissolve in the water there is an evil eye. If the drops remain separated from water in a form of a small circle there isnt. The first drops are the most important and the number of drops that dissolve in water indicates the strength of the evil eye. Note that a secret chant is spoken when these tests are conducted. The words of the chant are closed practiced and can only be passed from man to woman, or woman to man.There is another form of the "test" where the "healer" prepares a few cloves by piercing each one with a pin. Then she lights a candle and grabs a pinned clove with a pair of scissors. She then uses it to do the sign of the cross over the afflicted whilst the afflicted is asked to think of a person who may have given him the evil eye. Then the healer holds the clove over the flame. If the clove burns silently, there is no evil eye present; however, if the clove explodes or burns noisily, that means the person in the thoughts of the afflicted is the one who has cast the evil eye. As the clove explodes, the evil eye is released from the afflicted. Cloves that burn with some noise are considered to be λόγια - words - someone foul-mouthing you that you ought to be wary of. The burned cloves are extinguished into a glass of water and are later buried in the garden along with the pins as they are considered to be contaminated. Greek people will also ward off the evil eye by saying φτου να μη σε ματιάξω! which translates to "I spit so that I wont give you the evil eye." Contrary to popular belief, the evil eye is not necessarily given by someone wishing you ill, but it stems from admiration - if one considers admiration to be a compelled emotion of astonishment at a rivals success over ones evil plan. Since it is technically possible to give yourself the evil eye, it is advised to be humble. The Greek Fathers accepted the traditional belief in the evil eye, but attributed it to the Devil and envy. In Greek theology, the evil eye or vaskania (βασκανία) is considered harmful for the one whose envy inflicts it on others as well as for the sufferer. The Greek Church has an ancient prayer against vaskania from the Megan Hieron Synekdemon (Μέγαν Ιερόν Συνέκδημον) book of prayers. Assyrians Assyrians are also strong believers in the evil eye. They will usually wear a blue/turquoise bead around a necklace to be protected from the evil eye. Also, they might pinch the buttocks, comparable to Armenians. It is said that people with green or blue eyes are more prone to the evil eye effect. Turkey A typical nazar is made of handmade glass featuring concentric circles or teardrop shapes in dark blue, white, light blue and black, occasionally with a yellow/gold edge.Cultures that have nazars or some variation include Turkey, Romania, Albania, North Macedonia, Bosnia and Herzegovina, Greece, Cyprus, Syria, Lebanon, Jordan, Palestine, Egypt, Armenia, Iran, India, Israel, Pakistan, Uzbekistan, Afghanistan, Türkmenistan, Iraq and Azerbaijan, where the nazar is often hung in homes, offices, cars, childrens clothing, or incorporated in jewellery and ornaments.They are a popular choice of souvenir with tourists. Ethiopia Belief in the evil eye, or buda (var. bouda), is widespread in Ethiopia. Buda is generally believed to be a power held and wielded by those in a different social group, for example among the metalworkers. Some Ethiopian Christians carry an amulet or talisman, known as a kitab, or will invoke Gods name, to ward off the ill effects of buda. A debtera, who is either an unordained priest or educated layperson, will create these protective amulets or talismans. Senegal The equivalent of the evil eye in Wolof would be the "thiat". It is believed that beautiful objects may break if enviously stared at by others. To repel the effect of the evil eye, Senegalese people may wear cowrie shell bracelets. The sea shells are said to absorb the negative energy of the thiat, and gradually darken until the bracelet breaks. It is also common for superstitious people to wear "gris-gris" made by a marabouts to avoid misfortune. Indian subcontinent India In the northern states of India, like the Punjab, Uttar Pradesh, Rajasthan, Haryana, Uttarakhand, and Himachal Pradesh, the evil eye is called "nazar" (meaning gaze or vision) or more commonly Buri Nazar. A charm bracelet, tattoo or other object (Nazar battu), or a slogan (Chashme Baddoor (slogan)), may be used to ward off the evil eye. Some truck owners write the slogan to ward off the evil eye: "buri nazar wale tera muh kala" ("O evil-eyed one, may your face turn black"). In Andhra Pradesh and Telangana, people call it as Disti or Drusti, while people of Tamil Nadu call it drishti or kannu (translated, means evil eye). The people of Kerala also call it “kannu”, which translates to “eye”. To remove Drishti, people follow several methods based on their culture/area. Items often used are either rock salt, red chilies, white pumpkins, oiled cloth, or lemons coated with kumkuma. People remove Drishti by rotating any
Evil eye	one of these items around the affected person. The person who removes it will then burn the item, or discard it in a place where others are not likely to stamp on these items. People hang pictures of fierce and scary ogres in their homes or vehicles, to ward off the evil eye.In India, babies and newborn infants will usually have their eye adorned with kajal, or eyeliner. This would be black, as it is believed in India that black wards off the evil eye or any evil auras. The umbilical cord of babies is often preserved and cast into a metal pendant, and tied to a black string — babies can wear this as a chain, bracelet or belt—the belief, once more, is that this protects the infant from drishti. This is a practice that has been followed right from historical times. People usually remove drishti on full-moon or new-moon days, since these days are considered to be auspicious in India. Indians often leave small patches of rock salt outside their homes, and hang arrangements of green chilies, neem leaves, and lemons on their stoop. The belief is that this will ward away the evil eye cast on families by detractors. Pakistan In Pakistan, the evil eye is called Nazar (نظر). People usually may resort to reading the last three chapters of the Quran, namely Sura Ikhlas, Sura Al-Falaq and Sura Al-Nas. "MashaAllah" (ما شاء الله) ("God has willed it") is commonly said to ward off the evil eye. Understanding of the evil eye varies by the level of education. Some perceive the use of black color to be useful in protecting from the evil eye. Others use "taawiz" to ward off the evil eye. Truck owners and other public transport vehicles may commonly be seen using a small black cloth on the bumpers to prevent the evil eye. Italy The cornicello, "little horn", also called the cornetto ("little horn", plural cornetti), is a long, gently twisted horn-shaped amulet. Cornicelli are usually carved out of red coral or made from gold or silver. The type of horn they are intended to copy is not a curled-over sheep horn or goat horn but rather like the twisted horn of an African eland or a chili pepper. A tooth or tuft of fur of the Italian wolf was worn as a talisman against the evil eye.One idea that the ribald suggestions made by sexual symbols distract the witch from the mental effort needed to successfully bestow the curse. Another is that since the effect of the eye was to dry up liquids, the drying of the phallus (resulting in male impotence) would be averted by seeking refuge in the moist female genitals. Among the ancient Romans and their cultural descendants in the Mediterranean nations, those who were not fortified with phallic charms had to make use of sexual gestures to avoid the eye. Such gestures include scratching ones testicles (for men), as well as the mano cornuta gesture and the fig sign; a fist with the thumb pressed between the index and middle fingers, representing the phallus within the vagina. In addition to the phallic talismans, statues of hands in these gestures, or covered with magical symbols, were carried by the Romans as talismans. The wielder of the evil eye, the jettatore, is described as having a striking facial appearance, high arching brows with a stark stare that leaps from his eyes. He often has a reputation for clandestine involvement with dark powers and is the object of gossip about dealings in magic and other forbidden practices. Successful men having tremendous personal magnetism quickly gain notoriety as jettatori. Pope Pius IX was dreaded for his evil eye, and a whole cycle of stories about the disasters that happened in his wake were current in Rome during the latter decades of the 19th century. Public figures of every type, from poets to gangsters, have had their specialized abilities attributed to the power of their eyes. Malta The symbol of the eye, known as "l-għajn", is common on traditional fishing boats which are known as luzzu. They are said to protect fishermen from storms and malicious intentions. Brazil Brazilians generally will associate mau-olhado ("act of giving a bad look") or olho gordo ("fat eye" i.e. "gluttonous eye") with envy or jealousy on domestic and garden plants (that, after months or years of health and beauty, will suddenly weaken, wither and die, with no apparent signs of pest, after the visitation of a certain friend or relative), attractive hair and less often economic or romantic success and family harmony. Unlike in most cultures mau-olhado is not seen to be something that risks young babies. "Pagans" or non-baptized children are instead assumed to be at risk from bruxas (witches), that have malignant intention themselves rather than just mau-olhado. It probably reflects the Galician folktales about the meigas or Portuguese magas, (witches), as Colonial Brazil was primarily settled by Portuguese people, in numbers greater than all Europeans to settle pre-independence United States. Those bruxas are interpreted to have taken the form of moths, often very dark, that disturb children at night and take away their energy. For that reason, Christian Brazilians often have amulets in the form of crucifixes around, beside or inside beds where children sleep. Nevertheless, older children, especially boys, that fulfill the cultural ideals of behaving extremely well (for example, having no problems whatsoever in eating well a great variety of foods, being obedient and respectful toward adults, kind, polite, studious, and demonstrating no bad blood with other children or their siblings) who unexpectedly turn into problematic adolescents or adults (for example lacking good health habits, extreme laziness or lacking motivation towards their life goals, having eating disorders, or being prone to delinquency), are said to have been victims of mau-olhado coming from parents of children whose behavior was not as admirable. Amulets that protect against mau-olhado tend to be generally resistant, mildly to strongly toxic and dark plants in specific and strategic places of a garden or the entry to a house. Those include comigo-ninguém-pode ("against-me-nobody-can"), Dieffenbachia, espada-de-são-jorge ("St. Georges sword"), Sansevieria trifasciata, and Guiné ("Guinea"), Petiveria alliacea (the guinea henweed). For those lacking in space or wanting to "sanitize" specific places, they may all be planted together in a single sete ervas ("seven [lucky] herbs") pot, that will also include arruda (common rue), pimenteira (Capsicum annuum), manjericão (basil) and alecrim (rosemary). (Though the last four ones should not be used for their common culinary purposes by humans.) Other popular amulets against evil eye include: the use of mirrors, on the outside of your homes front door, or also inside your home facing your front door; an elephant figurine with its back to the front door; and coarse salt, placed in specific places at home. Spain and Latin America The evil eye or Mal de Ojo has been deeply embedded in Spanish popular culture throughout its history and Spain is the origin of this superstition in Latin America. In Mexico and Central America, infants are considered at special risk for the evil eye (see mal de ojo, above) and are often given an amulet bracelet as protection, typically with an eye-like spot painted on the amulet. Another preventive measure is allowing admirers to touch the infant or child; in a similar manner, a person wearing an item of clothing that might induce envy may suggest to others that they touch it or some other way dispel envy. One traditional cure in Latin America involves a curandero (folk healer) sweeping a raw chicken egg over the body of a victim to absorb the power of the person with the evil eye. The egg is later broken into a glass with water and placed under the bed of the patient near the head. Sometimes it is checked immediately because the egg appears as if it has been cooked. When this happens it means that the patient did have Mal de Ojo. Somehow the Mal de Ojo has transferred to the egg and the patient immediately gets well. (Fever, pain and diarrhea, nausea/vomiting goes away instantly) In the traditional Hispanic culture of the Southwestern United States and some parts of Latin America, the egg may be passed over the patient in a cross-shaped pattern all over the body, while reciting The Lords Prayer. The egg is also placed in a glass with water, under the bed and near the head, sometimes it is examined right away or in the morning and if the egg looks like it has been cooked then it means that they did have Mal de Ojo and the patient will start feeling better. Sometimes if the patient starts getting ill and someone knows that they had stared at the patient, usually a child, if the person who stared goes to the child and touches them, the childs illness goes away immediately so the Mal de Ojo energy is released.In some parts of South America the act of ojear, which could be translated as to give someone the evil eye, is an involuntary act. Someone may ojear babies, animals and inanimate objects just by staring and admiring them. This may produce illness, discomfort or possibly death on babies or animals and failures on inanimate objects like cars or houses. Its a common belief that since this is an involuntary act made by people with the heavy look, the proper way of protection is by attaching a red ribbon to the animal, baby or object, in order to attract the gaze to the ribbon rather than to the object intended to be protected. Mexico Mal de ojo (Mal: Illness - de ojo: Of eye. "To be made ill by an eyes gaze") often occurs without the dimension of envy, but insofar as envy is a part of ojo, it is a variant of this underlying sense of insecurity and relative vulnerability to powerful, hostile forces in the environment. In her study of medical attitudes in the Santa Clara Valley of California, Margaret Clark arrives at essentially the same conclusion: "Among the Spanish-speaking folk of Sal si Puedes, the patient is regarded as a passive and innocent victim of malevolent forces in his environment. These forces may be witches, evil spirits, the consequences of poverty, or virulent bacteria that invade his body. The scapegoat may be a visiting social worker who unwittingly cast the evil eye... Mexican folk concepts of disease are based in part on the notion that people can be victimized by the careless or malicious behavior of others".Another aspect of the mal ojo syndrome in Ixtepeji is a disturbance of the hot-cold equilibrium in the victim. According to folk belief, the bad effects of an attack result from the "hot" force of the aggressor entering the childs body and throwing it out of balance. Currier has shown how the Mexican hot-cold system is an unconscious folk model of social relations upon which social anxieties are projected. According to Currier, "the nature of Mexican peasant society is such that each individual must continuously attempt to achieve a balance between two opposing social forces: the tendency toward intimacy and that toward withdrawal. [It is therefore proposed] that the individuals continuous preoccupation with achieving a balance between heat and cold is a way of reenacting, in symbolic terms, a fundamental activity in social relations." Puerto Rico In Puerto Rico, Mal de Ojo or "Evil Eye" is believed to be caused when someone gives a wicked glare of jealousy to someone, usually when the person receiving the glare is unaware. The jealousy can be disguised into a positive aspect such as compliments or admiration. Mal de Ojo is considered a curse and illness. It is believed that without proper protection, bad luck, injury, and illness are expected to follow. Mal de Ojo impact is believed to affect speech, relationships, work, family and most notably, health. Since Mal de Ojo centers around envy and compliments, it creates fear of interacting with people that are outside of their culture. Indirect harm could be brought to them or their family. When it comes to children, they are considered to be more susceptible to Mal de Ojo and it is believed that it can weaken them, leading to illness. As a child grows every effort is taken to protect them. When diagnosing Mal de Ojo, it is important to notice the symptoms. Physical symptoms can include: loss of appetite, body weakness, stomach ache, insomnia, fever, nausea, eye infections, lack of energy, and temperament. Environmental symptoms can include financial, family, and personal problems as simple as a car breaking down. It is important for those who believe to be aware of anything that has gone wrong because it may be linked to Mal de Ojo. Puerto Ricans are protected through the use of Azabache bracelets. Mal de Ojo can also be avoided by touching an infant when giving admiration. The most common practice of protection in Puerto Rico is the use of Azabache bracelets. These bracelets traditionally have a black or red coral amulet attached. The amulet is in the shape of a fist with a protruding index finger knuckle. Eggs are the most common method to cure Mal De Ojo. The red string and oils also used are more common in other cultures but still used in Puerto Rico depending on the Healer, or the person who is believed to have the ability to cure those who have been targeted. Ultimately, the act of giving someone the "Evil Eye" is a rather simple process and is practiced throughout the world. United States In 1946, the American occultist Henri Gamache published a text called Terrors of the Evil Eye Exposed! (later reprinted as Protection against Evil), which offers directions to defend oneself against the evil eye. Media and press coverage In some cultures, both over-complimenting and envy are said to cast a curse. Since ancient times such maledictions have been collectively called the evil eye. According to the book The Evil Eye by folklorist Alan Dundes, the beliefs premise is that an individual can cause harm simply by looking at anothers person or property. However, protection is easy to come by with talismans that can be worn, carried, or hung in homes, most often incorporating the contours of a human eye. In Aegean countries, people with light-colored eyes are thought to be particularly powerful, and amulets in Greece and Turkey are usually blue orbs. Indians and Jews use charms with palm-forward hands with an eye in the center; Italians employ horns, phallic shapes meant to distract spell casters. Names in various languages In most languages, the name translates literally into English as "bad eye", "evil eye", "evil look", or just "the Eye". Some variants on this general pattern from around the world are: In Albanian it is known as "syri i keq" (Standard and Tosk), or as "syni keq" (Gheg) meaning "bad eye". Also "mësysh" is used commonly, meaning "cast an evil eye". In Arabic, ʿayn al-ḥasūd, عين الحسود, "the eye of envy". ʿAyn ḥārrah (عين حارّة) is also used, literally translating to "hot eye". In Armenian, char atchk (չար աչք) "evil eye" or "bad eye". Regarding the act of giving an evil gaze, it is said (directly translated), "to give with the eye" or in Armenian, "atchkov tal". In Azerbaijani, "Göz dəyməsi" – translating as being struck by an eye In Chinese it is called 邪惡之眼 (Traditional Chinese characters) / 邪恶之眼 (Simplified Chinese characters) (xié è zhī yǎn, literally "evil eye") or simply 邪眼 (xié yǎn). In Corsican it is called "lOchju" (The Eye). In Dutch it is called "het boze oog", literally "the malicious eye" or "the angry eye". In Esperanto, it is called "malica okulo" (malicious eye). In Estonian, its called "kuri silm" (evil/angry eye) In Finnish, its called "paha silmä" (evil/bad eye) In French, it is named "le mauvais œil" (The bad eye) In Galician, it is called "meigallo", from meiga, "witch" (and maybe -allo, diminutive or aumentative suffix; or contracted with either ollo, "eye"; or allo, "garlic"). In German, it is called "böser Blick", literally "evil gaze". In Greek, to matiasma (μάτιασμα) or mati (μάτι) someone refers to the act of casting the evil eye (mati being the Greek word for eye); also: vaskania (βασκανία, the Greek word for jinx) In Hebrew, ʿáyin hā-ráʿ (עַיִן הָרַע, "eye of evil") In Hindi and other languages of South Asia, (Hindi: nazar (नज़र); nazar lagna (नज़र लगना)) means to be afflicted by the evil eye. (However, it generally has no evil connotations because a doting mothers eye can supposedly also cause harm.) In Hungarian, gonosz szem means "evil eye", but more widespread is the expression szemmelverés (lit. "beating with eye"), which refers to the supposed/alleged act of harming one by an evil look In Irish, the term drochshúil is used for the evil eye, being a compound of droch (bad, poor, evil, ill) and súil (eye). This can also be used to refer to someone with weak eyesight. In Indonesian the word dengki refers to evil eye. In Italian, the word malocchio (pronounced [maˈlɔkkjo]) refers to the evil eye. In Japanese it is known as "邪視" ("jashi"). In Kurdish, it is called "Çav pîs/Chaw pis/ چاو پیس" In Lithuanian evil eye is known as "pikta akis", while act of evil watching is called "nužiūrėjimas" (noun), "nužiūrėti" (verb). In Malay, it is called mata jahat, meaning literally "bad/evil eye". In Malayalam it is known as kannu veykkuka – to cast an evil eye while "kannu peduka" means to be on the receiving end of the malefic influence. "kannu dosham" refers to a bad effect caused by an evil eye. In Maltese it is known as "l-għajn". It is a common symbol for warding off evil intentions. In Neapolitan it is known as "o mmauocchje" which translates literally into "the evil/bad/maleficent eye", which afflicts people, especially women and children who are supposedly the most vulnerable, with multiple issues and problems, stemming from pre-natal issues, miscarriages, early childhood death or sickness or death of a mother during birth, as well as afflicting women with infertility, sexual problems, early widowhood, etc., while afflicted men suffer from cancer, laziness, greed, gluttony, and other diseases, disabilities and ailments. In Persian it is known as "چشم‌ زخم" (injurious look/eyes causing injury) or "چشم شور" (omen eye) "Cheshmeh Hasood", meaning Jealous eye, or "Cheshme Nazar" meaning evil eye. In Polish it is known as "złe oko" or "złe spojrzenie" (evil eye/an evil glare). In Portuguese, it is called "mau olhado", ou "olho gordo" (literally "fat eye"). The first expression is used in Portugal and the second one is more common in Brazil. In Romanian, it is known as "deochi", meaning literally "By-eye": a curse put on you by a gaze with evil intentions/ jealousy. In Russian, "дурной глаз" (durnoy glaz) means "bad/evil eye"; "сглаз" (sglaz) literally means "from eye". In Sanskrit, an ancient Indo-Aryan language, it is called "drishti dosha" (दृष्टि दोष) meaning malice caused by evil eye. (But cf. "drishti (yoga)".) In Serbo-Croatian (Serbian, Croatian, Bosnian and Montenegrin), it is called Urokljivo oko (Cyr. Урокљиво око). The first word is an adjective of the word urok/урок, which means spell or curse, and the second word means eye. In Slovak, it is known as "z očí", meaning "(coming) from eyes". In Slovene, it is known as "Zlobno oko", meaning "evil eye". In Somali, it is called "il", or "ilaaco" or "sixir" (the first two words literally meaning "eye" and the other word meaning black magic) In Sinhala it is known as "ඇස්වහ" (æsvaha). In Spanish, mal de ojo literally means "evil from the Eye" as the name does not refer to the actual eye but to the evil that supposedly comes from it. Casting the evil eye is then echar mal de ojo, i.e. "to cast evil from the Eye". In Berber languages(Tamazight/Tamaziɣt/ⵜⴰⵎⴰⵣⵉⵖⵜ/ⵜⵎⵣⵗⵜ) it is called Tafust (ⵜⴰⴼⵓⵙⵜ) which means little hand In Tagalog, it is known as ohiya or usog, which is a culture-bound syndrome where a visit by a stranger afflicts a child with sudden illness and convulsions. In Tamil, "கண் படுதல்" (kan padudhal) literally means "casting an eye" (with an intention to cause harm). "கண்ணூறு" (kannooru) "harm from the eye" In Trinidadian Creole it is called maljo, derived from the French mal yeux meaning "bad eye" In Turkish kem göz means evil eye and the cure is having a "nazar boncuğu", the nazar amulet. In Urdu, nazar (نظر) Chashm-é bad (چشمِ بد) or Nazar-é bad (نظرِبد); nazar lagna means to be afflicted by the evil eye. In Welsh y llygad drwg, y llygad mall, drwglygad In Yiddish עין הרע (ayin hora עין הרע) See also Amulets and other protections Azabache – Spanish and Latin American amulet used to ward off the evil eye, especially in the form of a pin placed on infants Eyespot (mimicry) – as found in living organisms Fatimas hand – a palm-shaped amulet popular throughout North Africa and in the Middle East and commonly used in jewellery and wall hangings. Depicting the open right hand, an image recognized and used as a sign of protection in many times throughout history, Fatimas hand (a.k.a. Hamsa) has been traditionally believed to provide defence against the evil eye. Harmal – plant used as protection against the evil eye Mirror armour – believed to protect not from only cold steel and arrows, but also from the evil eye Red string (Kabbalah) – a bracelet in Judaism worn to ward off the evil eye Jumbie beads – poisonous seeds of the Rosary Pea tree which are used to make jewelry that wards off maljo (bad eye) and evil spirits in Trinbagonian tradition The color blue – in Trinidad and Tobago is believed to ward off the evil eye, particularly when worn as garments or accessories, as well as in indigo dye Creatures Balor – a character in Irish legend Basilisk – Death glance/petrifying glance Beholder (Dungeons & Dragons) – modern invention Cockatrice – Death glance/petrifying glance Medusa and Gorgon – Petrification glance, picture also used as protection from the evil eye Petrifaction in mythology and fiction Concepts Eye of Providence – a symbol showing an eye surrounded by rays of light or a glory, and usually enclosed by a triangle. Lashon hara – Jewish concept of the "evil tongue" Matthew 6:23 "If thine eye be evil" – The evil eye as ungenerosity of spirit, hence darkness/blindness/evil itself Rule of Three Scopophobia – fear of being stared at Usog – a Filipino version [South sotho] leihlo la bobe kapa sefahlamahlo. Meaning an eye for all bad things in others or an idea to make others stumble and fall..or a hot smack across the face. Explanatory notes References Further reading External links "The Evil Eye" at Fortean Times The Evil Eye by Frederick Thomas Elworthy Evil Eye by Hakim Bey "What is an Ayin Hara (evil eye)?" – "Ask the Rabbi" at Ohr Somayach Meaning of the Evil Eye Myth
Persistent polyclonal B-cell lymphocytosis	Persistent polyclonal B-cell lymphocytosis (PPBL) is an anomaly of the human immune system characterized by mildly elevated levels of white blood cells (called leukocytosis), chronic, stable absolute polyclonal B-cell lymphocytosis, elevated polyclonal IgM and binucleated cells. Although cases of non-smoking women or men have been reported, patients are predominantly young smoking women. Signs and symptoms Ten percent of patients present with splenomegaly and lymphadenopathy. Some patients report a varying degree of fatigue, consistent with a chronic fatigue syndrome, or postviral fatigue as seen in EBV infections while others remain asymptomatic. Genetics Genetically, PPBL has been associated with a few unusual genetic characteristics. Among them, it is associated with a particular genetic variant of the human leukocyte antigen called HLA-DR7. This variant is normally present in 26% in the Caucasian population. Chromosome analysis has detected an isochromosome +i(3q), with or without premature chromosome condensation. Also, a t(14;18)(q22;21) bcl-2/IgH rearrangement has been described, as usually seen in follicular lymphoma. Immunologically, peripheral B-cells show more functional IgD+ positive CD27 cells than usual. Prognosis In the followup of 111 patients, most remained stable and event free. However, two patients developed IgM gammopathy 2 lung cancer; one developed cervical cancer and three developed non-Hodgkins lymphoma. The possibility of developing a clonal proliferation, malignant lymphoma or secondary solid cancer led the authors to conclude not to classify PPBL as a benign pathology, as has been previously postulated but rather to recommend a careful and continued clinical and biological longterm follow-up. == References ==
Skin tag	A skin tag, or acrochordon (pl. acrochorda), is a small benign tumor that forms primarily in areas where the skin forms creases (or rubs together), such as the neck, armpit and groin. They may also occur on the face, usually on the eyelids. Though tags up to half an inch (12.7 mm) long have been seen, they are typically the size of a grain of rice. The surface of an acrochordon may be smooth or irregular in appearance and is often raised from the surface of the skin on a fleshy stalk called a peduncle. Microscopically, an acrochordon consists of a fibrovascular core, sometimes also with fat cells, covered by an unremarkable epidermis. However, tags may become irritated by shaving, clothing, jewellery or eczema. Etiology Skin tags are thought to occur from skin rubbing up against skin, since they are so often found in skin creases and folds. Studies have shown existence of low-risk human papillomaviruses 6 and 11 in skin tags, hinting at a possible role in its pathogenesis although one 2012 study found no association between skin tags and low risk or high risk HPV. Acrochorda have been reported to have a prevalence of 46% in the general population. A causal genetic component is thought to exist. They are also more common in women than in men. Acrochorda were once thought to be associated with colorectal polyps, but studies have shown no such connection exists. Rarely, they can be associated with Birt–Hogg–Dubé syndrome, acromegaly, or polycystic ovary syndrome.Elevated blood sugar and insulin is linked to an increased incidence of skin tags through an unknown mechanism. Treatment If removal is desired or warranted, it can be achieved by a dermatologist, general practitioner or similarly trained professional who may use cauterization, cryosurgery, excision, laser, or surgical ligation to remove the acrochorda. Varied home remedies are also available, but most are unproven and some (e.g. tea tree oil) may cause allergic skin reactions. See also Molluscum contagiosum (a viral disease which is similar in appearance and grows in similar areas) List of cutaneous neoplasms associated with systemic syndromes Papilloma Cutaneous horn References == External links ==
Thunderstorm asthma	Thunderstorm asthma (also referred to in the media as thunder fever or a pollen bomb) is the triggering of an asthma attack by environmental conditions directly caused by a local thunderstorm. It has been proposed that during a thunderstorm, pollen grains can absorb moisture and then burst into much smaller fragments with these fragments being easily dispersed by wind. While larger pollen grains are usually filtered by hairs in the nose, the smaller pollen fragments are able to pass through and enter the lungs, triggering the asthma attack. History The phenomenon has been recognised for a significant period of time with a study of an event in Birmingham, England, noting the correlation between thunderstorms and hospitalisations. This fact that these were not isolated events and were part of an ongoing pattern of events is clearly documented in the review "Thunderstorm asthma, an overview of the evidence base". A significant impetus in the study of the phenomenon occurred after an event in 2016 in Melbourne, Australia. Since then there have been further reports of widespread thunderstorm asthma in Wagga Wagga, Australia; London, England; Naples, Italy; Atlanta, United States; and Ahvaz, Iran. The outbreak in Melbourne, in November 2016, that overwhelmed the ambulance system and some local hospitals, resulted in at least nine deaths. There was a similar incident in Kuwait in early December, 2016 with at least 5 deaths and many admissions to the ICU. Statistics Many of those affected during a thunderstorm asthma outbreak may have never experienced an asthma attack before.It has been found 95% of those that were affected by thunderstorm asthma had a history of hayfever, and 96% of those people had tested positive to grass pollen allergies, particularly rye grass. A rye grass pollen grain can hold up to 700 tiny starch granules, measuring 0.6 to 2.5 μm, small enough to reach the lower airways in the lung. Prevention Patients with a history of grass allergies should be tested for asthma and treated for the grass allergies and asthma if also present. Patients with known asthma should be treated and counseled on the importance of adherence to preventative medication protocols. Preventative treatment found useful for severe asthma includes Allergen immunotherapy (AIT) particularly sublingual immunotherapy (SLIT). Significant events 6 July 1983 (1983-07-06) – 7 July 1983 (1983-07-07): Birmingham, England 8 November 1987 (1987-11-08): Melbourne, Australia 29 November 1989 (1989-11-29) – 30 November 1989 (1989-11-30): Melbourne, Australia 24 July 1994 (1994-07-24) – 25 July 1994 (1994-07-25): London, England 30 October 1997 (1997-10-30): Wagga Wagga, Australia 4 June 2004 (2004-06-04): Naples, Italy 25 November 2010 (2010-11-25): Melbourne, Australia 2 November 2013 (2013-11-02): Ahvaz, Iran 21 November 2016 (2016-11-21): Melbourne, Australia 1 December 2016 (2016-12-01): Kuwait and Riyadh, Saudi Arabia == References ==
Dysplasia	Dysplasia is any of various types of abnormal growth or development of cells (microscopic scale) or organs (macroscopic scale), and the abnormal histology or anatomical structure(s) resulting from such growth. Dysplasias on a mainly microscopic scale include epithelial dysplasia and fibrous dysplasia of bone. Dysplasias on a mainly macroscopic scale include hip dysplasia, myelodysplastic syndrome, and multicystic dysplastic kidney. In one of the modern histopathological senses of the term, dysplasia is sometimes differentiated from other categories of tissue change including hyperplasia, metaplasia, and neoplasia, and dysplasias are thus generally not cancerous. An exception is that the myelodysplasias include a range of benign, precancerous, and cancerous forms. Various other dysplasias tend to be precancerous. The words meanings thus cover a spectrum of histopathological variations. Microscopic scale Epithelial dysplasia Epithelial dysplasia consists of an expansion of immature cells (such as cells of the ectoderm), with a corresponding decrease in the number and location of mature cells. Dysplasia is often indicative of an early neoplastic process. The term dysplasia is typically used when the cellular abnormality is restricted to the originating tissue, as in the case of an early, in-situ neoplasm.Dysplasia, in which cell maturation and differentiation are delayed, can be contrasted with metaplasia, in which cells of one mature, differentiated type are replaced by cells of another mature, differentiated type. Myelodysplastic syndrome Myelodysplastic syndromes (MDS) are a group of cancers in which immature blood cells in the bone marrow do not mature and therefore do not become healthy blood cells. Problems with blood cell formation result in some combination of low red blood cells, low platelets, and low white blood cells. Some types have an increase in immature blood cells, called blasts, in the bone marrow or blood. Fibrous dysplasia of bone Fibrous dysplasia of bone is a disorder where normal bone and marrow is replaced with fibrous tissue, resulting in formation of bone that is weak and prone to expansion. As a result, most complications result from fracture, deformity, functional impairment and pain. Macroscopic scale Hip dysplasia Hip dysplasia is an abnormality of the hip joint where the socket portion does not fully cover the ball portion, resulting in an increased risk for joint dislocation. Hip dysplasia may occur at birth or develop in early life. Regardless, it does not typically produce symptoms in babies less than a year old. Occasionally one leg may be shorter than the other. The left hip is more often affected than the right. Complications without treatment can include arthritis, limping, and low back pain. Multicystic dysplastic kidney Multicystic dysplastic kidney (MCDK) is a condition that results from the malformation of the kidney during fetal development. The kidney consists of irregular cysts of varying sizes. Multicystic dysplastic kidney is a common type of renal cystic disease, and it is a cause of an abdominal mass in infants. Etymology From Ancient Greek δυσ- dys-, "bad" or "difficult" and πλάσις plasis, "formation". The equivalent surface analysis, in parallel with classical compounds, is dys- + -plasia. See also Pleomorphism List of biological development disorders References == Further reading ==
Thermal burn	A thermal burn is a type of burn resulting from making contact with heated objects, such as boiling water, steam, hot cooking oil, fire, and hot objects. Scalds are the most common type of thermal burn suffered by children, but for adults thermal burns are most commonly caused by fire. Burns are generally classified from first degree up to fourth degree, but the American Burn Association (ABA) has categorized thermal burns as minor, moderate, and major, based almost solely on the depth and size of the burn. Causes Hot liquids and steam Scalding is a type of thermal burn caused by boiling water and steam, commonly suffered by children. Scalds are commonly caused by accidental spilling of hot liquids, having water temperature too high for baths and showers, steam from boiling water or heated food, or getting splattered by hot cooking oil. Scalding is usually a first- or second-degree burn, and third-degree burn can sometimes result from prolonged contact. Nearly three quarters of all burn injuries suffered by young children are scalds. Fire Fire causes about 50% of all cases of thermal burns in the United States. The most frequent event where people get burned by fire is during house fires encountered by firefighters and trapped occupants, where 85% of all fire deaths take place. Fireworks are another notable cause of fire burns, especially among adolescent males on holidays such as Independence Day in the US. The most common cause of injury by fire or flame in children is touching candle flame. In some regions, such as the western United States, wildfires are responsible for an increase in burn injuries. Wildfires can suddenly shift due to changing wind directions, making it harder for firefighters and eyewitnesses to avoid getting burned. If clothing catches fire, third-degree burn can develop in a matter of just a few seconds. Hot objects Solid objects that are hot can also cause contact burns, especially in children, who may intentionally touch things they dont know are too hot to touch. Such burns imprinted on the skin usually form a pattern that resembles the object. Sources of burns from solid objects include ashes and coal, irons, soldering equipment, frying pans and pots, oven containers, light bulbs, and exhaust pipes. Pathophysiology There are three (or sometimes four) degrees of burns, in ascending order of severity and depth. For more information, see Signs and symptoms. According to Jacksons thermal wound theory, there are three zones of major burn injury. Zone of coagulation is the area that sustained maximum damage from the heat source. Proteins become denaturated, and cell death is imminent due to destruction of blood vessels, resulting in ischemia to the area. Injury at this area is irreversible (coagulative necrosis & gangrene) Zone of stasis surrounds the coagulation area, where tissue is potentially salvageable. This is the main area of focus when treating burn injuries. Zone of hyperemia is the area surrounding the zone of stasis. Perfusion is adequate due to patent blood vessels, and erythema occurs due to increased vascular permeability. Prevention It is important to teach children how to avoid fire and scalding. Firefighters and community leaders often lead such programs in schools and clinics.Smoke alarms installed in homes can reduce deaths resulting from fire by half. Homeowners should change batteries at least once a year and replace smoke alarms every decade. Before fire occurs, a family should practice evacuating the home, and when fire occurs the family must leave the residence immediately (within two minutes). Sources of flame, like matches, should be kept out of childrens reach. Stoves, ovens, space-heaters, and candles must not be left unattended, and flammable objects must be kept at least 30 cm away from open flames. Fire extinguishers should be stored in the kitchen, where most house fires start.To prevent children from getting burned, water temperature must not be set too high when taking baths or washing hands, nonflammable sleepwear should be worn, back burners should be used when cooking something on the stove, and hot foods, drinks, and irons should be kept away from the edge of counter and table. Oven mitts and potholders must be used in handling hot containers. Care should be taken when taking hot foods out of microwave ovens, and covers should be opened gently to reduce the risk of steam burns. Treatment The most important first action is to stop the burning process. The source of the burn should promptly be removed (or the patient removed from the source). If the person is on fire, he/she must be told to stop, drop and roll, or extinguish the fire by covering them with heavy blanket, wool, coat, or rug. Burning clothing should be removed as should all jewelry that could act as a tourniquet as swelling occurs, but burned clothing stuck to the skin must not be removed. Cooling the burn with cold running water has been shown to be beneficial if accomplished within 30 minutes of the injury. The pain or inflammation can then be effectively treated using acetaminophen (paracetamol), or ibuprofen. Ice, butter, cream and ointment cannot be used since they can worsen the burn.Severe burn patients are often treated through trauma resuscitation, airway management, fluid resuscitation, blood transfusion, wound management, and skin grafting, as well as the use of antibiotics. Outcome 95% of people hospitalized for thermal burns survive. Survival rates have increased steadily over the last half century due to advances in treatment and better burn centers. Patients with uncomplicated burns have a 99.7% survival rate. Three risk factors—patient age above 60, burns covering more than 40% of the body, and inhalation injury—greatly reduce the odds of survival, which decline to 97% with any one of these complications, to 67% with any two, and to only 10% in cases with all three. Epidemiology In the United States, over two million people required medical attention for thermal burns every year. About 1 in 30 of those victims (75,000) are hospitalized for thermal burns every year, with a third of those patients staying in the hospital for more than two months. About 14,000 Americans die each year from burns. Children Thermal burns are one of the most common early childhood injuries. In the United States, burns are the third most common cause of accidental death among children. Nearly 96,000 children around the world died as a result of thermal burns in 2004, and 61,400 died in 2008 from thermal injuries. Deaths from burns dropped by 55% from 1999 to 2011. Burns are the only mode of unintentional injury which more girls suffer from than boys worldwide, including by fire. References External links Burns at MedlinePlus
Aminoaciduria	Aminoaciduria occurs when the urine contains abnormally high amounts of amino acids. In the healthy kidney, the glomeruli filter all amino acids out of the blood, and the renal tubules then reabsorb over 95% of the filtered amino acids back into the blood.In overflow aminoaciduria, abnormally high concentrations of amino acids in the blood plasma overwhelm the resorptive capacity of the renal tubules, resulting in high concentrations of amino acids in the urine. This may be caused by congenital disorders of amino acid metabolism, for example, phenylketonuria, or may be secondary to liver disease.In renal aminoaciduria, the renal tubules are unable to reabsorb the filtered amino acids back into the blood, causing high concentrations of amino acids in the urine. This may be caused by a defect in the transport proteins in the renal tubule, for example, as occurs in Hartnup disease, or may be due to damage to the kidney tubule, for example, as occurs in Fanconi syndrome. References == External links ==
Bilateral frontoparietal polymicrogyria	Bilateral frontoparietal polymicrogyria is a genetic disorder with autosomal recessive inheritance that causes a cortical malformation. Our brain has folds in the cortex to increase surface area called gyri and patients with polymicrogyri have an increase number of folds and smaller folds than usual. Polymicrogyria is defined as a cerebral malformation of cortical development in which the normal gyral pattern of the surface of the brain is replaced by an excessive number of small, fused gyri separated by shallow sulci and abnormal cortical lamination. From ongoing research, mutation in GPR56, a member of the adhesion G protein-coupled receptor (GPCR) family, results in BFPP. These mutations are located in different regions of the protein without any evidence of a relationship between the position of the mutation and phenotypic severity. It is also found that GPR56 plays a role in cortical pattering. Presentation Symptoms: Developmental delay, Psychomotor delay, Mental retardation - moderate to severe, Exaggerated reflexes and Seizures (epilepsy) Associated conditions BFPP is a cobblestone-like cortical malformation of the brain. Disruptions of cerebral cortical development due to abnormal neuronal migration and positioning usually lead to cortical disorders, which includes cobblestone lissencephaly. Cobblestone lissencephaly is typically seen in three different human congenital muscular dystrophy syndromes: Fukuyama congenital muscular dystrophy, Walker-Warburg syndrome, and muscle-eye-brain disease. In cobblestone lissencephaly, the brain surface actually has a bumpy contour caused by the presence of collections of misplaced neurons and glial cells that have migrated beyond the normal surface boundaries of the brain. Sometimes regions populated by these misplaced cells have caused a radiologic misdiagnosis of polymicrogyria. However, the presence of other abnormalities in these cobblestone lissencephaly syndromes, including ocular anomalies, congenital muscular dystrophy, ventriculomegaly, and cerebellar dysplasia, usually distinguishes these disorders from polymicrogyria. There are no anatomopathologic studies that have characterized the pattern of cortical laminar alterations in patients with GPR56 gene mutations, but it has been suggested that the imaging characteristics of BFPP, including myelination defects and cerebellar cortical dysplasia, are reminiscent of those of the so-called cobblestone malformations (muscle-eye-brain disease and Fukuyama congenital muscular dystrophy) that are also associated with N-glycosylation defects in the developing brain.Lissencephaly ("smooth brain") is the extreme form of pachygyria. In lissencephaly, few or no sulci are seen on the cortical surface, resulting in a broad, smooth appearance to the entire brain. Lissencephaly can be radiologically confused with polymicrogyria, particularly with low-resolution imaging, but the smoothness and lack of irregularity in the gray-white junction, along with markedly increased cortical thickness, distinguishes lissencephaly. GPR56 mutation also can cause a severe encelphalopathy which is associated with electro clinical features of the Lennox-Gastaut syndrome. Lennox-Gastaut syndrome can be cryptogenic or symptomatic, but the symptomatic forms have been associated with multiple etiologies and abnormal cortical development. BFPP caused by GPR56 mutations is a manifestation of a malformation of cortical development that causes Lennox-Gastaut Syndrome.Polymicrogyria is often confused with pachygyria; therefore, it needs to be distinguished from pachygyria, a distinct brain malformation in which the surface folds are excessively broad and sparse. Pachygyria and polymicrogyria may look similar on low-resolution neuroimaging such as CT because the cortical thickness can appear to be increased and the gyri can appear to be broad and smooth in both conditions. This is why higher resolution neuroimaging, such as an MRI, is necessary for proper diagnosis. Genetics The GPR56 is grouped in the B family of GPCRs. This GPCR group have long N termini characterized by an extracellular “cysteine box” and hydrophilic, potentially mucin-rich. The cysteine box contains four conserved cysteines and two tryptophans arranged in a specific fashion (C-x2-W-x6-16-W-x4-C-x10-22-C-x-C) just before the first transmembrane domain and serves as a cleavage site in some members of this group of G protein–coupled receptors. Although, the molecular and cellular mechanisms of how GPR56 regulates brain development remain largely unknown. These types of receptors play an essential role in biological processes including embryonic development, central nervous system (CNS), immune system, and tumorigenesis. Mode of inheritance Parents of a proband The parents of an affected individual are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes (carriers) are asymptomatic.Sibs of a proband At conception, each sibling of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once an at-risk sibling is known to be unaffected, the risk of his/her being a carrier is 2/3. Heterozygotes (carriers) are asymptomatic.Offspring of a proband Offspring of a proband are obligate heterozygotes and will therefore carry one mutant allele. In populations with a high rate of consanguinity, the offspring of a person with GPR56-related BFPP and a reproductive partner who is a carrier of GPR56-related BFPP have a 50% chance of inheriting two GPR56 disease-causing alleles and having BFPP and a 50% chance of being carriers.Other family members of a proband. Each sibling of the probands parents is at a 50% risk of being a carrier Diagnosis Diagnostic criteria for a BFPP patient entails a heterozygous genotype for a deletion of chromosome 16q12.1-q21 region, including GPR56 gene. To date the only gene known to be associated with polymicrogyria is GPR56. Testing for GPR56-related bilateral frontoparietal polymicrogyria is available clinically. Mutations in GPR56 hinders Collagen III, its specific ligand, to bind in a developing brain. To date, a total of fourteen BFPP-associated mutations have been identified, including one deletion, two splicing, and eleven missense mutations. Two mutations in the GPCR proteolytic site (GPS) domain, C346S and W349S, cause a brain malformation through trapping the mutated proteins in the endoplasmic reticulum.GPR56 are a part of the B class of the GPCR family, the largest cell surface gene family in the human genome. Within this family there are different types of bio-active molecules that transduce their signal to the intracellular compartment via interaction with this type of receptor. Children often present with developmental delay, spasticity, or seizures; they are also often microcephalic. Some patients with polymicrogyria go undiagnosed until they produce children with the disorder who have more severe manifestations. Retrospectively, these patients will often report some difficulty in their medical or educational history. BFPP patients demonstrate mental retardation, language impairment, motor developmental delay, and seizure disorders such as epilepsy. The association of epilepsy is in approximately 50% to 85% of affected BFPP patients. The clinical manifestations of polymicrogyria are stable neurologic deficits: In the mildest form, polymicrogyria is unilateral with only one small region of the brain involved; neurologic problems may not be evident. In more severe forms, focal motor, sensory, visual, or cognitive problems may be present, depending on the location of the brain region affected. In the most severe forms, polymicrogyria is bilateral and generalized, resulting in severe intellectual disability, cerebral palsy, and refractory epilepsy. Individuals with the milder forms of polymicrogyria survive into adulthood, while those with the most severe forms, such as BFPP, may die at a young age as a result of such complications as seizures or pneumonia. The prevalence of isolated polymicrogyria is unknown. Researchers believe that it may be relatively common overall, although BFPP is probably rare. Radiological findings (MRI) demonstrated symmetric generalized polymicrogyria with decreasing anterior-posterior gradient, most prominent in frontoparietal cortex. Numerous gyrus on the cortex Small gyri and sulci Thin cortex Methods/tests There are different tests or methods used to determine GPR56 expression or visuals of the brain to analyze the specific sections that are affected. These tests for example, using animals such as mice, RNAi, Behavioral assay, Electron microscopy, CT scan, or MRI demonstrate different results that concludes an affected BFPP patient. MRIs reveal either irregularity to the cortical surface suggestive of multiple small folds or an irregular, scalloped appearance of the gray matter-white matter junction. Neuroimaging The diagnosis of polymicrogyria is typically made by magnetic resonance imaging (MRI) since computed tomography (CT) and other imaging methods generally do not have high enough resolution or adequate contrast to identify the small folds that define the condition. The cerebral cortex often appears abnormally thick as well because the multiple small gyri are fused, infolded, and superimposed in appearance.Neuropathology Gross neuropathologic examination reveals a pattern of complex convolutions to the cerebral cortex, with miniature gyri fused and superimposed together, often resulting in an irregular brain surface. The cortical ribbon can appear excessively thick as a result of the infolding and fusion of multiple small gyri.Microscopic examination demonstrates that the cerebral cortex is in fact abnormally thin and has abnormal lamination; typically the cortex is unlayered or has four layers, in contrast to the normal six layers. The most superficial layers between adjacent small gyri appear fused, with the pia (layer of the meninges) bridging across multiple gyri. Prenatal diagnosis for BFPP is also available for pregnancies at risk if the GPR56 mutations have been identified in an affected family member. Treatment Treatment plans will vary depending on the severity of the condition and its evidences in each patient. Areas that will probably need to be evaluated and assessed include speech, vision, hearing and EEG. Treatment measures may include physical therapy, occupational therapy, Speech therapy, anti-seizure drugs and orthotic devices. Surgery may be needed to assuage spastic motor problems. Various supportive measures such as joint contractures that could prevent complications. Genetic counseling may also be recommended Prognosis Once the diagnosis of polymicrogyria has been established in an individual, the following approach can be used for discussion of prognosis: A pregnancy history should be sought, with particular regard to infections, trauma, multiple gestations, and other documented problems. Screening for the common congenital infections associated with polymicrogyria with standard TORCH testing may be appropriate. Other specific tests targeting individual neurometabolic disorders can be obtained if clinically suggested. The following may help in determining a genetic etiology: Family history It is important to ask for the presence of neurologic problems in family members, including seizures, cognitive delay, motor impairment, pseudobulbar signs, and focal weakness because many affected family members, particularly those who are older, may not have had MRI performed, even if these problems came to medical attention. In addition, although most individuals with polymicrogyria do present with neurologic difficulties in infancy, childhood, or adulthood, those with mild forms may have no obvious deficit or only minor manifestations, such as a simple lisp or isolated learning disability. Therefore, if a familial polymicrogyria syndrome is suspected, it may be reasonable to perform MRI on relatives who are asymptomatic or have what appear to be minor findings. The presence of consanguinity in a childs parents may suggest an autosomal recessive familial polymicrogyria syndrome. Physical examination A general physical examination of the proband may identify associated craniofacial, musculoskeletal, or visceral malformations that could indicate a particular syndrome. Neurologic examination should assess cognitive and mental abilities, cranial nerve function, motor function, deep tendon reflexes, sensory function, coordination, and gait (if appropriate).Genetic testing See also Epilepsy Phenome/Genome Project References External links Bilateral Frontalparietal Polymicrogyria at NIHs Office of Rare Diseases
Agoraphobia without history of panic disorder	Agoraphobia without a history of panic disorder (also called primary agoraphobia) is an anxiety disorder where the individual with the diagnosis does not meet the DSM-5 criteria for panic disorder. Agoraphobia typically develops as a result of having panic disorder. In a small minority of cases, however, agoraphobia can develop by itself without being triggered by the onset of panic attacks. Agoraphobia can be caused by traumatic experiences, such as bullying or abuse. Historically, there has been debate over whether agoraphobia without panic genuinely existed, or whether it was simply a manifestation of other disorders such as panic disorder, generalized anxiety disorder, avoidant personality disorder and social phobia. One researcher said: "out of 41 agoraphobics seen (at a clinic) during a period of 1 year, only 1 fit the diagnosis of agoraphobia without panic attacks, and even this particular classification was questionable...Do not expect to see too many agoraphobics without panic". In spite of this earlier skepticism, current thinking is that agoraphobia without panic disorder is indeed a valid, unique illness which has gone largely unnoticed, since those with the condition are far less likely to seek clinical treatment. Diagnostic criteria (DSM-IV-TR) According to the DSM-IV-TR, a widely used manual for diagnosing mental disorders, the condition is diagnosed when agoraphobia is present without panic disorder where symptoms are not caused by or are unreasonable to an underlying medical problem or pharmacological influence. See also Panic disorder Agoraphobia References Spiti Raffaello, Scarpato Maria Alessandra, Spiti Alessandra (2011). "Primary agoraphobia specific symptoms: from natural information to mental representations". Italian Journal of Psychopathology, 17 (3): 265–276.http://www.gipsicopatol.it/issues/2011/vol17-3/02Spiti.pdf Agoraphobia Without a History or Panic Disorder May Be Part of the Panic Disorder Syndrome. Journal of Nervous & Mental Disease, 190(9):624-630, September 2002. The Relationship of Agoraphobia and Panic in a Community Sample of Adolescents and Young Adults. External links Anxiety Disorders Association of America Information for families, clinicians & researchers Anxiety Disorders Association of Canada Registered Canadian non-profit organization, promotes prevention, treatment & management of anxiety disorders ANXIETY UK (Formerly the National Phobics Society) Nationally registered charity in the UK; provides information, support & understanding The Phobic Trust (Of New Zealand) Registered charitable trust in New Zealand; provides information about treatment, education & support to people with anxiety disorders South African Depression and Anxiety group (National Charity) Counseling, mental health awareness programs: media & public speaking outreach & rural outreach initiatives Agoraphobia without history of panic disorder at Curlie Self help guide (NHS Direct)
Familial hypocalciuric hypercalcemia	Familial hypocalciuric hypercalcemia (FHH) is an inherited condition that can cause hypercalcemia, a serum calcium level typically above 10.2 mg/dL; although uncommon. It is also known as familial benign hypocalciuric hypercalcemia (FBHH) where there is usually a family history of hypercalcemia which is mild, a urine calcium to creatinine ratio <0.01, and urine calcium <200 mg/day. Signs and symptoms Most cases of familial hypocalciuric hypercalcemia are asymptomatic. Laboratory signs of FHH include: High blood levels of calcium (hypercalcemia) A low amount of calcium excreted in the urine (Ca excretion rate < 0.02 mmol/L) High blood levels of magnesium (hypermagnesemia) High normal to mildly elevated parathyroid hormone Causes Types include: Pathogenesis Most cases of FHH are associated with loss of function mutations in the calcium-sensing receptor (CaSR) gene, expressed in parathyroid and kidney tissue. These mutations decrease the receptors sensitivity to calcium, resulting in reduced receptor stimulation at normal serum calcium levels. As a result, inhibition of parathyroid hormone release does not occur until higher serum calcium levels are attained, creating a new equilibrium. This is the opposite of what happens with the CaSR sensitizer, cinacalcet. Functionally, parathyroid hormone (PTH) increases calcium resorption from the bone and increases phosphate excretion from the kidney which increases serum calcium and decreases serum phosphate. Individuals with FHH, however, typically have normal PTH levels, as normal calcium homeostasis is maintained, albeit at a higher equilibrium set point. As a consequence, these individuals are not at increased risk of the complications of hyperparathyroidism.Another form has been associated with chromosome 3q. Functions of the calcium-sensing receptor Parathyroid gland: mediates negative feedback mechanisms relating to PTH secretion. In normal individuals, PTH secretion decreases with increasing blood calcium levels. Loss of function abnormalities in the CaSR here cause hypercalcemia. Kidneys: mediates negative feedback mechanisms relating to calcium reabsorption from the tubular system. In normal individuals, reabsorption of calcium and other electrolytes decreases with increasing blood calcium level. Loss of function abnormalities in the CaSR here contribute to both hypercalcemia and hypocalciuria. Diagnosis As most cases of FHH are asymptomatic and benign, the diagnosis of FHH is less likely to be made. Typically, diagnosis is made in the pursuit of uncovering the etiology of hypercalcemia. Calcium levels are often in the high normal range or slightly elevated. Commonly, the parathyroid hormone level is checked and may be slightly elevated or also on the high normal end. Normally, high calcium should cause low PTH and so this level of PTH is inappropriately high due to the decreased sensitivity of the parathyroid to calcium. This may be mistaken for primary hyperparathyroidism. However, evaluation of urine calcium level will reveal a low level of urine calcium. This too is inappropriate as high serum calcium should result in high urine calcium. If urine calcium is not checked, this may lead to parathyroidectomy for presumed primary hyperparathyroidism Additionally as the name implies, there may be a family history of benign hypercalcemia.Ultimately, diagnosis of familial hypocalciuric hypercalcemia is made—as the name implies—by the combination of low urine calcium and high serum calcium. Treatment No treatment is generally required, as bone demineralisation and kidney stones are relatively uncommon in the condition. References == External links ==
Pituitary stalk interruption syndrome	Pituitary stalk interruption syndrome (PSIS) is a congenital disorder characterised by the triad of an absent or exceedingly thin pituitary stalk, an ectopic or absent posterior pituitary and/or absent or hypoplastic anterior pituitary. Presentation Affected individuals may present with hypoglycaemia during the neonatal period, or with growth retardation during childhood (those diagnosed in the neonatal period appear to be affected by a particularly severe form of the disorder). PSIS is a common cause of congenital hypopituitarism, and causes a permanent growth hormone deficit. Some PSIS-affected individuals may also present with adrenal hypoplasia (5-29%), diabetes insipidus (5-29%), primary amenorrhea (5-29%), hypothyroidism (30-79%), failure to thrive (80-99%), septooptic dysplasia (5-29%), and Fanconi anaemia. PSIS may be isolated, or, commonly, present with extra-pituitary malformations.PSIS features in neonates (may) include: hypoglycaemia (30-79%) (prolonged) jaundice micropenis (30-79%) cryptorchidism (5-29%) delayed intellectual development death in infancy (5-29%) congenital abnormalitiesPSIS features in later childhood (may) include: short stature (80-99%) seizures (5-29%) hypotension delayed intellectual development delayed puberty (30-79%)PSIS is associated with a higher frequency of breech presentation, Caeserian section, and/or low Apgar score, though these are likely consequences rather than causes. Cause The cause of the condition is as of yet unknown. Rare genetic mutations may cause familial cases, however, these account for less than 5% of cases. Diagnosis The diagnosis is confirmed through MRI. Management Treatment should commence as soon as a diagnosis is established to avoid complications, and consists of hormone replacement, particularly with growth hormone. Prognosis Prognosis is generally good in cases of prompt diagnosis and management. Delays may lead to seizures (due to hypoglycaemia), hypotension (due to cortisol deficiency), and/or intellectual disability (due to thyroid endocrine deficits). Due to the before-mentioned factors, mortality and morbidity is higher than that of the general population, particularly during the first 2 years of life. Epidemiology The prevalence of PSIS is unknown, however, some 1,000 cases have been reported either with or without the full triad. References == External links ==
Rash	A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell, and may be painful. The causes, and therefore treatments for rashes, vary widely. Diagnosis must take into account such things as the appearance of the rash, other symptoms, what the patient may have been exposed to, occupation, and occurrence in family members. The diagnosis may confirm any number of conditions. The presence of a rash may aid diagnosis; associated signs and symptoms are diagnostic of certain diseases. For example, the rash in measles is an erythematous, morbilliform, maculopapular rash that begins a few days after the fever starts. It classically starts at the head, and spreads downwards. Differential diagnosis Common causes of rashes include: Food allergy Medication side effects Anxiety Allergies, for example to food, dyes, medicines, insect stings, metals such as zinc or nickel; such rashes are often called hives. Skin contact with an irritant Fungal infection, such as ringworm Balsam of Peru Reaction to vaccination Skin diseases such as eczema or acne Exposure to sun (sunburn) or heat Friction due to chafing of the skin Irritation such as caused by abrasives impregnated in clothing rubbing the skin. The cloth itself may be abrasive enough for some people Secondary syphilis Poor personal hygieneUncommon causes: Autoimmune disorders such as psoriasis Lead poisoning Pregnancy Repeated scratching on a particular spot Lyme disease Scarlet fever COVID-19 (see Symptoms of COVID-19 § Other) Conditions Diagnostic approach The causes of a rash are numerous, which may make the evaluation of a rash extremely difficult. An accurate evaluation by a provider may only be made in the context of a thorough history, i.e. medications the patient is taking, the patients occupation, where the patient has been and complete physical examination. Points typically noted in the examination include: The appearance: e.g., purpuric (typical of vasculitis and meningococcal disease), fine and like sandpaper (typical of scarlet fever); circular lesions with a central depression are typical of molluscum contagiosum (and in the past, small pox); plaques with silver scales are typical of psoriasis. The distribution: e.g., the rash of scarlet fever becomes confluent and forms bright red lines in the skin creases of the neck, armpits and groins (Pastias lines); the vesicles of chicken pox seem to follow the hollows of the body (they are more prominent along the depression of the spine on the back and in the hollows of both shoulder blades); very few rashes affect the palms of the hands and soles of the feet (secondary syphilis, rickettsia or spotted fevers, guttate psoriasis, hand, foot and mouth disease, keratoderma blennorrhagicum); Symmetry: e.g., herpes zoster usually only affects one side of the body and does not cross the midline.A patch test may be ordered, for diagnostic purposes. Treatment Treatment differs according to which rash a patient has been diagnosed with. Common rashes can be easily remedied using steroid topical creams (such as hydrocortisone) or non-steroidal treatments. Many of the medications are available over the counter in the United States.The problem with steroid topical creams i.e. hydrocortisone; is their inability to penetrate the skin through absorption and therefore not be effective in clearing up the affected area, thus rendering the hydrocortisone almost completely ineffective in all except the most mild of cases. References External links Guide to rashes on Medline Plus Medical Encyclopedia – includes photographs Links to pictures of skin rashes (Hardin MD/Univ of Iowa) Pictures of common skin rashes compared (Dermapics)
Focal cortical dysplasia	Focal cortical dysplasia (FCD) is a congenital abnormality of brain development where the neurons in an area of the brain failed to migrate in the proper formation in utero. Focal means that it is limited to a focal zone in any lobe. Focal cortical dysplasia is a common cause of intractable epilepsy in children and is a frequent cause of epilepsy in adults. There are three types of FCD with subtypes, including type 1a, 1b, 1c, 2a, 2b, 3a, 3b, 3c, and 3d, each with distinct histopathological features. All forms of focal cortical dysplasia lead to disorganization of the normal structure of the cerebral cortex : Type 1 FCD exhibits subtle alterations in cortical lamination. Type 2a FCD exhibits neurons that are larger than normal that are called dysmorphic neurons (DN). FCD type 2b exhibits complete loss of laminar structure, and the presence of DN and enlarged cells are called balloon cells (BC) for their large elliptical cell body shape, laterally displaced nucleus, and lack of dendrites or axons. The developmental origin of balloon cells is currently believed to be derived from neuronal or glial progenitor cells. Balloon cells are similar in structure to giant cells in the disorder tuberous sclerosis complex. Type 3 FCDs are cortical disorganisation associated with other lesions such as hippocampal sclerosis (type 3a), long-term epilepsy-associated tumors (3b), vascular malformations (3c) or scar/hypoxic damages (3d).Recent studies have demonstrated that FCD types 2a and 2b result from somatic mutations in genes that encode components of the mammalian target of rapamycin (mTOR) pathway. Causative gene mutations for types 1 and 3 have not been identified. The mTOR pathway regulates a number of functions in the brain including establishment of cell size, cell motility, and differentiation. Gene mutations associated with FCD2a and FCD 2b include MTOR, PI3KCA, AKT3, and DEPDC5. Mutations in these genes lead to enhanced mTOR pathway signaling at critical periods in brain development. Some recent evidence may suggest a role for in utero infection with certain viruses such as cytomegalovirus and human papilloma virus.Seizures in FCD are likely caused by abnormal circuitry induced by the presence of DNs and BCs. These abnormal cell types generate abnormal electrical signals which spread out to affect other parts of the cerebral cortex. Medication is used to treat the seizures that may arise due to cortical dysplasia. Epilepsy surgery to remove areas of FCD is a viable treatment option for appropriate candidates. Treatment No specific treatment is required for cortical dysplasia, and all treatment is aimed at the resulting symptoms (typically seizures). When a cortical dysplasia is a cause of epilepsy, then seizure medications (anticonvulsants) are a first line treatment. If anticonvulsants fail to control seizure activity, neurosurgery may be an option to remove or disconnect the abnormal cells from the rest of the brain (depending on where the cortical dysplasia is located and the safety of the surgery relative to continued seizures). Neurosurgery can range from removing an entire hemisphere (hemispherectomy), a small lesionectomy, or multiple transsections to try to disconnect the abnormal tissue from the rest of the brain (multiple subpial transsections). Physical therapy should be considered for infants and children with muscle weakness. Educational therapy is often prescribed for those with developmental delays, but there is no complete treatment for the delays. See also Gray matter heterotopia References == External links ==
Oroantral fistula	Oroantral fistula (OAF) is an epithelialised oroantral communication (OAC). OAC refers to an abnormal connection between the oral cavity and antrum (or maxillary sinus). The creation of an OAC is most commonly due to the extraction of a maxillary (upper) tooth (typically a maxillary first molar) closely related to the antral floor (floor of the maxillary sinus). A small OAC (up to 5mm wide) may heal spontaneously but a larger OAC would require surgical closure to prevent the development of persistent OAF and chronic sinusitis. Classification Signs and symptoms of an OAC/OAF can include the following When looking in the mouth, a communication in the upper jaw (i.e. a hole) can be seen connecting the mouth to the maxillary sinus. Sometimes this can be the only sign, as pain (+/- other symptoms) is not always present. Symptoms · Same side nose blockage (unilateral nasal obstruction). When an OAC or OAF is present, the passage to the maxillary sinus can results in infection and inflammation in the maxillary sinus. This subsequently results in mucus build up presenting as a unilateral nasal blockage · Sinusitis can progress – this can present as a pain in the midface. Pain can be referred to the upper teeth and be mistaken for toothache· Fluid can flow from the mouth through the communication and into the maxillary sinus. The maxillary sinus is connected to the nose and therefore fluid can come out of the nostrils when drinking· Change in sounds produced from the nose and the voice – specifically a whistling sound whilst speaking· Taste can be affected Signs · Visible hole between mouth and sinus · Fracture of the floor of the maxillary sinus creating a communication to the oral cavity (e.g. as seen following trauma).· Air bubbles, blood or mucoid secretion around the orifice can be seen as air passes from the sinus into the oral cavity through the communication. Diagnosis - Patient history - Diagnosis is usually based on clinical examination and reported symptoms. Therefore, a good history and understanding of the patient’s symptoms is key. - Undertake a complete extraoral and intraoral examination using a dental mirror alongside good lighting. When assessing the socket following an extraction look for granulation tissue in the socket which may represent normal healing. Assess for the presence of visible an opening/hole between the oral cavity and the maxillary sinus. - Imaging can be useful. However, radiographs only show if there is a breach in the bony floor of the antrum. Even if there is a breach in the bony floor then the Schneiderian membrane may still be intact. Depending on the size of the potential communication and in what context, a small radiograph inside the mouth may be sufficient (a periapical) to assess for any break in the bone of the sinus floor which may indicate an OAC. - Panoramic radiographs can also be used to confirm the presence of an OAC. If simple radiographs are deemed not to give enough information, cone beam computed tomography (CBCT) (special x-ray equipment that can scan in 3 dimensions) may be used. Imaging can help locate the communication, determine the size of it and can give an indication as to whether there is any sinusitis and foreign bodies in the sinus. - Normally clinicians should be cautioned against probing or irrigating the site a newly formed OAC as this may reduce the chance of spontaneous healing. - Valsalva test (nose blowing test) The patient is asked to pinch their nostrils together and open their mouth and then blow gently through the nose. The clinician must observe if there is passage of air or bubbling of blood in the post extraction alveolus as the trapped air from closed nostrils is forced into the mouth through any oroantral communication. Gentle suction applied to the socket often produces a characteristic hollow sound. However, there are differing opinions about the appropriateness of carrying out this test. It can be argued that by performing this test, a small OAC may be made bigger thus preventing spontaneous healing. Causes Extraction of maxillary teeth The maxillary sinus is known for its thin floor and close proximity to the posterior maxillary (upper) teeth. The extraction of a maxillary tooth (typically a maxillary first molar which lies close to the lowest point of antral floor although any premolar or molar can be affected) is the most common cause of an OAC (which can then progress to an OAF as described above). Extraction of primary teeth are not considered a risk of OAC due to the presence of developing permanent teeth and the small size of the developing maxillary sinus. Other causes Other causes of an OAC are: maxillary fractures across the antral floor typically Le Fort I, displacement of posterior maxillary molar roots into antrum and direct trauma. An OAC can happen for many other more unusual reasons, such as acute or chronic inflammatory lesions around the tip of a tooth root which is in close proximity with the maxillary antrum, destructive lesions/tumours of the maxilla, failure of surgical incisions to heal (e.g. Caldwell-luc antrostomy), osteomyelitis of the maxilla, careless use of instruments during surgical procedures, Syphilis, implants and as a results of complex surgery (for example removal of a large cysts or resections of large tumours involving the maxilla. Diagnosis Clinical examination and x rays can help diagnose the condition. For examples : Valsalva test (nose blowing test): Ask the patient to pinch the nostrils together and open the mouth, then blow gently through the nose. Observe if there is passage of air or bubbling of blood in the post extraction alveolus as the trapped air from closed nostrils is forced into the mouth through any oroantral communication. Gentle suction applied to the socket often produces a characteristic hollow sound. Perform a complete extra- and intra-oral examination using a dental mirror under good lighting, look for granulation tissue in the socket and openings into the antrum. Panoramic radiograph or paranasal computed tomography can help to locate the fistula, the size of it and to determine the presence of sinusitis and other foreign bodies. Other methods like radiographs (occipitomental, OPG and periapical views) can also be used to confirm the presence of any oroantral fistulas. To test the patency of communication the patient is asked to rinse the mouth or water is flushed in the tooth socket. Unilateral epistaxis is seen in case of collection of blood in the sinus cavity. Do not probe or irrigate the site, because it may lead to sinusitis or push foreign bodies, such as contaminated fragments, or oral flora further into the antrum. Hence, leading to the formation of a new fistula or widen an existing one. Complications OAF is a complication of oroantral communication. Other complications may arise if left untreated. For example: Candidal infection Chronic maxillary sinus infection of bacterial origin Osteomyelitis Rhinosinusitis Sinus pathologyTherefore, OAF should be dealt with first, before treating the complications. Prevention Whilst in some circumstances, preventing development of an OAF following extraction of a tooth can be difficult, careful assessment is important. The following should be considered prior to carrying out any dental treatment: Size of the antrum and proximity to teeth – this can be assessed radiographically Shape and size of teeth and roots – this can be assessed radiographically Presence of periapical pathology – this can be assessed radiographically The age of the patient The patient’s past dental historyIf the above factors are assessed as increasing the risk of OAC development, the clinician should take appropriate steps to carefully remove the tooth in question, possibly carrying out a surgical extraction and in an appropriate setting. Hence, in such cases: Avoid using too much of apical pressure during tooth extraction Perform surgical extraction with roots sectioning Consider referral to OMFS at local hospital Treatment The primary aim of treatment of a newly formed oroantral communication is to prevent the development of an oroantral fistula as well as chronic sinusitis. The decision on how to treat OAC/OAF depends on various factors. Small size communications between 1 and 2 mm in diameter, if uninfected, are likely to form a clot and heal by itself later. Communications larger than this require treatments to close the defect and these interventions can be categorised into 3 types: surgical, non-surgical and pharmacological. Surgery Surgical methods are required if a large defect is present or if a defect persists. Surgery involves creating a flap utilising local tissue to close the communication. There are a number of different flaps that can be used such as the buccal advancement flap, the buccal fat pad flap, a combination of the two and a palatal flap. The flap used is dependent on the size and position of the defect. Buccal advancement flap The buccal advancement flap is the most commonly used due to its simplicity, reliability and versatility. It involves cutting a broad based trapezoid shaped mucoperiosteal flap with two vertical incisions. The flap is cut buccally, is three sided and extends to the full depth of the sulcus. Buccal fat pad flap The buccal fat pad flap is also a popular option due to its high success rate. It is a simple procedure where the buccal extension of the anatomical fat pad is used for closure. These two flaps can be used in combination where the buccal fat pad covers the communication followed by a further covering via the buccal mucosal flap described above. This double layer flap has advantages over a single layer as it provides stable soft tissue covering, reduces the incidences of wound breakdown and defect recurrence as well as reducing the risk of postoperative infection.Sutures, either non-resorbing or slowly resorbing, are generally used in the surgical repairs of OAC. Non-surgical interventions Ultimately, surgery is usually required to close an OAC/OAF. However, if surgery is not immediately available then non-surgical methods can be used to encourage the growth of oral mucosa between the oral cavity and the antrum. The aim of these methods is to protect the blood clot within the socket and help to prevent infection. One option is construction of a denture with an acrylic base plate or extension of the patient’s existing denture to protect the socket and support the clot. These options are particularly helpful in patients who smoke as it provides protection from smoke inhalation. The socket can also be sutured over with mattress sutures if there is adequate soft tissue available. Medication Medications may be needed as an adjunct to assist the closure of the defect. Antibiotics can help control or prevent any sinus infections. Preoperative nasal decongestants usage can reduce any existing sinus inflammation which will aid surgical manipulation of the mucosa over the bone. Postoperative care Following all methods of OAC/OAF closure, the patients are instructed to avoid activities that could produce pressure changes between the nasal passages and oral cavity for at least 2 weeks due to risk of disruption to the healing process. Nose blowing and sneezing with a closed mouth are prohibited. A soft diet is also often advocated during this period. Following surgery, nasal decongestants and prophylactic antibiotics are often prescribed to prevent postoperative infection. References == External links ==
Primary hyperoxaluria	Primary hyperoxaluria is a rare condition (autosomal recessive), resulting in increased excretion of oxalate (up to 600 mg a day from normal 50 mg a day), with oxalate stones being common. Signs and symptoms Primary hyperoxaluria is an autosomal recessive disease, meaning both copies of the gene contain the mutation. Both parents must have one copy of this mutated gene to pass it on to their child, but they do not typically show signs or symptoms of the disease. A single kidney stone in children or recurrent stones in adults is often the first warning sign of primary hyperoxaluria. Other symptoms range from recurrent urinary tract infections, severe abdominal pain or pain in the side, blood in the urine, to chronic kidney disease and kidney failure. The age of symptom onset, progression and severity can vary greatly from one person to another, even among members of the same family. Some individuals may have mild cases that go undiagnosed well into adulthood; others may develop severe complications during infancy, which may result in early death. Pathophysiology The buildup of oxalate in the body causes increased renal excretion of oxalate (hyperoxaluria), which in turn results in kidney and bladder stones. Stones cause urinary obstruction (often with severe and acute pain), secondary infection of urine and eventually kidney damage. Primary hyperoxaluria is caused by genetic defects that result in the overproduction of oxalate. This is different from secondary hyperoxaluria, which is caused by the increase in dietary and intestinal absorption of oxalate or excessive intake of oxalate precursors.Oxalate stones in primary hyperoxaluria tend to be severe, resulting in relatively early kidney damage (in teenage years to early adulthood), which impairs the excretion of oxalate leading to a further acceleration in accumulation of oxalate in the body.After the development of kidney failure patients may get deposits of oxalate in the bones, joints and bone marrow. Severe cases may develop haematological problems such as anaemia and thrombocytopaenia. The deposition of oxalate in the body is sometimes called "oxalosis" to be distinguished from "oxaluria" which refers to oxalate in the urine. Diagnosis A diagnosis of primary hyperoxaluria is suspected based on presenting patient characteristics such as kidney stones in infants or children, recurrent kidney stones in adults, or family history of hyperoxaluria. In these patients, stone analysis and urine analysis are recommended to rule out secondary causes of hyperoxaluria. A definitive diagnosis of primary hyperoxaluria requires genetic testing. This is performed using a gene panel covering known mutations for all three types of primary hyperoxaluria. Classification The three main types of primary hyperoxaluria (PH1, PH2, and PH3) are each associated with mutations in specific genes involved in the metabolism of glyoxylate, the precursor of oxalate. These mutations result in decreased production or activity of the proteins that are involved in the normal breakdown of glyoxylate, which results in an overproduction of oxalate. Mutations in the genes AGXT and GRHPR cause PH1 and PH2, respectively, through decreased production or activity of the proteins they make, which stops the normal breakdown of glyoxylate. Similarly, mutations in the gene HOGA1 cause PH3 due to loss-of-function mutations resulting in impaired protein function.PH1 is considered to be the most common and rapidly progressing form, accounting for about 80% of all currently diagnosed cases and PH2 and PH3 accounting for approximately 10% each of the current cases. However, recent evidence has suggested that PH2 and PH3 are not as benign as previously thought, with up to 50% of patients with PH2 developing kidney failure (chronic kidney disease [CKD] stage 5). While current estimates indicate that kidney failure is rarer in patients with PH3 compared to PH1 and PH2, CKD has been reported in patients with PH3. Moreover, the genetic prevalence based on known PH3 variants is much higher than the diagnosed prevalence of the disease, which could mean either incomplete penetrance (i.e. variant present with no clinical symptoms) or underdiagnosis (i.e. variant present with clinical symptoms but not diagnosed). Treatment Increased water intake and alkalinization of urine is advised to prevent oxalate precipitation in urinary tract. In addition, Vitamin B6 (pyridoxine) is used to treat PH1 because alanine glyoxylate transaminase requires pyridoxine as cofactor. In approximately one third of patients with PH1, pyridoxine treatment decreases oxalate excretion and prevent kidney stone formation. Conversely, a restriction in oxalate intake is of limited use as the main source of oxalate is endogenous in primary hyperoxaluria.Lumasiran, an RNA interference therapeutic drug, is indicated for the treatment of primary hyperoxaluria type 1 (PH1) in adults and children of all ages and is available under the UK Early Access to Medicines Scheme (EAMS). Lumasiran was approved for medical use in the European Union and in the United States in November 2020. In addition, there are a few agents under investigation in clinical trials for PH: Nedosiran (RNA interference therapeutic) for PH1, PH2, and PH3; Stiripentol (antiepileptic drug); Oxabact (lyophilized Oxalobacter formigenes; and Reloxaliase (oxalate-digesting enzyme) for PH Treatment of renal failure in primary hyperoxaluria Kidney failure is a serious complication requiring treatment in its own right. Dialysis can control kidney failure but tends to be inadequate to dispose of excess oxalate. Renal transplant is more effective and is the primary treatment of severe hyperoxaluria. Ultimately though, liver transplantation (often in addition to renal transplant) is required to correct the underlying metabolic defect. See also Peroxisomal disorder References External links GeneReview/NCBI/NIH/UW entry on Primary Hyperoxaluria Type 1 GeneReview/NCBI/NIH/UW entry on Primary Hyperoxaluria Type 2 Primary hyperoxaluria (A service of the U.S. National Library of Medicine)
Lupus erythematosus	Lupus erythematosus is a collection of autoimmune diseases in which the human immune system becomes hyperactive and attacks healthy tissues. Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs. The most common and most severe form is systemic lupus erythematosus. Signs and symptoms Symptoms vary from person to person, and may come and go. Almost everyone with lupus has joint pain and swelling. Some develop arthritis. Frequently affected joints are the fingers, hands, wrists, and knees. Other common symptoms include: chest pain during respiration joint pain (stiffness and swelling) painless oral ulcer fatigue weight loss headaches fever with no other cause Skin lesions that appear worse after sun exposure general discomfort, uneasiness, or ill feeling (malaise) hair loss sensitivity to sunlight a "butterfly" facial rash, seen in about half of people with SLE swollen lymph nodes Photosensitivity Photosensitivity is the amount to which an object reacts upon receiving photons especially in visible light. Photosensitivity is a known symptom of lupus, but its relationship to and influence on other aspects of the disease remain to be defined. Causes of photosensitivity may include: change in autoantibody location cytotoxicity induction of apoptosis with autoantigens in apoptotic blebs upregulation of adhesion molecules and cytokines induction of nitric oxide synthase expression ultraviolet-generated antigenic DNA Genetics It is typically believed that lupus is influenced by multiple genes. Lupus is usually influenced by gene polymorphisms, 30 of which have now been linked with the disorder. Some of these polymorphisms have been linked very tentatively, however, as the role that they play or the degree to which they influence the disease is unknown. Other genes that are commonly thought to be associated with lupus are those in the human leukocyte antigen (HLA) family. There have been several cases wherein a single gene influence appears to be present, but this is rare. When a single gene deficiency does cause lupus, it is usually attributed to the complement protein genes C1, C2, or C4. The influence of sex chromosomes and environmental factors are also noteworthy. Usually, these factors contribute to lupus by influencing the immune system. Several studies also indicate a potential association of lupus with mutations in DNA repair genes. Age difference Lupus can develop in people at any age, but it does most commonly at ages 15 to 44, with varying results. Typically, the manifestation of the disease tends to be more acute in those of younger age. Women are more likely to get it than men. Patients with juvenile-onset lupus are more vulnerable to mucocutaneous manifestations of the disease (alopecia, skin rash, and ulceration of the mucus membranes) than any other age group, and they are also more susceptible to evaluation of pulmonary artery pressure. However, patients with late-onset lupus have a much higher mortality rate. Nearly 50% of those with late-onset lupus die of their condition. Women who are of childbearing age are also particularly at risk. Differences in ethnicity Substantial data have been found to indicate that certain ethnic populations could be more at risk for lupus erythematosus and to have a better or worse prognosis. Asian, African, and Native Americans are more likely to get lupus than Caucasians. Caucasians seem generally to have a milder manifestation of the disease. Their survival rates after five years were typically around 94–96%, while patients of African and some Asian ethnicities had survival rates closer to 79–92%. The only documented ethnic group that had a higher survival rate than Caucasians was Koreans, who had survival rates nearer to 98%. Among Caucasians, the most common causes of death were complications involving the cardiovascular system, the respiratory system, and malignancies. Atherosclerotic cardiovascular disease is more prevalent in African Americans with lupus than in Caucasians with lupus. Diagnosis Diagnosis of lupus will vary from person to person. It is common to be diagnosed with other illnesses before a doctor can finally rule out lupus because a lot of the symptoms overlap with other common illness.Diagnosis of lupus erythematosis requires a physical examination, blood and urine tests, and a skin or kidney biopsy. Some other tests that may need to be run include: Antinuclear antibody (ANA) CBC with differential Chest X-ray Serum creatinine Urinalysis Classification Lupus erythematosus may manifest as systemic disease or in a purely cutaneous form also known as incomplete lupus erythematosus. Lupus has four main types: systemic discoid drug-induced neonatalOf these, systemic lupus erythematosus (also known as SLE) is the most common and serious form. A more thorough categorization of lupus includes the following types: acute cutaneous lupus erythematosus subacute cutaneous lupus erythematosus discoid lupus erythematosus (chronic cutaneous) childhood discoid lupus erythematosus generalized discoid lupus erythematosus localized discoid lupus erythematosus chilblain lupus erythematosus (Hutchinson) lupus erythematosus-lichen planus overlap syndrome lupus erythematosus panniculitis (lupus erythematosus profundus) tumid lupus erythematosus verrucous lupus erythematosus (hypertrophic lupus erythematosus) cutaneous lupus mucinosis complement deficiency syndromes drug-induced lupus erythematosus neonatal lupus erythematosus systemic lupus erythematosus Treatment There is still no cure for lupus but there are options to help control symptoms. The goal for treatment is to prevent flare ups and reduce organ damage. Doctors may prescribe a handful of different medications to help with their patients symptoms.Some medications are: Nonsteroidal anti-inflammatory drugs (NSAIDs). Corticosteroids Antimalarial drugs BLyS-specific inhibitors Immunosuppressive agents/chemotherapyAfter being diagnosed some treatment options that may be offered are: Treatment consists primarily of immunosuppressive drugs (e.g., hydroxychloroquine and corticosteroids). A second-line drug is methotrexate in its low-dose schedule. In 2011, the U.S. Food and Drug Administration (FDA) approved the first new drug for lupus in more than 50 years to be used in the US, belimumab. In addition to medical therapy, cognitive behavioral therapy has also been demonstrated to be effective in reducing stress, anxiety, and depression due to the psychological and social impacts that lupus may have.People with SLE treated with standard care experience a higher risk of opportunistic infections and death than the general population. This risk is higher in men and in African Americans. Epidemiology Worldwide An estimated 5 million people worldwide have some form of lupus disease. 70% of lupus cases diagnosed are systemic lupus erythematosus. 20% of people with lupus will have a parent or sibling who already has lupus or may develop lupus. about 5% of the children born to individuals with lupus will develop the illness. United Kingdom Females in the UK are seven times more likely to be diagnosed with SLE than males. The estimated number of females in the UK with SLE is 21,700, and the number of males is 3000 — a total of 24,700, or 0.041% of the population. SLE is more common amongst certain ethnic groups than others, especially those of African origin. United States Lupus occurs from infancy to old age, with peak occurrence between ages 15 and 40. Lupus affects females in the US 6 to 10 times more often than males. Prevalence data are limited. Estimates vary and range from 1.8 to 7.6 cases per 100,000 persons per year in parts of the continental United States. Culture and society In the early seasons of the television show House, members of the eponymous characters medical team often suggested lupus as a diagnosis for their patients, only to be rebuked. The rarity of legitimate lupus diagnoses in the show eventually became described as a running gag. See also List of cutaneous conditions List of target antigens in pemphigoid List of immunofluorescence findings for autoimmune bullous conditions List of human leukocyte antigen alleles associated with cutaneous conditions List of people with lupus References == External links ==
Phylloid hypomelanosis	Phylloid hypomelanosis is a cutaneous condition, a syndrome occurring in patients with mosaic trisomy 13 or translocation trisomy 13. See also Riehl melanosis List of cutaneous conditions == References ==
Congenital cytomegalovirus infection	Congenital cytomegalovirus (CMV) infection refers to a condition where cytomegalovirus is transmitted in the prenatal period. CMV is a member of the virus family herpesviridae and is the most common intrauterine infection.Human cytomegalovirus is one of the vertically transmitted infections that lead to congenital abnormalities. Others include toxoplasmosis, rubella, herpes simplex, and syphilis. Presentation For infants who are infected by their mothers before birth, two potential adverse scenarios exist: Generalized infection may occur in the infant, and can cause complications such as low birth weight, microcephaly, seizures, petechial rash similar to the "blueberry muffin" rash of congenital rubella syndrome, and moderate hepatosplenomegaly (with jaundice). Though severe cases can be fatal, with supportive treatment most infants with CMV disease will survive. However, from 80% to 90% will have complications within the first few years of life that may include hearing loss, vision impairment, and varying degrees of learning disability. Another 5% to 10% of infants who are infected but without symptoms at birth will subsequently have varying degrees of hearing and mental or coordination problems. CMV is the most common cause of non-genetic sensorineural hearing loss in children. The onset of hearing loss can occur at any point during childhood, although commonly within the first decade. It is progressive and can affect both ears. The earlier the mother contracts the virus during pregnancy the more severe the effects are on the fetus, similarly the incidence of SNHL is dependent on which trimester of pregnancy CMV is contracted. The virus accounts for 20% of sensorineural hearing loss in children.These risks appear to be almost exclusively associated with women who previously have not been infected with CMV and who are having their first infection with the virus during pregnancy. There appears to be little risk of CMV-related complications for women who have been infected at least 6 months prior to conception. For this group, which makes up 50% to 80% of the women of child-bearing age, the rate of newborn CMV infection is 1%, and these infants appear to have no significant illness or abnormalities.The virus can also be transmitted to the infant at delivery from contact with genital secretions or later in infancy through breast milk. However, these infections usually result in little or no clinical illness in the infant. CMV can also be transferred through blood transfusions and close contact with large groups of children.To summarise, during a pregnancy when a woman who has never had CMV infection becomes infected with CMV, there is a risk that after birth the infant may have CMV-related complications, the most common of which are associated with hearing loss, visual impairment, or diminished mental and motor capabilities. On the other hand, healthy infants and children who acquire CMV after birth have few, if any, symptoms or complications. However, infants born preterm and infected with CMV after birth (especially via breastmilk) may experience cognitive and motor impairments later in life.Symptoms associated with CMV, such as hearing loss, can result in further developmental delay. A delay in general speech and language development is more common in children with CMV. Children with symptomatic CMV have been found to have a greater incidence of long-term neurological and neurodevelopmental complications than children with fetal alcohol syndrome or down syndrome.Congenital cytomegalovirus infection can be an important cause of intraventricular hemorrhage and neonatal encephalopathy. Diagnosis CMV Testing People infected with CMV develop antibodies to it, initially IgM later IgG indicating current infection and immunity respectively. The virus can be diagnosed through viral isolation, or using blood, urine, or saliva samples.When infected with CMV, most women have no symptoms, but some may have symptoms resembling mononucleosis. Women who develop a mononucleosis-like illness during pregnancy should consult their medical provider.The Centers for Disease Control and Prevention (CDC) does not recommend routine maternal screening for CMV infection during pregnancy because there is no test that can definitively rule out primary CMV infection during pregnancy. Women who are concerned about CMV infection during pregnancy should practice CMV prevention measures. Considering that the CMV virus is present in saliva, urine, tears, blood, mucus, and other bodily fluids, frequent hand washing with soap and water is important after contact with diapers or oral secretions, especially with a child who is in daycare or interacting with other young children on a regular basis.A diagnosis of congenital CMV infection can be made if the virus is found in an infants urine, saliva, blood, or other body tissues during the first week after birth. Antibody tests cannot be used to diagnose congenital CMV; a diagnosis can only be made if the virus is detected during the first week of life. Congenital CMV cannot be diagnosed if the infant is tested more than one week after birth.Visually healthy infants are not routinely tested for CMV infection although only 10–20% will show signs of infection at birth though up to 80% may go onto show signs of prenatal infection in later life. If a pregnant woman finds out that she has become infected with CMV for the first time during her pregnancy, she should have her infant tested for CMV as soon as possible after birth.Treatment for CMV infection should start at 1 month of age and should occur for 6 months. The options for treatment are intravenous ganciclovir and oral valganciclovir. After diagnosis, it is important to further investigate any possible evidence of end-organ disease and symptoms through blood tests, imaging, ophthalmology tests, and hearing tests. Prevention Recommendations for pregnant women with regard to CMV infection: Throughout the pregnancy, practice good personal hygiene, especially handwashing with soap and water, after contact with diapers or oral secretions (particularly with a child who is in day care). Sharing of food, eating and drinking utensils, and contact with toddlers saliva should be avoided. Women who develop a mononucleosis-like illness during pregnancy should be evaluated for CMV infection and counseled about the possible risks to the unborn child. Laboratory testing for antibody to CMV can be performed to determine if a woman has already had CMV infection. Recovery of CMV from the cervix or urine of women at or before the time of delivery does not warrant a cesarean section. The demonstrated benefits of breast-feeding outweigh the minimal risk of acquiring CMV from the breast-feeding mother. There is no need to either screen for CMV or exclude CMV-excreting children from schools or institutions because the virus is frequently found in many healthy children and adults.Treatment with hyperimmune globulin in mothers with primary CMV infection has been shown to be effective in preventing congenital disease in several studies. One study did not show significant decrease in the risk of congenital cytomegalovirus infection. Childcare Most healthy people working with infants and children face no special risk from CMV infection. However, for women of child-bearing age who previously have not been infected with CMV, there is a potential risk to the developing unborn child (the risk is described above in the Pregnancy section). Contact with children who are in day care, where CMV infection is commonly transmitted among young children (particularly toddlers), may be a source of exposure to CMV. Since CMV is transmitted through contact with infected body fluids, including urine and saliva, child care providers (meaning day care workers, special education teachers, as well as mothers) should be educated about the risks of CMV infection and the precautions they can take. Day care workers appear to be at a greater risk than hospital and other health care providers, and this may be due in part to the increased emphasis on personal hygiene in the health care setting.Recommendations for individuals providing care for infants and children: Employees should be educated concerning CMV, its transmission, and hygienic practices, such as handwashing, which minimize the risk of infection. Susceptible nonpregnant women working with infants and children should not routinely be transferred to other work situations. Pregnant women working with infants and children should be informed of the risk of acquiring CMV infection and the possible effects on the unborn child. Routine laboratory testing for CMV antibody in female workers is not specifically recommended due to its high occurrence, but can be performed to determine their immune status. Epidemiology Worldwide, approximately 1 in 100 to 500 babies are born with congenital CMV. Approximately 1 in 3000 will show symptoms and 1 in 7000 will die. Congenital HCMV infection occurs when the mother has a primary infection (or reactivation) during pregnancy. Due to the lower seroprevalence of HCMV in industrialized countries and higher socioeconomic groups, congenital infections are actually less common in poorer communities, where more women of child-bearing age are already seropositive. In industrialized countries up to 8% of HCMV seronegative mothers contract primary HCMV infection during pregnancy, of which roughly 50% will transmit to the fetus. Between 10 and 15% of infected fetuses are then born with symptoms, which may include pneumonia, gastrointestinal, retinal and neurological disease. 10-15% of asymptomatic babies will develop long term neurological effects. SNHL is found in 35% of children with CMV, cognitive deficits have been found in 66% of children with CMV, and death occurs in 4% of children. HCMV infection occurs in roughly 1% of all neonates with those who are not congenitally infected contracting the infection possibly through breast milk. Other sources of neonatal infection are bodily fluids which are known to contain high titres in shedding individuals: saliva (<107copies/ml) and urine (<105copies/ml ) seem common routes of transmission. The incidence of primary CMV infection in pregnant women in the United States varies from 1% to 3%. Healthy pregnant women are not at special risk for disease from CMV infection. When infected with CMV, most women have no symptoms and very few have a disease resembling infectious mononucleosis. It is their developing fetuses that may be at risk for congenital CMV disease. CMV remains the most important cause of congenital viral infection in the United States. HCMV is the most common cause of congenital infection in humans and intrauterine primary infections are more common than other well-known infections and syndromes, including Down Syndrome, Fetal Alcohol Syndrome, Spina Bifida, and Pediatric HIV/AIDS. References External links Cytomegalovirus (CMV)—NHS Choices CMV: Congenital CMV Infection—CDC
Atrioventricular reentrant tachycardia	Atrioventricular reentrant tachycardia (AVRT), or atrioventricular reciprocating tachycardia, is a type of abnormal fast heart rhythm and is classified as a type of supraventricular tachycardia (SVT). AVRT is most commonly associated with Wolff–Parkinson–White syndrome, but is also seen in permanent junctional reentrant tachycardia (PJRT). In AVRT, an accessory pathway allows electrical signals from the hearts ventricles to enter the atria and cause earlier than normal contraction, which leads to repeated stimulation of the atrioventricular node. Signs and symptoms An episode of SVT may present with palpitations, dizziness, shortness of breath, or losing consciousness (fainting). The electrocardiogram (ECG) would appear as a narrow-complex SVT. Between episodes of tachycardia the affected person is likely to be asymptomatic; however, the ECG would demonstrate the classic delta wave in Wolff–Parkinson–White syndrome. Pathophysiology Two distinct pathways are involved: the normal atrioventricular conduction system, and an accessory pathway. During AVRT, the electrical signal passes in the normal manner from the AV node into the ventricles. Then, the electrical impulse pathologically passes back into the atria via the accessory pathway, causing atrial contraction, and returns to the AV node to complete the reentrant circuit (see figure). Once initiated, the cycle may continue causing the heart to beat faster than usual.Initiation of AVRT may be through a premature impulse of atrial, junctional, or ventricular origin. Treatment Acute management is as for SVT in general. The aim is to interrupt the circuit. In the shocked patient, DC cardioversion may be necessary. In the absence of shock, inhibition at the AV node is attempted. This is achieved first by a trial of specific physical maneuvers such as holding a breath in or bearing down. If these maneuvers fail, using intravenous adenosine causes complete electrical blockade at the AV node and interrupts the reentrant electrical circuit. Long-term management includes beta blocker therapy and radiofrequency ablation of the accessory pathway. See also AV nodal reentrant tachycardia Electrical conduction system of the heart Wolff-Parkinson-White syndrome Permanent junctional reentrant tachycardia (PJRT) References == External links ==
Leukonychia	Leukonychia (or leuconychia), is a medical term for white discoloration appearing on nails. It is derived from the Greek words leuko white and onyx nail. The most common cause is injury to the base of the nail (the matrix) where the nail is formed. Types Leukonychia totalis This condition consists of a whitening of the entire nail and mostly likely occurs on all nails. Whitening of one, and only one, entire nail is not recognized as a symptom of Leukonychia totalis but as a likely result of mechanical trauma. Leukonychia totalis may be a clinical sign of hypoalbuminaemia (low albumin), which can be seen in nephrotic syndrome (a form of kidney failure), liver failure, protein malabsorption and protein-losing enteropathies. A genetic condition or a side effect from taking sulphonamides (a family of antibiotics) can also cause this appearance. By 2011, only 6 cases of non-hereditary Leukonychia totalis were published.In familial cases of leukonychia totalis, this condition is caused by mutations in the PLCD1 gene, in chromosome 3p22.2, this mutation shows an autosomal dominant pattern of inheritance, but in some cases, this condition may be autosomal recessive Leukonychia partialis This condition consists of a whitening of parts of the nail plate in the form of small white dots. There are three different variations of partial leukonychia; punctate, transverse and longitudinal leukonychia. Some of the more serious variations of leukonychia partialis may lead to leukonychia totalis. Leukonychia striata Leukonychia striata, transverse leukonychia, or Mees lines are a whitening or discoloration of the nail in bands or "stria" that run parallel the lunula (nail base). This is commonly caused by physical injury or disruption of the nail matrix. Common examples include excessive biting or tapping of the nails, trauma or injury from accidents involving doors or windows, and extensive use of manicure. It may also occur in great toenails as a result of trauma from footwear. Alternatively, the condition can be caused by heavy metal poisoning, most commonly by lead. Finally, it can be caused by cirrhosis of the liver or chemotherapy. The tendency toward leukonychia striata is sometimes inherited in an autosomal dominant fashion. In other cases, it can be attributed to vigorous manicuring and trauma aforementioned, or to a wide variety of systemic illnesses. Serious infections known for high fevers, measles, malaria, herpes, and leprosy may also cause this condition. In many patients, there is no obvious cause, and the streaks resolve spontaneously. There is a similar condition called Muehrckes lines (apparent leukonychia) which differs from leukonychia in that the lines fade with digital compression and does not migrate with the growth of the nail. Leukonychia punctata Also known as "true" leukonychia, this is the most common form of leukonychia, in which small white spots appear on the nails. Picking and biting of the nails are a prominent cause in young children and nail biters. Besides parakeratosis, air that is trapped between the cells may also cause this appearance. It is also caused by trauma. In most cases, when white spots appear on a single or a couple of fingers or toes, the most common cause is injury to the base (matrix) of the nail. When this is the case, white spots disappear after around eight months, which is the amount of time necessary for nails to regrow completely. The pattern and number of spots may change as the nail grows. Longitudinal leukonychia Longitudinal leukonychia is far less common and features smaller 1mm white longitudinal lines visible under the nail plate and parallel to the nail bed. It may be associated with Dariers disease. Cause It is harmless and most commonly caused by minor injuries, such as nail biting, which occur while the nail is growing. Leukonychia occurs most commonly in healthy individuals, and is unrelated to any known nutritional or physiological deficiency. When caused by injury the marks will disappear as the nail grows outwards. While there are various sources that link dietary needs or vitamin deficiency with recurrent leukonychia, this notion has been challenged by some medical researchers.Other possible reasons for this problem with nail colour can be linked to: Arsenic poisoning Lead poisoning Pneumonia Heart disease Kidney failure Ill health Hypoalbuminemia Vitamin deficiency Ulcerative colitis Liver cirrhosis Psychogenic stresses Onychophagia Trauma injury Occupational trauma Zinc deficiency Protein deficiency Psoriasis Eczema Iron deficiency Diagnosis A doctor will take a thorough medical history, and may take blood tests as well as examining liver and kidney function. Intracellular (red blood cell) assays are more sensitive than tests for plasma levels. Treatment Improvements have been reported from treating malnutrition associated with zinc deficiency and other minerals. References == External links ==
Coffee ground vomiting	Coffee ground vomitus refers to a particular appearance of vomit. Within organic heme molecules of red blood cells is the element iron, which oxidizes following exposure to gastric acid. This reaction causes the vomitus to look like ground coffee. Coffee ground vomitus is a sign of possible upper gastrointestinal bleeding but studies show that it may not require urgent endoscopy. Causes Esophagitis, esophageal varices, gastritis, cirrhosis or gastric ulcers for example, may bleed and produce coffee-ground vomitus. When unaccompanied by melena, hematemesis or a fall in hemoglobin with corresponding urea rises and creates an unstable reaction, and other causes of coffee ground vomitus need to be elucidated; for example, gastric stasis, bowel obstruction or ileus, that can cause oxidised food material to be vomited. Vomiting iron supplements can also mimic coffee grounds to the untrained eye.Diseases such as Ebola, yellow fever, viral hepatitis, haemophilia B, fatty liver disease and cancers of stomach, pancreas, esophagus and, rarely, retrograde jejunogastric intussusception might also be the reason behind coffee-ground vomitus.When attributed to peptic inflammation, use of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective serotonin reuptake inhibitors (SSRIs) are commonly implicated. These drugs can interfere with the stomachs natural defenses against the strongly acidic environment, causing damage to the mucosa that can result in bleeding. Therefore, it is recommended that these class of drugs be taken with food or on a full stomach. Other causes of inflammation may be due to severe gastroesophageal reflux disease, Helicobacter pylori gastritis, portal hypertensive gastropathy or malignancy. When bright red blood is vomited, it is termed hematemesis. Hematemesis, in contrast to coffee ground vomitus, suggests that upper gastrointestinal bleeding is more acute or more severe, for example due to a Mallory–Weiss tear, gastric ulcer or Dieulafoys lesion, or esophageal varices. This condition may be a medical emergency and urgent care may be required.Oxidized blood from an upper gastrointestinal bleed can also be excreted in stool. It produces blackened, "tarry" stools known as melena. References External links Coffee Ground Vomitus
Primary ciliary dyskinesia	Primary ciliary dyskinesia (PCD) is a rare, autosomal recessive genetic ciliopathy, that causes defects in the action of cilia lining the upper and lower respiratory tract, sinuses, Eustachian tube, middle ear, Fallopian tube, and flagella of sperm cells. The alternative name of "immotile ciliary syndrome" is no longer favored as the cilia do have movement, but are merely inefficient or unsynchronized. When accompanied by situs inversus the condition is known as Kartagener syndrome.Respiratory epithelial motile cilia, which resemble microscopic "hairs" (although structurally and biologically unrelated to hair), are complex organelles that beat synchronously in the respiratory tract, moving mucus toward the throat. Normally, cilia beat 7 to 22 times per second, and any impairment can result in poor mucociliary clearance, with subsequent upper and lower respiratory infection. Cilia also are involved in other biological processes (such as nitric oxide production), currently the subject of dozens of research efforts. Signs and symptoms The main consequence of impaired ciliary function is reduced or absent mucus clearance from the lungs, and susceptibility to chronic recurrent respiratory infections, including sinusitis, bronchitis, pneumonia, and otitis media. Progressive damage to the respiratory system is common, including progressive bronchiectasis beginning in early childhood, and sinus disease (sometimes becoming severe in adults). However, diagnosis is often missed early in life despite the characteristic signs and symptoms. In males, immotility of sperm can lead to infertility, although conception remains possible through the use of in vitro fertilization, there also are reported cases where sperm were able to move. Trials have also shown that there is a marked reduction in fertility in females with Kartageners syndrome due to dysfunction of the oviductal cilia.Many affected individuals experience hearing loss and show symptoms of otitis media which demonstrates variable responsiveness to the insertion of myringotomy tubes or grommets. Some patients have a poor sense of smell, which is believed to accompany high mucus production in the sinuses (although others report normal – or even acute – sensitivity to smell and taste). Clinical progression of the disease is variable, with lung transplantation required in severe cases. Susceptibility to infections can be drastically reduced by an early diagnosis. Treatment with various chest physiotherapy techniques has been observed to reduce the incidence of lung infection and to slow the progression of bronchiectasis dramatically. Aggressive treatment of sinus disease beginning at an early age is believed to slow long-term sinus damage (although this has not yet been adequately documented). Aggressive measures to enhance clearance of mucus, prevent respiratory infections, and treat bacterial superinfections have been observed to slow lung-disease progression. Although the true incidence of the disease is unknown, it is estimated to be 1 in 32,000, although the actual incidence may be as high as 1 in 15,000. Genetics PCD is a genetically heterogeneous disorder affecting motile cilia which are made up of approximately 250 proteins. Around 90% of individuals with PCD have ultrastructural defects affecting protein(s) in the outer and/or inner dynein arms, which give cilia their motility, with roughly 38% of these defects caused by mutations on two genes, DNAI1 and DNAH5, both of which code for proteins found in the ciliary outer dynein arm.There is an international effort to identify genes that code for inner dynein arm proteins or proteins from other ciliary structures (radial spokes, central apparatus, etc.) associated with PCD. The role of DNAH5 in heterotaxy syndromes and left-right asymmetry is also under investigation. At least 32 genes have been implicated in this condition. Another gene associated with this condition is GAS2L2. Pathophysiology This condition is genetically inherited. Structures that make up the cilia, including inner and/or outer dynein arms, central apparatus, radial spokes, etc. are missing or dysfunctional and thus the axoneme structure lacks the ability to move. Axonemes are the elongated structures that make up cilia and flagella. Additionally, there may be chemical defects that interfere with ciliary function in the presence of adequate structure. Whatever the underlying cause, dysfunction of the cilia begins during and impacts the embryologic phase of development. Specialised monocilia known as nodal cilia are at the heart of this problem. They lack the central-pair microtubules of ordinary motile cilia and so rotate clockwise rather than beat; in the primitive node at the anterior end of the primitive streak in the embryo, these are angled posteriorly such that they describe a D-shape rather than a circle. This has been shown to generate a net leftward flow in mouse and chick embryos, and sweeps the protein to the left, triggering normal asymmetrical development.However, in some individuals with PCD, mutations thought to be in the gene coding for the key structural protein left-right dynein (lrd) result in monocilia which do not rotate. There is therefore no flow generated in the node, Shh moves at random within it, and 50% of those affected develop situs inversus, which can occur with or without dextrocardia, where the laterality of the internal organs is the mirror-image of normal. Affected individuals therefore have Kartagener syndrome. This is not the case with some PCD-related genetic mutations: at least 6% of the PCD population have a condition called situs ambiguus or heterotaxy, where organ placement or development is neither typical (situs solitus) nor totally reversed (situs inversus totalis) but is a hybrid of the two. Splenic abnormalities such as polysplenia, asplenia and complex congenital heart defects are more common in individuals with situs ambiguus and PCD, as they are in all individuals with situs ambiguus.The genetic forces linking failure of nodal cilia and situs issues and the relationship of those forces to PCD are the subject of intense research interest. However, knowledge in this area is constantly advancing. Relation to other rare genetic disorders Recent findings in genetic research have suggested that a large number of genetic disorders, both genetic syndromes and genetic diseases, that were not previously identified in the medical literature as related, may be, in fact, highly related in the genetypical root cause of the widely varying, phenotypically-observed disorders. Thus, PCD is a ciliopathy. Other known ciliopathies include Bardet–Biedl syndrome, polycystic kidney and liver disease, nephronophthisis, Alström syndrome, Meckel–Gruber syndrome and some forms of retinal degeneration. Diagnosis Several diagnostic tests for this condition have been proposed. These include nasal nitric oxide levels as a screening test, light microscopy of biopsies for ciliary beat pattern and frequency and electron microscopic examination of dynein arms, as the definite diagnosis method. Genetic testing has also been proposed but this is difficult given that there are multiple genes involved. Classification When accompanied by the combination of situs inversus (reversal of the internal organs), chronic sinusitis, and bronchiectasis, it is known as Kartagener syndrome (only 50% of primary ciliary dyskinesia cases include situs inversus). Treatment There are no standardized effective treatment strategies for the condition. Current therapies for PCD are extrapolated from Cystic Fibrosis and patients with non-CF bronchiectasis and lack validation for PCD-specific use. Severe fatal respiratory failure can develop; long-term treatment with macrolides such as clarithromycin, erythromycin and azithromycin has been empirically applied for the treatment of primary ciliary dyskinesia in Japan, though controversial due to the effects of the medications. Prognosis There is no reliable estimate of life expectancy for people with PCD. The largest multi-center study of lung function in people with PCD across many European countries found strong evidence refuting a common assumption that it is a mild disease. This study found that lung function of people with PCD is comparable to those with cystic fibrosis in childhood but is better in young adulthood. Both diseases, however, are progressive and lung function declines with age relative to peer groups. Survey data indicate that respiratory symptoms increase progressively and continuously beginning in the mid-20s relative to the population norm. History The classic symptom combination associated with PCD was first described in 1904 by A. K. Siewert, while Manes Kartagener published his first report on the subject in 1933. The disorder is often now referred to as Siewerts syndrome or Siewert-Kartagener syndrome. References Further reading GeneReview/NCBI/NIH/UW entry on Primary Ciliary Dyskinesia == External links ==
Focal dystonia	Focal dystonia, or focal task specific dystonia, is a neurological condition, a type of dystonia, that affects a muscle or group of muscles in a specific part of the body during specific activities, causing involuntary muscular contractions and abnormal postures. There are many different types of focal dystonia, each effecting a different region of the body. For example, in focal hand dystonia, or writers cramp, the fingers either curl into the palm or extend outward without control. In musicians, the condition is called musicians focal dystonia, or simply, musicians dystonia. In sports, it may be involved in what is commonly referred to as the yips. The condition appears to be associated with over-training, and individualized treatment strategies may involve medications, retraining techniques, and procedures. Signs and Symptoms People with dystonia experience tightness, cramping, fatigue, involuntary sustained or repetitive muscle contractions that can be painless or painful and resulting in abnormal posturing, twisting motions, and even tremors. Focal dystonia typically presents in adults, more commonly in women ranging from ages 30 through 40. Major types of focal dystonia affect the limbs, face, mouth, neck, and larynx. These focal dystonias can be exclusive to specific tasks, like writing or playing an instrument. Focal dystonia will typically have a subtle and slow onset before slowly worsening over years. During the beginning stages, symptoms can be intermittent and without clear associations and provocation. The progression of this disease can vary from person to person. During the first couple years of onset, symptoms can partially or completely disappear for days to months, but return in other parts of the body. Causes Current medical science does not precisely describe the causes of dystonia, however genetic and environmental factors may play a large role. Misfiring of neurons in the sensorimotor cortex, a thin layer of neural tissue that covers the brain, is thought to cause contractions. This misfiring may result from impaired inhibitory mechanisms during muscle contraction. When the brain tells a given muscle to contract, it simultaneously silences muscles that would oppose the intended movement. It appears that dystonia interferes with the brains ability to inhibit those surrounding muscles, leading to loss of selectivity.The sensorimotor cortex is organized as discrete "maps" of the human body. Under normal conditions, each body part (such as individual fingers) occupies a distinct area on these cortical maps. In dystonia, these maps lose their distinct borders and overlap occurs. Exploration of this initially involved over-training particular finger movements in non-human primates, which resulted in the development of focal hand dystonia. Examination of the primary somatosensory cortex in the trained animals showed grossly distorted representations of the maps pertaining to the fingers when compared to the untrained animals. Additionally, these maps in the dystonic animals had lost the distinct borders that were noted in the untrained animals. Imaging studies in humans with focal dystonia have confirmed this finding. Also, synchronous afferent stimulation of peripheral muscles induces organizational changes in motor representations, characterized both by an increase in map size of stimulated muscles and a reduction in map separation, as assessed using transcranial magnetic stimulation.The cross-connectivity between areas that are normally segregated in the sensory cortex may prevent normal sensorimotor feedback and so contribute to the observed co-contraction of antagonist muscle groups, and inappropriately timed and sequenced movements that underlie the symptoms of focal dystonia. It is hypothesized that a deficit in inhibition caused by a genetically mediated loss of inhibitory interneurons may be the underlying cause of the deficits observed in dystonia.While usually painless, in some instances the sustained contraction and abnormal posturing in dystonia cause pain. Focal dystonia most typically affects people who rely on fine motor skills—musicians, writers, surgeons, etc. It is thought that the excessive motor training those skills require may contribute to the development of dystonia as their cortical maps become enlarged and begin to overlap. Focal dystonia is generally "task-specific," meaning that it is only problematic during certain activities. Diagnosis The diagnosis of focal dystonia is highly dependent on the history of the patient, as physical exam is typically normal, and ruling out other causes of movement disorder. The main types of are blepharospasm, oromandibular dystonia, spasmodic dysphonia, spasmodic torticollis, and limb dystonia, all affecting a different region of the body. Labs and imaging may be ordered as workup to evaluate for other causes of dystonia. Focal dystonias involving are commonly misdiagnosed A provider can consider to rule in or out Dopamine-responsive dystonia with a levodopa trial. Treatment Treatment options would be based on the type of focal dystonia the patient has. If possible, incorporating rest earlier to symptom onset has shown to have greater improvement in symptoms for Writers cramp. Physical Therapy Physical therapy is commonly used as an adjunct or main form of treatment for focal dystonia, however more studies for its benefit are needed. Bass guitarist and instructor Scott Devine said that he wears a glove while playing bass guitar because of the condition. He finds that the glove stops the involuntary finger movements. He says it works for him but does not suggest that it may work for everyone with the condition. Medications Anticholinergics such as Artane can be prescribed for off-label use, as some patients have had success. Benzodiazepines, such as Clonazepam, can be used as a muscle relaxant. Other oral medications have been studied for different types of focal dystonia, such as baclofen, tetrabenazine, amantadine, antipsychotics, and amphetamine Procedures This condition is often treated with injections of botulinum neurotoxin type A (BoNT/A). BoNT/A reduces the symptoms of the disorder but it is not a cure for dystonia. Since the root of the problem is neurological, doctors have explored sensorimotor retraining activities to enable the brain to "rewire" itself and eliminate dystonic movements. The work of several doctors such as Nancy Byl and Joaquin Farias has shown that sensorimotor retraining activities and proprioceptive stimulation can induce neuroplasticity, making it possible for patients to recover substantial function that was lost to focal dystonia. For some dystonias, Deep brain stimulation may be considered where BoNT treatment fails. If the dystonia is cause by an underlying nerve entrapment, surgical decompression has shown to have improvement in some cases. Prognosis Recovery from focal dystonia has varying results, ranging from minimal improvement in function to complete recovery and ranging from weeks to years. Prevention Though studies on prevention of focal dystonia is limited, it is believed for musicians dystonia that mindfulness of muscle use and proper rest can help prevent focal dystonia and injury. Performing Arts Medicine Musicians Dystonia Musicians dystonia treatment studies have yielded varying results. This condition can often be misdiagnosed as psychogenic, as this was previously thought to be its cause. In this population, men are affected more than women from 20 to 60 years of age. Evaluation of musicians dystonia should include history before and after symptom onset and observation of playing the instrument, as deficits can be subtle and considered minor to the general population. Treatment modalities available, such as BoNT/A, leave many musicians unsatisfied due to muscle weakness and lack of improvement in muscle control. In musicians, this is commonly associated with overuse or high volume of practicing. Though musicians dystonia presents initially as task-specific, one study found that the dystonia can progress outside of playing their instrument.Treatments such as splinting and sensorimotor retraining for focal hand dystonia have shown to be beneficial with varying results. It is important to consider the mental health and social aspect of this condition as a musicians self-identity and career can be affected considerably. The approach to treating musicians dystonia requires an understanding and collaboration with the musician to obtain a complete history and tailor treatment and education effectively. The most successful treatment for musicians dystonia has been a multidisciplinary approach, involving physicians, physical therapists, physiotherapists, psychologists, and music instructors, focusing on rehabilitation that can involve retraining the brain to play their instrument again and even learning to play other instruments. Noted patients Scott Adams, the writer of the Dilbert comics, has focal dystonia of the right hand, which impedes his artwork. Tom Adams, bluegrass banjo player, has focal dystonia in his right hand, and has switched to the guitar. Badi Assad, Brazilian singer-guitarist, was diagnosed with focal dystonia in 1999; she eventually recovered and resumed her career. Andy Billups, bass guitarist with British rock group, The Hamsters, has made a partial recovery; he plays by using modified guitar plectrums. Liona Boyd, Canadian classical guitarist, publicized as the "First Lady of the Guitar", retired from the concert stage for six years in 2003, due to focal dystonia that affected her right hand. She worked to retrain her right hand, and since 2009 has been performing again as a guitarist, singer, and songwriter. Berkley Breathed, American Pulitzer Prize winning comic strip artist and book writer/illustrator. Known for Bloom County, Opus, and others. His work was featured as that of the main character, as an adult, of the film Second Hand Lions. Stuart Cassells, founder of the bagpipe rock group Red Hot Chilli Pipers, announced focal dystonia in September 2011; he has left the band. Andrew Dawes, noted violinist and co-founder of the Orford String Quartet. Warren Deck, former tubist of the New York Philharmonic. Keith Emerson, pianist and keyboard player Leon Fleisher, an international concert pianist, dealt with this condition in his right hand beginning in the 1960s and switched to only left hand playing. In the 2000s, he regained use of his right hand and recommenced performing and recording with two hands. Dominic Frasca, guitarist Reinhard Goebel, Baroque violinist, switched to playing left-handed. Gary Graffman, pianist, who changed to performing only with his left hand. Jang Jae-in, Korean singer-songwriter and guitarist diagnosed with dystonia in her left hand in 2012. In 2015, on You Hee-yeols Sketchbook, she announced that she quit playing guitar. Alex Klein, principal oboist of the Chicago Symphony Orchestra Alfred Koffler, guitarist of rock band Pink Cream 69, diagnosed in early 2000s. To help him with live shows, Uwe Reitenauer was hired as a second guitarist. Koffler continues to write and perform live on stage with the band. David Leisner, classical guitarist, has recovered the full use of his hand after a decade of disability. Billy McLaughlin, guitarist, switched to playing left-handed when affected by dystonia. Christian Münzner, lead guitarist of progressive extreme metal band Obscura Apostolos Paraskevas, Greek-American classical guitarist-composer, was struck by focal dystonia to his right hand in 2009. He fully recovered in 2013. Charlie Parr, American country blues musician from Minnesota Alex Webster, bassist Victor Wooten, bassist, has it on both hands References === Sources ===

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