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You function as a medical informant. Please provide in-depth yet accessible descriptions of medical terms, suitable for a broad audience.

What is the significance of the term 'Granular corneal dystrophy' in the medical field?

Granular corneal dystrophy is a slowly progressive corneal dystrophy that most often begins in early childhood. Granular corneal dystrophy has two types: Granular corneal dystrophy type I, also corneal dystrophy Groenouw type I, is a rare form of human corneal dystrophy. It was first described by German ophthalmologist Arthur Groenouw in 1890. Granular corneal dystrophy type II, also called Avellino corneal dystrophy or combined granular-lattice corneal dystrophy is also a rare form of corneal dystrophy. The disorder was first described by Folberg et al. in 1988. The name Avellino corneal dystrophy comes from the first four patients in the original study each tracing their family origin to the Italian province of Avellino. Presentation Granular corneal dystrophy is diagnosed during an eye examination by an ophthalmologist or optometrist. The lesions consist of central, fine, whitish granular lesions in the cornea. Visual acuity is slightly reduced. Genetics Granular corneal dystrophy is caused by a mutation in the TGFBI gene, located on chromosome 5q31. The disorder is inherited in an autosomal dominant manner. This indicates that the defective gene responsible for the disorder is located on an autosome (chromosome 5 is an autosome), and only one copy of the gene is sufficient to cause the disorder, when inherited from a parent who has the disorder. The gene TGFBI encodes the protein keratoepithelin. Diagnosis Treatment Corneal transplant is not needed except in very severe and late cases. Light sensitivity may be overcome by wearing tinted glasses. See also Corneal dystrophy == References ==

You are a guide to medical language. Please provide in-depth and understandable explanations of medical terms, highlighting their significance in healthcare.

I'm looking for a concise explanation of the medical term 'Hypochloremia.'

Hypochloremia (or Hypochloraemia) is an electrolyte disturbance in which there is an abnormally low level of the chloride ion in the blood. The normal serum range for chloride is 97 to 107 mEq/L. It rarely occurs in the absence of other abnormalities. It is sometimes associated with hypoventilation. It can be associated with chronic respiratory acidosis. If it occurs together with metabolic alkalosis (decreased blood acidity) it is often due to vomiting. It is usually the result of hyponatremia or elevated bicarbonate concentration. It occurs in cystic fibrosis. References == External links ==

You are a guide to medical language. Please provide in-depth and understandable explanations of medical terms, highlighting their significance in healthcare.

I've come across the term 'Thrombus' in a medical context, but I'm not sure what it means. Can you clarify?

A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cross-linked fibrin protein. The substance making up a thrombus is sometimes called cruor. A thrombus is a healthy response to injury intended to stop and prevent further bleeding, but can be harmful in thrombosis, when a clot obstructs blood flow through healthy blood vessels in the circulatory system. In the microcirculation consisting of the very small and smallest blood vessels the capillaries, tiny thrombi known as microclots can obstruct the flow of blood in the capillaries. This can cause a number of problems particularly affecting the alveoli in the lungs of the respiratory system resulting from reduced oxygen supply. Microclots have been found to be a characteristic feature in severe cases of COVID-19, and in long COVID.Mural thrombi are thrombi that adhere to the wall of a large blood vessel or heart chamber. They are most commonly found in the aorta, the largest artery in the body, more often in the descending aorta, and less often in the aortic arch or abdominal aorta. They can restrict blood flow but usually do not block it entirely. They appear grey-red with alternating light and dark lines (known as lines of Zahn) which represent bands of white blood cells and red blood cells (darker) entrapped in layers of fibrin. Classification Thrombi are classified into two major groups depending on their location and the relative amount of platelets and red blood cells (RBCs). The two major groups are: Arterial or white thrombi (characterized by predominance of platelets) Venous or red thrombi (characterized by predominance of red blood cells). Microclots In the microcirculation consisting of the very small and smallest blood vessels the capillaries, tiny thrombi known as microclots can obstruct the flow of blood in the capillaries. This can cause a number of problems particularly affecting the alveoli in the lungs of the respiratory system resulting from reduced oxygen supply. Microclots have been found to be a characteristic feature in severe cases of COVID-19, and in long COVID. Mural thrombi Mural thrombi are thrombi that adhere to the wall of a large blood vessel or heart chamber. They are most commonly found in the aorta, the largest artery in the body, more often in the descending aorta, and less often in the aortic arch or abdominal aorta. They can restrict blood flow but usually do not block it entirely. Mural thrombi are not usually found in vessels already damaged by atherosclerosis.A mural thrombus can affect any heart chamber. When found in the left ventricle it is often a result of a heart attack complication. The thrombus in this case can separate from the chamber, be carried through arteries and block a blood vessel. They appear grey-red with alternating light and dark lines (known as lines of Zahn) which represent bands of white blood cells and red blood cells (darker) entrapped in layers of fibrin. Cause Virchows triad describes the pathogenesis of thrombus formation: Endothelial injury: Injury to the endothelium (interior surface of blood vessel), causing platelet activation and aggregation; Common causes include: trauma, smoking, hypertension, atheroma. Hemodynamic changes (stasis, turbulence): Blood stasis promotes greater contact between platelets/coagulative factors with vascular endothelium. If rapid blood circulation (e.g., because of tachycardia) occurs within vessels that have endothelial injuries, that creates disordered flow (turbulence) that can lead to the formation of thrombosis;Common causes of stasis include anything that leads to prolonged immobility and reduced blood flow such as: trauma/broken bones and extended air travel. Hypercoagulability (also called thrombophilia; any disorder of the blood that predisposes to thrombosis); Common causes include: cancer (leukaemia), factor V mutation (Leiden) - prevents Factor V inactivation leading to increased coagulability.Disseminated intravascular coagulation (DIC) involves widespread microthrombi formation throughout the majority of the blood vessels. This is due to excessive consumption of coagulation factors and subsequent activation of fibrinolysis using all of the bodys available platelets and clotting factors. The result is hemorrhaging and ischemic necrosis of tissue/organs. Causes are septicaemia, acute leukaemia, shock, snake bites, fat emboli from broken bones, or other severe traumas. DIC may also be seen in pregnant females. Treatment involves the use of fresh frozen plasma to restore the level of clotting factors in the blood, as well as platelets and heparin to prevent further thrombi formation. Pathophysiology A thrombus occurs when the hemostatic process, which normally occurs in response to injury, becomes activated in an uninjured or slightly injured vessel. A thrombus in a large blood vessel will decrease blood flow through that vessel (termed a mural thrombus). In a small blood vessel, blood flow may be completely cut off (termed an occlusive thrombus), resulting in death of tissue supplied by that vessel. If a thrombus dislodges and becomes free-floating, it is considered an embolus. If an embolus becomes trapped within a blood vessel, it blocks blood flow and is termed as an embolism. Embolisms, depending on their specific location, can cause more significant effects like strokes, heart attacks, or even death.Some of the conditions which increase the risk of blood clots developing include atrial fibrillation (a form of cardiac arrhythmia), heart valve replacement, a recent heart attack (also known as a myocardial infarction), extended periods of inactivity (see deep venous thrombosis), and genetic or disease-related deficiencies in the bloods clotting abilities. Formation Platelet activation occurs through injuries that damage the endothelium of the blood vessels, exposing the enzyme called factor VII, a protein normally circulating within the vessels, to the tissue factor, which is a protein encoded by the F3 gene. The platelet activation can potentially cause a cascade, eventually leading to the formation of the thrombus. This process is regulated through thromboregulation. Prevention Anticoagulants are drugs used to prevent the formation of blood clots, reducing the risk of stroke, heart attack and pulmonary embolism. Heparin and warfarin are used to inhibit the formation and growth of existing thrombi, with the former used for acute anticoagulation while the latter is used for long-term anticoagulation. The mechanism of action of heparin and warfarin are different as they work on different pathways of the coagulation cascade. Heparin works by binding to and activating the enzyme inhibitor antithrombin III, an enzyme that acts by inactivating thrombin and factor Xa. In contrast, warfarin works by inhibiting vitamin K epoxide reductase, an enzyme needed to synthesize vitamin K dependent clotting factors II, VII, IX, and X. Bleeding time with heparin and warfarin therapy can be measured with the partial thromboplastin time (PTT) and prothrombin time (PT), respectively. Treatment Once clots have formed, other drugs can be used to promote thrombolysis or clot breakdown. Streptokinase, an enzyme produced by streptococcal bacteria, is one of the oldest thrombolytic drugs. This drug can be administered intravenously to dissolve blood clots in coronary vessels. However, streptokinase causes systemic fibrinolytic state and can lead to bleeding problems. Tissue plasminogen activator (tPA) is a different enzyme that promotes the degradation of fibrin in clots but not free fibrinogen. This drug is made by transgenic bacteria and converts plasminogen into the clot-dissolving enzyme, plasmin. Recent research indicates that tPA could have toxic effects in the central nervous system. In cases of severe stroke, tPA can cross the blood-brain barrier and enter interstitial fluid, where it then increases excitotoxicity, potentially affecting permeability of the blood-brain barrier, and causing cerebral hemorrhage.There are also some anticoagulants that come from animals that work by dissolving fibrin. For example, Haementeria ghilianii, an Amazon leech, produces an enzyme called hementin from its salivary glands. Prognosis Thrombus formation can have one of four outcomes: propagation, embolization, dissolution, and organization and recanalization. Propagation of a thrombus occurs towards the direction of the heart and involves the accumulation of additional platelets and fibrin. This means that it is anterograde in veins or retrograde in arteries. Embolization occurs when the thrombus breaks free from the vascular wall and becomes mobile, thereby traveling to other sites in the vasculature. A venous embolus (mostly from deep vein thrombosis in the lower limbs) will travel through the systemic circulation, reach the right side of the heart, and travel through the pulmonary artery, resulting in a pulmonary embolism. Arterial thrombosis resulting from hypertension or atherosclerosis can become mobile and the resulting emboli can occlude any artery or arteriole downstream of the thrombus formation. This means that cerebral stroke, myocardial infarction, or any other organ can be affected. Dissolution occurs when the fibrinolytic mechanisms break up the thrombus and blood flow is restored to the vessel. This may be aided by fibrinolytic drugs such as Tissue Plasminogen Activator (tPA) in instances of coronary artery occlusion. The best response to fibrinolytic drugs is within a couple of hours, before the fibrin meshwork of the thrombus has been fully developed. Organization and recanalization involves the ingrowth of smooth muscle cells, fibroblasts and endothelium into the fibrin-rich thrombus. If recanalization proceeds it provides capillary-sized channels through the thrombus for continuity of blood flow through the entire thrombus but may not restore sufficient blood flow for the metabolic needs of the downstream tissue. See also Thrombogenicity (the tendency to clot) National Blood Clot Alliance Hemorrhoid References External links Muscle Relaxing Drugs Can Reduce Lethal Blood Clots Archived 2009-02-04 at the Wayback Machine Air Pollution Triggers Blood Clots - US Study.

You function as a medical dictionary. Offer comprehensive and accurate descriptions of medical terms, ensuring clarity and depth in your explanations.

Could you please explain the term 'Nasal septum deviation' in simple language?

Nasal septum deviation is a physical disorder of the nose, involving a displacement of the nasal septum. Some displacement is common, affecting 80% of people, mostly without their knowledge. Signs and symptoms The nasal septum is the bone and cartilage in the nose that separates the nasal cavity into the two nostrils. The cartilage is called the quadrangular cartilage and the bones comprising the septum include the maxillary crest, vomer and the perpendicular plate of the ethmoid. Normally, the septum lies centrally, and thus the nasal passages are symmetrical. A deviated septum is an abnormal condition in which the top of the cartilaginous ridge leans to the left or the right, causing obstruction of the affected nasal passage. It is common for nasal septa to depart from the exact centerline; the septum is only considered deviated if the shift is substantial or causes problems. By itself, a deviated septum can go undetected for years and thus be without any need for correction.Symptoms of a deviated septum include infections of the sinus and sleep apnea, snoring, repetitive sneezing, facial pain, nosebleeds, mouth breathing, difficulty with breathing and mild to severe loss of the ability to smell. Only more severe cases of a deviated septum will cause symptoms of difficulty breathing and require treatment. Causes It is most frequently caused by impact trauma, such as by a blow to the face. It can also be a congenital disorder, caused by compression of the nose during childbirth. Deviated septum is associated with genetic connective tissue disorders such as Marfan syndrome, Homocystinuria and Ehlers–Danlos syndrome. Diagnosis Nasal septum deviation is the most common cause of nasal obstruction. A history of trauma to the nose is often present including trauma from the process of birth or microfractures. A medical professional, such as an otorhinolaryngologist (ears, nose, and throat doctor), typically makes the diagnosis after taking a thorough history from the affected person and performing a physical examination. Imaging of the nose is sometimes used to aid in making the diagnosis as well. Treatment Medical therapy with nasal sprays including decongestants, antihistamines, or nasal corticosteroid sprays is typically tried first before considering a surgical approach to correct nasal septum deviation. Medication temporarily relieves symptoms, but does not correct the underlying condition. Non-medical relief can also be obtained using nasal strips. A minor surgical procedure known as septoplasty can cure symptoms related to septal deviations. The surgery lasts roughly one hour and does not result in any cosmetic alteration or external scars. Nasal congestion, pain, drainage, or swelling may occur within the first few days after the surgery. Recovery from the procedure may take anywhere from 2 days to 4 weeks to heal completely. Septal bones never regrow. If symptoms reappear they are not related to deviations. Reappearance of symptoms may be due to mucosal metaplasia of the nose.Currently, the most gentle and effective treatment is laser septo-chondroplasty for the septal cartilage segment deformity and ultrasound septoplasty — effective for the septal cartilage and bone deformation. Complications of septoplasty Nasal septum perforation due to bilateral trauma of the mucoperichondrial flaps opposite each other. Incomplete correction with persistent nasal symptoms External nasal deformity Septal hematoma and septal abscess. Scarring inside the nose and nose bleeding Adhesions and synechiae between septal mucosa and lateral nasal wall Saddle nose due to over-resection of the dorsal wall of the septal cartilage Dropped nasal tip due to resection of the caudal margin See also Nasal septum perforation References == External links ==

You function as a medical dictionary. Offer comprehensive and accurate descriptions of medical terms, ensuring clarity and depth in your explanations.

Please help me grasp the concept behind the medical term 'GM1 gangliosidoses.'

The GM1 gangliosidoses, usually shortened to GM1, are gangliosidoses caused by mutation in the GLB1 gene resulting in a deficiency of beta-galactosidase. The deficiency causes abnormal storage of acidic lipid materials in cells of the central and peripheral nervous systems, but particularly in the nerve cells, resulting in progressive neurodegeneration. GM1 is a rare lysosomal storage disorder with a prevalence of 1 to every 100,000 to 200,000 live births worldwide, although rates are higher in some regions. Cause GM1 Gangliosidoses disorders are caused by mutations in the GLB1 gene, which codes for lysosomal hydrolase, acid beta-galactosidase (β-gal). Low levels of β-gal cause an accumulation of GM1 gangliosides. They are inherited, autosomal recessive sphingolipidoses, a class of lipid storage disorders. Diagnosis Diagnosis of GM1 can be obtained by genetic and enzymatic testing. Types GM1 has three forms classified by age of onset. Type 1: early infantile Type 2: late infantile/juvenile Type 3: adult Early infantile GM1 Symptoms of early infantile GM1 (the most severe subtype, with onset shortly after birth) may include neurodegeneration, seizures, liver enlargement (hepatomegaly), spleen enlargement (splenomegaly), coarsening of facial features, skeletal irregularities, joint stiffness, distended abdomen, muscle weakness, exaggerated startle response to sound, and problems with gait.About half of affected patients develop cherry-red spots in the eye. Children may be deaf and blind by age 1 and often die by age 3 from cardiac complications or pneumonia. Early psychomotor deterioration: decreased activity and lethargy in the first weeks; never sit; feeding problems - failure to thrive; visual failure (nystagmus noted) by 6 months; initial hypotonia; later spasticity with pyramidal signs; secondary microcephaly develops; decerebrate rigidity by 1 year and death by age 1–2 years (due to pneumonia and respiratory failure); some have hyperacusis. Macular cherry-red spots in 50% by 6–10 months; corneal opacities in some Facial dysmorphology: frontal bossing, wide nasal bridge, facial edema (puffy eyelids); peripheral edema, epicanthus, long upper lip, microretrognathia, gingival hypertrophy (thick alveolar ridges), macroglossia Hepatomegaly by 6 months and splenomegaly later; some have cardiac failure Skeletal deformities: flexion contractures noted by 3 months; early subperiosteal bone formation (may be present at birth); diaphyseal widening later; demineralization; thoracolumbar vertebral hypoplasia and beaking at age 3–6 months; kyphoscoliosis. *Dysostosis multiplex (as in the mucopolysaccharidoses) 10–80% of peripheral lymphocytes are vacuolated; foamy histiocytes in bone marrow; visceral mucopolysaccharide storage similar to that in Hurler disease; GM1 storage in cerebral gray matter is 10-fold elevated (20–50-fold increased in viscera) Galactose-containing oligosacchariduria and moderate keratan sulfaturia Morquio disease Type B: Mutations with higher residual beta-galactosidase activity for the GM1 substrate than for keratan sulfate and other galactose-containing oligosaccharides have minimal neurologic involvement but severe dysostosis resembling Morquio disease type A (Mucopolysaccharidosis type 4). Late infantile/Juvenile GM1 Onset of late infantile GM1 is typically between ages 1 and 3 years. The juvenile form may be diagnosed into childhood. Some children live into adolescence or early adulthood. This subtype is characterized by a trajectory in which some developmental skills are gained, then they stabilize and delays occur, and these are followed by regression. Early symptoms include difficulty crawling and walking, hypotonia, speech and swallowing problems, and seizures. Neurological symptoms include ataxia, seizures, dementia, and difficulties with speech. Adult GM1 Onset of adult GM1 is typically in adolescence or adulthood and is the slowest progressing of the subtypes. Symptoms include muscle atrophy, neurological complications that are less severe and progress at a slower rate than in other forms of the disorder, corneal clouding in some patients, and dystonia (sustained muscle contractions that cause twisting and repetitive movements or abnormal postures). Angiokeratomas may develop on the lower part of the trunk of the body. Most patients have a normal size liver and spleen. Prenatal diagnosis is possible by measurement of Acid Beta Galactosidase in cultured amniotic cells. Treatment There is no cure for GM1, although several gene therapy trials are underway. More information for these can be found at ClinicalTrials.gov. Treatment for GM1 is symptom-based and palliative. References External links CureGM1 Foundations mission is to fund research for the benefit of all those who suffer from GM1 gangliosidosis. National Tay-Sachs & Allied Diseases Association (NTSAD) provides support for families Tay-Sachs, Canavan, GM1, and Sandhoff diseases by driving research, forging collaboration, and fostering community. MPS Society is based in the UK and provides support and resources for families with MPS (Mucopolysaccharide), Fabry and related disorders, including GM1.

You are a guide to medical language. Please provide in-depth and understandable explanations of medical terms, highlighting their significance in healthcare.

I'm not familiar with the medical term 'Femur.' Could you provide some insights?

The femur (; pl. femurs or femora ), or thigh bone, is the proximal bone of the hindlimb in tetrapod vertebrates. The head of the femur articulates with the acetabulum in the pelvic bone forming the hip joint, while the distal part of the femur articulates with the tibia (shinbone) and patella (kneecap), forming the knee joint. By most measures the two (left and right) femurs are the strongest bones of the body, and in humans, the largest and thickest. Structure The femur is the only bone in the upper leg. The two femurs converge medially toward the knees, where they articulate with the proximal ends of the tibiae. The angle of convergence of the femora is a major factor in determining the femoral-tibial angle. Human females have thicker pelvic bones, causing their femora to converge more than in males. In the condition genu valgum (knock knee) the femurs converge so much that the knees touch one another. The opposite extreme is genu varum (bow-leggedness). In the general population of people without either genu valgum or genu varum, the femoral-tibial angle is about 175 degrees.The femur is the largest and thickest bone in the human body. By some measures, it is also the strongest bone in the human body. This depends on the type of measurement taken to calculate strength. Some strength tests show the temporal bone in the skull to be the strongest bone. The femur length on average is 26.74% of a persons height, a ratio found in both men and women and most ethnic groups with only restricted variation, and is useful in anthropology because it offers a basis for a reasonable estimate of a subjects height from an incomplete skeleton. The femur is categorised as a long bone and comprises a diaphysis (shaft or body) and two epiphyses (extremities) that articulate with adjacent bones in the hip and knee. Upper part The upper or proximal extremity (close to the torso) contains the head, neck, the two trochanters and adjacent structures. The upper extremity is the shortest femoral extremity, the lower extremity is the thickest femoral extremity. The head of the femur, which articulates with the acetabulum of the pelvic bone, comprises two-thirds of a sphere. It has a small groove, or fovea, connected through the round ligament to the sides of the acetabular notch. The head of the femur is connected to the shaft through the neck or collum. The neck is 4–5 cm. long and the diameter is smallest front to back and compressed at its middle. The collum forms an angle with the shaft in about 130 degrees. This angle is highly variant. In the infant it is about 150 degrees and in old age reduced to 120 degrees on average. An abnormal increase in the angle is known as coxa valga and an abnormal reduction is called coxa vara. Both the head and neck of the femur is vastly embedded in the hip musculature and can not be directly palpated. In skinny people with the thigh laterally rotated, the head of the femur can be felt deep as a resistance profound (deep) for the femoral artery.The transition area between the head and neck is quite rough due to attachment of muscles and the hip joint capsule. Here the two trochanters, greater and lesser trochanter, are found. The greater trochanter is almost box-shaped and is the most lateral prominent of the femur. The highest point of the greater trochanter is located higher than the collum and reaches the midpoint of the hip joint. The greater trochanter can easily be felt. The trochanteric fossa is a deep depression bounded posteriorly by the intertrochanteric crest on the medial surface of the greater trochanter. The lesser trochanter is a cone-shaped extension of the lowest part of the femur neck. The two trochanters are joined by the intertrochanteric crest on the back side and by the intertrochanteric line on the front.A slight ridge is sometimes seen commencing about the middle of the intertrochanteric crest, and reaching vertically downward for about 5 cm. along the back part of the body: it is called the linea quadrata (or quadrate line). About the junction of the upper one-third and lower two-thirds on the intertrochanteric crest is the quadrate tubercle located. The size of the tubercle varies and it is not always located on the intertrochanteric crest and that also adjacent areas can be part of the quadrate tubercle, such as the posterior surface of the greater trochanter or the neck of the femur. In a small anatomical study it was shown that the epiphyseal line passes directly through the quadrate tubercle. Body The body of the femur (or shaft) is large, thick and almost cylindrical in form. It is a little broader above than in the center, broadest and somewhat flattened from before backward below. It is slightly arched, so as to be convex in front, and concave behind, where it is strengthened by a prominent longitudinal ridge, the linea aspera which diverges proximally and distal as the medial and lateral ridge. Proximally the lateral ridge of the linea aspera becomes the gluteal tuberosity while the medial ridge continues as the pectineal line. Besides the linea aspera the shaft has two other bordes; a lateral and medial border. These three bordes separates the shaft into three surfaces: One anterior, one medial and one lateral. Due to the vast musculature of the thigh the shaft can not be palpated.The third trochanter is a bony projection occasionally present on the proximal femur near the superior border of the gluteal tuberosity. When present, it is oblong, rounded, or conical in shape and sometimes continuous with the gluteal ridge. A structure of minor importance in humans, the incidence of the third trochanter varies from 17–72% between ethnic groups and it is frequently reported as more common in females than in males. Lower part The lower extremity of the femur (or distal extremity) is the thickest femoral extremity, the upper extremity is the shortest femoral extremity. It is somewhat cuboid in form, but its transverse diameter is greater than its antero-posterior (front to back). It consists of two oblong eminences known as the condyles.Anteriorly, the condyles are slightly prominent and are separated by a smooth shallow articular depression called the patellar surface. Posteriorly, they project considerably and a deep notch, the Intercondylar fossa of femur, is present between them. The lateral condyle is the more prominent and is the broader both in its antero-posterior and transverse diameters. The medial condyle is the longer and, when the femur is held with its body perpendicular, projects to a lower level. When, however, the femur is in its natural oblique position the lower surfaces of the two condyles lie practically in the same horizontal plane. The condyles are not quite parallel with one another; the long axis of the lateral is almost directly antero-posterior, but that of the medial runs backward and medialward. Their opposed surfaces are small, rough, and concave, and form the walls of the intercondyloid fossa. This fossa is limited above by a ridge, the intercondyloid line, and below by the central part of the posterior margin of the patellar surface. The posterior cruciate ligament of the knee joint is attached to the lower and front part of the medial wall of the fossa and the anterior cruciate ligament to an impression on the upper and back part of its lateral wall.The articular surface of the lower end of the femur occupies the anterior, inferior, and posterior surfaces of the condyles. Its front part is named the patellar surface and articulates with the patella; it presents a median groove which extends downward to the intercondyloid fossa and two convexities, the lateral of which is broader, more prominent, and extends farther upward than the medial.Each condyle is surmounted by an elevation, the epicondyle. The medial epicondyle is a large convex eminence to which the tibial collateral ligament of the knee-joint is attached. At its upper part is the adductor tubercle and behind it is a rough impression which gives origin to the medial head of the gastrocnemius. The lateral epicondyle which is smaller and less prominent than the medial, gives attachment to the fibular collateral ligament of the knee-joint. Development The femur develops from the limb buds as a result of interactions between the ectoderm and the underlying mesoderm, formation occurs roughly around the fourth week of development.By the sixth week of development, the first hyaline cartilage model of the femur is formed by chondrocytes. Endochondral ossification begins by the end of the embryonic period and primary ossification centers are present in all long bones of the limbs, including the femur, by the 12th week of development. The hindlimb development lags behind forelimb development by 1–2 days. Function As the femur is the only bone in the thigh, it serves as an attachment point for all the muscles that exert their force over the hip and knee joints. Some biarticular muscles – which cross two joints, like the gastrocnemius and plantaris muscles – also originate from the femur. In all, 23 individual muscles either originate from or insert onto the femur. In cross-section, the thigh is divided up into three separate fascial compartments divided by fascia, each containing muscles. These compartments use the femur as an axis, and are separated by tough connective tissue membranes (or septa). Each of these compartments has its own blood and nerve supply, and contains a different group of muscles. These compartments are named the anterior, medial and posterior fascial compartments. Muscle attachments Clinical significance Fractures A femoral fracture that involves the femoral head, femoral neck or the shaft of the femur immediately below the lesser trochanter may be classified as a hip fracture, especially when associated with osteoporosis. Femur fractures can be managed in a pre-hospital setting with the use of a traction splint. Diversity among animals In primitive tetrapods, the main points of muscle attachment along the femur are the internal trochanter and third trochanter, and a ridge along the ventral surface of the femoral shaft referred to as the adductor crest. The neck of the femur is generally minimal or absent in the most primitive forms, reflecting a simple attachment to the acetabulum. The greater trochanter was present in the extinct archosaurs, as well as in modern birds and mammals, being associated with the loss of the primitive sprawling gait. The lesser trochanter is a unique development of mammals, which lack both the internal and fourth trochanters. The adductor crest is also often absent in mammals or alternatively reduced to a series of creases along the surface of the bone. Structures analogous to the third trochanter are present in mammals, including some primates.Some species of whales, snakes, and other non-walking vertebrates have vestigial femurs. In some snakes the protruding end of a pelvic spur, a vestigial pelvis and femur remnant which is not connected to the rest of the skeleton, plays a role in mating. This role in mating is hypothesized to have possibly occurred in Basilosauridae, an extinct family of whales with well-defined femurs, lower legs and feet. Occasionally, the genes that code for longer extremities cause a modern whale to develop miniature legs (atavism).One of the earliest known vertebrates to have a femur is the eusthenopteron, a prehistoric lobe-finned fish from the Late Devonian period. Viral metagenomics A recent study revealed that bone is a much richer source of persistent DNA viruses than earlier perceived. Besides Parvovirus 19 and hepatitis B virus, ten additional ones were discovered, namely several members of the herpes- and polyomavirus families, as well as human papillomavirus 31 and torque teno virus. Invertebrates In invertebrate zoology the name femur appears in arthropodology. The usage is not homologous with that of vertebrate anatomy; the term "femur" simply has been adopted by analogy and refers, where applicable, to the most proximal of (usually) the two longest jointed segments of the legs of the arthropoda. The two basal segments preceding the femur are the coxa and trochanter. This convention is not followed in carcinology but it applies in arachnology and entomology. In myriapodology another segment, the prefemur, connects the trochanter and femur. Additional media References External links Media related to Femur at Wikimedia Commons The dictionary definition of Femur at Wiktionary The dictionary definition of thighbone at Wiktionary

You serve as a guide in the medical field. Explain medical terms thoroughly, ensuring the information is both insightful and comprehensible.

Can you demystify the medical term 'Oculocutaneous albinism' for me?

Oculocutaneous albinism is a form of albinism involving the eyes (oculo-), the skin (-cutaneous), and the hair. Overall, an estimated 1 in 20,000 people worldwide are born with oculocutaneous albinism. OCA is caused by mutations in several genes that control the synthesis of melanin within the melanocytes. Seven types of oculocutaneous albinism have been described, all caused by a disruption of melanin synthesis and all autosomal recessive disorders.: 864  Oculocutaneous albinism is also found in non-human animals. Types The following types of oculocutaneous albinism have been identified in humans. See also Piebaldism List of skin conditions List of cutaneous conditions associated with increased risk of nonmelanoma skin cancer References External links Oculocutaneous albinism information at RareDiseases.org NCBI Genetic Testing Registry

You function as a medical explainer. Your task is to convey the meanings of medical terms in a detailed, yet easy-to-understand manner.

What does the medical term 'Dolichocolon' encompass?

Dolichocolon is an abnormally long large intestine. It should not be confused with an abnormally wide large intestine, which is called a megacolon.Dolichocolon may predispose to abnormal rotation (see volvulus) and interposition between the diaphragm and the liver (see Chilaiditi syndrome). It is more commonly seen in the elderly, some psychiatric patients or in institutionalised individuals. It is not, however, a part of normal aging. The exact cause remains unknown.Dolichocolon is often an incidental finding on abdominal X-rays or colonoscopy. It is not by itself a disease and as such requires no treatment. The term is from ancient Greek dolichos, the long distance in running, and colon. References == External links ==

You are a guide to medical language. Please provide in-depth and understandable explanations of medical terms, highlighting their significance in healthcare.

Could you please explain the term 'Dexmedetomidine' in simple language?

Dexmedetomidine, sold under the trade name Precedex among others, is a medication used for sedation. It is also used to treat acute agitation associated with schizophrenia or bipolar I or II disorder.Similar to clonidine, it is a sympatholytic drug that acts as an agonist of α2-adrenergic receptors in certain parts of the brain. Veterinarians use dexmedetomidine for similar purposes in treating cats, dogs, and horses. It was developed by Orion Pharma. Medical uses Intensive care unit sedation Studies suggest dexmedetomidine for sedation in mechanically ventilated adults may reduce time to extubation and ICU stay.Compared with other sedatives, some studies suggest dexmedetomidine may be associated with less delirium. However, this finding is not consistent across multiple studies. At the very least, when aggregating many study results together, use of dexmedetomidine appears to be associated with less neurocognitive dysfunction compared to other sedatives. Whether this observation has a beneficial psychological impact is unclear. From an economic perspective, dexmedetomidine is associated with lower ICU costs, largely due to a shorter time to extubation. Procedural sedation Dexmedetomidine can also be used for procedural sedation such as during colonoscopy. It can be used as an adjunct with other sedatives like benzodiazepines, opioids, and propofol to enhance sedation and help maintain hemodynamic stability by decreasing the requirement of other sedatives. Dexmedetomidine is also used for procedural sedation in children.It can be used for sedation required for awake fibreoptic nasal intubation in patients with a difficult airway. Other Dexmedetomidine may be useful for the treatment of the negative cardiovascular effects of acute amphetamines and cocaine intoxication and overdose. Dexmedetomidine has also been used as an adjunct to neuroaxial anesthesia for lower limb procedures.In 2022 it was approved by the FDA for the treatment of agitation in schizophrenia and bipolar disorder. Side effects There is no absolute contraindication to the use of dexmedetomidine. It has a biphasic effect on blood pressure with lower readings at lower drug concentrations and higher readings at higher concentrations. Interactions Dexmedetomidine may enhance the effects of other sedatives and anesthetics when co-administered. Similarly, drugs that lower blood pressure and heart rate, such as beta blockers, may also have enhanced effects when co-administered with dexmedetomidine. Pharmacology Pharmacodynamics Dexmedetomidine is a highly selective α2-adrenergic agonist. It possesses an α2:α1 selectivity ratio of 1620:1, making it eight times more selective for the α2-receptor than clonidine. Unlike opioids and other sedatives such as propofol, dexmedetomidine is able to achieve its effects without causing respiratory depression. Dexmedetomidine induces sedation by decreasing activity of noradrenergic neurons in the locus ceruleus in the brain stem, thereby increasing the downstream activity of inhibitory gamma-aminobutyric acid (GABA) neurons in the ventrolateral preoptic nucleus. In contrast, other sedatives like propofol and benzodiazepines directly increase activity of gamma-aminobutyric acid neurons. Through action on this endogenous sleep-promoting pathway the sedation produced by dexmedetomidine more closely mirrors natural sleep (specifically stage 2 non-rapid eye movement sleep), as demonstrated by EEG studies. As such, dexmedetomidine provides less amnesia than benzodiazepines. Dexmedetomidine also has analgesic effects at the spinal cord level and other supraspinal sites. Pharmacokinetics Intravenous dexmedetomidine exhibits linear pharmacokinetics with a rapid distribution half-life of approximately 6 minutes in healthy volunteers, and a longer and more variable distribution half-life in ICU patients. The terminal elimination half-life of intravenous dexmedetomidine ranged 2.1 to 3.1 hours in healthy adults and 2.2 to 3.7 hours in ICU patients. Plasma protein binding of dexmedetomidine is about 94% (mostly albumin).Dexmedetomidine is metabolized by the liver, largely by glucuronidation (34%) as well as by oxidation via CYP2A6 and other Cytochrome P450 enzymes. As such, it should be used with caution in people with liver disease.The majority of metabolized dexmedetomidine is excreted in the urine (~95%).It can be absorbed sublingually. History Dexmedetomidine was approved in 1999 by the US Food and Drug Administration (FDA) as a short-term sedative and analgesic (<24 hours) for critically ill or injured people on mechanical ventilation in the intensive care unit (ICU). The rationale for its short-term use was due to concerns over withdrawal side effects such as rebound high blood pressure. These effects have not been consistently observed in research studies, however. Veterinary use Dexmedetomidine, under the trade name Dexdomitor (Orion Corporation), was approved in the European Union in for use in cats and dogs in 2002, for sedation and induction of general anesthesia. The FDA approved dexmedetomidine for use in dogs in 2006 and cats in 2007.In 2015, the European Medicines Agency and the FDA approved an oromucosal gel form of dexmedetomidine marketed as Sileo (Zoetis) for use in dogs for relief of noise aversion. References External links "Dexmedetomidine". Drug Information Portal. U.S. National Library of Medicine. "Dexmedetomidine hydrochloride". Drug Information Portal. U.S. National Library of Medicine.

You function as a medical explainer. Your task is to convey the meanings of medical terms in a detailed, yet easy-to-understand manner.

I'd like to learn more about the medical term 'Myospherulosis.' Can you provide some details?

Myospherulosis, also known as spherulocytosis, is a foreign body-type granulomatous reaction to lipid-containing material and blood.It may be seen in various settings including: Fat necrosis. Malignancy, e.g. renal cell carcinoma. Placement of topical tetracycline in a petrolatum base into a surgical site.The resultant histopathologic pattern is most unusual and initially was mistakenly thought to represent a previously undescribed endosporulating fungus. See also Fat necrosis == References ==

You are an expert in medical terminology. Explain medical terms in a way that is both precise and easy to understand for non-medical audiences.

I'm seeking clarification on the medical term 'Vanishing twin.' Could you explain it?

A vanishing twin, also known as twin resorption, is a fetus in a multigestation pregnancy that dies in utero and is then partially or completely reabsorbed. In some instances, the dead twin is compressed into a flattened, parchment-like state known as fetus papyraceus.Vanishing twins occur in up to one of every eight multifetus pregnancies and may not even be known in most cases. "High resorption rates, which cannot be explained on the basis of the expected abortion rate, suggest intense fetal competition for space, nutrition, or other factors during early gestation, with frequent loss or resorption of the other twin(s)."In pregnancies achieved by in vitro fertilization, "it frequently happens that more than one amniotic sac can be seen in early pregnancy, whereas a few weeks later there is only one to be seen and the other has vanished." See also Chimera (genetics) Mosaicism Parasitic twin References Further reading External links Vanishing twin at eMedicine.com 50 articles about vanishing twin phenomenon in PubMed

You are a conduit for medical education. Your task is to offer detailed explanations of medical terms, ensuring they are understandable and precise.

I've encountered the term 'Nicotine replacement therapy' while reading about medical topics. What does it refer to exactly?

Nicotine replacement therapy (NRT) is a medically approved way to treat people with tobacco use disorder by taking nicotine by means other than tobacco. It is used to help with quitting smoking or stopping chewing tobacco. It increases the chance of quitting tobacco smoking by about 55%. Often it is used along with other behavioral techniques. NRT has also been used to treat ulcerative colitis. Types of NRT include the adhesive patch, chewing gum, lozenges, nose spray, and inhaler. The use of multiple types of NRT at a time may increase effectiveness.Common side effects depend on the formulation of nicotine. Common side effects with the gum include nausea, hiccups, and irritation of the mouth. Common side effects with the patch include skin irritation and a dry mouth while the inhaler commonly results in a cough, runny nose, or headaches. Serious risks include nicotine poisoning and continued addiction. They do not appear to increase the risk of heart attacks. There are possible harms to the baby if used during pregnancy. Nicotine replacement therapy works by reducing cravings caused by nicotine addiction.They were first approved for use in 1984, in the United States. Nicotine replacement products are on the World Health Organizations List of Essential Medicines. They are available as generic medications. Medical uses Nicotine replacement therapy, in the form of gum, patches, nasal spray, inhaler and lozenges all improve the ability of people trying to quit tobacco products. Nicotine replacement therapy is as effective as medications, such as bupropion, in helping people quit smoking for at least six months. All forms of nicotine replacement therapy, including nicotine gum, patches, nasal spray, inhalers, and lozenges, have similar success rates in terms of helping people stop smoking. However, the likelihood that someone will stick to a certain treatment varies, with compliance being the highest with nicotine patches, followed by nicotine gum, inhalers, and nasal sprays. Using a few different nicotine replacement methods in combination may improve success rates in stopping tobacco use. Additionally, using nicotine replacement with counseling has been proven to improve tobacco abstinence rates. These other strategies include: creating a plan to quit and utilizing quit programs, a quit phone line, or app that provides tips and inspiration to help quit.Using nicotine replacement therapy to quit smoking should be considered for people who are severely dependent on nicotine. People who are severely dependent include those who smoke: more than one pack per day, within five minutes of awakening, while ill, when they wake up in the middle of the night, to ease withdrawal signs and symptoms.Nicotine replacement products are most beneficial for heavy smokers who smoke more than 15 cigarettes per day. There are not enough studies to show whether NRT helps those who smoke fewer than 10 cigarettes per day. Effectiveness Evaluation of NRT in real-world studies produces more modest outcomes than efficacy studies conducted by industry-funded trials. The National Health Service (NHS) in England has a smoking cessation service based on pharmacotherapy in combination with counseling support. An Action on Smoking and Health (UK) (ASH) report claims that the average cost per life-year gained for every smoker successfully treated by these services is less than £1,000 (below the NICE guidelines of £20,000 per QALY (quality-adjusted life year). However, the investment in NHS stop smoking services is relatively low. A comparison with treatment costs for illicit drug users shows that £585 million is committed for 350,000 problem drug users compared to £56 million for 9 million users of tobacco. This is £6.20 for each smoker, compared to £1,670 per illegal drug user.The claims for high efficacy and cost-effectiveness of NRT have not been substantiated in real-world effectiveness studies. Pierce and Gilpin (2002) stated their conclusion as follows: “Since becoming available over the counter, NRT appears no longer effective in increasing long-term successful cessation” (p. 1260). Efficacy studies, which are conducted using randomized controlled trials, do not transfer very well to real-world effectiveness. Bauld, Bell, McCullough, Richardson and Greaves (2009) reviewed 20 studies on the effectiveness of intensive NHS treatments for smoking cessation published between 1990 and 2007. Quit rates showed a dramatic decrease between 4-weeks and one year. A quit rate of 53% at four weeks fell to only 15% at one year. Younger smokers, females, pregnant smokers and more deprived smokers had lower quit rates than other groups. The efficacy for each of the formulations alone (lozenges, nasal spray, gum, and transdermal patch) to aid in smoking cessation is equal. Efficacy increases 15% to 36% with combining treatments such as gum and lozenges. Higher doses increase the chance of stopping smoking for a period of six months and more. For patches, the most efficient doses were 25 mg worn over 16 hours or 21 mg worn over 24 hours. The evidence suggests that 4 mg nicotine gum leads to higher quit rates compared with 2 mg in heavy smokers.E-cigarettes are twice as effective as NRT in helping people quit smoking. Toxicity N-Nitrosonornicotine, a strong carcinogen present in unburned tobacco and cigarette smoke, has been found in the urine of some users of oral NRT products. Nicotine patches is an alternative. Side effects Some side effects are caused by the nicotine, and are common to NRT products. Other common side effects depend on the formulation of nicotine. Common side effects with the gum include nausea, hiccups, and irritation of the mouth. Common side effects with the patch include skin irritation and a dry mouth while the inhaler commonly results in a cough, runny nose, or headaches. To minimize local skin reactions from the patch, the application site should be moved daily. The nicotine patch can also cause strange dreams if worn while asleep. Nasal sprays commonly cause nasal irritation, watering eyes, and coughing.Serious risks include nicotine poisoning, which includes symptoms like visual disturbances, hyper-salivation, nausea, and vomiting; and continued addiction to nicotine products. Avoiding smoking and other products with nicotine are recommended since it may lead to nicotine overdose. Although overdose is rare, it can be problematic, especially in children and pets. The symptoms of nicotine overdose include headache, pale skin and mouth, belly pain, weakness, diarrhea, tremors or seizures, agitation, confusion, restlessness, high or low blood pressure, fast or irregular heartbeat, fast breathing, and cold sweats.Limited evidence exists regarding long-term NRT use. Safety Pregnancy Nicotine is not safe to use in any amount during pregnancy. Nicotine crosses the placenta and is found in the breast milk of mothers who smoke as well as mothers who inhale passive smoke. There are possible harms to the baby if NRT is used during pregnancy. Thus, pregnant women and those who are breastfeeding should also consult a physician before initiating NRT. The gum, lozenge, and nasal spray are pregnancy category C. The transdermal patch is pregnancy category D. The transdermal patch is considered less safe for the fetus because it delivers continuous nicotine exposure, as opposed to the gum or lozenge, which delivers intermittent and thus lower nicotine exposure.Strong evidence suggests that nicotine cannot be regarded as a safe substance of cigarette use. Nicotine itself could be at least partly responsible for many of the adverse after birth health results related to cigarette use while the mother was pregnant. There is evidence that nicotine negatively affects fetal brain development and pregnancy outcomes. There is also risk of stillbirth and pre-term birth. Nicotine use will probably harm fetal neurological development. Risks to the child later in life from nicotine exposure during pregnancy include type 2 diabetes, obesity, hypertension, neurobehavioral defects, respiratory dysfunction, and infertility. Nicotine exposure during pregnancy can result in attention deficit hyperactivity disorder (ADHD) and learning disabilities in the child. It also puts the child at increased risk for nicotine addiction in the future.Pregnant women should consider behavioral therapy before NRT is considered. Youth In people under the age of eighteen, a physician is often consulted before starting NRT. The evidence suggests that exposure to nicotine between the ages of 10 and 25 years causes lasting harm to the brain and cognitive ability. Evidence is unclear whether adolescents gain benefit from cognitive-behavioral therapy or smoking cessation over the long-term as of 2017. Most tobacco users are under-eighteens when they start, and almost no-one over the age of 25 starts using. Cardiovascular conditions While there is no evidence that NRT can increase the risk of heart attacks, individuals with pre-existing cardiovascular conditions or recent heart attacks should consult a physician before initiating NRT.Smoking is known to cause cardiovascular diseases such as coronary heart disease, hypertension, heart attack, stroke, and peripheral artery disease. Cigarette smoking is the cause of 20% of all cardiovascular deaths in the United States, which is the leading cause of mortality. Other conditions Nicotine replacement therapies should be used cautiously in individuals with the following conditions: severe reactive airway diseases (for nasal spray), chronic nasal disorders such as sinusitis, polyps, rhinitis, or allergy (for nasal spray), diabetes (insulin-dependent), gastrointestinal diseases such as esophagitis, active gastric or peptic ulcer disease, liver problems, hyperthyroidism,pheochromocytoma, phenylketonuria (for lozenges), renal problems, and skin conditions such as psoriasis or dermatitis (for the transdermal patch). Mechanism of action Nicotine replacement therapy works by reducing cravings due to nicotine addiction. Smoking cigarettes releases high doses of nicotine to the brain in a matter of seconds as opposed to low doses released over a period of minutes to hours by the various forms of nicotine replacement therapy. Nicotine from NRT does not reach as high a concentration in the blood as does nicotine from smoke inhalation due to different absorption methods. NRT relies on systemic venous absorption, whereas nicotine from cigarettes reaches the arterial system. Nicotine replacement products vary in the time it takes for the nicotine to enter the body and the total time nicotine stays in the body. The more quickly a dose of nicotine is delivered and absorbed, the higher the addiction risk. It is possible to become dependent on some NRTs.Nicotine patches are applied to the skin and continuously administer a stable dose of nicotine slowly over 16–24 hours. Nicotine gum, nicotine sprays, nicotine toothpicks, nicotine sublingual tablets, and nicotine lozenges administer nicotine orally with quicker nicotine uptake into the body but lasting a shorter amount of time. Nicotine inhalers are metered-dose inhalers that administer nicotine through the lungs and mucous membranes of the throat quickly, lasting for a short amount of time. For example, blood nicotine levels are the highest 5–10 minutes after using the nicotine nasal spray, 20 minutes after using a nicotine inhaler or chewing nicotine gum, and 2–4 hours after using a nicotine patch. Society and culture NRT products were first approved for use in the United States in 1984. Nicotine replacement products are on the World Health Organizations List of Essential Medicines.. They are available as generic medication. Formulations The nicotine patch is a once-daily, longer-acting form of NRT. An advantage of the nicotine patch is its simple compliance; it does not require active use throughout the day. The gum, lozenge, sublingual tablet, oral inhaler, oral spray, and nasal spray are acutely dosed products, providing the user with the benefit and ability of self-titrating based on cravings.Brand names include Commit Lozenge, Nicoderm, Nicogum, Nicorette, Nicotex, Nicotinell, and Thrive. NRT products contain similar pharmaceutical grade nicotine as is used in e-cigarettes. Medicines In 2015, the United States Public Health Service listed seven agents for the stopping of tobacco, which included five nicotine replacement treatments (nicotine patches, gum, lozenges, inhalers, and nasal sprays) and two oral medications (bupropion and varenicline). Other NRT options are available, including nicotine mouth sprays and sublingual tablets. Dosing The dose of nicotine replacement therapy products is generally based on if the user is considered a heavy, average, or light smoker. A cigarette delivers an average of 1 mg to 3 mg of the nicotine contained in it. NRT products typically aim to parallel this, but the amount of nicotine absorbed by the user is less than the original dose. Nicotine nasal sprays are formulated in doses of lowest strength, available in 0.5 mg and 1 mg strengths. Nicotine lozenges deliver doses as low as 1 mg up to 4 mg. It is not chewed as the gum would be, and dissolves in approximately 30 minutes. This formulation may be preferred by those individuals who do not find gum chewing to be acceptable. Nicotine gum is available in doses of 2 mg and 4 mg. Using 4 mg nicotine gum versus 2 mg gum increases the likelihood of successful smoking cessation. When using the gum, acidic beverages like soda, coffee, or beer should be avoided fifteen minutes prior and during use because they can impede proper absorption of nicotine.Nicotine inhalers come in 10 mg and 15 mg cartridge strengths and typically deliver around 4 mg in one dose. The inhaler may be preferred in individuals who want to satisfy the hand-to-mouth ritual that smoking provides.Transdermal patches deliver between 5 mg and 52.5 mg of nicotine, which results in plasma levels similar to that of heavy smokers. Combining nicotine patch treatment with a faster nicotine-delivery means, like nicotine gum or spray, improves the likelihood of successful treatment. Not approved as NRTs Some smokeless consumer products available can function as alternative nicotine delivery systems (ANDS) but they have not received FDA approval as smoking-cessation therapy aids that are safe and effective. Snus and nasal snuff also allow for nicotine administration outside of tobacco smoking. Nicotine pouches are described as similar to or a tobacco-free variant of snus. They are pre-portioned and are held in the users lip or cheek allowing for sublingual or buccal delivery of flavors and high doses of nicotine. The small pouches are not like chewing tobacco, as the user does not need to spit since the contents of the pouches stay inside during use. Swedish pouches have been available on the American consumer market since at least 2016 but their popularity and controversy surged in 2019 & 2020. In the US and UK concerns have been raised that nicotine pouches are seemingly too similar to banned snus products, is aimed at teenagers, further complicating the youth vaping trend, falling into the hands of adolescents easily, and are discrete enough to easily pass for regular gums or lozenges.Nicotine infused toothpicks are another product that has been available in the United States since at least 2013. They can have a total nicotine delivery that is comparable to that of nicotine gum. Nicotine toothpicks generally are infused with food-grade flavorings and 1–3 mg of nicotine, which is similar to that of other oral-delivery nicotine products and some cigarettes. In spite of these similarities, as of 2018 they have been a subject of controversy. Online retailers have been under scrutiny for allowing their products to be too easily purchased by youth. Various news outlets and school districts have expressed the concern that these products have a high appeal to minors wanting to experiment with nicotine due to; the multitude of sweet flavors offered, ease & speed of use, seeming innocuous, and having a discrete nature. In 2015, NRT sales fell for the first time since 2008 while sales for e-cigarettes or electronic nicotine delivery systems (ENDS) continued to increase at a substantial rate. The evidence is that UK smokers are trying to quit with e-cigarettes rather than NRT methods.E-cigarettes are often, although not always, designed to look and feel like cigarettes. They have been marketed as less harmful alternatives to cigarettes, but very few are as yet approved as NRTs in any jurisdiction. Some electronic cigarettes have coarsely adjustable nicotine levels. Some healthcare groups have hesitated to recommend e-cigarettes for quitting smoking, because of limited evidence of effectiveness and safety. E-cigarettes are more effective than NRT in terms of abstinence from smoking at twelve months.The U.S. Food and Drug Administration (FDA) has a list of additional tobacco products they are seeking to regulate, including electronic cigarettes. Most approved NRT products have been approved for over 20 years, however the FDA has also approved nicotine inhalers as a form of NRT.Future approaches of NRT could include nicotine preloading, a true pulmonary inhaler, and nicotine vaccines. Nicotine preloading, otherwise known as pre-cessation or pre-quitting NRT, has found that using the patch for a few weeks before the quit date produces significantly higher quit rates than if it was started on the quit day. The true pulmonary inhaler would deliver nicotine to the lungs in a manner that more resembles cigarette smoking, which would provide better relief of background cravings as well as acute cravings. Nicotine vaccines are under investigation as a method to treat tobacco dependence through priming the body to mount an immune response against nicotine. References External links "Nicotine". Drug Information Portal. U.S. National Library of Medicine. University of Wisconsin Center for Tobacco Research and Intervention Recommendations for special populations "Nicotine Lozenges". MedlinePlus. 2018-08-15. "Nicotine Nasal Spray". MedlinePlus. 2016-07-15. "Nicotine Oral Inhalation". MedlinePlus. 2016-07-15. "Nicotine Gum". MedlinePlus. 2017-10-15.

You are a medical advisor. Your role is to break down medical terminology into clear, detailed explanations for a general audience.

I'm encountering the term 'Amebic encephalitis' in medical literature. What's its definition?

Amebic encephalitis may refer to: Primary amoebic meningoencephalitis Granulomatous amoebic encephalitis

You are a medical educator. Your role is to provide detailed and clear explanations for medical terms, suitable for both professionals and laypersons.

What does the medical term 'Nocturia' encompass?

Nocturia is defined by the International Continence Society (ICS) as “the complaint that the individual has to wake at night one or more times for voiding (i.e. to urinate).” The term is derived from Latin nox, night, and Greek [τα] ούρα, urine. Causes are varied and can be difficult to discern. Although not every patient needs treatment, most people seek treatment for severe nocturia, waking up to void more than 2–3 times per night. Prevalence Studies show that 5–15% of people who are 20–50 years old, 20–30% of people who are 50–70 years old, and 10–50% of people 70+ years old, urinate at least twice a night. Nocturia becomes more common with age. More than 50 percent of men and women over the age of 60 have been measured to have nocturia in many communities. Even more over the age of 80 are shown to experience symptoms of nocturia nightly. Nocturia symptoms also often worsen with age. Although nocturia rates are about the same for both genders, data shows that there is a higher prevalence in younger women than younger men and older men than older women. Impact Research suggests that more than 60% of people are negatively affected by nocturia. The resulting insomnia and sleep deprivation can cause exhaustion, changes in mood, sleepiness, impaired productivity, fatigue, increased risk of accidents, and cognitive dysfunction. 25% of falls that older individuals experience happen during the night, of which 25% occur while waking up to void.A quality of life test for people who experience nocturia was published in 2004. The pilot study was conducted only on men. Diagnosis Nocturia diagnosis requires knowing the patients nocturnal urine volume (NUV). The ICS defines NUV as “the total volume of urine passed between the time the individual goes to bed with the intention of sleeping and the time of waking with the intention of rising.” Thus, NUV excludes the last void before going to bed, but includes the first morning void if the urge to urinate woke the patient. The amount of sleep a patient gets, and the amount they intend to get, are also considered in a diagnosis.As with any patient, a detailed history of the problem is required to establish what is normal for that patient. The principal diagnostic tool for nocturia is the voiding bladder diary. Based on information recorded in the diary, a physician can classify the patient as having global polyuria, nocturnal polyuria, or bladder storage problems. A voiding bladder diary should record: number of voids timing of voids volume voided volume and time of fluid intakePatients should include the first morning void in the NUV. However, the first morning void is not included with the number of nightly voids. Causes Polyuria Polyuria is excessive or an abnormally large production or passage of urine. Increased production and passage of urine may also be termed diuresis. Polyuria is usually viewed as a symptom or sign of another disorder (not a disease by itself), but it can be classed as a disorder, at least when its underlying causes are not clear. Global polyuria Global polyuria is the continuous overproduction of urine that is not only limited to sleep hours. Global polyuria occurs in response to increased fluid intake and is defined as urine outputs of greater than 40 mL/kg/24 hours. The common causes of global polyuria are primary thirst disorders such as diabetes mellitus and diabetes insipidus (DI). Urination imbalance may lead to polydipsia or excessive thirst to prevent circulatory collapse. Central diabetes insipidus is caused by low levels of Vasopressin (also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin). ADH is produced in the hypothalamus and stored in and released from the posterior pituitary gland. ADH increases water absorption in the collecting duct systems of kidney nephrons, subsequently decreasing urine production. ADH regulate hydration levels in the body. that helps regulates water levels. In nephrogenic DI, the kidneys do not respond properly to the normal amount of ADH.Diagnosis of DI can be made by an overnight water deprivation test. This test requires the patient to eliminate fluid intake for a fixed period of time, usually around 8–12 hours. If the first morning void is not highly concentrated, the patient is diagnosed with DI. Central DI usually can be treated with a synthetic replacement of ADH, called desmopressin. Desmopressin is taken to control thirst and frequent urination. Although there is no substitute for nephrogenic DI, it may be treated with careful regulation of fluid intake. Nocturnal polyuria Nocturnal polyuria is defined as an increase in urine production during the night but with a proportional decrease in daytime urine production that results in a normal 24-hour urine volume. With the 24-hour urine production within normal limits, nocturnal polyuria can be translated to having a nocturnal polyuria index (NPi) greater than 35% of the normal 24-hour urine volume. NPi is calculated simply by dividing NUV by the 24-hour urine volume. Similar to the inability of control urination, a disruption of arginine vasopressin (ADH) levels has been proposed for nocturia. Compared with the normal patients, nocturia patients have a nocturnal decrease in ADH level.Other causes of nocturnal polyuria include diseases such as congestive heart failure nephritic syndrome liver failure lifestyle patterns such as excessive nighttime drinking sleep apnea increasing obstructive airway resistance. Obstructive sleep apnea sufferers have shown to have increases in renal sodium and water excretion that are mediated by elevated plasma atrial natriuretic hormone (ANH) levels. ANH is released by cardiac muscle cells in response to high blood volume. When activated, ANH releases water, subsequently increasing urine production. Bladder storage Normal human bladder storage capacity varies from person to person and is considered 400 – 600 mL. A bladder storage disorder is any factor that increases the frequency of small volume voids. These factors are usually related to lower urinary tract symptoms that affect the capacity of the bladder. Some patients with nocturia have neither global nor nocturnal polyuria according to the above criteria. Such patients most likely have a bladder storage disorder that impacts their nighttime voiding or a sleep disorder. Nocturnal bladder capacity (NBC) is defined as the largest voided volume during the sleep period.Decreased NBC can be traced to a decreased maximum voided volume or decreased bladder storage. Decreased NBC can be related to other disorders such as: benign prostatic hyperplasia (BPH), also known as prostate enlargement neurogenic bladder dysfunction learned voiding dysfunction anxiety disorders urinary tract infection certain pharmacological agents. Mixed cause A significant number of nocturia cases occur from a combination of causes. Mixed nocturia is more common than many realise and is a combination of nocturnal polyuria and decreased nocturnal bladder capacity. In a study of 194 nocturia patients: 7% were determined to solely have nocturnal polyuria 57% solely had decreased NBC 36% had a mixed cause of the twoMultifactor caused nocturia is often unrelated to an underlying urological condition. Mixed nocturia is diagnosed through the maintenance and analysis of bladder diaries of the patient. Assessment of cause contributions are done through formulas. Management Lifestyle changes Although there is no cure for nocturia, many actions can manage the symptoms. Prohibiting caffeine and alcohol intake. Both are diuretic. Beverage consumption regulation. In regard to nocturia, this specifically means avoiding consuming fluids for three or more hours before bedtime so giving the bladder less fluid to store overnight. This especially helps people with urgency incontinence. However, one study regarding geriatric patients showed that it reduced voiding at night by only a small amount and is suboptimal for managing nocturia in older people. Fluid restriction does not help people who have nocturia due to gravity-induced third spacing of fluid because fluid is mobilized when they lie in a reclining position. Compression stockings may be worn through the day to prevent fluid from accumulating in the legs, unless heart failure or another contraindication is present. Drugs that increase the passing of urine can help decrease the third spacing of fluid, but they could also increase nocturia. Medications ADH replacements such as Desmopressin and Vasopressin Selective Alpha-1 blockers are the most commonly used medicine to treat BPH. Alpha-1 blockers are first line treatment for the symptoms of BPH in men. Doxazosin, terazosin, alfuzosin and tamsulosin have all been well established in treatment to reduce lower urine tract symptoms (LUTS) caused by benign prostatic hyperplasia. They are all believed to be similarly effective for this purpose. First generation alpha-1 blockers, like prazosin are not recommended to treat lower urinary tract symptoms because of their blood-pressure-lowering effect. Later generation drugs in this class are used for this purpose. In some cases alpha-1 blockers have been used in combined therapy with 5-alpha reductase blockers. Dutasteride and tamsulosin are on the market as combined therapy and results have shown that they improve symptoms significantly versus monotherapy. If urinary tract infection is causative, it can be treated with urinary antimicrobials. Antimuscarinic agents such as oxybutynin, tolterodine, solifenacin are especially used in patients who suffer from nocturia due to an overactive bladder and urgency incontinence because they help bladder contractility. Surgery If the cause of nocturia is related to benign prostatic hyperplasia or an overactive bladder, surgical actions may be sought out. Surgery for benign prostatic hyperplasia includes increasingly popular and minimally invasive laser surgery. Surgical correction of the pelvic organ prolapse sacral nerve stimulation Bladder augmentation Detrusor muscle myectomy See also Polyuria Enuresis References External links http://nocturia.elsevierresource.com/ Nocturia Resource Centre", linked to the journal European Urology , has been providing a continuous update on nocturia, causes, consequences and clinical approaches.

You serve as a guide in the medical field. Explain medical terms thoroughly, ensuring the information is both insightful and comprehensible.

I'm trying to expand my medical knowledge. Can you elucidate the term 'Clorazepate'?

Clorazepate, sold under the brand name Tranxene among others, is a benzodiazepine medication. It possesses anxiolytic, anticonvulsant, sedative, hypnotic, and skeletal muscle relaxant properties. Clorazepate is an unusually long-lasting benzodiazepine and serves as a majoritive prodrug for the equally long-lasting desmethyldiazepam, which is rapidly produced as an active metabolite. Desmethyldiazepam is responsible for most of the therapeutic effects of clorazepate.It was patented in 1965 and approved for medical use in 1967. Medical uses Clorazepate is used in the treatment of anxiety disorders and insomnia. It may also be prescribed as an anticonvulsant or muscle relaxant. It is also used as a premedication.Clorazepate is prescribed principally in the treatment of alcohol withdrawal and epilepsy, although it is also a useful anxiolytic because of its long half-life. The normal starting dosage range of Clorazepate is 15 to 60 mg per day. The drug is to be taken two to four times per day. Dosages as high as 90 to 120 mg per day may be used in the treatment of acute alcohol withdrawal. In the United States and Canada, Clorazepate is available in 3.75, 7.5, and 15 mg capsules or tablets. In Europe, tablet formations are 5 mg, 10 mg, 20 mg and 50 mg. Clorazepate SD (controlled release) is available and may have a reduced incidence of adverse effects. The sustained-release formulation of clorazepate has some advantages in that, if a dose is missed, less profound fluctuations in blood plasma levels occur, which may be helpful to some people with epilepsy at risk of break-through seizures. Adverse effects Adverse effects of clorazepate include tolerance, dependence, withdrawal reactions, cognitive impairment, confusion, anterograde amnesia, falls in the elderly, ataxia, hangover effects, and drowsiness. It is unclear whether cognitive deficits resulting from the long-term use of benzodiazepines return to normal or persist indefinitely after withdrawal from benzodiazepines. Benzodiazepines are also known to cause or worsen depression. Paradoxical effects including excitement and paradoxical worsening of seizures can sometimes result from the use of benzodiazepines. Children, the elderly, individuals with a history of alcohol use disorder or a history of aggressive behavior and anger are at greater risk of developing paradoxical reactions to benzodiazepines.In September 2020, the U.S. Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of non-medical use, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class. Tolerance, dependence and withdrawal Delirium has been noted from discontinuation from clorazepate. A benzodiazepine dependence occurs in approximately one third of patients who take benzodiazepines for longer than 4 weeks, which is characterised by a withdrawal syndrome upon dose reduction. When used for seizure control, tolerance may manifest itself with an increased rate of seizures as well an increased risk of withdrawal seizures. In humans, tolerance to the anticonvulsant effects of clorazepate occurs frequently with regular use. Due to the development of tolerance, benzodiazepines are, in general, not considered appropriate for the long-term management of epilepsy; increasing the dose may result only in the developing of tolerance to the higher dose combined with worsened adverse effects. Cross-tolerance occurs between benzodiazepines, meaning that, if individuals are tolerant to one benzodiazepine, they will display a tolerance to equivalent doses of other benzodiazepines. Withdrawal symptoms from benzodiazepines include a worsening of pre-existing symptoms as well as the appearance of new symptoms that were not pre-existing. The withdrawal symptoms may range from mild anxiety and insomnia to severe withdrawal symptoms such as seizures and psychosis. Withdrawal symptoms can be difficult in some cases to differentiate between pre-existing symptoms and withdrawal symptoms. Use of high doses, long-term use and abrupt or over-rapid withdrawal increases increase the severity of withdrawal syndrome. However, tolerance to the active metabolite of clorazepate may occur more slowly than with other benzodiazepines. Regular use of benzodiazepines causes the development of dependence characterised by tolerance to the therapeutic effects of benzodiazepines and the development of the benzodiazepine withdrawal syndrome including symptoms such as anxiety, apprehension, tremor, insomnia, nausea, and vomiting upon cessation of benzodiazepine use. Withdrawal from benzodiazepines should be gradual as abrupt withdrawal from high doses of benzodiazepines may cause confusion, toxic psychosis, convulsions, or a condition resembling delirium tremens. Abrupt withdrawal from lower doses may cause depression, nervousness, rebound insomnia, irritability, sweating, and diarrhea. Interactions All sedatives or hypnotics e.g. other benzodiazepines, barbiturates, antiepileptic drugs, alcohol, antihistamines, opioids, neuroleptics, sleep aids are likely to magnify the effects of clorazepate on the central nervous system. Drugs that may interact with clorazepate include, digoxin, disulfiram, fluoxetine, isoniazid, ketoconazole, levodopa, metoprolol, hormonal contraceptives, probenecid, propranolol, rifampin, theophylline, valproic acid. Selective serotonin reuptake inhibitors, cimetidine, macrolide antibiotics and antimycotics inhibit the metabolism of benzodiazepines and may result in increased plasma levels with resultant enhancement of adverse effects. Phenytoin, phenobarbital, and carbamazepine have the opposite effect, with coadministration leading to increased metabolism and decreased therapeutic effects of clorazepate. Contraindications and special caution Benzodiazepines require special precaution if used in the elderly, children, alcohol- or drug-dependent individuals and individuals with comorbid psychiatric disorders.Clorazepate if used late in pregnancy, the third trimester, causes a definite risk of severe benzodiazepine withdrawal syndrome in the neonate with symptoms including hypotonia, and reluctance to suck, to apnoeic spells, cyanosis, and impaired metabolic responses to cold stress. Floppy infant syndrome and sedation in the newborn may also occur. Symptoms of floppy infant syndrome and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth.Special precaution is required when using clorazepate in the elderly because the elderly metabolise clorazepate more slowly, which may result in excessive drug accumulation. Additionally the elderly are more sensitive to the adverse effects of benzodiazepines compared to younger individuals even when blood plasma levels are the same. Use of benzodiazepines in the elderly is only recommended for 2 weeks and it is also recommended that half of the usual daily dose is prescribed. Pharmacology Clorazepate is a "classical" benzodiazepine. Other classical benzodiazepines include chlordiazepoxide, diazepam, clonazepam, oxazepam, lorazepam, nitrazepam, bromazepam and flurazepam. Clorazepate is a long-acting benzodiazepine drug. Clorazepate produces the active metabolite desmethyl-diazepam, which is a partial agonist of the GABAA receptor and has a half life of 20 – 179 hours; a small amount of desmethyldiazepam is further metabolised into oxazepam. Clorazepate exerts its pharmacological properties via increasing the opening frequency of the chloride ion channel of GABAA receptors. This effect of benzodiazepines requires the presence of the neurotransmitter GABA and results in enhanced inhibitory effects of the neurotransmitter GABA acting on GABAA receptors. Clorazepate, like other benzodiazepines, is widely distributed and is highly bound to plasma proteins; clorazepate also crosses readily over the placenta and into breast milk. Peak plasma levels of the active metabolite desmethyl-diazepam are seen between 30 minutes and 2 hours after oral administration of clorazepate. Clorazepate is completely metabolised to desmethyl-diazepam in the gastrointestinal tract and thus the pharmacological properties of clorazepate are largely due to desmethyldiazepam. Chemistry Clorazepate is used in the form of a dipotassium salt. It is unusual among benzodiazepines in that it is freely soluble in water. Clorazepate can be synthesized starting from 2-amino-5-chlorobenzonitrile, which upon reaction with phenylmagnesium bromide is transformed into 2-amino-5-chlorbenzophenone imine. Reacting this with aminomalonic ester gives a heterocyclization product, 7-chloro-1,3-dihydro-3-carbethoxy-5-phenyl-2H-benzodiazepin-2-one. Upon hydrolysis using an alcoholic solution of potassium hydroxide forms a dipotassium salt, chlorazepate. Legal status In the United States, clorazepate is listed under Schedule IV of the Controlled Substances Act. References External links Rx-List.com - Clorazepate Inchem.org - Clorazepate

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I'm not familiar with the medical term 'Angioma serpiginosum.' Could you provide some insights?

Angioma serpiginosum is characterized by minute, copper-colored to bright red angiomatous puncta that have a tendency to become papular.: 592–3 See also Skin lesion List of cutaneous conditions References == External links ==

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I need a basic explanation for the medical term 'Priapism.'

Priapism is a condition in which a penis remains erect for hours in the absence of stimulation or after stimulation has ended. There are three types: ischemic (low-flow), nonischemic (high-flow), and recurrent ischemic (intermittent). Most cases are ischemic. Ischemic priapism is generally painful while nonischemic priapism is not. In ischemic priapism, most of the penis is hard; however, the glans penis is not. In nonischemic priapism, the entire penis is only somewhat hard. Very rarely, clitoral priapism occurs in women.Sickle cell disease is the most common cause of ischemic priapism. Other causes include medications such as antipsychotics, SSRIs, blood thinners and prostaglandin E1, as well as drugs such as cocaine. Ischemic priapism occurs when blood does not adequately drain from the penis. Nonischemic priapism is typically due to a connection forming between an artery and the corpus cavernosum or disruption of the parasympathetic nervous system resulting in increased arterial flow. Nonischemic priapism may occur following trauma to the penis or a spinal cord injury. Diagnosis may be supported by blood gas analysis of blood aspirated from the penis or an ultrasound.Treatment depends on the type. Ischemic priapism is typically treated with a nerve block of the penis followed by aspiration of blood from the corpora cavernosa. If this is not sufficient, the corpus cavernosum may be irrigated with cold, normal saline or injected with phenylephrine. Nonischemic priapism is often treated with cold packs and compression. Surgery may be done if usual measures are not effective. In ischemic priapism, the risk of permanent scarring of the penis begins to increase after four hours and definitely occurs after 48 hours. Priapism occurs in about 1 in 20,000 to 1 in 100,000 males per year. Classification Priapism is classified into three groups: ischemic (low-flow), nonischemic (high-flow), and recurrent ischemic. The majority of cases (19 out of 20) are ischemic in nature.Some sources give a duration of four hours as a definition of priapism, but others give six. "The duration of a normal erection before it is classifiable as priapism is still controversial. Ongoing penile erections for more than 6 hours can be classified as priapism."Priapism in females (continued, painful erection of the clitoris) is significantly rarer than priapism in men and is known as clitoral priapism or clitorism. It is associated with persistent genital arousal disorder (PGAD). Only a few case reports of women experiencing clitoral priapism exist. Signs and symptoms Complications Because ischemic priapism causes the blood to remain in the penis for unusually long periods of time, the blood becomes deprived of oxygen, which can cause damage to the penile tissue. Such damage can result in erectile dysfunction or disfigurement of the penis. In extreme cases, if the penis develops severe vascular disease, the priapism can result in penile gangrene. Low-flow priapism Causes of low-flow priapism include sickle cell anemia (most common in children), leukemia, and other blood dyscrasias such as thalassemia and multiple myeloma, and the use of various drugs, as well as cancers. A genome-wide association study on Brazilian patients with sickle cell disease identified four single nucleotide polymorphisms in LINC02537 and NAALADL2 significantly associated with priapism.Other conditions such as Fabrys disease, as well as neurologic disorders such as spinal cord lesions and spinal cord trauma (priapism has been reported in people who have been hanged; see death erection). Priapism can also be caused by reactions to medications. The most common medications that cause priapism are intra-cavernous injections for the treatment of erectile dysfunction (papaverine, alprostadil). Other medication groups reported are antihypertensives, antipsychotics (e.g., chlorpromazine, clozapine), antidepressants (most notably trazodone), anti-convulsant and mood stabilizer drugs such as sodium valproate. Anticoagulants, cantharides (Spanish Fly) and recreational drugs (alcohol, heroin and cocaine) have been associated. Priapism is also known to occur from bites of the Brazilian wandering spider. High-flow priapism Causes of high-flow priapism include: blunt trauma to the perineum or penis, with laceration of the cavernous artery, which can generate an arterial-lacunar fistula. Anticoagulants (heparin and warfarin). Antihypertensives (i.e., hydralazine, guanethidine and propranolol). Hormones (i.e., gonadotropin releasing hormone and testosterone). Diagnosis The diagnosis is often based on the history of the condition as well as a physical exam.Blood gas testing the blood from the cavernosa of the penis can help in the diagnosis. If the low-flow type of priapism is present, the blood typically has a low pH, while if the high-flow type is present, the pH is typically normal. Color Doppler ultrasound may also help differentiate the two. Testing a person to make sure they do not have a hemoglobinopathy may also be reasonable. Ultrasonography Penile ultrasonography with Doppler is the imaging method of choice, because it is noninvasive, widely available, and highly sensitive. By means of this method, it is possible to diagnose priapism and differentiate between its low- and high-flow forms.In low-flow (ischemic) priapism the flow in the cavernous arteries is reduced or absent. As the condition progresses, there is an increase in echogenicity of the corpora cavernosa, attributed to tissue edema. Eventually, changes in the echotexture of the corpora cavernosa can be observed due to the fibrotic transformation generated by tissue anoxia.In high-flow priapism normal or increased, turbulent blood flow in the cavernous arteries is seen. The area surrounding the fistula presents a hypoechoic, irregular lesion in the cavernous tissue. Treatment Medical evaluation is recommended for erections that last for longer than four hours. Pain can often be reduced with a dorsal penile nerve block or penile ring block. For those with nonischemic priapism, cold packs and pressure to the area may be sufficient. Pseudoephedrine Orally administered pseudoephedrine is a first-line treatment for priapism. Erection is largely a parasympathetic response, so the sympathetic action of pseudoephedrine may serve to relieve this condition. Pseudoephedrine is an alpha-agonist agent that exerts a constriction effect on smooth muscle of corpora cavernosum, which in turn facilitates venous outflow. Pseudoephedrine is no longer available in some countries. Aspiration For those with ischemic priapism, the initial treatment is typically aspiration of blood from the corpus cavernosum. This is done on either side. If this is not sufficiently effective, then cold normal saline may be injected and removed. Medications If aspiration is not sufficient, a small dose of phenylephrine may be injected into the corpus cavernosum. Side effects of phenylephrine may include: high blood pressure, slow heart rate, and arrhythmia. If this medication is used, it is recommended that people be monitored for at least an hour after. For those with recurrent ischemic priapism, diethylstilbestrol (DES) or terbutaline may be tried. Surgery Distal shunts, such as the Winters, involve puncturing the glans (the distal part of the penis) into one of the cavernosa, where the old, stagnant blood is held. This causes the blood to leave the penis and return to the circulation. This procedure can be performed by a urologist at the bedside. Winters shunts are often the first invasive technique used, especially in hematologically induced priapism, as it is relatively simple and repeatable.Proximal shunts, such as the Quackels, are more involved and entail operative dissection in the perineum where the corpora meet the spongiosum while making an incision in both and suturing both openings together. Shunts created between the corpora cavernosa and great saphenous vein called a Grayhack shunt can be done though this technique is rarely used.As the complication rates with prolonged priapism are high, early penile prosthesis implantation may be considered. As well as allowing early resumption of sexual activity, early implantation can avoid the formation of dense fibrosis and, hence, a shortened penis. Sickle cell anemia In sickle cell anemia, treatment is initially with intravenous fluids, pain medication, and oxygen therapy. The typical treatment of priapism may be carried out as well. Blood transfusions are not usually recommended as part of the initial treatment, but if other treatments are not effective, exchange transfusion may be done. History Persistent semi-erections and intermittent states of prolonged erections have historically been sometimes called semi-priapism. Terminology The name comes from the Greek god Priapus (Ancient Greek: Πρίαπος), a fertility god, often represented with a disproportionately large, permanent erection. References External links Guideline on the Management of Priapism (2003) - American Urological Association website - The unabridged 275-page version of this guideline. Media related to Priapism at Wikimedia Commons

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I need a basic explanation for the medical term 'Tolmetin.'

Tolmetin is a nonsteroidal anti-inflammatory drug (NSAID) of the heterocyclic acetic acid derivative class. It is used primarily to reduce hormones that cause pain, swelling, tenderness, and stiffness in conditions such as osteoarthritis and rheumatoid arthritis, including juvenile rheumatoid arthritis. In the United States it is marketed as Tolectin and comes as a tablet or capsule. Clinical trials Tolmetin is applicable in the treatment of rheumatoid arthritis, osteoarthrosis, pain, and ankylosing spondylitis. Mechanism of action Although the mechanism of action of tolmetin is unknown, research involving humans and animals has shown that tolmetin does not achieve anti-inflammatory response by stimulation of the adrenal or pituitary gland, but it has shown tolmetin restrains prostaglandin synthetase in vitro and reduces plasma levels of prostaglandin E, possibly causing the anti-inflammatory response. When tested in rats, tolmetin prevented experimentally stimulated polyarthritis and reduced inflammation. In patients with rheumatoid arthritis or osteoarthritis tolmetin restrained disease activity as efficiently as aspirin and indometacin, although the occurrence of mild gastrointestinal adverse effects and tinnitus was lower in patients treated with tolmetin than it was with aspirin-treated patients and the occurrence of adverse effects of the central nervous system was lower with tolmetin than it was with indometacin. Side effects Tolmetin can increase the risk of heart or circulatory conditions such as heart attacks and strokes. It should not be taken shortly before or after coronary artery bypass surgery. Tolmetin can also increase the risk of gastrointestinal conditions such as perforation or bleeding, which is fatal. Antacids can be taken with tolmetin to relieve stomachaches that often occur. Overdose can result in drowsiness, nausea, epigastric pain, and vomiting. In October 2020, the U.S. Food and Drug Administration (FDA) required the drug label to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in unborn babies that result from low amniotic fluid. They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy. == References ==

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The term 'Leukoplakia' keeps coming up in medical discussions. What does it stand for?

Oral leukoplakia is a potentially malignant disorder affecting the oral mucosa. It is defined as "essentially an oral mucosal white lesion that cannot be considered as any other definable lesion." Oral leukoplakia is a white patch or plaque that develops in the oral cavity and is strongly associated with smoking. Leukoplakia is a firmly attached white patch on a mucous membrane which is associated with increased risk of cancer. The edges of the lesion are typically abrupt and the lesion changes with time. Advanced forms may develop red patches. There are generally no other symptoms. It usually occurs within the mouth, although sometimes mucosa in other parts of the gastrointestinal tract, urinary tract, or genitals may be affected.The cause of leukoplakia is unknown. Risk factors for formation inside the mouth include smoking, chewing tobacco, excessive alcohol, and use of betel nuts. One specific type is common in HIV/AIDS. It is a precancerous lesion, a tissue alteration in which cancer is more likely to develop. The chance of cancer formation depends on the type, with between 3–15% of localized leukoplakia and 70–100% of proliferative leukoplakia developing into squamous cell carcinoma.Leukoplakia is a descriptive term that should only be applied after other possible causes are ruled out. Tissue biopsy generally shows increased keratin build up with or without abnormal cells, but is not diagnostic. Other conditions that can appear similar include yeast infections, lichen planus, and keratosis due to repeated minor trauma. The lesions from a yeast infection can typically be rubbed off while those of leukoplakia cannot.Treatment recommendations depend on features of the lesion. If abnormal cells are present or the lesion is small surgical removal is often recommended; otherwise close follow up at three to six month intervals may be sufficient. People are generally advised to stop smoking and limit the drinking of alcohol. In potentially half of cases leukoplakia will shrink with stopping smoking; however, if smoking is continued up to 66% of cases will become more white and thick. The percentage of people affected is estimated at 1–3%. Leukoplakia becomes more common with age, typically not occurring until after 30. Rates may be as high as 8% in men over the age of 70. Classification Leukoplakia could be classified as mucosal disease, and also as a premalignant condition. Although the white color in leukoplakia is a result of hyperkeratosis (or acanthosis), similarly appearing white lesions that are caused by reactive keratosis (smokers keratosis or frictional keratoses e.g. morsicatio buccarum) are not considered to be leukoplakias. Leukoplakia could also be considered according to the affected site, e.g. oral leukoplakia, leukoplakia of the urinary tract, including bladder leukoplakia or leukoplakia of the penis, vulvae, cervix or vagina. Leukoplakia may also occur in the larynx, possibly in association with gastro-esophageal reflux disease. Oropharyngeal leukoplakia is linked to the development of esophageal squamous cell carcinoma, and sometimes this is associated with tylosis, which is thickening of the skin on the palms and soles of the feet (see: Leukoplakia with tylosis and esophageal carcinoma). Dyskeratosis congenita may be associated with leukoplakia of the oral mucosa and of the anal mucosa. Mouth Within the mouth, leukoplakia is sometimes further classified according to the site involved, e.g. leukoplakia buccalis (leukoplakia of the buccal mucosa) or leukoplakia lingualis (leukoplakia of the lingual mucosa). There are two main clinical variants of oral leukoplakia, namely homogeneous leukoplakia and non-homogeneous (heterogenous) leukoplakia, which are described below. The word leukoplakia is also included within the nomenclature of other oral conditions which present as white patches, however, these are specific diagnoses that are generally considered separate from leukoplakia, with the notable exception of proliferative verrucous leukoplakia, which is a recognized sub-type of leukoplakia. Homogeneous leukoplakia Homogeneous leukoplakia (also termed "thick leukoplakia") is usually well defined white patch of uniform, flat appearance and texture, although there may be superficial irregularities. Homogeneous leukoplakia is usually slightly elevated compared to surrounding mucosa, and often has a fissured, wrinkled or corrugated surface texture, with the texture generally consistent throughout the whole lesion. This term has no implications on the size of the lesion, which may be localized or extensive. When homogeneous leukoplakia is palpated, it may feel leathery, dry, or like cracked mud. Non-homogeneous leukoplakia Non-homogeneous leukoplakia is a lesion of non-uniform appearance. The color may be predominantly white or a mixed white and red. The surface texture is irregular compared to homogeneous leukoplakia, and may be flat (papular), nodular or exophytic. "Verrucous leukoplakia" (or "verruciform leukoplakia") is a descriptive term used for thick, white, papillary lesions. Verrucous leukoplakias are usually heavily keratinized and are often seen in elderly people. Some verrucous leukoplakias may have an exophytic growth pattern, and some may slowly invade surrounding mucosa, when the term proliferative verrucous leukoplakia may be used. Non-homogeneous leukoplakias have a greater risk of cancerous changes than homogeneous leukoplakias. Proliferative verrucous leukoplakia Proliferative verrucous leukoplakia (PVL) is a recognized high risk subtype of non-homogeneous leukoplakia. It is uncommon, and usually involves the buccal mucosa and the gingiva (the gums). This condition is characterized by (usually) extensive, papillary or verrucoid keratotic plaques that tends to slowly enlarge into adjacent mucosal sites. An established PVL lesion is usually thick and exophytic (prominent), but initially it may be flat. Smoking does not seem to be as strongly related as it is to leukoplakia generally, and another dissimilarity is the preponderance for women over 50. There is a very high risk of dysplasia, transformation to squamous cell carcinoma with high mortality (PVL does not transform into verrucous carcinoma, which is a lesion with a good prognosis usually; the similarity of names does not reflect the common origin, but only the resemblance of their appearance). Erythroleukoplakia Erythroleukoplakia (also termed speckled leukoplakia, erythroleukoplasia or leukoerythroplasia) is a non-homogeneous lesion of mixed white (keratotic) and red (atrophic) color. Erythroplakia (erythroplasia) is an entirely red patch that cannot be attributed to any other cause. Erythroleukoplakia can therefore be considered a variant of either leukoplakia or erythroplakia since its appearance is midway between. Erythroleukoplakia frequently occurs on the buccal mucosa in the commissural area (just inside the cheek at the corners of the mouth) as a mixed lesion of white nodular patches on an erythematous background, although any part of the mouth may be affected. Erythroleukoplakia and erythroplakia have a higher risk of cancerous changes than homogeneous leukoplakia. Sublingual keratosis Sometimes leukoplakia of the floor of mouth or under the tongue is called sublingual keratosis,. though this is not universally accepted to be a distinct clinical entity from idiopathic leukoplakia generally, as it is distinguished from the latter by location only. Usually sublingual keratoses are bilateral and possess a parallel-corrugated, wrinkled surface texture described as "ebbing tide". Candidal leukoplakia Candidal leukoplakia is usually considered to be a largely historical synonym for a type of oral candidiasis, now more commonly termed chronic hyperplastic candidiasis, rather than a subtype of true leukoplakia. However, some sources use this term to refer to leukoplakia lesions that become colonized secondarily by Candida species, thereby distinguishing it from hyperplastic candidiasis. Oral hairy leukoplakia Oral hairy leukoplakia is a corrugated ("hairy") white lesion on the sides of the tongue caused by opportunistic infection with Epstein-Barr virus on a systemic background of immunodeficiency, almost always human immunodeficiency virus (HIV) infection. This condition is not considered to be a true idiopathic leukoplakia since the causative agent has been identified. It is one of the most common oral lesions associated with HIV infection, along with pseudomembraneous candidiasis. The appearance of the lesion often heralds the transition from HIV to acquired immunodeficiency syndrome (AIDS). Syphilitic leukoplakia This term refers to a white lesion associated with syphilis, specifically in the tertiary stage of the infection. It is not considered to be a type of idiopathic leukoplakia, since the causative agent Treponema pallidum is known. It is now rare, but when syphilis was more common, this white patch usually appeared on the top surface of the tongue and carried a high risk of cancerous changes. It is unclear if this lesion was related to the condition itself or whether it was caused by the treatments for syphilis at the time. Esophagus Leukoplakia of the esophagus is rare compared to oral leukoplakia. The relationship with esophageal cancer is unclear because the incidence of esophageal leukoplakia is so low. It usually appears as a small, nearly opaque white lesion that may resemble early esophageal squamous cell carcinoma. The histologic appearance is similar to oral leukoplakia, with hyperkeratosis and possible dysplasia. Bladder In the context of lesions of the mucous membrane lining of the bladder, leukoplakia is a historic term for a visualized white patch which histologically represents keratinization in an area of squamous metaplasia. The symptoms may include frequency, suprapubic pain (pain felt above the pubis), hematuria (blood in the urine), dysuria (difficult urination or pain during urination), urgency, and urge incontinence. The white lesion may be seen during cystoscopy, where it appears as a whitish-gray or yellow lesion, on a background of inflamed urothelium and there may be floating debris in the bladder. Leukoplakia of the bladder may undergo cancerous changes, so biopsy and long term follow up are usually indicated. Anal canal Leukoplakia of the anal canal is rare. It may extend up to the anorectal junction. On digital examination it feels hard and granular, and at proctoscopy, it appears as white plaques which may be diffuse, circumferential, or circumscribed. The histologic appearance is similar to oral leukoplakia, with hyperkeratosis and acanthosis. It may be asymptomatic, with symptoms due to other lesions such as hemorrhoids or fissures. Progression to anal stenosis has been described. The malignant potential is seemingly low, and few cases of anal carcinoma have been reported associated with anal leukoplaka. Signs and symptoms Most cases of leukoplakia cause no symptoms, but infrequently there may be discomfort or pain. The exact appearance of the lesion is variable. Leukoplakia may be white, whitish yellow or grey. The size can range from a small area to much larger lesions. The most common sites affected are the buccal mucosa, the labial mucosa and the alveolar mucosa, although any mucosal surface in the mouth may be involved. The clinical appearance, including the surface texture and color, may be homogeneous or non-homogeneous (see: classification). Some signs are generally associated with a higher risk of cancerous changes (see: prognosis). Leukoplakia may rarely be associated with esophageal carcinoma.: 805 Causes The exact underlying cause of leukoplakia is largely unknown, but it is likely multifactorial, with the main factor being the use of tobacco. Tobacco use and other suggested causes are discussed below. The mechanism of the white appearance is thickening of the keratin layer, called hyperkeratosis. The abnormal keratin appears white when it becomes hydrated by saliva, and light reflects off the surface evenly. This hides the normal pink-red color of mucosae (the result of underlying vasculature showing through the epithelium). A similar situation can be seen on areas of thick skin such as the soles of the feet or the fingers after prolonged immersion in water. Another possible mechanism is thickening of the stratum spinosum, called acanthosis. Tobacco Tobacco smoking or chewing is the most common causative factor, with more than 80% of persons with leukoplakia having a positive smoking history. Smokers are much more likely to develop leukoplakia than non-smokers. The size and number of leukoplakia lesions in an individual is also correlated with the level of smoking and how long the habit has lasted for. Other sources argue that there is no evidence for a direct causative link between smoking and oral leukoplakia. Cigarette smoking may produce a diffuse leukoplakia of the buccal mucosa, lips, tongue and rarely the floor of mouth. Reverse smoking, where the lit end of the cigarette is held in the mouth is also associated with mucosal changes. Tobacco chewing, e.g. betel leaf and areca nut, called paan, tends to produce a distinctive white patch in a buccal sulcus termed "tobacco pouch keratosis". In the majority of persons, cessation triggers shrinkage or disappearance of the lesion, usually within the first year after stopping. Alcohol Although the synergistic effect of alcohol with smoking in the development of oral cancer is beyond doubt, there is no clear evidence that alcohol is involved in the development of leukoplakia, but it does appear to have some influence. Excessive use of a high alcohol-containing mouth wash (> 25%) may cause a grey plaque to form on the buccal mucosa, but these lesions are not considered true leukoplakia. Sanguinaria Sanguinaria (Bloodroot) is a herbal extract that is included in some toothpastes and mouthwashes. Its use is strongly associated with development of leukoplakia, usually in the buccal sulcus. This type of leukoplakia has been termed "sanguinaria associated keratosis" and more than 80% of people with leukoplakia in the vestibule of the mouth have used this substance. Upon stopping contact with the causative substance, the lesions may persist for many years. Although this type of leukoplakia may show dysplasia, the potential for malignant transformation is unknown. Ultraviolet radiation Ultraviolet radiation is believed to be a factor in the development of some leukoplakia lesions of the lower lip, usually in association with actinic cheilitis. Micro-organisms Candida in its pathogenic hyphal form is occasionally seen in biopsies of idiopathic leukoplakia. It is debated whether candida infection is a primary cause of leukoplakia with or without dysplasia, or a superimposed (secondary) infection that occurs after the development of the lesion. It is known that Candida species thrive in altered tissues. Some leukoplakias with dysplasia reduce or disappear entirely following use of antifungal medication. Smoking, which as discussed above can lead to the development of leukoplakia, can also promote oral candidiasis. Candida in association with leukoplakia should not be confused with white patches which are primarily caused by candida infection, such as chronic hyperplastic candidiasis ("candidal leukoplakia").The involvement of viruses in the formation of some oral white lesions is well established, e.g. Epstein-Barr virus in oral hairy leukoplakia (which is not a true leukoplakia). Human papilloma virus (HPV), especially HPV 16 and 18, is sometimes found in areas of leukoplakia, however, since this virus can be coincidentally found on normal, healthy mucosal surfaces in the mouth, it is unknown if this virus is involved in the development of some leukoplakias. In vitro experimentation has demonstrated that HPV 16 is capable of inducing dysplastic changes in previously normal squamous epithelium. Epithelial atrophy Leukoplakia is more likely to develop in areas of epithelial atrophy. Conditions associated with mucosal atrophy include iron deficiency, some vitamin deficiencies, oral submucous fibrosis, syphilis and sideropenic dysphagia. Trauma Another very common cause of white patches in the mouth is frictional or irritational trauma leading to keratosis. Examples include nicotine stomatitis, which is keratosis in response to heat from tobacco smoking (rather than a response to the carcinogens in tobacco smoke). The risk of malignant transformation is similar to normal mucosa. Mechanical trauma, e.g. caused by a sharp edge on a denture, or a broken tooth, may cause white patches which appear very similar to leukoplakia. However, these white patches represent a normal hyperkeratotic reaction, similar to a callus on the skin, and will resolve when the cause is removed. Where there is a demonstrable cause such as mechanical or thermal trauma, the term idiopathic leukoplakia should not be used. Pathophysiology Tumor suppressor genes Tumor suppressor genes are genes involved in the regulation of normal cell turnover and apoptosis (programmed cell death). One of the most studied tumor suppressor genes is p53, which is found on the short arm of chromosome 17. Mutation of p53 can disrupt its regulatory function and lead to uncontrolled cell growth. Mutations of p53 have been demonstrated in the cells from areas of some leukoplakias, especially those with dysplasia and in individuals who smoke and drink heavily. Diagnosis Definition Leukoplakia is a diagnosis of exclusion, meaning that which lesions are included depends upon what diagnoses are currently considered acceptable. Accepted definitions of leukoplakia have changed over time and are still controversial. It is possible that the definition will be further revised as new knowledge becomes available. In 1984 an international symposium agreed upon the following definition: "a whitish patch or plaque, which cannot be characterized clinically or pathologically as any other disease, and is not associated with any physical or chemical agent except the use of tobacco." There were, however, problems and confusion in applying this definition. At a second international symposium held in 1994, it was argued that whilst tobacco was a likely causative factor in the development of leukoplakia, some white patches could be linked directly to the local effects of tobacco by virtue of their disappearance following smoking cessation, suggesting that this kind of white patch represents a reactive lesion to local tissue irritation rather than a lesion caused by carcinogens in cigarette smoke, and could be better termed to reflect this etiology, e.g. smokers keratosis. The second international symposium, therefore, revised the definition of leukoplakia to: "a predominantly white lesion of the oral mucosa that cannot be characterized as any other definable lesion." In the mouth, the current definition of oral leukoplakia adopted by the World Health Organization is "white plaques of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer". However, this definition is inconsistently applied in the medical literature, and some refer to any oral white patch as "leukoplakia".The term has been incorrectly used for white patches of any cause (rather than specifically referring to idiopathic white patches) and also to refer only to white patches which have a risk of cancerous changes. It has been suggested that leukoplakia is an unhelpful term since there is so much inconsistency surrounding its use, and some clinicians now avoid using it at all. Biopsy Tissue biopsy is usually indicated to rule out other causes of white patches and also to enable a detailed histologic examination to grade the presence of any epithelial dysplasia. This is an indicator of malignant potential and usually determines the management and recall interval. The sites of a leukoplakia lesion that are preferentially biopsied are the areas that show induration (hardening) and erythroplasia (redness), and erosive or ulcerated areas. These areas are more likely to show any dysplasia than homogeneous white areas.Brush biopsy/exfoliative cytology is an alternative to incisional biopsy, where a stiff brush is scraped against the lining of the mouth to remove a sample of cells. This is then made into a smear which can be examined microscopically. Sometimes the biopsy site can be selected with adjunct methods which aim to highlight areas of dysplasia. Toluidine blue staining, where the dye is preferentially retained by dysplastic tissue, is sometimes used, but there is high false positive rate. Other methods involve the use of luminescence, relying on either the property of normal autoflorescent molecules in mucosa such as collagen and keratin which is lost from areas of dysplasia or carcinoma under blue light or by initially staining of the mucosa with toluidine blue or dilute acetic acid and examination under white light. Histologic appearance Leukoplakia has a wide range of possible histologic appearances. The degree of hyperkeratosis, epithelial thickness (acanthosis/atrophy), dysplasia and inflammatory cell infiltration in the underlying lamina propria are variable. In mucous membranes, hyperkeratosis can be defined as "an increase in the thickness of the keratin layer of the epithelium, or the presence of such a layer in a site where none would normally be expected." In leukoplakia, the hyperkeratosis varies in thickness and may be either ortho- or para-keratosis, (depending upon whether cell nuclei are lost or retained in the superficial layers respectively), or a mixture of both in different areas of the lesion.The epithelium may show hypertrophy (e.g. acanthosis) or atrophy. Red areas within leukoplakia represent atrophic or immature epithelium which has lost the ability to keratinize. The transition between the lesion and normal surrounding mucosa may be well-demarcated, or poorly defined. Melanin, a pigment naturally produced in oral mucosa, can leak from cells and give a grey color to some leukoplakia lesions.Hyperkeratosis and altered epithelial thickness may be the only histologic features of a leukoplakia lesion, but some show dysplasia. The word "dysplasia" generally means "abnormal growth", and specifically, in the context of oral red or white lesions, refers to microscopic changes ("cellular atypia") in the mucosa that indicate a risk of malignant transformation. When dysplasia is present, there is generally an inflammatory cell infiltration in the lamina propria. The following are commonly cited as being possible features of epithelial dysplasia in leukoplakia specimens: Cellular pleomorphism, in which cells are of abnormal and different shapes. Nuclear atypia, in which the nuclei of cells varies in size, any may be increased in size relative to the cytoplasm, shape, and may stain more intensely. There may also be more prominent nucleoli. Increased number of cells seen undergoing mitosis, including both normal and abnormal mitoses. Abnormal mitosis may be abnormally located, e.g. occurring in suprabasal cells (cell layers more superficial to the basal cell layer) or of abnormal form, e.g. "tri-radiate mitoses" (a cell splitting into 3 daughter cells rather than only 2) Loss the normal organization of the epithelial layers. The distinction between the epithelial layers may be lost. Normally stratified squamous epithelium shows progressive changes in the form of cells from the basal to the superficial layers, with cells becoming more flat ("squames") towards the surface as a continuous maturation process. In dysplastic epithelium, cells may become vertically orientated rather than becoming flat towards the surface. There may be abnormal keratinization, where keratin is formed below the normal keratin layer. This can occur in individual cells or groups of cells, forming an intraepithelial keratin pearl. There may be an increase in the number of basal cells, and they may lose their cellular orientation (losing their polarity and long axis). Alteration of the normal epithelial-connective tissue architecture - the rete pegs may become "drop shaped". wider at their base than more superficially.Generally, dysplasia is subjectively graded by pathologists into mild, moderate or severe dysplasia. This requires experience as it is a difficult skill to learn. It has been shown that there is high degree of inter-observer variation and poor reproducibility in how dysplasia is graded. Severe dysplasia is synonymous with the term carcinoma in situ, denoting the presence of neoplastic cells which have not yet penetrated the basement membrane and invaded other tissues. Differential diagnosis There are many known conditions that present with a white lesion of the oral mucosa, but the majority of oral white patches have no known cause. These are termed leukoplakia once other likely possibilities have been ruled out. There are also few recognized subtypes of leukoplakia, described according to the clinical appearance of the lesion. Almost all oral white patches are usually the result of keratosis. For this reason, oral white patches are sometimes generally described as keratoses, although a minority of oral white lesions are not related to hyperkeratosis, e.g. epithelial necrosis and ulceration caused by a chemical burn (see: Oral ulceration#Chemical injury). In keratosis, the thickened keratin layer absorbs water from saliva in the mouth and appears white in comparison with normal mucosa. Normal oral mucosa is a red-pink color due to the underlying vasculature in the lamina propria showing through the thin layer of epithelium. Melanin produced in the oral mucosa also influences the color, with a darker appearance being created by higher levels of melanin in the tissues (associated with racial/physiologic pigmentation, or with disorders causing melanin overproduction such as Addisons disease). Other endogenous pigments can be overproduced to influence the color, e.g. bilirubin in hyperbilirubinemia or hemosiderin in hemochromatosis, or exogenous pigments such as heavy metals can be introduced into the mucosa, e.g. in an amalgam tattoo. Almost all white patches are benign, i.e. non-malignant. The differential diagnosis of a white lesion in the mouth can be considered according to a surgical sieve (see table).Leukoplakia cannot be rubbed off the mucosa, distinguishing it readily from white patches such as pseudomembraneous candidiasis, where a white layer can be removed to reveal an erythematous, sometimes bleeding surface underneath. The white color associated with leukoedema disappears when the mucosa is stretched. A frictional keratosis will generally be adjacent to a sharp surface such as a broken tooth or rough area on a denture and will disappear when the causative factor is removed. Some have a suggested as general rule that any lesion that does not show signs of healing within 2 weeks should be biopsied. Morsicatio buccarum and linea alba are located at the level of the occlusal plane (the level at which the teeth meet). A chemical burn has a clear history of placing an aspirin tablet (or other caustic substance such as eugenol) against the mucosa in an attempt to relieve toothache. Developmental white patches usually are present from birth or become apparent earlier in life, whilst leukoplakia generally affects middle aged or elderly people. Other causes of white patches generally require pathologic examination of a biopsy specimen to distinguish with certainty from leukoplakia. Management A systematic review found that no treatments commonly used for leukoplakia have been shown to be effective in preventing malignant transformation. Some treatments may lead to healing of leukoplakia, but do not prevent relapse of the lesion or malignant change. Regardless of the treatment used, a diagnosis of leukoplakia almost always leads to a recommendation that possible causative factors such as smoking and alcohol consumption be stopped, and also involves long term review of the lesion, to detect any malignant change early and thereby improve the prognosis significantly. Predisposing factors and review Beyond advising smoking cessation, many clinicians will employ watchful waiting rather than intervene. Recommended recall intervals vary. One suggested program is every 3 months initially, and if there is no change in the lesion, then annual recall thereafter. Some clinicians use clinical photographs of the lesion to help demonstrate any changes between visits. Watchful waiting does not rule out the possibility of repeated biopsies. If the lesion changes in appearance repeat biopsies are especially indicated. Since smoking and alcohol consumption also places individuals at higher risk of tumors occurring in the respiratory tract and pharynx, "red flag" symptoms (e.g. hemoptysis - coughing blood) often trigger medical investigation by other specialties. Surgery Surgical removal of the lesion is the first choice of treatment for many clinicians. However, the efficacy of this treatment modality cannot be assessed due to insufficient available evidence. This can be carried out by traditional surgical excision with a scalpel, with lasers, or with eletrocautery or cryotherapy. Often, if biopsy demonstrates moderate or severe dysplasia then the decision to excise them is taken more readily. Sometimes, white patches are too large to remove completely and instead they are monitored closely. Even if the lesion is completely removed, long term review is still usually indicated since leukoplakia can recur, especially if predisposing factors such as smoking are not stopped. Medications Many different topical and systemic medications have been studied, including anti-inflammatories, antimycotics (target Candida species), carotenoids (precursors to vitamin A, e.g. beta carotene), retinoids (drugs similar to vitamin A), and cytotoxics, but none have evidence that they prevent malignant transformation in an area of leukoplakia. Vitamins C and E have also been studied with regards a therapy for leukoplakia. Some of this research is carried out based upon the hypothesis that antioxidant nutrients, vitamins and cell growth suppressor proteins (e.g. p53) are antagonistic to oncogenesis. High doses of retinoids may cause toxic effects. Other treatments that have been studied include photodynamic therapy. Prognosis The annual malignant transformation rate of leukoplakia rarely exceeds 1%, i.e. the vast majority of oral leukoplakia lesions will remain benign. A number of clinical and histopathologic features are associated with varying degrees of increased risk of malignant transformation, although other sources argue that there are no universally accepted and validated factors which can reliably predict malignant change. It is also unpredictable to an extent if an area of leukoplakia will disappear, shrink or remain stable. Presence and degree of dysplasia (mild, moderate or severe/carcinoma in situ). While the degree of dysplasia has been shown to be an important predictor of malignant change, many have challenged its use due to the low predictive value from the lack of objectivity of grading dysplasia. While 10% of leukoplakia lesions show dysplasia when biopsied, as many as 18% of oral lesions undergo malignant change in the absence of dysplasia. Leukoplakia located on the floor of the mouth, the posterior and lateral tongue, and the retromolar areas (the region behind the wisdom teeth) have higher risk, whereas white patches in areas such as the top surface of the tongue and the hard palate do not have significant risk. Although these "high risk" sites are recognized, statistically, leukoplakia is more common on the buccal mucosa, alveolar mucosa, and the lower labial mucosa. Leukoplakia of the floor of the mouth and tongue accounts for over 90% of leukoplakias showing dysplasia or carcinoma on biopsy. This is thought to be due to pooling of saliva in the lower part of the mouth, exposing these areas to more carcinogens held in suspension. Red lesions (erythroplasia) and mixed red and white lesions (erythroleukoplakia/"speckled leukoplakia") have a higher risk of malignant change than homogeneous leukoplakia. Verrucous or nodular areas have a higher risk. Although smoking increases risk of malignant transformation, smoking also causes many white patches with no dysplasia. This means that statistically, white patches in non-smokers have a higher risk. Older people with white patches are at higher risk. Larger white patches are more likely to undergo malignant transformation than smaller lesions. White patches which have been present for a long period of time have a higher risk. Persons with a positive family history of cancer in the mouth. Candida infection in the presence of dysplasia has a small increased risk. A change in the appearance of the white patch, apart from a change in the color, has a higher risk. Changes in the lesion such as becoming fixed to underlying tissues, ulceration, cervical lymphadenopathy (enlargement of lymph nodes in the neck), and bone destruction may herald the appearance of malignancy. White patches present in combination with other conditions that carry a higher risk (e.g. oral submucous fibrosis), are more likely to turn malignant. Although overall, oral cancer is more common in males, females with white patches are at higher risk than men. Epidemiology The prevalence of oral leukoplakia varies around the world, but generally speaking it is not an uncommon condition. Reported prevalence estimates range from less than 1% to more than 5% in the general population. Leukoplakia is, therefore, the most common premalignant lesion that occurs in the mouth. Leukoplakia is more common in middle-aged and elderly males. The prevalence increases with increasing age. In areas of the world where smokeless tobacco use is common, there is a higher prevalence. In the Middle East region, the prevalence of leukoplakia is less than 1% (0.48%). Etymology The word leukoplakia means "white patch", and is derived from the Greek words λευκός - "white" and πλάξ - "plate". History The term leukoplakia was coined in 1861 by Karl Freiherr von Rokitansky, who used it to refer to white lesions of the urinary tract. In 1877, Schwimmer first used the term for an oral white lesion. It is now thought that this white lesion on the tongue represented syphilitic glossitis, a condition not included in the modern definitions of oral leukoplakia. Since then, the word leukoplakia has been incorporated into the names for several other oral lesions (e.g. candidal leukoplakia, now more usually termed hyperplastic candidiasis). In 1930, it was shown experimentally that leukoplakia could be induced in rabbits that were subjected to tobacco smoke for 3 minutes per day. According to one source from 1961, leukoplakia can occur on multiple different mucous membranes of the body, including in the urinary tract, rectum, vagina, uterus, vulva, paranasal sinuses, gallbladder, esophagus, eardrums, and pharynx. Generally, oral leukoplakia is the only context where the term is in common usage in modern medicine. In 1988, a case report used the term acquired dyskeratotic leukoplakia to refer to an acquired condition in a female where dyskeratotic cells were present in the epithelia of the mouth and genitalia.: 480 : 806 References == External links ==

You act as a medical communicator. Your goal is to translate medical terms into comprehensive, yet straightforward language for all readers.

I'm looking for a concise explanation of the medical term 'Weill–Marchesani syndrome.'

Weill–Marchesani syndrome is a rare genetic disorder characterized by short stature; an unusually short, broad head (brachycephaly) and other facial abnormalities; hand defects, including unusually short fingers (brachydactyly); and distinctive eye (ocular) abnormalities. It was named after ophthalmologists Georges Weill (1866–1952) and Oswald Marchesani (1900–1952) who first described it in 1932 and 1939, respectively. The eye manifestations typically include unusually small, round lenses of the eyes (microspherophakia), which may be prone to dislocating (ectopia lentis), as well as other ocular defects. Due to such abnormalities, affected individuals may have varying degrees of visual impairment, ranging from nearsightedness myopia to blindness. Weill–Marchesani syndrome may have autosomal recessive inheritance involving the ADAMTS10 gene, or autosomal dominant inheritance involving the FBN1 gene. In some cases there is no association with either of these genes. Diagnosis Diagnosis is made when several characteristic clinical signs are observed. There is no single test to confirm the presence of Weill–Marchesani syndrome. Exploring family history or examining other family members may prove helpful in confirming this diagnosis. Treatment Eye surgery has been documented to help those with ocular diseases, such as some forms of glaucoma. Prognosis However, long term medical management of glaucoma has not proven to be successful for patients with Weill–Marchesani syndrome. Physical therapy and orthopedic treatments are generally prescribed for problems stemming from mobility from this connective tissue disorder. However, this disorder has no cure, and generally, treatments are given to improve quality of life. See also ADAMTS17 LTBP2 References External links GeneReviews/NCBI/NIH/UW entry on Weill-Marchesani Syndrome

You act as a medical communicator. Your goal is to translate medical terms into comprehensive, yet straightforward language for all readers.

What does the medical term 'Moxifloxacin' encompass?

Moxifloxacin is an antibiotic, used to treat bacterial infections, including pneumonia, conjunctivitis, endocarditis, tuberculosis, and sinusitis. It can be given by mouth, by injection into a vein, and as an eye drop.Common side effects include diarrhea, dizziness, and headache. Severe side effects may include spontaneous tendon ruptures, nerve damage, and worsening of myasthenia gravis. Safety of use in pregnancy and breastfeeding is unclear. Moxifloxacin is in the fluoroquinolone family of medications. It usually kills bacteria by blocking their ability to duplicate DNA.Moxifloxacin was patented in 1988 and approved for use in the United States in 1999. It is on the World Health Organizations List of Essential Medicines. Medical uses Moxifloxacin treats a number of infections, including respiratory-tract infections, cellulitis, anthrax, intra-abdominal infections, endocarditis, meningitis, and tuberculosis.In the United States, moxifloxacin is licensed for the treatment of acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, community-acquired pneumonia, complicated and uncomplicated infections of the skin and of the skin structure, and complicated intra-abdominal infections. In the European Union, it is licensed for acute bacterial exacerbations of chronic bronchitis, non-severe community-acquired pneumonia, and acute bacterial sinusitis. On the basis of its investigation into reports of rare but severe cases of liver toxicity and skin reactions, the European Medicines Agency recommended in 2008 that the use of the oral (but not the intravenous) form of moxifloxacin be restricted to infections in which other antibacterial agents cannot be used or have failed. In the United States, the marketing approval does not contain these restrictions, though the label contains prominent warnings of skin reactions. The initial approval by the Food and Drug Administration of the United States (December 1999) encompassed these indications: Acute exacerbations of chronic bronchitis Acute bacterial sinusitis Community acquired pneumoniaAdditional indications approved by the Food and Drug Administration: April 2001: Uncomplicated skin and skin-structure infections May 2004: Community-acquired pneumonia caused by multidrug-resistant Streptococcus pneumoniae June 2005: Complicated skin and skin-structure infections November 2005: Complicated intra-abdominal infectionsThe European Medicines Agency has advised that, for pneumonia, acute bacterial sinusitis, and acute exacerbations of COPD, it should only be used when other antibiotics are inappropriate.Oral and intravenous moxifloxacin have not been approved for children. Several drugs in this class, including moxifloxacin, are not licensed by the Food and Drug Administration for use in children, because of the risk of permanent injury to the musculoskeletal system. Moxifloxacin eye drops are approved for conjunctival infections caused by susceptible bacteria.Recently, alarming reports of moxifloxacin resistance rates among anaerobes have been published. In Austria 36% of Bacteroides have been reported to be reistant to moxifloxacin, while in Italy resistance rates as high as 41% have been reported. Susceptible bacteria A broad spectrum of bacteria is susceptible, including the following: Staphylococcus aureus Staphylococcus epidermidis Streptococcus pneumoniae Haemophilus influenzae Klebsiella spp. Moraxella catarrhalis Enterobacter spp. Mycobacterium spp. Bacillus anthracis Mycoplasma genitalium Adverse effects Rare but serious adverse effects that may occur as a result of moxifloxacin therapy include irreversible peripheral neuropathy, spontaneous tendon rupture and tendonitis, hepatitis, psychiatric effects (hallucinations, depression), torsades de pointes, Stevens–Johnson syndrome and Clostridium difficile-associated disease, and photosensitivity/phototoxicity reactions.Several reports suggest the use of moxifloxacin may lead to uveitis. Pregnancy and breastfeeding Exposure of the developing fetus to quinolones, including levofloxacin, during the first-trimester is not associated with an increased risk of stillbirths, premature births, birth defects, or low birth weight. There is limited data about the appearance of moxifloxacin in human breastmilk. Animal studies have found that moxifloxacin appears in significant concentration in breastmilk. Decisions as to whether to continue therapy during pregnancy or while breast feeding should take the potential risk of harm to the fetus or child into account, as well as the importance of the drug to the well-being of the mother. Contraindications Only two listed contraindications are found within the 2008 package insert: "Nonsteroidal anti-inflammatory drugs (NSAIDs): Although not observed with moxifloxacin in preclinical and clinical trials, the concomitant administration of a nonsteroidal anti-inflammatory drug with a fluoroquinolone may increase the risks of CNS stimulation and convulsions." "Moxifloxacin is contraindicated in persons with a history of hypersensitivity to moxifloxacin, any member of the quinolone class of antimicrobial agents, or any of the product components."Though not stated as such within the package insert, ziprasidone is also considered to be contraindicated, as it may have the potential to prolong QT interval. Moxifloxacin should also be avoided in patients with uncorrected hypokalemia, or concurrent administration of other medications known to prolong the QT interval (antipsychotics and tricyclic antidepressants).Moxifloxacin should be used with caution in patients with diabetes, as glucose regulation may be significantly altered.Moxifloxacin is also considered to be contraindicated within the pediatric population, pregnancy, nursing mothers, patients with a history of tendon disorder, patients with documented QT prolongation, and patients with epilepsy or other seizure disorders. Coadministration of moxifloxacin with other drugs that also prolong the QT interval or induce bradycardia (e.g., beta-blockers, amiodarone) should be avoided. Careful consideration should be given in the use of moxifloxacin in patients with cardiovascular disease, including those with conduction abnormalities. Children and adolescents The safety of moxifloxacin in human patients under age 18 has not been established. Animal studies suggest a risk of musculoskeletal harm in juveniles. Interactions Moxifloxacin is not believed to be associated with clinically significant drug interactions due to inhibition or stimulation of hepatic metabolism. Thus, it should not, for the most part, require special clinical or laboratory monitoring to ensure its safety. Moxifloxacin has a potential for a serious drug interaction with NSAIDs.The combination of corticosteroids and moxifloxacin has increased potential to result in tendonitis and disability.Antacids containing aluminium or magnesium ions inhibit the absorption of moxifloxacin. Drugs that prolong the QT interval (e.g., pimozide) may have an additive effect on QT prolongation and lead to increased risk of ventricular arrhythmias. The international normalised ratio may be increased or decreased in patients treated with warfarin. Overdose "In the event of acute overdose, the stomach should be emptied and adequate hydration maintained. ECG monitoring is recommended due to the possibility of QT interval prolongation. The patient should be carefully observed and given supportive treatment. The administration of activated charcoal as soon as possible after oral overdose may prevent excessive increase of systemic moxifloxacin exposure. About 3% and 9% of the dose of moxifloxacin, as well as about 2% and 4.5% of its glucuronide metabolite are removed by continuous ambulatory peritoneal dialysis and hemodialysis, respectively." (Quoting from 29 December 2008 package insert for Avelox) Pharmacology Mechanism of action Moxifloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. It functions by inhibiting DNA gyrase, a type II topoisomerase, and topoisomerase IV, enzymes necessary to separate bacterial DNA, thereby inhibiting cell replication. Pharmacokinetics About 52% of an oral or intravenous dose of moxifloxacin is metabolized via glucuronide and sulfate conjugation. The cytochrome P450 system is not involved in moxifloxacin metabolism, and is not affected by moxifloxacin. The sulfate conjugate (M1) accounts for around 38% of the dose, and is eliminated primarily in the feces. Approximately 14% of an oral or intravenous dose is converted to a glucuronide conjugate (M2), which is excreted exclusively in the urine. Peak plasma concentrations of M2 are about 40% those of the parent drug, while plasma concentrations of M1 are, in general, less than 10% those of moxifloxacin.In vitro studies with cytochrome (CYP) P450 enzymes indicate that moxifloxacin does not inhibit 80 CYP3A4, CYP2D6, CYP2C9, CYP2C19, or CYP1A2, suggesting that moxifloxacin is unlikely to alter the pharmacokinetics of drugs metabolized by these enzymes.The pharmacokinetics of moxifloxacin in pediatric subjects have not been studied.The elimination half-life of moxifloxacin is 11.5 to 15.6 hours (single-dose, oral). About 45% of an oral or intravenous dose of moxifloxacin is excreted as unchanged drug (about 20% in urine and 25% in feces). A total of 96 ± 4% of an oral dose is excreted as either unchanged drug or known metabolites. The mean (± SD) apparent total body clearance and renal clearance are 12 ± 2 L/h and 2.6 ± 0.5 L/h, respectively. The CSF penetration of moxifloxacin is 70% to 80% in patients with meningitis. Chemistry Moxifloxacin monohydrochloride is a slightly yellow to yellow crystalline substance. It is synthesized in several steps, the first involving the preparation of racemic 2,8-diazabicyclo[4.3.0]nonane which is then resolved using tartaric acid. A suitably derivatised quinolinecarboxylic acid is then introduced, in the presence of DABCO, followed by acidification to form moxifloxacin hydrochloride. History Moxifloxacin was first patented (United States patent) in 1991 by Bayer A.G., and again in 1997. Avelox was subsequently approved by the U.S. Food and Drug Administration (FDA) for use in the United States in 1999 to treat specific bacterial infections. Ranking 140th within the top 200 prescribed drugs in the United States for 2007, Avelox generated sales of $697.3 million worldwide.Moxifloxacin is also manufactured by Alcon as Vigamox. Patent A United States patent application was made on 30 June 1989, for Avelox, Bayer A.G. being the assignee, which was subsequently approved on 5 February 1991. This patent was scheduled to expire on 30 June 2009. However, this patent was extended for an additional two and one half years on 16 September 2004, and as such was not expected to expire until 2012. Moxifloxacin was subsequently (ten years later) approved by the FDA for use in the United States in 1999. At least four additional United States patents have been filed regarding moxifloxacin hydrochloride since the 1989 United States application, as well as patents outside of the US. Society and culture Regulatory actions Regulatory agencies have taken actions to address certain rare but serious adverse events associated with moxifloxacin therapy. Based on its investigation into reports of rare but severe cases of liver toxicity and skin reactions, the European Medicines Agency recommended in 2008 that the use of the oral (but not the IV) form of moxifloxacin be restricted to infections in which other antibacterial agents cannot be used or have failed. Similarly, the Canadian label includes a warning of the risk of liver injury.The U.S. label does not contain restrictions similar to the European label, but a carries a "black box" warning of the risk of tendon damage and/or rupture and warnings regarding the risk of irreversible peripheral neuropathy. Generic equivalents In 2007, the U.S. District Court for the District of Delaware held that two Bayer patents on Avelox are valid and enforceable, and infringed by Dr. Reddys ANDA for a generic version of Avelox. The district court sided with Bayer, citing the Federal Circuits prior decision in Takeda v. Alphapharm as "affirming the district courts finding that defendant failed to prove a prima facie case of obviousness where the prior art disclosed a broad selection of compounds, any one of which could have been selected as a lead compound for further investigation, and defendant did not prove that the prior art would have led to the selection of the particular compound singled out by defendant." According to Bayers press release announcing the courts decision, it was noted that Teva had also challenged the validity of the same Bayer patents at issue in the Dr. Reddys case. Within Bayers first-quarter 2008 stockholders newsletter Bayer stated that they had reached an agreement with Teva Pharmaceuticals USA, Inc., the adverse party, to settle their patent litigation with regard to the two Bayer patents. Under the settlement terms agreed upon, Teva would obtain a license to sell its generic moxifloxacin tablet product in the U.S. shortly before the second of the two Bayer patents expires in March 2014. In Bangladesh, it is available with brand name of Optimox. References External links "Moxifloxacin". Drug Information Portal. U.S. National Library of Medicine. "Moxifloxacin hydrochloride". Drug Information Portal. U.S. National Library of Medicine.

You act as a mediator between medical professionals and the public. Provide comprehensive explanations of medical terms, ensuring they are both precise and easily understood.

I'm not familiar with the medical term 'Pelvic girdle pain.' Could you provide some insights?

Pelvic girdle pain (abbreviated PGP) can be described as a pregnancy discomfort for some women and a severe disability for others. PGP can cause pain, instability and limitation of mobility and functioning in any of the three pelvic joints. PGP has a long history of recognition, mentioned by Hippocrates and later described in medical literature by Snelling. The affection appears to consist of relaxation of the pelvic articulations, becoming apparent suddenly after parturition or gradually during pregnancy and permitting a degree of mobility of the pelvic bones which effectively hinders locomotion and gives rise to the most peculiar and alarming sensations. Classification Prior to the 20th century, specialists of pregnancy-related PGP used varying terminologies. It is now referred to as Pregnancy Related Pelvic Girdle Pain that may incorporate the following conditions: Diastasis of the symphysis pubis (DSP) Symphysis pubis dysfunction (SPD) Pelvic Joint Syndrome Physiological Pelvic Girdle Relaxation Symptom Giving Pelvic Girdle Relaxation Posterior Pelvic Pain Pelvic Arthropathy Inferior Pubic Shear/ Superior Pubic Shear /Symphyseal Shear Symphysiolysis Osteitis pubis (usually postpartum) Sacroiliitis One-sided Sacroiliac Syndrome /Double Sided Sacroiliac Syndrome Hypermobility"The classification between hormonal and mechanical pelvic girdle instability is no longer used. For treatment and/or prognosis it makes no difference whether the complaints started during pregnancy or after childbirth." Mens (2005) Signs and symptoms A combination of postural changes, baby, unstable pelvic joints under the influence of pregnancy hormones, and changes in the centre of gravity can all add to the varying degrees of pain or discomfort. In some cases it can come on suddenly or following a fall, sudden abduction of the thighs (opening too wide too quickly) or an action that has strained the joint. PGP can begin as early as the first trimester of pregnancy. Pain is usually felt low down over the symphyseal joint, and this area may be extremely tender to the touch. Pain may also be felt in the hips, groin and lower abdomen and can radiate down the inner thighs. Women with PGP may begin to waddle or shuffle, and may be aware of an audible clicking sound coming from the pelvis. PGP can develop slowly during pregnancy, gradually gaining in severity as the pregnancy progresses. During pregnancy and postpartum, the symphyseal gap can be felt moving or straining when walking, climbing stairs or turning over in bed; these activities can be difficult or even impossible. The pain may remain static, e.g., in one place such as the front of the pelvis, producing the feeling of having been kicked; in other cases it may start in one area and move to other areas. It is also possible that a woman may experience a combination of symptoms. Any weight bearing activity has the potential of aggravating an already unstable pelvis, producing symptoms that may limit the ability of the woman to carry out many daily activities. She may experience pain involving movements such as dressing, getting in and out of the bath, rolling in bed, climbing the stairs or sexual activity. Pain may also be present when lifting, carrying, pushing or pulling. The symptoms (and their severity) experienced by women with PGP vary, but include: Present swelling and/or inflammation over joint. Difficulty lifting leg. Pain pulling legs apart. Inability to stand on one leg. Inability to transfer weight through pelvis and legs. Pain in hips and/or restriction of hip movement. Transferred nerve pain down leg. Can be associated with bladder and/or bowel dysfunction. A feeling of the symphysis pubis giving way. Stooped back when standing. Malalignment of pelvic and/or back joints. Struggle to sit or stand. Pain may also radiate down the inner thighs. Waddling or shuffling gait. Audible clicking sound coming from the pelvis. Severity The severity and instability of the pelvis can be measured on a three level scale. Pelvic type 1:The pelvic ligaments support the pelvis sufficiently. Even when the muscles are used incorrectly, no complaints will occur when performing everyday activities. This is the most common situation in persons who have never been pregnant, who have never been in an accident, and who are not hypermobile. Pelvic type 2:The ligaments alone do not support the joint sufficiently. A coordinated use of muscles around the joint will compensate for ligament weakness. In case the muscles around the joint do not function, the patient will experience pain and weakness when performing everyday activities. This type often occurs after giving birth to a child weighing 3000 grams or more, in cases of hypermobility, and sometimes after an accident involving the pelvis. Type 2 is the most common form of pelvic instability. Treatment is based on learning how to use the muscles around the pelvis more efficiently. Pelvic type 3:The ligaments do not support the joint sufficiently. This is a serious situation whereby the muscles around the joint are unable to compensate for ligament weakness. This type of pelvic instability usually only occurs after an accident, or occasionally after a (small) accident in combination with giving birth. Sometimes a small accident occurring long before giving birth is forgotten so that the pelvic instability is attributed only to the childbirth. Although the difference between Type 2 and 3 is often difficult to establish, in case of doubt an exercise program may help the patient. However, if Pelvic Type 3 has been diagnosed then invasive treatment is the only option: in this case parts of the pelvis are screwed together. (Mens 2005) Psychosocial impact PGP in pregnancy seriously interferes with participation in society and activities of daily life; the average sick leave due to posterior pelvic pain during pregnancy is 7 to 12 weeks.In some cases women with PGP may also experience emotional problems such as anxiety over the cause of pain, resentment, anger, lack of self-esteem, frustration and depression; she is three times more likely to develop postpartum depressive symptoms. Other psychosocial risk factors associated with woman experiencing PGP include higher level of stress, low job satisfaction and poorer relationship with spouse. Causes Sometimes there is no obvious explanation for the cause of PGP but usually there is a combination of factors such as: The pelvic joints moving unevenly. A change in the activity of the muscles in the pelvis, hip, abdomen, back and pelvic floor. A history of pelvic trauma. The position of the baby altering the loading stresses on the pelvic ligaments and joints. Strenuous work. Previous lower back pain. Previous pelvic girdle pain during pregnancy. Hypermobility, genetical ability to stretch joints beyond normal range. An event during the pregnancy or birth that caused injury or strain to the pelvic joints or rupture of the fibrocartilage. The occurrence of PGP is associated with twin pregnancy, first pregnancy and a higher age at first pregnancy. Mechanism Pregnancy related Pelvic Girdle Pain (PGP) can be either specific (trauma or injury to pelvic joints or genetical i.e. connective tissue disease) and non-specific. PGP disorder is complex and multi-factorial and likely to be also represented by a series of sub-groups driven by pain varying from peripheral or central nervous system, altered laxity/stiffness of muscles, laxity to injury of tendinous/ligamentous structures to mal-adaptive body mechanics.Pregnancy begins the physiological changes through a pattern of hormonal secretion and signal transduction thus initiating the remodelling of soft tissues, cartilage and ligaments. Over time, the ligaments could be stretched either by injury or excess strain and in turn may cause PGP. Anatomy The pelvis is the largest bony part of the skeleton and contains three joints: the pubic symphysis, and two sacroiliac joints. A highly durable network of ligaments surrounds these joints giving them tremendous strength. The pubic symphysis has a fibrocartilage joint which may contain a fluid filled cavity and is avascular; it is supported by the superior and arcuate ligaments. The sacroiliac joints are synovial, but their movement is restricted throughout life and they are progressively obliterated by adhesions. The nature of the bony pelvic ring with its three joints determines that no one joint can move independently of the other two. Relaxin hormone Relaxin is a hormone produced mainly by the corpus luteum of the ovary and breast, in both pregnant and non-pregnant females. During pregnancy it is also produced by the placenta, chorion, and decidua. The body produces relaxin during menstruation that rises to a peak within approximately 14 days of ovulation and then declines. In pregnant cycles, rather than subsiding, relaxin secretion continues to rise during the first trimester and then again in the final weeks. During pregnancy relaxin has a diverse range of effects, including the production and remodelling of collagen thus increasing the elasticity of muscles, tendons, ligaments and tissues of the birth canal in view of delivery. Although relaxins main cellular action in pregnancy is to remodel collagen by biosynthesis (thus facilitating the changes of connective tissue) it does not seem to generate musculoskeletal problems. European Research has determined that relaxin levels are not a predictor of PGP during pregnancy. Gait changes The pregnant woman has a different pattern of "gait". The step lengthens as the pregnancy progresses due to weight gain and changes in posture. Both the length and height of the footstep shortens with PGP. Sometimes the foot can turn inwards due to the rotation of the hips when the pelvic joints are unstable. On average, a womans foot can grow by a half size or more during pregnancy. Pregnancy hormones that are released to adapt the bodily changes also remodel the ligaments in the foot. In addition, the increased body weight of pregnancy, fluid retention and weight gain lowers the arches, further adding to the foots length and width. There is an increase of load on the lateral side of the foot and the hind foot. These changes may also be responsible for the musculoskeletal complaints of lower limb pain in pregnant women. During the motion of walking, an upward movement of the pelvis, one side then the other, is required to let the leg follow through. The faster or longer each step the pelvis adjusts accordingly. The flexibility within the knees, ankles and hips are stabilized by the pelvis. Normal gait tends to minimize displacement of centre of gravity whereas abnormal gait through pelvic instability tends to amplify displacement. During pregnancy there may be an increased demand placed on hip abductor, hip extensor, and ankle plantar flexor muscles during walking. To avoid pain on weight bearing structures a very short stance phase and limp occurs on the injured side(s), this is called Antalgic Gait. Treatment A number of treatments have some evidence for benefits include an exercise program. Paracetamol (acetaminophen) has not been found effective but is safe. NSAIDs are sometimes effective but should not be used after 30 weeks of pregnancy. There is tentative evidence for acupuncture.Some pelvic joint trauma will not respond to conservative type treatments and orthopedic surgery might become the only option to stabilize the joints. Prognosis and epidemiology For most women, PGP resolves in weeks after delivery but for some it can last for years resulting in a reduced tolerance for weight bearing activities. PGP can take from 11 weeks, 6 months or even up to 2 years postpartum to subside. However, some research supports that the average time to complete recovery is 6.25 years, and the more severe the case is, the longer recovery period.Overall, about 45% of all pregnant women and 25% of all women postpartum have PGP. During pregnancy, serious pain occurs in about 25%, and severe disability in about 8% of patients. After pregnancy, problems are serious in about 7%. There is no correlation between age, culture, nationality and numbers of pregnancies that determine a higher incidence of PGP.If a woman experiences PGP during one pregnancy, she is more likely to experience it in subsequent pregnancies; but the severity cannot be determined. References Further reading Recommendations for the Nomenclature of Receptors for Relaxin Family Peptides Pharmacol Rev 58:7-31,2006 Ross A. Bathgate, Richard Ivell, Barbara M. Sanborn, O. David Sherwood and Roger J. Summers

You are a medical advisor. Your role is to break down medical terminology into clear, detailed explanations for a general audience.

Could you offer a clear explanation of the term 'Carbidopa' as used in the medical field?

Carbidopa (Lodosyn) is a drug given to people with Parkinsons disease in order to inhibit peripheral metabolism of levodopa. This property is significant in that it allows a greater proportion of administered levodopa to cross the blood–brain barrier for central nervous system effect, instead of being peripherally metabolised into substances unable to cross said barrier. Pharmacology Carbidopa inhibits aromatic-L-amino-acid decarboxylase (DOPA decarboxylase or DDC), an enzyme important in the biosynthesis of L-tryptophan to serotonin and in the biosynthesis of L-DOPA to dopamine (DA). DDC exists both outside of (body periphery) and within the confines of the blood–brain barrier. Carbidopa is used in the treatment of, among other diseases, Parkinsons disease (PD), a condition characterized by death of dopaminergic neurons in the substantia nigra. Increased dopamine availability may increase the effectiveness of the remaining neurons and alleviate symptoms for a time. The pharmacologic objective is to get an exogenous dopamine-precursor known as levodopa/L-DOPA into the dopamine-deficient brains of PD patients. Levodopa/L-DOPA can cross the blood–brain barrier, but dopamine cannot. The use of carbidopa seems counter-intuitive in Parkinsons disease (PD) in that it prevents DDC conversion of levodopa/L-DOPA to dopamine. However, exogenously provided, levadopa/L-DOPA gets metabolized peripherally to its active metabolite dopamine before reaching the blood–brain barrier. Therefore, the PD brain, which is deficient in dopamine, will not receive as much of its prodrug precursor levodopa/L-DOPA due to peripheral DDC breakdown. However, carbidopa can decrease peripheral DDC conversion of levodopa/L-DOPA before it crosses the blood–brain barrier. Carbidopa acts as a peripheral DDC inhibitor, as carbidopa, itself, cannot cross the blood–brain barrier. In other words, carbidopa has no effect on brain DDC conversion of levodopa/L-DOPA to dopamine. Ultimately, a greater proportion of the exogenously provided levodopa/L-DOPA reaches the brain. Commercially, carbidopa/levodopa combinations are available in the treatment of central dopamine deficiencies. Along with carbidopa, other DDC inhibitors are benserazide (Ro-4-4602), difluromethyldopa, and α-methyldopa. pharmacology 2 Carbidopa, an inhibitor of aromatic amino acid decarboxylation, is a white, crystalline compound, slightly soluble in water, with a molecular weight of 244.3. It is designated chemically as N-amino-α-methyl-3-hydroxy-L-tyrosine monohydrate. Its empirical formula is C10H14N2O4•H2O. Used in tandem with L-DOPA (also known as levodopa, a dopamine precursor converted in the body to dopamine), it increases the plasma half-life of levodopa from 50 minutes to 1½ hours. CarbiDOPA cannot cross the blood–brain barrier, so it inhibits only peripheral DDC. It thus prevents the conversion of L-DOPA to dopamine peripherally. This reduces the side effects caused by dopamine on the periphery, as well as increasing the concentration of L-DOPA and dopamine in the brain. The combination of carbidopa/levodopa carries the brand names of Kinson, Sinemet, Pharmacopa and Atamet; while Stalevo is a combination with entacapone, which enhances the bioavailability of carbidopa and levodopa. Carbidopa is most commonly used as a method to inhibit the activity of dopamine decarboxylase. This is an enzyme that breaks down L-Dopa in the periphery and converts it to dopamine. This results in the newly formed dopamine being unable to cross the blood–brain barrier and the effectiveness of L-Dopa treatments is greatly decreased. Carbidopa reduces the amount of levodopa required to produce a given response by about 75% and, when administered with levodopa, increases both plasma levels and the plasma half-life of levodopa, and decreases plasma and urinary dopamine and homovanillic acid. Elimination half-life of levodopa in the presence of carbidopa is about 1.5 hours. Following SINEMET CR, the apparent half-life of levodopa may be prolonged because of continuous absorption. This is extremely useful in the treatment of Parkinsons disease symptoms because the amount of levodopa administered to the patient can be greatly reduced. This reduction in dosage is extremely useful due to the side effects that may occur from an overdose of L-Dopa within the body. Carbidopa is also used in combination with 5-HTP, a naturally occurring amino acid which is a precursor to the neurotransmitter serotonin and an intermediate in tryptophan metabolism. carbidopa, which is used in PD to prevent conversion of the levodopa to dopamine, prevents 5-Hydroxytryptophan’s (5-HTP) metabolism in the liver and causes decreased levels of serotonin in the blood. Research shows that co-administration of 5-HTP and carbidopa greatly increases plasma 5-HTP levels. Several cases of scleroderma-like illness have been reported in patients using carbidopa and 5-HTP. In Europe, 5-HTP is prescribed with carbidopa to prevent the conversion of 5-HTP into serotonin until it reaches the brain. Synthesis The synthesis begins with a modified Strecker reaction using hydrazine and potassium cyanide on arylacetone (1) to give 2. This is then hydrolyzed with cold HCl to give carboxamide 3. More vigorous hydrolysis with 48% HBr cleaves the amide bond and the aryl ether group to produce carbidopa (4). References External links Lodosyn prescribing information Sinemet datasheet for New Zealand

You are a medical advisor. Your role is to break down medical terminology into clear, detailed explanations for a general audience.

I'm curious about the meaning of the medical term 'Valvular heart disease.' Can you give me some insights?

Valvular heart disease is any cardiovascular disease process involving one or more of the four valves of the heart (the aortic and mitral valves on the left side of heart and the pulmonic and tricuspid valves on the right side of heart). These conditions occur largely as a consequence of aging, but may also be the result of congenital (inborn) abnormalities or specific disease or physiologic processes including rheumatic heart disease and pregnancy.Anatomically, the valves are part of the dense connective tissue of the heart known as the cardiac skeleton and are responsible for the regulation of blood flow through the heart and great vessels. Valve failure or dysfunction can result in diminished heart functionality, though the particular consequences are dependent on the type and severity of valvular disease. Treatment of damaged valves may involve medication alone, but often involves surgical valve repair or valve replacement. Classification Stenosis and insufficiency/regurgitation represent the dominant functional and anatomic consequences associated with valvular heart disease. Irrespective of disease process, alterations to the valve occur that produce one or a combination of these conditions. Insufficiency and regurgitation are synonymous terms that describe an inability of the valve to prevent backflow of blood as leaflets of the valve fail to join (coapt) correctly. Stenosis is characterized by a narrowing of the valvular orifice that prevents adequate outflow of blood. Stenosis can also result in insufficiency if thickening of the annulus or leaflets results in inappropriate leaf closure. Aortic and mitral valve disorders Aortic and mitral valve disorders are left heart diseases that are more prevalent than diseases of the pulmonary or tricuspid valve in the right heart due to the higher pressures in the left heart.Stenosis of the aortic valve is characterized by a thickening of the valvular annulus or leaflets that limits the ability of blood to be ejected from the left ventricle into the aorta. Stenosis is typically the result of valvular calcification but may be the result of a congenitally malformed bicuspid aortic valve. This defect is characterized by the presence of only two valve leaflets. It may occur in isolation or in concert with other cardiac anomalies.Aortic insufficiency, or regurgitation, is characterized by an inability of the valve leaflets to appropriately close at the end systole, thus allowing blood to flow inappropriately backward into the left ventricle. Causes of aortic insufficiency in the majority of cases are unknown, or idiopathic. It may be the result of connective tissue or immune disorders, such as Marfan syndrome or systemic lupus erythematosus, respectively. Processes that lead to aortic insufficiency usually involve dilation of the valve annulus, thus displacing the valve leaflets, which are anchored in the annulus.Mitral stenosis is caused largely by rheumatic heart disease, though is rarely the result of calcification. In some cases, vegetations form on the mitral leaflets as a result of endocarditis, an inflammation of the heart tissue. Mitral stenosis is uncommon and not as age-dependent as other types of valvular disease.Mitral insufficiency can be caused by dilation of the left heart, often a consequence of heart failure. In these cases, the left ventricle of the heart becomes enlarged and causes displacement of the attached papillary muscles, which control the mitral. Pulmonary and tricuspid valve disorders Pulmonary and tricuspid valve diseases are right heart diseases. Pulmonary valve diseases are the least common heart valve disease in adults.Pulmonary valve stenosis is often the result of congenital malformations and is observed in isolation or as part of a larger pathologic process, as in Tetralogy of Fallot, Noonan syndrome, and congenital rubella syndrome. Unless the degree of stenosis is severe, individuals with pulmonary stenosis usually have excellent outcomes and better treatment options. Often patients do not require intervention until later in adulthood as a consequence of calcification that occurs with aging.Pulmonary valve insufficiency occurs commonly in healthy individuals to a very mild extent and does not require intervention. More appreciable insufficiency is typically the result of damage to the valve due to cardiac catheterization, intra-aortic balloon pump insertion, or other surgical manipulations. Additionally, insufficiency may be the result of carcinoid syndrome, inflammatory processes such a rheumatoid disease or endocarditis, or congenital malformations. It may also be secondary to severe pulmonary hypertension.Tricuspid valve stenosis without co-occurrent regurgitation is highly uncommon and typically the result of rheumatic disease. It may also be the result of congenital abnormalities, carcinoid syndrome, obstructive right atrial tumors (typically lipomas or myxomas), or hypereosinophilic syndromes.Minor tricuspid insufficiency is common in healthy individuals. In more severe cases it is a consequence of dilation of the right ventricle, leading to displacement of the papillary muscles which control the valves ability to close. Dilation of the right ventricle occurs secondary to ventricular septal defects, right to left shunting of blood, eisenmenger syndrome, hyperthyroidism, and pulmonary stenosis. Tricuspid insufficiency may also be the result of congenital defects of the tricuspid valve, such as Ebsteins anomaly. Signs and symptoms Aortic stenosis Symptoms of aortic stenosis may include heart failure symptoms, such as dyspnea on exertion (most frequent symptom), orthopnea and paroxysmal nocturnal dyspnea, angina pectoris, and syncope, usually exertional.Medical signs of aortic stenosis include pulsus parvus et tardus, that is, diminished and delayed carotid pulse, fourth heart sound, decreased A2 sound, sustained apex beat, precordial thrill. Auscultation may reveal a systolic murmur of a harsh crescendo-decrescendo type, heard in 2nd right intercostal space and radiating to the carotid arteries. Aortic regurgitation Patients with aortic regurgitation may experience heart failure symptoms, such as dyspnea on exertion, orthopnea and paroxysmal nocturnal dyspnea, palpitations, and angina pectoris. In acute cases patients may experience cyanosis and circulatory shock.Medical signs of aortic regurgitation include increased pulse pressure by increased systolic and decreased diastolic blood pressure, but these findings may not be significant if acute. The patient may have a diastolic decrescendo murmur best heard at left sternal border, water hammer pulse, Austin Flint murmur, and a displaced apex beat down and to the left. A third heart sound may be present Mitral stenosis Patients with mitral stenosis may present with heart failure symptoms, such as dyspnea on exertion, orthopnea and paroxysmal nocturnal dyspnea, palpitations, chest pain, hemoptysis, thromboembolism, or ascites and edema (if right-sided heart failure develops). Symptoms of mitral stenosis increase with exercise and pregnancyOn auscultation of a patient with mitral stenosis, typically the most prominent sign is a loud S1. Another finding is an opening snap followed by a low-pitched diastolic rumble with presystolic accentuation. The opening snap follows closer to the S2 heart tone with worsening stenosis. The murmur is heard best with the bell of the stethoscope lying on the left side and its duration increases with worsening disease. Advanced disease may present with signs of right-sided heart failure such as parasternal heave, jugular venous distension, hepatomegaly, ascites and/or pulmonary hypertension (presenting with a loud P2). Signs increase with exercise and pregnancy. Mitral regurgitation Patients with mitral regurgitation may present with heart failure symptoms, such as dyspnea on exertion, orthopnea and paroxysmal nocturnal dyspnea, palpitations, or pulmonary edema.On auscultation of a patient with mitral stenosis, there may be a holosystolic murmur at the apex, radiating to the back or clavicular area, a third heart sound, and a loud, palpable P2, heard best when lying on the left side. Patients also commonly have atrial fibrillation. Patients may have a laterally displaced apex beat, often with heave In acute cases, the murmur and tachycardia may be only distinctive signs. Tricuspid regurgitation Patients with tricuspid regurgitation may experience symptoms of right-sided heart failure, such as ascites, hepatomegaly, edema and jugular venous distension.Signs of tricuspid regurgitation include pulsatile liver, prominent V waves and rapid y descents in jugular venous pressure. Auscultatory findings include inspiratory third heart sound at left lower sternal border (LLSB) and a blowing holosystolic murmur at LLSB, intensifying with inspiration, and decreasing with expiration and Valsalva maneuver. Patients may have a parasternal heave along LLSB. Atrial fibrillation is usually present in patients with tricuspid regurgitation Causes Calcific disease Calcification of the leaflets of the aortic valve is a common with increasing age, but the mechanism is likely to be more related to increased lipoprotein deposits and inflammation than the "wear and tear" of advance age. Aortic stenosis due to calcification of tricuspid aortic valve with age comprises >50% of the disease. Aortic stenosis due to calcification of a bicuspid aortic valve comprises about 30-40% of the disease. Hypertension, diabetes mellitus, hyperlipoproteinemia and uremia may speed up the process of valvular calcification. Dysplasia Heart valve dysplasia is an error in the development of any of the heart valves, and a common cause of congenital heart defects in humans as well as animals; tetralogy of Fallot is a congenital heart defect with four abnormalities, one of which is stenosis of the pulmonary valve. Ebsteins anomaly is an abnormality of the tricuspid valve, and its presence can lead to tricuspid valve regurgitation. A bicuspid aortic valve is an aortic valve with only 2 cusps as opposed to the normal 3. It is present in about 0.5% to 2% of the general population and causes increased calcification due to higher turbulent flow through the valve. Connective tissue disorders Marfans Syndrome is a connective tissue disorder that can lead to chronic aortic or mitral regurgitation. Osteogenesis imperfecta is a disorder in formation of type I collagen and can also lead to chronic aortic regurgitation. Inflammatory disorders Inflammation of the heart valves due to any cause is called valvular endocarditis; this is usually due to bacterial infection but may also be due to cancer (marantic endocarditis), certain autoimmune conditions (Libman-Sacks endocarditis, seen in systemic lupus erythematosus) and hypereosinophilic syndrome (Loeffler endocarditis). Endocarditis of the valves can lead to regurgitation through that valve, which is seen in the tricuspid, mitral, and aortic valves. Certain medications have been associated with valvular heart disease, most prominently ergotamine derivatives pergolide and cabergoline.Valvular heart disease resulting from rheumatic fever is referred to as rheumatic heart disease. Acute rheumatic fever, which frequently manifests with carditis and valvulitis, is a late sequela of Group A beta-hemolytic streptococcus infection in the throat, often lagging the initial infection by weeks to months. Cardiac involvement is dependent on the cross-reaction of antibodies directed against M proteins produced by bacteria with human proteins present in the myocardium or endocardium (although acute rheumatic fever may present as pancarditis with additional involvement of the pericardium). This results in generalized inflammation in the heart, producing acute erosions and vegetations with fibrin deposition in the mitral valve that may be followed by chronic changes over years to decades, including shortening of the chordae tendinae and thickening or fusion of the mitral leaflets, leading to a severely compromised "buttonhole" or "fish mouth" valve.In 70% of cases rheumatic heart disease involves only the mitral valve, while 25% of cases involve both the aortic and mitral valves. Involvement of other heart valves without damage to the mitral is exceedingly rare. Mitral stenosis is almost always caused by rheumatic heart disease. Less than 10% of aortic stenosis is caused by rheumatic heart disease. Rheumatic fever can also cause chronic mitral and aortic regurgitation.While developed countries once had a significant burden of rheumatic fever and rheumatic heart disease, medical advances and improved social conditions have dramatically reduced their incidence. Many developing countries, as well as indigenous populations within developed countries, still carry a significant burden of rheumatic fever and rheumatic heart disease and there has been a resurgence in efforts to eradicate the diseases in these populations. Among persons who have experienced rheumatic fever, long-term intramuscular antibiotic therapy is used as secondary prophylaxis against additional streptococcal infections, which can contribute to progression of rheumatic heart disease. In people with severe valvular disease, however, short-term risks of cardiovascular compromise after intramuscular injections may outweigh the benefits, and oral therapy may be considered instead of IM injections in this subset of patients.Diseases of the aortic root can cause chronic aortic regurgitation. These diseases include syphilitic aortitis, Behçets disease, and reactive arthritis. Heart disease Tricuspid regurgitation is usually secondary to right ventricular dilation which may be due to left ventricular failure (the most common cause), right ventricular infarction, inferior myocardial infarction, or cor pulmonale Other causes of tricuspid regurgitation include carcinoid syndrome and myxomatous degeneration. Diagnosis Aortic stenosis Patients with aortic stenosis can have chest X-ray findings showing dilation of the ascending aorta, but they may also have a completely normal chest X-ray. Direct visualization of calcifications on chest X-ray is uncommon. Other findings include dilation of the left ventricle. ECG typically shows left ventricular hypertrophy in patients with severe stenosis, but it may also show signs of left heart strain. Echocardiography is the diagnostic gold standard, which shows left ventricular hypertrophy, leaflet calcification, and abnormal leaflet closure. Aortic regurgitation Chest X-ray is not as sensitive as other tests, but it may show aortic root dilation (especially in causes involving the aortic root) and apex displacement. An ECG may show left ventricular hypertrophy and signs of left heart strain. Left axis deviation can be a sign of advanced disease. An echocardiogram can be helpful in determining the root cause of the disease, as it will clearly show aortic root dilation or dissection if it exists. Typically the pump function of the heart during systole is normal, but an echocardiogram will show flow reversal during diastole. This disease is classified using regurgitant fraction (RF), or the amount of volume that flows back through the valve divided by the total forward flow through the valve during systole. Severe disease has an RF of >50%, while progressive aortic regurgitation has an RF of 30–49%. Mitral stenosis Chest x-ray in mitral stenosis will typically show an enlarged left atrium, and may show dilation of the pulmonary veins. ECG can show left atrial enlargement, due to increased pressures in the left atrium. Echocardiography is helpful in determining the severity of the disease by estimating the pulmonary artery systolic pressure. This test can also show leaflet calcification and the pressure gradient over the mitral valve. Severe mitral stenosis is defined as a mitral valve area <1.5 cm2. Progressive mitral stenosis has a normal valve area but will have increased flow velocity across the mitral valve. Mitral regurgitation Chest x-ray in mitral regurgitation can show an enlarged left atrium, as well as pulmonary venous congestion. It may also show valvular calcifications specifically in combined mitral regurgitation and stenosis due to rheumatic heart disease. ECG typically shows left atrial enlargement, but can also show right atrial enlargement if the disease is severe enough to cause pulmonary hypertension. Echocardiography is useful in visualizing the regurgitant flow and calculating the RF. It can also be used to determine the degree of calcification, and the function and closure of the valve leaflets. Severe disease has an RF of >50%, while progressive mitral regurgitation has an RF of <50%. Treatment Some of the most common treatments of valvular heart disease are avoiding smoking and excessive alcohol consumption, antibiotics, antithrombotic medications such as aspirin, anticoagulants, balloon dilation, and water pills. In some cases, surgery may be necessary. Aortic stenosis Treatment of aortic stenosis is not necessary in asymptomatic patients, unless the stenosis is classified as severe based on valve hemodynamics. Both asymptomatic severe and symptomatic aortic stenosis are treated with aortic valve replacement (AVR) surgery. Trans-catheter Aortic Valve Replacement (TAVR) is an alternative to AVR and is recommended in high risk patients who may not be suitable for surgical AVR. Any angina is treated with short-acting nitrovasodilators, beta-blockers and/or calcium blockers. Any hypertension is treated aggressively, but caution must be taken in administering beta-blockers. Any heart failure is treated with digoxin, diuretics, nitrovasodilators and, if not contraindicated, cautious inpatient administration of ACE inhibitors. Moderate stenosis is monitored with echocardiography every 1–2 years, possibly with supplementary cardiac stress test. Severe stenosis should be monitored with echocardiography every 3–6 months. Aortic regurgitation Aortic regurgitation is treated with aortic valve replacement, which is recommended in patients with symptomatic severe aortic regurgitation. Aortic valve replacement is also recommended in patients that are asymptomatic but have chronic severe aortic regurgitation and left ventricular ejection fraction of less than 50%. Hypertension is treated in patients with chronic aortic regurgitation, with the anti-hypersensives of choice being calcium channel blockers, ACE inhibitors, or ARBs. Also, endocarditis prophylaxis is indicated before dental, gastrointestinal or genitourinary procedures. Mild to moderate aortic regurgitation should be followed with echocardiography and a cardiac stress test once every 1–2 years. In severe moderate/severe cases, patients should be followed with echocardiography and cardiac stress test and/or isotope perfusion imaging every 3–6 months. Mitral stenosis For patients with symptomatic severe mitral stenosis, percutaneous balloon mitral valvuloplasty (PBMV) is recommended. If this procedure fails, then it may be necessary to undergo mitral valve surgery, which may involve valve replacement, repair, or commisurotomy. Anticoagulation is recommended for patients that have mitral stenosis in the setting of atrial fibrillation or a previous embolic event. No therapy is required for asymptomatic patients. Diuretics may be used to treat pulmonary congestion or edema. Mitral regurgitation Surgery is recommended for chronic severe mitral regurgitation in symptomatic patients with left ventricular ejection fraction (LVEF) of greater than 30%, and asymptomatic patients with LVEF of 30-60% or left ventricular end diastolic volume (LVEDV) > 40%. Surgical repair of the leaflets is preferred to mitral valve replacement as long as the repair is feasible. Mitral regurgitation may be treated medically with vasodilators, diuretics, digoxin, antiarrhythmics, and chronic anticoagulation. Mild to moderate mitral regurgitation should be followed with echocardiography and cardiac stress test every 1–3 years. Severe mitral regurgitation should be followed with echocardiography every 3–6 months. Epidemiology In the United States, about 2.5% of the population has moderate to severe valvular heart disease. The prevalence of these diseases increase with age, and 75 year-olds in the United States have a prevalence of about 13%. In industrially underdeveloped regions, rheumatic disease is the most common cause of valve diseases, and it can cause up to 65% of the valve disorders seen in these regions. Aortic stenosis Aortic stenosis is typically the result of aging, occurring in 12.4% of the population over 75 years of age, and represents the most common cause of outflow obstruction in the left ventricle. Bicuspid aortic valves are found in up to 1% of the population, making it one of the most common cardiac abnormalities. Aortic regurgitation The prevalence of aortic regurgitation also increases with age. Moderate to severe disease has a prevalence of 13% in patients between the ages of 55 and 86. This valve disease is primarily caused by aortic root dilation, but infective endocarditis has been an increased risk factor. It has been found to be the cause of aortic regurgitation in up to 25% of surgical cases. Mitral stenosis Mitral stenosis is caused almost exclusively by rheumatic heart disease, and has a prevalence of about 0.1% in the United States. Mitral stenosis is the most common valvular heart disease in pregnancy. Mitral regurgitation Mitral regurgitation is significantly associated with normal aging, rising in prevalence with age. It is estimated to be present in over 9% of people over 75. Special populations Pregnancy The evaluation of individuals with valvular heart disease who are or wish to become pregnant is a difficult issue. Issues that have to be addressed include the risks during pregnancy to the mother and the developing fetus by the presence of maternal valvular heart disease as a pre-existing disease in pregnancy. Normal physiological changes during pregnancy require, on average, a 50% increase in circulating blood volume that is accompanied by an increase in cardiac output that usually peaks between the midportion of the second and third trimesters. The increased cardiac output is due to an increase in the stroke volume, and a small increase in heart rate, averaging 10 to 20 beats per minute. Additionally uterine circulation and endogenous hormones cause systemic vascular resistance to decrease and a disproportionately lowering of diastolic blood pressure causes a wide pulse pressure. Inferior vena caval obstruction from a gravid uterus in the supine position can result in an abrupt decrease in cardiac preload, which leads to hypotension with weakness and lightheadedness. During labor and delivery cardiac output increases more in part due to the associated anxiety and pain, as well as due to uterine contractions which will cause an increase in systolic and diastolic blood pressure.Valvular heart lesions associated with high maternal and fetal risk during pregnancy include: Severe aortic stenosis with or without symptoms Aortic regurgitation with NYHA functional class III-IV symptoms Mitral stenosis with NYHA functional class II-IV symptoms Mitral regurgitation with NYHA functional class III-IV symptoms Aortic and/or mitral valve disease resulting in severe pulmonary hypertension (pulmonary pressure greater than 75% of systemic pressures) Aortic and/or mitral valve disease with severe LV dysfunction (EF less than 0.40) Mechanical prosthetic valve requiring anticoagulation Marfan syndrome with or without aortic regurgitationIn individuals who require an artificial heart valve, consideration must be made for deterioration of the valve over time (for bioprosthetic valves) versus the risks of blood clotting in pregnancy with mechanical valves with the resultant need of drugs in pregnancy in the form of anticoagulation. == References ==

You function as a medical informant. Please provide in-depth yet accessible descriptions of medical terms, suitable for a broad audience.

I need a basic explanation for the medical term 'Irbesartan.'

Irbesartan, sold under the brand name Avapro among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combination irbesartan/hydrochlorothiazide.Common side effects include dizziness, diarrhea, feeling tired, muscle pain, and heartburn. Serious side effects may include kidney problems, low blood pressure, and angioedema. Use in pregnancy may harm the baby and use when breastfeeding is not recommended. It is an angiotensin II receptor antagonist and works by blocking the effects of angiotensin II.Irbesartan was patented in 1990, and approved for medical use in 1997. It is available as a generic medication. In 2019, it was the 181st most commonly prescribed medication in the United States, with more than 3 million prescriptions. Structure activity relationship Irbesartan has the common structural features seen within the Angiotensin-II Receptor blockers or ARB medications. The medicine has an extended diphenyl group with a tetrazole at the 2-prime position. At the 4prime position, the molecule has a diazaspiro04-none, which is on a methyl. Medical uses Irbesartan is used for the treatment of hypertension. It may also delay progression of diabetic nephropathy and is also indicated for the reduction of renal disease progression in patients with type 2 diabetes, hypertension and microalbuminuria (>30 mg/24 h) or proteinuria (>900 mg/24 h). Combination with diuretic Irbesartan is also available in a fixed-dose combination formulation with hydrochlorothiazide, a thiazide diuretic, to achieve an additive antihypertensive effect. Irbesartan/hydrochlorothiazide combination preparations are marketed under various brand names. Society and culture It was developed by Sanofi Research (part of Sanofi-Aventis). It is jointly marketed by Sanofi-Aventis and Bristol-Myers Squibb under the brand names Aprovel, Karvea, and Avapro. References External links "Irbesartan". Drug Information Portal. U.S. National Library of Medicine. "Hydrochlorothiazide mixture with irbesartan". Drug Information Portal. U.S. National Library of Medicine.

You are a facilitator of medical knowledge. Provide thorough and accessible explanations of medical terms, catering to both specialists and non-specialists.

I'm not familiar with the medical term 'Itraconazole.' Could you provide some insights?

Itraconazole, sometimes abbreviated ITZ, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, blastomycosis, coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis. It may be given by mouth or intravenously.Common side effects include nausea, diarrhea, abdominal pain, rash, and headache. Severe side effects may include liver problems, heart failure, Stevens–Johnson syndrome and allergic reactions including anaphylaxis. It is unclear if use during pregnancy or breastfeeding is safe. It is in the triazole family of medications. It stops fungal growth by affecting the cell membrane or affecting their metabolism.Itraconazole was patented in 1978 and approved for medical use in the United States in 1992. It is on the World Health Organizations List of Essential Medicines.Recent research works suggest itraconazole (ITZ) could also be used in the treatment of cancer by inhibiting the hedgehog pathway in a similar way to sonidegib. Medical uses Itraconazole has a broader spectrum of activity than fluconazole (but not as broad as voriconazole or posaconazole). In particular, it is active against Aspergillus, which fluconazole is not. It is also licensed for use in blastomycosis, sporotrichosis, histoplasmosis, and onychomycosis. Itraconazole is over 99% protein-bound and has virtually no penetration into cerebrospinal fluid. Therefore, it should not be used to treat meningitis or other central nervous system infections. According to the Johns Hopkins Abx Guide, it has "negligible CSF penetration, however treatment has been successful for cryptococcal and coccidioidal meningitis".It is also prescribed for systemic infections, such as aspergillosis, candidiasis, and cryptococcosis, where other antifungal drugs are inappropriate or ineffective. In the past decade, itraconazole has been explored as an anticancer agent for patients with basal cell carcinoma, non-small cell lung cancer, and prostate cancer. For example, in a phase II study involving men with advanced prostate cancer, high-dose itraconazole (600 mg/day) was associated with significant PSA responses and a delay in tumor progression. Itraconazole also showed activity in a phase II trial in men with non-small cell lung cancer when it was combined with the chemotherapy agent, pemetrexed. A recent review has also highlights its use topically and orally in conjunction with other chemotherapeutic agents for advanced and metastatic basal cell carcinomas that cannot be treated surgically. Available forms Itraconazole is produced as blue 22 mm (0.87 in) capsules with tiny 1.5 mm (0.059 in) blue pellets inside. Each capsule contains 100 mg and is usually taken twice a day at twelve-hour intervals. The Sporanox brand of itraconazole has been developed and marketed by Janssen Pharmaceutica, a subsidiary of Johnson & Johnson. The three-layer structure of these blue capsules is complex because itraconazole is insoluble and is sensitive to pH. The complicated procedure not only requires a specialized machine to create it, but also the method used has manufacturing problems. Also, the pill is quite large, making it difficult for many patients to swallow. Parts of the processes of creating Sporanox were discovered by the Korean Patent Laid-open No. 10-2001-2590. The tiny blue pellets contained in the capsule are manufactured in Beerse, Belgium.The oral solution is better absorbed. The cyclodextrin contained in the oral solution can cause an osmotic diarrhea, and if this is a problem, then half the dose can be given as oral solution and half as capsule to reduce the amount of cyclodextrin given. "Sporanox" itraconazole capsules should always be taken with food, as this improves absorption, however the manufacturers of "Lozanoc" assert that it may be taken "without regard to meals". Itraconazole oral solution should be taken an hour before food, or two hours after food (and likewise if a combination of capsules and oral solution are used). Itraconazole may be taken with orange juice or cola, as absorption is also improved by acid. Absorption of itraconazole is impaired when taken with an antacid, H2 blocker or proton pump inhibitor. Side effects Itraconazole is a relatively well-tolerated drug (although not as well tolerated as fluconazole or voriconazole) and the range of adverse effects it produces is similar to the other azole antifungals: elevated alanine aminotransferase levels are found in 4% of people taking itraconazole "small but real risk" of developing congestive heart failure liver failure, sometimes fatalThe cyclodextrin used to make the syrup preparation can cause diarrhea. Side effects that may indicate a greater problem include: Interactions The following drugs should not be taken with itraconazole: Pharmacology Pharmacodynamics The mechanism of action of itraconazole is the same as the other azole antifungals: it inhibits the fungal-mediated synthesis of ergosterol, via inhibition of lanosterol 14α-demethylase. Because of its ability to inhibit cytochrome P450 3A4 CC-3, caution should be used when considering interactions with other medications.Itraconazole is pharmacologically distinct from other azole antifungal agents in that it is the only inhibitor in this class that has been shown to inhibit both the hedgehog signaling pathway and angiogenesis. These distinct activities are unrelated to inhibition of the cytochrome P450 lanosterol 14 alpha-demethylase and the exact molecular targets responsible remain unidentified. Functionally, the antiangiogenic activity of itraconazole has been shown to be linked to inhibition of glycosylation, VEGFR2 phosphorylation, trafficking, and cholesterol biosynthesis pathways. Evidence suggests the structural determinants for inhibition of hedgehog signaling by itraconazole are recognizably different from those associated with antiangiogenic activity. Pharmacokinetics Itraconazole, like cyclosporine, quinidine, and clarithromycin, can inhibit P-glycoprotein, causing drug interactions by reducing elimination and increasing absorption of organic cation drugs. With conventional itraconazole preparations serum levels can vary greatly between patients, often resulting in serum concentrations lower than the therapeutic index. It has therefore been conventionally advised that patients take itraconazole after a fatty meal rather than prior to eating.A product (Lozanoc) licensed through the European union decentralised procedure has increased bioavailability, decreased sensitivity to co ingestion of food, and hence decreased variability of serum levels. Chemistry The itraconazole molecule has three chiral carbons. The two chiral centers in the dioxolane ring are fixed in relation to one another, and the triazolomethylene and aryloxymethylene dioxolane-ring substituents are always cis to each other. The clinical formulation is a 1:1:1:1 mixture of four stereoisomers (two enantiomeric pairs). History Itraconazole was approved for medical use in the United States in 1992.It was designated an orphan drug by both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). References External links Media related to Itraconazole at Wikimedia Commons "Itraconazole". Drug Information Portal. U.S. National Library of Medicine.

You function as a medical explainer. Your task is to convey the meanings of medical terms in a detailed, yet easy-to-understand manner.

What is the significance of the term 'Cat-scratch disease' in the medical field?

Cat-scratch disease (CSD) or felinosis is an infectious disease that most often results from a scratch or bite of a cat. Symptoms typically include a non-painful bump or blister at the site of injury and painful and swollen lymph nodes. People may feel tired, have a headache, or a fever. Symptoms typically begin within 3–14 days following infection.Cat-scratch disease is caused by the bacterium Bartonella henselae which is believed to be spread by the cats saliva. Young cats pose a greater risk than older cats. Occasionally dog scratches or bites may be involved. Diagnosis is generally based on symptoms. Confirmation is possible by blood tests.The primary treatment is supportive. Antibiotics speed healing and are recommended in those with severe disease or immune problems. Recovery typically occurs within 4 months but can require a year. About 1 in 10,000 people are affected. It is more common in children. Signs and symptoms Cat-scratch disease commonly presents as tender, swollen lymph nodes near the site of the inoculating bite or scratch or on the neck, and is usually limited to one side. This condition is referred to as regional lymphadenopathy and occurs 1–3 weeks after inoculation. Lymphadenopathy most commonly occurs in the axilla, arms, neck, or jaw, but may also occur near the groin or around the ear. A vesicle or an erythematous papule may form at the site of initial infection.Most people also develop systemic symptoms such as malaise, decreased appetite, and aches. Other associated complaints include headache, chills, muscular pains, joint pains, arthritis, backache, and abdominal pain. It may take 7 to 14 days, or as long as two months, for symptoms to appear. Most cases are benign and self-limiting, but lymphadenopathy may persist for several months after other symptoms disappear. The disease usually resolves spontaneously, with or without treatment, in one month. In rare situations, CSD can lead to the development of serious neurologic or cardiac sequelae such as meningoencephalitis, encephalopathy, seizures, or endocarditis. Endocarditis associated with Bartonella infection has a particularly high mortality. Parinauds oculoglandular syndrome is the most common ocular manifestation of CSD, and is a granulomatous conjunctivitis with concurrent swelling of the lymph node near the ear. Optic neuritis or neuroretinitis is one of the atypical presentations.People who are immunocompromised are susceptible to other conditions associated with B. henselae and B. quintana, such as bacillary angiomatosis or bacillary peliosis. Bacillary angiomatosis is primarily a vascular skin lesion that may extend to bone or be present in other areas of the body. In the typical scenario, the patient has HIV or another cause of severe immune dysfunction. Bacillary peliosis is caused by B. henselae that most often affects people with HIV and other conditions causing severe immune compromise. The liver and spleen are primarily affected, with findings of blood-filled cystic spaces on pathology. Cause Bartonella henselae is a fastidious, intracellular, Gram-negative bacterium. Transmission The cat was recognized as the natural reservoir of the disease in 1950 by Robert Debré. Kittens are more likely to carry the bacteria in their blood, so may be more likely to transmit the disease than adult cats. However, fleas serve as a vector for transmission of B. henselae among cats, and viable B. henselae are excreted in the feces of Ctenocephalides felis, the cat flea. Cats could be infected with B. henselae through intradermal inoculation using flea feces containing B. henselae.As a consequence, a likely means of transmission of B. henselae from cats to humans may be inoculation with flea feces containing B. henselae through a contaminated cat scratch wound or by cat saliva transmitted in a bite. Ticks can also act as vectors and occasionally transmit the bacteria to humans. Combined clinical and PCR-based research has shown that other organisms can transmit Bartonella, including spiders. Cryptic Bartonella infection may be a much larger problem than previously thought, constituting an unrecognized occupational health hazard of veterinarians. Diagnosis The best diagnostic method available is polymerase chain reaction, which has a sensitivity of 43-76% and a specificity (in one study) of 100%. The Warthin–Starry stain can be helpful to show the presence of B. henselae, but is often difficult to interpret. B. henselae is difficult to culture and can take 2–6 weeks to incubate. Histology Cat-scratch disease is characterized by granulomatous inflammation on histological examination of the lymph nodes. Under the microscope, the skin lesion demonstrates a circumscribed focus of necrosis, surrounded by histiocytes, often accompanied by multinucleated giant cells, lymphocytes, and eosinophils. The regional lymph nodes demonstrate follicular hyperplasia with central stellate necrosis with neutrophils, surrounded by palisading histiocytes (suppurative granulomas) and sinuses packed with monocytoid B cells, usually without perifollicular and intrafollicular epithelioid cells. This pattern, although typical, is only present in a minority of cases. Prevention Cat-scratch disease can be primarily prevented by taking effective flea control measures; since cats are mostly exposed to fleas when they are outside, keeping cats inside can help prevent infestation. Strictly-indoor cats without exposure to indoor-outdoor animals are generally at negligible risk of infestation. Cats which are carrying the bacterium, B. henselae, are asymptomatic, thus thoroughly washing hands after handling a cat or cat feces is an important factor in preventing potential cat-scratch disease transmission from possibly infected cats to humans. Treatment Most healthy people clear the infection without treatment, but in 5 to 14% of individuals, the organisms disseminate and infect the liver, spleen, eye, or central nervous system. Although some experts recommend not treating typical CSD in immunocompetent people with mild to moderate illness, treatment of all people with antimicrobial agents (Grade 2B) is suggested due to the probability of disseminated disease. The preferred antibiotic for treatment is azithromycin, since this agent is the only one studied in a randomized controlled study.Azithromycin is preferentially used in pregnancy to avoid the teratogenic side effects of doxycycline. However, doxycycline is preferred to treat B. henselae infections with optic neuritis due to its ability to adequately penetrate the tissues of the eye and central nervous system. Epidemiology Cat-scratch disease has a worldwide distribution, but it is a nonreportable disease in humans, so public health data on this disease are inadequate. Geographical location, present season, and variables associated with cats (such as exposure and degree of flea infestation) all play a factor in the prevalence of CSD within a population. In warmer climates, the CSD is more prevalent during the fall and winter, which may be attributed to the breeding season for adult cats, which allows for the birth of kittens. B henselae, the bacterium responsible for causing CSD, is more prevalent in younger cats (less than one year old) than it is in adult cats.To determine recent incidence of CSD in the United States, the Truven Health MarketScan Commercial Claims and Encounters database was analyzed in a case control study from 2005 to 2013. The database consisted of healthcare insurance claims for employees, their spouses, and their dependents. All participants were under 65 years of age, from all 50 states. The length of the study period was 9 years and was based on 280,522,578 person-years; factors such as year, length of insurance coverage, region, age, and sex were used to calculate the person-years incidence rate to eliminate confounding variables among the entire study population.A total of 13,273 subjects were diagnosed with CSD, and both in- and outpatient cases were analyzed. The study revealed an incidence rate of 4.5/100,000 outpatient cases of cat-scratch disease. For inpatient cases, the incidence rate was much lower at 0.19/100,000 population. Incidence of CSD was highest in 2005 among outpatient cases and then slowly declined. The Southern states had the most significant decrease of incidence over time. Mountain regions have the lowest incidence of this disease because fleas are not commonly found in these areas.Distribution of CSD among children aged 5–9 was of the highest incidence in the analyzed database, followed by women aged 60–64. Incidence among females was higher than that among males in all age groups. According to data on social trends, women are more likely to own a cat over men; which supports higher incidence rates of this disease in women. Risk of contracting CSD increases as the number of cats residing in the home increases. The number of pet cats in the United States is estimated to be 57 million. Due to the large population of cats residing in the United States, the ability of this disease to continue to infect humans is vast. Laboratory diagnosis of CSD has improved in recent years, which may support an increase in incidence of the disease in future populations. Outbreaks Historically, the number of reported cases of CSD has been low, there has been a significant increase in reports in urban and suburban areas in the northeast region of United States. An example of the increased incidence can be found in Essex County, New Jersey. In 2016, there were 6 reported cases. In 2017, there were 51 reported cases. In 2018, there were 263 reported cases. Based on preliminary data, it is expected that there will be over 1,000 reported cases of CSD in Essex County, New Jersey. Although usually treated with antibiotics and minimal long-term effects, there have been 3 reported case of tachycardia more than one year after exposure. Pathologists believe that the increased incidence of CSD is due to cat owners neglecting to vaccinate their cats. History Symptoms similar to CSD were first described by Henri Parinaud in 1889, and the clinical syndrome was first described in 1950 by Robert Debré. In 1983, the Warthin-Starry silver stain was used to discover a Gram-negative bacillus which was named Afipia felis in 1991 after it was successfully cultured and isolated. The causative organism of CSD was originally believed to be Afipia felis, but this was disproved by immunological studies in the 1990s demonstrating that people with cat-scratch fever developed antibodies to two other organisms, B. henselae (originally known as Rochalimea henselae before the genera Bartonella and Rochalimea were combined) and B. clarridgeiae, which is a rod-shaped Gram-negative bacterium. References External links https://www.cdc.gov/bartonella/cat-scratch/index.html DermNet bacterial/catscratchCat Scratch Disease on National Organization for Rare Disorders site

You function as a medical explainer. Your task is to convey the meanings of medical terms in a detailed, yet easy-to-understand manner.

Can you demystify the medical term '5' for me?

5 (five) is a number, numeral and digit. It is the natural number, and cardinal number, following 4 and preceding 6, and is a prime number. It has attained significance throughout history in part because typical humans have five digits on each hand. In mathematics 5 {\displaystyle 5} is the third smallest prime number, and the second super-prime. It is the first safe prime, the first good prime, the first balanced prime, and the first of three known Wilson primes. Five is the second Fermat prime and the third Mersenne prime exponent, as well as the third Catalan number, and the third Sophie Germain prime. Notably, 5 is equal to the sum of the only consecutive primes, 2 + 3, and is the only number that is part of more than one pair of twin primes, (3, 5) and (5, 7). It is also a sexy prime with the fifth prime number and first prime repunit, 11. Five is the third factorial prime, an alternating factorial, and an Eisenstein prime with no imaginary part and real part of the form 3 p {\displaystyle 3p} − 1 {\displaystyle 1} . In particular, five is the first congruent number, since it is the length of the hypotenuse of the smallest integer-sided right triangle.Five is the second Fermat prime of the form 2 2 n {\displaystyle 2^{2^{n}}} + 1 {\displaystyle 1} , and more generally the second Sierpiński number of the first kind, n n {\displaystyle n^{n}} + 1 {\displaystyle 1} . There are a total of five known Fermat primes, which also include 3, 17, 257, and 65537. The sum of the first 3 Fermat primes, 3, 5 and 17, yields 25 or 52, while 257 is the 55th prime number. Combinations from these 5 Fermat primes generate 31 polygons with an odd number of sides that can be constructed purely with a compass and straight-edge, which includes the five-sided regular pentagon. Apropos, 31 is also equal to the sum of the maximum number of areas inside a circle that are formed from the sides and diagonals of the first five n {\displaystyle n} -sided polygons, and equal to the maximum number of areas formed by a six-sided polygon; per Mosers circle problem.The number 5 is the fifth Fibonacci number, being 2 plus 3. It is the only Fibonacci number that is equal to its position aside from 1, which is both the first and second Fibonacci numbers. Five is also a Pell number and a Markov number, appearing in solutions to the Markov Diophantine equation: (1, 2, 5), (1, 5, 13), (2, 5, 29), (5, 13, 194), (5, 29, 433), ... (OEIS: A030452 lists Markov numbers that appear in solutions where one of the other two terms is 5). Whereas 5 is unique in the Fibonacci sequence, in the Perrin sequence 5 is both the fifth and sixth Perrin numbers.5 is the third Mersenne prime exponent of the form 2 n {\displaystyle 2^{n}} − 1 {\displaystyle 1} , which yields 31 {\displaystyle 31} : the prime index of the third Mersenne prime and second double Mersenne prime 127, as well as the third double Mersenne prime exponent for the number 2,147,483,647, which is the largest value that a signed 32-bit integer field can hold. There are only four known double Mersenne prime numbers, with a fifth candidate double Mersenne prime M M 61 {\displaystyle M_{M_{61}}} = 223058...93951 − 1 too large to compute with current computers. In a related sequence, the first 5 terms in the sequence of Catalan–Mersenne numbers M c n {\displaystyle M_{c_{n}}} are the only known prime terms, with a sixth possible candidate in the order of 101037.7094. These prime sequences are conjectured to be prime up to a certain limit. Every odd number greater than 1 {\displaystyle 1} is the sum of at most five prime numbers, and every odd number greater than 5 {\displaystyle 5} is conjectured to be expressible as the sum of three prime numbers. Helfgott has provided a proof of the latter, also known as the odd Goldbach conjecture, that is already widely acknowledged by mathematicians as it still undergoes peer-review. The sums of the first five non-primes greater than zero 1 {\displaystyle 1} + 4 {\displaystyle 4} + 6 {\displaystyle 6} + 8 {\displaystyle 8} + 9 {\displaystyle 9} and the first five prime numbers 2 {\displaystyle 2} + 3 {\displaystyle 3} + 5 {\displaystyle 5} + 7 {\displaystyle 7} + 11 {\displaystyle 11} both equal 28 {\displaystyle 28} ; the 7th triangular number and like 6 {\displaystyle 6} a perfect number, which also includes 496 {\displaystyle 496} , the 31st triangular number and perfect number of the form 2 p {\displaystyle 2^{p}} −1( 2 p {\displaystyle 2^{p}} − 1 {\displaystyle 1} ) with a p {\displaystyle p} of 5 {\displaystyle 5} , by the Euclid–Euler theorem.There are a total of five known unitary perfect numbers, which are numbers that are the sums of their positive proper unitary divisors. A sixth unitary number, if discovered, would have at least nine odd prime factors.Five is conjectured to be the only odd untouchable number, and if this is the case then five will be the only odd prime number that is not the base of an aliquot tree.In figurate numbers, 5 is a pentagonal number, with the sequence of pentagonal numbers starting: 1, 5, 12, 22, 35, ... 5 is a centered tetrahedral number: 1, 5, 15, 35, 69, ... Every centered tetrahedral number with an index of 2, 3 or 4 modulo 5 is divisible by 5. 5 is a square pyramidal number: 1, 5, 14, 30, 55, ... The sum of the first four members is 50 while the fifth indexed member in the sequence is 55. 5 is a centered square number: 1, 5, 13, 25, 41, ... The fifth square number or 52 is 25, which features in the proportions of the two smallest (3, 4, 5) and (5, 12, 13) primitive Pythagorean triples.The factorial of five, or 5 {\displaystyle 5} ! = 120 {\displaystyle 120} , is the sum of the first fifteen non-zero positive integers, and 15th triangular number, which in turn is the sum of the first five non-zero positive integers and 5th triangular number. 35, which is the fourth or fifth pentagonal and tetrahedral number, is equal to the sum of the first five triangular numbers: 1, 3, 6, 10, 15.5 is the value of the central cell of the only non-trivial normal magic square, also called the Lo Shu square. Its 3 {\displaystyle 3} x 3 {\displaystyle 3} array of squares has a magic constant M {\displaystyle M} of 15 {\displaystyle 15} , where the sums of its rows, columns, and diagonals are all equal to fifteen. 5 is also the value of the central cell the only non-trivial order-3 normal magic hexagon that is made of nineteen cells.Polynomial equations of degree 4 and below can be solved with radicals, while quintic equations of degree 5, and higher, cannot generally be so solved. This is the Abel–Ruffini theorem. This is related to the fact that the symmetric group S n {\displaystyle \mathrm {S} _{n}} is a solvable group for n ⩽ 4 and not solvable for n ⩾ 5. Eulers identity, e i π {\displaystyle e^{i\pi }} + 1 {\displaystyle 1} = 0 {\displaystyle 0} , contains five essential numbers used widely in mathematics: Archimedes constant π {\displaystyle \pi } , Eulers number e {\displaystyle e} , the imaginary number i {\displaystyle i} , unity 1 {\displaystyle 1} , and zero 0 {\displaystyle 0} , which makes this formula a renown example of beauty in mathematics. In geometry A pentagram, or five-pointed polygram, is the first proper star polygon constructed from the diagonals of a regular pentagon as self-intersecting edges that are proportioned in golden ratio, φ {\displaystyle \varphi } . Its internal geometry appears prominently in Penrose tilings, and is a facet inside Kepler-Poinsot star polyhedra and Schläfli–Hess star polychora, represented by its Schläfli symbol {5/2}. A similar figure to the pentagram is a five-pointed simple isotoxal star ☆ without self-intersecting edges. Generally, star polytopes that are regular only exist in dimensions 2 ⩽ n {\displaystyle n} < 5. In graph theory, all graphs with 4 or fewer vertices are planar, however, there is a graph with 5 vertices that is not: K5, the complete graph with 5 vertices, where every pair of distinct vertices in a pentagon is joined by unique edges belonging to a pentagram. By Kuratowskis theorem, a finite graph is planar iff it does not contain a subgraph that is a subdivision of K5, or the complete bipartite utility graph K3,3. A similar graph is the Petersen graph, which is strongly connected and also nonplanar. It is most easily described as graph of a pentagram embedded inside a pentagon, with a total of 5 crossings, a girth of 5, and a Thue number of 5. The Petersen graph, which is also a distance-regular graph, is one of only 5 known connected vertex-transitive graphs with no Hamiltonian cycles. The automorphism group of the Petersen graph is the symmetric group S 5 {\displaystyle \mathrm {S} _{5}} of order 120 = 5!. The chromatic number of the plane is at least five, depending on the choice of set-theoretical axioms: the minimum number of colors required to color the plane such that no pair of points at a distance of 1 has the same color. Whereas the hexagonal Golomb graph and the regular hexagonal tiling generate chromatic numbers of 4 and 7, respectively, a chromatic coloring of 5 can be attained under a more complicated graph where multiple four-coloring Moser spindles are linked so that no monochromatic triples exist in any coloring of the overall graph, as that would generate an equilateral arrangement that tends toward a purely hexagonal structure. The plane contains a total of five Bravais lattices, or arrays of points defined by discrete translation operations: hexagonal, oblique, rectangular, centered rectangular, and square lattices. The plane can also be tiled monohedrally with convex pentagons in fifteen different ways, three of which have Laves tilings as special cases.Five points are needed to determine a conic section, in the same way that two points are needed to determine a line. A Veronese surface in the projective plane P 5 {\displaystyle \mathbb {P} ^{5}} of a conic generalizes a linear condition for a point to be contained inside a conic. There are 5 {\displaystyle 5} Platonic solids in three-dimensional space: the tetrahedron, cube, octahedron, dodecahedron, and icosahedron. The dodecahedron in particular contains pentagonal faces, while the icosahedron, its dual polyhedron, has a vertex figure that is a regular pentagon. There are also 5 {\displaystyle 5} : ☆ Regular polyhedron compounds: the stella octangula, compound of five tetrahedra, compound of five cubes, compound of five octahedra, and compound of ten tetrahedra. Icosahedral symmetry I h {\displaystyle \mathrm {I} _{h}} is isomorphic to the alternating group on 5 letters A 5 {\displaystyle \mathrm {A} _{5}} of order 120, realized by actions on these uniform polyhedron compounds. ☆ Space-filling convex polyhedra: the triangular prism, hexagonal prism, cube, truncated octahedron, and gyrobifastigium. While the cube is the only Platonic solid that can tessellate space on its own, the truncated octahedron and the gyrobifastigium are the only Archimedean and Johnson solids, respectively, that can also tessellate space with their own copies. ☆ Cell-transitive parallelohedra: any parallelepiped, as well as the rhombic dodecahedron and elongated dodecahedron, and the hexagonal prism and truncated octahedron. The cube is a special case of a parallelepiped, with the rhombic dodecahedron the only Catalan solid to tessellate space on its own. ☆ Regular abstract polyhedra, which include the excavated dodecahedron and the dodecadodecahedron. They have combinatorial symmetries transitive on flags of their elements, with topologies equivalent to that of toroids and the ability to tile the hyperbolic plane. The 5-cell, or pentatope, is the self-dual fourth-dimensional analogue of the tetrahedron, with Coxeter group symmetry A 4 {\displaystyle \mathrm {A} _{4}} of order 120 = 5! and S 5 {\displaystyle \mathrm {S} _{5}} group structure. Made of five tetrahedra, its Petrie polygon is a regular pentagon and its orthographic projection is equivalent to the complete graph K5. It is one of six regular 4-polytopes, made of thirty-one elements: five vertices, ten edges, ten faces, five tetrahedral cells and one 4-face. A regular 120-cell, the dual polychoron to the regular 600-cell, can fit one hundred and twenty 5-cells. Also, five 24-cells fit inside a small stellated 120-cell, the first stellation of the 120-cell.A subset of the vertices of the small stellated 120-cell are matched by the great duoantiprism star, which is the only uniform nonconvex duoantiprismatic solution in the fourth dimension, constructed from the polytope cartesian product {5}⊗{5/3} and made of fifty tetrahedra, ten pentagrammic crossed antiprisms, ten pentagonal antiprisms, and fifty vertices.The grand antiprism, which is the only known non-Wythoffian construction of a uniform polychoron, is made of twenty pentagonal antiprisms and three hundred tetrahedra, with a total of one hundred vertices and five hundred edges.The abstract four-dimensional 57-cell is made of fifty-seven hemi-icosahedral cells, in-which five surround each edge. The 11-cell, another abstract 4-polytope with eleven vertices and fifty-five edges, is made of eleven hemi-dodecahedral cells each with fifteen dodecahedra. The skeleton of the hemi-dodecahedron is the Petersen graph.Overall, the fourth dimension contains five Weyl groups that form a finite number of uniform polychora: A 4 {\displaystyle \mathrm {A} _{4}} , B 4 {\displaystyle \mathrm {B} _{4}} , D 4 {\displaystyle \mathrm {D} _{4}} , F 4 {\displaystyle \mathrm {F} _{4}} , and H 4 {\displaystyle \mathrm {H} _{4}} , with four of these Coxeter groups capable of generating the same finite forms without D 4 {\displaystyle \mathrm {D} _{4}} ; accompanied by a fifth or sixth general group of unique 4-prisms of Platonic and Archimedean solids. There are also a total of five Coxeter groups that generate non-prismatic Euclidian honeycombs in 4-space, alongside five compact hyperbolic Coxeter groups that generate five regular compact hyperbolic honeycombs with finite facets, as with the order-5 5-cell honeycomb and the order-5 120-cell honeycomb, both of which have five cells around each face. Compact hyperbolic honeycombs only exist through the fourth dimension, or rank 5, with paracompact hyperbolic solutions existing through rank 10. Likewise, analogues of three-dimensional icosahedral symmetry I h {\displaystyle \mathrm {I} _{h}} or four-dimensional H 4 {\displaystyle \mathrm {H} _{4}} symmetry do not exist in dimensions n ⩾ 5; however, there is the uniform prismatic group H 4 {\displaystyle \mathrm {H} _{4}} × A 1 {\displaystyle \mathrm {A} _{1}} in the fifth dimension which contains prisms of regular and uniform 4-polytopes that have H 4 {\displaystyle \mathrm {H} _{4}} symmetry. The 5-simplex is the five-dimensional analogue of the 5-cell, or 4-simplex; the fifth iteration of n {\displaystyle n} -simplexes in any n {\displaystyle n} dimensions. The 5-simplex has the Coxeter group A 5 {\displaystyle \mathrm {A} _{5}} as its symmetry group, of order 720 = 6!, whose group structure is represented by the symmetric group S 6 {\displaystyle \mathrm {S} _{6}} , the only finite symmetric group which has an outer automorphism. The 5-cube, made of ten tesseracts and the 5-cell as its vertex figure, is also regular and one of thirty-one uniform 5-polytopes under the Coxeter B 5 {\displaystyle \mathrm {B} _{5}} hypercubic group. The demipenteract, with one hundred and twenty cells, is the only fifth-dimensional semiregular polytope, and has the rectified 5-cell as its vertex figure, which is one of only three semiregular 4-polytopes alongside the rectified 600-cell and the snub 24-cell. In the fifth dimension, there are five regular paracompact honeycombs, all with infinite facets and vertex figures. There are exclusively twelve complex aperiotopes in C n {\displaystyle \mathbb {C} ^{n}} complex spaces of dimensions n {\displaystyle n} ⩾ 5 {\displaystyle 5} , with fifteen in C 4 {\displaystyle \mathbb {C} ^{4}} and sixteen in C 3 {\displaystyle \mathbb {C} ^{3}} ; alongside complex polytopes in C 5 {\displaystyle \mathbb {C} ^{5}} and higher under simplex, hypercubic and orthoplex groups, the latter with van Oss polytopes. There are five exceptional Lie groups: g 2 {\displaystyle {\mathfrak {g}}_{2}} , f 4 {\displaystyle {\mathfrak {f}}_{4}} , e 6 {\displaystyle {\mathfrak {e}}_{6}} , e 7 {\displaystyle {\mathfrak {e}}_{7}} , and e 8 {\displaystyle {\mathfrak {e}}_{8}} . The smallest of these, g 2 {\displaystyle {\mathfrak {g}}_{2}} , can be represented in five-dimensional complex space and projected in the same number of dimensions as a ball rolling on top of another ball, whose motion is described in two-dimensional space. e 8 {\displaystyle {\mathfrak {e}}_{8}} , the largest of all five exceptional groups, also contains the other four as subgroups and is constructed with one hundred and twenty quaternionic unit icosians that make up the vertices of the 600-cell. There are also five solvable groups that are excluded from finite simple groups of Lie type. The five Mathieu groups constitute the first generation in the happy family of sporadic groups. These are also the first five sporadic groups to have been described, defined as M n {\displaystyle \mathrm {M} _{n}} multiply transitive permutation groups on n {\displaystyle n} objects, with n {\displaystyle n} ∈ {11, 12, 22, 23, 24}. In particular, M 11 {\displaystyle \mathrm {M} _{11}} , the smallest of all sporadic groups, has a rank 3 action on fifty-five points from an induced action on unordered pairs, as well as two five-dimensional faithful complex irreducible representations over the field with three elements, which is the lowest irreducible dimensional representation of all sporadic group over their respective fields with n elements. Of precisely five different conjugacy classes of maximal subgroups of M 11 {\displaystyle \mathrm {M} _{11}} , one is the almost simple symmetric group S 5 {\displaystyle \mathrm {S} _{5}} (of order 5!), and another is M 10 {\displaystyle \mathrm {M} _{10}} , also almost simple, that functions as a point stabilizer which has 5 {\displaystyle 5} as its largest prime factor in its group order: 24·32·5 = 2·3·4·5·6 = 8·9·10 = 720. On the other hand, whereas M 11 {\displaystyle \mathrm {M} _{11}} is sharply 4-transitive, M 12 {\displaystyle \mathrm {M} _{12}} is sharply 5-transitive and M 24 {\displaystyle \mathrm {M} _{24}} is 5-transitive, and as such they are the only two 5-transitive groups that are not symmetric groups or alternating groups. M 22 {\displaystyle \mathrm {M} _{22}} has the first five prime numbers as its distinct prime factors in its order of 27·32·5·7·11, and is the smallest of five sporadic groups with five distinct prime factors in their order. All Mathieu groups are subgroups of M 24 {\displaystyle \mathrm {M} _{24}} , which under the Witt design W 24 {\displaystyle \mathrm {W} _{24}} of Steiner system S(5, 8, 24) emerges a construction of the extended binary Golay code B 24 {\displaystyle \mathrm {B} _{24}} that has M 24 {\displaystyle \mathrm {M} _{24}} as its automorphism group. W 24 {\displaystyle \mathrm {W} _{24}} generates octads from code words of Hamming weight 8 from the extended binary Golay code, one of five different Hamming weights the extended binary Golay code uses: 0, 8, 12, 16, and 24. The Witt design and the extended binary Golay code in turn can be used to generate a faithful construction of the 24-dimensional Leech lattice Λ24, which is the subject of the second generation of seven sporadic groups that are subquotients of the automorphism of the Leech lattice, Conway group C o 0 {\displaystyle \mathrm {Co} _{0}} . There are five non-supersingular primes: 37, 43, 53, 61, and 67, all smaller than the largest of fifteen supersingular prime divisors of the friendly giant, 71. List of basic calculations In decimal 5 is the only prime number to end in the digit 5 in decimal because all other numbers written with a 5 in the ones place are multiples of five, which makes it a 1-automorphic number. All multiples of 5 will end in either 5 or 0, and vulgar fractions with 5 or 2 in the denominator do not yield infinite decimal expansions because they are prime factors of 10, the base. In the powers of 5, every power ends with the number five, and from 53 onward, if the exponent is odd, then the hundreds digit is 1, and if it is even, the hundreds digit is 6. A number n {\displaystyle n} raised to the fifth power always ends in the same digit as n {\displaystyle n} . Evolution of the Arabic digit The evolution of the modern Western digit for the numeral 5 cannot be traced back to the Indian system, as for the digits 1 to 4. The Kushana and Gupta empires in what is now India had among themselves several different forms that bear no resemblance to the modern digit. The Nagari and Punjabi took these digits and all came up with forms that were similar to a lowercase "h" rotated 180°. The Ghubar Arabs transformed the digit in several different ways, producing from that were more similar to the digits 4 or 3 than to 5. It was from those digits that Europeans finally came up with the modern 5. While the shape of the character for the digit 5 has an ascender in most modern typefaces, in typefaces with text figures the glyph usually has a descender, as, for example, in . On the seven-segment display of a calculator, it is represented by five segments at four successive turns from top to bottom, rotating counterclockwise first, then clockwise, and vice-versa. Science The atomic number of boron. The number of appendages on most starfish, which exhibit pentamerism. The most destructive known hurricanes rate as Category 5 on the Saffir–Simpson hurricane wind scale. The most destructive known tornadoes rate an F-5 on the Fujita scale or EF-5 on the Enhanced Fujita scale. Astronomy Messier object M5, a magnitude 7.0 globular cluster in the constellation Serpens. The New General Catalogue object NGC 5, a magnitude 13 spiral galaxy in the constellation Andromeda. The Roman numeral V stands for dwarfs (main sequence stars) in the Yerkes spectral classification scheme. The Roman numeral V (usually) stands for the fifth-discovered satellite of a planet or minor planet (e.g. Jupiter V). There are five Lagrangian points in a two-body system. Biology There are generally considered to be five senses. The five basic tastes are sweet, salty, sour, bitter, and umami. Almost all amphibians, reptiles, and mammals which have fingers or toes have five of them on each extremity. Computing 5 is the ASCII code of the Enquiry character, which is abbreviated to ENQ. Religion and culture Hinduism The god Shiva has five faces and his mantra is also called panchakshari (five-worded) mantra. The goddess Saraswati, goddess of knowledge and intellectual is associated with panchami or the number 5. There are five elements in the universe according to Hindu cosmology: dharti, agni, jal, vayu evam akash (earth, fire, water, air and space respectively). The most sacred tree in Hinduism has 5 leaves in every leaf stunt. Most of the flowers have 5 petals in them. The epic Mahabharata revolves around the battle between Duryodhana and his 99 other brothers and the 5 pandava princes—Dharma, Arjuna, Bhima, Nakula and Sahadeva. Christianity There are traditionally five wounds of Jesus Christ in Christianity: the Scourging at the Pillar, the Crowning with Thorns, the wounds in Christs hands, the wounds in Christs feet, and the Side Wound of Christ. Gnosticism The number five was an important symbolic number in Manichaeism, with heavenly beings, concepts, and others often grouped in sets of five. Five Seals in Sethianism Five Trees in the Gospel of Thomas Islam The Five Pillars of Islam Muslims pray to Allah five times a day According to Shia Muslims, the Panjetan or the Five Holy Purified Ones are the members of Muhammads family: Muhammad, Ali, Fatimah, Hasan, and Husayn and are often symbolically represented by an image of the Khamsa. Judaism The Torah contains five books—Genesis, Exodus, Leviticus, Numbers, and Deuteronomy—which are collectively called the Five Books of Moses, the Pentateuch (Greek for "five containers", referring to the scroll cases in which the books were kept), or Humash (חומש, Hebrew for "fifth"). The book of Psalms is arranged into five books, paralleling the Five Books of Moses. The Khamsa, an ancient symbol shaped like a hand with four fingers and one thumb, is used as a protective amulet by Jews; that same symbol is also very popular in Arabic culture, known to protect from envy and the evil eye. Sikhism The five sacred Sikh symbols prescribed by Guru Gobind Singh are commonly known as panj kakars or the "Five Ks" because they start with letter K representing kakka (ਕ) in the Punjabi languages Gurmukhi script. They are: kesh (unshorn hair), kangha (the comb), kara (the steel bracelet), kachhehra (the soldiers shorts), and kirpan (the sword) (in Gurmukhi: ਕੇਸ, ਕੰਘਾ, ਕੜਾ, ਕਛਹਰਾ, ਕਿਰਪਾਨ). Also, there are five deadly evils: kam (lust), krodh (anger), moh (attachment), lobh (greed), and ankhar (ego). Daoism 5 Elements 5 Emperors Other religions and cultures According to ancient Greek philosophers such as Aristotle, the universe is made up of five classical elements: water, earth, air, fire, and ether. This concept was later adopted by medieval alchemists and more recently by practitioners of Neo-Pagan religions such as Wicca. The pentagram, or five-pointed star, bears religious significance in various faiths including Baháʼí, Christianity, Freemasonry, Satanism, Taoism, Thelema, and Wicca. In Cantonese, "five" sounds like the word "not" (character: 唔). When five appears in front of a lucky number, e.g. "58", the result is considered unlucky. In East Asian tradition, there are five elements: (water, fire, earth, wood, and metal). The Japanese names for the days of the week, Tuesday through Saturday, come from these elements via the identification of the elements with the five planets visible with the naked eye. Also, the traditional Japanese calendar has a five-day weekly cycle that can be still observed in printed mixed calendars combining Western, Chinese-Buddhist, and Japanese names for each weekday. In numerology, 5 or a series of 555, is often associated with change, evolution, love and abundance. Members of The Nation of Gods and Earths, a primarily African American religious organization, call themselves the "Five-Percenters" because they believe that only 5% of mankind is truly enlightened. Art, entertainment, and media Fictional entities James the Red Engine, a fictional character numbered 5. Johnny 5 is the lead character in the film Short Circuit (1986) Number Five is a character in Lorien Legacies Sankara Stones, five magical rocks in Indiana Jones and the Temple of Doom that are sought by the Thuggees for evil purposes The Mach Five Mahha-gō? (マッハ号), the racing car Speed Racer (Go Mifune in the Japanese version) drives in the anime series of the same name (known as "Mach Go! Go! Go!" in Japan) In the works of J. R. R. Tolkien, five wizards (Saruman, Gandalf, Radagast, Alatar and Pallando) are sent to Middle-earth to aid against the threat of the Dark Lord Sauron In the A Song of Ice and Fire series, the War of the Five Kings is fought between different claimants to the Iron Throne of Westeros, as well as to the thrones of the individual regions of Westeros (Joffrey Baratheon, Stannis Baratheon, Renly Baratheon, Robb Stark and Balon Greyjoy) In The Wheel of Time series, the "Emonds Field Five" are a group of five of the series main characters who all come from the village of Emonds Field (Rand alThor, Matrim Cauthon, Perrin Aybara, Egwene alVere and Nynaeve alMeara) Myst uses the number 5 as a unique base counting system. In The Myst Reader series, it is further explained that the number 5 is considered a holy number in the fictional Dni society. Number Five is also a character in The Umbrella Academy comic book and TV series adaptation Films Towards the end of the film Monty Python and the Holy Grail (1975), the character of King Arthur repeatedly confuses the number five with the number three. Five Go Mad in Dorset (1982) was the first of the long-running series of The Comic Strip Presents... television comedy films The Fifth Element (1997), a science fiction film Fast Five (2011), the fifth installment of the Fast and Furious film series. V for Vendetta (2005), produced by Warner Bros., directed by James McTeigue, and adapted from Alan Moores graphic novel V for Vendetta prominently features number 5 and Roman Numeral V; the story is based on the historical event in which a group of men attempted to destroy Parliament on November 5, 1605 Music Groups Five (group), a UK Boy band The Five (composers), 19th-century Russian composers 5 Seconds of Summer, pop band that originated in Sydney, Australia Five Americans, American rock band active 1965–1969 Five Finger Death Punch, American heavy metal band from Las Vegas, Nevada. Active 2005–present Five Man Electrical Band, Canadian rock group billed (and active) as the Five Man Electrical Band, 1969–1975 Maroon 5, American pop rock band that originated in Los Angeles, California MC5, American punk rock band Pentatonix, a Grammy-winning a cappella group originated in Arlington, Texas The 5th Dimension, American pop vocal group, active 1977–present The Dave Clark Five, a.k.a. DC5, an English pop rock group comprising Dave Clark, Lenny Davidson, Rick Huxley, Denis Payton, and Mike Smith; active 1958–1970 The Jackson 5, American pop rock group featuring various members of the Jackson family; they were billed (and active) as The Jackson 5, 1966–1975 Hi-5, Australian pop kids group, where it has several international adaptations, and several members throughout the history of the band. It was also a TV show. We Five: American folk rock group active 1965–1967 and 1968–1977 Grandmaster Flash and the Furious Five: American rap group, 1970–80s Fifth Harmony, an American girl group. Ben Folds Five, an American alternative rock trio, 1993–2000, 2008 and 2011–2013 R5 (band), an American pop and alternative rock group, 2009–2018 Other uses A perfect fifth is the most consonant harmony, and is the basis for most western tuning systems. Modern musical notation uses a musical staff made of five horizontal lines. In harmonics – the fifth partial (or 4th overtone) of a fundamental has a frequency ratio of 5:1 to the frequency of that fundamental. This ratio corresponds to the interval of 2 octaves plus a pure major third. Thus, the interval of 5:4 is the interval of the pure third. A major triad chord when played in just intonation (most often the case in a cappella vocal ensemble singing), will contain such a pure major third. The number of completed, numbered piano concertos of Ludwig van Beethoven, Sergei Prokofiev, and Camille Saint-Saëns. Using the Latin root, five musicians are called a quintet. A scale with five notes per octave is called a pentatonic scale. Five is the lowest possible number that can be the top number of a time signature with an asymmetric meter. Television StationsChannel 5 (UK), a television channel that broadcasts in the United Kingdom 5 (TV channel) (formerly known as ABC 5 and TV5) (DWET-TV channel 5 In Metro Manila) a television network in the Philippines. SeriesBabylon 5, a science fiction television series The number 5 features in the television series Battlestar Galactica in regards to the Final Five cylons and the Temple of Five Hi-5 (Australian TV series), a television series from Australia Hi-5 (UK TV series), a television show from the United Kingdom Hi-5 Philippines a television show from the Philippines Odyssey 5, a 2002 science fiction television series Tillbaka till Vintergatan, a Swedish childrens television series featuring a character named "Femman" (meaning five), who can only utter the word five. The Five (talk show): Fox News Channel roundtable current events television show, premiered 2011, so-named for its panel of five commentators. Yes! PreCure 5 is a 2007 anime series which follows the adventures of Nozomi and her friends. It is also followed by the 2008 sequel Yes! Pretty Cure 5 GoGo! The Quintessential Quintuplets is a 2019 slice of life romance anime series which follows the everyday life of five identical quintuplets and their interactions with their tutor. It has two seasons, and a final movie is scheduled in summer 2022. Hawaii Five-0, CBS American TV series. Literature The Famous Five is a series of childrens books by British writer Enid Blyton The Power of Five is a series of childrens books by British writer and screenwriter Anthony Horowitz The Fall of Five is a book written under the collective pseudonym Pittacus Lore in the series Lorien Legacies The Book of Five Rings is a text on kenjutsu and the martial arts in general, written by the swordsman Miyamoto Musashi circa 1645 Slaughterhouse-Five is a book by Kurt Vonnegut about World War II Sports The Olympic Games have five interlocked rings as their symbol, representing the number of inhabited continents represented by the Olympians (Europe, Asia, Africa, Australia and Oceania, and the Americas). In AFL Womens, the top level of womens Australian rules football, each team is allowed 5 "interchanges" (substitute players), who can be freely substituted at any time. In baseball scorekeeping, the number 5 represents the third basemans position. In basketball: The number 5 is used to represent the position of center. Each team has five players on the court at a given time. Thus, the phrase "five on five" is commonly used to describe standard competitive basketball. The "5-second rule" refers to several related rules designed to promote continuous play. In all cases, violation of the rule results in a turnover. Under the FIBA (used for all international play, and most non-US leagues) and NCAA womens rule sets, a team begins shooting bonus free throws once its opponent has committed five personal fouls in a quarter. Under the FIBA rules, A player fouls out and must leave the game after committing five fouls Five-a-side football is a variation of association football in which each team fields five players. In ice hockey: A major penalty lasts five minutes. There are five different ways that a player can score a goal (teams at even strength, team on the power play, team playing shorthanded, penalty shot, and empty net). The area between the goaltenders legs is known as the five-hole. In most rugby league competitions, the starting left wing wears this number. An exception is the Super League, which uses static squad numbering. In rugby union: A try is worth 5 points. One of the two starting lock forwards wears number 5, and usually jumps at number 4 in the line-out. In the French variation of the bonus points system, a bonus point in the league standings is awarded to a team that loses by 5 or fewer points. Technology 5 is the most common number of gears for automobiles with manual transmission. In radio communication, the term "Five by five" is used to indicate perfect signal strength and clarity. On almost all devices with a numeric keypad such as telephones, computers, etc., the 5 key has a raised dot or raised bar to make dialing easier. Persons who are blind or have low vision find it useful to be able to feel the keys of a telephone. All other numbers can be found with their relative position around the 5 button (on computer keyboards, the 5 key of the numpad has the raised dot or bar, but the 5 key that shifts with % does not). On most telephones, the 5 key is associated with the letters J, K, and L, but on some of the BlackBerry phones, it is the key for G and H. The Pentium, coined by Intel Corporation, is a fifth-generation x86 architecture microprocessor. The resin identification code used in recycling to identify polypropylene. Miscellaneous fields Five can refer to: "Give me five" is a common phrase used preceding a high five. An informal term for the British Security Service, MI5. Five babies born at one time are quintuplets. The most famous set of quintuplets were the Dionne quintuplets born in the 1930s. In the United States legal system, the Fifth Amendment to the United States Constitution can be referred to in court as "pleading the fifth", absolving the defendant from self-incrimination. Pentameter is verse with five repeating feet per line; iambic pentameter was the most popular form in Shakespeare. Quintessence, meaning "fifth element", refers to the elusive fifth element that completes the basic four elements (water, fire, air, and earth) The designation of an Interstate Highway (Interstate 5) that runs from San Diego, California to Blaine, Washington. In addition, all major north-south Interstate Highways in the United States end in 5. In the computer game Riven, 5 is considered a holy number, and is a recurring theme throughout the game, appearing in hundreds of places, from the number of islands in the game to the number of bolts on pieces of machinery. The Garden of Cyrus (1658) by Sir Thomas Browne is a Pythagorean discourse based upon the number 5. The holy number of Discordianism, as dictated by the Law of Fives. The number of Justices on the Supreme Court of the United States necessary to render a majority decision. The number of dots in a quincunx. The number of permanent members with veto power on the United Nations Security Council. The number of sides and the number of angles in a pentagon. The number of points in a pentagram. The number of Korotkoff sounds when measuring blood pressure The drink Five Alive is named for its five ingredients. The drink punch derives its name after the Sanskrit पञ्च (pañc) for having five ingredients. The Keating Five were five United States Senators accused of corruption in 1989. The Inferior Five: Merryman, Awkwardman, The Blimp, White Feather, and Dumb Bunny. DC Comics parody superhero team. No. 5 is the name of the iconic fragrance created by Coco Chanel. The Committee of Five was delegated to draft the United States Declaration of Independence. The five-second rule is a commonly used rule of thumb for dropped food. 555 95472, usually referred to simply as 5, is a minor male character in the comic strip Peanuts. See also Five Families Five Nations (disambiguation) 555 (number) List of highways numbered 5 References Wells, D. The Penguin Dictionary of Curious and Interesting Numbers London: Penguin Group. (1987): 58–67 External links Media related to 5 (number) at Wikimedia Commons The dictionary definition of five at Wiktionary The Number 5 The Positive Integer 5 Prime curiosities: 5

You are a medical lexicon. Explain medical terminology with depth and clarity, making sure the information is both accurate and easy to grasp.

I'm trying to understand 'Istradefylline' within a medical context. Could you shed some light on it?

Istradefylline, sold under the brand name Nourianz, is a medication used as an add-on treatment to levodopa/carbidopa in adults with Parkinsons disease (PD) experiencing "off" episodes. Istradefylline reduces "off" periods resulting from long-term treatment with the antiparkinson drug levodopa. An "off" episode is a time when a patients medications are not working well, causing an increase in PD symptoms, such as tremor and difficulty walking.Relatively common side effects include involuntary muscle movements (dyskinesia), constipation, hallucinations, dizziness and, much like its parent molecule caffeine, nausea and sleeplessness.The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. Mechanism of action Istradefylline is a selective antagonist at the adenosine A2A receptor (A2AR), but the precise mechanism by which it exerts its therapeutic effect in Parkinsons disease is unknown. However, it is known that dimers of these receptors form heterotetramers with the dimers of dopamine D2 receptors (D2R) within striatum. Adenosine acts as an endogenous A2AR agonist, but also as a negative allosteric modulator (NAM) within these tetramers towards D2Rs, thus inhibiting the D2R mediated effects of dopamine, an endogenous D2R agonist. Istradefylline is believed to bind an A2AR within an A2AR-D2R-tetramer and function as a NAM towards the other A2AR (instead of D2R), thus inhibiting the effects of adenosine and enhancing the movement (locomotion) promoting effects exerted by dopamine via D2R. However, at high istradefylline concentration, it causes locomotion depression akin to caffeine (which is a broad-spectrum adenosine receptor antagonist), and might do so by displacing adenosine, and working as a NAM towards D2R (instead of A2AR). History It was first approved in Japan in 2013.The effectiveness of Nourianz in treating "off" episodes in patients with Parkinsons disease who are already being treated with levodopa/carbidopa was shown in four 12-week placebo-controlled clinical studies that included a total of 1,143 participants. In all four studies, people treated with Nourianz experienced a statistically significant decrease from baseline in daily "off" time compared to patients receiving a placebo.It was approved for medical use in the United States in 2019. and approval was granted to Kyowa Kirin, Inc. References External links "Istradefylline". Drug Information Portal. U.S. National Library of Medicine.

You are a medical educator. Your role is to provide detailed and clear explanations for medical terms, suitable for both professionals and laypersons.

I've encountered the term 'Ghons complex' while reading about medical topics. What does it refer to exactly?

Ghons complex is a lesion seen in the lung that is caused by tuberculosis. The lesions consist of a Ghon focus along with pulmonary lymphadenopathy within a nearby pulmonary lymph node. A Ghons complex retains viable bacteria, making them sources of long-term infection, which may reactivate and trigger secondary tuberculosis later in life.In countries where cow milk infected with Mycobacterium bovis has been eliminated (due to culling of infected cows and pasteurization), primary tuberculosis is usually caused by Mycobacterium tuberculosis and almost always begins in the lungs. Typically, the inhaled bacilli implant in the distal airspaces of the lower part of the upper lobe or the upper part of the lower lobe, usually close to the pleura. As sensitization develops, a 1 to 1.5 cm area of gray-white inflammation with consolidation emerges, known as the Ghon focus. In most cases, the center of this focus undergoes caseous necrosis. Tubercle bacilli, either free or within phagocytes, drain to the regional nodes, which also often caseate. This combination of parenchymal lung lesion and nodal involvement is referred to as the Ghon complex. During the first few weeks, there is also lymphatic and hematogenous dissemination to other parts of the body.In approximately 95% of cases, development of cell-mediated immunity controls the infection. Differentiation The Ghon complex undergoes progressive fibrosis, often followed by radiologically detectable calcification (Ranke complex), and despite seeding of other organs, no lesions develop. Although they are often confused, Ranke complex and Ghon complex are not synonymous. The Ranke complex is an evolution of the Ghon complex (resulting from further healing and calcification of the lesion).The Ghon complex is named after Austrian pathologist Anton Ghon; the Ranke complex is named in honour of German pulmonologist Karl Ernst Ranke. == References ==

You are a medical knowledge base. Your task is to elucidate medical terminology, offering insights into their meanings, origins, and applications.

Could you offer a clear explanation of the term 'Pruritus of genital organs' as used in the medical field?

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

You are an assistant in medical learning. Your role is to clarify medical terminology, ensuring the information is both accurate and accessible.

I'm looking for a concise explanation of the medical term 'Amnesia.'

Amnesia is a deficit in memory caused by brain damage or disease, but it can also be caused temporarily by the use of various sedatives and hypnotic drugs. The memory can be either wholly or partially lost due to the extent of damage that was caused. There are two main types of amnesia: retrograde amnesia and anterograde amnesia. Retrograde amnesia is the inability to retrieve information that was acquired before a particular date, usually the date of an accident or operation. In some cases the memory loss can extend back decades, while in others the person may lose only a few months of memory. Anterograde amnesia is the inability to transfer new information from the short-term store into the long-term store. People with anterograde amnesia cannot remember things for long periods of time. These two types are not mutually exclusive; both can occur simultaneously.Case studies also show that amnesia is typically associated with damage to the medial temporal lobe. In addition, specific areas of the hippocampus (the CA1 region) are involved with memory. Research has also shown that when areas of the diencephalon are damaged, amnesia can occur. Recent studies have shown a correlation between deficiency of RbAp48 protein and memory loss. Scientists were able to find that mice with damaged memory have a lower level of RbAp48 protein compared to normal, healthy mice. In people with amnesia, the ability to recall immediate information is still retained, and they may still be able to form new memories. However, a severe reduction in the ability to learn new material and retrieve old information can be observed. People can learn new procedural knowledge. In addition, priming (both perceptual and conceptual) can assist amnesiacs in the learning of fresh non-declarative knowledge. Individuals with amnesia also retain substantial intellectual, linguistic, and social skill despite profound impairments in the ability to recall specific information encountered in prior learning episodes.The term is from Ancient Greek forgetfulness; from ἀ- (a-) without, and μνήσις (mnesis) memory. Signs and symptoms Individuals with amnesia can learn new information, particularly if the information is non-declarative knowledge. However, in some situations, people with dense anterograde amnesia do not remember the episodes during which they previously learned or observed the information. Some people with amnesia show abnormal amounts of memory loss, confusion, and difficulty recalling other people or places. People who recover often do not remember having amnesia. Declarative information Declarative memory can be broken down into semantic memory and episodic memory, semantic memory being that of facts, episodic memory being that of memory related to events. While a patient with amnesia might have a loss of declarative memory, this loss might vary in severity as well as the declarative information that it affects, depending on many factors. For example, LSJ was a patient that had retrograde declarative memory loss as the result of bilateral medial temporal lobe damage, but she was still able to remember how to perform some declarative skills. She was able to remember how to read music and the techniques used in art. She had preserved skill-related declarative memory for some things even though she had deficits in other declarative memory tasks. She even scored higher on skill-related declarative memory than the control in watercolor techniques, a technique that she used in her professional career before she acquired amnesia. Semantic Information The loss of semantic information in amnesia is most closely related with damage to the medial temporal lobe or to the neocortex.Some patients with anterograde amnesia can still acquire some semantic information, even though it might be more difficult and might remain rather unrelated to more general knowledge. H.M. could accurately draw a floor plan of the home in which he lived after surgery, even though he had not lived there in years. There is evidence that the hippocampus and the medial temporal lobe may help to consolidate semantic memories, but then they are more correlated with the neocortex. While lesions of the hippocampus normally lead to the loss of episodic memory, if there is any effect on semantic memory, it is more varied and usually does not last as long. Episodic Information One reason that patients could not form new episodic memories is likely because the CA1 region of the hippocampus has a lesion, and thus the hippocampus could not make connections to the cortex. After an ischemic episode (an interruption of the blood flow to the brain), an MRI of patient R.B. following surgery showed his hippocampus to be intact except for a specific lesion restricted to the CA1 pyramidal cells. In one instance, transient global amnesia was caused by a hippocampal CA1 lesion. While this was a temporary case of amnesia, it still shows the importance of the CA1 region of the hippocampus in memory. Episodic memory loss is most likely to occur when there has been damage to the hippocampus. There is evidence that damage to the medial temporal lobe correlates to a loss of autobiographical episodic memory. Non-declarative information Some retrograde and anterograde amnesiacs are capable of non-declarative memory, including implicit learning and procedural learning. For example, some patients show improvement on the pseudorandom sequences experiment just as healthy people; therefore, procedural learning can proceed independently of the brain system required for declarative memory. Some patients with amnesia are able to remember skills that they had learned without being able to consciously recall where they had learned that information. For example, they may learn to do a task and then be able to perform the task later without any recollection of learning the task. According to fMRI studies, the acquisition of procedural memories activates the basal ganglia, the premotor cortex and the supplementary motor area, regions which are not normally associated with the formation of declarative memories. This type of dissociation between declarative and procedural memory can also be found in patients with diencephalic amnesia such as Korsakoffs syndrome. Another example demonstrated by some patients, such as K.C. and H.M, who have medial temporal damage and anterograde amnesia, still have perceptual priming. Priming was accomplished in many different experiments of amnesia, and it was found that the patients can be primed; they have no conscious recall of the event, but the response is there. Those patients did well in the word fragment completion task. There is some evidence that non-declarative memory can be held onto in the form of motor skills. This idea was disputed, though, because it is argued that motor skills require both declarative and non-declarative information. Causes There are three generalized categories in which amnesia could be acquired by a person. The three categories are head trauma (example: head injuries), traumatic events (example: seeing something devastating to the mind), or physical deficiencies (example: atrophy of the hippocampus). The majority of amnesia and related memory issues derive from the first two categories as these are more common and the third could be considered a subcategory of the first. Head trauma is a very broad range as it deals with any kind of injury or active action toward the brain which might cause amnesia. Retrograde and anterograde amnesia is more often seen from events like this, an exact example of a cause of the two would be electroconvulsive therapy, which would cause both briefly for the receiving patient. Traumatic events are more subjective. What is traumatic is dependent on what the person finds to be traumatic. Regardless, a traumatic event is an event where something so distressing occurs that the mind chooses to forget rather than deal with the stress. A common example of amnesia that is caused by traumatic events is dissociative amnesia, which occurs when the person forgets an event that has deeply disturbed them. An example would be a person forgetting a fatal and graphic car accident involving their loved ones. Physical deficiencies are different from head trauma because physical deficiencies lean more toward passive physical issues. Examples of physical deficiencies include Alzheimers disease, neurological paraneoplastic syndromes such as anti-NMDA receptor encephalitis, and vitamin B12 deficiency.Among specific causes of amnesia are the following: Electroconvulsive therapy in which seizures are electrically induced in patients for therapeutic effect can have acute effects including both retrograde and anterograde amnesia. Alcohol can both cause blackouts and have deleterious effects on memory formation. Diagnosis Types Anterograde amnesia is the inability to create new memories due to brain damage, while long-term memories from before the event remain intact. The brain damage can be caused by the effects of long-term alcoholism, severe malnutrition, stroke, head trauma, encephalitis, surgery, Wernicke–Korsakoff syndrome, cerebrovascular events, anoxia or other trauma. The two brain regions related with this condition are medial temporal lobe and medial diencephalon. Anterograde amnesia cannot be treated with pharmacological methods due to neuronal loss. However, treatment exists in educating patients to define their daily routines and after several steps they begin to benefit from their procedural memory. Procedural memory can be intact even when other forms of memory is not, although not always the case. Likewise, social and emotional support is critical to improving quality of life for those with anterograde amnesia. Fentanyl use by opioid users has been identified as a potential cause in a cluster of cases that occurred in Boston, MA. Retrograde amnesia is inability to recall memories before onset of amnesia. One may be able to encode new memories after the incident. Retrograde is usually caused by head trauma or brain damage to parts of the brain besides the hippocampus. The hippocampus is responsible for encoding new memory. Episodic memory is more likely to be affected than semantic memory. The damage is usually caused by head trauma, cerebrovascular accident, stroke, tumor, hypoxia, encephalitis, or chronic alcoholism. People with retrograde amnesia are more likely to remember general knowledge rather than specifics. Recent memories are less likely to be recovered, but older memories will be easier to recall due to strengthening over time. Retrograde amnesia is usually temporary and can be treated by exposing them to memories from the loss. Another type of consolidation (process by which memories become stable in the brain) occurs over much longer periods of time/days, weeks, months and years and likely involves transfer of information from the hippocampus to more permanent storage site in the cortex. The operation of this longer-term consolidation process is seen in the retrograde amnesia of patients with hippocampal damage who can recall memories from childhood relatively normally, but are impaired when recalling experiences that occurred just a few years prior to the time they became amnesic. (Kirwan et al.,2008)In the case of LSJ, her case shows that retrograde amnesia can affect many different parts of knowledge. LSJ was not able to remember things from her child or adult life. She was not able to remember things that most people pick up in everyday life such as logos or the names of common songs. Post-traumatic amnesia is generally due to a head injury (example: a fall, a knock on the head). Traumatic amnesia is often transient, but may be permanent or either anterograde, retrograde, or mixed type. The extent of the period covered by the amnesia is related to the degree of injury and may give an indication of the prognosis for recovery of other functions. Mild trauma, such as a car accident that results in no more than mild whiplash, might cause the occupant of a car to have no memory of the moments just before the accident due to a brief interruption in the short/long-term memory transfer mechanism. The patient may also lose knowledge of who people are. Having longer periods of amnesia or consciousness after an injury may be an indication that recovery from remaining concussion symptoms will take much longer. Dissociative amnesia results from a psychological cause as opposed to direct damage to the brain caused by head injury, physical trauma or disease, which is known as organic amnesia. Individuals with organic amnesia have difficulty with emotion expression as well as undermining the seriousness of their condition. The damage to the memory is permanent. Dissociative amnesia can include: Repressed memory is the inability to recall information, usually about stressful or traumatic events in persons lives, such as a violent attack or disaster. The memory is stored in long-term memory, but access to it is impaired because of psychological defense mechanisms. Persons retain the capacity to learn new information and there may be some later partial or complete recovery of memory. Formerly known as "Psychogenic Amnesia". Dissociative fugue (formerly psychogenic fugue) is also known as fugue state. It is caused by psychological trauma, is usually temporary and unresolved, and therefore, may return. It must exist outside the influence of pre-existing medical conditions, such as a lobotomy, and immediate influence of any mind-altering substances, such as alcohol or drugs. An individual with dissociative fugue disorder either completely forgets or is confused about their identity, and may even assume a new one. They can travel hundreds miles from their home or work; they can also engage in other uncharacteristic, and occasionally unsafe, behavior. For example, two men in a study of five individuals with dissociative fugue had engaged in criminal activity while in their fugue state, having had no criminal record before the episodes. While popular in fiction, this type of amnesia is extremely rare. Posthypnotic amnesia occurs when events during hypnosis are forgotten, or where memories are unable to be recalled. The failure to remember those events is induced by suggestions made during the hypnosis. Some characteristics of posthypnotic amnesia include inability to remember specific events while under hypnotic influence, reversibility, and having no relation between the implicit and explicit memory. Research has shown that there could be selectivity with amnesia when posthypnotic amnesia occurs. Lacunar amnesia is the loss of memory about one specific event. It is a type of amnesia that leaves a lacuna (a gap) in the record of memory in the cortex region of the brain. The cause of this type of amnesia is the result of brain damage to the limbic system which control our memories and emotions. Childhood amnesia (also known as infantile amnesia) is the common inability to remember events from ones own childhood. Sigmund Freud notoriously attributed this to sexual repression, while modern scientific approaches generally attribute it to aspects of brain development or developmental psychology, including language development, which may be why people do not easily remember pre-language events. Some research states that most adults cannot remember memories as early as two or three years old. Research suggests there are cultural influences that affect memories that are recalled. Researchers have found that implicit memories cannot be recalled or described. Remembering how to play the piano is a common example of implicit memory, as are walking, speaking, and other everyday activities that would be difficult to focus on if they had to be relearned every time one got up in the morning. Explicit memories, on the other hand, can be recalled and described in words. Remembering the first time meeting a teacher is an example of an explicit memory. Transient global amnesia is a well-described medical and clinical phenomenon. This form of amnesia is distinct in that abnormalities in the hippocampus can sometimes be visualized using a special form of magnetic resonance imaging of the brain known as diffusion-weighted imaging (DWI). Symptoms typically last for less than a day and there is often no clear precipitating factor or any other neurological deficits. The cause of this syndrome is not clear. The hypothesis of the syndrome includes transient reduced blood flow, possible seizure or an atypical type of a migraine. Patients are typically amnestic of events more than a few minutes in the past, though immediate recall is usually preserved. Source amnesia is the inability to remember where, when or how previously learned information has been acquired, while retaining the factual knowledge. When individuals are unable to remember, false memories can occur and cause great confusion. Korsakoffs syndrome can result from long-term alcoholism or malnutrition. It is caused by brain damage due to a vitamin B1 deficiency and will be progressive if alcohol intake and nutrition pattern are not modified. Other neurological problems are likely to be present in combination with this type of Amnesia, such as problems with the medial temporal lobe and frontal lobe dysfunction. Korsakoffs syndrome is also known to be connected with confabulation. The persons short-term memory may appear to be normal, but the person may have a difficult time attempting to recall a past story, or with unrelated words, as well as complicated patterns. Korsakoffs syndrome is unique because it involves both anterograde and retrograde amnesia. Drug-induced amnesia is intentionally caused by injection of an amnestic drug to help a patient forget surgery or medical procedures, particularly those not performed under full anesthesia, or likely to be particularly traumatic. Such drugs are also referred to as "premedicants". Most commonly, a 2-halogenated benzodiazepine such as midazolam or flunitrazepam is the drug of choice, although other strongly amnestic drugs such as propofol or scopolamine may also be used for this application. Memories of the short time-frame in which the procedure was performed are permanently lost or at least substantially reduced, but once the drug wears off, memory is no longer affected. Situation-specific amnesia can arise in a variety of circumstances (for example, committing an offence, child sexual abuse) resulting in PTSD. It has been claimed that it involves a narrowing of consciousness with attention focused on central perceptual details and/or that the emotional or traumatic events are processed differently from ordinary memories. Transient epileptic amnesia is a rare and unrecognized form of temporal lobe epilepsy, which is typically an episodic isolated memory loss. It has been recognized as a treatment-responsive syndrome congenial to anti-epileptic drugs. Semantic amnesia affects semantic memory and primarily expresses itself in the form of problems with language use and acquisition. Semantic amnesia can lead to dementia. Pseudodementia (otherwise known as depression-related cognitive dysfunction) is a condition where mental cognition can be temporarily decreased. The term pseudodementia is applied to the range of functional psychiatric conditions such as depression and schizophrenia, that may mimic organic dementia, but are essentially reversible on treatment. Pseudodementia typically involves three cognitive components: memory issues, deficits in executive functioning, and deficits in speech and language. Specific cognitive symptoms might include trouble recalling words or remembering things in general, decreased attentional control and concentration, difficulty completing tasks or making decisions, decreased speed and fluency of speech, and impaired processing speed. People with pseudodementia are typically very distressed about the cognitive impairment they experience. With in this condition, there are two specific treatments that have been found to be effective for the treatment of depression, and these treatments may also be beneficial in the treatment of pseudodementia. Cognitive behavioral therapy (CBT) involves exploring and changing thought patterns and behaviors in order to improve ones mood. Interpersonal therapy focuses on the exploration of an individuals relationships and identifying any ways in which they may be contributing to feelings of depression. Treatment Many forms of amnesia fix themselves without being treated. However, there are a few ways to cope with memory loss if treatment is needed. Since there are a variety of causes that form different amnesia, it is important to note that there are different methods that response better with the certain type of amnesia. Emotional support and love as well as medication and psychological therapy have been proven effective.One technique for amnesia treatment is cognitive or occupational therapy. In therapy, amnesiacs will develop the memory skills they have and try to regain some they have lost by finding which techniques help retrieve memories or create new retrieval paths. This may also include strategies for organizing information to remember it more easily and for improving understanding of lengthy conversation.Another coping mechanism is taking advantage of technological assistance, such as a personal digital device to keep track of day-to-day tasks. Reminders can be set up for appointments when to take medications, birthdays and other important events. Many pictures can also be stored to help amnesiacs remember names of friends, family, and co-workers. Notebooks, wall calendars, pill reminders and photographs of people and places are low-tech memory aids that can help as well.While there are no medications available to treat amnesia, underlying medical conditions can be treated to improve memory. Such conditions include but are not limited to low thyroid function, liver or kidney disease, stroke, depression, bipolar disorder and blood clots in the brain. Wernicke–Korsakoff syndrome involves a lack of thiamin and replacing this vitamin by consuming thiamin-rich foods such as whole-grain cereals, legumes (beans and lentils), nuts, lean pork, and yeast. Treating alcoholism and preventing alcohol and illicit drug use can prevent further damage, but in most cases will not recover lost memory.Although improvements occur when patients receive certain treatments, there is still no actual cure remedy for amnesia so far. To what extent the patient recovers and how long the amnesia will continue depends on the type and severity of the lesion. History French psychologist Theodule-Armand Ribot was among the first scientists to study amnesia. He proposed Ribots Law which states that there is a time gradient in retrograde amnesia. The law follows a logical progression of memory loss due to disease. First, a patient loses the recent memories, then personal memories, and finally intellectual memories. He implied that the most recent memories were lost first.Case studies have played a large role in the discovery of amnesia and the parts of the brain that were affected. The studies gave important insight into how amnesia affects the brain. The studies also gave scientists the resources into improving their knowledge about amnesia and insight into a cure or prevention. There are several extremely important case studies: Henry Molaison, R.B, and G.D. Henry Molaison Henry Molaison, formerly known as H.M., changed the way people thought of memory. The case was first reported in a paper by William Beecher Scoville and Brenda Milner in 1957. He was a patient who had severe epilepsy attributed to a bicycle accident at the age of nine. Physicians were unable to control his seizures with drugs, so the neurosurgeon Scoville tried a new approach involving brain surgery. He removed his medial temporal lobe bilaterally by doing a temporal lobectomy. His epilepsy did improve, but Molaison lost the ability to form new long-term memories (anterograde amnesia). He exhibited normal short-term memory ability. If he was given a list of words, he would forget them in about a minutes time. In fact, he would forget that he had even been given a list in the first place. However, H.M.s working and short-term memory seemed to be intact. He had a normal digit span and could hold a conversation that did not require him to recall past parts of the conversation. Once Molaison stopped thinking about the lists he was unable to recall them again from long-term memory. This gave researchers evidence that short-term and long-term memory are in fact two different processes. Even though he forgot about the lists, he was still able to learn things through his implicit memory. The psychologists would ask him to draw something on a piece of paper, but to look at the paper using a mirror. Though he could never remember ever doing that task, he would improve after doing it over and over again. This showed the psychologists that he was learning and remembering things unconsciously. In some studies it was found that H.M.s perceptual learning was intact and that his other cognitive skills were working appropriately. It was also found that some people with declarative information amnesia are able to be primed.Studies were completed consistently throughout Molaisons lifetime to discover more about amnesia. Researchers did a 14-year follow-up study on Molaison. They studied him for a period of two weeks to learn more about his amnesia. After 14 years, Molaison still could not recall things that had happened since his surgery. However, he could still remember things that had happened prior to the operation. Researchers also found that, when asked, Molaison could answer questions about national or international events, but he could not remember his own personal memories. After his death Molaison donated his brain to science, where they were able to discover the areas of the brain that had the lesions which caused his amnesia, particularly the medial temporal lobe. This case study provided important insight to the areas of the brain that are affected in anterograde amnesia, as well as how amnesia works. H.M.s case showed us that memory processes are consolidated into different parts of the brain and that short-term and working memory are not usually impaired in cases of amnesia. Clive Wearing Another famous historical case of amnesia was that of Clive Wearing. Clive Wearing was a conductor and musician who contracted herpes simplex virus. This virus affected the hippocampal regions of the brain. Because of this damage, Wearing was unable to remember information for more than a few moments. Wearings non-declarative memory was still functioning but his declarative memory was impaired. To him, he felt that he had just come to consciousness for the first time every time he was unable to hold on to information. This case also can be used as evidence that there are different memory systems for declarative and non-declarative memory. This case was more evidence that the hippocampus is an important part of the brain in remembering past events and that declarative and non-declarative memories have different processes in different parts of the brain. Patient R.B. Patient R.B. was a normally functioning man until the age of 52. At age 50, he had been diagnosed with angina and had surgery for heart problems on two occasions. After an ischemic episode (reduction of blood to the brain) that was caused from a heart bypass surgery, R.B. demonstrated a loss of anterograde memory, but almost no loss of retrograde memory, with the exception of a couple of years before his surgery, and presented no sign of any other cognitive impairment. It wasnt until after his death that researchers had the chance to examine his brain, when they found his lesions were restricted to the CA1 portion of the hippocampus. This case study led to important research involving the role of the hippocampus and the function of memory. Patient G.D. Patient G.D. was a white male born in 1940 who served in the Navy. He was diagnosed with chronic kidney failure and received hemodialysis treatment for the rest of his life. In 1983, he went to the hospital for elective parathyroidectomy. He also had a left thyroid lobectomy because of the severe loss of blood in his left lobe. He began having cardiac problems as a result of the surgery and became very agitated. Even five days after being released from the hospital he was unable to remember what had happened to him. Aside from memory impairment, none of his other cognitive processes seemed to be affected. He did not want to be involved in much research, but through memory tests he took with doctors, they were able to ascertain that his memory problems were present for the next 9.5 years until his death. After he died, his brain was donated to science, photographed, and preserved for future study. In fiction Global amnesia is a common motif in fiction despite being extraordinarily rare in reality. In the introduction to his anthology The Vintage Book of Amnesia, Jonathan Lethem writes: Real, diagnosable amnesia – people getting knocked on the head and forgetting their names – is mostly just a rumor in the world. Its a rare condition, and usually a brief one. In books and movies, though, versions of amnesia lurk everywhere, from episodes of Mission Impossible to metafictional and absurdist masterpieces, with dozens of stops in between. Amnesiacs might not much exist, but amnesiac characters stumble everywhere through comic books, movies, and our dreams. Weve all met them and been them. Lethem traces the roots of literary amnesia to Franz Kafka and Samuel Beckett, among others, fueled in large part by the seeping into popular culture of the work of Sigmund Freud, which also strongly influenced genre films such as film noir. Amnesia is so often used as a plot device in films, that a widely recognized stereotypical dialogue has even developed around it, with the victim melodramatically asking "Where am I? Who am I? What am I?", or sometimes inquiring of their own name, "Bill? Whos Bill?"In movies and television, particularly sitcoms and soap operas, it is often depicted that a second blow to the head, similar to the first one which caused the amnesia, will then cure it. In reality, however, repeat concussions may cause cumulative deficits including cognitive problems, and in extremely rare cases may even cause deadly swelling of the brain associated with second-impact syndrome.In science fiction involving a masquerade that hides magical or alien societies from humanity, such as Men in Black or the SCP Foundation, fictional organizations can induce deliberate amnesia via drugs or advanced technology to wipe the minds of those that view supernatural phenomena. See also References == External links ==

You are a medical interpreter. Your duty is to translate medical terms into easily digestible information, maintaining accuracy and detail.

I'm encountering the term 'Polymyositis' in medical literature. What's its definition?

Polymyositis (PM) is a type of chronic inflammation of the muscles (inflammatory myopathy) related to dermatomyositis and inclusion body myositis. Its name means "inflammation of many muscles" (poly- + myos- + -itis). The inflammation of polymyositis is mainly found in the endomysial layer of skeletal muscle, whereas dermatomyositis is characterized primarily by inflammation of the perimysial layer of skeletal muscles. Signs and symptoms The hallmark of polymyositis is weakness and/or loss of muscle mass in the proximal musculature, as well as flexion of the neck and torso. These symptoms can be associated with marked pain in these areas as well. The hip extensors are often severely affected, leading to particular difficulty in climbing stairs and rising from a seated position. The skin involvement of dermatomyositis is absent in polymyositis. Dysphagia (difficulty swallowing) or other problems with esophageal motility occur in as many as 1/3 of patients. Low grade fever and enlarged lymph nodes may be present. Foot drop in one or both feet can be a symptom of advanced polymyositis and inclusion body myositis. The systemic involvement of polymyositis includes interstitial lung disease (ILD) and heart disease, such as heart failure and conduction abnormalities.Polymyositis tends to become evident in adulthood, presenting with bilateral proximal muscle weakness often noted in the upper legs due to early fatigue while walking. Sometimes the weakness presents itself as an inability to rise from a seated position without help or an inability to raise ones arms above ones head. The weakness is generally progressive, accompanied by lymphocytic inflammation (mainly cytotoxic T cells). Associated illnesses Polymyositis and the associated inflammatory myopathies have an associated increased risk of cancer. The features they found associated with an increased risk of cancer were older age, age greater than 45, male sex, difficulty swallowing, death of skin cells, cutaneous vasculitis, rapid onset of myositis (<4 weeks), elevated creatine kinase, higher erythrocyte sedimentation rate and higher C-reactive protein levels. Several factors were associated with lower-than-average risk, including the presence of interstitial lung disease, joint inflammation/joint pain, Raynauds syndrome, or anti-Jo-1 antibody. The malignancies that are associated are nasopharyngeal cancer, lung cancer, non-Hodgkins lymphoma and bladder cancer, amongst others.Cardiac involvement manifests itself typically as heart failure and is present in up to 77% of patients. Interstitial lung disease is found in up to 65% of patients with polymyositis, as defined by HRCT or restrictive ventilatory defects compatible with interstitial lung disease. Causes Polymyositis is an inflammatory myopathy mediated by cytotoxic T cells with an as yet unknown autoantigen, while dermatomyositis is a humorally mediated angiopathy resulting in myositis and a typical dermatitis.The cause of polymyositis is unknown and may involve viruses and autoimmune factors. Cancer may trigger polymyositis and dermatomyositis, possibly through an immune reaction against cancer that also attacks a component of muscles. There is tentative evidence of an association with celiac disease. Diagnosis Diagnosis is fourfold: History and physical examination, elevation of creatine kinase, electromyograph (EMG) alteration, and a positive muscle biopsy.The hallmark clinical feature of polymyositis is proximal muscle weakness, with less important findings being muscle pain and dysphagia. Cardiac and pulmonary findings will be present in approximately 25% of cases of patients with polymyositis.Sporadic inclusion body myositis (sIBM) is often misdiagnosed as polymyositis or dermatomyositis but it can be differentiated as myositis that does not respond to treatment is likely IBM. sIBM comes on over months to years; polymyositis comes on over weeks to months. Polymyositis tends to respond well to treatment, at least initially; IBM does not. Treatment The first line treatment for polymyositis is corticosteroids. Specialized exercise therapy may supplement treatment to enhance quality of life. Epidemiology Polymyositis strikes females with greater frequency than males. Polymyositis as a distinct diagnosis The discovery of several myositis-specific autoantibodies during the past decades has enabled the description of other discrete subsets of diagnosis, specifically the discovery of Antisynthetase syndrome in reducing the number of diagnoses of polymyositis. Society and culture Notable cases Dan Christensen, painter of abstract art. Died due to heart failure caused by polymyositis. Robert Erickson, American composer and teacher who was a leading modernist exponent of "12-tone" composition. Died from the effects of polymyositis. David Lean, film director. Eric Samuelsen, playwright. Victor Manuel Resendiz Ruiz, wrestler. Cardinal John Wright See also Limb girdle syndrome References == External links ==

You function as a medical explainer. Your task is to convey the meanings of medical terms in a detailed, yet easy-to-understand manner.

I'm not familiar with the medical term 'Tocolytic.' Could you provide some insights?

Tocolytics (also called anti-contraction medications or labor suppressants) are medications used to suppress premature labor (from Greek τόκος tókos, "childbirth", and λύσις lúsis, "loosening"). Preterm birth accounts for 70% of neonatal deaths. Therefore, tocolytic therapy is provided when delivery would result in premature birth, postponing delivery long enough for the administration of glucocorticoids, which accelerate fetal lung maturity but may require one to two days to take effect. Commonly used tocolytic medications include β2 agonists, calcium channel blockers, NSAIDs, and magnesium sulfate. These can assist in delaying preterm delivery by suppressing uterine muscle contractions and their use is intended to reduce fetal morbidity and mortality associated with preterm birth. The suppression of contractions is often only partial and tocolytics can only be relied on to delay birth for a matter of days. Depending on the tocolytic used, the pregnant woman or fetus may require monitoring (e.g., blood pressure monitoring when nifedipine is used as it reduces blood pressure; cardiotocography to assess fetal well-being). In any case, the risk of preterm labor alone justifies hospitalization. Indications Tocolytics are used in preterm labor, which refers to when a baby is born too early before 37 weeks of pregnancy. As preterm birth represents one of the leading causes of neonatal morbidity and mortality, the goal is to prevent neonatal morbidity and mortality through delaying delivery and increasing gestational age by gaining more time for other management strategies like corticosteroids therapy that may help with fetus lung maturity. Tocolytics are considered for women with confirmed preterm labor between 24 and 34 weeks of gestation age and used in conjunction with other therapies that may include corticosteroids administration, fetus neuroprotection, and safe transfer to facilities. Types of agents There is no clear first-line tocolytic agent. Current evidence suggests that first line treatment with β2 agonists, calcium channel blockers, or NSAIDs to prolong pregnancy for up to 48 hours is the best course of action to allow time for glucocorticoid administration.Various types of agents are used, with varying success rates and side effects. Some medications are not specifically approved by the U.S. Food and Drug Administration (FDA) for use in stopping uterine contractions in preterm labor, instead being used off-label. Calcium-channel blockers (such as nifedipine) and oxytocin antagonists (such as atosiban) may delay delivery by 2 to 7 days, depending on how quickly the medication is administered. NSAIDs (such as indomethacin) and calcium channel blockers (such as nifedipine) are the most likely to delay delivery for 48 hours, with the least amount of maternal and neonatal side effects. Otherwise, tocolysis is rarely successful beyond 24 to 48 hours because current medications do not alter the fundamentals of labor activation. However, postponing premature delivery by 48 hours appears sufficient to allow pregnant women to be transferred to a center specialized for management of preterm deliveries, and thus administer corticosteroids for the possibility to reduce neonatal organ immaturity.The efficacy of β-adrenergic agonists, atosiban, and indomethacin is a decreased odds ratio (OR) of delivery within 24 hours of 0.54 (95% confidence interval (CI): 0.32-0.91) and 0.47 within 48 hours (OR 0.47, 95% CI: 0.30-0.75).Antibiotics were thought to delay delivery, but no studies have shown any evidence that using antibiotics during preterm labor effectively delays delivery or reduces neonatal morbidity. Antibiotics are used in people with premature rupture of membranes, but this is not characterized as tocolysis. Contraindications to tocolytics In addition to drug-specific contraindications, several general factors may contraindicate delaying childbirth with the use of tocolytic medications. Fetus is older than 34 weeks gestation Fetus weighs less than 2.5 kg, or has intrauterine growth restriction (IUGR) or placental insufficiency Lethal congenital or chromosomal abnormalities Cervical dilation is greater than 4 centimeters Chorioamnionitis or intrauterine infection is present Pregnant woman has severe pregnancy-induced hypertension, severe eclampsia/preeclampsia, active vaginal bleeding, placental abruption, a cardiac disease, or another condition which indicates that the pregnancy should not continue. Maternal hemodynamic instability with bleeding Intrauterine fetal demise, lethal fetal anomaly, or non-reassuring fetal status Future direction of tocolytics Most tocolytics are currently being used off-label. The future direction of the development of tocolytics agents should be directed toward better efficacy in intentionally prolonging pregnancy. This will potentially result in less maternal, fetal, and neonatal adverse effects when delaying preterm childbirth. A few tocolytic alternatives worth pursuing include Barusiban, a last generation of oxytocin receptor antagonists, as well as COX-2 inhibitors. More studies on the use of multiple tocolytics must be directed to research overall health outcomes rather than solely pregnancy prolongation. See also Labor induction == References ==

You act as a medical communicator. Your goal is to translate medical terms into comprehensive, yet straightforward language for all readers.

Can you demystify the medical term 'Pleomorphism (cytology)' for me?

Pleomorphism is a term used in histology and cytopathology to describe variability in the size, shape and staining of cells and/or their nuclei. Several key determinants of cell and nuclear size, like ploidy and the regulation of cellular metabolism, are commonly disrupted in tumors. Therefore, cellular and nuclear pleomorphism is one of the earliest hallmarks of cancer progression and a feature characteristic of malignant neoplasms and dysplasia. Certain benign cell types may also exhibit pleomorphism, e.g. neuroendocrine cells, Arias-Stella reaction. A rare type of rhabdomyosarcoma that is found in adults is known as pleomorphic rhabdomyosarcoma.Despite the prevalence of pleomorphism in human pathology, its role in disease progression is unclear. In epithelial tissue, pleomorphism in cellular size can induce packing defects and disperse aberrant cells. But the consequence of atypical cell and nuclear morphology in other tissues is unknown. See also Anaplasia Cell growth Cytopathology Giant cell carcinoma of the lung Nuclear atypia == References ==

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I'm encountering the term 'Ichthyosis acquisita' in medical literature. What's its definition?

Ichthyosis acquisita is a disorder clinically and histologically similar to ichthyosis vulgaris.: 565 Presentation Associated conditions The development of ichthyosis in adulthood can be a manifestation of systemic disease, and it has been described in association with malignancies, drugs, endocrine and metabolic disease, HIV, infection, and autoimmune conditions.: 494 It usually is associated with people who have Hodgkins disease but it is also occurs in people with mycosis fungoides, other malignant sarcomas, Kaposis sarcoma and visceral carcinomas. It can occur in people with leprosy, AIDS, tuberculosis, and typhoid fever. See also Ichthyosis Confluent and reticulated papillomatosis of Gougerot and Carteaud List of cutaneous conditions References == External links ==

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I'm trying to expand my medical knowledge. Can you elucidate the term 'Idiopathic pulmonary fibrosis'?

Idiopathic pulmonary fibrosis (IPF), or (formerly) fibrosing alveolitis, is a rare, progressive illness of the respiratory system, characterized by the thickening and stiffening of lung tissue, associated with the formation of scar tissue. It is a type of chronic scarring lung disease characterized by a progressive and irreversible decline in lung function. The tissue in the lungs becomes thick and stiff, which affects the tissue that surrounds the air sacs in the lungs. Symptoms typically include gradual onset of shortness of breath and a dry cough. Other changes may include feeling tired, and abnormally large and dome shaped finger and toenails (nail clubbing). Complications may include pulmonary hypertension, heart failure, pneumonia or pulmonary embolism.The cause is unknown, hence the term idiopathic. Risk factors include cigarette smoking, acid reflux disease (GERD), certain viral infections, and genetic predisposition. The underlying mechanism involves scarring of the lungs. Diagnosis requires ruling out other potential causes. It may be supported by a HRCT scan or lung biopsy which show usual interstitial pneumonia (UIP). It is a type of interstitial lung disease (ILD).People often benefit from pulmonary rehabilitation and supplemental oxygen. Certain medications like pirfenidone (Esbriet) or nintedanib (Ofev) may slow the progression of the disease. Lung transplantation may also be an option.About 5 million people are affected globally. The disease newly occurs in about 12 per 100,000 people per year. Those in their 60s and 70s are most commonly affected. Males are affected more often than females. Average life expectancy following diagnosis is about four years. Updated international guidelines were published in 2022, which some simplification in diagnosis and the removal of antacids as a possible adjunct therapy. Signs and symptoms In many people, symptoms are present for a considerable time before diagnosis. The most common clinical features of IPF include the following: Age over 50 years Dry, non-productive cough on exertion Progressive exertional dyspnea (shortness of breath with exercise) Dry, inspiratory bibasilar "velcro-like" crackles on auscultation (a crackling sound in the lungs during inhalation similar to Velcro being torn apart slowly, heard with a stethoscope). Clubbing of the digits, a disfigurement of the finger tips or toes (see image) Abnormal pulmonary function test results, with evidence of restriction and impaired gas exchange.Some of these features are due to chronic hypoxemia (oxygen deficiency in the blood), are not specific for IPF, and can occur in other pulmonary disorders. IPF should be considered in all patients with unexplained chronic exertional dyspnea who present with cough, inspiratory bibasilar crackles, or finger clubbing.Assessment of "velcro" crackles on lung auscultation is a practical way to improve the earlier diagnosis of IPF. Fine crackles are easily recognized by clinicians and are characteristic of IPF.If bilateral fine crackles are present throughout the inspiratory time and are persisting after several deep breaths, and if remaining present on several occasions several weeks apart in a subject aged ≥60 years, this should raise the suspicion of IPF and lead to consideration of an HRCT scan of the chest which is more sensitive than a chest X-ray. As crackles are not specific for IPF, they must prompt a thorough diagnostic process. Causes The cause of IPF is unknown but certain environmental factors and exposures have been shown to increase the risk of getting IPF. Cigarette smoking is the best recognized and most accepted risk factor for IPF, and increases the risk of IPF by about twofold. Other environmental and occupation exposures such as exposure to metal dust, wood dust, coal dust, silica, stone dust, biologic dusts coming from hay dust or mold spores or other agricultural products, and occupations related to farming/livestock have also been shown to increase the risk for IPF. There is some evidence that viral infections may be associated with idiopathic pulmonary fibrosis and other fibrotic lung diseases. Pathogenesis Despite extensive investigation, the cause of IPF remains unknown. The fibrosis in IPF has been linked to cigarette smoking, environmental factors (e.g. occupational exposure to gases, smoke, chemicals or dusts), other medical conditions including gastroesophageal reflux disease (GERD), or to genetic predisposition (familial IPF). However, none of these is present in all people with IPF and therefore do not provide a completely satisfactory explanation for the disease.IPF is believed to be the result of an aberrant wound healing process including/involving abnormal and excessive deposition of collagen (fibrosis) in the pulmonary interstitium with minimal associated inflammation. Cellular senescence is suspected to be a central contributing cause, a belief which is supported by benefits seen in patients given senolytic therapy.It is hypothesized that the initial or repetitive injury in IPF occurs to the lung cells, called alveolar epithelial cells (AECs, pneumocytes), which line the majority of the alveolar surface. When type I AECs are damaged or lost, it is thought that type II AECs undergo proliferation to cover the exposed basement membranes. In normal repair, the hyperplastic type II AECs die and the remaining cells spread and undergo a differentiation process to become type I AECs. Under pathologic conditions and in the presence of transforming growth factor beta (TGF-β), fibroblasts accumulate in these areas of damage and differentiate into myofibroblasts that secrete collagen and other proteins. In the current classification of the pathogenesis of IPF, it is believed that it occurs by way of the formation of a UIP (usual interstitial pneumonia) lesion, which then undergoes the aforementioned pathological condition characteristic of IPF. Other proposed repeated injury mechanisms indicate that IPF may result not just from a UIP lesion, but also from NSIP and DAD (nonspecific interstitial pneumonia and diffuse alveolar damage) lesions, or a combination of several. In the past, it was thought that inflammation was the first event in initiating lung tissue scarring. Later findings showed that the development of fibroblastic foci precedes the accumulation of inflammatory cells and the consequent deposition of collagen. This pathogenetic model is indirectly supported by the clinical features of IPF, including an insidious onset over several years, relatively infrequent acute exacerbations, and failure to respond to immunosuppressive therapy. However, it is the belief of some researchers that the disease is a multi-mechanistic one, wherein the trigger for the disease may stem from abnormalities in any number of wound healing pathways, including the inflammatory response. Such abnormalities could occur in any number of the nine implicated pathways (clotting cascade, antioxidant pathways, apoptosis, inflammatory cytokines, angiogenesis and vascular remodelling, growth factors, surfactant and matrix regulatory factors), and that through further investigation into all nine, novel therapies and approaches could be proposed on a unique or case-by-case basis should attempts at treating or circumventing complications in any one pathway prove unsuccessful. A number of therapies that target fibroblast activation or the synthesis of extracellular matrix are currently in early testing or are being considered for development.Familial IPF accounts for less than 5% of the total of patients with IPF and is clinically and histologically indistinguishable from sporadic IPF. Genetic associations include mutations in pulmonary surfactant proteins A1, A2, C (SFTPA1, SFTPA2B) and mucin (MUC5B). A remarkable aspect of the MUC5B variant is its high frequency of detection, as it is found in approximately 20% of individuals with Northern and Western European ancestry and in 19% of the Framingham Heart Study population. Mutations in human telomerase genes are also associated with familial pulmonary fibrosis and in some patients with sporadic IPF (e.g. the TERT, TERC genes). Recently an X-linked mutation in a third telomerase-associated gene, dyskerin (DKC1), has been described in a family with IPF. Diagnosis An earlier diagnosis of IPF is a prerequisite for earlier treatment and, potentially, improvement of the long-term clinical outcome of this progressive and ultimately fatal disease. If IPF is suspected, diagnosis can be challenging but a multidisciplinary approach involving a pulmonologist, radiologist and pathologist expert in interstitial lung disease has been shown to improve the accuracy of IPF diagnosis.A Multidisciplinary Consensus Statement on the Idiopathic Interstitial Pneumonias published by the American Thoracic Society (ATS) and the European Respiratory Society (ERS) in 2000 proposed specific major and minor criteria for establishing the diagnosis of IPF. However, in 2011, new simplified and updated criteria for the diagnosis and management of IPF were published by the ATS, ERS, together with the Japanese Respiratory Society (JRS) and Latin American Thoracic Association (ALAT). Currently, a diagnosis of IPF requires: Exclusion of known causes of ILD, e.g., domestic and occupational environmental exposures, connective tissue disorders, or drug exposure/toxicity The presence of a typical radiological pattern of usual interstitial pneumonia (UIP) on high-resolution computed tomography (HRCT).In the right clinical setting, it is possible to make the diagnosis of IPF by HRCT alone, obviating the need for surgical lung biopsy.Various technologies using Artificial Intelligence have been developed to help with diagnosis. A deep learning algorithm for categorizing high-resolution CT images reported high accuracy and a research project led by Nagoya University Graduate School of Medicine and Riken used a combination of Deep learning and Machine learning algorithm to accurately diagnose the disease. Differential diagnosis Recognizing IPF in clinical practice can be challenging as symptoms often appear similar to those of more common diseases, such as asthma, chronic obstructive pulmonary disease (COPD) and congestive heart failure (www.diagnoseipf.com). The key issue facing clinicians is whether the presenting history, symptoms (or signs), radiology, and pulmonary function testing are collectively in keeping with the diagnosis of IPF or whether the findings are due to another process. It has long been recognized that patients with ILD related to asbestos exposure, drugs (such as chemotherapeutic agents or nitrofurantoin), rheumatoid arthritis and scleroderma/systemic sclerosis may be difficult to distinguish from IPF. Other differential diagnostic considerations include interstitial lung disease related to mixed connective tissue disease, advanced sarcoidosis, chronic hypersensitivity pneumonitis, pulmonary Langerhans cell histiocytosis and radiation-induced lung injury. Classification Idiopathic pulmonary fibrosis (IPF) belongs to a large group of more than 200 lung diseases known as interstitial lung diseases (ILDs), which are characterized by the involvement of the lung interstitium, the tissue between the air sacs of the lung. IPF is one specific presentation of idiopathic interstitial pneumonia (IIP), which is in turn a type of ILD, also known as diffuse parenchymal lung disease (DPLD).The 2002 American Thoracic Society/European Respiratory Society (ATS/ERS) classification of IIPs was updated in 2013. In this new classification there are three main categories of idiopathic interstitial pneumonias (IIPs): major IIPs, rare IIPs, and unclassifiable IIPs. The major IIPs are grouped into chronic fibrosing IPs (this includes IPF and non-specific interstitial pneumonia [NSIP]); smoking-related IPs (i.e. respiratory bronchiolitis–interstitial lung disease [RB-ILD] and desquamative interstitial pneumonia [DIP]); and acute/subacute IPs (i.e. cryptogenic organizing pneumonia [COP] and acute interstitial pneumonia [AIP]).The diagnosis of IIPs requires exclusion of known causes of ILD. Examples of ILD of known cause include hypersensitivity pneumonitis, pulmonary Langerhans cell histiocytosis, asbestosis, and collagen vascular disease. However, these disorders frequently affect not only the interstitium, but also the airspaces, peripheral airways, and blood vessels. Radiology Chest X-rays are useful in the follow up routine of IPF patients. Plain chest X-rays are unfortunately not diagnostic but may reveal decreased lung volumes, typically with prominent reticular interstitial markings near the lung bases. The radiological evaluation through HRCT is an essential point in the diagnostic pathway in IPF. HRCT is performed using a conventional computed axial tomographic scanner without injection of contrast agents. Evaluation slices are very thin, 1–2 mm. Typical HRCT of the chest of IPF demonstrates fibrotic changes in both lungs, with a predilection for the bases and the periphery. According to the joint ATS/ERS/JRS/ALAT 2011 guidelines, HRCT is an essential component of the diagnostic pathway in IPF which can identify UIP by the presence of: Reticular opacities, often associated with traction bronchiectasis Honeycombing manifested as cluster cystic airspaces, typically of comparable diameters (3–10 mm) but occasionally large. Usually sub-pleural and characterized by well-defined walls and disposed in at least two lines. Generally one line of cysts is not sufficient to define honeycombing Ground-glass opacities are common but less extensive than the reticulation Distribution characteristically basal and peripheral though often patchy. Histology According to the updated 2011 guidelines, in the absence of a typical UIP pattern on HRCT, a surgical lung biopsy is required for confident diagnosis.Histologic specimens for the diagnosis of IPF must be taken at least in three different places and be large enough that the pathologist can comment on the underlying lung architecture. Small biopsies, such as those obtained via transbronchial lung biopsy (performed during bronchoscopy) are usually not sufficient for this purpose. Hence, larger biopsies obtained surgically via a thoracotomy or thoracoscopy are usually necessary.Lung tissue from people with IPF usually show a characteristic histopathologic UIP pattern and is therefore the pathologic counterpart of IPF. Although a pathologic diagnosis of UIP often corresponds to a clinical diagnosis of IPF, a UIP histologic pattern can be seen in other diseases as well, and fibrosis of known origin (rheumatic diseases for example). There are four key features of UIP including interstitial fibrosis in a patchwork pattern, interstitial scarring, honeycomb changes and fibroblast foci.Fibroblastic foci are dense collections of myofibroblasts and scar tissue and, together with honeycombing, are the main pathological findings that allow a diagnosis of UIP. Bronchoalveolar lavage Bronchoalveolar lavage (BAL) is a well-tolerated diagnostic procedure in ILD. BAL cytology analyses (differential cell counts) should be considered in the evaluation of patients with IPF at the discretion of the treating physician based on availability and experience at their institution. BAL may reveal alternative specific diagnoses: malignancy, infections, eosinophilic pneumonia, histiocytosis X, or alveolar proteinosis. In the evaluation of patients with suspected IPF, the most important application of BAL is in the exclusion of other diagnoses. Prominent lymphocytosis (>30%) generally allows excluding a diagnosis of IPF. Pulmonary function tests Spirometry classically reveals a reduction in the vital capacity (VC) with either a proportionate reduction in airflows, or increased airflows for the observed vital capacity. The latter finding reflects the increased lung stiffness (reduced lung compliance) associated with pulmonary fibrosis, which leads to increased lung elastic recoil.Measurement of static lung volumes using body plethysmography or other techniques typically reveals reduced lung volumes (restriction). This reflects the difficulty encountered in inflating the fibrotic lungs. The diffusing capacity for carbon monoxide (DLCO) is invariably reduced in IPF and may be the only abnormality in mild or early disease. Its impairment underlies the propensity of patients with IPF to exhibit oxygen desaturation with exercise which can also be evaluated using the 6-minute walk test (6MWT).Terms such as mild, moderate, and severe are sometimes used for staging disease and are commonly based on resting pulmonary function test measurements. However, there is no clear consensus regarding the staging of IPF patients and what are the best criteria and values to use. Mild-to-moderate IPF has been characterized by the following functional criteria: Forced vital capacity (FVC) of ≥50% DLCO of ≥30% 6MWT distance ≥150 meters. Treatment The goals of treatment in IPF are essentially to reduce the symptoms, stop disease progression, prevent acute exacerbations, and prolong survival. Preventive care (e.g. vaccinations) and symptom-based treatment should be started early in every patient. Oxygen therapy In the 2011 IPF guidelines, oxygen therapy, or supplementary oxygen for home use, became a strong recommendation for use in those patients with significantly low oxygen levels at rest. Although oxygen therapy has not been shown to improve survival in IPF, some data indicate an improvement in exercise capacity. Pulmonary rehabilitation Fatigue and loss of muscular mass are common and disabling problems for patients with IPF. Pulmonary rehabilitation may alleviate the overt symptoms of IPF and improve functional status by stabilizing and/or reversing the extrapulmonary features of the disease. The number of published studies on the role of pulmonary rehabilitation in idiopathic pulmonary fibrosis is small, but most of these studies have found significant short-term improvements in functional exercise tolerance, quality of life, and dyspnea on exertion. Typical programs of rehabilitation include exercise training, nutritional modulation, occupational therapy, education and psychosocial counseling. In the late phase of disease, IPF patients tend to discontinue physical activity due to increasing dyspnea. Whenever possible, this should be discouraged. Medications A number of treatments have been investigated in the past for IPF, including interferon gamma-1β, bosentan, ambrisentan, and anticoagulants, but these are no longer considered effective treatment options. Many of these earlier studies were based on the hypothesis that IPF is an inflammatory disorder. Pirfenidone A Cochrane review comparing pirfenidone with placebo, found a reduced risk of disease progression by 30%. FVC or VC was also improved, even if a mild slowing in FVC decline could be demonstrated only in one of the two CAPACITY trials. A third study, which was completed in 2014 found reduced decline in lung function and IPF disease progression. The data from the ASCEND study were also pooled with data from the two CAPACITY studies in a pre-specified analysis which showed that pirfenidone reduced the risk of death by almost 50% over one year of treatment. N-acetylcysteine and triple therapy N-Acetylcysteine (NAC) is a precursor to glutathione, an antioxidant. It has been hypothesized that treatment with high doses of NAC may repair an oxidant–antioxidant imbalance that occurs in the lung tissue of patients with IPF. In the first clinical trial of 180 patients (IFIGENIA), NAC was shown in previous study to reduce the decline in VC and DLCO over 12 months of follow-up when used in combination with prednisone and azathioprine (triple therapy).More recently, a large randomized, controlled trial (PANTHER-IPF) was undertaken by the National Institutes of Health (NIH) in the US to evaluate triple therapy and NAC monotherapy in IPF patients. This study found that the combination of prednisone, azathioprine, and NAC increased the risk of death and hospitalizations and the NIH announced in 2012 that the triple-therapy arm of the PANTHER-IPF study had been terminated early.This study also evaluated NAC alone and the results for this arm of the study were published in May 2014 in the New England Journal of Medicine, concluding that "as compared with placebo, acetylcysteine offered no significant benefit with respect to the preservation of FVC in patients with idiopathic pulmonary fibrosis with mild-to-moderate impairment in lung function". Nintedanib Nintedanib is a triple angiokinase inhibitor that targets receptor tyrosine kinases involved in the regulation of angiogenesis: fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR), which have also been implicated in the pathogenesis of fibrosis and IPF. In both phase III trials, nintedanib reduced the decline in lung function by approximately 50% over one year. It was approved by the US FDA in October 2014 and authorised in Europe in January 2015. Lung transplantation Lung transplantation may be suitable for those patients physically eligible to undergo a major transplant operation. In IPF patients, lung transplant has been shown to reduce the risk of death by 75% as compared with patients who remain on the waiting list. Since the introduction of the lung allocation score (LAS), which prioritizes transplant candidates based on survival probability, IPF has become the most common indication for lung transplantation in the USA.Symptomatic patients with IPF younger than 65 years of age and with a body mass index (BMI) ≤26 kg/m2 should be referred for lung transplantation, but there are no clear data to guide the precise timing for LTx. Although controversial, the most recent data suggest that bilateral lung transplantation is superior to single lung transplantation in patients with IPF. Five-year survival rates after lung transplantation in IPF are estimated at between 50 and 56%. Palliative care Palliative care focuses on reducing symptoms and improving the comfort of patients rather than treating the disease. This may include treatment of worsening symptoms with the use of chronic opioids for severe dyspnea and cough. Further, oxygen therapy may be useful for palliation of dyspnea in hypoxemic patients. Palliative care also includes relief of physical and emotional suffering and psychosocial support for patients and caregivers. With disease progression, patients may experience fear, anxiety and depression and psychological counseling should therefore be considered. In a recent study of outpatients with ILDs, including IPF, depression score, functional status (as assessed by walk test), as well as pulmonary function, all contributed to the severity of dyspnea.In selected cases of particularly severe dyspnea morphine could be considered. It can reduce dyspnea, anxiety and cough without significant decrease in oxygen saturation. Follow-up IPF is often misdiagnosed, at least until physiological and/or imaging data suggest the presence of an ILD leading to delay in accessing appropriate care. Considering that IPF is a disease with a median survival of three years after diagnosis, early referral to a center with specific expertise should therefore be considered for any patient with suspected or known ILD. On the basis of the complex differential diagnostic, multidisciplinary discussion between pulmonologists, radiologists, and pathologists experienced in the diagnosis of ILD is of the utmost importance to an accurate diagnosis.Those with IPF have higher chances of getting lung cancer, at a rate of 13.5% where the most common cancer type is Squamous-cell carcinoma of the lung. a routine evaluation every 3 to 6 months, including spirometry (body plethysmography), diffusion capacity testing, chest X-rays, 6MWT, assessment of dyspnea, quality of life, oxygen requirement is mandatory.In addition, the increasing awareness of complications and common concomitant conditions frequently associated with IPF requires a routinely evaluation of comorbidities, most of them simply reflecting concurrent diseases of aging, and medications with their interaction and side effects. Acute exacerbations Acute exacerbations of IPF (AE-IPF) are defined as an unexplained worsening or development of dyspnea within 30 days with new radiological infiltrates at HRCT abnormality often superimposed on a background consistent with UIP pattern. The yearly incidence of AE-IPF is between 10 and 15% of all patients. The prognosis of AE-IPF is poor, with mortality ranging from 78% to 96%. Other causes of AE-IPF such as pulmonary embolism, congestive heart failure, pneumothorax, or infection need to be excluded. Pulmonary infection have to be ruled out by endotracheal aspirate or BAL. Many patients experiencing acute deterioration require intensive care treatment, particularly when respiratory failure is associated with hemodynamic instability, significant comorbidities or severe hypoxemia. However, mortality during hospitalization is high. Mechanical ventilation should be introduced only after carefully weighing the persons long-term prognosis and, whenever possible, the persons wishes. However, current guidelines discourage the use of mechanical ventilation in patients with respiratory failure secondary to IPF. Prognosis The clinical course of IPF can be unpredictable. IPF progression is associated with an estimated median survival time of 2 to 5 years following diagnosis. The 5-year survival for IPF ranges between 20 and 40%, a mortality rate higher than that of a number of malignancies, including colon cancer, multiple myeloma and bladder cancer.Recently a multidimensional index and staging system has been proposed to predict mortality in IPF. The name of the index is GAP and is based on gender [G], age [A], and two lung physiology variables [P] (FVC and DLCO that are commonly measured in clinical practice to predict mortality in IPF. The highest stage of GAP (stage III) has been found to be associated with a 39% risk of mortality at 1 year. This model has also been evaluated in IPF and other ILDs and shown good performance in predicting mortality in all main ILD subtypes. A modified ILD-GAP Index has been developed for application across ILD subtypes to provide disease-specific survival estimates. In IPF patients, the overall mortality at 5 years rate is high but the annual rate of all-cause mortality in patients with mild to moderate lung impairment is relatively low. This is the reason why change in lung function (FVC) is usually measured in 1-year clinical trials of IPF treatments rather than survival.In addition to clinical and physiological parameters to predict how rapidly patients with IPF might progress, genetic and molecular features are also associated with IPF mortality. For example, it has been shown that IPF patients who have a specific genotype in the mucin MUC5B gene polymorphism (see above) experience slower decline in FVC and significantly improved survival. Even if such data are interesting from a scientific point of view, the application in the clinical routine of a prognostic model based on specific genotypes is still not possible. Epidemiology Although rare, IPF is the most common form of IIP. The prevalence of IPF has been estimated between 14.0 and 42.7 per 100,000 persons based on a USA analysis of healthcare claims data, with variation depending on the case definitions used in this analyses. IPF is more common in men than in women and is usually diagnosed in people over 50 years of age.The incidence of IPF is difficult to determine as uniform diagnostic criteria have not been applied consistently. A recent study from the USA estimated the incidence of IPF to be between 6.8 and 16.3 per 100,000 persons. In the 27 European Union countries, a range of sources estimate an incidence of 4.6–7.4 people per 100,000 of the population, suggesting that approximately 30,000–35,000 new patients will be diagnosed with IPF each year.A recent single-centre, retrospective, observational cohort study including incident patients diagnosed with ILD at Aarhus University Hospital (Denmark) between 2003 and 2009 revealed an incidence of 4.1 per 100,000 inhabitants/year for ILD. IPF was the most common diagnosis (28%) followed by connective tissue disease-related ILD (14%), hypersensitivity pneumonitis (7%) and non-specific interstitial pneumonia (NSIP) (7%). IPF incidence was 1.3 per 100,000 inhabitants/year.Due to a heterogeneous distribution of the disease across European countries, epidemiological data needs to be updated through a Europe-wide registry for ILD and IPF. Other animals IPF has been recognized in several breeds of both dogs and cats, and has been best characterized in West Highland White Terriers. Veterinary patients with the condition share many of the same clinical signs as their human counterparts, including progressive exercise intolerance, increased respiratory rate, and eventual respiratory distress. Prognosis is generally poor. Research A number of agents are currently being investigated in Phase II clinical trials for IPF, including the monoclonal antibodies simtuzumab, tralokinumab, lebrikizumab and FG-3019, a lysophosphatidic acid receptor antagonist (BMS-986020). A Phase II study of STX-100 is also ongoing. These molecules are directed against several growth factors and cytokines that are known to play a role in the proliferation, activation, differentiation or inappropriate survival of fibroblasts.mir-29 microRNA precursor investigations in mice have produced reversal of induced IPF. MRG-201 is currently being tested as-of 2016, but not in IPF patients yet, and no human trials for IPF use have been scheduled as of January 2016.Stem cell therapies for IPF are an area of research.A machine learning algorithm has been proposed that discovers subtle patterns in individual history of medical encounters to reliably estimate the risk of a future IPF diagnosis, up to four years before current medical practice. The algorithm outputs a score (ZCoR) using medical history on file with no new tests, and might be deployable as a universal IPF screening tool in primary care. ZCoR has been trained and validated on nearly 3 million patients across multiple databases, achieving high predictive performance in out-of-sample data (positive likelihood ratio > 30 with 99% specificity). The authors conclude that past respiratory disorders maximally contribute to IPF risk, followed by known IPF comorbidities, metabolic diseases, cardiovascular abnormalities, and diseases of the eye, with the overall pattern of the importance ranking substantially invariant across the sexes. References External links Idiopathic pulmonary fibrosis at Curlie

You are a medical lexicon. Explain medical terminology with depth and clarity, making sure the information is both accurate and easy to grasp.

Can you demystify the medical term 'Franceschetti–Klein syndrome' for me?

Franceschetti–Klein syndrome (also known as "mandibulofacial dysostosis") is a syndrome that includes palpebral antimongoloid fissures, hypoplasia of the facial bones, macrostomia, vaulted palate, malformations of both the external and internal ear, buccal-auricular fistula, abnormal development of the neck with stretching of the cheeks, accessory facial fissures, and skeletal deformities.: 577 It is sometimes equated with Treacher Collins syndrome. See also Dysostosis References == External links ==

You are a resource for medical understanding. Offer detailed explanations of medical terms, making complex concepts clear and comprehensible.

I'm looking for a concise explanation of the medical term 'Pulseless electrical activity.'

Pulseless electrical activity (PEA) refers to cardiac arrest in which the electrocardiogram shows a heart rhythm that should produce a pulse, but does not. Pulseless electrical activity is found initially in about 55% of people in cardiac arrest.Under normal circumstances, electrical activation of muscle cells precedes mechanical contraction of the heart (known as electromechanical coupling). In PEA, there is electrical activity but insufficient cardiac output to generate a pulse and supply blood to the organs, whether the heart itself is failing to contract or otherwise. While PEA is classified as a form of cardiac arrest, significant cardiac output may still be present, which may be determined and best visualized by bedside ultrasound (echocardiography). Cardiopulmonary resuscitation (CPR) is the first treatment for PEA, while potential underlying causes are identified and treated. The medication epinephrine (aka adrenaline) may be administered. Survival is about 20%. Signs and symptoms Pulseless electrical activity leads to a loss of cardiac output, and the blood supply to the brain is interrupted. As a result, PEA is usually noticed when a person loses consciousness and stops breathing spontaneously. This is confirmed by examining the airway for obstruction, observing the chest for respiratory movement, and feeling the pulse (usually at the carotid artery) for a period of 10 seconds. Causes These possible causes are remembered as the 6 Hs and the 6 Ts. See Hs and Ts Hypovolemia Hypoxia Hydrogen ions (Acidosis) Hyperkalemia or Hypokalemia Hypoglycemia Hypothermia Tablets or Toxins Cardiac Tamponade Tension pneumothorax Thrombosis (e.g., myocardial infarction, pulmonary embolism) Tachycardia Trauma (e.g., hypovolemia from blood loss)The possible mechanisms by which the above conditions can cause pulseless in PEA are the same as those recognized as producing circulatory shock states. These are (1) impairment of cardiac filling, (2) impaired pumping effectiveness of the heart, (3) circulatory obstruction and (4) pathological vasodilation causing loss of vascular resistance and excess capacitance. More than one mechanism may be involved in any given case. Diagnosis The absence of a pulse confirms a clinical diagnosis of cardiac arrest, but PEA can only be distinguished from other causes of cardiac arrest with a device capable of electrocardiography (ECG/EKG). In PEA, there is organised or semi-organised electrical activity in the heart as opposed to asystole (flatline) or to the disorganised electrical activity of either ventricular fibrillation or ventricular tachycardia. Treatment Cardiac resuscitation guidelines (ACLS/BCLS) advise that cardiopulmonary resuscitation should be initiated promptly to maintain cardiac output until the PEA can be corrected. The approach in treatment of PEA is to treat the underlying cause, if known (e.g. relieving a tension pneumothorax). Where an underlying cause for PEA cannot be determined and/or reversed, the treatment of pulseless electrical activity is similar to that for asystole. There is no evidence that external cardiac compression can increase cardiac output in any of the many scenarios of PEA, such as hemorrhage, in which impairment of cardiac filling is the underlying mechanism producing loss of a detectable pulse.A priority in resuscitation is placement of an intravenous or intraosseous line for administration of medications. The mainstay of drug therapy for PEA is epinephrine (adrenaline) 1 mg every 3–5 minutes. Although previously the use of atropine was recommended in the treatment of PEA/asystole, this recommendation was withdrawn in 2010 by the American Heart Association due to lack of evidence for therapeutic benefit. Epinephrine too has a limited evidence base, and it is recommended on the basis of its mechanism of action.Sodium bicarbonate 1meq per kilogram may be considered in this rhythm as well, although there is little evidence to support this practice. Its routine use is not recommended for patients in this context, except in special situations (e.g. preexisting metabolic acidosis, hyperkalemia, tricyclic antidepressant overdose).All of these drugs should be administered along with appropriate CPR techniques. Defibrillators cannot be used to correct this rhythm, as the problem lies in the response of the myocardial tissue to electrical impulses. References == External links ==

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I'm seeking clarification on the medical term 'Periodic breathing.' Could you explain it?

Periodic breathing is clusters of breaths separated by intervals of apnea or near-apnea. As opposed to normal breathing which is usually regular, periodic breathing is defined as three or more episodes of central apnea lasting at least 4 seconds, separated by no more than 30 seconds of normal breathing.Periodic breathing was originally thought to arise from serious neurologic or cardiovascular disease and therefore to carry a poor outlook. It is now known that periodic breathing also tends to occur during sleep, it can occur in healthy persons, and the apnea in periodic breathing is usually central sleep apnea rather than obstructive sleep apnea. Periodic breathing during sleep occurs typically in adult patients with congestive heart failure. Periodic breathing is also a normal variation of breathing found in premature and full term infants. It occurs when the infant has pauses in breathing for no more than 10 seconds at a time followed by a series of rapid, shallow breaths. Then the breathing returns to normal without any stimulation or intervention. These pauses in breathing may be accompanied by minor oxygen desaturation and bradycardia. It usually occurs when the infant is sleeping deeply, but may occur with light sleep or even when awake. Studies have shown that 78% of healthy full-term infants experience episodes of periodic breathing in the first two weeks of life, which typically resolves in the first six months of life. == References ==

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The term 'Amok' keeps coming up in medical discussions. What does it stand for?

Amok may refer to: Running amok, the act of behaving disruptively or uncontrollably. Film Amok (1934 film), a French film Amok (1944 film), a Mexican romantic drama Amok (1983 film), a Moroccan drama Literature Amok (comics), an Italian comic book series Amok (novella), by Stefan Zweig, 1922 Amok, a 1974 novel by Harry Thürk Amok, a 2003 novel by Krystian Bala Music Amok (The Late B.P. Helium album), 2004 Amok (Sentenced album), 1995 Amok (Atoms for Peace album), 2013 Other uses Steamed curry (Khmer: អាម៉ុក, amŏk), name in Cambodia for a curry steam-cooked in banana leaves Fish amok, a Cambodian steamed fish curry Amok (video game), a 1996 video game for the Sega Saturn Mok language, also known as Amok Amok (publisher), now Frémok, a Franco-Belgian comics publishing house Amok Press, a defunct American book imprint See also All pages with titles beginning with Amok All pages with titles containing Amok "Amok Time", a 1967 episode of Star Trek: The Original Series Amuck!, a 1972 Italian giallo film AMOC (disambiguation)

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I'd like to learn more about the medical term 'Glycation.' Can you provide some details?

Glycation (sometimes called non-enzymatic glycosylation) is the covalent attachment of a sugar to a protein or lipid. Typical sugars that participate in glycation are glucose, fructose, and their derivatives. Glycation is the non-enzymatic process responsible for many (e.g. micro and macrovascular) complications in diabetes mellitus and is implicated in some diseases and in aging. Glycation end products are believed to play a causative role in the vascular complications of diabetes mellitus.In contrast with glycation, glycosylation is the enzyme-mediated ATP-dependent attachment of sugars to protein or lipid. Glycosylation occurs at defined sites on the target molecule. It is a common form of post-translational modification of proteins and is required for the functioning of the mature protein. Biochemistry Glycations occur mainly in the bloodstream to a small proportion of the absorbed simple sugars: glucose, fructose, and galactose. It appears that fructose has approximately ten times the glycation activity of glucose, the primary body fuel. Glycation can occur through Amadori reactions, Schiff base reactions, and Maillard reactions; which lead to advanced glycation end products (AGEs). Biomedical implications Red blood cells have a consistent lifespan of 120 days and are accessible for measurement of glycated hemoglobin. Measurement of HbA1c—the predominant form of glycated hemoglobin—enables medium-term blood sugar control to be monitored in diabetes. Some glycation product are implicated in many age-related chronic diseases, including cardiovascular diseases (the endothelium, fibrinogen, and collagen are damaged) and Alzheimers disease (amyloid proteins are side-products of the reactions progressing to AGEs).Long-lived cells (such as nerves and different types of brain cell), long-lasting proteins (such as crystallins of the lens and cornea), and DNA can sustain substantial glycation over time. Damage by glycation results in stiffening of the collagen in the blood vessel walls, leading to high blood pressure, especially in diabetes. Glycations also cause weakening of the collagen in the blood vessel walls, which may lead to micro- or macro-aneurysm; this may cause strokes if in the brain. See also Advanced glycation end-product Alagebrium Fructose Galactose Glucose Glycosylation Glycated hemoglobin List of aging processes Additional reading Ahmed N, Furth AJ (July 1992). "Failure of common glycation assays to detect glycation by fructose". Clin. Chem. 38 (7): 1301–3. doi:10.1093/clinchem/38.7.1301. PMID 1623595. Vlassara H (June 2005). "Advanced glycation in health and disease: role of the modern environment". Annals of the New York Academy of Sciences. 1043 (1): 452–60. Bibcode:2005NYASA1043..452V. doi:10.1196/annals.1333.051. PMID 16037266. S2CID 20952378. == References ==

You act as a mediator between medical professionals and the public. Provide comprehensive explanations of medical terms, ensuring they are both precise and easily understood.

I need a basic explanation for the medical term 'Asciminib.'

Asciminib, sold under the brand name Scemblix, is a medication used to treat Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). Asciminib is a protein kinase inhibitor.The most common adverse reactions include upper respiratory tract infections, musculoskeletal pain, fatigue, nausea, rash, and diarrhea.Asciminib was approved for medical use in the United States in October 2021, and in the European Union in August 2022.The U.S. Food and Drug Administration (FDA) granted the application for asciminib priority review, fast track, orphan drug, and breakthrough therapy designations. Mechanism of action Asciminib is described as a "STAMP inhibitor," which means "specifically targeting the ABL myristoyl pocket." The wild-type ABL has a myristoylated N-terminus, which binds to an allosteric site, but the ABL fusion protein does not have the myristoylated domain. In the wild-type protein, when myristoylated N-terminus binds to the allosteric site, the kinase has reduced activity. Since the mutant fusion protein does not have the myristoylated N-terminus domain, it is not subject to this form of regulation, and thus the fusion protein is constitutively active. Asciminib binds to the allosteric site, resulting in an inhibition of bcr-abl activity.Unlike other bcr-abl inhibitors, such as imatinib, asciminib does not bind to the ATP-binding site on the active site of the enzyme. Asciminib and active site bcr-abl inhibitors have non-overlapping resistance mutations. The mutations A337V and P223S overcome the inhibitory activity of asciminib, but asciminib is not affected by the notorious T315I mutation that affects most ATP-competitive active site inhibitors, except ponatinib. Adverse effects Common side effects of Asciminib are symptoms of a cold, muscle pain, joint pain, bone pain, fatigue, nausea, diarrhea, rash as well as the patient displaying abnormal blood tests. Serious side effects of the medication include high blood pressure, low blood cell count, problems with the pancreas, and heart issues. Side effects of the medication on the pancreas may be observed via changes in serum lipase and amylase levels. Pharmacodynamics Asciminib is a substrate of the CYP3A4 enzyme. Asciminib is an inhibitor of CYP3A4, CYP2C9, and P-glycoprotein. Asciminib reaches steady state in 3 days. The volume of distribution of Asciminib is 151 L. Society and culture Legal status On 23 June 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Scemblix, intended for the treatment of adults with Philadelphia chromosome‑positive chronic myeloid leukemia in chronic phase who have previously been treated with two or more tyrosine kinase inhibitors. The applicant for this medicinal product is Novartis Europharm Limited. Asciminib was approved for medical use in the European Union in August 2022. References External links "Asciminib". Drug Information Portal. U.S. National Library of Medicine. Clinical trial number NCT02081378 for "A Phase I Study of Oral ABL001 in Patients With CML or Ph+ ALL" at ClinicalTrials.gov Clinical trial number NCT03106779 for "Study of Efficacy of CML-CP Patients Treated With ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs" at ClinicalTrials.gov

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I'm seeking clarification on the medical term 'Zygomycosis.' Could you explain it?

Zygomycosis is the broadest term to refer to infections caused by bread mold fungi of the zygomycota phylum. However, because zygomycota has been identified as polyphyletic, and is not included in modern fungal classification systems, the diseases that zygomycosis can refer to are better called by their specific names: mucormycosis (after Mucorales), phycomycosis (after Phycomycetes) and basidiobolomycosis (after Basidiobolus). These rare yet serious and potentially life-threatening fungal infections usually affect the face or oropharyngeal (nose and mouth) cavity. Zygomycosis type infections are most often caused by common fungi found in soil and decaying vegetation. While most individuals are exposed to the fungi on a regular basis, those with immune disorders (immunocompromised) are more prone to fungal infection. These types of infections are also common after natural disasters, such as tornadoes or earthquakes, where people have open wounds that have become filled with soil or vegetative matter.The condition may affect the gastrointestinal tract or the skin, often beginning in the nose and paranasal sinuses. It is one of the most rapidly spreading fungal infections in humans. Treatment consists of prompt and intensive antifungal drug therapy and surgery to remove the infected tissue. Causes Pathogenic zygomycosis is caused by species in two orders: Mucorales or Entomophthorales, with the former causing far more disease than the latter. These diseases are known as "mucormycosis" and "entomophthoramycosis", respectively. Order Mucorales (mucormycosis) Family Mucoraceae Absidia (Absidia corymbifera) Apophysomyces (Apophysomyces elegans and Apophysomyces trapeziformis) Mucor (Mucor indicus) Rhizomucor (Rhizomucor pusillus) Rhizopus (Rhizopus oryzae) Family Cunninghamellaceae Cunninghamella (Cunninghamella bertholletiae) Family Thamnidiaceae Cokeromyces (Cokeromyces recurvatus) Family Saksenaeaceae Saksenaea (Saksenaea vasiformis) Family Syncephalastraceae Syncephalastrum (Syncephalastrum racemosum) Order Entomophthorales (entomophthoramycosis) Family Basidiobolaceae Basidiobolus (Basidiobolus ranarum) Family Ancylistaceae Conidiobolus (Conidiobolus coronatus/Conidiobolus incongruus) Epidemiology Zygomycosis has been found in survivors of the 2004 Indian Ocean earthquake and tsunami and in survivors of the 2011 Joplin, Missouri tornado. Symptoms In the primary cutaneous form, the lesions are usually painful and necrotic, with black eschar, accompanied by a fever. Patients will usually present with a history of poorly controlled diabetes or malignancy. Myocutaneous infections may lead to amputation. Pulmonary tract infections seen with lung transplant patients, who are at high risk for fatal invasive mycoses. Rhinocerebral infection is characterized by paranasal swelling with necrotic tissues. Patient may have hemorrhagic exudates (tissue fluid from lesions tinged with blood) from the nose and eyes as the fungi penetrate through blood vessels and other anatomical structures. Diagnosis Diagnosis is done with potassium hydroxide (KOH) preparation in tissue. On light microscopy, there will be broad, ribbon-like septate hyphae with 90 degree angles on branches. KOH wet mount of the black eschar will show aseptate fungal hyphae with right angle branching. Periodic Acid Schiff (PAS) staining will reveal similar broad hyphae in the dermis and cutis. Fungal culture can also confirm the organism. Diagnosis remains difficult due to the lack of laboratory tests as mortality remains high. In 2005, a multiplex PCR test was able to identify five species of Rhizopus and may prove useful as a screening method for visceral mucormycosis in the future.The clinical approach to diagnosis includes radiologic, where more than ten nodules and pleural effusion are associated to pulmonary forms of the disease. In CT, a reverse halo sign is noted. Direct microscopy and histopathology, and cultures remain the gold standards for diagnoses. Zygomycophyta share close clinical and radiological features to Aspergillosis. Invasive procedures such as bronchial endoscopy and lung biopsy may be necessary to confirm pulmonary diagnosis are no validated indirect tests are available. Quantitative polymerase chain reaction to detect serum DNA of the pathogen shows promise. Treatment The condition may affect the gastrointestinal tract or the skin In non-trauma cases, it usually begins in the nose and paranasal sinuses and is one of the most rapidly spreading fungal infections in humans. Common symptoms include thrombosis and tissue necrosis.Due to the organisms rapid growth and invasion, zygomycosis presents with a high fatality rate. Treatment must begin immediately with debridement of the necrotic tissue plus Amphotericin B. Complete excision of the infectious tissue may be required as suspected dead tissue must be excised aggressively. Documented case of conservative surgical drainage, intravenous amphotericin B in an insulin-dependent diabetic have proven effective in sino-orbital infection. The prognosis varies vastly depending upon an individual patients circumstances. Other animals The term oomycosis is used to describe oomycete infections. These are more common in animals, notably dogs and horses. These are heterokonts, not true fungi. Types include pythiosis (caused by Pythium insidiosum) and lagenidiosis. Zygomycosis has been described in a cat, where fungal infection of the tracheobronchus led to respiratory disease requiring euthanasia. References == External links ==

You are a resource for medical understanding. Offer detailed explanations of medical terms, making complex concepts clear and comprehensible.

What is the significance of the term 'Bremelanotide' in the medical field?

Bremelanotide, sold under the brand name Vyleesi, is a medication used to treat low sexual desire in women. Specifically it is used for low sexual desire which occurs before menopause and is not due to medical problems, psychiatric problems, or problems within the relationship. It is given by an injection just under the skin of the thigh or abdomen.Common side effects include nausea, pain at the site of injection, and headache. It may also cause a temporary increase in blood pressure and decrease in heart rate after each dose, and darkening of the gums, face, and breasts. The medication is a peptide and acts by activating the melanocortin receptors.Bremelanotide was approved for medical use in the United States in 2019. It was developed by Palatin Technologies. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. Medical uses Bremelanotide is used for the treatment of generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. Specifically it is only recommended in those who have the condition without an underlying cause, such as medical, psychiatric, or relationship problems.It should be used at least 45 minutes before anticipated sexual activity. Only one dose per 24 hours or no more than eight doses per month is recommended. It should be stopped after eight weeks if there is no improvement in sexual desire and associated distress. Contraindications Due to its effects on blood pressure (generally a transient increase in systolic blood pressure by 6 mmHg, and diastolic blood pressure by 3 mmHg), bremelanotide is considered contraindicated in people with uncontrolled high blood pressure or cardiovascular disease. As long as bremelanotide is not used more than once in one day, it is not expected to cause more severe increases in blood pressure. Side effects The most frequently encountered side effect of bremelanotide is nausea (40.0%), which may be intolerable to some people. The use of anti-nausea medications (e.g. ondansetron) prior to administration of bremelanotide may help to reduce the nausea. Other side effects may include flushing (20.3%), injection site reactions (13.2%), headache (11.3%), vomiting (4.8%), cough (3.3%), fatigue (3.2%), hot flushes (2.7%), paresthesia (2.6%), dizziness (2.2%), and nasal congestion (2.1%). Discoloration of the skin, specifically hyperpigmentation, may occur—especially if bremelanotide is used more than eight times in one month. The discoloration may not resolve upon stopping use of bremelanotide, and may occur on the face, gums, or breasts. Experiments in animals, even at high doses, failed to find any negative consequence of bremelanotide on fertility. Interactions Bremelanotide does not meaningfully interact with alcohol, unlike flibanserin (for which the interaction with alcohol is a major barrier to its use). However, bremelanotide does interact with certain medications that people take by mouth. By slowing gastric motility, bremelanotide is thought to reduce the oral absorption (bioavailability) of certain medications, such as naltrexone and indomethacin. Pharmacology Pharmacodynamics Bremelanotide is a non-selective agonist of the melanocortin receptors, MC1 through MC5 (with the exception of MC2, the receptor of ACTH), but acting primarily as an MC3 and MC4 receptor agonist. Pharmacokinetics The bioavailability of bremelanotide with subcutaneous injection is about 100%. Following a subcutaneous injection of bremelanotide, maximal levels occur after about one hour, with a range of 0.5 to 1.0 hours. The plasma protein binding of bremelanotide is 21%. Bremelanotide is metabolized via hydrolysis of its peptide bonds. The elimination half-life of bremelanotide is 2.7 hours, with a range of 1.9 to 4.0 hours. Bremelanotide is excreted 64.8% in urine and 22.8% in feces. Chemistry Bremelanotide is a cyclic heptapeptide lactam analogue of α-melanocyte-stimulating hormone (α-MSH). It has the amino acid sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH, and is also known as cyclo-[Nle4,Asp5,D-Phe7,Lys10]α-MSH-(4-10). Bremelanotide is an active metabolite of melanotan II that lacks the C-terminal amide group.Aside from melanotan II and endogenous melanocyte-stimulating hormones like α-MSH, other peptide analogues of the same family as bremelanotide include afamelanotide (NDP-α-MSH), modimelanotide, and setmelanotide. History Studies in the early 1960s showed that administration of α-MSH caused sexual arousal in rats, sparking interest in α-MSH. In the 1980s, scientists at University of Arizona began developing α-MSH and analogs as potential sunless tanning agents. They synthesized and tested several analogs, including peptides they subsequently named, melanotan-I and melanotan II.Very early in the process one of the scientists, Mac Hadley, who was conducting experiments on himself with the peptide melanotan II, injected himself with twice the dose he intended and experienced an eight-hour erection, along with nausea and vomiting.To pursue the tanning agent, melanotan-I was licensed by Competitive Technologies, a technology transfer company operating on behalf of University of Arizona, to an Australian startup called Epitan, which changed its name to Clinuvel in 2006.To pursue the sexual dysfunction agent, melanotan II was licensed by Competitive Technologies to Palatin Technologies. Palatin ceased development of melanotan-II in 2000, and synthesized, patented, and began to develop bremelanotide, a likely metabolite of melanotan-II that differs from melanotan-II in that it has a hydroxyl group where melanotan-II has an amide. Competitive Technologies sued Palatin for breach of contract and to try to claim ownership of bremelanotide; the parties settled in 2008, with Palatin retaining rights to bremelanotide, returning rights to melanotan-II to Competitive Technologies, and paying $800,000.In August 2004, Palatin signed an agreement with King Pharmaceuticals to co-develop bremelanotide in the US and jointly license it outside the US; King paid Palatin $20M upfront.Palatin conducted Phase II trials of intranasal bremelanotide in both female sexual dysfunction (FSD) and male erectile dysfunction (ED) but these trials were halted by the FDA in 2007, due to increased blood pressure in clinical trial subjects; Palatin stopped development of the intranasal formulation in 2008. Four trials were conducted in ED, the last being a Phase IIb published in 2008. King terminated the co-development agreement shortly after the FDA halted the trials.The drug was then reformulated to be delivered by injection and trials continued in FSD. A phase II dose-finding trial in FSD in which the drug was administered 45 minutes before sex showed promise at the highest dose and only transient signs of high blood pressure; two Phase III trials were launched at the end of 2014. Palatin launched the Phase III trials with bremelanotide administered via an autoinjector.In 2014, Palatin licensed European rights to bremelanotide to Gedeon Richter Plc. for around $10 million, and Palatin received a milestone payment of around $3 million when it started the Phase III trials in the US. In September 2016, Palatin and Gedeon RIchter terminated that agreement.In November 2016, Palatin announced results of the Phase III trials, and shortly thereafter began seeking a partner to complete development in the US. In January 2017, Palatin and AMAG Pharmaceuticals agreed that AMAG exclusively would complete development and market bremelanotide in North America and the two would work together to license it in other territories; AMAG agreed to pay $60 million upfront, up to $80 million in regulatory milestones, up to $300 million in sales milestones, and tiered royalties ranging from high single digit to low double digit percentages.A New Drug Application of bremelanotide for female sexual dysfunction was accepted by the U.S. Food and Drug Administration (FDA) in June 2018, with a Prescription Drug User Fee Act (PDUFA) goal date set for 23 March 2019. It was approved for use in the United States in June 2019. References External links "Bremelanotide Acetate". Drug Information Portal. U.S. National Library of Medicine. "Drug Approval Package: Vyleesi". U.S. Food and Drug Administration (FDA).

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I'm looking for a concise explanation of the medical term 'Gilberts syndrome.'

Gilbert syndrome (GS) is a syndrome in which the liver of affected individuals processes bilirubin more slowly than the majority. Many people never have symptoms. Occasionally jaundice (a slight yellowish color of the skin or whites of the eyes) may occur.Gilbert syndrome is due to a genetic variant in the UGT1A1 gene which results in decreased activity of the bilirubin uridine diphosphate glucuronosyltransferase enzyme. It is typically inherited in an autosomal recessive pattern and occasionally in an autosomal dominant pattern depending on the type of variant. Episodes of jaundice may be triggered by stress such as exercise, menstruation, or not eating. Diagnosis is based on higher levels of unconjugated bilirubin in the blood without either signs of other liver problems or red blood cell breakdown.Typically no treatment is needed. Gilbert syndrome is associated with decreased cardiovascular health risks. If jaundice is significant phenobarbital may be used, which aids in the conjugation of bilirubin. Gilbert syndrome affects about 5% of people in the United States. Males are more often diagnosed than females. It is often not noticed until late childhood to early adulthood. The condition was first described in 1901 by Augustin Nicolas Gilbert. Signs and symptoms Jaundice Gilbert syndrome produces an elevated level of unconjugated bilirubin in the bloodstream, but normally has no consequences. Mild jaundice may appear under conditions of exertion, stress, fasting, and infections, but the condition is otherwise usually asymptomatic. Severe cases are seen by yellowing of the skin tone and yellowing of the conjunctiva in the eye.Gilbert syndrome has been reported to contribute to an accelerated onset of neonatal jaundice. The syndrome cannot cause severe indirect hyperbilirubinemia in neonates by itself, but it may have a summative effect on rising bilirubin when combined with other factors, for example in the presence of increased red blood cell destruction due to diseases such as G6PD deficiency. This situation can be especially dangerous if not quickly treated, as the high bilirubin causes irreversible neurological disability in the form of kernicterus. Detoxification of certain drugs The enzymes that are defective in GS – UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) – are also responsible for some of the livers ability to detoxify certain drugs. For example, Gilbert syndrome is associated with severe diarrhea and neutropenia in patients who are treated with irinotecan, which is metabolized by UGT1A1.While paracetamol (acetaminophen) is not metabolized by UGT1A1, it is metabolized by one of the other enzymes also deficient in some people with GS. A subset of people with GS may have an increased risk of paracetamol toxicity. Cardiovascular effects The mild increase in unconjugated bilirubin due to Gilbert syndrome is closely related to the reduction in the prevalence of chronic diseases, especially cardiovascular disease and type 2 diabetes, related risk factors, and all-cause mortality. Observational studies emphasize that the antioxidant effects of unconjugated bilirubin may bring survival benefits to patients.Several analyses have found a significantly decreased risk of coronary artery disease (CAD) in individuals with GS.Specifically, people with mildly elevated levels of bilirubin (1.1 mg/dl to 2.7 mg/dl) were at lower risk for CAD and at lower risk for future heart disease. These researchers went on to perform a meta-analysis of data available up to 2002, and confirmed the incidence of atherosclerotic disease (hardening of the arteries) in subjects with GS had a close and inverse relationship to the serum bilirubin. This beneficial effect was attributed to bilirubin IXα which is recognized as a potent antioxidant, rather than confounding factors such as high-density lipoprotein levels.This association was also seen in long-term data from the Framingham Heart Study. Moderately elevated levels of bilirubin in people with GS and the (TA)7/(TA)7 genotype were associated with one-third the risk for both coronary heart disease and cardiovascular disease as compared to those with the (TA)6/(TA)6 genotype (i.e. a normal, nonmutated gene locus).Platelet counts and MPV (mean platelet volume) are decreased in patients with Gilberts syndrome. The elevated levels of bilirubin and decreasing levels of MPV and CRP in Gilberts syndrome patients may have an effect on the slowing down of the atherosclerotic process. Other Symptoms, whether connected or not to GS, have been reported in a subset of those affected: fatigue (feeling tired all the time), difficulty maintaining concentration, unusual patterns of anxiety, loss of appetite, nausea, abdominal pain, loss of weight, itching (with no rash), and others, such as humor change or depression. But scientific studies found no clear pattern of adverse symptoms related to the elevated levels of unconjugated bilirubin in adults. However, other substances glucuronidized by the affected enzymes in those with Gilberts syndrome could theoretically, at their toxic levels, cause these symptoms. Consequently, debate exists about whether GS should be classified as a disease. However, Gilbert syndrome has been linked to an increased risk of gallstones. Cause Mutations in the UGT1A1 gene lead to Gilbert Syndrome. The gene provides instructions for making the bilirubin uridine diphosphate glucuronosyltransferase (bilirubin-UGT) enzyme, which can be found in the liver cells and responsible for the removal of bilirubin from the body.The bilirubin-UGT enzyme performs a chemical reaction called glucuronidation. Glucuronic acid is transferred to unconjugated bilirubin, which is a yellowish pigment made when your body breaks down old red blood cells, and then being converted to conjugated bilirubin during the reaction. Conjugated bilirubin passes from the liver into the intestines with bile. Its then excreted in stool. People with Gilbert syndrome have approximately 30 percent of normal bilirubin-UGT enzyme function, which contributes to a lower rate of glucuronidation of unconjugated bilirubin. This toxic substance then accumulates in the body, causing mild hyperbilirubinemia. Genetics Gilbert syndrome is a phenotypic effect, mostly associated with increased blood bilirubin levels, but also sometimes characterized by mild jaundice due to increased unconjugated bilirubin, that arises from several different genotypic variants of the gene for the enzyme responsible for changing bilirubin to the conjugated form.Gilberts syndrome is characterized by a 70–80% reduction in the glucuronidation activity of the enzyme (UGT1A1). The UGT1A1 gene is located on human chromosome 2.More than 100 polymorphisms of the UGT1A1 gene are known, designated as UGT1A1*n (where n is the general chronological order of discovery), either of the gene itself or of its promoter region. UGT1A1 is associated with a TATA box promoter region; this region most commonly contains the genetic sequence A(TA)6TAA; this variant accounts for about 50% of alleles in many populations. However, several allelic polymorphic variants of this region occur, the most common of which results from adding another dinucleotide repeat TA to the promoter region, resulting in A(TA)7TAA, which is called UGT1A1*28; this common variant accounts for about 40% of alleles in some populations, but is seen less often, around 3% of alleles, in Southeast and East Asian people and Pacific Islanders.In most populations, Gilbert syndrome is most commonly associated with homozygous A(TA)7TAA alleles. In 94% of GS cases, two other glucuronosyltransferase enzymes, UGT1A6 (rendered 50% inactive) and UGT1A7 (rendered 83% ineffective), are also affected.However, Gilbert syndrome can arise without TATA box promoter polymorphic variants; in some populations, particularly healthy Southeast and East Asians, Gilberts syndrome is more often a consequence of heterozygote missense mutations (such as Gly71Arg also known as UGT1A1*6, Tyr486Asp also known as UGT1A1*7, Pro364Leu also known as UGT1A1*73) in the actual gene coding region, which may be associated with significantly higher bilirubin levels.Because of its effects on drug and bilirubin breakdown and because of its genetic inheritance, Gilberts syndrome can be classed as a minor inborn error of metabolism. Diagnosis People with GS predominantly have elevated unconjugated bilirubin, while conjugated bilirubin is usually within the normal range or is less than 20% of the total. Levels of bilirubin in GS patients are reported to be from 20 μM to 90 μM (1.2 to 5.3 mg/dl) compared to the normal amount of < 20 μM. GS patients have a ratio of unconjugated/conjugated (indirect/direct) bilirubin commensurately higher than those without GS.The level of total bilirubin is often further increased if the blood sample is taken after fasting for two days, and a fast can, therefore, be useful diagnostically. A further conceptual step that is rarely necessary or appropriate is to give a low dose of phenobarbital: the bilirubin will decrease substantially. Tests can also detect DNA variants of UGT1A1 by polymerase chain reaction or DNA fragment sequencing. Differential diagnosis While Gilbert syndrome is considered harmless, it is clinically important because it may give rise to a concern about a blood or liver condition, which could be more dangerous. However, these conditions have additional indicators: In GS, unless another disease of the liver is also present, the liver enzymes ALT/SGPT and AST/SGOT, as well as albumin, are within normal ranges. More severe types of glucuronyl transferase disorders such as Crigler–Najjar syndrome (types I and II) are much more severe, with 0–10% UGT1A1 activity, with affected individuals at risk of brain damage in infancy (type I) and teenage years (type II). Hemolysis of any cause can be excluded by a full blood count, haptoglobin, lactate dehydrogenase levels, and the absence of reticulocytosis (elevated reticulocytes in the blood would usually be observed in haemolytic anaemia). Dubin–Johnson syndrome and Rotor syndrome are rarer autosomal recessive disorders characterized by an increase of conjugated bilirubin. Viral hepatitis associated with increase of conjugated bilirubin can be excluded by negative blood samples for antigens specific to the different hepatitis viruses. Cholestasis can be excluded by normal levels of bile acids in plasma, the absence of lactate dehydrogenase, low levels of conjugated bilirubin, and ultrasound scan of the bile ducts. Vitamin B12 deficiency - elevated bilirubin levels (and MCV counts above 90–92) can be associated with a vitamin B12 deficiency. Treatment Typically no treatment is needed. If jaundice is significant phenobarbital may be used. History Gilbert syndrome was first described by French gastroenterologist Augustin Nicolas Gilbert and co-workers in 1901. In German literature, it is commonly associated with Jens Einar Meulengracht.Alternative, less common names for this disorder include: Familial benign unconjugated hyperbilirubinaemia Constitutional liver dysfunction Familial non-hemolytic non-obstructive jaundice Icterus intermittens juvenilis Low-grade chronic hyperbilirubinemia Unconjugated benign bilirubinemia Society and culture Notable cases Napoleon Arthur Kornberg, Nobel laureate in Physiology or Medicine, 1959 Nicky Wire, Manic Street Preachers bassist Alexandr Dolgopolov (tennis player) Jonas Folger, MotoGP riderHuo Yuanjia (master of Chinese martial art)David Barnea (Mossad Chief) References External links Understanding Gilberts Syndrome and living better with Gilberts Syndrome symptoms Gilberts syndrome at NIHs Office of Rare Diseases Gilberts Syndrome BMJ Best Practices monograph

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I'm seeking clarification on the medical term 'Fosphenytoin.' Could you explain it?

Fosphenytoin, also known as fosphenytoin sodium, and sold under the brand name Cerebyx among others, is a water-soluble phenytoin prodrug that is administered intravenously to deliver phenytoin, potentially more safely than intravenous phenytoin. It is used in the acute treatment of convulsive status epilepticus. Fosphenytoin was developed in 1996. On 18 November 2004, Sicor (a subsidiary of Teva) received a tentative approval letter from the United States Food and Drug Administration for a generic version of fosphenytoin. Medical uses Fosphenytoin is approved in the United States for the short-term (five days or fewer) treatment of epilepsy when more widely used means of phenytoin administration are not possible or are ill-advised, such as endotracheal intubation, status epilepticus or some other type of repeated seizures; cluster seizure, vomiting, and/or the patient is unalert or not awake or both. Other In 2003, it was reported that even though anticonvulsants are often very effective in mania, and acute mania requires rapid treatment, fosphenytoin had no antimanic effect. Metabolism One millimole of phenytoin is produced for every millimole of fosphenytoin administered; the hydrolysis of fosphenytoin also yields phosphate and formaldehyde, the latter of which is subsequently metabolized to formate, which is in turn metabolized by a folate dependent mechanism. Side effects Side effects are similar to intravenous phenytoin and include hypotension, cardiac arrhythmias, CNS adverse events (nystagmus, dizziness, sedation/somnolence, ataxia and stupor), and local dermatological reactions. Purple glove syndrome probably occurs with fosphenytoin but possibly at lower frequency than with intravenous phenytoin. Fosphenytoin can cause hyperphosphatemia in end-stage renal failure patients. History Phenytoin, in both its acidic and sodium salt forms, is erratically bioavailable whether it is injected or taken orally due to its high melting point, weak acidity, and its being only sparingly soluble in water. Simply putting patients on other drugs is not always an option; this was especially true before 1993, when the number of anticonvulsants available was much more limited. One solution was to develop a prodrug that did not have these drawbacks. Fosphenytoin was approved by the Food and Drug Administration (FDA) on August 5, 1996, for use in epilepsy. See also Ethotoin Hydantoin Mephenytoin Phenytoin References External links "Fosphenytoin". Drug Information Portal. U.S. National Library of Medicine. "Fosphenytoin sodium". Drug Information Portal. U.S. National Library of Medicine.

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I'm looking for a concise explanation of the medical term 'Progressive outer retinal necrosis.'

Progressive outer retinal necrosis (PORN) syndrome is a form of chorio-retinitis, an infection in the retina, the back of the eye. The disease is most commonly caused by the Varicella zoster virus and is found almost exclusively in patients with HIV/AIDS (acquired immunodeficiency syndrome). Progressive outer retinal necrosis is the second most common opportunistic retinal infection in North America among people with AIDS. The reason this disease process is considered opportunistic is precisely because it only presents in patients with AIDS, a disease that attacks and weakens the immune system, making space for other infections, like Varicella zoster virus (VZV) and Herpes simplex virus (HSV), to attack the body. The syndrome, PORN, falls under the umbrella of Necrotizing Herpetic Retinopathy, along with Acute Retinal Necrosis (ARN). Although fairly similar processes, the two forms of retinopathy have different presenting symptoms. Acute Retinal Necrosis, or ARN, is damage more central in the retinal portion of the eye with dead or necrotic areas well defined. ARN also presents with inflammation within the eye and is often painful. Progressive outer retinal necrosis (PORN) is a chorioretinitis presenting with multiple lesions in the peripheral retina. Unlike ARN, this disease process has no signs of intraocular inflammation, the hallmark feature, or vascular involvement. Presentation (Signs and Symptoms) The presentation of the disease is dependent on the patients AIDS prognosis. If the immune system has been significantly weakened by AIDS, a patient will likely present with worse and faster progressing PORN. Commonly presenting symptoms of PORN include: Blurry vision Acute onset bilateral visual loss OR painless progressive visual loss Decreased vision with pain Floaters Headaches Diagnosis The diagnosis of Progressive outer retinal necrosis (PORN) syndrome is made primarily through history and physical exam. A patients medical history of AIDS increases the likelihood of PORN as the diagnosis. An eye exam will show specific hallmark features, including opacified lesions in the peripheral retina without inflammation. There are medical tests that can aid in diagnosing the severity of the disease process, however are not necessary for initial diagnosis. Imaging studies: may help diagnose the extent of retinal involvement Optical coherence tomography (OCT): this test allows ophthalmologists to look at outer and inner layers of the retina Fundus autofluorescence: shows areas of unhealthy cells in the retina Blood work: the labs can show how immuno-compromised an individual is Vitreous Tap: Analysis of the fluid in the eye can show the causative organism, such as VZV.Other possible diseases to consider when a patient presents with symptoms similar to PORN include: CMV retinitis, ARN, Syphilitic retinitis, Toxoplasma retinochoroiditis, tuberculosis, toxocariasis, fungal or bacterial endophthalmitis Inflammatory: Sarcoidosis, Behcets, other retinal vasculitides, Neoplastic: intraocular lymphoma, leukemia, metastasis. Prognosis If left untreated, PORN syndrome can become bilateral, affecting both eyes. The retina can also atrophy, or decay, over time as the blood supply decreases. This leads to retinal detachment, a process where the retina breaks off the back of the eye. Retinal detachments are considered surgical emergencies, as they can lead to blindness if not promptly fixed. Treatment When AIDS first became a diagnosis, ophthalmologists began seeing patients with infectious processes such as Progressive outer retinal necrosis (PORN). With the use of HAART (3 drug regimen standard) treatment for HIV/AIDS in the 1990s, the presentation of these chorioretinitis diseases became less severe and less frequent.Treatment for Necrotizing Herpetic Retinopathy, including ARN and PORN, includes the anti-viral medications Ganciclovir and Foscarnet. These medications are given as intra-vitreal injections (injected into the fluid of the eye). This treatment has shown success in reversing the disease process and improving vision to an extent. See also Cytomegalovirus retinitis List of systemic diseases with ocular manifestations == References ==

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The term 'Lysinuric protein intolerance' keeps coming up in medical discussions. What does it stand for?

Lysinuric protein intolerance (LPI) is an autosomal recessive metabolic disorder affecting amino acid transport. About 140 patients have been reported, almost half of them of Finnish origin. Individuals from Japan, Italy, Morocco and North Africa have also been reported plus one in Bixby, Oklahoma. Signs and symptoms Infants with LPI are usually symptom-free when breastfed because of the low protein concentration in human milk, but develop vomiting and diarrhea after weaning. The patients show failure to thrive, poor appetite, growth retardation, enlarged liver and spleen, prominent osteoporosis and osteopenia, delayed bone age and spontaneous protein aversion. Forced feeding of protein may lead to convulsions and coma. Mental development is normal if prolonged episode of hyperammonemia can be avoided. Some patients develop severe pulmonary and kidney complications. High levels of plasma glutamine and glycine are observed. Causes It has been associated with SLC7A7. Mechanism In LPI, urinary excretion of cationic amino acids (ornithine, arginine and lysine) is increased and these amino acids are poorly absorbed from the intestine. Therefore, their plasma concentrations are low and their body pools become depleted. Deficiency of arginine and ornithine restricts the function of the urea cycle and leads to hyperammonemia after protein-rich meals. Deficiency of lysine may play a major role in the skeletal and immunological abnormalities observed in LPI patients. Diagnosis The diagnosis is based on the biochemical findings (increased concentrations of lysine, arginine and ornithine in urine and low concentrations of these amino acids in plasma, elevation of urinary orotic acid excretion after protein-rich meals, and inappropriately high concentrations of serum ferritin and lactate dehydrogenase isoenzymes) and the screening of known mutations of the causative gene from a DNA sample. Treatment Treatment of LPI consists of protein-restricted diet and supplementation with oral *GeneReview/NIH/UW entry on Lysinuric Protein Intolerance citrulline. Citrulline is a neutral amino acid that improves the function of the urea cycle and allows sufficient protein intake without hyperammonemia. Prognosis Under proper dietary control and supplementation, the majority of the LPI patients are able to have a nearly normal life. However, severe complications including pulmonary alveolar proteinosis and chronic kidney disease may develop even with proper treatment.Fertility appears to be normal in women, but mothers with LPI have an increased risk for complications during pregnancy and delivery. References External links GeneReview/NIH/UW entry on Lysinuric Protein Intolerance

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Could you please explain the term 'Cross-species transmission' in simple language?

Cross-species transmission (CST), also called interspecies transmission, host jump, or spillover, is the transmission of an infectious pathogen, such as a virus, between hosts belonging to different species. Once introduced into an individual of a new host species, the pathogen may cause disease for the new host and/or acquire the ability to infect other individuals of the same species, allowing it to spread through the new host population. The phenomenon is most commonly studied in virology, but cross-species transmission may also occur with bacterial pathogens or other types of microorganisms.Steps involved in the transfer of pathogens to new hosts include contact between the pathogen and the host; the successful infection of an initial individual host, which may lead to amplification and an outbreak; and the adaptation of the pathogen, within either the original or new host, which may render it capable of spreading efficiently between individuals in populations of the new host. The concept is important in understanding and controlling emerging infectious diseases in humans, especially those caused by viruses. Most viral diseases of humans are zoonotic in origin, having been historically transmitted to human populations from various animal species; examples include SARS, Ebola, swine flu, rabies, and avian influenza.The exact mechanisms which facilitate cross-species transmission vary by pathogen, and even for common diseases are often poorly understood. It is believed that viruses with high mutation rates are able to rapidly adapt to new hosts and thereby overcome host-specific immunological defenses, allowing their continued transmission. A host shifting event occurs when a strain that was previously zoonotic begins to circulate exclusively among the new host species.Pathogen transfer is most likely to occur between species which are frequently in close contact with each other. It can also occur indirectly between species with less frequent contact if facilitated by an intermediary species; for example, a reservoir species may transfer the virus to a vector species, which in turn transfers the virus to humans. The degree of phylogenetic relatedness between host species also influences the likelihood that a pathogen is transmitted between them, likely because of the similarity of the hosts immunological defenses; for example, most human zoonotic transmissions come from other species of mammals. Pathogens of more distantly related species, on the other hand, such as plant viruses, may not be capable of infecting humans at all. Other factors influencing transmission rates include geographic proximity and intraspecies behaviors. Due to climate change and land use expansion, the risk of viral spillover is predicted to significantly increase. Prevalence and control Cross-species transmission is the most significant cause of disease emergence in humans and other species. Wildlife zoonotic diseases of microbial origin are also the most common group of human emerging diseases, and CST between wildlife and livestock has appreciable economic impacts in agriculture by reducing livestock productivity and imposing export restrictions. This makes CST of major concern for public health, agriculture, and wildlife management. The authors of a study on the bubonic plague in Oran stress that the disease "is primarily a bacterial zoonosis affecting rodents. It is caused by Yersinia pestis and is transmitted from animal to animal by fleas. Humans usually become infected through the bite of an infected rodent flea." The sanitary control measure instituted by the public health authority was chemical in nature: "Intra- and peridomestic spraying with permethrin was conducted. Deltamethrin was dusted on the tracks and around the burrows of rodents located in a radius of 10 km around the dwelling of the patients. Uncontrolled killing of rats was prohibited."A large proportion of viral pathogens that have emerged recently in humans are considered to have originated from various animal species. This is shown by several recent epidemics such as, avian flu, Ebola, monkeypox, and Hanta viruses. There is evidence to suggest that some diseases can potentially be re-introduced to human populations through animal hosts after they have been eradicated in humans. There is a risk of this phenomenon occurring with morbilliviruses as they can readily cross species barriers. CST can also have a significant effect on produce industries. Genotype VI-Avian paramyxovirus serotype 1 (GVI-PMV1) is a virus that arose through cross-species transmission events from Galliformes (i.e. chicken) to Columbiformes, and has become prevalent in the poultry industry.CST of rabies virus variants between many different species populations is a major concern of wildlife management. Introduction of these variants into non-reservoir animals increases the risk of human exposures and threatens current advances toward rabies control.Many pathogens are thought to have host specialization, which explains the maintenance of distinct strains in host species. Pathogens would have to overcome their host specificity to cross to a new host species. Some studies have argued that host specializations may be exaggerated, and pathogens are more likely to exhibit CST than previously thought. Original hosts usually have low death rates when infected with a pathogen, with fatality rates tending to be much higher in new hosts Between non-human primates and humans Due to the close relation of nonhuman primates (NHP) and humans, disease transmission between NHP and humans is relatively common and can become a major public health concern. Diseases such as HIV and human adenoviruses have been associated with NHP interactions.In places where contact between humans and NHPs is frequent, precautions are often taken to prevent disease transmission. Simian foamy viruses (SFV) is an enzootic retrovirus that has high rates of cross-species transmission and has been known to affect humans bitten by infected NHPs. It has caused health concerns in places like Indonesia where visitors at monkey temples can contract SFV from temple macaques (Macaca fascicularis). TMAdV (titi monkey adenovirus) is a highly divergent, sharing <57% pairwise nucleotide identity with other adenoviruses, NHP virus that had a high fatality rate (83%) in monkeys and is capable of spreading through human hosts. Predicting and preventing transmission between species Prediction and monitoring are important for the study of CSTs and their effects. However, factors that determine the origin and fate of cross-species transmission events remain unclear for the majority of human pathogens. This has resulted in the use of different statistical models for the analysis of CST. Some of these include risk-analysis models, single rate dated tip (SRDT) models, and phylogenetic diffusion models. The study of the genomes of pathogens involved in CST events is very useful in determining their origin and fate. This is because a pathogens genetic diversity and mutation rate are key factors in determining if it can transmit across multiple hosts. This makes it important for the genomes of transmission species to be partially or completely sequenced. A change in genomic structure could cause a pathogen that has a narrow host range to become capable of exploiting a wider host range. Genetic distance between different species, geographical range, and other interaction barriers will also influence cross-species transmission.One approach to risk assessment analysis of CST is to develop risk-analysis models that break the ‘‘process’’ of disease transmission into parts. Processes and interactions that could lead to cross-species disease transmission are explicitly described as a hypothetical infection chain. Data from laboratory and field experiments are used to estimate the probability of each component, expected natural variation, and margins of error.Different types of CST research would require different analysis pathways to meet their needs. A study on identification of viruses in bats that could spread to other mammals used the workflow: sequencing of genomic samples → “cleaning” of raw reads → elimination of host reads and eukaryotic contaminants → de novo assembly of the remaining reads → annotation of viral contigs → molecular detection of specific viruses → phylogenetic analysis → interpretation of data.Detecting CST and estimating its rate based on prevalence data is challenging. Due to these difficulties, computational methods are used to analyse CST events and the pathogens associated with them. The explosive development of molecular techniques has opened new possibilities for using phylogenetic analysis of pathogen genetics to infer epidemiological parameters. This provides some insight into the origins of these events and how they could be addressed. Methods of CST prevention are currently using both biological and computational data. An example of this is using both cellular assays and phylogenetic comparisons to support a role for TRIM5α, the product of the TRIM5 gene, in suppressing interspecies transmission and emergence of retroviruses in nature. Analysis Phylogeny The comparison of genomic data is very important for the study of cross-species transmission. Phylogenetic analysis is used to compare genetic variation in both pathogens associated with CST and the host species that they infect. Taken together, it is possible to infer what allowed a pathogen to crossover to a new host (i.e. mutation in a pathogen, change in host susceptibility) and how this can be prevented in the future. If the mechanisms a pathogens uses to initially enter a new species are well characterized and understood a certain level of risk control and prevention can be obtained. In contact, a poor understanding of pathogens, and their associated diseases, makes it harder for preventive measures to be takenAlternative hosts can also potentially have a critical role in the evolution and diffusion of a pathogen. When a pathogen crosses species it often acquires new characteristics that allow it to breach host barriers. Different pathogen variants can have very different effects on host species. Thus it can be beneficial to CST analysis to compare the same pathogens occurring in different host species. Phylogenetic analysis can be used to track a pathogens history through different species populations. Even if a pathogen is new and highly divergent, phylogenetic comparison can be very insightful. A useful strategy for investigating the history of epidemics caused by pathogen transmission combines molecular clock analysis, to estimate the timescale of the epidemic, and coalescent theory, to infer the demographic history of the pathogen. When constructing phylogenies, computer databases and tools are often used. Programs, such as BLAST, are used to annotate pathogen sequences, while databases like GenBank provide information about functions based on the pathogens genomic structure. Trees are constructed using computational methods such as MPR or Bayesian Inference, and models are created depending on the needs of the study. Single rate dated tip (SRDT) models, for example, allows for estimates of timescale under a phylogenetic tree. Models for CST prediction will vary depending on what parameters need to be accounted for when constructing the model. Most parsimonious reconstruction (MPR) Parsimony is the principle in which one chooses the simplest scientific explanation that fits the evidence. In terms of building phylogenetic trees, the best hypothesis is the one that requires the fewest evolutionary changes. Using parsimony to reconstruct ancestral character states on a phylogenetic tree is a method for testing ecological and evolutionary hypotheses. This method can be used in CST studies to estimate the number of character changes that exist between pathogens in relation to their host. This makes MPR useful for tracking a CST pathogen to its origins. MPR can also be used to the compare traits of host species populations. Traits and behaviours within a population could make them more susceptible to CST. For example, species which migrate regionally are important for spreading viruses through population networks.Despite the success of parsimony reconstructions, research suggests they are often sensitive and can sometimes be prone to bias in complex models. This can cause problems for CST models that have to consider many variables. Alternatives methods, such as maximum likelihood, have been developed as an alternative to parsimony reconstruction. Using genetic markers Two methods of measuring genetic variation, variable number tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs), have been very beneficial to the study of bacterial transmission. VNTRs, due to the low cost and high mutation rates, make them particularly useful to detect genetic differences in recent outbreaks, and while SNPs have a lower mutation rate per locus than VNTRs, they deliver more stable and reliable genetic relationships between isolates. Both methods are used to construct phylogenies for genetic analysis, however, SNPs are more suitable for studies on phylogenies contraction. However, it can be difficult for these methods to accurately simulate CSTs everts. Estimates of CST based on phylogenies made using the VNTR marker can be biased towards detecting CST events across a wide range of the parameters. SNPs tend to be less biased and variable in estimates of CST when estimations of CST rates are low and a low number of SNPs is used. In general, CST rate estimates using these methods are most reliable in systems with more mutations, more markers, and high genetic differences between introduced strains. CST is very complex and models need to account for a lot of parameters to accurately represent the phenomena. Models that oversimplify reality can result in biased data. Multiple parameters such as number of mutations accumulated since introduction, stochasticity, the genetic difference of strains introduced, and the sampling effort can make unbiased estimates of CST difficult even with whole-genome sequences, especially if sampling is limited, mutation rates are low, or if pathogens were recently introduced. More information on the factors that influence CST rates is needed for the contraction of more appropriate models to study these events. The process of using genetic markers to estimate CST rates should take into account several important factors to reduce bias. One is that the phylogenetic tree constructed in the analysis needs to capture the underlying epidemiological process generating the tree. The models need to account for how the genetic variability of a pathogen influences a disease in a species, not just general differences in genomic structure. Two, the strength of the analysis will depend on the amount of mutation accumulated since the pathogen was introduced in the system. This is due to many models using the number of mutations as an indicator of CST frequency. Therefore, efforts are focused on estimating either time since the introduction or the substitution rate of the marker (from laboratory experiments or genomic comparative analysis). This is important not only when using the MPR method but also for Likelihood approaches that require an estimation of the mutation rate. Three, CST will also affect disease prevalence in the potential host, so combining both epidemiological time series data with genetic data may be an excellent approach to CST study Bayesian analysis Bayesian frameworks are a form of maximum likelihood-based analyses and can be very effective in cross-species transmission studies. Bayesian inference of character evolution methods can account for phylogenetic tree uncertainty and more complex scenarios, with models such as the character diffusion model currently being developed for the study of CST in RNA viruses. A Bayesian statistical approach presents advantages over other analyses for tracking CST origins. Computational techniques allow integration over an unknown phylogeny, which cannot be directly observed, and unknown migration process, which is usually poorly understood.The Bayesian frameworks are also well suited to bring together different kinds of information. The BEAST software, which has a strong focus on calibrated phylogenies and genealogies, illustrates this by offering a large number of complementary evolutionary models including substitution models, demographic and relaxed clock models that can be combined into a full probabilistic model. By adding spatial reconstruction, these models create the probability of biogeographical history reconstruction from genetic data. This could be useful for determining the origins of cross-species transmissions. The high effectiveness of Bayesian statistical methods has made them instrumental in evolutionary studies. Bayesian ancestral host reconstruction under discrete diffusion models can be used to infer the origin and effects of pathogens associated with CST. One study on Human adenoviruses using Bayesian supported a gorilla and chimpanzee origin for the viral species, aiding prevention efforts. Despite presumably rare direct contact between sympatric populations of the two species, CST events can occur between them. The study also determined that two independent HAdV-B transmission events to humans occurred and that the HAdV-Bs circulating in humans are of zoonotic origin and have probably affected global health for most of our species lifetime.Phylogenetic diffusion models are frequently used for phylogeographic analyses, with the inference of host jumping becoming of increasing interest. The Bayesian inference approach enables model averaging over several potential diffusion predictors and estimates the support and contribution of each predictor while marginalizing over phylogenetic history. For studying viral CST, the flexibility of the Bayesian statistical framework allows for the reconstruction of virus transmission between different host species while simultaneously testing and quantifying the contribution of multiple ecological and evolutionary influences of both CST spillover and host shifting. One study on rabies in bats showed geographical range overlap is a modest predictor for CST, but not for host shifts. This highlights how Bayesian inferences in models can be used for CST analysis. See also Mathematical modelling of infectious disease Reverse zoonosis Spillover infection Vector Zoonosis Feline zoonosis References External links Theo Kypraios. "A Gentle Tutorial in Bayesian Statistics" (PDF). Retrieved 10 July 2020. {{cite journal}}: Cite journal requires |journal= (help) Bayesian modeling book and examples available for downloading. Bayesian statistics at Wikiversity Smith, Tara C. (2022-04-27). "What Happens When We Give Animals Our Diseases?". Quanta Magazine.

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Can you demystify the medical term 'Vulvodynia' for me?

Vulvodynia is a chronic pain syndrome that affects the vulvar area and occurs without an identifiable cause. Symptoms typically include a feeling of burning or irritation. It has been established by the ISSVD that for the diagnosis to be made symptoms must last at least three months.The exact cause is unknown but is believed to involve a number of factors, including genetics, immunology, and possibly diet. Diagnosis is by ruling out other possible causes. This may or may not include a biopsy of the area.Treatment may involve a number of different measures; however, none is universally effective, and the evidence to support their effectiveness is often poor. Some of these measures include improved vulvar care, dietary changes, medications, counselling, and, if conservative treatment is not effective, surgery. It is estimated to affect up to 16% of women. Signs and symptoms Pain is the most notable symptom of vulvodynia, and can be characterized as a burning, stinging, irritation or sharp pain that occurs in the vulva and entrance to the vagina. It may be constant, intermittent or happen only when the vulva is touched, but vulvodynia usually has a long duration.Symptoms may occur in one place or the entire vulvar area. It can occur during or after sexual activity, when tampons are inserted, or when prolonged pressure is applied to the vulva, such as during sitting, bike riding, or horseback riding. Some cases of vulvodynia are idiopathic where no particular cause can be determined. Vulvar vestibulitis Vulvar vestibulitis syndrome (VVS), vestibulodynia, or simply vulvar vestibulitis or "localized (to the vestibule) provoked vulvodynia" refers to pain localized to the vestibular region. It tends to be associated with a highly localized "burning" or "cutting" type of pain. The pain of vulvodynia may extend into the clitoris; this is referred to as clitorodynia.Vulvar vestibulitis syndrome is the most common subtype of vulvodynia that affects premenopausal women – the syndrome has been cited as affecting about 10%–15% of women seeking gynecological care. Causes A wide variety of possible causes and treatments for vulvodynia are currently being explored. Moreover, there are probably several causes of vulvodynia, and some may be individual to the patient.Possible causes include Sjögren syndrome, the symptoms of which include chronic vaginal dryness. Others include genetic predisposition to inflammation, allergy or other sensitivity (for example: oxalates in the urine), an autoimmune disorder similar to lupus erythematosus or to eczema or to lichen sclerosus, infection (e.g., yeast infections, bacterial vaginosis, HPV, HSV), injury, and neuropathy—including an increased number of nerve endings in the vaginal area. Some cases seem to be negative outcomes of genital surgery, such as a labioplasty. Initiation of hormonal contraceptives that contain low- dose estrogen before the age of 16 could predispose women to vulvar vestibulitis syndrome. A significantly lower pain threshold, especially in the posterior vestibulum, has also been associated with the use of hormonal contraceptives in women without vulvar vestibulitis syndrome. Pelvic floor dysfunction may be the underlying cause of some womens pain. Diagnosis The condition is one of exclusion and other vulvovaginal problems should be ruled out. The diagnosis is based on the typical complaints of the patient, essentially normal physical findings, and the absence of identifiable causes per the differential diagnosis. Cotton swab testing is used to differentiate between generalized and localized pain and delineate the areas of pain and categorize their severity. Patients often will describe the touch of a cotton ball as extremely painful, like the scraping of a knife. A diagram of pain locations may be helpful in assessing the pain over time. The vagina should be examined, and tests, including wet mount, vaginal pH, fungal culture, and Gram stain, should be performed as indicated. Fungal culture may identify resistant strains.It is estimated that only half of affected women will seek medical help, among whom many will see several doctors before a correct diagnosis is made. Only 2% of the people that seek help do obtain a diagnostic. Many gynecologists are not familiar with this family of conditions, but awareness has spread with time. Affected women are also often hesitant to seek treatment for chronic vulvar pain, especially since many women begin experiencing symptoms around the same time they become sexually active. Moreover, the absence of any visible symptoms means that before being successfully diagnosed many patients have been told that the pain is "in their head" (a medical stance more associated with the 1970s than with modern medicine). Differential diagnosis Infections: urinary tract infection, candidiasis, herpes, HPV Inflammation: lichen planus Neoplasm: Pagets disease, vulvar carcinoma Neurologic disorder: neuralgia secondary to herpes virus, spinal nerve injury Treatment There are a number of possible treatments with none being uniformly effective. Treatments include: Lifestyle A number of lifestyle changes are often recommended such as using cotton underwear, not using substances that may irritate the area, and using lubricant during sex. The use of alternative medicine has not been sufficiently studied to make recommendations. Counseling Education and accurate information about vestibulodynia: Gynaecologist-led educational seminars delivered in a group format have a significant positive impact on psychological symptoms and sexual functioning in women who have provoked (caused by a stimulus such as touch or sexual activity) vestibulodynia. Provoked vestibulodynia, whilst similar in some respects, is different to vulvodynia which this article refers to. Biofeedback, physical therapy and relaxation: Biofeedback, often done by physical therapists, involves inserting a vaginal sensor to get a sense of the strength of the muscles and help a patient get greater control of her muscles to feel the difference between contraction and relaxation. Sessions are linked with at-home recommendations including often Kegel exercises (e.g., hold for 9 seconds, relax for 30 seconds, for 10–15 sets), and relaxation. Medications A number of medications have been used to treat vulvodynia. Evidence to support their use, however, is often poor. These include creams and ointments containing lidocaine, estrogen or tricyclic antidepressants. Antidepressants and anticonvulsants in pill form are sometimes tried but have been poorly studied. Injectable medications included steroids and botulinum toxin have been tried with limited success. Surgery Vestibulectomy, during which the nerve fibers to the area are cut out, may be recommended if other treatments have not been found to be effective. There have been no high quality studies looking at surgery as a treatment. While improvement has been noted in 60% to 90%, those who were treated without surgery improved in 40 to 80% of cases. Epidemiology The percentage of women affected is not entirely clear, but estimates range as high as 16%. Many other conditions that are not truly vulvodynia (diagnosis is made by ruling out other causes of vulvar pain) could be confused with it. Vulvar pain is a quite frequent complaint in womens health clinics. Vulvodynia is a new term in the medical literature. References External links Vulvodynia at Curlie

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I've come across the term 'Nasopharyngeal angiofibroma' in a medical context, but I'm not sure what it means. Can you clarify?

Nasopharyngeal angiofibroma is an angiofibroma also known as juvenile nasal angiofibroma, fibromatous hamartoma, and angiofibromatous hamartoma of the nasal cavity. It is a histologically benign but locally aggressive vascular tumor of the nasopharynx that arises from the superior margin of the sphenopalatine foramen and grows in the back of the nasal cavity. It most commonly affects adolescent males (because it is a hormone-sensitive tumor). Though it is a benign tumor, it is locally invasive and can invade the nose, cheek, orbit (frog face deformity), or brain. Patients with nasopharyngeal angiofibroma usually present with one-sided nasal obstruction with profuse epistaxis. Signs and symptoms Frequent chronic epistaxis or blood-tinged nasal discharge Nasal obstruction and rhinorrhea Facial dysmorphism (when locally invasive) Conductive hearing loss from eustachian-tube obstruction Diplopia, which occurs secondary to erosion into superior orbital fissure and due to third and sixth nerve palsy. Proptosis when having intraorbital extension. Rarely anosmia, recurrent otitis media, and eye pain. Diagnosis If nasopharyngeal angiofibroma is suspected based on physical examination (a smooth vascular submucosal mass in the posterior nasal cavity of an adolescent male), imaging studies such as CT or MRI should be performed. Biopsy should be avoided as to avoid extensive bleeding since the tumor is composed of blood vessels without a muscular coat.Antral sign or Holman-Miller sign (forward bowing of posterior wall of maxilla) is pathognomic of angiofibroma.DSA (digital subtraction angiography) of carotid artery to see the extension of tumors and feeding vessels Differential diagnosis Antro-choanal polyp (benign non neoplastic growth) Rhinosporidiosis (as bleeding point is here too) Malignancy—nasopharyngeal carcinoma, lymphoma, plasmacytoma, rhabdomyosarcoma Chordoma Nasopharyngeal cyst Pyogenic granuloma Staging There are many different staging- systems published. One of the most used is that of Radkowsky: Treatment Treatment for Nasopharyngeal angiofibroma (JNA) is primarily surgical. The tumor is primarily excised by external or endoscopic approach. Medical treatment and radiation therapy are only of historical interest.External approaches: transpalatine approach transpalatine + sublabial (Sardanas) Approach infratemporal Approach nasal endoscopic Approach transmaxillary Approach maxillary swing Approach or Facial translocationEndoscopic approach is an excellent tool in primary and recurrent JNA, it allows visualisation and precise removal of the lesion. Preoperative embolisation of tumour may be of some use in reducing intraoperative bleeding.Direct visualization is not common- If the tumor is limited to nasopharynx and nose, for endoscopic approach or Wilsons transpalatal approach is used. It can be extended into Sardanas approach if the tumor extends laterally. For tumors of infratemporal fossa, Maxillary Swing approach is used. Transmaxillary Le Fort 1 approach is used for tumors extending into maxillary and ethmoid sinuses and pterygopalatine fossa. If the tumor extend up to the cheek, for Weber–Ferguson approach should be used. Prognosis Prognosis for nasopharyngeal angiofibroma is favorable. Because these tumors are benign, metastasis to distal sites does not occur. However, these tumors are highly vascularized and grow rapidly. Removal is important in preventing nasal obstruction and recurrent epistaxis. Mortality is not associated with nasopharyngeal angiofibroma. References == External links ==

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I'm seeking clarification on the medical term 'Eosinophilic esophagitis.' Could you explain it?

Eosinophilic esophagitis (EoE) is an allergic inflammatory condition of the esophagus that involves eosinophils, a type of white blood cell. In healthy individuals, the esophagus is typically devoid of eosinophils. In EoE, eosinophils migrate to the esophagus in large numbers. When a trigger food is eaten, the eosinophils contribute to tissue damage and inflammation. Symptoms include swallowing difficulty, food impaction, vomiting, and heartburn.Eosinophilic esophagitis was first described in children but also occurs in adults. The condition is not well understood, but food allergy may play a significant role. The treatment may consist of removal of known or suspected triggers and medication to suppress the immune response. In severe cases, it may be necessary to enlarge the esophagus with an endoscopy procedure. While knowledge about EoE has been increasing rapidly, diagnosis of EoE can be challenging because the symptoms and histo-pathologic findings are not specific. Epidemiology The prevalence of eosinophilic esophagitis has increased over time and currently ranges from 1 to 6 per 10,000 persons. Gender and ethnic variations exist in the prevalence of EoE, with the majority of cases reported in Caucasian males.In addition to gender (male predominance) and race (mainly a disease of Caucasian individuals), established risk factors for EoE include atopy and other allergic conditions. Other recognized genetic and environmental risk factors for EoE include alterations in gut barrier function (e.g. GERD), variation in the nature and timing of oral antigen exposure, lack of early exposure to microbes, and an altered microbiome. A study comparing active EoE children to non EoE children found an altered microbiome due to a positive correlation between a relatively high abundance of Haemophilus and disease activity seen through an increasing Eosinophilic Esophagitis Endoscopic Reference Score and Eosinophilic Esophagitis Histologic Scoring System (q value = 5e-10). Measuring the relative abundance of specific taxa in children’s salivary microbiome could serve as a noninvasive marker for eosinophilic esophagitis. Signs and symptoms EoE often presents with difficulty swallowing, food impaction, stomach pains, regurgitation or vomiting, and decreased appetite. Although the typical onset of EoE is in childhood, the disease can be found in all age groups, and symptoms vary depending on the age of presentation. In addition, young children with EoE may present with feeding difficulties and poor weight gain. It is more common in males, and affects both adults and children.Predominant symptoms in school-aged children and adolescents include difficulty swallowing, food impaction, and choking/gagging with meals- particularly when eating foods with coarse textures. Other symptoms in this age group can include abdominal/chest pain, vomiting, and regurgitation. The predominant symptom in adults is difficulty swallowing; however, intractable heartburn and food avoidance may also be present. Due to the long-standing inflammation and possible resultant scarring that may have gone unrecognized, adults presenting with EoE tend to have more episodes of esophageal food impaction as well as other esophageal abnormalities such as Schatzki ring, esophageal webs, and in some cases, achalasia.Although many of these symptoms overlap with the symptoms of GERD, the majority of patients with EoE exhibit a poor response to acid-suppression therapy. Many people with EoE have other autoimmune and allergic diseases such as asthma and celiac disease. Mast cell disorders such as Mast Cell Activation Syndrome or Mastocytosis are also frequently associated with it. Pathophysiology Eosinophils are inflammatory cells that release a variety of chemical signals which inflame the surrounding esophageal tissue. This results in the signs and symptoms of pain, visible redness on endoscopy, and a natural history that may include stricturing. Eosinophils are normally present in other parts of a healthy gastrointestinal tract, these white blood cells are not normally found in the esophagus of a healthy individual. The reason for the migration of eosinophils to the tissue of the esophagus is not fully understood but is being studied extensively. It is thought the migration of eosinophils to the esophagus may be due to genetic, environmental, and host immune system factors.At a tissue level, EoE is characterized by a dense infiltrate with white blood cells of the eosinophil type into the epithelial lining of the esophagus. This is thought to be an allergic reaction against ingested food, based on the important role eosinophils play in allergic reactions. The eosinophils are recruited into the tissue in response to local production of eotaxin-3 by IL-13 stimulated esophageal epithelial cells. Diagnosis The diagnosis of EoE is typically made on the combination of symptoms and findings on diagnostic testing. To properly diagnose EoE, various diseases such as GERD, esophageal cancer, achalasia, hypereosinophilic syndrome, infection, Crohns disease, and drug allergies need to be ruled out. Prior to the development of the EE Diagnostic Panel, EoE could only be diagnosed if gastroesophageal reflux did not respond to a six-week trial of twice-a-day high-dose proton-pump inhibitors (PPIs) or if a negative ambulatory pH study ruled out gastroesophageal reflux disease (GERD).Radiologically, the term "ringed esophagus" has been used for the appearance of eosinophilic esophagitis on barium swallow studies to contrast with the appearance of transient transverse folds sometimes seen with esophageal reflux (termed "feline esophagus"). Endoscopy Endoscopically, ridges, furrows, or rings may be seen in the esophageal wall. Sometimes, multiple rings may occur in the esophagus, leading to the term "corrugated esophagus" or "feline esophagus" due to similarity of the rings to the cat esophagus. Presence of white exudates in esophagus is also suggestive of the diagnosis. On biopsy taken at the time of endoscopy, numerous eosinophils can be seen in the superficial epithelium. A minimum of 15 eosinophils per high-power field are required to make the diagnosis. Eosinophilic inflammation is not limited to the esophagus alone, and does extend through the whole gastrointestinal tract. Profoundly degranulated eosinophils may also be present, as may micro-abscesses and an expansion of the basal layer.Patients found to have signs of EoE on endoscopy should undergo an empiric 8-week trial of high-dose proton pump inhibitor therapy (twice daily) before repeat endoscopy in order to rule out GERD. Although endoscopic findings are helpful in identifying patients with EoE, they are not diagnostic of the disease if the patient has no clinical symptoms. Esophageal mucosal biopsy Currently, endoscopic mucosal biopsy remains the most important diagnostic test for EoE, and is required to confirm the diagnosis. Biopsy specimens from both the proximal/mid and distal esophagus should be obtained regardless of the gross appearance of the mucosa. Specimens should also be obtained from areas revealing endoscopic abnormalities. At least four biopsies are required to obtain adequate sensitivity for the detection of EoE. A definitive diagnosis of EoE is based on the presence of at least 15 eosinophils/HPF in the esophageal biopsies of patients despite treatment with high-dose PPI. GERD can increase eosinophilic infiltration in the distal esophagus, however, eosinophils associated with GERD generally occur at a lower density (i.e. < 15/HPF). Allergy assessment A thorough personal and family history of other atopic conditions is recommended in all patients with EoE. Testing for allergic sensitization may be considered using skin prick testing or blood testing for allergen-specific IgE. This is particularly important for the 10–20% of EoE patients who also have symptoms of immediate IgE-mediated food allergy. Atopy patch testing has been used in some cases for the potential identification of delayed, non-IgE (cell-mediated) reactions. Diagnostic criteria The diagnosis of eosinophilic esophagitis requires all of the following: Symptoms related to esophageal dysfunction. Eosinophil-predominant inflammation on esophageal biopsy, characteristically consisting of a peak value of ≥15 eosinophils per high power field (HPF). Exclusion of other causes that may be responsible for symptoms and esophageal eosinophilia. Treatment The goal of EoE treatment is to control the symptoms by decreasing the number of eosinophils in the esophagus and, subsequently, reducing the esophageal inflammation. Management consists of dietary, pharmacological, and endoscopic treatment. Dietary management Dietary treatment can be effective, as there does appear to be a role of allergy in the development of EOE. Allergy testing is not particularly effective in predicting which foods are driving the disease process. If no specific allergenic food or agent is present, a trial of the six food elimination diet (SFED) can be pursued. Various approaches have been tried, where either six food groups (cows milk, wheat, egg, soy, nuts and fish/seafood), four groups (animal milk, gluten-containing cereals, egg, legumes) or two groups (animal milk and gluten-containing cereals) are excluded for a period of time, usually six weeks. A "top down" (starting with six foods, then reintroducing) approach may be very restrictive. Four- or even two-group exclusion diets may be less difficult to follow and reduce the need for many endoscopies if the response to the limited restriction is good.Alternative options to SFED includes the elemental diet, which is an amino acid based diet. The elemental diet demonstrates a high rate of response (almost 90% in children, 70% in adults), with a rapid relief of symptoms associated with histological remission. This diet involves using amino-acid based liquid formulas for 4-6 wk, followed by the histological evaluation of response. If remission is achieved, foods are slowly reintroduced. Pharmacologic treatment In patients diagnosed with EoE, a trial of proton-pump inhibitors (PPI), such as esomeprazole 20 mg to 40 mg oral daily or twice daily as a first line therapy is a reasonable option. Nexium®, brand name esomeprazole, may be preferred as these tablets can be dispersed in half a glass of water and drank for those with difficulty swallowing pills. Those who respond to PPI therapy with symptomatic improvement, should have endoscopy with esophageal biopsy should be repeated. If no eosinophils are present in the repeat biopsy, the diagnosis is either acid mediated GERD with eosinophilia or non GERD PPI responsive EoE with unknown mechanism. If both symptoms and eosinophils persists after treatment with PPI, the diagnosis is immune mediated EoE.Medical therapy for immune mediated EoE primarily involves using corticosteroids. Systemic (oral) corticosteroids were one of the first treatment options shown to be effective in patients with EoE. Both clinical and histologic improvement have been noted in approximately 95% of EoE patients using systemic corticosteroids. However, upon discontinuation of therapy, 90% of patients using corticosteroids experience a recurrence in symptoms. In May 2022, U.S. Food and Drug Administration approved dupilumab (Dupixent) to treat eosinophilic esophagitis (EoE) in adults and pediatric patients 12 years and older weighing at least 40 kilograms (which is about 88 pounds) making it the first US FDA approved treatment for EoE. Endoscopic dilatation In patients who present with food impaction, flexible upper endoscopy is recommended to remove impacted food. Dilation is deferred in EoE until patients are adequately treated with pharmacological or dietary therapy, and the result of a response to therapy is available. The goals of therapy for treating EoE is to improve the patients symptoms as well as to reduce the number of eosinophils on biopsy. This procedure is effective in 84% of people who require it.Esophageal strictures and rings can be safely dilated in EoE. It is recommended to use a graduated balloon catheter for gradual dilation. The patient should be informed that after dilation they might experience chest pain and in addition risk of esophageal perforation and bleeding. Prognosis The long-term prognosis for patients with EoE is unknown. Some patients may follow a “waxing and waning” course characterized by symptomatic episodes followed by periods of remission. There have also been reports of apparent spontaneous disease remission in some patients; however, the risk of recurrence in these patients is unknown. It is possible that long-standing, untreated disease may result in esophageal remodeling, leading to strictures, Schatzki ring and, eventually, achalasia. Risk Factors There are many environmental factors that can increase the risk of developing EoE along with genetic factors for the disorder. The prevalence of EoE seems to be trending and there are many ongoing studies to try and find out why this may be. Risk factors for EoE include autoimmune conditions such as, inflammatory bowel disease and rheumatoid arthritis. Those with celiac disease, another autoimmune condition, are at higher risk of developing EoE as well. Individuals living in dry or cold climates as well as those living in areas of low population density are associated with higher rates of EoE. Food allergens are a risk factor of EoE and can often be directly attributed to the disease. Often times removing these food allergens from the diet can resolve EoE symptoms. History The first case of eosinophilic esophagitis was reported in 1978. In the early 1990s, it became recognized as a distinct disease. See also Eosinophilic gastroenteritis References == External links ==

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I'm seeking clarification on the medical term 'Temazepam.' Could you explain it?

Temazepam (sold under the brand names Restoril among others) is a medication of the benzodiazepine class which is now generally used to treat severe or debilitating insomnia. Such use should generally be for less than ten days. It is taken by mouth. Temazepam is rapidly absorbed, and significant hypnotic effects begin in less than 30 minutes and can last for up to eight hours. Many studies, some going as far back as the early 1980s out of Australia and the United Kingdom, both of which have had serious temazepam abuse epidemics and related mortality, have all mostly corroborated each other and proven that the potential for abuse and physical dependence is very high, even in comparison to many other benzodiazepines. As a result, prescriptions for hypnotics such as temazepam have seen a dramatic decrease since 2010, while anxiolytics such as alprazolam (Xanax), clonazepam (Rivitrol, Klonopin), and lorazepam (Ativan) have increased or remained stable. Temazepam and similar hypnotics, such as triazolam (Halcion) are generally reserved for severe and debilitating insomnia. They have largely been replaced by z-drugs (zopiclone, zolpidem) and atypical antidepressants (trazodone, mirtazapine) as first line treatment for insomnia. Even when a benzodiazepine is required, in many cases, smaller doses of anxiolytics such as diazepam (Valium) or alprazolam (Xanax) are recommended over hypnotic agents.Common side effects include drowsiness, motor and cognitive impairment, lethargy, confusion, euphoria, and dizziness. Serious side effects may include hallucinations, hypotension, respiratory depression, abuse, anaphylaxis, and suicide. Use is generally not recommended together with alcohol or opioids. If the dose is rapidly decreased withdrawal may occur. Use during pregnancy or breastfeeding is not recommended. Temazepam is a short-acting benzodiazepine and hypnotic. It works by affecting GABA within the brain.Temazepam was patented in 1962 and came into medical use in 1969. It is available as a generic medication. In 2019, it was the 214th most commonly prescribed medication in the United States, with more than 2 million prescriptions. Medical uses In sleep laboratory studies, temazepam significantly decreased the number of nightly awakenings, but has the drawback of distorting the normal sleep pattern. It is officially indicated for severe insomnia and other severe or disabling sleep disorders. The prescribing guidelines in the UK limit the prescribing of hypnotics to two to four weeks due to concerns of tolerance and dependence.The American Academy of Sleep Medicines 2017 clinical practice guidelines recommended the use of temazepam in the treatment of sleep-onset and sleep-maintenance insomnia. It rated the recommendation as weak, the quality of evidence as moderate, and concluded that the potential benefits outweighed the potential harms. The guidelines found that temazepam at a dose of 15 mg reduces sleep latency by 37 minutes (95% CI 21 to 53 minutes), increases total sleep time by 99 minutes (95% CI 63 to 135 minutes), and provides a small improvement to sleep quality. The improvements in sleep latency and total sleep time were numerically much greater than any of the other included sleep medications, including eszopiclone, zopiclone, zolpidem, triazolam, estazolam, quazepam, flurazepam, trazodone, diphenhydramine, gabapentin, among others.The United States Air Force uses temazepam as one of the hypnotics approved as a "no-go pill" to help aviators and special-duty personnel sleep in support of mission readiness. "Ground tests" are necessary prior to required authorization being issued to use the medication in an operational situation, and a 12-hour restriction is imposed on subsequent flight operation. The other hypnotics used as "no-go pills" are zaleplon and zolpidem, which have shorter mandatory recovery periods. Available forms Temazepam is available in the form of 7.5, 15, 22.5, and 30 mg oral capsules in North America (Canada and United States). Although banned in some European countries (Norway, Sweden), it is available in most other European countries and the rest of the world, including in Australia and New Zealand, as 5, 10, 15 and 20 mg tablets or capsules. Contraindications Use of temazepam should be avoided, when possible, in individuals with these conditions: Ataxia (gross lack of coordination of muscle movements) Severe hypoventilation Acute narrow-angle glaucoma Severe hepatic deficiencies (hepatitis and liver cirrhosis decrease elimination by a factor of two) Severe renal deficiencies (e.g. patients on dialysis) Sleep apnea Severe depression, particularly when accompanied by suicidal tendencies Acute intoxication with alcohol, narcotics, or other psychoactive substances Myasthenia gravis (autoimmune disorder causing muscle weakness) Hypersensitivity or allergy to any drug in the benzodiazepine class Special caution needed Temazepam should not be used in pregnancy, as it may cause harm to the fetus. The safety and effectiveness of temazepam has not been established in children; therefore, temazepam should generally not be given to individuals under 18 years of age, and should not be used at all in children under six months old. Benzodiazepines also require special caution if used in the elderly, alcohol- or drug-dependent individuals, and individuals with comorbid psychiatric disorders.Temazepam, similar to other benzodiazepines and nonbenzodiazepine hypnotic drugs, causes impairments in body balance and standing steadiness in individuals who wake up at night or the next morning. Falls and hip fractures are frequently reported. The combination with alcohol increases these impairments. Partial but incomplete tolerance develops to these impairments. The smallest possible effective dose should be used in elderly or very ill patients, as a risk of apnea and/or cardiac arrest exists. This risk is increased when temazepam is given concomitantly with other drugs that depress the central nervous system (CNS). Misuse and dependence Because benzodiazepines can be abused and lead to dependence, their use should be avoided in people in certain particularly high-risk groups. These groups include people with a history of alcohol or drug dependence, people significantly struggling with their mood or people with longstanding mental health difficulties. If temazepam must be prescribed to people in these groups, they should generally be monitored very closely for signs of misuse and development of dependence. Adverse effects In September 2020, the U.S. Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class. Common Side effects typical of hypnotic benzodiazepines are related to CNS depression, and include somnolence, sedation, dizziness, fatigue, ataxia, headache, lethargy, impairment of memory and learning, longer reaction time and impairment of motor functions (including coordination problems), slurred speech, decreased physical performance, numbed emotions, reduced alertness, muscle weakness, blurred vision (in higher doses), and inattention. Euphoria was rarely reported with its use. According to the U.S. Food and Drug Administration, temazepam had an incidence of euphoria of 1.5%, much more rarely reported than headaches and diarrhea. Anterograde amnesia may also develop, as may respiratory depression in higher doses. A 2009 meta-analysis found a 44% higher rate of mild infections, such as pharyngitis or sinusitis, in people taking Temazepam or other hypnotic drugs compared to those taking a placebo. Less common Hyperhydrosis, hypotension, burning eyes, increased appetite, changes in libido, hallucinations, faintness, nystagmus, vomiting, pruritus, gastrointestinal disturbances, nightmares, palpitation and paradoxical reactions including restlessness, aggression, violence, overstimulation and agitation have been reported, but are rare (less than 0.5%). Before taking temazepam, one should ensure that at least 8 hours are available to dedicate to sleep. Failing to do so can increase the side effects of the drug. Like all benzodiazepines, the use of this drug in combination with alcohol potentiates the side effects, and can lead to toxicity and death. Though rare, residual "hangover" effects after night-time administration of temazepam occasionally occur. These include sleepiness, impaired psychomotor and cognitive functions which may persist into the next day, impaired driving ability, and possible increased risks of falls and hip fractures, especially in the elderly. Tolerance Chronic or excessive use of temazepam may cause drug tolerance, which can develop rapidly, so this drug is not recommended for long-term use. In 1979, the Institute of Medicine (USA) and the National Institute on Drug Abuse stated that most hypnotics lose their sleep-inducing properties after about three to 14 days. In use longer than one to two weeks, tolerance will rapidly develop towards the ability of temazepam to maintain sleep, resulting in a loss of effectiveness. Some studies have observed tolerance to temazepam after as little as one weeks use. Another study examined the short-term effects of the accumulation of temazepam over seven days in elderly inpatients, and found little tolerance developed during the accumulation of the drug. Other studies examined the use of temazepam over six days and saw no evidence of tolerance. A study in 11 young male subjects showed significant tolerance occurs to temazepams thermoregulatory effects and sleep inducing properties after one week of use of 30-mg temazepam. Body temperature is well correlated with the sleep-inducing or insomnia-promoting properties of drugs.In one study, the drug sensitivity of people who had used temazepam for one to 20 years was no different from that of controls. An additional study, in which at least one of the authors is employed by multiple drug companies, examined the efficacy of temazepam treatment on chronic insomnia over three months, and saw no drug tolerance, with the authors even suggesting the drug might become more effective over time.Establishing continued efficacy beyond a few weeks can be complicated by the difficulty in distinguishing between the return of the original insomnia complaint and withdrawal or rebound related insomnia. Sleep EEG studies on hypnotic benzodiazepines show tolerance tends to occur completely after one to four weeks with sleep EEG returning to pretreatment levels. The paper concluded that due to concerns about long-term use involving toxicity, tolerance and dependence, as well as to controversy over long-term efficacy, wise prescribers should restrict benzodiazepines to a few weeks and avoid continuing prescriptions for months or years. A review of the literature found the nonpharmacological treatment options were a more effective treatment option for insomnia due to their sustained improvements in sleep quality. Physical dependence Temazepam, like other benzodiazepine drugs, can cause physical dependence and addiction. Withdrawal from temazepam or other benzodiazepines after regular use often leads to benzodiazepine withdrawal syndrome, which resembles symptoms during alcohol and barbiturate withdrawal. The higher the dose and the longer the drug is taken, the greater the risk of experiencing unpleasant withdrawal symptoms. Withdrawal symptoms can also occur from standard dosages and after short-term use. Abrupt withdrawal from therapeutic doses of temazepam after long-term use may result in a severe benzodiazepine withdrawal syndrome. Gradual and careful reduction of the dosage, preferably with a long-acting benzodiazepine with long half-life active metabolites, such as chlordiazepoxide or diazepam, are recommended to prevent severe withdrawal syndromes from developing. Other hypnotic benzodiazepines are not recommended. A study in rats found temazepam is cross tolerant with barbiturates and is able to effectively substitute for barbiturates and suppress barbiturate withdrawal signs. Rare cases are reported in the medical literature of psychotic states developing after abrupt withdrawal from benzodiazepines, even from therapeutic doses. Antipsychotics increase the severity of benzodiazepine withdrawal effects with an increase in the intensity and severity of convulsions. Patients who were treated in the hospital with temazepam or nitrazepam have continued taking these after leaving the hospital. Hypnotic uses in the hospital were recommended to be limited to five nights use only, to avoid the development of withdrawal symptoms such as insomnia. Interactions As with other benzodiazepines, temazepam produces additive CNS-depressant effects when coadministered with other medications which themselves produce CNS depression, such as barbiturates, alcohol, opiates, tricyclic antidepressants, nonselective MAO inhibitors, phenothiazines and other antipsychotics, skeletal muscle relaxants, antihistamines, and anaesthetics. Administration of theophylline or aminophylline has been shown to reduce the sedative effects of temazepam and other benzodiazepines. Unlike many benzodiazepines, pharmacokinetic interactions involving the P450 system have not been observed with temazepam. Temazepam shows no significant interaction with CYP3A4 inhibitors (e.g. itraconazole, erythromycin). Oral contraceptives may decrease the effectiveness of temazepam and speed up its elimination half-life. Overdose Overdosage of temazepam results in increasing CNS effects, including: Somnolence (difficulty staying awake) Mental confusion Respiratory depression Hypotension Impaired motor functions Impaired or absent reflexes Impaired coordination Impaired balance Dizziness, sedation Coma DeathTemazepam had the highest rate of drug intoxication, including overdose, among common benzodiazepines in cases with and without combination with alcohol in a 1985 study. Temazepam and nitrazepam were the two benzodiazepines most commonly detected in overdose-related deaths in an Australian study of drug deaths. A 1993 British study found temazepam to have the highest number of deaths per million prescriptions among medications commonly prescribed in the 1980s (11.9, versus 5.9 for benzodiazepines overall, taken with or without alcohol).A 1995 Australian study of patients admitted to hospital after benzodiazepine overdose corroborated these results, and found temazepam overdose much more likely to lead to coma than other benzodiazepines (odds ratio 1.86). The authors noted several factors, such as differences in potency, receptor affinity, and rate of absorption between benzodiazepines, could explain this higher toxicity. Although benzodiazepines have a high therapeutic index, temazepam is one of the more dangerous of this class of drugs. The combination of alcohol and temazepam makes death by alcohol poisoning more likely. Pharmacology Pharmacodynamics The main pharmacological action of temazepam is to increase the effect of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABAA receptor. This causes sedation, motor impairment, ataxia, anxiolysis, an anticonvulsant effect, muscle relaxation, and a reinforcing effect.As a medication before surgery, temazepam decreased cortisol in elderly patients. In rats, it triggered the release of vasopressin into paraventricular nucleus of the hypothalamus and decreased the release of ACTH under stress. Pharmacokinetics Oral administration of 15 to 45 mg of temazepam in humans resulted in rapid absorption with significant blood levels achieved in fewer than 30 minutes and peak levels at two to three hours.In a single- and multiple-dose absorption, distribution, metabolism, and excretion (ADME) study, using tritium-labelled drug, temazepam was well absorbed and found to have minimal (8%) first-pass drug metabolism. No active metabolites were formed and the only significant metabolite present in blood was the O-conjugate. The unchanged drug was 96% bound to plasma proteins. The blood-level decline of the parent drug was biphasic, with the short half-life ranging from 0.4 to 0.6 hours and the terminal half-life from 3.5 to 18.4 hours (mean 8.8 hours), depending on the study population and method of determination.Temazepam has very good bioavailability, with almost 100% being absorbed following being taken by mouth. The drug is metabolized through conjugation and demethylation prior to excretion. Most of the drug is excreted in the urine, with about 20% appearing in the faeces. The major metabolite was the O-conjugate of temazepam (90%); the O-conjugate of N-desmethyl temazepam was a minor metabolite (7%). Chemistry Temazepam is a benzodiazepine. It is a white, crystalline substance, very slightly soluble in water, and sparingly soluble in alcohol. Synthesis Pharmacologically active metabolite of diazepam, q.v. N-oxides are prone to undergo the Polonovski rearrangement when treated with acetic anhydride, and this was illustrated by the synthesis of oxazepam. It is not surprising that the N-methyl analogue (1) also undergoes this process, and hydrolysis of the resulting acetate gives temazepam (2). Care must be exacted with the conditions, or the inactive rearrangement product (3) results. History Temazepam was synthesized in 1964, but it came into use in 1981 when its ability to counter insomnia was realized. By the late 1980s, temazepam was one of the most popular and widely prescribed hypnotics on the market and it became one of the most widely prescribed drugs. Society and culture Recreational use Temazepam is a drug with a high potential for misuse.Benzodiazepines have been abused orally and intravenously. Different benzodiazepines have different abuse potential; the more rapid the increase in the plasma level following ingestion, the greater the intoxicating effect and the more open to abuse the drug becomes. The speed of onset of action of a particular benzodiazepine correlates well with the popularity of that drug for abuse. The two most common reasons for preference were that a benzodiazepine was strong and that it gave a good high.A 1995 study found that temazepam is more rapidly absorbed and oxazepam is more slowly absorbed than most other benzodiazepines.A 1985 study found that temazepam and triazolam maintained significantly higher rates of self-injection than a variety of other benzodiazepines. The study tested and compared the abuse liability of temazepam, triazolam, diazepam, lorazepam, oxazepam, flurazepam, alprazolam, chlordiazepoxide, clonazepam, nitrazepam, flunitrazepam, bromazepam, and clorazepate. The study tested self-injection rates on human, baboon, and rat subjects. All test subjects consistently showed a strong preference for temazepam and triazolam over all the rest of the benzodiazepines included in the study. North America In North America, temazepam misuse is not widespread. Other benzodiazepines are more commonly prescribed for insomnia. In the United States, temazepam is the fifth-most prescribed benzodiazepine, however there is a major drop off from the top four most prescribed (alprazolam, lorazepam, diazepam, and clonazepam in that order). Individuals abusing benzodiazepines obtain the drug by getting prescriptions from several doctors, forging prescriptions, or buying diverted pharmaceutical products on the illicit market. North America has never had a serious problem with temazepam misuse, but is becoming increasingly vulnerable to the illicit trade of temazepam. Australia Temazepam is a Schedule 4 drug and requires a prescription. The drug accounts for most benzodiazepine sought by forgery of prescriptions and through pharmacy burglary in Victoria. Due to rife intravenous abuse, the Australian government decided to put it under a more restrictive schedule than it had been, and since March 2004 temazepam capsules have been withdrawn from the Australian market, leaving only 10 mg tablets available.Benzodiazepines are commonly detected by Customs at different ports and airports, arriving by mail, also found occasionally in the baggage of air passengers, mostly small or medium quantities (up to 200–300 tablets) for personal use. From 2003 to 2006, customs detected about 500 illegal importations of benzodiazepines per year, most frequently diazepam. Quantities varied from single tablets to 2,000 tablets. United Kingdom In 1987, temazepam was the most widely abused legal prescription drug in the United Kingdom. The use of benzodiazepines by street-drug abusers was part of a polydrug abuse pattern, but many of those entering treatment facilities were declaring temazepam as their main drug of abuse. Temazepam was the most commonly used benzodiazepine in a study, published 1994, of injecting drug users in seven cities, and had been injected from preparations of capsules, tablets, and syrup. The increase in use of heroin, often mixed with other drugs, which most often included temazepam, diazepam, and alcohol, was a major factor in the increase in drug-related deaths in Glasgow and Edinburgh in 1990–1992. Temazepam use was particularly associated with violent or disorderly behaviours and contact with the police in a 1997 study of young single homeless people in Scotland. The BBC series Panorama featured an episode titled "Temazepam Wars", dealing with the epidemic of temazepam abuse and directly related crime in Paisley, Scotland. The trend was mocked in the 1995 Black Grape song "Temazi Party" (also called "Tramazi Party"). Medical research issues The Journal of Clinical Sleep Medicine published a paper expressing concerns about benzodiazepine receptor agonist drugs, the benzodiazepines and the Z-drugs used as hypnotics in humans. The paper cites a systematic review of the medical literature concerning insomnia medications and states almost all trials of sleep disorders and drugs are sponsored by the pharmaceutical industry, while this is not the case in general medicine or psychiatry. It cites another study that "found that the odds ratio for finding results favorable to industry in industry-sponsored trials was 3.6 times as high as in non–industry-sponsored studies". Issues discussed regarding industry-sponsored studies include: comparison of a drug to a placebo, but not to an alternative treatment; unpublished studies with unfavorable outcomes; and trials organized around a placebo baseline followed by drug treatment, but not counterbalanced with parallel-placebo-controlled studies. Quoting a 1979 report that too little research into hypnotics was independent of the drug manufacturers, the authors conclude, "the public desperately needs an equipoised assessment of hypnotic benefits and risks" and the NIH and VA should provide leadership to that end. Street terms Street terms for temazepam include king kong pills (formerly referred to barbiturates, now more commonly refers to temazepam), jellies, jelly, Edinburgh eccies, tams, terms, mazzies, temazies, tammies, temmies, beans, eggs, green eggs, wobbly eggs, knockouts, hardball, norries, oranges (common term in Australia and New Zealand), rugby balls, ruggers, terminators, red and blue, no-gos, num nums, blackout, green devils, drunk pills, brainwash, mind erasers, neurotrashers, tem-tems (combined with buprenorphine), mommys big helper, vitamin T, big T, TZ, the mazepam, resties (North America) and others. Availability Temazepam is available in English-speaking countries under the following brand names: Euhypnos Normison Norkotral Nortem Remestan Restoril Temaze Temtabs In Spain, the drug is sold as temzpem. In Hungary the drug is sold as Signopam. Legal status In Austria, temazepam is listed in UN71 Schedule III under the Psychotropic Substances Decree of 1997. The drug is considered to have a high potential for abuse and addiction, but has accepted medical use for the treatment of severe insomnia.In Australia, temazepam is a Schedule 4 - Prescription Only medicine. It is primarily used for the treatment of insomnia, and is also seen as pre-anaesthetic medication.In Canada, temazepam is a Schedule IV controlled substance requiring a registered doctors prescription.In Denmark, temazepam is listed as a Class D substance under the Executive Order 698 of 1993 on Euphoric Substances which means it has a high potential for abuse, but is used for medical and scientific purposes.In Finland, temazepam is more tightly controlled than other benzodiazepines. The temazepam product Normison was pulled out of shelves and banned because the liquid inside gelatin capsules had caused a large increase in intravenous temazepam use. The other temazepam product, Tenox, was not affected and remains as prescription medicine. Temazepam intravenous use has not decreased to the level before Normison came to the market.In France, temazepam is listed as a psychotropic substance as are other similar drugs. It is prescribed with a nonrenewable prescription (a new doctor visit every time), available only in 7 or 14-pill packaging for one or two weeks. One brand was withdrawn from the market in 2013.In Hong Kong, temazepam is regulated under Schedule 1 of Hong Kongs Chapter 134 Dangerous Drugs Ordinance. Temazepam can only be used legally by health professionals and for university research purposes. The substance can be given by pharmacists under a prescription. Anyone who supplies the substance without prescription can be fined HKD$10,000. The penalty for trafficking or manufacturing the substance is a $5,000,000-fine and life imprisonment. Possession of the substance for consumption without license from the Department of Health is illegal with a $1,000,000-fine and/or seven years of jail time.In Ireland, temazepam is a Schedule 3 controlled substance with strict restrictions.In the Netherlands, temazepam is available for prescription as 10- or 20-mg tablets and capsules. Formulations of temazepam containing less than 20 mg are included in List 2 of the Opium Law, while formulations containing 20 mg or more of the drug (along with the gel-capsules) are a List 1 substance of the Opium Law, thus subject to more stringent regulation. Besides being used for insomnia, it is also occasionally used as a preanesthetic medication.In Norway, temazepam is not available as a prescription drug. It is regulated as a Class A substance under Norways Narcotics Act.In Portugal, temazepam is a Schedule IV controlled drug under Decree-Law 15/93.In Singapore, temazepam is a Class A controlled drug (Schedule I), making it illegal to possess and requiring a private prescription from a licensed physician to be dispensed. In Slovenia, it is regulated as a Group II (Schedule 2) controlled substance under the Production and Trade in Illicit Drugs Act.In South Africa, temazepam is a Schedule 5 drug, requiring a special prescription, and is restricted to 10– to 30-mg doses.In Sweden, temazepam is classed as a "narcotic" drug listed as both a List II (Schedule II) which denotes it is a drug with limited medicinal use and a high risk of addiction, and is also listed as a List V (Schedule V) substance which denotes the drug is prohibited in Sweden under the Narcotics Drugs Act (1968). Temazepam is banned in Sweden and possession and distribution of even small amounts is punishable by a prison sentence and a fine.In Switzerland, temazepam is a Class B controlled substance, like all other benzodiazepines. This means it is a prescription-only drug.In Thailand, temazepam is a Schedule II controlled drug under the Psychotropic Substances Act. Possession and distribution of the drug is illegal. In the United Kingdom, temazepam is a Class C controlled drug under the Misuse of Drugs Act 1971 (Schedule 3 under the Misuse of Drugs Regulations 2001). If prescribed privately (not on the NHS), temazepam is available only by a special controlled drug prescription form (FP10PCD) and pharmacies are obligated to follow special procedures for storage and dispensing. Additionally, all manufacturers in the UK have replaced the gel-capsules with solid tablets. Temazepam requires safe custody and up until June 2015 was exempt from CD prescription requirements. In the United States, Temazepam is currently a Schedule IV drug under the international Convention on Psychotropic Substances of 1971 and is only available by prescription. Specially coded prescriptions may be required in certain states. References External links "Temazepam". Drug Information Portal. U.S. National Library of Medicine. Temazepam | Inchem Panorama document - 1995 - YouTube video

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I'm curious about the meaning of the medical term 'Megalencephaly.' Can you give me some insights?

Megalencephaly (or macrencephaly; abbreviated MEG) is a growth development disorder in which the brain is abnormally large. It is characterized by a brain with an average weight that is 2.5 standard deviations above the mean of the general population. Approximately 1 out of 50 children (2%) are said to have the characteristics of megalencephaly in the general population.A mutation in the PI3K-AKT pathway is believed to be the primary cause of brain proliferation and ultimately the root cause of megalencephaly. This mutation has produced a classification of brain overdevelopment that consists of two syndromes including megalencephaly-capillary malformation (MCAP) and megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH). Megalencephaly is usually diagnosed at birth and is confirmed with an MRI. There are several neuropsychiatric disorders linked with megalencephaly; however, studies have shown that autism is the most prevalent association with the malformation of MEG. Although no treatment currently exists for megalencephaly, management methods are focused at reducing deficits linked with autism. Most recent research is targeted at creating inhibitors to reduce the mutational pathway that causes megalencephaly. Classification Macrocephaly Macrocephaly is a term used to refer to a person who has an abnormally large head. The circumference of the head must be above the 95th percentile or at least 2.5 standard deviations from the mean of normal weight and gender groups in the United States. A person with macrocephaly does not necessarily indicate that megalencephaly is also present. Large skulls usually exhibit no neurodevelopment conditions at all, meaning most individuals with macrocephaly are healthy. Hemimegalencephaly Hemimegalencephaly is an extremely rare form of macrocephaly and is characterized by uneven development of brain hemispheres (one-half of brain is larger than other). The syndrome can be presented by itself or in association with phakomatosis or hemigigantism. Additionally, hemimegalencephaly will frequently cause severe epilepsy, focal neuro-logical deficits, macrocrania, and mild to severe intellectual disability. MCAP Megalencephaly-capillary (MCAP) is one of the two major syndromes of megalencephaly. Typically, MCAP and MPPH can be distinguished by somatic features. MCAP includes many characteristics that are observed at birth including: cutaneous vascular malformations, especially capillary malformations of the face and cutis marmorata, polydactyly, connective tissue dysplasia, and focal or segmental body overgrowth. Furthermore, MCAP can occasionally be linked with asymmetric brain overgrowth (hemimegalencephaly) as well as segmental overgrowth of the body (hemihypertrophy). MPPH Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) is one of the two major syndromes contributing to megalencephaly. Typically MCAP and MPPH can be distinguished by somatic features. In differentiation to MCAP, MPPH lacks consistent somatic features other than postaxial polydactyly. Furthermore, brain and body development is normally symmetric in the majority of patients that appear to have MPPH symptoms. Presentation Autism There is an extremely high association between megalencephaly and autism. Approximately 20% of autistic children have megalencephaly, making it the most common physical characteristic of autism. People who present both megalencephaly and autistic characteristics usually also show signs of hyperactivity as a major symptom. However, there is no definitive evidence that autism is the primary cause/result of megalencephaly.Since most children with megalencephaly also have autism, the goal of treatment for MEG is focused on managing the signs and symptoms associated with autism. Other associations Achondroplasia Beckwith–Wiedemann syndrome Neurofibromatosis type I (NF1) Tuberous sclerosis (TS) Klippel–Trénaunay syndrome Epidermal nevus syndrome Causes Although very little is still known as to the direct cause of megalencephaly, recent studies have begun to provide early indications of possible sources for its formation. Recent research has shown that there is a strong link between genetic pathways that cause brain develop and mutations in that pathway that result in brain overgrowth. PI3K-AKT Recent studies have shown that mutations in phosphoinositide 3-kinase (PI3K) and AKT (also known as protein kinase B) pathway have been identified in MCAP and MPPH. This pathway has proven to be an integral part of brain growth and development and is an area of interest to many researchers who study the cause of megalencephaly. Mutations in this pathway have been shown to cause a gain of function in the activation of the PI3K-AKT pathway. This cellular pathway is critical in the regulation of diverse cell functions including, cell growth, proliferation, metabolism, survival, apoptosis, angiogenesis, tumorigenesis and most importantly in regards to megalencephaly, brain development. AKT is a crucial signaling molecule part of the PI3K pathway and is also involved in many cellular functions. These functions include, brain development, synaptic plasticity and neurodevelopment. Loss of function in AKT can cause microcephaly in humans while inactivation of the pathway can cause hemimegalencephaly. There are also several cancers that have been shown to be linked with mutations in the AKT pathway, including melanoma and lung cancer. Pur-alpha Pur-alpha (purα) is a sequence-specific single-stranded DNA and RNA-binding protein. Studies have shown that the protein is primarily active during early development and is believed to have a role in brain enlargement. Although the exact function is still controversial, it is believed that pur-alpha is responsible for neuronal proliferation during neurogenesis as well as the maturation of dendrites. Thus, pur-alpha is also considered a potential root cause of megalencephaly and brain overgrowth. Pathophysiology One impact of megalencephaly is the complete lack of motor development. One medical study assessed three patients presenting megalencephaly who showed severely impaired motor and speech development as well as distinct facial abnormalities including skull bossing, a low nasal bridge and large eyes. Diagnoses Diagnosis of megalencephaly has changed over the years, however, with the development of more advanced equipment, physicians have been able to confirm the disorder with better accuracy. Usually, a physical exam is first performed when characteristics of megalencephaly have appeared. This typically occurs at birth or during early child development. A physician will then take head measurements in order to determine the circumference. This is known as the head circumference. Then a family background will be recorded in order to determine if there has been a history of megalencephaly in the family.A neurological exam will then be performed using the technology of an MRI machine in order to confirm the diagnosis of megalencephaly. These imaging tests give detailed information regarding brain size, volume asymmetry and other irregular developments linked with MCAP, MPPH and hemimegalencephaly.There is also a strong correlation of epilepsy and megalencephaly and this can aid doctors in their diagnosis.If a diagnosis of megalencephaly is confirmed, the child is referred to a specialist who focuses on managing the symptoms and improving lifestyle. Since megalencephaly is usually presented with autism, the goal of treatment is to improve deficiencies associated with autistic causes. Additionally, since each patient has unique symptoms, there is no one specific treatment method and therefore is heavily reliant on symptoms associated with an individual. Prevention Since there are very few treatment methods focused on managing megalencephaly, future research is targeted at inhibiting mutation of the pathway. However, this next step could be met with several complications as understanding the underlying mechanism of the mutation is a difficult task. The genetic coding that initiates a single mutation is sporadic and patterns are hard to detect in many cases. Even though very little research has been done to create inhibitors of the PI3K-AKT pathway, several pharmaceutical companies have begun to focus their interests in designing a prevention method for this purpose. Treatment There is currently no specific treatment for megalencephaly, however periodic head measurements may be assessed to determine the rate of brain growth. Those individuals who develop neurological disorders may be prescribed anti-epileptic drugs for seizures. Studies have shown that reducing epilepsy can increase cell apoptosis and reduce the proliferation of neurons that ultimately leads to brain overgrowth. Prognosis The prognosis of megalencephaly depends heavily on the underlying cause and associated neurological disorders. Because the majority of megalencephaly cases are linked with autism, the prognosis is equivalent to the corresponding condition. Since hemimegalencephaly is associated with severe seizures, hemiparesis and intellectual disability, the result is a poor prognosis. In most cases, those diagnosed with this type of megalencephaly usually do not survive through adulthood. Epidemiology Approximately one out of every 50 (2%) children in the general population are said to have megalencephaly. Additionally, it is said that megalencephaly affects 3–4 times more males than females. Those individuals that are classified with macrocephaly, or general head overgrowth, are said to have megalencephaly at a rate of 10–30% of the time. History It is believed that megalencephaly was discovered in 1972. Prior to diagnoses that used MRI scanning as a way to confirm brain overgrowth, cases of megalencephaly were diagnosed by autopsy in which the physical brain was measured and weighed. Research Future research is targeted at further understanding mutations and how they lead to MCAP and MPPH syndromes. The majority of studies of megalencephaly have included mice who present brain abnormalities and overgrowth. The next step is to move to clinical trials involving humans in order to determine the exact genetic mutation causing the sequences. Additionally, scientists and pharmaceutical companies have begun to show interest in mutation inhibition and designing preventative methods to eliminate the underlying cause of megalencephaly altogether. Other relations Intracranial volume also affects this pathology, since it is related with the size of the brain. References External links Megalencephaly information page (provided by National Institute of Neurological Disorders and Stroke)

You function as a medical explainer. Your task is to convey the meanings of medical terms in a detailed, yet easy-to-understand manner.

What does the medical term 'Vaginal disease' encompass?

A vaginal disease is a pathological condition that affects part or all of the vagina. Types Sexually transmitted infections Sexually transmitted disease that affect the vagina include: Herpes genitalis. The herpes simplex virus (HSV) can infect the vulva, vagina, and cervix, and this may result in small, painful, recurring blisters and ulcers. It is also common for there to be an absence of any noticeable symptoms. Gonorrhea Chlamydia Trichomoniasis Human papillomavirus (HPV), which may cause genital warts.Because of STIs, health authorities and other health outlets recommend safe sex practices when engaging in sexual activity. Other infectious diseases Candidal vulvovaginitis Bacterial vaginosis (BV) associated with the Gardnerella, formerly called "nonspecific vaginitis" Vaginismus Vaginismus, which is not the same thing as vaginitis (an inflammation of the vagina), is an involuntary tightening of the vagina due to a conditioned reflex of the muscles in the area during vaginal penetration. It can affect any form of vaginal penetration, including sexual intercourse, insertion of tampons and menstrual cups, and the penetration involved in gynecological examinations. Various psychological and physical treatments are possible to help alleviate it. Obstruction A vaginal obstruction is often caused by an imperforate hymen or, less commonly, a transverse vaginal septum. A sign of vaginal obstruction is hydrocolpos, that is, accumulation of watery fluid within the vagina. It may extend to become hydrometrocolpos, that is, accumulation of watery fluid within the vagina as well as within the uterus. Hypoplasia Vaginal hypoplasia is the underdevelopment or incomplete development of the vagina. Vaginal hypoplasia can vary in severity from being smaller than normal to being completely absent. The absence of a vagina is a result of vaginal agenesis. Diagnostically, it may look similar to a vaginal obstruction. It is frequently associated with Mayer-Rokitansky-Küstner-Hauser (MRKH) syndrome, in which the most common result is an absent uterus in conjunction with a deformed or missing vagina, despite the presence of normal ovaries and normal external genitalia. It is also associated with cervical agenesis, in which the uterus is present but the uterine cervix is absent. Lumps The presence of unusual lumps in the wall or base of the vagina is always abnormal. The most common of these is Bartholins cyst. The cyst, which can feel like a pea, is formed by a blockage in glands which normally supply the opening of the vagina. This condition is easily treated with minor surgery or silver nitrate. Other less common causes of small lumps or vesicles are herpes simplex. They are usually multiple and very painful with a clear fluid leaving a crust. They may be associated with generalized swelling and are very tender. Lumps associated with cancer of the vaginal wall are very rare and the average age of onset is seventy years. The most common form is squamous cell carcinoma, then cancer of the glands or adenocarcinoma and finally, and even more rarely, vaginal melanoma. Persistent genital arousal disorder Persistent genital arousal disorder (PGAD), which results in a spontaneous, persistent, and uncontrollable genital arousal, with or without orgasm, unrelated to any feelings of sexual desire. Because PGAD is relatively rare and, as its own concept apart from clitoral priapism (a rare, potentially painful medical condition in which, for an unusually extended period of time, the erect clitoris does not return to its relaxed state), has only been researched since 2001, there is little research into what may cure or remedy the disorder. In some recorded cases, PGAD was caused by, or caused, a pelvic arterial-venous malformation with arterial branches to the clitoris; surgical treatment was effective in these cases. Other Vulvodynia Vaginal prolapse may result in the case of weakened pelvic muscles, which is a common result of childbirth; in the case of this prolapse, the rectum, uterus, or bladder pushes on the vagina, and severe cases result in the vagina protruding out of the body. Kegel exercises have been used to strengthen the pelvic floor, and may help prevent or remedy vaginal prolapse. Cervical cancer (may be prevented by Pap smear screening and HPV vaccines) Vaginal cancer is very rare, but its symptoms include abnormal vaginal bleeding or vaginal discharge. Air embolism is a potentially fatal condition where an air bubble travels throughout the bloodstream and can obstruct a vessel. It can result if air is blown into a pregnant womans vagina during cunnilingus; this is because pregnant women have an increased vascularity of the vagina and uterus, and an air embolism can force air into the uterine veins. Symptoms Discharge Most vaginal discharges occur due to normal bodily functions, such as menstruation or sexual arousal (vaginal lubrication). Abnormal discharges, however, can indicate disease. Normal vaginal discharges include blood or menses (from the uterus), the most common, and clear fluid either as a result of sexual arousal or secretions from the cervix. Other non-infective causes include dermatitis. Non-sexually transmitted discharges occur from bacterial vaginosis, aerobic vaginitis and thrush or candidiasis. The final group of discharges include the sexually transmitted diseases gonorrhea, chlamydia, and trichomoniasis. The discharge from thrush is slightly pungent and white, that from trichomoniasis more foul and greenish, and that from foreign bodies resembling the discharge of gonorrhea, greyish or yellow and purulent (pus-like). Sores All sores involve a breakdown in the walls of the fine membrane of the vaginal wall. The most common of these are abrasions and small ulcers caused by trauma. While these can be inflicted during rape most are actually caused by excessive rubbing from clothing or improper insertion of a sanitary tampon. The typical ulcer or sore caused by syphilis is painless with raised edges. These are often undetected because they occur mostly inside the vagina. The sores of herpes which occur with vesicles are extremely tender and may cause such swelling that passing urine is difficult. In the developing world, a group of parasitic diseases also cause vaginal ulceration, such as leishmaniasis, but these are rarely encountered in the west. All of the aforementioned local vulvovaginal diseases are easily treated. Often, only shame prevents patients from presenting for treatment. Inflammation Vaginitis an inflammation of the vagina, such as caused by infection, hormone disturbance and irritation/allergy. See also List of bacterial vaginosis microbiota == References ==

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I've encountered the term 'Agoraphobia without history of panic disorder' while reading about medical topics. What does it refer to exactly?

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)

You function as a medical explainer. Your task is to convey the meanings of medical terms in a detailed, yet easy-to-understand manner.

I've come across the term 'Letermovir' in a medical context, but I'm not sure what it means. Can you clarify?

Letermovir (INN; trade name Prevymis) is an antiviral drug for the treatment of cytomegalovirus (CMV) infections. It has been tested in CMV infected patients with allogeneic stem cell transplants and may also be useful for other patients with a compromised immune system such as those with organ transplants or HIV infections. The drug was initially developed by the anti-infective division at Bayer, which became AiCuris Anti-infective Cures AG through a spin-out and progressed the development to end of Phase 2 before the project was sold to Merck & Co for Phase 3 development and approval.The drug was granted fast track status by the US Food and Drug Administration (FDA) and orphan drug status by the European Medicines Agency. It is now approved for prevention of CMV infection and disease in recipients of an allogeneic stem cell transplant.The FDA considers it to be a first-in-class medication. Medical use In the US as well as in the EU, letermovir is used for the prevention of cytomegalovirus infection and disease in adult CMV-seropositive recipients of an allogeneic stem cell transplant. The therapy is started shortly after the transplantation and typically lasts for 100 days. Although letermovir is a relatively new antiviral, CMV resistance has been documented in stem cell transplantation recipients; although rare, breakthrough infections of prophylactic treatment with letermovir underscores the ongoing selective pressure on CMVs viral evolution and its continued ability to evade therapeutic suppression through mutations in critical gene regions such as within the UL56 amplicon. Contraindications Combining the drug with pimozide or ergot alkaloids (such as ergotamine or methylergometrine) is contraindicated because these drugs are metabolized by the liver enzyme CYP3A4, and letermovir inhibits this enzyme. In people who also take ciclosporin, which increases letermovir concentrations in the body, combination with the cholesterol lowering drugs simvastatin and pitavastatin is also contraindicated. In Canada, this also applies to bosentan, lovastatin and rosuvastatin; and in the EU, to dabigatran, atorvastatin, and rosuvastatin. Adverse effects Side effects from the use of letermovir are uncommon, but gastrointestinal symptoms such as gastritis and nausea may occur, as can dyspnea (difficulties breathing) and hepatitis. In general, side effects of the drug are comparable to those under placebo treatment. Overdose In studies, giving the threefold therapeutic dose for 14 days resulted in no additional adverse effects. It is unknown whether the substance can be removed from the system by hemodialysis. Pharmacology Mechanism of action Letermovir is a viral terminase inhibitor. It specifically inhibits the CMV viral terminase complex which is encoded by the CMV genes UL56, UL51 and UL89. This inhibition has the effect of preventing cleavage of CMV DNA concatamers, resulting in long uncleaved DNA and noninfectious viral particles. Letermovir is only active against CMV and has no effect on other herpesviruses. Pharmacokinetics Letermovir is quickly absorbed from the gut, reaching its highest concentrations in the blood plasma after 1.5 to 3 hours. Its bioavailability is estimated to be 37%. Ciclosporin increases this bioavailability to about 85%. When in the bloodstream, the substance is almost completely (98.2%) bound to plasma proteins. It is mostly (96.6%) circulating in its original form; only a small proportion is metabolized by the liver enzymes UGT1A1 and UGT1A3, resulting in a glucuronide.The drug is mainly excreted via the faeces (93.3%). Less than 2% is found in the urine. Chemistry Letermovir is used as the free acid. It is a white to off-white, amorphous powder that is slightly hygroscopic, very slightly soluble in water, and very soluble in acetonitrile, acetone, dimethylacetamide, ethanol, and 2-propanol.The molecule has one asymmetric carbon atom, which is in S configuration. References External links "Letermovir". Drug Information Portal. U.S. National Library of Medicine. "Letermovir Injection". MedlinePlus.

You are an assistant in medical learning. Your role is to clarify medical terminology, ensuring the information is both accurate and accessible.

The term 'Melkersson–Rosenthal syndrome' keeps coming up in medical discussions. What does it stand for?

Melkersson–Rosenthal syndrome is a rare neurological disorder characterized by recurring facial paralysis, swelling of the face and lips (usually the upper lip: cheilitis granulomatosis) and the development of folds and furrows in the tongue (fissured tongue).: 799  Onset is in childhood or early adolescence. After recurrent attacks (ranging from days to years in between), swelling may persist and increase, eventually becoming permanent. The lip may become hard, cracked, and fissured with a reddish-brown discoloration. The cause of Melkersson–Rosenthal syndrome is unknown, but there may be a genetic predisposition. It has been noted to be especially prevalent among certain ethnic groups in Bolivia. It can be symptomatic of Crohns disease or sarcoidosis. Approximately 400 cases have been reported worldwide. Cause Not to be confused with Rosenthal syndrome a.k.a. hemophilia C which is caused by clotting factor XI deficiency. Only genetic causation is established as it is associated with twins and family members. Diagnosis Diagnosis is mainly based on clinical features. However, biopsy has been useful in diagnosis as well as in differentiating between the different types of the disease. Treatment Treatment is symptomatic and may include nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids to reduce swelling, antibiotics and immunosuppressants. Surgery may be indicated to relieve pressure on the facial nerves and reduce swelling, but its efficacy is uncertain. Massage and electrical stimulation may also be prescribed. Prognosis Melkersson–Rosenthal syndrome may recur intermittently after its first appearance. It can become a chronic disorder. Follow-up care should exclude the development of Crohns disease or sarcoidosis. Eponym The condition is named after Ernst Melkersson and Curt Rosenthal. Research The NINDS supports research on neurological disorders such as Melkersson–Rosenthal syndrome. Much of this research is aimed at increasing knowledge of these disorders and finding ways to treat, prevent, and ultimately cure them. See also List of cutaneous conditions References The original version of this article was taken from the public domain source at Melkersson–Rosenthal syndrome at nih.gov == External links ==

You are a resource for medical understanding. Offer detailed explanations of medical terms, making complex concepts clear and comprehensible.

The term 'Advanced sleep phase disorder' keeps coming up in medical discussions. What does it stand for?

Advanced Sleep Phase Disorder (ASPD), also known as the advanced sleep-phase type (ASPT) of circadian rhythm sleep disorder, is a condition that is characterized by a recurrent pattern of early evening (e.g. 7-9 PM) sleepiness and very early morning awakening (e.g. 2-4 AM). This sleep phase advancement can interfere with daily social and work schedules, and results in shortened sleep duration and excessive daytime sleepiness. The timing of sleep and melatonin levels are regulated by the bodys central circadian clock, which is located in the suprachiasmatic nucleus in the hypothalamus. Symptoms Individuals with ASPD report being unable to stay awake until conventional bedtime, falling asleep early in the evening, and being unable to stay asleep until their desired waking time, experiencing early morning insomnia. When someone has advanced sleep phase disorder their melatonin levels and core body temperature cycle hours earlier than an average person. These symptoms must be present and stable for a substantial period of time to be correctly diagnosed. Diagnosis Individuals expressing the above symptoms may be diagnosed with ASPD using a variety of methods and tests. Sleep specialists measure the patients sleep onset and offset, dim light melatonin onset, and evaluate Horne-Ostberg morningness-eveningness questionnaire results. Sleep specialists may also conduct a polysomnography test to rule out other sleep disorders like narcolepsy. Age and family history of the patient is also taken into consideration. Treatment Once diagnosed, ASPD may be treated with bright light therapy in the evenings, or behaviorally with chronotherapy, in order to delay sleep onset and offset. The use of pharmacological approaches to treatment are less successful due to the risks of administering sleep-promoting agents early in the morning. Additional methods of treatment, like timed melatonin administration or hypnotics have been proposed, but determining their safety and efficacy will require further research. Unlike other sleep disorders, ASPD does not necessarily disrupt normal functioning at work during the day and some patients may not complain of excessive daytime sleepiness. Social obligations may cause an individual to stay up later than their circadian rhythm requires, however, they will still wake up very early. If this cycle continues, it can lead to chronic sleep deprivation and other sleep disorders. Epidemiology ASPD is more common among middle and older adults. The estimated prevalence of ASPD is about 1% in middle-age adults, and is believed to affect men and women equally. The disorder has a strong familial tendency, with 40-50% of affected individuals having relatives with ASPD. A genetic basis has been demonstrated in one form of ASPD, familial advanced sleep phase disorder (FASPS), which implicates missense mutations in genes hPER2 and CKIdelta in producing the advanced sleep phase phenotype. The identification of two different genetic mutations suggests that there is heterogeneity of this disorder. Familial advanced sleep phase syndrome FASPS symptoms While advanced sleep and wake times are relatively common, especially among older adults, the extreme phase advance characteristic of familial advanced sleep phase syndrome (also known as familial advanced sleep phase disorder) is rare. Individuals with FASPS fall asleep and wake up 4–6 hours earlier than the average population, generally sleeping from 7:30pm to 4:30am. They also have a free running circadian period of 22 hours, which is significantly shorter than the average human period of slightly over 24 hours. The shortened period associated with FASPS results in a shortened period of activity, causing earlier sleep onset and offset. This means that individuals with FASPS must delay their sleep onset and offset each day in order to entrain to the 24-hour day. On holidays and weekends, when the average persons sleep phase is delayed relative to their workday sleep phase, individuals with FASPS experience further advance in their sleep phase.Aside from the unusual timing of sleep, FASPS patients experience normal quality and quantity of sleep. Like general ASPD, this syndrome does not inherently cause negative impacts, however, sleep deprivation may be imposed by social norms causing individuals to delay sleep until a more socially acceptable time, causing them to losing sleep due to earlier-than-usual wakeup time.Another factor that distinguishes FASPS from other advanced sleep phase disorders is its strong familial tendency and life-long expression. Studies of affected lineages have found that approximately 50% of directly related family members experience the symptoms of FASPS, which is an autosomal dominant trait. Diagnosis of FASPS can be confirmed through genetic sequencing analysis by locating genetic mutations known to cause the disorder. Treatment with sleep and wake scheduling and bright light therapy can be used to try to delay sleep phase to a more conventional time frame, however treatment of FASPS has proven largely unsuccessful. Bright light exposure in the evening (between 7:00 and 9:00), during the delay zone as indicated by the phase response curve to light, has been shown to delay circadian rhythms, resulting in later sleep onset and offset in patients with FASPS or other advanced sleep phase disorders. Discovery In 1999, Louis Ptáček conducted a study at the University of Utah in which he coined the term familial advanced sleep phase disorder after identifying individuals with a genetic basis for an advanced sleep phase. The first patient evaluated during the study reported "disabling early evening sleepiness" and "early morning awakening"; similar symptoms were also reported in her family members. Consenting relatives of the initial patient were evaluated, as well as those from two additional families. The clinical histories, sleep logs and actigraphy patterns of subject families were used to define a hereditary circadian rhythm variant associated with a short endogenous (i.e. internally-derived) period. The subjects demonstrated a phase advance of sleep-wake rhythms that was distinct not only from control subjects, but also to sleep-wake schedules widely considered to be conventional. The subjects were also evaluated using the Horne-Östberg questionnaire, a structured self-assessment questionnaire used to determine morningness-eveningness in human circadian rhythms. The Horne-Östberg scores of first-degree relatives of affected individuals were higher than those of marry-in spouses and unrelated control subjects. While much of morning and evening preference is heritable, the allele causing FASPS was hypothesized to have a quantitatively larger effect on clock function than the more common genetic variations that influence these preferences. Additionally, the circadian phase of subjects was determined using plasma melatonin and body core temperature measurements; these rhythms were both phase-advanced by 3–4 hours in FASPS subjects compared with control subjects. The Ptáček group also constructed a pedigree of the three FASPS kindreds which indicated a clear autosomal dominant transmission of the sleep phase advance.In 2001, the research group of Phyllis C. Zee phenotypically characterized an additional family affected with ASPS. This study involved an analysis of sleep/wake patterns, diurnal preferences (using a Horne-Östberg questionnaire), and the construction of a pedigree for the affected family. Consistent with established ASPS criteria, the evaluation of subject sleep architecture indicated that the advanced sleep phase was due to an alteration of circadian timing rather than an exogenous (i.e. externally-derived) disruption of sleep homeostasis, a mechanism of sleep regulation. Furthermore, the identified family was one in which an ASPS-affected member was present in every generation; consistent with earlier work done by the Ptáček group, this pattern suggests that the phenotype segregates as a single gene with an autosomal dominant mode of inheritance.In 2001, the research groups of Ptáček and Ying-Hui Fu published a genetic analysis of subjects experiencing the advanced sleep phase, implicating a mutation in the CK1-binding region of PER2 in producing the FASPS behavioral phenotype. FASPS is the first disorder to link known core clock genes directly with human circadian sleep disorders. As the PER2 mutation is not exclusively responsible for causing FASPS, current research has continued to evaluate cases in order to identify new mutations that contribute to the disorder. Mechanisms (Per2 and CK1) Two years after reporting the finding of FASPS, Ptáčeks and Fus groups published results of genetic sequencing analysis on a family with FASPS. They genetically mapped the FASPS locus to chromosome 2q where very little human genome sequencing was then available. Thus, they identified and sequenced all the genes in the critical interval. One of these was Period2 (Per2) which is a mammalian gene sufficient for the maintenance of circadian rhythms. Sequencing of the hPer2 gene (h denoting a human strain, as opposed to Drosophila or mouse strains) revealed a serine-to-glycine point mutation in the Casein Kinase I (CK1) binding domain of the hPER2 protein that resulted in hypophosphorylation of hPER2 in vitro. The hypophosphorylation of hPER2 disrupts the transcription-translation (negative) feedback loop (TTFL) required for regulating the stable production of hPER2 protein. In a wildtype individual, Per2 mRNA is transcribed and translated to form a PER2 protein. Large concentrations of PER2 protein inhibits further transcription of Per2 mRNA. CK1 regulates PER2 levels by binding to a CK1 binding site on the protein, allowing for phosphorylation which marks the protein for degradation, reducing protein levels. Once proteins become phosphorylated, PER2 levels decrease again, and Per2 mRNA transcription can resume. This negative feedback regulates the levels and expression of these circadian clock components.Without proper phosphorylation of hPER2 in the instance of a mutation in the CK1 binding site, less Per2 mRNA is transcribed and the period is shortened to less than 24 hours. Individuals with a shortened period due to this phosphorylation disruption entrain to a 24h light-dark cycle, which may lead to a phase advance, causing earlier sleep and wake patterns. However, a 22h period does not necessitate a phase shift, but a shift can be predicted depending on the time the subject is exposed to the stimulus, visualized on a Phase Response Curve (PRC). This is consistent with studies of the role of CK1ɛ (a unique member of the CK1 family) in the TTFL in mammals and more studies have been conducted looking at specific regions of the Per2 transcript. In 2005, Fus and Ptáčeks labs reported discovery of a mutation in CKIδ (a functionally redundant form of CK1ɛ in the phosphorylation process of PER2) also causing FASPS. An A-to-G missense mutation resulted in a threonine-to-alanine alteration in the protein. This mutation prevented the proper phosphorylation of PER2. The evidence for both a mutation in the binding domain of PER2 and a mutation in CKIδ as causes of FASPS is strengthened by the lack of the FASPS phenotype in wild type individuals and by the observed change in the circadian phenotype of these mutant individuals in vitro and an absence of said mutations in all tested control subjects. Fruit flies and mice engineered to carry the human mutation also demonstrated abnormal circadian phenotypes, although the mutant flies had a long circadian period while the mutant mice had a shorter period. The genetic differences between flies and mammals that account for this difference circadian phenotypes are not known. Most recently, Ptáček and Fu reported additional studies of the human Per2 S662G mutation and generation of mice carrying the human mutation. These mice had a circadian period almost 2 hours shorter than wild-type animals under constant darkness. Genetic dosage studies of CKIδ on the Per2 S662G mutation revealed that depending on the binding site on Per2 that CK1δ interacts with, CK1δ may lead to hypo- or hyperphosphorylation of the Per2 gene. See also Delayed sleep phase disorder Irregular sleep–wake rhythm Non-24-hour sleep–wake disorder References == External links ==

You are a medical lexicon. Explain medical terminology with depth and clarity, making sure the information is both accurate and easy to grasp.

I'm not familiar with the medical term 'Healing.' Could you provide some insights?

With physical trauma or disease suffered by an organism, healing involves the repairing of damaged tissue(s), organs and the biological system as a whole and resumption of (normal) functioning. Medicine includes the process by which the cells in the body regenerate and repair to reduce the size of a damaged or necrotic area and replace it with new living tissue. The replacement can happen in two ways: by regeneration in which the necrotic cells are replaced by new cells that form "like" tissue as was originally there; or by repair in which injured tissue is replaced with scar tissue. Most organs will heal using a mixture of both mechanisms.Within surgery, healing is more often referred to as recovery, and postoperative recovery has historically been viewed simply as restitution of function and readiness for discharge. More recently, it has been described as an energy‐requiring process to decrease physical symptoms, reach a level of emotional well‐being, regain functions, and re‐establish activitiesHealing is also referred to in the context of the grieving process.In psychiatry and psychology, healing is the process by which neuroses and psychoses are resolved to the degree that the client is able to lead a normal or fulfilling existence without being overwhelmed by psychopathological phenomena. This process may involve psychotherapy, pharmaceutical treatment or alternative approaches such as traditional spiritual healing. Regeneration In order for an injury to be healed by regeneration, the cell type that was destroyed must be able to replicate. Cells also need a collagen framework along which to grow. Alongside most cells there is either a basement membrane or a collagenous network made by fibroblasts that will guide the cells growth. Since ischaemia and most toxins do not destroy collagen, it will continue to exist even when the cells around it are dead. Example Acute tubular necrosis (ATN) in the kidney is a case in which cells heal completely by regeneration. ATN occurs when the epithelial cells that line the kidney are destroyed by either a lack of oxygen (such as in hypovolemic shock, when blood supply to the kidneys is dramatically reduced), or by toxins (such as some antibiotics, heavy metals or carbon tetrachloride).Although many of these epithelial cells are dead, there is typically patchy necrosis, meaning that there are patches of epithelial cells still alive. In addition, the collagen framework of the tubules remains completely intact.The existing epithelial cells can replicate, and, using the basement membrane as a guide, eventually bring the kidney back to normal. After regeneration is complete, the damage is undetectable, even microscopically.Healing must happen by repair in the case of injury to cells that are unable to regenerate (e.g. neurons). Also, damage to the collagen network (e.g. by enzymes or physical destruction), or its total collapse (as can happen in an infarct) cause healing to take place by repair. Genetics Many genes play a role in healing. For instance, in wound healing, P21 has been found to allow mammals to heal spontaneously. It even allows some mammals (like mice) to heal wounds without scars. The LIN28 gene also plays a role in wound healing. It is dormant in most mammals. Also, the proteins MG53 and TGF beta 1 play important roles in wound healing. Wound healing In response to an incision or wound, a wound healing cascade is unleashed. This cascade takes place in four phases: clot formation, inflammation, proliferation, and maturation. Clotting phase Healing of a wound begins with clot formation to stop bleeding and to reduce infection by bacteria, viruses and fungi. Clotting is followed by neutrophil invasion three to 24 hours after the wound has been incurred, with mitoses beginning in epithelial cells after 24 to 48 hours. Inflammation phase In the inflammatory phase, macrophages and other phagocytic cells kill bacteria, debride damaged tissue and release chemical factors such as growth hormones that encourage fibroblasts, epithelial cells and endothelial cells which make new capillaries to migrate to the area and divide. Proliferative phase In the proliferative phase, immature granulation tissue containing plump, active fibroblasts forms. Fibroblasts quickly produce abundant type III collagen, which fills the defect left by an open wound. Granulation tissue moves, as a wave, from the border of the injury towards the center.As granulation tissue matures, the fibroblasts produce less collagen and become more spindly in appearance. They begin to produce the much stronger type I collagen. Some of the fibroblasts mature into myofibroblasts which contain the same type of actin found in smooth muscle, which enables them to contract and reduce the size of the wound. Maturation phase During the maturation phase of wound healing, unnecessary vessels formed in granulation tissue are removed by apoptosis, and type III collagen is largely replaced by type I. Collagen which was originally disorganized is cross-linked and aligned along tension lines. This phase can last a year or longer. Ultimately a scar made of collagen, containing a small number of fibroblasts is left. Tissue damaged by inflammation After inflammation has damaged tissue (when combatting bacterial infection for example) and pro-inflammatory eicosanoids have completed their function, healing proceeds in 4 phases. Recall phase In the recall phase the adrenal glands increase production of cortisol which shuts down eicosanoid production and inflammation. Resolution phase In the Resolution phase, pathogens and damaged tissue are removed by macrophages (white blood cells). Red blood cells are also removed from the damaged tissue by macrophages. Failure to remove all of the damaged cells and pathogens may retrigger inflammation. The two subsets of macrophage M1 & M2 plays a crucial role in this phase, M1 macrophage being a pro inflammatory while as M2 is a regenerative and the plasticity between the two subsets determine the tissue inflammation or repair. Regeneration phase In the Regeneration phase, blood vessels are repaired and new cells form in the damaged site similar to the cells that were damaged and removed. Some cells such as neurons and muscle cells (especially in the heart) are slow to recover. Repair phase In the Repair phase, new tissue is generated which requires a balance of anti-inflammatory and pro-inflammatory eicosanoids. Anti-inflammatory eicosanoids include lipoxins, epi-lipoxins, and resolvins, which cause release of growth hormones. See also Scar free healing Health References External links How wounds heal and tumors form With this simple Flash demonstration, Harvard professor Donald Ingber explains how wounds heal, why scars form, and how tumors develop. Presented by Childrens Hospital Boston. Wound Healing and Repair Lorenz H.P. and Longaker M.T. Wounds: Biology, Pathology, and Management. Stanford University Medical Center. Romo T. and McLaughlin L.A. 2003. Wound Healing, Skin. Emedicine.com. Rosenberg L. and de la Torre J. 2003. Wound Healing, Growth Factors. Emedicine.com. After the Injury- Childrens Hospital Of Philadelphia

You act as a medical communicator. Your goal is to translate medical terms into comprehensive, yet straightforward language for all readers.

I'm not familiar with the medical term 'Phenelzine.' Could you provide some insights?

Phenelzine, sold under the brand name Nardil, among others, is a nonselective and irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class which is used as an antidepressant and anxiolytic. Along with tranylcypromine and isocarboxazid, phenelzine is one of the few nonselective and irreversible MAOIs still in widespread clinical use. It is available in Australia, the United Kingdom, the United States, and Canada. It is taken by mouth. Indications Phenelzine is used primarily in the treatment of major depressive disorder (MDD). Patients with depressive symptomology characterized as "atypical", "nonendogenous", and/or "neurotic" respond particularly well to phenelzine. The medication is also useful in patients who do not respond favorably to first and second-line treatments for depression, or are "treatment-resistant". In addition to being a recognized treatment for major depressive disorder, phenelzine is effective in treating dysthymia, bipolar depression (BD), panic disorder (PD), social anxiety disorder, bulimia, post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD). Pharmacology Pharmacodynamics Phenelzine is a non-selective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It inhibits both of the respective isoforms of MAO, MAO-A and MAO-B, and does so almost equally, with slight preference for the former. By inhibiting MAO, phenelzine prevents the breakdown of the monoamine neurotransmitters serotonin, melatonin, norepinephrine, epinephrine, and dopamine, as well as the trace amine neuromodulators such as phenethylamine, tyramine, octopamine, and tryptamine. This leads to an increase in the extracellular concentrations of these neurochemicals and therefore an alteration in neurochemistry and neurotransmission. This action is thought to be the primary mediator in phenelzines therapeutic benefits. Phenelzine and its metabolites also inhibit at least two other enzymes to a lesser extent, of which are alanine transaminase (ALA-T), and γ-aminobutyric acid transaminase (GABA-T), the latter of which is not caused by phenelzine itself, but by a phenelzine metabolite phenylethylidenehydrazine (PEH). By inhibiting ALA-T and GABA-T, phenelzine causes an increase in the alanine and GABA levels in the brain and body. GABA is the major inhibitory neurotransmitter in the mammalian central nervous system, and is very important for the normal suppression of anxiety, stress, and depression. Phenelzines action in increasing GABA concentrations may significantly contribute to its antidepressant, and especially, anxiolytic/antipanic properties, the latter of which have been considered superior to those of other antidepressants. As for ALA-T inhibition, though the consequences of disabling this enzyme are currently not well understood, there is some evidence to suggest that it is this action of the hydrazines (including phenelzine) which may be responsible for the occasional incidence of hepatitis and liver failure. Phenelzine has also been shown to metabolize to phenethylamine (PEA). PEA acts as a releasing agent of norepinephrine and dopamine, and this occurs in the same manner as amphetamine (very similar in structure) by being taken up into vesicles, and displacing, and causing the release of those monoamines (though with markedly different pharmacokinetics such as a far shorter duration of action). Although this is indeed the same mechanism to which some (but not all) of amphetamines effects are attributable to, this is not all that uncommon a property among phenethylamines in general, many of which do not have psychoactive properties comparable to amphetamine. Amphetamine is different in that it binds with high affinity to the reuptake pumps of dopamine, norepinephrine, and serotonin, which phenethylamine and related molecules may as well to some extent, but with far less potency, such that it is basically insignificant in comparison. And, often being metabolized too quickly or not having the solubility to enable it to have a psychostimulant effect in humans. Claims that phenethylamine has comparable or roughly similar effects to psychostimulants such as amphetamine when administered are misconstrued. Phenethylamine does not have any obvious, easily discernible, reliably induced effects when administered to humans. Phenelzines enhancement of PEA levels may contribute further to its overall antidepressant effects to some degree. In addition, phenethylamine is a substrate for MAO-B, and treatment with MAOIs that inhibit MAO-B such as phenelzine have been shown to consistently and significantly elevate its concentrations. Phenelzine usually requires six to eight weeks of treatment, and a minimum dose of 60 mg/day, to achieve therapeutic effects. The reason for the delay in therapeutic effect is not fully understood, but it is believed to be due to many factors, including achieving steady-state levels of MAO inhibition and the resulting adaptations in mean neurotransmitter levels, the possibility of necessary desensitization of autoreceptors which normally inhibit the release of neurotransmitters like serotonin and dopamine, and also the upregulation of enzymes such as serotonin N-acetyltransferase. Typically, a therapeutic response to MAOIs is associated with an inhibition of at least 80-85% of monoamine oxidase activity. Pharmacokinetics Phenelzine is administered orally in the form of phenelzine sulfate and is rapidly absorbed from the gastrointestinal tract. Time to peak plasma concentration is 43 minutes and half-life is 11.6 hours. Unlike most other drugs, phenelzine irreversibly disables MAO, and as a result, it does not necessarily need to be present in the blood at all times for its effects to be sustained. Because of this, upon phenelzine treatment being ceased, its effects typically do not actually wear off until the body replenishes its enzyme stores, a process which can take as long as 2–3 weeks. Phenelzine is metabolized primarily in the liver and its metabolites are excreted in the urine. Oxidation is the primary routine of metabolism, and the major metabolites are phenylacetic acid and parahydroxyphenylacetic acid, recovered as about 73% of the excreted dose of phenelzine in the urine over the course of 96 hours after single doses. Acetylation to N2-acetylphenelzine is a minor pathway. Phenelzine may also interact with cytochrome P450 enzymes, inactivating these enzymes through formation of a heme adduct. Two other minor metabolites of phenelzine, as mentioned above, include phenylethylidenehydrazine and phenethylamine. Adverse effects Common side effects of phenelzine may include dizziness, blurry vision, dry mouth, headache, lethargy, sedation, somnolence, insomnia, anorexia, weight gain or loss, nausea and vomiting, diarrhea, constipation, urinary retention, mydriasis, muscle tremors, hyperthermia, sweating, hypertension or hypotension, orthostatic hypotension, paresthesia, hepatitis, and sexual dysfunction (consisting of loss of libido and anorgasmia). Rare side effects usually only seen in susceptible individuals may include hypomania or mania, psychosis and acute liver failure, the last of which is usually only seen in people with pre-existing liver damage, old age, long-term effects of alcohol consumption, or viral infection. Interactions The MAOIs have certain dietary restrictions and drug interactions. The amount of such restrictions and interactions is far less than previously thought, and MAOIs are generally safe medications when administered correctly. Hypertensive crisis is generally a rare occurrence while taking MAOIs, yet may result from the overconsumption of tyramine-containing foods. As a result, patients on phenelzine and other MAOIs must avoid excess quantities of certain foods that contain tyramine such as aged cheeses and cured meats, among others. Serotonin syndrome may result from an interaction with certain drugs which increase serotonin activity such as selective serotonin reuptake inhibitors, serotonin releasing agents, and serotonin agonists. As is the case with other MAOIs, there is a concern regarding phenelzine and the use of both local and general anesthetics. Anyone taking phenelzine should inform their dentist before proceeding with dental surgery, and surgeon in any other contexts. Phenelzine has also been linked to vitamin B6 deficiency. Transaminases such as GABA-transaminase have been shown to be dependent upon vitamin B6 and may be involved in a potentially related process, since the phenelzine metabolite phenylethylidenehydrazine (PEH) is a GABA transaminase inhibitor. Both phenelzine and vitamin B6 are rendered inactive upon these reactions occurring. For this reason, it may be recommended to supplement with vitamin B6 while taking phenelzine. The pyridoxine form of B6 is recommended for supplementation, since this form has been shown to reduce hydrazine toxicity from phenelzine and, in contrast, the pyridoxal form has been shown to increase the toxicity of hydrazines. Research Phenelzine showed promise in a phase II clinical trial from March 2020 in treating prostate cancer. Phenelzine has also been shown to have neuroprotective effects in animal models. History Synthesis of phenelzine was first described by Emil Votoček and Otakar Leminger in 1932. See also Phenylethylidenehydrazine Hydrazine (antidepressant) Isocarboxazid Libby Zion Law (a case involving phenelzine and pethidine) Monoamine oxidase inhibitor Tranylcypromine References External links "Phenelzine". Drug Information Portal. U.S. National Library of Medicine.

You are a guide to medical language. Please provide in-depth and understandable explanations of medical terms, highlighting their significance in healthcare.

I'm not familiar with the medical term 'Prurigo.' Could you provide some insights?

Prurigo is an itchy eruption of the skin.Specific types include: Prurigo nodularis Actinic prurigo Besniers prurigo (a specific type of atopic dermatitis). References == External links ==

You are a medical lexicon. Explain medical terminology with depth and clarity, making sure the information is both accurate and easy to grasp.

I'm trying to expand my medical knowledge. Can you elucidate the term 'Adenosine'?

Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of the four nucleoside building blocks of RNA (and its derivative deoxyadenosine is a building block of DNA), which are essential for all life. Its derivatives include the energy carriers adenosine mono-, di-, and triphosphate, also known as AMP/ADP/ATP. Cyclic adenosine monophosphate (cAMP) is pervasive in signal transduction. Adenosine is used as an intravenous medication for some cardiac arrhythmias. Adenosyl (abbreviated Ado or 5-dAdo) is the chemical group formed by removal of the 5′-hydroxy (OH) group. It is found in adenosylcobalamin (an active form of vitamin B12) and as a radical in radical SAM enzymes. Medical uses Supraventricular tachycardia In individuals with supraventricular tachycardia (SVT), adenosine is used to help identify and convert the rhythm.Certain SVTs can be successfully terminated with adenosine. This includes any re-entrant arrhythmias that require the AV node for the re-entry, e.g., AV reentrant tachycardia (AVRT) and AV nodal reentrant tachycardia (AVNRT). In addition, atrial tachycardia can sometimes be terminated with adenosine.Fast rhythms of the heart that are confined to the atria (e.g., atrial fibrillation and atrial flutter) or ventricles (e.g., monomorphic ventricular tachycardia), and do not involve the AV node as part of the re-entrant circuit, are not typically converted by adenosine. However, the ventricular response rate is temporarily slowed with adenosine in such cases.Because of the effects of adenosine on AV node-dependent SVTs, adenosine is considered a class V antiarrhythmic agent. When adenosine is used to cardiovert an abnormal rhythm, it is normal for the heart to enter ventricular asystole for a few seconds. This can be disconcerting to a normally conscious patient, and is associated with angina-like sensations in the chest. Nuclear stress test Adenosine is used as an adjunct to thallium (TI 201) or technetium (Tc99m) myocardial perfusion scintigraphy (nuclear stress test) in patients unable to undergo adequate stress testing with exercise. Dosage When given for the evaluation or treatment of a supraventricular tachycardia (SVT), the initial dose is 6 mg to 12 mg, depending on standing orders or provider preference, given as a rapid parenteral infusion. Due to adenosines extremely short half-life, the IV line is started as proximal (near) to the heart as possible, such as the antecubital fossa. The IV push is often followed with a flush of 10–20 mL of normal saline. If this has no effect (i.e., no evidence of transient AV block), a dose of 12 mg can be given 1–2 minutes after the first dose. When given to dilate the arteries, such as in a "stress test", the dosage is typically 0.14 mg/kg/min, administered for 4 or 6 minutes, depending on the protocol. The recommended dose may be increased in patients on theophylline since methylxanthines prevent binding of adenosine at receptor sites. The dose is often decreased in patients on dipyridamole (Persantine) and diazepam (Valium) because adenosine potentiates the effects of these drugs. The recommended dose is also reduced by half in patients presenting congestive heart failure, myocardial infarction, shock, hypoxia, and/or chronic liver disease or chronic kidney disease, and in elderly patients. Drug interactions Dipyridamole potentiates the action of adenosine, requiring the use of lower doses. Methylxanthines (e.g. caffeine found in coffee, theophylline found in tea, or theobromine found in chocolate) have a purine structure and bind to some of the same receptors as adenosine. Methylxanthines act as competitive antagonists of adenosine and can blunt its pharmacological effects. Individuals taking large quantities of methylxanthines may require increased doses of adenosine. Contraindications Common contraindications for adenosine include Asthma, traditionally considered an absolute contraindication. This is being contended and it is now considered a relative contraindication (however, selective adenosine antagonists are being investigated for use in treatment of asthma) Pharmacological effects Adenosine is an endogenous purine nucleoside that modulates many physiological processes. Cellular signaling by adenosine occurs through four known adenosine receptor subtypes (A1, A2A, A2B, and A3).Extracellular adenosine concentrations from normal cells are approximately 300 nM; however, in response to cellular damage (e.g., in inflammatory or ischemic tissue), these concentrations are quickly elevated (600–1,200 nM). Thus, in regard to stress or injury, the function of adenosine is primarily that of cytoprotection preventing tissue damage during instances of hypoxia, ischemia, and seizure activity. Activation of A2A receptors produces a constellation of responses that in general can be classified as anti-inflammatory. Enzymatic production of adenosine can be anti-inflammatory or immunosuppressive. Adenosine receptors All adenosine receptor subtypes (A1, A2A, A2B, and A3) are G-protein-coupled receptors. The four receptor subtypes are further classified based on their ability to either stimulate or inhibit adenylate cyclase activity. The A1 receptors couple to Gi/o and decreases cAMP levels, while the A2 adenosine receptors couple to Gs, which stimulates adenylate cyclase activity. In addition, A1 receptors couple to Go, which has been reported to mediate adenosine inhibition of Ca2+ conductance, whereas A2B and A3 receptors also couple to Gq and stimulate phospholipase activity. Researchers at Cornell University have recently shown adenosine receptors to be key in opening the blood-brain barrier (BBB). Mice dosed with adenosine have shown increased transport across the BBB of amyloid plaque antibodies and prodrugs associated with Parkinsons disease, Alzheimers, multiple sclerosis, and cancers of the central nervous system. Ghrelin/growth hormone secretagogue receptor Adenosine is an endogenous agonist of the ghrelin/growth hormone secretagogue receptor. However, while it is able to increase appetite, unlike other agonists of this receptor, adenosine is unable to induce the secretion of growth hormone and increase its plasma levels. Mechanism of action When it is administered intravenously, adenosine causes transient heart block in the atrioventricular (AV) node. This is mediated via the A1 receptor, inhibiting adenylyl cyclase, reducing cAMP and so causing cell hyperpolarization by increasing K+ efflux via inward rectifier K+ channels, subsequently inhibiting Ca2+ current. It also causes endothelial-dependent relaxation of smooth muscle as is found inside the artery walls. This causes dilation of the "normal" segments of arteries, i.e. where the endothelium is not separated from the tunica media by atherosclerotic plaque. This feature allows physicians to use adenosine to test for blockages in the coronary arteries, by exaggerating the difference between the normal and abnormal segments. The administration of adenosine also reduces blood flow to coronary arteries past the occlusion. Other coronary arteries dilate when adenosine is administered while the segment past the occlusion is already maximally dilated, which is a process called coronary steal. This leads to less blood reaching the ischemic tissue, which in turn produces the characteristic chest pain. Metabolism Adenosine used as a second messenger can be the result of de novo purine biosynthesis via adenosine monophosphate (AMP), though it is possible other pathways exist.When adenosine enters the circulation, it is broken down by adenosine deaminase, which is present in red blood cells and the vessel wall. Dipyridamole, an inhibitor of adenosine nucleoside transporter, allows adenosine to accumulate in the blood stream. This causes an increase in coronary vasodilatation. Adenosine deaminase deficiency is a known cause of immunodeficiency. Research Viruses The adenosine analog NITD008 has been reported to directly inhibit the recombinant RNA-dependent RNA polymerase of the dengue virus by terminating its RNA chain synthesis. This interaction suppresses peak viremia and rise in cytokines and prevents lethality in infected animals, raising the possibility of a new treatment for this flavivirus. The 7-deaza-adenosine analog has been shown to inhibit the replication of the hepatitis C virus. BCX4430 is protective against Ebola and Marburg viruses. Such adenosine analogs are potentially clinically useful since they can be taken orally. Anti-inflammatory properties Adenosine is believed to be an anti-inflammatory agent at the A2A receptor. Topical treatment of adenosine to foot wounds in diabetes mellitus has been shown in lab animals to drastically increase tissue repair and reconstruction. Topical administration of adenosine for use in wound-healing deficiencies and diabetes mellitus in humans is currently under clinical investigation. Methotrexates anti-inflammatory effect may be due to its stimulation of adenosine release. Central nervous system In general, adenosine has an inhibitory effect in the central nervous system (CNS). Caffeines stimulatory effects are credited primarily (although not entirely) to its capacity to block adenosine receptors, thereby reducing the inhibitory tonus of adenosine in the CNS. This reduction in adenosine activity leads to increased activity of the neurotransmitters dopamine and glutamate. Experimental evidence suggests that adenosine and adenosine agonists can activate Trk receptor phosphorylation through a mechanism that requires the adenosine A2A receptor. Hair Adenosine has been shown to promote thickening of hair on people with thinning hair. A 2013 study compared topical adenosine with minoxidil in male androgenetic alopecia, finding it was as potent as minoxidil (in overall treatment outcomes) but with higher satisfaction rate with patients due to “faster prevention of hair loss and appearance of the newly grown hairs” (further trials were called for to clarify the findings). Sleep The principal component of cannabis delta-9-tetrahydrocannabinol (THC) and the endocannabinoid anandamide (AEA) induce sleep in rats by increasing adenosine levels in the basal forebrain. They also significantly increase slow-wave sleep during the third hour, mediated by CB1 receptor activation. These findings identify a potential therapeutic use of cannabinoids to induce sleep in conditions where sleep may be severely attenuated. Vasodilation It also plays a role in regulation of blood flow to various organs through vasodilation. See also Adenosine receptor Adenosine reuptake inhibitor List of growth hormone secretagogues == References ==

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I'm trying to understand 'Lymphomatoid papulosis' within a medical context. Could you shed some light on it?

Lymphomatoid papulosis (LyP) is a rare skin disorder. The overall prevalence rate of lymphomatoid papulosis is estimated at 1.2 to 1.9 cases per 1,000,000 population. [This is a widespread misinterpretation of a 1992 study saying "the period prevalence rate of lymphomatoid papulosis was estimated to be 1.9 per 1,000,000 population for Massachusetts and 1.2 per 1,000,000 population for Pennsylvania". The authors of that study said clearly "Our estimate of 1.2-1.9 cases per 1,000,000 population should be considered a minimum estimate of the prevalence rate". That estimate was based on the 78 patients involved in the study, not the LvP population. The study recruited 11 patients from Massachusetts and 15 from Pennsylvania ]. This rare condition has only been studied in depth since 1968. Presentation It can appear very similar to anaplastic large cell lymphoma. Type "A" is CD30 positive, while type "B" is CD30 negative.It has been described as "clinically benign but histologically malignant." Treatment It may respond to methotrexate or PUVA. Prognosis It can evolve into lymphoma. See also Cutaneous T-cell lymphoma Parapsoriasis Secondary cutaneous CD30+ large cell lymphoma List of cutaneous conditions References == External links ==

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I'm trying to expand my medical knowledge. Can you elucidate the term 'Osteopoikilosis'?

Osteopoikilosis is a benign, autosomal dominant sclerosing dysplasia of bone characterized by the presence of numerous bone islands in the skeleton. Presentation The radiographic appearance of osteopoikilosis on an X-ray is characterized by a pattern of numerous white densities of similar size spread throughout all the bones. This is a systemic condition. It must be differentiated from blastic metastasis, which can also present radiographically as white densities interspersed throughout bone. Blastic metastasis tends to present with larger and more irregular densities in less of a uniform pattern. Another differentiating factor is age, with blastic metastasis mostly affecting older people, and osteopoikilosis being found in people 20 years of age and younger. The distribution is variable, though it does not tend to affect the ribs, spine, or skull. Cause Epidemiology Men and women are affected in equal number, reflecting the fact that osteopoikilosis attacks indiscriminately. Additionally, the disease is often associated with melorheostosis, despite the apparent lack of correlation between melorheostosis and genetic heritability. It has been tied to LEMD3. Buschke–Ollendorff syndrome is a similar condition, which is also associated with LEMD3. See also List of radiographic findings associated with cutaneous conditions References == External links ==

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What is the significance of the term 'Cat eye syndrome' in the medical field?

Cat eye syndrome (CES) or Schmid–Fraccaro syndrome is a rare condition caused by an abnormal extra chromosome, i.e. a small supernumerary marker chromosome. This chromosome consists of the entire short arm and a small section of the long arm of chromosome 22. In consequence, individuals with the cat eye syndrome have three (trisomic) or four (tetrasomic) copies of the genetic material contained in the abnormal chromosome instead of the normal two copies. The prognosis for patients with CES varies depending on the severity of the condition and their associated signs and symptoms, especially when heart or kidney abnormalities are seen. Signs and symptoms Unilateral or bilateral iris coloboma (absence of tissue from the colored part of the eyes) Preauricular pits/tags (small depressions/growths of skin on the outer ears) Anal atresia (abnormal obstruction of the anus) Downward-slanting palpebral fissures (openings between the upper and lower eyelids) Cleft palate Kidney problems (missing, extra, or underdeveloped kidneys) Short stature Scoliosis/skeletal problems Cardiac defects (such as TAPVR) Micrognathia (smaller jaw) Hernias Biliary atresia Rarer malformations can affect almost any organ Intellectual disability – many are intellectually normal; about 30% of CES patients have moderately impaired mental development, although severe intellectual disability is rare.The term "cat eye" syndrome was coined because of the particular appearance of the vertical colobomas in the eyes of some patients, but over half of the CES patients in the literature do not present with this trait. Genetics The small supernumerary marker chromosome (sSMC) in CES usually arises spontaneously. It may be hereditary and parents may be mosaic for the marker chromosome, but show no phenotypic symptoms of the syndrome. This sSMC may be small, large, or ring-shaped, and typically includes 2 Mb, i.e. 2 million DNA base pairs, termed the CES critical region, located on its q arm(s) between its band 11 and terminus (area notated as 22pter→q11)(also see small supernumerary marker chromosomes in cat eye syndrome). This area contains the CECR1, SLC25A18, and ATP6V1E1 genes which are strong candidate genes for causing or promoting at least some of the birth defects in CES. Diagnosis History The abnormalities common to CES were first cataloged in 1899, and described in association with a small marker chromosome in 1965. Early reports of CES discuss the possibility of chromosome 13 involvement. Now, CES is considered to be present with the chromosome 22 trisomy findings. See also Trisomy 22 References == External links ==

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What does the medical term 'X-linked complicated corpus callosum dysgenesis' encompass?

X-linked complicated corpus callosum dysgenesis is a genetic disorder characterized by dysplasia, hypoplasia or agenesis of the corpus callosum alongside variable intellectual disability and spastic paraplegia. Only 13 cases (all male) have been described in medical literature. Transmission is X-linked recessive. It is the mildest subtype of L1 syndrome.This condition differs from other L1 syndromes due to the fact that neither hydrocephalus, adducted thumbs, or speech difficulties are common in patients with the condition. Genetics This condition is caused by X-linked recessive mutations in the L1CAM gene, located in the long arm of the X chromosome. Mutations involved in the milder variants of L1 syndrome (including X-linked complicated corpus callosum dysgenesis) usually work by changing the L1 protein structure. Cases The following list comprises all cases of X-linked complicated corpus callosum dysgenesis described in medical literature (from OMIM): 1964: Menkes et al. describes 5 males from 4 sibships of a 2-generation American family. The males (all infants) had partial corpus callosum agenesis, severe intellectual disabilities, developmental delays, and epilepsy. The disorder first manifested right after birth, with recurrent seizures occurring hours after it. Out of these 5 babies, 3 had died. Post-mortem examination of one of the dead infants revealed chemical and anatomical abnormalities. 1983: Kaplan et al. describes 2 males from a 2-generation Canadian family. The proband was a 2 year old male, the first-born child of healthy, non-consanguineous Ashkenazi Jewish parents in their mid-20s, his pregnancy was uneventful (besides slight vaginal bleeding experienced by the mother sometime during her first three months of pregnancy). He was noted to have unilateral congenital ptosis, clinodactyly affecting the index and ring fingers, bilateral thumb adduction, and upper limb weakness at birth, with symptoms of Hirschsprungs disease showing 24 hours after he was born. He was psychomotorly delayed. CT scans showed brain growth delay, corpus callosum agenesis, and a hypoplastic inferior vermis and cerebellum. Electroencephalograms gave abnormal results. He was born weighing 3.09 kilograms, being 49 cm long, and with a head circumference of 33.5 cm. The second case was his 24-year-old maternal uncle. He was psychomotorly delayed like his nephew, and he noted to have pectus excavatum and speckled irises only. CT scans showed only corpus callosum agenesis. His head circumference at the time was 52 cm. Chromosomal analysis done on the proband child, his mother and his uncle was normal. Family history on the mothers family only revealed a distant third-cousin with Hirschsprungs disease, her two other brothers were normal, and she went on to have a normal female pregnancy. 1992: Kang et al. describes 4 male children each from 4 different sibships belonging to an ethnic Chinese Taiwanese family, constituting the first case report of X-linked complicated corpus callosum dysgenesis in China. Said children had microcephaly, spasticity, intellectual disabilities, hydrocephalus, and facial dysmorphisms. Some of them had an interhemispheric cyst. 2006: Basel-Vanagaite et al. describes 2 Israeli Jewish brothers who both had partial corpus callosum agenesis alongside mild intellectual disability. One of the siblings had bilateral congenital radial head dislocation and Hirschsprungs disease. Genetic testing revealed a missense mutation (p.P240L) in exon 7 of the L1CAM gene. == References ==

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I'm encountering the term 'Nasal spray' in medical literature. What's its definition?

Nasal sprays are used to deliver medications locally in the nasal cavities or systemically. They are used locally for conditions such as nasal congestion and allergic rhinitis. In some situations, the nasal delivery route is preferred for systemic therapy because it provides an agreeable alternative to injection or pills. Substances can be assimilated extremely quickly and directly through the nose. Many pharmaceutical drugs exist as nasal sprays for systemic administration (e.g. sedative-analgesics, treatments for migraine, osteoporosis and nausea). Other applications include hormone replacement therapy, treatment of Alzheimers disease and Parkinsons disease. Nasal sprays are seen as a more efficient way of transporting drugs with potential use in crossing the blood–brain barrier. Antihistamines Antihistamines work by competing for receptor sites to block the function of histamine, thereby reducing the inflammatory effect. Antihistamine nasal sprays include: Azelastine hydrochloride Levocabastine hydrochloride Olopatadine hydrochloride Corticosteroids Corticosteroid nasal sprays can be used to relieve the symptoms of sinusitis, hay fever, allergic rhinitis and non-allergic (perennial) rhinitis. They can reduce inflammation and histamine production in the nasal passages, and have been shown to relieve nasal congestion, runny nose, itchy nose and sneezing. Side effects may include headaches, nausea and nose bleeds. Corticosteroid nasal sprays include: Beclomethasone dipropionate Budesonide Ciclesonide Flunisolide Fluticasone furoate Fluticasone propionate Mometasone Triamcinolone acetonide Saline Saline sprays are typically non medicated. A mist of saline solution containing sodium chloride is delivered to help moisturize dry or irritated nostrils. This is a form of nasal irrigation. They can also relieve nasal congestion and remove airborne irritants such as pollen and dust thereby providing sinus allergy relief. Three types of nasal sprays preparations of sodium chloride are available including hypertonic (3% sodium chloride or sea water), isotonic (0.9% sodium chloride) and hypotonic (0.65% sodium chloride). Isotonic solutions have the same salt concentration as the human body, whereas hypertonic solutions have a higher salt content and hypotonic solutions have a lower salt content. Isotonic saline nasal sprays are commonly used in infants and children to wash out the thick mucus from the nose in case of allergic rhinitis. Hypertonic solutions may be more useful at drawing moisture from the mucous membrane and relieving nasal congestion. Natural nasal sprays that include chemical complexes derived from plant sources such as ginger, capsaicin and tea-tree oil are also available. There is however no trial-verified evidence that they have a measurable effect on symptoms. Topical decongestants Decongestant nasal sprays are available over-the-counter in many countries. They work to very quickly open up nasal passages by constricting blood vessels in the lining of the nose. Prolonged use of these types of sprays can damage the delicate mucous membranes in the nose. This causes increased inflammation, an effect known as rhinitis medicamentosa or the rebound effect. Decongestant nasal sprays are advised for short-term use only, preferably 5 to 7 days at maximum. Some doctors advise to use them 3 days at maximum. A recent clinical trial has shown that a corticosteroid nasal spray may be useful in reversing this condition. Topical nasal decongestants include: Oxymetazoline Phenylephrine Xylometazoline Allergy combinations Combination use of two medications as nasal spray preparation has been frequently prescribed by doctors. List of combination nasal sprays: Azelastine together with fluticasone propionate (trade names including Dymista) Xylometazoline together with cromoglicic acid See also Olopatadine/mometasone References External links Media related to Nasal sprays at Wikimedia Commons

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I'd like to learn more about the medical term 'CREST syndrome.' Can you provide some details?

CREST syndrome, also known as the limited cutaneous form of systemic sclerosis (lcSSc), is a multisystem connective tissue disorder. The acronym "CREST" refers to the five main features: calcinosis, Raynauds phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia.CREST syndrome is associated with detectable antibodies against centromeres (a component of the cell nucleus), and usually spares the kidneys (a feature more common in the related condition systemic scleroderma). If the lungs are involved, it is usually in the form of pulmonary arterial hypertension. Signs and symptoms Calcinosis CREST causes thickening and tightening of the skin with deposition of calcific nodules ("calcinosis"). Raynauds phenomenon Raynauds phenomenon is frequently the first manifestation of CREST/lcSSc, preceding other symptoms by years. Stress and cold temperature induce an exaggerated vasoconstriction of the small arteries, arterioles, and thermoregulatory vessels of the skin of the digits. Clinically this manifests as a white-blue-red transition in skin color. Underlying this transition is pallor and cyanosis of the digits, followed by a reactive hyperemia as they rewarm. When extreme and frequent, this phenomenon can lead to digital ulcerations, gangrene, or amputation. Ulceration can predispose to chronic infections of the involved site. Esophageal dysmotility Presents as a sensation of food getting stuck (dysphagia) in the mid- or lower esophagus, atypical chest pain, or cough. People often state they must drink liquids to swallow solid food. This motility problem results from atrophy of the gastrointestinal tract wall smooth muscle. This change may occur with or without pathologic evidence of significant tissue fibrosis. Sclerodactyly Though it is the most easily recognizable manifestation, it is not prominent in all patients. Thickening generally only involves the skin of the fingers distal to the metacarpophalangeal joints in CREST. Early in the course of the disease, the skin may appear edematous and inflamed. Eventually, dermal fibroblasts overproduce extracellular matrix leading to increased tissue collagen deposition in the skin. Collagen cross-linking then causes a progressive skin tightening. Digital ischemic ulcers commonly form on the distal fingers in 30–50% of patients. Telangiectasias Marked telangiectasias (dilated capillaries) occur on the skin of the face, the palmar surface of the hands, and the mucous membranes. Telangiectasias tend to be more numerous in people with other scleroderma related vascular disease (i.e., pulmonary arterial hypertension). The number of telangiectasias and the sites involved tend to increase over time.... Other Other symptoms of CREST syndrome can be exhaustion, weakness, difficulties with breathing, pain in hands and feet, dizziness and badly healing wounds. Patients with lcSSc commonly induce pulmonary artery hypertension which may result in cor pulmonale (heart failure due to increased pulmonary artery pressure). Cause CREST syndrome involves the production of autoimmune anti-nuclear and anti-centromere antibodies, though their cause is not currently understood. There is no known infectious cause. Diagnosis CREST is not easily diagnosed as it closely mimics symptoms of other connective tissue and autoimmune diseases. Diagnoses are usually given when a patient presents two or more of the five major clinical symptoms. Additionally, blood exams can be given to test for a positive ANAs and ACAs or skin biopsies can be given to help confirm a diagnosis. Treatment Disease progression may be slowed with immunosuppressives and other medications, and esophageal reflux, pulmonary hypertension and Raynaud phenomenon may benefit from symptomatic treatment. However, there is no cure for this disease as there is no cure for scleroderma in general. Epidemiology CREST syndrome can be noted in up to 10% of patients with primary biliary cholangitis. History The combination of symptoms was first reported in 1964 by R.H. Winterbauer, at that point a medical student at Johns Hopkins School of Medicine. See also Scleroderma References == External links ==

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Could you please explain the term 'Epidermal nevus syndrome' in simple language?

Epidermal nevus syndrome (also known as "Feuerstein and Mims syndrome", and "Solomons syndrome": 775 ) is a rare disease that was first described in 1968 and consists of extensive epidermal nevi with abnormalities of the central nervous system (CNS), skeleton, skin, cardiovascular system, genitourinary system and eyes.: 634  However, since the syndromes first description, a broader concept for the "epidermal nevus" syndrome has been proposed, with at least six types being described:: 776  Schimmelpenning syndrome Nevus comedonicus syndrome Pigmented hairy epidermal nevus syndrome Proteus syndrome CHILD syndrome Phakomatosis pigmentokeratotica See also Epidermis List of cutaneous conditions References == External links ==

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I've encountered the term 'Periodontal disease' while reading about medical topics. What does it refer to exactly?

Periodontal disease, also known as gum disease, is a set of inflammatory conditions affecting the tissues surrounding the teeth. In its early stage, called gingivitis, the gums become swollen and red and may bleed. It is considered the main cause of tooth loss for adults worldwide. In its more serious form, called periodontitis, the gums can pull away from the tooth, bone can be lost, and the teeth may loosen or fall out. Bad breath may also occur.Periodontal disease is generally due to bacteria in the mouth infecting the tissue around the teeth. Factors that increase the risk of disease include smoking, diabetes, HIV/AIDS, family history, and certain medications. Diagnosis is by inspecting the gum tissue around the teeth both visually and with a probe and X-rays looking for bone loss around the teeth.Treatment involves good oral hygiene and regular professional teeth cleaning. Recommended oral hygiene include daily brushing and flossing. In certain cases antibiotics or dental surgery may be recommended. Clinical trials show that smoking cessation and dietary improvements improve disease outcomes. Globally 538 million people were estimated to be affected in 2015 and has been known to affect 10-15% of the population generally. In the United States nearly half of those over the age of 30 are affected to some degree, and about 70% of those over 65 have the condition. Males are affected more often than females. Signs and symptoms In the early stages, periodontitis has very few symptoms, and in many individuals the disease has progressed significantly before they seek treatment. Symptoms may include: Redness or bleeding of gums while brushing teeth, using dental floss or biting into hard food (e.g., apples) (though this may also occur in gingivitis, where there is no attachment loss gum disease ) Gum swelling that recurs Spitting out blood after brushing teeth Halitosis, or bad breath, and a persistent metallic taste in the mouth Gingival recession, resulting in apparent lengthening of teeth (this may also be caused by heavy-handed brushing or with a stiff toothbrush) Deep pockets between the teeth and the gums (pockets are sites where the attachment has been gradually destroyed by collagen-destroying enzymes, known as collagenases) Loose teeth, in the later stages (though this may occur for other reasons, as well)Gingival inflammation and bone destruction are largely painless. Hence, people may wrongly assume painless bleeding after teeth cleaning is insignificant, although this may be a symptom of progressing periodontitis in that person. Associated conditions Periodontitis has been linked to increased inflammation in the body, such as indicated by raised levels of C-reactive protein and interleukin-6. It is associated with an increased risk of stroke, myocardial infarction, atherosclerosis and hypertension. It also linked in those over 60 years of age to impairments in delayed memory and calculation abilities. Individuals with impaired fasting glucose and diabetes mellitus have higher degrees of periodontal inflammation, and often have difficulties with balancing their blood glucose level owing to the constant systemic inflammatory state, caused by the periodontal inflammation. Although no causal association was proven, there is an association between chronic periodontitis and erectile dysfunction, inflammatory bowel disease, heart disease, and pancreatic cancer. Diabetes and Periodontal Disease A positive correlation between raised levels of glucose within the blood and the onset or progression of periodontal disease has been shown in the current literature. Data has also shown that there is a significant increase in the incidence or progression of periodontitis in patients with uncontrolled diabetes compared to those who do not have diabetes or have well-controlled diabetes. In uncontrolled diabetes, the formation of reactive oxygen species can damage cells such as those in the connective tissue of the periodontal ligament, resulting in cell necrosis or apoptosis. Furthermore, individuals with uncontrolled diabetes mellitus who have frequent exposure to periodontal pathogens have a greater immune response to these bacteria. This can subsequently cause and/or accelerate periodontal tissue destruction leading to periodontal disease.Oral Cancer and Periodontal Disease Current literature suggests a link between periodontal disease and oral cancer. Studies have confirmed an increase in systemic inflammation markers such as C-Reactive Protein and Interleukin-6 to be found in patients with advanced periodontal disease. The link between systemic inflammation and oral cancer has also been well established. Both periodontal disease and cancer risk are associated with genetic susceptibility and it is possible that there is a positive association by a shared genetic susceptibility in the two diseases. Due to the low incidence rate of oral cancer, studies have not been able to conduct quality studies to prove the association between the two, however future larger studies may aid in the identification of individuals at a higher risk.Systemic implications Periodontal disease (PD) can be described as an inflammatory condition affecting the supporting structures of the teeth. Studies have shown that PD is associated with higher levels of systemic inflammatory markers such as Interleukin-6 (IL-6), C-Reactive Protein (CRP) and Tumor Necrosis Factor (TNF). To compare, elevated levels of these inflammatory markers are also associated with cardiovascular disease and cerebrovascular events such as ischemic strokes.The presence of a wide spectrum inflammatory oral diseases can increase the risk of an episode of stroke in an acute or chronic phase. Inflammatory markers, CRP, IL-6 are known risk factors of stroke. Both inflammatory markers are also biomarkers of PD and found to be an increased level after daily activities, such as mastication or toothbrushing, are performed. Bacteria from the periodontal pockets will enter the bloodstream during these activities and the current literature suggests that this may be a possible triggering of the aggravation of the stroke process.Other mechanisms have been suggested, PD is a known chronic infection. It can aid in the promotion of atherosclerosis by the deposition of cholesterol, cholesterol esters and calcium within the subendothelial layer of vessel walls. Atherosclerotic plaque that is unstable may rupture and release debris and thrombi that may travel to different parts of the circulatory system causing embolization and therefore, an ischemic stroke. Therefore, PD has been suggested as an independent risk factor for stroke. A variety of cardiovascular diseases can also be associated with periodontal disease. Patients with higher levels of inflammatory markers such as TNF, IL-1, IL-6 and IL-8 can lead to progression of atherosclerosis and the development and perpetuation of atrial fibrillation, as it is associated with platelet and coagulation cascade activations, leading to thrombosis and thrombotic complications. Experimental animal studies have shown a link between periodontal disease, oxidative stress and cardiac stress. Oxidative stress favours the development and progression of heart failure as it causes cellular dysfunction, oxidation of proteins and lipids, and damage to the deoxyribonucleic acid (DNA), stimulating fibroblast proliferation and metalloproteinases activation favouring cardiac remodelling. Clinical Significance Inadequate Nutrition and Periodontal Disease Periodontal disease is multifactorial, and nutrition can significantly affect its prognosis. Studies have shown that a healthy and well-balanced diet is crucial to maintaining periodontal health. Nutritional deficiencies can lead to oral manifestations such as those in scurvy and rickets disease. Different vitamins will play a different role in periodontal health: Vitamin C: Deficiencies may lead to gingival inflammation and bleeding, subsequently advancing periodontal disease Vitamin D: Deficiencies may lead to delayed post-surgical healing Vitamin E: Deficiencies may lead to impaired gingival wound healing Vitamin K: Deficiencies may lead to gingival bleedingNutritional supplements of vitamins have also been shown to positively affect healing after periodontal surgery and many of these vitamins can be found in a variety of food that we eat within a regular healthy diet. Therefore, vitamin intakes (particularly vitamin C) and dietary supplements not only play a role in improving periodontal health, but also influence the rate of bone formation and periodontal regeneration. However, studies supporting the correlation between nutrition and periodontal health are limited, and more long-term research is required to confirm this. Causes Periodontitis is an inflammation of the periodontium, i.e., the tissues that support the teeth. The periodontium consists of four tissues: gingiva, or gum tissue, cementum, or outer layer of the roots of teeth, alveolar bone, or the bony sockets into which the teeth are anchored, and periodontal ligaments (PDLs), which are the connective tissue fibers that run between the cementum and the alveolar bone. The primary cause of gingivitis is poor or ineffective oral hygiene, which leads to the accumulation of a mycotic and bacterial matrix at the gum line, called dental plaque. Other contributors are poor nutrition and underlying medical issues such as diabetes. Diabetics must be meticulous with their homecare to control periodontal disease. New finger prick tests have been approved by the Food and Drug Administration in the US, and are being used in dental offices to identify and screen people for possible contributory causes of gum disease, such as diabetes. In some people, gingivitis progresses to periodontitis – with the destruction of the gingival fibers, the gum tissues separate from the tooth and deepened sulcus, called a periodontal pocket. Subgingival microorganisms (those that exist under the gum line) colonize the periodontal pockets and cause further inflammation in the gum tissues and progressive bone loss. Examples of secondary causes are those things that, by definition, cause microbic plaque accumulation, such as restoration overhangs and root proximity. Smoking is another factor that increases the occurrence of periodontitis, directly or indirectly, and may interfere with or adversely affect its treatment. It is arguably the most important environmental risk factor for periodontitis. Research has shown that smokers have more bone loss, attachment loss and tooth loss compared to non-smokers. This is likely due to several effects of smoking on the immune response including decreased wound healing, suppression of antibody production, and the reduction of phagocytosis by neutrophilsEhlers–Danlos syndrome and Papillon–Lefèvre syndrome (also known as palmoplantar keratoderma) are also risk factors for periodontitis. If left undisturbed, microbial plaque calcifies to form calculus, which is commonly called tartar. Calculus above and below the gum line must be removed completely by the dental hygienist or dentist to treat gingivitis and periodontitis. Although the primary cause of both gingivitis and periodontitis is the microbial plaque that adheres to the tooth surfaces, there are many other modifying factors. A very strong risk factor is ones genetic susceptibility. Several conditions and diseases, including Down syndrome, diabetes, and other diseases that affect ones resistance to infection, also increase susceptibility to periodontitis. Periodontitis may be associated with higher stress. Periodontitis occurs more often in people from the lower end of the socioeconomic scale than people from the upper end of the socioeconomic scale.Genetics appear to play a role in determining the risk for periodontitis. It is believed genetics could explain why some people with good plaque control have advanced periodontitis, whilst some others with poor oral hygiene are free from the disease. Genetic factors which could modify the risk of a person developing periodontitis include: Defects of phagocytosis: person may have hypo-responsive phagocytes. Hyper-production of interleukins, prostaglandins and cytokines, resulting in an exaggerated immune response. Interleukin 1 (IL-1) gene polymorphism: people with this polymorphism produce more IL-1, and subsequently are more at risk of developing chronic periodontitis.Diabetes appears to exacerbate the onset, progression, and severity of periodontitis. Although the majority of research has focused on type 2 diabetes, type 1 diabetes appears to have an identical effect on the risk for periodontitis. The extent of the increased risk of periodontitis is dependent on the level of glycaemic control. Therefore, in well managed diabetes there seems to be a small effect of diabetes on the risk for periodontitis. However, the risk increases exponentially as glycaemic control worsens. Overall, the increased risk of periodontitis in diabetics is estimated to be between two and three times higher. So far, the mechanisms underlying the link are not fully understood, but it is known to involve aspects of inflammation, immune functioning, neutrophil activity, and cytokine biology. Mechanism As dental plaque or biofilm accumulates on the teeth near and below the gums there is some dysbiosis of the normal oral microbiome. As of 2017 it was not certain what species were most responsible for causing harm, but gram-negative anaerobic bacteria, spirochetes, and viruses have been suggested; in individual people it is sometimes clear that one or more species is driving the disease. Research in 2004 indicated three gram negative anaerobic species: Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Bacteroides forsythus and Eikenella corrodens.Plaque may be soft and uncalcified, hard and calcified, or both; for plaques that are on teeth the calcium comes from saliva; for plaques below the gumline, it comes from blood via oozing of inflamed gums.The damage to teeth and gums comes from the immune system as it attempts to destroy the microbes that are disrupting the normal symbiosis between the oral tissues and the oral microbe community. As in other tissues, Langerhans cells in the epithelium take up antigens from the microbes, and present them to the immune system, leading to movement of white blood cells into the affected tissues. This process in turn activates osteoclasts which begin to destroy bone, and it activates matrix metalloproteinases that destroy ligaments. So, in summary, it is bacteria which initiates the disease, but key destructive events are brought about by the exaggerated response from the hosts immune system. Classification There were several attempts to introduce an agreed-upon classification system for periodontal diseases: in 1989, 1993, 1999, and 2017. 1999 classification The 1999 classification system for periodontal diseases and conditions listed seven major categories of periodontal diseases, of which 2–6 are termed destructive periodontal disease, because the damage is essentially irreversible. The seven categories are as follows: Gingivitis Chronic periodontitis Aggressive periodontitis Periodontitis as a manifestation of systemic disease Necrotizing ulcerative gingivitis/periodontitis Abscesses of the periodontium Combined periodontic-endodontic lesionsMoreover, terminology expressing both the extent and severity of periodontal diseases are appended to the terms above to denote the specific diagnosis of a particular person or group of people. Severity The "severity" of disease refers to the amount of periodontal ligament fibers that have been lost, termed "clinical attachment loss". According to the 1999 classification, the severity of chronic periodontitis is graded as follows: Slight: 1–2 mm (0.039–0.079 in) of attachment loss Moderate: 3–4 mm (0.12–0.16 in) of attachment loss Severe: ≥ 5 mm (0.20 in) of attachment loss Extent The "extent" of disease refers to the proportion of the dentition affected by the disease in terms of percentage of sites. Sites are defined as the positions at which probing measurements are taken around each tooth and, generally, six probing sites around each tooth are recorded, as follows: Mesiobuccal Mid-buccal Distobuccal Mesiolingual Mid-lingual DistolingualIf up to 30% of sites in the mouth are affected, the manifestation is classified as "localized"; for more than 30%, the term "generalized" is used. 2017 classification The 2017 classification of periodontal diseases is as follows:Periodontal health, gingival disease and conditions Periodontal health and gingival health Clinical gingival health on an intact periodontium Clinical gingival health on an intact periodontium Stable periodontitis Non periodontitis person Gingivitis - Dental biofilm induced Associated with the dental biofilm alone Mediated by systemic and local risk factors Drug induced gingival enlargement. Gingival diseases - Non dental biofilm induced Genetic/developmental disorders Specific infections Inflammatory and immune conditions Reactive processes Neoplasms Endocrine, nutritional and metabolic Traumatic lesions Gingival pigmentation.Periodontitis Necrotizing periodontal diseases Necrotizing Gingivitis Necrotizing Periodontitis Necrotizing Stomatitis Periodontitis as a manifestation of systemic disease PeriodontitisOther conditions affecting the periodontium (Periodontal Manifestations of Systemic Diseases and Developmental and Acquired Conditions) Systemic disease of conditions affecting the periodontal support tissues Other Periodontal Conditions Periodontal abscesses Endodontic- periodontal lesions Mucogingival deformities and conditions Gingival Phenotype Gingival/Soft Tissue Recession Lack of Gingiva Decreased Vestibular Depth Aberrant Frenum/muscle position Gingival Excess Abnormal Color Condition of the exposed root surface Traumatic occlusal forces Primary Occlusal Trauma Secondary Occlusal Trauma Tooth and prosthesis related factors Localized tooth-related factors Localized dental prostheses-related factorsPeri-implant diseases and conditions Peri-implant health Peri-implant mucositis Peri-implantitis Peri-implant soft and hard tissue deficiencies Staging The goals of staging periodontitis is to classify the severity of damage and assess specific factors that may affect management.According to the 2017 classification, periodontitis is divided into four stages; after considering a few factors such as: Amount and percentage bone loss radiographically Clinical attachment loss, probing depth Presence of furcation Vertical bony defects History of tooth loss related to periodontitis Tooth hypermobility due to secondary occlusal trauma Grading According to the 2017 classification, the grading system for periodontitis consists of three grades: Grade A: Slow progression of disease; no evidence of bone loss over last five years Grade B: Moderate progression; < 2mm of bone loss over last five years Grade C: Rapid progression or future progression at high risk; ≥ 2mm bone loss over five yearsRisk factors affecting which grade a person is classified into include: Smoking Diabetes Prevention Daily oral hygiene measures to prevent periodontal disease include: Brushing properly on a regular basis (at least twice daily), with the person attempting to direct the toothbrush bristles underneath the gumline, helps disrupt the bacterial-mycotic growth and formation of subgingival plaque. Flossing daily and using interdental brushes (if the space between teeth is large enough), as well as cleaning behind the last tooth, the third molar, in each quarter Using an antiseptic mouthwash: Chlorhexidine gluconate-based mouthwash in combination with careful oral hygiene may cure gingivitis, although they cannot reverse any attachment loss due to periodontitis. Regular dental check-ups and professional teeth cleaning as required: Dental check-ups serve to monitor the persons oral hygiene methods and levels of attachment around teeth, identify any early signs of periodontitis, and monitor response to treatment.Clinical trials show that smoking cessation abd dietary improvements improve disease outcomes.Typically, dental hygienists (or dentists) use special instruments to clean (debride) teeth below the gumline and disrupt any plaque growing below the gumline. This is a standard treatment to prevent any further progress of established periodontitis. Studies show that after such a professional cleaning (periodontal debridement), microbial plaque tends to grow back to precleaning levels after about three to four months. Nonetheless, the continued stabilization of a persons periodontal state depends largely, if not primarily, on the persons oral hygiene at home, as well as on the go. Without daily oral hygiene, periodontal disease will not be overcome, especially if the person has a history of extensive periodontal disease. Management The cornerstone of successful periodontal treatment starts with establishing excellent oral hygiene. This includes twice-daily brushing with daily flossing. Also, the use of an interdental brush is helpful if space between the teeth allows. For smaller spaces, products such as narrow picks with soft rubber bristles provide excellent manual cleaning. Persons with dexterity problems, such as with arthritis, may find oral hygiene to be difficult and may require more frequent professional care and/or the use of a powered toothbrush. Persons with periodontitis must realize it is a chronic inflammatory disease and a lifelong regimen of excellent hygiene and professional maintenance care with a dentist/hygienist or periodontist is required to maintain affected teeth. Initial therapy Removal of microbial plaque and calculus is necessary to establish periodontal health. The first step in the treatment of periodontitis involves nonsurgical cleaning below the gum line with a procedure called "root surface instrumentation" or "RSI", this causes a mechanical disturbance to the bacterial biofilm below the gumline. This procedure involves the use of specialized curettes to mechanically remove plaque and calculus from below the gumline, and may require multiple visits and local anesthesia to adequately complete. In addition to initial RSI, it may also be necessary to adjust the occlusion (bite) to prevent excessive force on teeth that have reduced bone support. Also, it may be necessary to complete any other dental needs, such as replacement of rough, plaque-retentive restorations, closure of open contacts between teeth, and any other requirements diagnosed at the initial evaluation. It is important to note that RSI is different to scaling and root planing: RSI only removes the calculus, while scaling and root planing removes the calculus as well as underlying softened dentine, which leaves behind a smooth and glassy surface, which is not a requisite for periodontal healing. Therefore, RSI is now advocated over root planing. Reevaluation Nonsurgical scaling and root planing are usually successful if the periodontal pockets are shallower than 4–5 mm (0.16–0.20 in). The dentist or hygienist must perform a re-evaluation four to six weeks after the initial scaling and root planing, to determine if the persons oral hygiene has improved and inflammation has regressed. Probing should be avoided then, and an analysis by gingival index should determine the presence or absence of inflammation. The monthly reevaluation of periodontal therapy should involve periodontal charting as a better indication of the success of treatment, and to see if other courses of treatment can be identified. Pocket depths of greater than 5–6 mm (0.20–0.24 in) which remain after initial therapy, with bleeding upon probing, indicate continued active disease and will very likely lead to further bone loss over time. This is especially true in molar tooth sites where furcations (areas between the roots) have been exposed. Surgery If nonsurgical therapy is found to have been unsuccessful in managing signs of disease activity, periodontal surgery may be needed to stop progressive bone loss and regenerate lost bone where possible. Many surgical approaches are used in the treatment of advanced periodontitis, including open flap debridement and osseous surgery, as well as guided tissue regeneration and bone grafting. The goal of periodontal surgery is access for definitive calculus removal and surgical management of bony irregularities which have resulted from the disease process to reduce pockets as much as possible. Long-term studies have shown, in moderate to advanced periodontitis, surgically treated cases often have less further breakdown over time and, when coupled with a regular post-treatment maintenance regimen, are successful in nearly halting tooth loss in nearly 85% of diagnosed people. Local drug delivery Local drug deliveries in periodontology has gained acceptance and popularity compared to systemic drugs due to decreased risk in development of resistant flora and other side effects. A meta analysis of local tetracycline found improvement. Local application of statin may be useful. Systemic drug delivery Systemic drug delivery in conjunction with non-surgical therapy may be used as a means to reduce the percentage of the bacterial plaque load in the mouth. Many different antibiotics and also combinations of them have been tested; however, there is yet very low-certainty evidence of any significant difference in the short and long term compared to non-surgical therapy alone. It may be beneficial to limit the use of systemic drugs, since bacteria can develop antimicrobial resistance and some specific antibiotics might induce temporary mild adverse effects, such as nausea, diarrhoea and gastrointestinal disturbances. Adjunctive systemic antimicrobial treatment There is currently low-quality evidence suggesting if adjunctive systemic antimicrobials are beneficial for the non-surgical treatment of periodontitis. It is not sure whether some antibiotics are better than others when used alongside scaling and root planing). Maintenance Once successful periodontal treatment has been completed, with or without surgery, an ongoing regimen of "periodontal maintenance" is required. This involves regular checkups and detailed cleanings every three months to prevent repopulation of periodontitis-causing microorganisms, and to closely monitor affected teeth so early treatment can be rendered if the disease recurs. Usually, periodontal disease exists due to poor plaque control resulting from inappropriate brushing. Therefore, if the brushing techniques are not modified, a periodontal recurrence is probable. Other Most alternative "at-home" gum disease treatments involve injecting antimicrobial solutions, such as hydrogen peroxide, into periodontal pockets via slender applicators or oral irrigators. This process disrupts anaerobic micro-organism colonies and is effective at reducing infections and inflammation when used daily. A number of other products, functionally equivalent to hydrogen peroxide, are commercially available, but at substantially higher cost. However, such treatments do not address calculus formations, and so are short-lived, as anaerobic microbial colonies quickly regenerate in and around calculus. Doxycycline may be given alongside the primary therapy of scaling (see § initial therapy). Doxycycline has been shown to improve indicators of disease progression (namely probing depth and attachment level). Its mechanism of action involves inhibition of matrix metalloproteinases (such as collagenase), which degrade the teeths supporting tissues (periodontium) under inflammatory conditions. To avoid killing beneficial oral microbes, only small doses of doxycycline (20 mg) are used.Phage therapy may be a new therapeutic alternative. Prognosis Dentists and dental hygienists measure periodontal disease using a device called a periodontal probe. This thin "measuring stick" is gently placed into the space between the gums and the teeth, and slipped below the gumline. If the probe can slip more than 3 mm (0.12 in) below the gumline, the person is said to have a gingival pocket if no migration of the epithelial attachment has occurred or a periodontal pocket if apical migration has occurred. This is somewhat of a misnomer, as any depth is, in essence, a pocket, which in turn is defined by its depth, i.e., a 2-mm pocket or a 6-mm pocket. However, pockets are generally accepted as self-cleansable (at home, by the person, with a toothbrush) if they are 3 mm or less in depth. This is important because if a pocket is deeper than 3 mm around the tooth, at-home care will not be sufficient to cleanse the pocket, and professional care should be sought. When the pocket depths reach 6 to 7 mm (0.24 to 0.28 in) in depth, the hand instruments and ultrasonic scalers used by the dental professionals may not reach deeply enough into the pocket to clean out the microbial plaque that causes gingival inflammation. In such a situation, the bone or the gums around that tooth should be surgically altered or it will always have inflammation which will likely result in more bone loss around that tooth. An additional way to stop the inflammation would be for the person to receive subgingival antibiotics (such as minocycline) or undergo some form of gingival surgery to access the depths of the pockets and perhaps even change the pocket depths so they become 3 mm or less in depth and can once again be properly cleaned by the person at home with his or her toothbrush. If people have 7-mm or deeper pockets around their teeth, then they would likely risk eventual tooth loss over the years. If this periodontal condition is not identified and people remain unaware of the progressive nature of the disease, then years later, they may be surprised that some teeth will gradually become loose and may need to be extracted, sometimes due to a severe infection or even pain. According to the Sri Lankan tea laborer study, in the absence of any oral hygiene activity, approximately 10% will experience severe periodontal disease with rapid loss of attachment (>2 mm/year). About 80% will experience moderate loss (1–2 mm/year) and the remaining 10% will not experience any loss. Epidemiology Periodontitis is very common, and is widely regarded as the second most common dental disease worldwide, after dental decay, and in the United States has a prevalence of 30–50% of the population, but only about 10% have severe forms. Chronic periodontitis affects about 750 million people or about 10.8% of the world population as of 2010.Like other conditions intimately related to access to hygiene and basic medical monitoring and care, periodontitis tends to be more common in economically disadvantaged populations or regions. Its occurrence decreases with a higher standard of living. In Israeli population, individuals of Yemenite, North-African, South Asian, or Mediterranean origin have higher prevalence of periodontal disease than individuals from European descent. Periodontitis is frequently reported to be socially patterned, i.e. people from the lower end of the socioeconomic scale are affected more often than people from the upper end of the socioeconomic scale. History An ancient hominid from 3 million years ago had gum disease. Records from China and the Middle East, along with archaeological studies, show that mankind has had Periodontal disease for at least many thousands of years. In Europe and the Middle East archaeological research looking at ancient plaque DNA, shows that in the ancient hunter-gatherer lifestyle there was less gum disease, but that it became more common when more cereals were eaten. The Otzi Iceman was shown to have had severe gum disease. Furthermore, research has shown that in the Roman era in the UK, there was less periodontal disease than in modern times. The researchers suggest that smoking may be a key to this. Society and culture Etymology The word "periodontitis" (Greek: περιοδοντίτις) comes from the Greek peri, "around", odous (GEN odontos), "tooth", and the suffix -itis, in medical terminology "inflammation". The word pyorrhea (alternative spelling: pyorrhoea) comes from the Greek pyorrhoia (πυόρροια), "discharge of matter", itself from pyon, "discharge from a sore", rhoē, "flow", and the suffix -ia. In English this term can describe, as in Greek, any discharge of pus; i.e. it is not restricted to these diseases of the teeth. Economics It is estimated that lost productivity due to severe periodontitis costs the global economy about US$54 billion each year. Other animals Periodontal disease is the most common disease found in dogs and affects more than 80% of dogs aged three years or older. Its prevalence in dogs increases with age, but decreases with increasing body weight; i.e., toy and miniature breeds are more severely affected. Recent research undertaken at the Waltham Centre for Pet Nutrition has established that the bacteria associated with gum disease in dogs are not the same as in humans. Systemic disease may develop because the gums are very vascular (have a good blood supply). The blood stream carries these anaerobic micro-organisms, and they are filtered out by the kidneys and liver, where they may colonize and create microabscesses. The microorganisms traveling through the blood may also attach to the heart valves, causing vegetative infective endocarditis (infected heart valves). Additional diseases that may result from periodontitis include chronic bronchitis and pulmonary fibrosis. Footnotes External links Canadian Academy of Periodontology — What is periodontitis? Periodontal disease and braces. Orthodontics Australia.

You are a medical advisor. Your role is to break down medical terminology into clear, detailed explanations for a general audience.

Can you break down the meaning of the medical term 'Nonvenereal endemic syphilis' for me?

Bejel, or endemic syphilis, is a chronic skin and tissue disease caused by infection by the endemicum subspecies of the spirochete Treponema pallidum. Bejel is one of the "endemic treponematoses" (endemic infections caused by spiral-shaped bacteria called treponemes), a group that also includes yaws and pinta. Typically, endemic trepanematoses begin with localized lesions on the skin or mucous membranes. Pinta is limited to affecting the skin, whereas bejel and yaws are considered to be invasive because they can also cause disease in bone and other internal tissues. Signs and symptoms Bejel usually begins in childhood as a small patch on the mucosa, often on the interior of the mouth, followed by the appearance of raised, eroding lesions on the limbs and trunk. Periostitis (inflammation) of the leg bones is commonly seen, and gummas of the nose and soft palate develop in later stages. Causes Although the organism that causes bejel, Treponema pallidum endemicum, is morphologically and serologically indistinguishable from Treponema pallidum pallidum, which causes venereal syphilis, transmission of bejel is not venereal in nature, generally resulting from mouth-to-mouth contact or sharing of domestic utensils, and the courses of the two diseases are somewhat different. Diagnosis The diagnosis of bejel is based on the geographic history of the patient as well as laboratory testing of material from the lesions (dark-field microscopy). The responsible spirochaete is readily identifiable on sight in a microscope as a treponema. Treatment It is treatable with penicillin or other antibiotics, resulting in a complete recovery. Epidemiology Bejel is mainly found in arid countries of the eastern Mediterranean region and in West Africa, where it is known as sahel. (Sahel disease should be distinguished from "Sahel", the geographical band between the Northern Sahara and Southern Sudan.) See also Pinta (disease) Syphilis Yaws References == External links ==

You are a facilitator of medical knowledge. Provide thorough and accessible explanations of medical terms, catering to both specialists and non-specialists.

I'm trying to understand 'Trichorrhexis' within a medical context. Could you shed some light on it?

Trichorrhexis can refer to: Trichorrhexis invaginata Trichorrhexis nodosa

You act as a bridge between medical jargon and everyday language. Explain medical terms in a manner that is comprehensive yet approachable for non-experts.

Could you provide a brief overview of 'Diffuse panbronchiolitis' in a medical context?

Diffuse panbronchiolitis (DPB) is an inflammatory lung disease of unknown cause. It is a severe, progressive form of bronchiolitis, an inflammatory condition of the bronchioles (small air passages in the lungs). The term diffuse signifies that lesions appear throughout both lungs, while panbronchiolitis refers to inflammation found in all layers of the respiratory bronchioles (those involved in gas exchange). DPB causes severe inflammation and nodule-like lesions of terminal bronchioles, chronic sinusitis, and intense coughing with large amounts of sputum production. The disease is believed to occur when there is susceptibility, or a lack of immune system resistance, to DPB-causing bacteria or viruses, caused by several genes that are found predominantly in individuals of East Asian descent. The highest incidence occurs among Japanese people, followed by Koreans. DPB occurs more often in males and usually begins around age 40. It was recognized as a distinct new disease in the early 1960s and was formally named diffuse panbronchiolitis in 1969. If left untreated, DPB progresses to bronchiectasis, an irreversible lung condition that involves enlargement of the bronchioles, and pooling of mucus in the bronchiolar passages. Daily treatment of DPB with macrolide antibiotics such as erythromycin eases symptoms and increases survival time, but the disease currently has no known cure. The eventual result of DPB can be respiratory failure and heart problems. Classification The term "bronchiolitis" generally refers to inflammation of the bronchioles. DPB is classified as a form of "primary bronchiolitis", which means that the underlying cause of bronchiolitis is originating from or is confined to the bronchioles. Along with DPB, additional forms of primary bronchiolitis include bronchiolitis obliterans, follicular bronchiolitis, respiratory bronchiolitis, mineral dust airway disease, and a number of others. Unlike DPB, bronchiolitis that is not considered "primary" would be associated with diseases of the larger airways, such as chronic bronchitis. Signs and symptoms Symptoms of DPB include chronic sinusitis (inflamed paranasal sinuses), wheezing, crackles (respiratory sounds made by obstructions such as phlegm and secretions in the lungs), dyspnea (shortness of breath), and a severe cough that yields large amounts of sputum (coughed-up phlegm). There may be pus in the sputum, and affected individuals may have fever. Typical signs of DPB progression include dilation (enlargement) of the bronchiolar passages and hypoxemia (low levels of oxygen in the blood). If DPB is left untreated, bronchiectasis will occur; it is characterized by dilation and thickening of the walls of the bronchioles, inflammatory damage to respiratory and terminal bronchioles, and pooling of mucus in the lungs. DPB is associated with progressive respiratory failure, hypercapnia (increased levels of carbon dioxide in the blood), and can eventually lead to pulmonary hypertension (high blood pressure in the pulmonary vein and artery) and cor pulmonale (dilation of the right ventricle of the heart, or "right heart failure"). Cause DPB is idiopathic, which means an exact physiological, environmental, or pathogenic cause of the disease is unknown. However, several factors are suspected to be involved with its pathogenesis (the way in which the disease works).The major histocompatibility complex (MHC) is a large genomic region found in most vertebrates that is associated with the immune system. It is located on chromosome 6 in humans. A subset of MHC in humans is human leukocyte antigen (HLA), which controls the antigen-presenting system, as part of adaptive immunity against pathogens such as bacteria and viruses. When human cells are infected by a pathogen, some of them can present parts of the pathogens proteins on their surfaces; this is called "antigen presentation". The infected cells then become targets for types of cytotoxic T-cells, which kill the infected cells so they can be removed from the body.Genetic predisposition for DPB susceptibility has been localized to two HLA haplotypes (a nucleotide or gene sequence difference between paired chromosomes, that is more likely to occur among a common ethnicity or trait) common to people of East Asian descent. HLA-B54 is associated with DPB in the Japanese, while HLA-A11 is associated with the disease in Koreans. Several genes within this region of class I HLA are believed to be responsible for DPB, by allowing increased susceptibility to the disease. The common genetic background and similarities in the HLA profile of affected Japanese and Korean individuals were considered in the search for a DPB gene. It was suggested that a mutation of a suspected disease-susceptibility gene located somewhere between HLA-B and HLA-A had occurred on an ancestral chromosome carrying both HLA-B54 and HLA-A11. Further, it is possible that a number of genetic recombination events around the disease locus (location on a chromosome) could have resulted in the disease being associated with HLA-B54 in the Japanese and HLA-A11 in Koreans. After further study, it was concluded that a DPB susceptibility gene is located near the HLA-B locus at chromosome 6p21.3. Within this area, the search for a genetic cause of the disease has continued.Because many genes belonging to HLA remain unidentified, positional cloning (a method used to identify a specific gene, when only its location on a chromosome is known) has been used to determine that a mucin-like gene is associated with DPB. In addition, diseases caused by identified HLA genes in the DPB-susceptibility region have been investigated. One of these, bare lymphocyte syndrome I (BLS I), exhibits a number of similarities with DPB in those affected, including chronic sinusitis, bronchiolar inflammation and nodules, and the presence of H. influenzae. Also like DPB, BLS I responds favorably to erythromycin therapy by showing a resolution of symptoms. The similarities between these two diseases, the corresponding success with the same mode of treatment, and the fact that the gene responsible for BLS I is located within the DPB-causing area of HLA narrows the establishment of a gene responsible for DPB. Environmental factors such as inhaling toxic fumes and cigarette smoking are not believed to play a role in DPB, and unknown environmental and other non-genetic causes—such as unidentified bacteria or viruses—have not been ruled out.Cystic fibrosis (CF), a progressive multi-system lung disease, has been considered in the search for a genetic cause of DPB. This is for a number of reasons. CF, like DPB, causes severe lung inflammation, abundant mucus production, infection, and shows a genetic predominance among Caucasians of one geographic group to the rarity of others; whereas DPB dominates among East Asians, CF mainly affects individuals of European descent. While no gene has been implicated as the cause of DPB, mutation in a specific gene—much more likely to occur in Europeans—causes CF. This mutation in the CF-causing gene is not a factor in DPB, but a unique polymorphism (variation) in this gene is known to occur in many Asians not necessarily affected by either disease. It is being investigated whether this gene in any state of mutation could contribute to DPB. Pathophysiology Inflammation is a normal part of the human immune response, whereby leukocytes (white blood cells), including neutrophils (white blood cells that specialize in causing inflammation), gather, and chemokines (proteins released from certain cells, which activate or elicit a response from other cells) accumulate at any location in the body where bacterial or viral infections occur. Inflammation interferes with the activity of bacteria and viruses, and serves to clear them from the body. In DPB, bacteria such as Haemophilus influenzae and Pseudomonas aeruginosa can cause the proliferation of inflammatory cells into the bronchiolar tissues. However, when neither bacteria are present with DPB, the inflammation continues for an as yet unknown reason. In either circumstance, inflammation in DPB can be so severe that nodules containing inflammatory cells form in the walls of the bronchioles. The presence of inflammation and infection in the airways also results in the production of excess mucus, which must be coughed up as sputum. The combination of inflammation, nodule development, infection, mucus, and frequent cough contributes to the breathing difficulties in DPB.The fact that inflammation in DPB persists with or without the presence of P. aeruginosa and H. influenzae provides a means to determine several mechanisms of DPB pathogenesis. Leukotrienes are eicosanoids, signaling molecules made from essential fatty acids, which play a role in many lung diseases by causing the proliferation of inflammatory cells and excess mucus production in the airways. In DPB and other lung diseases, the predominant mediator of neutrophil-related inflammation is leukotriene B4, which specializes in neutrophil proliferation via chemotaxis (the movement of some types of cells toward or away from certain molecules).Inflammation in DPB is also caused by the chemokine MIP-1alpha and its involvement with CD8+ T cells. Beta defensins, a family of antimicrobial peptides found in the respiratory tract, are responsible for further inflammation in DPB when a pathogen such as P. aeruginosa is present. If present with DPB, the human T-lymphotropic virus, type I, a retrovirus, modifies DPB pathogenesis by infecting T helper cells and altering their effectiveness in recognizing the presence of known or unknown pathogens involved with DPB. Diagnosis The diagnosis of DPB requires analysis of the lungs and bronchiolar tissues, which can require a lung biopsy, or the more preferred high resolution computed tomography (HRCT) scan of the lungs. The diagnostic criteria include severe inflammation in all layers of the respiratory bronchioles and lung tissue lesions that appear as nodules within the terminal and respiratory bronchioles in both lungs. The nodules in DPB appear as opaque lumps when viewed on X-rays of the lung, and can cause airway obstruction, which is evaluated by a pulmonary function test, or PFT. Lung X-rays can also reveal dilation of the bronchiolar passages, another sign of DPB. HRCT scans often show blockages of some bronchiolar passages with mucus, which is referred to as the "tree-in-bud" pattern. Hypoxemia, another sign of breathing difficulty, is revealed by measuring the oxygen and carbon dioxide content of the blood, using a blood test called arterial blood gas. Other findings observed with DPB include the proliferation of lymphocytes (white blood cells that fight infection), neutrophils, and foamy histiocytes (tissue macrophages) in the lung lining. Bacteria such as H. influenzae and P. aeruginosa are also detectable, with the latter becoming more prominent as the disease progresses. The white blood, bacterial and other cellular content of the blood can be measured by taking a complete blood count (CBC). Elevated levels of IgG and IgA (classes of immunoglobulins) may be seen, as well as the presence of rheumatoid factor (an indicator of autoimmunity). Hemagglutination, a clumping of red blood cells in response to the presence of antibodies in the blood, may also occur. Neutrophils, beta-defensins, leukotrienes, and chemokines can also be detected in bronchoalveolar lavage fluid injected then removed from the bronchiolar airways of individuals with DPB, for evaluation. Differential diagnosis In the differential diagnosis (finding the correct diagnosis between diseases that have overlapping features) of some obstructive lung diseases, DPB is often considered. A number of DPB symptoms resemble those found with other obstructive lung diseases such as asthma, chronic bronchitis, and emphysema. Wheezing, coughing with sputum production, and shortness of breath are common symptoms in such diseases, and obstructive respiratory functional impairment is found on pulmonary function testing. Cystic fibrosis, like DPB, causes severe lung inflammation, excess mucus production, and infection; but DPB does not cause disturbances of the pancreas nor the electrolytes, as does CF, so the two diseases are different and probably unrelated. DPB is distinguished by the presence of lesions that appear on X-rays as nodules in the bronchioles of both lungs; inflammation in all tissue layers of the respiratory bronchioles; and its higher prevalence among individuals with East Asian lineage.DPB and bronchiolitis obliterans are two forms of primary bronchiolitis. Specific overlapping features of both diseases include strong cough with large amounts of often pus-filled sputum; nodules viewable on lung X-rays in the lower bronchi and bronchiolar area; and chronic sinusitis. In DPB, the nodules are more restricted to the respiratory bronchioles, while in OB they are often found in the membranous bronchioles (the initial non-cartilaginous section of the bronchiole, that divides from the tertiary bronchus) up to the secondary bronchus. OB is a bronchiolar disease with worldwide prevalence, while DPB has more localized prevalence, predominantly in Japan. Prior to clinical recognition of DPB in recent years, it was often misdiagnosed as bronchiectasia, COPD, IPF, phthisis miliaris, sarcoidosis or alveolar cell carcinoma. Treatment Macrolide antibiotics, such as erythromycin, are an effective treatment for DPB when taken regularly over an extended period of time. Clarithromycin or roxithromycin are also commonly used. The successful results of macrolides in DPB and similar lung diseases stems from managing certain symptoms through immunomodulation (adjusting the immune response), which can be achieved by taking the antibiotics in low doses. Treatment consists of daily oral administration of erythromycin for two to three years, an extended period that has been shown to dramatically improve the effects of DPB. This is apparent when an individual undergoing treatment for DPB, among a number of disease-related remission criteria, has a normal neutrophil count detected in BAL fluid, and blood gas (an arterial blood test that measures the amount of oxygen and carbon dioxide in the blood) readings show that free oxygen in the blood is within the normal range. Allowing a temporary break from erythromycin therapy in these instances has been suggested, to reduce the formation of macrolide-resistant P. aeruginosa. However, DPB symptoms usually return, and treatment would need to be resumed. Although highly effective, erythromycin may not prove successful in all individuals with the disease, particularly if macrolide-resistant P. aeruginosa is present or previously untreated DPB has progressed to the point where respiratory failure is occurring.With erythromycin therapy in DPB, great reduction in bronchiolar inflammation and damage is achieved through suppression of not only neutrophil proliferation, but also lymphocyte activity and obstructive mucus and water secretions in airways. The antibiotic effects of macrolides are not involved in their beneficial effects toward reducing inflammation in DPB. This is evident because the treatment dosage is much too low to fight infection, and in DPB cases with the occurrence of macrolide-resistant P. aeruginosa, erythromycin therapy still reduces inflammation.A number of factors are involved in suppression of inflammation by erythromycin and other macrolides. They are especially effective at inhibiting the proliferation of neutrophils, by diminishing the ability of interleukin 8 and leukotriene B4 to attract them. Macrolides also reduce the efficiency of adhesion molecules that allow neutrophils to stick to bronchiolar tissue linings. Mucus production in the airways is a major culprit in the morbidity and mortality of DPB and other respiratory diseases. The significant reduction of inflammation in DPB attributed to erythromycin therapy also helps to inhibit the production of excess mucus. Prognosis Untreated DPB leads to bronchiectasis, respiratory failure, and death. A journal report from 1983 indicated that untreated DPB had a five-year survival rate of 62.1%, while the 10-year survival rate was 33.2%. With erythromycin treatment, individuals with DPB now have a much longer life expectancy due to better management of symptoms, delay of progression, and prevention of associated infections like P. aeruginosa. The 10-year survival rate for treated DPB is about 90%. In DPB cases where treatment has resulted in significant improvement, which sometimes happens after about two years, treatment has been allowed to end for a while. However, individuals allowed to stop treatment during this time are closely monitored. As DPB has been proven to recur, erythromycin therapy must be promptly resumed once disease symptoms begin to reappear. In spite of the improved prognosis when treated, DPB currently has no known cure. Epidemiology DPB has its highest prevalence among the Japanese, at 11 per 100,000 population. Korean, Chinese, and Thai individuals with the disease have been reported as well. A genetic predisposition among East Asians is suggested. The disease is more common in males, with the male to female ratio at 1.4–2:1 (or about 5 men to 3 women). The average onset of the disease is around age 40, and two-thirds of those affected are non-smokers, although smoking is not believed to be a cause. The presence of HLA-Bw54 increases the risk of diffuse panbronchiolitis 13.3-fold.In Europe and the Americas, a relatively small number of DPB cases have been reported in Asian immigrants and residents, as well as in individuals of non-Asian ancestry. Misdiagnosis has occurred in the West owing to less recognition of the disease than in Asian countries. Relative to the large number of Asians living in the west, the small number of them thought to be affected by DPB suggests non-genetic factors may play some role in its cause. This rarity seen in Western Asians may also be partly associated with misdiagnosis. History In the early 1960s, a relatively new chronic lung disease was being observed and described by physicians in Japan. In 1969, the name "diffuse panbronchiolitis" was introduced to distinguish it from chronic bronchitis, emphysema, alveolitis, and other obstructive lung disease with inflammation. Between 1978 and 1980, the results of a nationwide survey initiated by the Ministry of Health and Welfare of Japan revealed more than 1,000 probable cases of DPB, with 82 histologically confirmed. By the 1980s, it was internationally recognized as a distinct disease of the lungs.Before the 1980s, the prognosis or expected outcome of DPB was poor, especially in cases with superinfection (the emergence of a new viral or bacterial infection, in addition to the currently occurring infection) by P. aeruginosa. DPB continued to have a very high mortality rate before generalized antibiotic treatment and oxygen therapy were beginning to be used routinely in the effort to manage symptoms. Around 1985, when long-term treatment with the antibiotic erythromycin became the standard for managing DPB, the prognosis significantly improved. In 1990, the association of DPB with HLA was initially asserted. References == External links ==

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Could you provide a brief overview of 'Secondary sclerosing cholangitis' in a medical context?

Secondary sclerosing cholangitis (SSC) is a chronic cholestatic liver disease. SSC is a sclerosing cholangitis with a known cause. Alternatively, if no cause can be identified, then primary sclerosing cholangitis is diagnosed. SSC is an aggressive and rare disease with complex and multiple causes. It is characterized by inflammation, fibrosis, destruction of the biliary tree and biliary cirrhosis. It can be treated with minor interventions such as continued antibiotic use and monitoring, or in more serious cases, laparoscopic surgery intervention, and possibly a liver transplant. Cause SSC is thought to develop as a consequence of known injuries or pathological processes of the biliary tree, such as biliary obstruction, surgical trauma to the bile duct, or ischemic injury to the biliary tree. Secondary causes of SSC include intraductal stone disease, surgical or blunt abdominal trauma, intra-arterial chemotherapy, and recurrent pancreatitis. It has been clearly demonstrated that sclerosing cholangitis can develop after an episode of severe bacterial cholangitis. Also it was suggested that it can result from insult to the biliary tree by obstructive cholangitis secondary to choledocholithiasis, surgical damage, trauma, vascular insults, parasites, or congenital fibrocystic disorders. Additional causes of secondary SC are toxic, due to chemical agents or drugs. Diagnosis SSC is clinically related to primary sclerosing cholangitis (PSC), but originates from a known pathological process. Diagnosis of PSC requires the exclusion of all secondary causes of sclerosing cholangitis; else, if a known aetiology can be uncovered, SSC is diagnosed. Its clinical and cholangiographic features may mimic PSC, yet its natural history may be more favorable if recognition is prompt and appropriate therapy is introduced. Sclerosing cholangitis in critically ill patients, however, is associated with rapid disease progression and poor outcome. Serologic testing, radiological imaging and histological analysis can help diagnose SSC. Treatment First lines of treatment can include mass spectrum antibiotics or drainage of the bile duct that is infected followed by close monitoring. Endoscopic surgery is favored over open procedures to reduce infection and quicker recovery times. If these fail a liver transplant may be necessary. References == External links ==

You act as a medical communicator. Your goal is to translate medical terms into comprehensive, yet straightforward language for all readers.

I need a basic explanation for the medical term 'Uveitic glaucoma.'

Uveitic glaucoma (or uveitis glaucoma, or anterior uveitic glaucoma, or anterior noninfectious uveitic glaucoma, or uveitis associated with glaucoma, or iritic glaucoma) is most commonly a progression stage of noninfectious anterior uveitis or iritis. Noninfectious anterior uveitis is an inflammation of the anterior (front) part of the eye and is instigated by autoimmune or other noninfectious causes (noninfectious uveitis can also affect the posterior segments of the eye, and then is called posterior, pan or intermediate uveitis). The onset of noninfectious uveitis occurs in patients in their thirties, with up to 10% of cases diagnosed in children under the age of 16. The condition may persist as a chronic disease. Noninfectious uveitis is the most common form of uveitis in developed countries. Approximately 30% of uveitis patients develop glaucoma as a result of the inflammation that occurs in uveitis, as a complication of steroid treatment or a combination of both.Uveitis, as well as steroid treatment for uveitis, can cause an increased resistance to the flow of aqueous humour (the clear liquid suspended between the lens and the cornea) from the eye. This leads to an excess of fluid buildup, which exerts elevated pressure on the inside parts of the eye, or elevated intraocular pressure (IOP). Elevated intraocular pressure can in turn lead to optic nerve damage and glaucoma. Based on epidemiological studies of uveitis, approximately 34-94/100,000 people will develop uveitic glaucoma (see Epidemiology section). Uveitic glaucoma patients are at significantly higher risk for visual field loss in the long term compared to patients who only have uveitis. Patients with uveitic glaucoma also experience a particularly high burden of care. Signs and symptoms Because uveitic glaucoma is a progressive stage of anterior non infectious uveitis, uveitic glaucoma involves signs and symptoms of both glaucoma and uveitis. Patients with acute non infectious anterior uveitis may experience the following symptoms: pain, blurry vision, headache, photophobia (discomfort or pain due to light exposure), or the observance of haloes around lights. An ophthalmologist may be able to observe the main sign of active noninfectious anterior uveitis, which is the presence of immune cells (anterior chamber cells, or ACCs) floating within the anterior segment of the eye (see "Noninfectious anterior uveitis" in Diagnosis section). The ophthalmologist also may observe peripheral anterior synechiae (PAS), or adhesions between the iris and trabecular meshwork, the tissue responsible for draining aqueous humour from the eye.Patients with uveitis who also experience symptoms of glaucoma may have uveitic glaucoma. In an eye with uveitic glaucoma, the following glaucoma signs may be observed: elevated intraocular pressure, scotomas in the field of vision, defects in the fiber layer of the retinal nerve, and/or excavation (a regional deformation or depression of the optic nerve). Pupillary blocks, or the obstruction of "the flow of aqueous humor from the posterior chamber to the anterior chamber" due to a "functional block between the pupillary portion of the iris and the lens" may also be detected. Finally, the ophthalmologist may observe peripheral anterior synechiae (PAS), or adhesions between the iris and trabecular meshwork.The dual presence of glaucoma and uveitis symptoms points to a diagnosis of uveitic glaucoma. Causes Uveitic glaucoma is a progressive stage of anterior noninfectious uveitis. Patients diagnosed with anterior noninfectious uveitis may also develop glaucoma; in this case the condition is termed uveitic glaucoma. Uveitic glaucoma can arise from the inflammation that occurs in uveitis; from steroid treatment for uveitis; or a combination of both. Uveitis inflammation The inflammatory response associated with uveitis may lead to glaucoma. Active anterior uveitis flare-ups may develop quickly; in these cases, the inflammation can damage the tissues in the front part of the eye. Anterior uveitis may also be chronic; in these cases, repeated inflammation can cause progressive, accumulating damage to the eye tissues. In all cases — acute one-time episodes, recurrent chronic inflammation or acute-on-chronic inflammation — damage to the eye tissues can cause increased resistance to the outflow of aqueous humour from the eye, which then increases the pressure inside the eye. In some chronic uveitis cases, the pressure inside the eye waxes and wanes due to the uveitis flare-ups.Elevated pressure inside the eye can lead to irreversible optic nerve damage and glaucoma. Steroid treatment for uveitis Topical corticosteroids are the first-line treatment for an active flare-up of noninfectious anterior uveitis, and the only effective treatment available for active inflammation. However, steroid treatment for uveitis can lead to uveitic glaucoma. Corticosteroids increase the fluid pressure inside the eye by increasing resistance to the outflow of aqueous humour, which can cause optic nerve damage and glaucoma. Steroid treatment can therefore cause or worsen uveitic glaucoma.Elevated pressure inside the eye typically develops 2 to 6 weeks after starting corticosteroid therapy, but can occur at any time during corticosteroid therapy and may continue for weeks after steroid use has been stopped. According to the Glaucoma Research Foundation, the risk of developing chronic steroid-induced glaucoma increases with every week of steroid use.Around 90% of patients with open angle glaucoma experience a steroid response of elevated intraocular pressure following steroid treatment. Therefore, once uveitis patients have developed uveitic glaucoma, they should ideally avoid steroids wherever possible. Combination of uveitis inflammation and steroid treatment In some cases, uveitis inflammation and steroid treatment both contribute to elevated pressure inside the eye, which leads to optic nerve damage and glaucoma. Pathogenesis Uveitic glaucoma as a result of recurring uveitic inflammation Uveitic glaucoma can develop as a complication of anterior uveitis resulting from the inflammatory response associated with the disease. The inflammatory response can be characterized by occlusion of the trabecular meshwork, or blocking of the tissue that is responsible for draining aqueous humour from the eye. Another characteristic that presents in some patients is peripheral anterior synechiae (PAS), or adhesions between the iris and trabecular meshwork. These two characteristics of the inflammatory uveitic response can lead to an increase in intraocular pressure, and consequently to irreversible optic nerve damage and glaucoma. Noninfectious uveitis is characterized by an inflammatory process that may be acute, recurrent, chronic or acute-on-chronic. Uveitic glaucoma is associated with an aggressive disease course caused by very high levels of intraocular pressure that wax and wane. When uveitis is acute, the onset of inflammation is rapid, with obstruction of intertrabecular spaces. When uveitis is chronic, recurrent bouts lead to tissue destruction from direct inflammation. Obstruction of the intertrabecular spaces characteristic of acute onset uveitis, as well as the repeated inflammation characteristic to chronic uveitis, can lead to elevated intraocular pressure. This can consequently cause optic nerve damage and glaucoma. Uveitic glaucoma as a response to steroid treatment of uveitis Uveitic glaucoma can also develop as a response to steroid treatment of uveitis. Corticosteroids cause a rise in the fluid pressure inside the eye. While the pathogenesis of corticosteroid-induced ocular hypertension is not fully understood, it likely involves swelling and remodeling (alterations to the extracellular matrix) of the trabecular meshwork, which leads to increased resistance to aqueous humour outflow and an increase in intraocular pressure. Another possible mechanism by which corticosteroids increase fluid pressure inside the eye is as follows: Corticosteroids inhibit (partly prevent and slow) the breakdown of glycosaminoglycans (GAGs) in the trabecular meshwork. GAGs accumulate in the meshwork. Fluid drainage is decreased. Fluid pressure in the eye is increased.It has also been suggested that corticosteroids may be capable of modifying the trabecular meshwork cells, modulating their size as well as their cytoskeletal arrangement, which in turn could limit fluid drainage. Diagnosis Uveitic glaucoma is a progression stage of noninfectious acute anterior uveitis. In order to diagnose uveitic glaucoma, a dual diagnosis of non-infectious anterior uveitis and glaucoma is required. A thorough examination of the eye by an ophthalmologist is performed in order to diagnose uveitic glaucoma. Noninfectious anterior uveitis [Main article: Uveitis] The main diagnostic sign of noninfectious acute anterior uveitis is the presence of anterior chamber cells (ACCs), or immune cells, in the anterior, or front, chamber of the eye. The anterior chamber of healthy eyes does not contain any immune cells, hence the main indicator of noninfectious anterior uveitis is the presence of immune blood cells inside the anterior chamber of the eye. The more cells found floating in the anterior chamber, the more severe the uveitis.The quantity of immune cells present in the anterior chamber can be determined via a slit lamp examination.In 2005, an International Working Group on SUN (Standardization of Uveitis Nomenclature) took steps towards standardizing the methods for reporting clinical data in the field of uveitis. One of their products was a grading scheme for anterior chamber cells. In 2021, a new slit lamp–based ACC assessment method, TGIS (Tarsier Grading Image Scale), was developed. TGIS uses a visual analog scale to enable pattern recognition-based evaluation of ACC density during a uveitic flare-up. This is achieved by graphically representing a high-power field slit beam through the anterior chamber, from the cornea to the lens surface. Another important clinical measurement of ocular inflammation is flare. Flare is the leakage of various proteins (such as fibrin and cytokines) into the ocular anterior chamber, as a manifestation of inflammation. It will usually have a "milky" appearance. Flare can also be observed via slit lamp examination. Glaucoma [Main article: Glaucoma] Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss.Glaucoma is challenging to diagnose and relies on several different methods of assessment to determine the level of optic nerve damage. These may include tonometry, a procedure to determine pressure inside the eye; a visual field test, which assesses peripheral vision; and imaging tests of the optic nerve. Treatment Treatment for uveitic glaucoma requires addressing the noninfectious anterior uveitis as well as the glaucoma present in uveitic glaucoma patients. Most urgently, the inflammation associated with uveitis must be identified and treated, to ensure as little damage to the eye as possible. Secondly, the elevated intraocular pressure associated with glaucoma must be treated. Steroid treatment may be discouraged because of the associated side effects. Treatment of noninfectious anterior uveitis Topical corticosteroid eyedrops are first-line treatment for uveitis and represent the only approved topical treatment for active non-infectious anterior uveitis. They are the only effective treatment for the short term available today. Corticosteroids can also be administered via periocular injection or intravitreal (IVT) injection. In more severe cases, treatment may be administered systemically via oral or intravenous corticosteroids. Other treatments, including systemic immunosuppressive agents — which require close monitoring — may be considered where corticosteroids are ineffective or if there are concerns regarding side effects. Immunosuppressive agents include T-cell inhibitors such as cyclosporine and tacrolimus; antimetabolites such as azathioprine, methotrexate, mycophenolate mofetil, and leflunomide; alkylating agents such as cyclophosphamides and chlorambucil; and biological drugs such as adalimumab. Most uveitis patients are treated with local steroids in the acute phase but may also need long-term treatment with lower-dose steroids as a preventive measure between flare-ups. This precaution is employed in order to minimize the use of topical corticosteroids, due to their severe ocular side effects. Despite significant advances in therapeutics, the prevalence of blindness secondary to uveitis has not been reduced in the U.S. for the past 30 years. Challenges related to steroid treatment of noninfectious anterior uveitis Steroid treatment for uveitis can lead to uveitic glaucoma. Corticosteroids increase the fluid pressure inside the eye (by increasing the resistance to the outflow of aqueous humour), which can cause optic nerve damage and glaucoma. Steroid treatment can therefore cause or worsen uveitic glaucoma.Studies show that 40% to 50% of patients treated with the corticosteroid triamcinolone via intravitreal injection developed clinically significant ocular hypertension. Corticosteroid-induced ocular hypertension typically develops 2 to 6 weeks after starting therapy but can occur at any time during corticosteroid therapy and may persist for weeks after corticosteroids have been discontinued. According to the Glaucoma Research Foundation, "every week of steroid use averaged over a lifetime leads to a 4% increased risk of chronic steroid[-induced] glaucoma".In addition, around 90% of patients with pre-existing open angle glaucoma develop an additional adverse response to steroid treatment. Treatment of uveitic glaucoma Glaucoma medications, glaucoma surgery and steroids are the primary options for addressing uveitic glaucoma. Approximately 30% of uveitic glaucoma patients require surgical intervention due to insufficient intraocular pressure control while on maximum medicinal therapy.Available surgical interventions to treat the glaucoma in uveitic glaucoma patients pose a high risk to the eye, with a lower success rate compared to glaucoma surgeries in non-uveitic eyes. Steroids for treating uveitic glaucoma patients also carry high risks. Because of the risks inherent in steroid treatment and the ineffectiveness of surgical interventions for uveitic glaucoma, there is currently no approved treatment for uveitic patients who also have glaucoma. A steroid-free medication for uveitis in uveitic glaucoma patients, formulated by Tarsier Pharma, is currently undergoing clinical trials [see Research section]. Challenges related to surgical treatment of uveitic glaucoma Uveitic glaucoma patients respond poorly to glaucoma surgery; surgery in uveitic glaucoma patients commonly has complications. These complications are caused by either the surgical wound healing improperly or unhealthy levels of pressure inside the eye.Glaucoma surgery usually leads to increased levels of inflammation in the eyes. This is an undesirable consequence, especially in uveitis patients, who already have a high tendency to develop inflammation. Because of this, 80% of uveitis experts report that glaucoma surgeries for uveitic glaucoma patients are likely to fail. Surgery in an eye with uveitis is associated with a higher complication rate, and in some cases surgeries such as valve implantation are too complicated to perform. Prognosis for uveitic glaucoma patients About 30% of uveitis patients also develop uveitic glaucoma. Uveitic glaucoma patients are at significantly higher risk for visual field loss in the long term (>5 years) compared to patients who only have uveitis. A patient who only has glaucoma (without uveitis) will, on average, become blind in one eye within 20 years of glaucoma onset. This is especially devastating given that the majority of uveitic glaucoma patients are diagnosed with uveitis at a relatively young age (in their thirties). Thus developing glaucoma at a young age and the cumulative damage of uveitis flare-ups put these patients at high risk of losing their eyesight. The burden of care for uveitis glaucoma patients is also higher than that of uveitis patients without glaucoma. On average, doctors report 60% more visits from uveitic glaucoma patients than non-glaucomatous uveitis patients. Doctor visits are 40% longer for patients with uveitic glaucoma than for uveitis patients without glaucoma. Epidemiology According to epidemiological studies, the prevalence of uveitis is estimated at 115-316 occurrences in 100,000 people. About 30% of patients with non-infectious anterior uveitis also develop glaucoma. Accordingly, 34-94 people in every 100,000 patients with uveitis will develop glaucoma. Research Steroid-free medication for uveitis and uveitic glaucoma A steroid-free eyedrop medication for uveitis and uveitic glaucoma patients, TRS01, is undergoing clinical investigation (as of May 2022). TRS01 is intended as an anti-inflammatory medication for uveitis and uveitic glaucoma that is not anticipated to contribute to elevated intraocular pressure and glaucoma. Up to May 2022, two Phase I/II clinical trials testing TRS01 have been completed. Several dozen patients have undergone these trials. TRS01 is now being investigated in a Phase III clinical trial in patients with noninfectious anterior uveitis, including some with uveitic glaucoma. == References ==

You act as a mediator between medical professionals and the public. Provide comprehensive explanations of medical terms, ensuring they are both precise and easily understood.

Could you offer a clear explanation of the term 'Leontiasis ossea' as used in the medical field?

Leontiasis ossea, also known as leontiasis, lion face or lion face syndrome, is a rare medical condition, characterized by an overgrowth of the facial and cranial bones. It is not a disease in itself, but a symptom of other diseases, including Pagets disease, fibrous dysplasia, hyperparathyroidism and renal osteodystrophy.The common form is that in which one or other maxilla is affected, its size progressively increasing, and thus encroaching on the cavities of the orbit, the mouth, the nose and its accessory sinuses. Exophthalmos gradually develops, going on later to a complete loss of sight due to compression of the optic nerve by the overgrowth of bone. There may also be interference with the nasal respiration and with the taking of food. In the somewhat less common form of this rare disease the overgrowth of bone affects all the cranial bones as well as those of the face, the senses being lost one by one and death finally resulting from cerebral pressure. There is no treatment other than exposing the overgrown bone, and chipping away pieces, or excising entirely where possible. Great Sphinx Surgeon Hutan Ashrafian from Imperial College London has analysed the Great Sphinx to identify that it may have represented an individual suffering from prognathism which may have been a reflection of a disease suffered by the sculptures human inspiration. Furthermore, as the Sphinx represented a lion, the same person may have suffered from leontiasis ossea. See also Lionitis References This article incorporates text from a publication now in the public domain: Chisholm, Hugh, ed. (1911). "Leontiasis Ossea". Encyclopædia Britannica. Vol. 16 (11th ed.). Cambridge University Press. p. 455. Lee VS, Webb MS Jr, Martinez S, McKay CP, Leight GS Jr (April 1996). "Uremic leontiasis ossea: "bighead" disease in humans? Radiologic, clinical, and pathologic features". Radiology. 199 (1): 233–240. doi:10.1148/radiology.199.1.8633151. PMID 8633151.{{cite journal}}: CS1 maint: multiple names: authors list (link)

You are a facilitator of medical knowledge. Provide thorough and accessible explanations of medical terms, catering to both specialists and non-specialists.

Can you break down the meaning of the medical term 'Indigestion' for me?

Indigestion, also known as dyspepsia or upset stomach, is a condition of impaired digestion. Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain. People may also experience feeling full earlier than expected when eating. Indigestion is relatively common, affecting 20% of people at some point during their life, and is frequently caused by gastroesophageal reflux disease (GERD) or gastritis.Indigestion is subcategorized as "organic" or "functional", but making the diagnosis can prove challenging for physicians. Organic indigestion is the result of an underlying disease, such as gastritis, peptic ulcer disease (an ulcer of the stomach or duodenum), or cancer. Functional indigestion (previously called nonulcer dyspepsia) is indigestion without evidence of underlying disease. Functional indigestion is estimated to affect about 15% of the general population in western countries and accounts for a majority of dyspepsia cases.In elderly patients (60 years of age or older) or with worrisome symptoms such as trouble swallowing, weight loss, or blood loss, an endoscopy (a procedure whereby a camera attached to a flexible tube is inserted down the throat and into the stomach) is recommended to further assess and find a potential cause. In patients younger than 60 years of age, testing for the bacteria H. pylori and if positive, treatment of the infection is recommended. More details about how indigestion is diagnosed and treated can be found below. Signs and symptoms Symptoms Patients experiencing indigestion likely report one, a combination of, or all of the following symptoms: upper abdominal pain or discomfort bloating early satiety postprandial fullness nausea with or without vomiting anorexia regurgitation belching Signs There may be abdominal tenderness, but this finding is nonspecific and is not required to make a diagnosis. However, there are physical exam signs that may point to a different diagnosis and underlying cause for a patients reported discomfort. A positive Carnett sign (focal tenderness that increases with abdominal wall contraction and palpation) suggests an etiology involving the abdominal wall musculature. Cutaneous dermatomal distribution of pain may suggest a thoracic polyradiculopathy. Tenderness to palpation over the right upper quadrant, or Murphys sign, may suggest cholecystitis or gallbladder inflammation. Alarm symptoms Also known as Alarm features, alert features, red flags, or warning signs in gastrointestinal (GI) literature. Alarm features are thought to be associated with serious gastroenterologic disease and include: chronic gastrointestinal bleeding progressive unintentional weight loss progressive difficulty swallowing (dysphagia) persistent vomiting Iron deficiency anemia Vitamin B12 deficiency (Pernicious anemia) epigastric mass Cause Indigestion is a diagnosis related to a combination of symptoms that can be attributed to "organic" or "functional" causes. Organic dyspepsia should have pathological findings upon endoscopy, like an ulcer in the stomach lining in peptic ulcer disease. Functional dyspepsia is unlikely to be detected on endoscopy but can be broken down into two subtypes, epigastric pain syndrome (EPS) and post-prandial distress syndrome (PDS). In addition, indigestion could be caused by medications, food, or other disease processes. Psychosomatic and cognitive factors are important in the evaluation of people with chronic dyspepsia. Studies have shown a high occurrence of mental disorders, notably anxiety and depression, amongst patients with dyspepsia; however, there is little evidence to prove causation. Organic Dyspepsia Esophagitis Esophagitis is an inflammation of the esophagus, most commonly caused by gastroesophageal reflux disease (GERD). It is defined by the sensation of "heartburn" or a burning sensation in the chest as a result of inappropriate relaxation of the lower esophageal sphincter at the site where the esophagus connects to the stomach. It is often treated with proton pump inhibitors. If left untreated, the chronic damage to the esophageal tissues poses a risk of developing cancer. A meta-analysis showed risk factors for developing GERD included age equal to or greater than 50, smoking, the use of non-steroid anti-inflammatory medications, and obesity. Gastritis Common causes of gastritis include peptic ulcer disease, infection, or medications. Peptic Ulcer Disease Gastric and/or duodenal ulcers are the defining feature of peptic ulcer disease (PUD). PUD is most commonly caused by an infection with H. pylori or NSAID use. Helicobacter pylori (H.pylori) infection The role of H. pylori in functional dyspepsia is controversial, and treatment for H. pylori may not lead to complete improvement of a patients dyspepsia. However, a recent systemic review and meta-analysis of 29 studies published in 2022 suggests that successful treatment of H. pylori modestly improves indigestion symptoms. Pancreatobiliary Disease These include cholelithiasis, chronic pancreatitis, and pancreatic cancer. Duodenal micro-inflammation Duodenal micro-inflammation caused by an altered duodenal gut microbiota, reactions to foods (mainly gluten proteins) or infections may induce dyspepsia symptoms in a subset of people. Functional Dyspepsia Functional dyspepsia is a common cause of chronic heartburn. More than 70% of people have no obvious organic cause for their symptoms after evaluation. Symptoms may arise from a complex interaction of increased visceral afferent sensitivity, gastric delayed emptying (gastroparesis) or impaired accommodation to food. Diagnostic criteria for functional dyspepsia categorize it into two subtypes by symptom: epigastric pain syndrome and post-prandial distress syndrome. Anxiety is also associated with functional dyspepsia. In some people, it appears before the onset of gut symptoms; in other cases, anxiety develops after onset of the disorder, which suggests that a gut-driven brain disorder may be a possible cause. Although benign, these symptoms may be chronic and difficult to treat. Epigastric Pain Syndrome (EPS) Defined by stomach pain and/or burning that interferes with daily life, without any evidence of organic disease. Post-Prandial Distress Syndrome (PDS) Defined by post-prandial fullness or early satiation that interferes with daily life, without any evidence of organic disease. Food, herb, or drug intolerance Acute, self-limited dyspepsia may be caused by overeating, eating too quickly, eating high-fat foods, eating during stressful situations, or drinking too much alcohol or coffee. Many medications cause dyspepsia, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics (metronidazole, macrolides), bronchodilators (theophylline), diabetes drugs (acarbose, metformin, Alpha-glucosidase inhibitor, amylin analogs, GLP-1 receptor antagonists), antihypertensive medications (angiotensin converting enzyme [ACE] inhibitors, Angiotensin II receptor antagonist), cholesterol-lowering agents (niacin, fibrates), neuropsychiatric medications (cholinesterase inhibitors [donepezil, rivastigmine]), SSRIs (fluoxetine, sertraline), serotonin-norepinephrine-reuptake inhibitors (venlafaxine, duloxetine), Parkinson drugs (Dopamine agonist, monoamine oxidase [MAO]-B inhibitors), weight-loss medications (orlistat), corticosteroids, estrogens, digoxin, iron, and opioids. Common herbs have also been show to cause indigestion, like white willow berry, garlic, ginkgo, chaste tree berry, saw palmetto, and feverfew. Studies have shown that wheat and dietary fats can contribute to indigestion and suggest foods high in short-chain carbohydrates (FODMAP) may be associated with dyspepsia. This suggests reducing or consuming a gluten-free, low-fat, and/or FODMAP diet may improve symptoms. Additionally, some people may experience dyspepsia when eating certain spices or spicy food as well as foods like peppers, chocolate, citrus, and fish. Systemic Diseases There are a number of systemic diseases that may involve dyspepsia, including coronary disease, congestive heart failure, diabetes mellitus, hyperparathyroidism, thyroid disease, and chronic kidney disease. Post-infectious Causes of Dyspepsia Gastroenteritis increases the risk of developing chronic dyspepsia. Post-infectious dyspepsia is the term given when dyspepsia occurs after an acute gastroenteritis infection. It is believed that the underlying causes of post-infectious IBS and post-infectious dyspepsia may be similar and represent different aspects of the same pathophysiology. Pathophysiology The pathophysiology for indigestion is not well understood; however, there are many theories. For example, there are studies that suggest a gut-brain interaction, as patients who received an antibiotic saw a reduction in their indigestion symptoms. Other theories propose issues with gut motility, a hypersensitivity of gut viscera, and imbalance of the microbiome. A genetic predisposition is plausible, but there is limited evidence to support this theory. Diagnosis A diagnosis for indigestion is based on symptoms, with a possible need for more diagnostic tests. In younger patients (less than 60 years of age) without red flags (e.g., weight loss), it is recommended to test for H. pylori noninvasively, followed by treatment with antibiotics in those who test positively. A negative test warrants discussing additional treatments, like proton pump inhibitors, with your doctor. An upper GI endoscopy may also be recommended. In older patients (60 or older), an endoscopy is often the next step in finding out the cause of newly onset indigestion regardless of the presence of alarm symptoms. However, for all patients regardless of age, an official diagnosis requires symptoms to have started at least 6 months ago with a frequency of at least once a week over the last 3 months. Treatment Functional and organic dyspepsia have similar treatments. Traditional therapies used for this diagnosis include lifestyle modification (e.g., diet), antacids, proton-pump inhibitors (PPIs), H2-receptor antagonists (H2-RAs), prokinetic agents, and antiflatulents. PPIs and H2-RAs are often first-line therapies for treating dyspepsia, having shown to be better than placebo medications. Anti-depressants, notably tricyclic antidepressants, have also been shown to be effective treatments for patients who do not respond to traditional therapies. Diet A lifestyle change that may help with indigestion is a change in diet, such as a stable and consistent eating schedule and slowing the pace of eating. Additionally, there are studies that support a reduction in the consumption of fats may also alleviate dyspepsia. While some studies suggest a correlation between dyspepsia and celiac disease, not everyone with indigestion needs to refrain from gluten in their diet. However, a gluten-free diet can relieve the symptoms in some patients without celiac disease. Lastly, a FODMAPs diet or diet low/free from certain complex sugars and sugar alcohols has also been shown to be potentially beneficial in patients with indigestion. Acid suppression Proton pump inhibitors (PPIs) were found to be better than placebo in a literature review, especially when looking at long-term symptom reduction. H2 receptor antagonists (H2-RAs) have similar effect on symptoms reduction when compared to PPIs. However, there is little evidence to support prokinetic agents are an appropriate treatment for dyspepsia.Currently, PPIs are FDA indicated for erosive esophagitis, gastroesophageal reflux disease (GERD), Zollinger-Ellison syndrome, eradication of H. pylori, duodenal and gastric ulcers, and NSAID-induced ulcer healing and prevention, but not functional dyspepsia. Prokinetics Prokinetics (medications focused on increasing gut motility), such as metoclopramide or erythromycin, has a history of use as a secondary treatment for dyspepsia. While multiple studies show that it is more effective than placebo, there are multiple concerns about the side effects surrounding the long-term use of these medications. Alternative medicine A 2021 meta-analysis concluded that herbal remedies, like menthacarin (a combination of peppermint and caraway oils), ginger, artichoke, licorice, and jollab (a combination of rose water, saffron, and candy sugar), may be as beneficial as conventional therapies when treating dyspepsia symptoms. However, it is important to note that herbal products are not regulated by the FDA and therefore it is difficult to assess the quality and safety of the ingredients found in alternative medications. Epidemiology Indigestion is a common problem and frequent reason for primary care physicians to refer patients to GI specialists. Worldwide, dyspepsia affects about a third of the population. It can affect a persons quality of life even if the symptoms within themselves are usually not life-threatening. Additionally, the financial burden on the patient and healthcare system is costly - patients with dyspepsia were more likely to have lower work productivity and higher healthcare costs compared to those without indigestion. Risk factors include NSAID-use, H. pylori infection, and smoking. See also Functional bowel disorder References == External links ==

You are an expert in medical terminology. Explain medical terms in a way that is both precise and easy to understand for non-medical audiences.

Could you provide a brief overview of 'Factitious disorder imposed on self' in a medical context?

Factitious disorder imposed on self, also known as Munchausen syndrome, is a factitious disorder in which those affected feign or induce disease, illness, injury, abuse, or psychological trauma to draw attention, sympathy, or reassurance to themselves. Munchausen syndrome fits within the subclass of factitious disorder with predominantly physical signs and symptoms, but patients also have a history of recurrent hospitalization, travelling, and dramatic, extremely improbable tales of their past experiences. The condition derives its name from the fictional character Baron Munchausen. Factitious disorder imposed on self is related to factitious disorder imposed on another, which refers to the abuse of another person, typically a child, in order to seek attention or sympathy for the abuser. This drive to create symptoms for the victim can result in unnecessary and costly diagnostic or corrective procedures. Signs and symptoms In factitious disorder imposed on self, the affected person exaggerates or creates symptoms of illnesses in themselves to gain examination, treatment, attention, sympathy or comfort from medical personnel. It often involves elements of victim playing and attention seeking. In some extreme cases, people with Munchausen syndrome are highly knowledgeable about the practice of medicine and are able to produce symptoms that result in lengthy and costly medical analysis, prolonged hospital stays, and unnecessary operations. The role of patient is a familiar and comforting one, and it fills a psychological need in people with this syndrome. This disorder is distinct from hypochondriasis and other somatoform disorders in that those with the latter do not intentionally produce their somatic symptoms. Factitious disorder is distinct from malingering in that people with factitious disorder imposed on self do not fabricate symptoms for material gain such as financial compensation, absence from work, or access to drugs. The exact cause of factitious disorder is not known, but researchers believe both biological and psychological factors play a role in the development of this disorder. Risk factors for developing factitious disorder may include childhood traumas, growing up with parents/caretakers who were emotionally unavailable due to illness or emotional problems, a serious illness as a child, failed aspirations to work in the medical field, personality disorders, and low self-esteem. While there are no reliable statistics regarding the number of people in the United States who have factitious disorder, FD is believed to be most common in mothers having the above risk factors. Those with a history of working in healthcare are also at greater risk of developing it.Arrhythmogenic Munchausen syndrome describes individuals who simulate or stimulate cardiac arrhythmias to gain medical attention.A related behavior called factitious disorder imposed on another has been documented in the parent or guardian of a child or the owner of a pet animal. The adult ensures that their child will experience some medical condition, therefore compelling the child to suffer through treatments and spend a significant portion during youth in hospitals. Furthermore, a disease may actually be initiated in the child by the parent or guardian. This condition is considered distinct from Munchausen syndrome. There is growing consensus in the pediatric community that this disorder should be renamed "medical abuse" to highlight the harm caused by the deception and to make it less likely that the sufferer can use a psychiatric defense when harm is done. Diagnosis Due to the behaviors involved, diagnosing factitious disorder is very difficult. If the healthcare provider finds no physical reason for the symptoms, they may refer the person to a psychiatrist or psychologist (mental health professionals who are specially trained to diagnose and treat mental illnesses). Psychiatrists and psychologists use thorough history, physical examinations, laboratory tests, imagery, and psychological testing to evaluate a person for physical and mental conditions. Once the persons history has been thoroughly evaluated, diagnosing factitious disorder imposed on self requires a clinical assessment. Clinicians should be aware that those presenting with symptoms (or persons reporting for that person) may exaggerate, and caution should be taken to ensure there is evidence for a diagnosis. Lab tests may be required, including complete blood count (CBC), urine toxicology, drug levels from blood, cultures, coagulation tests, assays for thyroid function, or DNA typing. In some cases CT scan, magnetic resonance imaging, psychological testing, electroencephalography, or electrocardiography may also be employed. A summary of more common and reported cases of factitious disorder (Munchausen syndrome), and the laboratory tests used to differentiate these from physical disease is provided below: There are several criteria that together may point to factitious disorder, including frequent hospitalizations, knowledge of several illnesses, frequently requesting medication such as pain killers, openness to extensive surgery, few or no visitors during hospitalizations, and exaggerated or fabricated stories about several medical problems. Factitious disorder should not be confused with hypochondria, as people with factitious disorder syndrome do not really believe they are sick; they only want to be sick, and thus fabricate the symptoms of an illness. It is also not the same as pretending to be sick for personal benefit such as being excused from work or school.People may fake their symptoms in multiple ways. Other than making up past medical histories and faking illnesses, people might inflict harm on themselves by consuming laxatives or other substances, self-inflicting injury to induce bleeding, and altering laboratory samples". Many of these conditions do not have clearly observable or diagnostic symptoms and sometimes the syndrome will go undetected because patients will fabricate identities when visiting the hospital several times. Factitious disorder has several complications, as these people will go to great lengths to fake their illness. Severe health problems, serious injuries, loss of limbs or organs, and even death are possible complications. Treatment Because there is uncertainty in treating suspected factitious disorder imposed on self, some advocate that health care providers first explicitly rule out the possibility that the person has another early-stage disease. Then they may take a careful history and seek medical records to look for early deprivation, childhood abuse, or mental illness. If a person is at risk to themself, psychiatric hospitalization may be initiated.Healthcare providers may consider working with mental health specialists to help treat the underlying mood or other disorder as well as to avoid countertransference. Therapeutic and medical treatment may center on the underlying psychiatric disorder: a mood disorder, an anxiety disorder, or borderline personality disorder. The patients prognosis depends upon the category under which the underlying disorder falls; depression and anxiety, for example, generally respond well to medication or cognitive behavioral therapy, whereas borderline personality disorder, like all personality disorders, is presumed to be pervasive and more stable over time, and thus offers a worse prognosis. People affected may have multiple scars on their abdomen due to repeated "emergency" operations. History The name "Munchausen syndrome" derives from Baron Munchausen, a literary character loosely based on the German nobleman Hieronymus Karl Friedrich, Freiherr von Münchhausen (1720–1797). The historical baron became a well-known storyteller in the late 18th century for entertaining dinner guests with tales about his adventures during the Russo-Turkish War. In 1785, German-born writer and con artist Rudolf Erich Raspe anonymously published a book in which a heavily fictionalized version of "Baron Munchausen" tells many fantastic and impossible stories about himself. Raspes Munchausen became a sensation, establishing a literary exemplar of a bombastic liar or exaggerator.In 1951, Richard Asher was the first to describe a pattern of self-harm, wherein individuals fabricated histories, signs, and symptoms of illness. Remembering Baron Munchausen, Asher named this condition Munchausens Syndrome in his article in The Lancet in February 1951, quoted in his obituary in the British Medical Journal: Here is described a common syndrome which most doctors have seen, but about which little has been written. Like the famous Baron von Munchausen, the persons affected have always travelled widely; and their stories, like those attributed to him, are both dramatic and untruthful. Accordingly the syndrome is respectfully dedicated to the Baron, and named after him. Ashers nomenclature sparked some controversy, with medical authorities debating the appropriateness of the name for about fifty years. While Asher was praised for bringing cases of factitious disorder to light, participants in the debate objected variously that a literary allusion was inappropriate given the seriousness of the disease; that its use of the anglicized spelling "Munchausen" showed poor form; that the name linked the disease with the real-life Münchhausen, who did not have it; and that the names connection to works of humor and fantasy, and to the essentially ridiculous character of the fictional Baron Munchausen, was disrespectful to patients with the disorder.Originally, this term was used for all factitious disorders. Now, however, in the DSM-5, "Munchausen syndrome" and "Munchausen by proxy" have been replaced with "factitious disorder imposed on self" and "factitious disorder imposed on another" respectively. Munchausen by Internet Munchausen by Internet is a term describing the pattern of behavior in factitious disorder imposed on self, wherein those affected feign illnesses in online venues. It has been described in medical literature as a manifestation of factitious disorder imposed on self. Reports of users who deceive Internet forum participants by portraying themselves as gravely ill or as victims of violence first appeared in the 1990s due to the relative newness of Internet communications. The specific internet pattern was named "Münchausen by Internet" in 1998 by psychiatrist Marc Feldman. New Zealand PC World Magazine called Munchausen by Internet "cybermunch", and those who posed online "cybermunchers".People may attempt to gain sympathy from a group whose sole reason for existence is to support others. Some have speculated that health care professionals, with their limited time, greater medical knowledge, and tendency to be more skeptical in their diagnoses, may be less likely to provide that support.In an article published in The Guardian, Steve Jones, speculated that the anonymity of the Internet impedes peoples abilities to realize when someone is lying. Online interaction has only been possible since the 1980s, steadily growing over the years.When discovered, forum members are frequently banned from some online forums. Because no money is exchanged and laws are rarely broken, there is little legal recourse to take upon discovery of someone faking illness.Such dramatic situations can polarize online communities. Members may feel ashamed for believing elaborate lies, while others remain staunch supporters. Feldman admits that an element of sadism may be evident in some of the more egregious abuses of trust.Other perpetrators react by issuing general accusations of dishonesty to everyone, following the exposure of such fabrications. The support groups themselves often bar discussion about the fraudulent perpetrator, in order to avoid further argument and negativity. Many forums do not recover, often splintering or shutting down.In 2004, members of the blog hosting service LiveJournal established a forum dedicated to investigating cases of members of online communities dying—sometimes while online. In 2007 The LiveJournal forum reported that, of the deaths reported to them, about 10% were real. See also Hypochondriasis Psychosomatic illness Sickened, an autobiography by Julie Gregory References Bibliography Feldman, Marc (2004). Playing sick?: untangling the web of Munchausen syndrome, Munchausen by proxy, malingering & factitious disorder. Philadelphia: Brunner-Routledge. ISBN 978-0-415-94934-7. Fisher JA (2006). "Playing patient, playing doctor: Munchausen syndrome, clinical S/M, and ruptures of medical power". The Journal of Medical Humanities. 27 (3): 135–49. doi:10.1007/s10912-006-9014-9. PMID 16817003. S2CID 40739963. Fisher JA (2006). "Investigating the Barons: narrative and nomenclature in Munchausen syndrome". Perspect. Biol. Med. 49 (2): 250–62. doi:10.1353/pbm.2006.0024. PMID 16702708. S2CID 12418075. Friedel, Robert O., MD (4 August 2004). Borderline Personality Disorder Demystified. pp. 9–10. ISBN 978-1-56924-456-2.{{cite book}}: CS1 maint: multiple names: authors list (link) Davidson, G.; et al. (2008). Abnormal Psychology - 3rd Canadian Edition. Mississauga: John Wiley & Sons Canada, Ltd. p. 412. ISBN 978-0-470-84072-6. Prasad, A.; Oswald, A. G. (1985). "Munchausens syndrome: an annotation". Acta Psychiatrica Scandinavica. 72 (4): 319–22. doi:10.1111/j.1600-0447.1985.tb02615.x. PMID 4072733. S2CID 40707. Leila Schneps and Coralie Colmez (2013). "[Chapter 1:] Math error number 1: multiplying non-independent probabilities. The case of Sally Clark: motherhood under attack". Math on trial. How numbers get used and abused in the courtroom. Basic Books. ISBN 978-0-465-03292-1. Staff, Mayo Clinic (13 May 2011). "Munchausen syndrome". Mayo Foundation for Medical Education and Research. Retrieved 11 April 2013. External links Article in Discover magazine, July 1993, by Abigail Zuger

You are an assistant in medical learning. Your role is to clarify medical terminology, ensuring the information is both accurate and accessible.

I'm seeking clarification on the medical term 'Congenital afibrinogenemia.' Could you explain it?

Congenital afibrinogenemia is a rare, genetically inherited blood fibrinogen disorder in which the blood does not clot normally due to the lack of fibrinogen, a blood protein necessary for coagulation. This disorder is autosomal recessive, meaning that two unaffected parents can have a child with the disorder. The lack of fibrinogen expresses itself with excessive and, at times, uncontrollable bleeding. Signs and symptoms As this is a disorder that is present in an individual from birth, there are no warning signs to look for. The first symptom usually seen is hemorrhage from the umbilical cord that is difficult to stop.Other symptoms include: Nasal and oral mucosa bleeds Gastrointestinal bleeding Excessive/spontaneous bleeding or bruising from minor injury Prolonged menstruation in women Spontaneous abortion during pregnancy CNS hemorrhagingSpontaneous bleeding of the mouth, nose, and gastrointestinal tract are common. Since blood clots can not be formed, minor injuries tend to lead to excessive bleeding or bruising. The biggest concern for individuals with afibrinogenemia is CNS hemorrhage, bleeding in the brain, which can be fatal. Many of these symptoms are chronic, and will continue to occur for the entirety of the affected individuals life. Causes A missense or nonsense mutation to the genes that code for the fibrinogen protein are affected. Usually the mutation leads to an early stop in the production of the protein. Due to the problem being genetically based, there is no way to prevent the disease. Individuals can get genetic testing done to see if they are a carrier of the trait, and if so may choose to complete genetic counseling to better understand the disorder and help manage family planning. Parents can choose to do prenatal genetic testing for the disorder to determine if their child will have the disease. The only risk factor is if both parents of a child carry the recessive allele linked to the disorder. Mechanism Individuals with the disorder have a mutation to their fibrinogen gene that prevents the formation of the protein. In normal conditions, fibrinogen is converted to fibrin when it is cleaved by the enzyme thrombin in the blood. The newly formed fibrin forms a fiber-rich network that helps trap red blood cells to start the coagulation process and form a clot. Since there is no fibrinogen present during afibrinogenemia, fibrin can not be formed to aid in this process. Diagnosis Diagnostic tests When a problem of fibrinogen is suspected, the following tests can be ordered: PT PTT Fibrinogen level in blood (total and clottable) Reptilase time Thrombin timeBlood fibrinogen levels of less than 0.1 g/L and prolonged bleeding test times are indicators of an individual having afibrinogenemia.A suspicion of congenital afibrinogenemia may appear on a platelet aggregation function test. Treatment The most common treatment is fibrinogen replacement therapy, including cryoprecipitate, blood plasma, and fibrinogen concentration transfusions to help with bleeding episodes or prior to surgery. Although some thrombotic complications have been reported following replacement theory, transfusions of fibrinogen concentrate are widely considered to be the most beneficial. Fibrinogen concentrate is pure, contains a known quantity of fibrinogen, is virally inactivated, and is transfused in small amounts. There is a lower chance of allergic reaction in response to transfusion. Alternatively, cryoprecipitate contains other coagulation factors, factors VIII, XIII, and von Willebrand factor. There are no known cures or forms of holistic care to date. Most complications arise from the symptoms of the disorder. Prognosis As there is not much data out on the life expectancy of an individual with afibrinogenemia, it is difficult to determine the average lifespan. However, the leading cause of death thus far is linked to CNS hemorrhage and postoperative bleeding. History It was first described in 1920 by German doctors, Fritz Rabe and Eugene Salomon, studying a bleeding disorder presenting itself in a child from birth. This disorder may also be simply called afibrinogenemia or familial afibrinogenemia. About 1 in 1 million individuals are diagnosed with the disease; typically at birth. Both males and females seem to be affected equally, but it has a higher occurrence in regions where consanguinity is prevalent. Research Currently research is based in pharmacological treatments. A case from 2015 was seen in which congenital afibrinogenemia was resolved in a patient after receiving a liver transplant. See also Factor I Deficiency References == External links ==

You are a guide to medical language. Please provide in-depth and understandable explanations of medical terms, highlighting their significance in healthcare.

Could you offer a clear explanation of the term 'Pearly penile papules' as used in the medical field?

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 ==

You function as a medical informant. Please provide in-depth yet accessible descriptions of medical terms, suitable for a broad audience.

I'm not familiar with the medical term 'Hypokinesia.' Could you provide some insights?

Hypokinesia is one of the classifications of movement disorders, and refers to decreased bodily movement. Hypokinesia is characterized by a partial or complete loss of muscle movement due to a disruption in the basal ganglia. Hypokinesia is a symptom of Parkinsons disease shown as muscle rigidity and an inability to produce movement. It is also associated with mental health disorders and prolonged inactivity due to illness, amongst other diseases. The other category of movement disorder is hyperkinesia that features an exaggeration of unwanted movement, such as twitching or writhing in Huntingtons disease or Tourette syndrome. Spectrum of disorders Hypokinesia describes a variety of more specific disorders: Causes The most common cause of Hypokinesia is Parkinsons disease, and conditions related to Parkinsons disease. Other conditions may also cause slowness of movements. These include hypothyroidism and severe depression. These conditions need to be carefully ruled out, before a diagnosis of Parkinsonism is made. The remainder of this article describes Hypokinesia associated with Parkinsons disease, and conditions related to Parkinsons disease. Pathophysiology Associated neurotransmitters Dopamine The main neurotransmitter thought to be involved in hypokinesia is dopamine. Essential to the basal ganglionic-thalamocortical loop, which processes motor function, dopamine depletion is common in these areas of hypokinesic patients. Bradykinesia is correlated with lateralized dopaminergic depletion in the substantia nigra. The dopamine pathway in the substantia nigra is essential to motor function, and commonly a lesion in this area correlates with displayed hypokinesia. Tremor and rigidity, however, seem to be only partially due to dopamine deficits in the substantia nigra, suggesting other processes are involved in motor control. Treatments for hypokinesia often either attempt to prevent dopamine degradation by MAO-B or increase the amount of neurotransmitter present in the system.GABA and glutamate The inhibitory neurotransmitter GABA and the excitatory glutamate are found in many parts of the central nervous system, including in the motor pathways that involve hypokinesia. In one pathway, glutamate in the substantia nigra excites the release of GABA into the thalamus, which then inhibits the release of glutamate in the cortex and thereby reduces motor activity. If too much glutamate is initially in the substantia nigra, then through interaction with GABA in the thalamus and glutamate in the cortex, movements will be reduced or will not occur at all.Another direct pathway from the basal ganglia sends GABA inhibitory messages to the globus pallidus and substantia nigra, which then send GABA to the thalamus. In the indirect pathway, the basal ganglia send GABA to the globus pallidus which then sends it to the subthalamic nucleus, which then disinhibited sends glutamate to the output structures of the basal ganglia. Inhibition of GABA release could disrupt the feedback loop to the basal ganglia and produce hypokinesic movements.GABA and glutamate often interact with each other and with dopamine directly. In the basal ganglia, the nigrostriatal pathway is where GABA and dopamine are housed in the same neurons and released together. Neurobiology Hypokinetic symptoms arise from damage to the basal ganglia, which plays a role in producing force and computing the effort necessary to make a movement. Two possible neural pathways enable the basal ganglia to produce movement. When activated, the direct pathway sends sensory and motor information from the cerebral cortex to the first structure of the basal ganglia, the putamen. That information directly inhibits the globus pallidus internal and allows free movement. The indirect pathway, traveling through the putamen, globus pallidus external, and subthalamic nucleus, activates the globus pallidus internal threshold and inhibits the thalamus from communicating with the motor cortex, producing hypokinetic symptoms. When levels of dopamine decrease, the normal wave-firing pattern of basal ganglia neural oscillations changes and the tendency for oscillations increases, particularly in the beta wave of the basal ganglia. Recent research indicates, when oscillations fire simultaneously, processing is disrupted at the thalamus and cortex, affecting activities such as motor planning and sequence learning, as well as causing hypokinetic tremors. Treatments Dopaminergic drugs Dopaminergic drugs are commonly used in the early stages of the hypokinesia to treat patients. With increased intake, though, they can become ineffective because of the development of noradrenergic lesions. While initially the dopaminergic drugs may be effective, these noradrenergic lesions are associated with hypokinesic gait disorder development later on.Some Parkinsons patients are unable to move during sleep, prompting the diagnosis of "nocturnal hypokinesia". Physicians have experienced success treating this sleep disorder with slow-release or night-time dopaminergic drugs, and in some cases, continuous stimulation by the dopamine agonist rotigotine. Despite improved mobility during sleep, many Parkinsons patients report an extremely uncomfortable sleeping experience even after dopaminergic treatments. Deep brain stimulation Once the reaction to dopaminergic drugs begins to fluctuate in Parkinsons patients, deep brain stimulation (DBS) of the subthalamic nucleus and internal globus pallidus is often used to treat hypokinesia. DBS, like dopaminergic drugs, initially provides relief, but chronic use causes worse hypokinesia and freezing of gait. Lower-frequency DBS in irregular patterns has been shown to be more effective and less detrimental in treatment. Posteroventral pallidotomy (PVP) is a specific kind of DBS that destroys a small part of the globus pallidus by scarring the neural tissue, reducing brain activity and therefore tremors and rigidity. PVP is suspected to recalibrate basal ganglia activity in the thalamocortical pathway. PVP in the dominant hemisphere has been reported to disrupt executive function verbal processing abilities, and bilateral PVP may disturb processes of focused attention.Many akinesia patients also form a linguistic akinesia in which their ability to produce verbal movements mirrors their physical akinesia symptoms, especially after unsuccessful PVP. Patients are usually able to maintain normal levels of fluency, but often stop midsentence, unable to remember or produce a desired word. According to a study of Parkinsons patients with articulatory hypokinesia, subjects with faster rates of speech experienced more problems trying to produce conversational language than those who normally spoke at slower rates. Methylphenidate Methylphenidate, commonly used to treat ADHD, has been used in conjunction with levodopa to treat hypokinesia in the short term. The two work together to increase dopamine levels in the striatum and prefrontal cortex. Methylphenidate mainly inhibits dopamine and noradrenaline reuptake by blocking presynaptic transporters, and levodopa increases the amount of dopamine, generally improving hypokinesic gait. Some patients, however, have adverse reactions of nausea and headache to the treatment and the long-term effects of the drug treatment still need to be assessed. Stem cells New treatments include increasing the number of dopamine cells by transplanting stem cells into the basal ganglia or stimulating endogenous stem cell production and movement to the basal ganglia. The successful integration of stem cells can relieve hypokinetic symptoms and decrease the necessary dose of dopaminergic drugs. However, a variety of complications, including possible tumor formation, inappropriate cell migration, rejection of cells by the immune system, and cerebral hemorrhage are possible, causing many physicians to believe the risks outweigh the possible benefits. NOP receptor antagonists Another treatment, still in an experimental stage, is the administration of nociception FQ peptide (NOP) receptor antagonists. This treatment has been shown to reduce hypokinesia in animal studies when increasing nociception FQ in the substantia nigra and subthalamic nucleus. Low doses can be taken with dopaminergic treatment to decrease the amount of L-dopa needed, which can reduce its long-term side effects and improve motor performance. Dance therapy Dance therapy has also been shown to reduce hypokinesic movements and rigidity, though targeted more at the muscular aspects of the disorder than the neural activity. Associations Cognitive impairment Bradykinesia has been shown to precede impairment of executive functions, working memory, and attention. These cognitive deficiencies can be tied to nonfunction of the basal ganglia and prefrontal cortex, which is also linked to the motor-dysfunction of hypokinesia. Tremor and rigidity have not had observable connections to cognitive impairments, supporting the idea that they are not as involved in the dopamine pathway in the basal ganglionic-thalamocortical loop. Dopaminergic treatments have shown improvement in cognitive functions associated with hypokinesia, suggesting they are also dependent on dopamine levels in the system. Motor motivation Often debated is whether the efficiency, vigor, and speed of movements in patients with hypokinesia are tied to motivation for rewarding and against punishing stimuli. The basal ganglia have been tied to the incentives behind movement, therefore suggesting a cost/benefit analysis of planned movement could be affected in hypokinesia. Rewards have not been shown to change the aspects of a hypokinesic individuals movement. In fact, the motor planning and control of a patient with hypokinesia is already as efficient as possible (as shown by slightly faster, but generally the same movement after deep brain stimulation of the subthalamic nucleus). This suggests that hypokinetic individuals simply have a narrower range of movement that does not increase relative to motivation.Other studies have come to the same conclusion about rewards and hypokinesia, but have shown that aversive stimuli can, in fact, reduce hypokinesic movement. Dopamine is either less involved or has a more complex role in the response to punishment than it does to rewards, as the hypodopaminergic striatum allows more movement in response to aversive stimuli. Demographic differentiation Gender More men than women typically develop hypokinesia, which is reflected in young and middle-aged populations where females have displayed higher levels of nigrostriatal dopamine than males. In the elderly, however, this differentiation is not present. Typically, women exhibit more tremor in the beginning development of hypokinesia. In the disorder, men tend to display more rigidity and women more bradykinesic motor behavior.Age of onset Hypokinesia is displayed in the brain and outwardly slightly different depending on when an individual is first affected. In young-onset hypokinesia (younger than 45 years of age), typically slightly more cell loss occurs in the substantia nigra with more displayed dystonia and muscle stiffness. In old-onset hypokinesia (older than 70 years of age), typically more of a hypokinesic gait and difficulty walking and no dystonia are seen. Both onsets can display resting tremor, although more generally found in old-onset cases. Symptoms Stress causes alterations of cerebral circulation, increasing blood flow in the supramarginal gyrus and angular gyrus of the parietal lobe, the frontal lobe, and the superior temporal gyrus of the left hemisphere. Also, an increase in cardiac activity and change in the tonus of the heart vessels occurs, which is an elementary indication of stress development. In patients with normal stress, an adaptive fight-or-flight response is usually triggered by sympathetic nervous system activation. Hypokinesia patients experience these typical stress symptoms on a regular basis because of damage to the basal ganglia system. Therefore, when a hypokinesia victim is under stress, he or she does not display a typical fight-or-flight response, placing the patient under greater danger from potentially harmful stimuli. Low-impact exercise, elimination of drug and alcohol use, and regular meditation can help to restore normal stress responses in hypokinesia patients. Connections to other medical conditions Though it is often most associated with Parkinsons disease, hypokinesia can be present in a wide variety of other conditions. See also Akinetic mutism Hyperkinesia == References ==

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I'm trying to expand my medical knowledge. Can you elucidate the term 'Mouth breathing'?

Mouth breathing, medically known as chronic oral ventilation, is long-term breathing through the mouth. It often is caused by an obstruction to breathing through the nose, the innate breathing organ in the human body. Chronic mouth breathing may be associated with illness. The term "mouth-breather" has developed a pejorative slang meaning. Etymology In the early 20th century, "mouth-breather" was a technical term used by doctors to describe children who were breathing through their mouths due to an underlying medical condition. English lexicographer Jonathon Green notes that by 1915, the phrase "mouth-breather" had developed a pejorative connotation within English slang, defined as a "stupid person." Currently, the Macmillan Dictionary defines the term "mouth breather" as a pejorative noun that is used to mean "a stupid person." Overview Jason Turowski, MD of the Cleveland Clinic states that "we are designed to breathe through our noses from birth — its the way humans have evolved." Thus, the impact of chronic mouth breathing on health is a research area within orthodontics (and the related field of myofunctional therapy) and anthropology. It is classified into three types: obstructive, habitual, and anatomic.: 281 Nasal breathing produces nitric oxide within the body, while mouth breathing does not. In addition, the Boston Medical Center notes that the nose filters out particles that enter the body, humidifies the air we breathe and warms it to body temperature. In contrast, however, mouth breathing "pulls all pollution and germs directly into the lungs; dry cold air in the lungs makes the secretions thick, slows the cleaning cilia, and slows down the passage of oxygen into the bloodstream." As a result, chronic mouth breathing may lead to illness. In about 85% of cases, it is an adaptation to nasal congestion,: 281  and frequently occurs during sleep. More specialized causes include: antrochoanal polyps;: 350  a short upper lip which prevents the lips from meeting at rest (lip incompetence);: 281  and pregnancy rhinitis which tends to occur in the third trimester of pregnancy.: 435 Potential effects Conditions associated with mouth breathing include cheilitis glandularis,: 490  Down syndrome,: 365  anterior open bite,: 225  tongue thrusting habit,: 225  cerebral palsy,: 422  ADHD, sleep apnea, and snoring. In addition, gingivitis,: 85  gingival enlargement,: 85  and increased levels of dental plaque: 108  are common in persons who chronically breathe through their mouths. The usual effect on the gums is sharply confined to the anterior maxillary region, especially the incisors (the upper teeth at the front). The appearance is erythematous (red), edematous (swollen) and shiny. This region receives the greatest exposure to airflow during mouth breathing, and it is thought that the inflammation and irritation is related to surface dehydration, but in animal experimentation, repeated air drying of the gums did not create such an appearance.: 85 Breathing through your mouth decreases saliva flow. Saliva has minerals to help neutralize bacteria, clean off the teeth, and rehydrate the tissues. Without it, your risk of gum disease and cavities increases.Chronic mouth breathing in children may affect dental and facial growth. It may also lead to the development of a long, narrow face, sometimes termed long face syndrome. Conversely, it has been suggested that a long thin face type, with corresponding thin nasopharyngeal airway, predisposes to nasal obstruction and mouth breathing. Additional approaches to mouth breathing George Catlin George Catlin was a 19th-century American painter, author, and traveler, who specialized in portraits of Native Americans in the Old West. Travelling to the American West five times during the 1830s, he wrote about, and painted portraits that depicted, the life of the Plains Indians. He was also the author of several books, including The Breath of Life (later retitled as Shut Your Mouth and Save Your Life) in 1862. It was based on his experiences traveling through the West, where he observed a consistent lifestyle habit among the Native American communities he encountered: a preference for nose breathing over mouth breathing. He also observed that they had perfectly straight teeth. He repeatedly heard that this was because they believed that mouth breathing made an individual weak and caused disease, while nasal breathing made the body strong and prevented disease. He also observed that mothers repeatedly closed the mouth of their infants while they were sleeping, to instill nasal breathing as a habit. Yoga Yogis such as B. K. S. Iyengar advocate both inhaling and exhaling through the nose in the practice of yoga, rather than inhaling through the nose and exhaling through the mouth, using the phrase, "the nose is for breathing, the mouth is for eating." References Further reading Nestor, James (2020). Breath: The New Science of a Lost Art. Riverhead Books. ISBN 978-0735213616. External links Effects of Mouth Breathing - WebMD (video clip)

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I'm looking for a concise explanation of the medical term 'Osteoclast.'

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

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The term 'Intravenous leiomyomatosis' keeps coming up in medical discussions. What does it stand for?

Intravenous leiomyomatosis is a rare condition seen exclusively in women in which leiomyomata, benign smooth muscle tumors, are found in veins. The masses are benign-appearing but can spread throughout the venous system leaving the uterus and even cause death when growing into the heart from the IVC. While the possibility that these arose de novo from the smooth muscle in the blood vessel wall was considered, chromosomal analysis suggests a uterine origin. Intravenous leiomyomata are usually but not always associated with uterine fibroids, and tend to recur. This condition is related to benign metastasizing leiomyoma, in which the masses appear in more distant locations such as the lung and lymph nodes. See also Uterine fibroids References External links IV Leiomyomas Video

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What does the medical term 'Neoplasm' encompass?

A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, when it may be called a tumor.ICD-10 classifies neoplasms into four main groups: benign neoplasms, in situ neoplasms, malignant neoplasms, and neoplasms of uncertain or unknown behavior. Malignant neoplasms are also simply known as cancers and are the focus of oncology. Prior to the abnormal growth of tissue, as neoplasia, cells often undergo an abnormal pattern of growth, such as metaplasia or dysplasia. However, metaplasia or dysplasia does not always progress to neoplasia and can occur in other conditions as well. The word is from Ancient Greek νέος- neo new and πλάσμα plasma formation, creation. Types A neoplasm can be benign, potentially malignant, or malignant (cancer). Benign tumors include uterine fibroids, osteophytes and melanocytic nevi (skin moles). They are circumscribed and localized and do not transform into cancer. Potentially-malignant neoplasms include carcinoma in situ. They are localised, do not invade and destroy but in time, may transform into a cancer. Malignant neoplasms are commonly called cancer. They invade and destroy the surrounding tissue, may form metastases and, if untreated or unresponsive to treatment, will generally prove fatal. Secondary neoplasm refers to any of a class of cancerous tumor that is either a metastatic offshoot of a primary tumor, or an apparently unrelated tumor that increases in frequency following certain cancer treatments such as chemotherapy or radiotherapy. Rarely there can be a metastatic neoplasm with no known site of the primary cancer and this is classed as a cancer of unknown primary origin. Clonality Neoplastic tumors are often heterogeneous and contain more than one type of cell, but their initiation and continued growth is usually dependent on a single population of neoplastic cells. These cells are presumed to be monoclonal – that is, they are derived from the same cell, and all carry the same genetic or epigenetic anomaly – evident of clonality. For lymphoid neoplasms, e.g. lymphoma and leukemia, clonality is proven by the amplification of a single rearrangement of their immunoglobulin gene (for B cell lesions) or T cell receptor gene (for T cell lesions). The demonstration of clonality is now considered to be necessary to identify a lymphoid cell proliferation as neoplastic.It is tempting to define neoplasms as clonal cellular proliferations but the demonstration of clonality is not always possible. Therefore, clonality is not required in the definition of neoplasia. Neoplasm vs. tumor The word tumor or tumour comes from the Latin word for swelling, which is one of the cardinal signs of inflammation. The word originally referred to any form of swelling, neoplastic or not. In modern English, tumor is used as a synonym for neoplasm (a solid or fluid-filled cystic lesion that may or may not be formed by an abnormal growth of neoplastic cells) that appears enlarged in size. Some neoplasms do not form a tumor - these include leukemia and most forms of carcinoma in situ. Tumor is also not synonymous with cancer. While cancer is by definition malignant, a tumor can be benign, precancerous, or malignant. The terms mass and nodule are often used synonymously with tumor. Generally speaking, however, the term tumor is used generically, without reference to the physical size of the lesion. More specifically, the term mass is often used when the lesion has a maximal diameter of at least 20 millimeters (mm) in greatest direction, while the term nodule is usually used when the size of the lesion is less than 20 mm in its greatest dimension (25.4 mm = 1 inch). Causes Tumors in humans occur as a result of accumulated genetic and epigenetic alterations within single cells, which cause the cell to divide and expand uncontrollably. A neoplasm can be caused by an abnormal proliferation of tissues, which can be caused by genetic mutations. Not all types of neoplasms cause a tumorous overgrowth of tissue, however (such as leukemia or carcinoma in situ) and similarities between neoplasmic growths and regenerative processes, e.g., dedifferentiation and rapid cell proliferation, have been pointed out.Tumor growth has been studied using mathematics and continuum mechanics. Vascular tumors such as hemangiomas and lymphangiomas (formed from blood or lymph vessels) are thus looked at as being amalgams of a solid skeleton formed by sticky cells and an organic liquid filling the spaces in which cells can grow. Under this type of model, mechanical stresses and strains can be dealt with and their influence on the growth of the tumor and the surrounding tissue and vasculature elucidated. Recent findings from experiments that use this model show that active growth of the tumor is restricted to the outer edges of the tumor and that stiffening of the underlying normal tissue inhibits tumor growth as well.Benign conditions that are not associated with an abnormal proliferation of tissue (such as sebaceous cysts) can also present as tumors, however, but have no malignant potential. Breast cysts (as occur commonly during pregnancy and at other times) are another example, as are other encapsulated glandular swellings (thyroid, adrenal gland, pancreas). Encapsulated hematomas, encapsulated necrotic tissue (from an insect bite, foreign body, or other noxious mechanism), keloids (discrete overgrowths of scar tissue) and granulomas may also present as tumors. Discrete localized enlargements of normal structures (ureters, blood vessels, intrahepatic or extrahepatic biliary ducts, pulmonary inclusions, or gastrointestinal duplications) due to outflow obstructions or narrowings, or abnormal connections, may also present as a tumor. Examples are arteriovenous fistulae or aneurysms (with or without thrombosis), biliary fistulae or aneurysms, sclerosing cholangitis, cysticercosis or hydatid cysts, intestinal duplications, and pulmonary inclusions as seen with cystic fibrosis. It can be dangerous to biopsy a number of types of tumor in which the leakage of their contents would potentially be catastrophic. When such types of tumors are encountered, diagnostic modalities such as ultrasound, CT scans, MRI, angiograms, and nuclear medicine scans are employed prior to (or during) biopsy or surgical exploration/excision in an attempt to avoid such severe complications. Malignant neoplasms DNA damage DNA damage is considered to be the primary underlying cause of malignant neoplasms known as cancers. Its central role in progression to cancer is illustrated in the figure in this section, in the box near the top. (The central features of DNA damage, epigenetic alterations and deficient DNA repair in progression to cancer are shown in red.) DNA damage is very common. Naturally occurring DNA damages (mostly due to cellular metabolism and the properties of DNA in water at body temperatures) occur at a rate of more than 60,000 new damages, on average, per human cell, per day [also see article DNA damage (naturally occurring) ]. Additional DNA damages can arise from exposure to exogenous agents. Tobacco smoke causes increased exogenous DNA damage, and these DNA damages are the likely cause of lung cancer due to smoking. UV light from solar radiation causes DNA damage that is important in melanoma. Helicobacter pylori infection produces high levels of reactive oxygen species that damage DNA and contributes to gastric cancer. Bile acids, at high levels in the colons of humans eating a high fat diet, also cause DNA damage and contribute to colon cancer. Katsurano et al. indicated that macrophages and neutrophils in an inflamed colonic epithelium are the source of reactive oxygen species causing the DNA damages that initiate colonic tumorigenesis. Some sources of DNA damage are indicated in the boxes at the top of the figure in this section. Individuals with a germ line mutation causing deficiency in any of 34 DNA repair genes (see article DNA repair-deficiency disorder) are at increased risk of cancer. Some germ line mutations in DNA repair genes cause up to 100% lifetime chance of cancer (e.g., p53 mutations). These germ line mutations are indicated in a box at the left of the figure with an arrow indicating their contribution to DNA repair deficiency. About 70% of malignant neoplasms have no hereditary component and are called "sporadic cancers". Only a minority of sporadic cancers have a deficiency in DNA repair due to mutation in a DNA repair gene. However, a majority of sporadic cancers have deficiency in DNA repair due to epigenetic alterations that reduce or silence DNA repair gene expression. For example, of 113 sequential colorectal cancers, only four had a missense mutation in the DNA repair gene MGMT, while the majority had reduced MGMT expression due to methylation of the MGMT promoter region (an epigenetic alteration). Five reports present evidence that between 40% and 90% of colorectal cancers have reduced MGMT expression due to methylation of the MGMT promoter region.Similarly, out of 119 cases of mismatch repair-deficient colorectal cancers that lacked DNA repair gene PMS2 expression, PMS2 was deficient in 6 due to mutations in the PMS2 gene, while in 103 cases PMS2 expression was deficient because its pairing partner MLH1 was repressed due to promoter methylation (PMS2 protein is unstable in the absence of MLH1). In the other 10 cases, loss of PMS2 expression was likely due to epigenetic overexpression of the microRNA, miR-155, which down-regulates MLH1.In further examples, epigenetic defects were found at frequencies of between 13%-100% for the DNA repair genes BRCA1, WRN, FANCB, FANCF, MGMT, MLH1, MSH2, MSH4, ERCC1, XPF, NEIL1 and ATM. These epigenetic defects occurred in various cancers (e.g. breast, ovarian, colorectal and head and neck). Two or three deficiencies in expression of ERCC1, XPF or PMS2 occur simultaneously in the majority of the 49 colon cancers evaluated by Facista et al. Epigenetic alterations causing reduced expression of DNA repair genes is shown in a central box at the third level from the top of the figure in this section, and the consequent DNA repair deficiency is shown at the fourth level. When expression of DNA repair genes is reduced, DNA damages accumulate in cells at a higher than normal level, and these excess damages cause increased frequencies of mutation or epimutation. Mutation rates strongly increase in cells defective in DNA mismatch repair or in homologous recombinational repair (HRR).During repair of DNA double strand breaks, or repair of other DNA damages, incompletely cleared sites of repair can cause epigenetic gene silencing. DNA repair deficiencies (level 4 in the figure) cause increased DNA damages (level 5 in the figure) which result in increased somatic mutations and epigenetic alterations (level 6 in the figure). Field defects, normal appearing tissue with multiple alterations (and discussed in the section below), are common precursors to development of the disordered and improperly proliferating clone of tissue in a malignant neoplasm. Such field defects (second level from bottom of figure) may have multiple mutations and epigenetic alterations. Once a cancer is formed, it usually has genome instability. This instability is likely due to reduced DNA repair or excessive DNA damage. Because of such instability, the cancer continues to evolve and to produce sub clones. For example, a renal cancer, sampled in 9 areas, had 40 ubiquitous mutations, demonstrating tumor heterogeneity (i.e. present in all areas of the cancer), 59 mutations shared by some (but not all areas), and 29 “private” mutations only present in one of the areas of the cancer. Field defects Various other terms have been used to describe this phenomenon, including "field effect", "field cancerization", and "field carcinogenesis". The term "field cancerization" was first used in 1953 to describe an area or "field" of epithelium that has been preconditioned by (at that time) largely unknown processes so as to predispose it towards development of cancer. Since then, the terms "field cancerization" and "field defect" have been used to describe pre-malignant tissue in which new cancers are likely to arise.Field defects are important in progression to cancer. However, in most cancer research, as pointed out by Rubin “The vast majority of studies in cancer research has been done on well-defined tumors in vivo, or on discrete neoplastic foci in vitro. Yet there is evidence that more than 80% of the somatic mutations found in mutator phenotype human colorectal tumors occur before the onset of terminal clonal expansion. Similarly, Vogelstein et al. point out that more than half of somatic mutations identified in tumors occurred in a pre-neoplastic phase (in a field defect), during growth of apparently normal cells. Likewise, epigenetic alterations present in tumors may have occurred in pre-neoplastic field defects.An expanded view of field effect has been termed "etiologic field effect", which encompasses not only molecular and pathologic changes in pre-neoplastic cells but also influences of exogenous environmental factors and molecular changes in the local microenvironment on neoplastic evolution from tumor initiation to patient death.In the colon, a field defect probably arises by natural selection of a mutant or epigenetically altered cell among the stem cells at the base of one of the intestinal crypts on the inside surface of the colon. A mutant or epigenetically altered stem cell may replace the other nearby stem cells by natural selection. Thus, a patch of abnormal tissue may arise. The figure in this section includes a photo of a freshly resected and lengthwise-opened segment of the colon showing a colon cancer and four polyps. Below the photo, there is a schematic diagram of how a large patch of mutant or epigenetically altered cells may have formed, shown by the large area in yellow in the diagram. Within this first large patch in the diagram (a large clone of cells), a second such mutation or epigenetic alteration may occur so that a given stem cell acquires an advantage compared to other stem cells within the patch, and this altered stem cell may expand clonally forming a secondary patch, or sub-clone, within the original patch. This is indicated in the diagram by four smaller patches of different colors within the large yellow original area. Within these new patches (sub-clones), the process may be repeated multiple times, indicated by the still smaller patches within the four secondary patches (with still different colors in the diagram) which clonally expand, until stem cells arise that generate either small polyps or else a malignant neoplasm (cancer).In the photo, an apparent field defect in this segment of a colon has generated four polyps (labeled with the size of the polyps, 6mm, 5mm, and two of 3mm, and a cancer about 3 cm across in its longest dimension). These neoplasms are also indicated, in the diagram below the photo, by 4 small tan circles (polyps) and a larger red area (cancer). The cancer in the photo occurred in the cecal area of the colon, where the colon joins the small intestine (labeled) and where the appendix occurs (labeled). The fat in the photo is external to the outer wall of the colon. In the segment of colon shown here, the colon was cut open lengthwise to expose the inner surface of the colon and to display the cancer and polyps occurring within the inner epithelial lining of the colon.If the general process by which sporadic colon cancers arise is the formation of a pre-neoplastic clone that spreads by natural selection, followed by formation of internal sub-clones within the initial clone, and sub-sub-clones inside those, then colon cancers generally should be associated with, and be preceded by, fields of increasing abnormality reflecting the succession of premalignant events. The most extensive region of abnormality (the outermost yellow irregular area in the diagram) would reflect the earliest event in formation of a malignant neoplasm.In experimental evaluation of specific DNA repair deficiencies in cancers, many specific DNA repair deficiencies were also shown to occur in the field defects surrounding those cancers. The Table, below, gives examples for which the DNA repair deficiency in a cancer was shown to be caused by an epigenetic alteration, and the somewhat lower frequencies with which the same epigenetically caused DNA repair deficiency was found in the surrounding field defect. Some of the small polyps in the field defect shown in the photo of the opened colon segment may be relatively benign neoplasms. Of polyps less than 10mm in size, found during colonoscopy and followed with repeat colonoscopies for 3 years, 25% were unchanged in size, 35% regressed or shrank in size while 40% grew in size. Genome instability Cancers are known to exhibit genome instability or a mutator phenotype. The protein-coding DNA within the nucleus is about 1.5% of the total genomic DNA. Within this protein-coding DNA (called the exome), an average cancer of the breast or colon can have about 60 to 70 protein altering mutations, of which about 3 or 4 may be “driver” mutations, and the remaining ones may be “passenger” mutations. However, the average number of DNA sequence mutations in the entire genome (including non-protein-coding regions) within a breast cancer tissue sample is about 20,000. In an average melanoma tissue sample (where melanomas have a higher exome mutation frequency) the total number of DNA sequence mutations is about 80,000. This compares to the very low mutation frequency of about 70 new mutations in the entire genome between generations (parent to child) in humans.The high frequencies of mutations in the total nucleotide sequences within cancers suggest that often an early alteration in the field defects giving rise to a cancer (e.g. yellow area in the diagram in this section) is a deficiency in DNA repair. The large field defects surrounding colon cancers (extending to at about 10 cm on each side of a cancer) were shown by Facista et al. to frequently have epigenetic defects in 2 or 3 DNA repair proteins (ERCC1, XPF or PMS2) in the entire area of the field defect. Deficiencies in DNA repair cause increased mutation rates. A deficiency in DNA repair, itself, can allow DNA damages to accumulate, and error-prone translesion synthesis past some of those damages may give rise to mutations. In addition, faulty repair of these accumulated DNA damages may give rise to epimutations. These new mutations or epimutations may provide a proliferative advantage, generating a field defect. Although the mutations/epimutations in DNA repair genes do not, themselves, confer a selective advantage, they may be carried along as passengers in cells when the cells acquire additional mutations/epimutations that do provide a proliferative advantage. Etymology The term neoplasm is a synonym of tumor. Neoplasia denotes the process of the formation of neoplasms/tumors, and the process is referred to as a neoplastic process. The word neoplastic itself comes from Greek neo new and plastic formed, molded.The term tumor derives from the Latin noun tumor a swelling, ultimately from the verb tumēre to swell. In the British Commonwealth, the spelling tumour is commonly used, whereas in the U.S. the word is usually spelled tumor.In its medical sense, tumor has traditionally meant an abnormal swelling of the flesh. The Roman medical encyclopedist Celsus (c. 30 BC–38 AD) described the four cardinal signs of acute inflammation as tumor, dolor, calor, and rubor (swelling, pain, increased heat, and redness). (His treatise, De Medicina, was the first medical book printed in 1478 following the invention of the movable-type printing press.) In contemporary English, the word tumor is often used as a synonym for a cystic (liquid-filled) growth or solid neoplasm (cancerous or non-cancerous), with other forms of swelling often referred to as "swellings".Related terms occur commonly in the medical literature, where the nouns tumefaction and tumescence (derived from the adjective tumescent) are current medical terms for non-neoplastic swelling. This type of swelling is most often caused by inflammation caused by trauma, infection, and other factors. Tumors may be caused by conditions other than an overgrowth of neoplastic cells, however. Cysts (such as sebaceous cysts) are also referred to as tumors, even though they have no neoplastic cells. This is standard in medical-billing terminology (especially when billing for a growth whose pathology has yet to be determined). See also Somatic evolution in cancer List of biological development disorders Epidemiology of cancer Pleomorphism References == External links ==

You are an assistant in medical learning. Your role is to clarify medical terminology, ensuring the information is both accurate and accessible.

I'm curious about the meaning of the medical term 'Uveitis–glaucoma–hyphema syndrome.' Can you give me some insights?

Uveitis–glaucoma–hyphaema (UGH) syndrome, also known as Ellingson syndrome, is a complication of cataract surgery, caused by intraocular lens subluxation or dislocation. The chafing of mispositioned intraocular lens over iris, ciliary body or iridocorneal angle cause elevated intraocular pressure (IOP) anterior uveitis and hyphema. It is most commonly caused by anterior chamber IOLs and sulcus IOLs but, the condition can be seen with any type of IOL, including posterior chamber lenses and cosmetic iris implants. Pathophysiology The mechanical irritation of mispositioned intraocular lens over iris, ciliary body or iridocorneal angle cause spectrum of iris transillumination defects including anterior uveitis, hyphema and elevated intraocular pressure (IOP). Uveitis results from mechanical breakdown of the blood–aqueous barrier and resultant intraocular inflammation. A hyphema results from damage to vascular tissue of the iris, ciliary body, or angle by mispositioned IOL. Elevated intraocular pressure can be caused by pigment dispersion, uveitis, hyphema or direct blocking of aqueous humor drainage system.UGH syndrome is most commonly caused by anterior chamber IOLs and sulcus IOLs, but it can be seen with any type of IOL, including posterior chamber lenses and cosmetic iris implants. The condition has significantly reduced due to increased use of posterior chamber IOLs, advancements in lens design, IOL material and surgical techniques etc. Currently, majority of IOLs are implanted in the capsular bag, minimizing the chance of IOL contacting uveal structures. Signs and symptoms Uvietis, Glaucoma, and Hyphema are the classic sins of UGH syndrome, but the term is often used when one, two, or all three signs are present in the presence of any IOL causing mechanical irritation of the iris or angle structures. Blurred vision, transient vision loss, eye pain, photophobia, erythropsia (objects appear red) are the main symptoms. Diagnosis The diagnosis of UGH Syndrome is mainly based on patient history and eye examination. Patient will have history of cataract surgery with intraocular lens implantation. Slit-lamp examination may reveal hyphaema, aqueous cells and flare, iris neovascularization, mispositioned IOL, iris-lens contact, iris transillumination defects etc. Variations UGH Plus and IPUGH (Incomplete Posterior UGH) are the variations of UGH syndrome. IPUGH is defined as bleeding into the posterior chamber with/ without glaucoma and no uveitis. UGH Plus is defined as a UGH syndrome plus a vitreous hemorrhage and occurs more frequently with anterior chamber IOLs but can occur with any IOLs. Treatment Initially, topical and systemic medication to control inflammation and raised IOP is appropriate, but the definitive treatment is an IOL reposition or exchange. Topical corticosteroids may be used to control anterior inflammation. Raised IOP can be lowered using topical and systemic anti-glaucoma medications such as prostaglandin analogs, beta-adrenergic antagonists, alpha-adrenergic agonists, and carbonic anhydrase inhibitors etc. History The UGH Syndrome was originally described by Ellingson in 1978 and classically included uveitis, glaucoma, and hyphaema in the setting of an anterior chamber IOL. == References ==

You are a medical interpreter. Your duty is to translate medical terms into easily digestible information, maintaining accuracy and detail.

I'm trying to understand 'Colonoscopy' within a medical context. Could you shed some light on it?

Colonoscopy () or coloscopy () is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It can provide a visual diagnosis (e.g., ulceration, polyps) and grants the opportunity for biopsy or removal of suspected colorectal cancer lesions. Colonoscopy can remove polyps smaller than one millimeter. Once polyps are removed, they can be studied with the aid of a microscope to determine if they are precancerous or not. It can take up to 15 years for a polyp to turn cancerous.Colonoscopy is similar to sigmoidoscopy—the difference being related to which parts of the colon each can examine. A colonoscopy allows an examination of the entire colon (1,200–1,500 mm in length). A sigmoidoscopy allows an examination of the distal portion (about 600 mm) of the colon, which may be sufficient because benefits to cancer survival of colonoscopy have been limited to the detection of lesions in the distal portion of the colon.A sigmoidoscopy is often used as a screening procedure for a full colonoscopy, often done in conjunction with a fecal occult blood test (FOBT). About 5% of these screened patients are referred to colonoscopy.Virtual colonoscopy, which uses 2D and 3D imagery reconstructed from computed tomography (CT) scans or from nuclear magnetic resonance (MR) scans, is also possible, as a totally non-invasive medical test. Virtual colonoscopy does not allow therapeutic maneuvers such as polyp and tumour removal or biopsy, nor visualization of lesions smaller than five millimeters; if a growth or polyp is detected using CT colonography, it would require removal during a standard colonoscopy. Surgeons have used the term pouchoscopy to refer to a colonoscopy of the ileo-anal pouch. Medical uses Conditions that call for colonoscopies include gastrointestinal hemorrhage, unexplained changes in bowel habit and suspicion of malignancy. Colonoscopies are often used to diagnose colon polyp and colon cancer, but are also frequently used to diagnose inflammatory bowel disease. In older patients (sometimes even younger ones) an unexplained drop in hematocrit (one sign of anemia) is an indication that calls for a colonoscopy, usually along with an esophagogastroduodenoscopy (EGD), even if no obvious blood has been seen in the stool (feces).Fecal occult blood is a quick test which can be done to test for microscopic traces of blood in the stool. A positive test is almost always an indication to do a colonoscopy. In most cases the positive result is just due to hemorrhoids; however, it can also be due to diverticulosis, inflammatory bowel disease (Crohns disease, ulcerative colitis), colon cancer, or polyps. Colonic polypectomy has become a routine part of colonoscopy, allowing quick and simple removal of polyps during the procedure, without invasive surgery. Colon cancer screening Colonoscopy is one of the colorectal cancer screening tests available to people in the US who are 45 years of age and older. The other screening tests include flexible sigmoidoscopy, double-contrast barium enema, computed tomographic (CT) colongraphy (virtual colonoscopy), guaiac-based fecal occult blood test (gFOBT), fecal immunochemical test (FIT), and multitarget stool DNA screening test (Cologuard).Subsequent rescreenings are then scheduled based on the initial results found, with a five- or ten-year recall being common for colonoscopies that produce normal results. People with a family history of colon cancer are often first screened during their teenage years. Among people who have had an initial colonoscopy that found no polyps, the risk of developing colorectal cancer within five years is extremely low. Therefore, there is no need for those people to have another colonoscopy sooner than five years after the first screening.Some medical societies in the US recommend a screening colonoscopy every 10 years beginning at age 50 for adults without increased risk for colorectal cancer. Research shows that the risk of cancer is low for 10 years if a high-quality colonoscopy does not detect cancer, so tests for this purpose are indicated every ten years.Colonoscopy screening prevents approximately two-thirds of deaths due to colorectal cancers on the left side of the colon, and is not associated with a significant reduction in deaths from right-sided disease.Colonoscopy reduces cancer rates by detecting some colon polyps and cancers on the left side of the colon early enough that they may be treated, and a smaller number on the right side; many of these left-sided growths would have been detected by a sigmoidoscopy procedure.Since polyps often take 10 to 15 years to transform into cancer in someone at average risk of colorectal cancer, guidelines recommend 10 years after a normal screening colonoscopy before the next colonoscopy. (This interval does not apply to people at high risk of colorectal cancer, or to those who experience symptoms of colorectal cancer.)Although widely touted in the US as the "gold standard" of colon cancer screening, colonoscopy has never been studied as a screening tool. Most of the potential benefits of colonoscopy have been extrapolated from randomized trials of the sigmoidoscopy. The CONFIRM trial, a randomized trial on colonoscopy vs. FIT is currently ongoing. Recommendations The American Cancer Society recommends, beginning at age 45, both men and women follow one of these testing schedules for screening to find colon polyps and/or cancer: Flexible sigmoidoscopy every 5 years, or Colonoscopy every 10 years, or Double-contrast barium enema every 5 years, or CT colonography (virtual colonoscopy) every 5 years Yearly guaiac-based fecal occult blood test (gFOBT) Yearly fecal immunochemical test (FIT) Stool DNA test (sDNA) every 3 years Medicare coverage In the United States, Medicare insurance covers the following colorectal-cancer screening tests: Colonoscopy: average risk — every 10 years beginning at age 50, high risk — every 2 years with no age restriction Flexible sigmoidoscopy — every 4 years beginning at age 50 Double-contrast barium enema: average risk — every 4 years beginning at age 50, high risk — every 2 years (CT) colongraphy: not covered by Medicare gFOBT: average risk — every year beginning at age 50 FIT: average risk — every year beginning at age 50 Cologuard: average risk — every 3 years beginning at age 50 Risks About 1 in 200 people who undergo a colonoscopy experience a serious complication. Perforation of the colon occurs in about 1 in 2000 procedures, bleeding in 2.6 per 1000, and death in 3 per 100,000, with an overall risk of serious complications of 0.35%.In some low-risk populations screening by colonoscopy in the absence of symptoms does not outweigh the risks of the procedure. For example, the odds of developing colorectal cancer between the ages of 20 and 40 in the absence of specific risk factors are about 1 in 1,250 (0.08%).The rate of complications varies with the practitioner and institution performing the procedure, and other variables. Perforation The most serious complication generally is gastrointestinal perforation, which is life-threatening and in most cases requires immediate major surgery for repair. Fewer than 20% of cases may be successfully managed with a conservative (non-surgical) approach.A 2003 analysis of the relative risks of sigmoidoscopy and colonoscopy brought into attention that the risk of perforation after colonoscopy is approximately double that after sigmoidoscopy (consistent with the fact that colonoscopy examines a longer section of the colon), a difference that appeared to be decreasing. Bleeding Bleeding complications may be treated immediately during the procedure by cauterization using the instrument. Delayed bleeding may also occur at the site of polyp removal up to a week after the procedure, and a repeat procedure can then be performed to treat the bleeding site. Even more rarely, splenic rupture can occur after colonoscopy because of adhesions between the colon and the spleen. Anaesthesia As with any procedure involving anaesthesia, other complications would include cardiopulmonary complications such as a temporary drop in blood pressure and oxygen saturation usually the result of overmedication, and are easily reversed. Anesthesia can also increase the risk of developing blood clots and lead to pulmonary embolism or deep venous thrombosis. (DVT) In rare cases, more serious cardiopulmonary events such as a heart attack, stroke, or even death may occur; these are extremely rare except in critically ill patients with multiple risk factors. In rare cases, coma associated with anesthesia may occur. Bowel preparation Dehydration caused by the laxatives that are usually administered during the bowel preparation for colonoscopy also may occur. Therefore, patients must drink large amounts of fluids during the day of colonoscopy preparation to prevent dehydration. Loss of electrolytes or dehydration is a potential risk that can even prove deadly. In rare cases, severe dehydration can lead to kidney damage or dysfunction under the form of phosphate nephropathy. Other Virtual colonoscopies carry risks that are associated with radiation exposure.Colonoscopy preparation and colonoscopy procedure can cause inflammation of the bowels and diarrhea or bowel obstruction.During colonoscopies where a polyp is removed (a polypectomy), the risk of complications has been higher, although still low at about 2.3 percent. One of the most serious complications that may arise after colonoscopy is the postpolypectomy syndrome. This syndrome occurs due to potential burns to the bowel wall when the polyp is removed, and may cause fever and abdominal pain. It is a rare complication, treated with intravenous fluids and antibiotics. Bowel infections are a potential colonoscopy risk, although rare. The colon is not a sterile environment; many bacteria that normally live in the colon ensure the well-functioning of the bowel, and the risk of infections is minimal. Infections can occur during biopsies when too much tissue is removed and bacteria protrude in areas they do not belong to, or in cases when the lining of the colon is perforated and the bacteria get into the abdominal cavity. Infection may also be transmitted between patients if the colonoscope is not cleaned and sterilized properly between tests. Minor colonoscopy risks may include nausea, vomiting or allergies to the sedatives that are used. If medication is given intravenously, the vein may become irritated. Most localized irritations to the vein leave a tender lump lasting a number of days but going away eventually. The incidence of these complications is less than 1%. On rare occasions, intracolonic explosion may occur. A meticulous bowel preparation is the key to prevent this complication.Signs of complications include severe abdominal pain, fevers and chills, or rectal bleeding (more than half a cup or 100ml). Procedure Preparation The colon must be free of solid matter for the test to be performed properly. For one to three days, the patient is required to follow a low fiber or clear-liquid-only diet. Examples of clear fluids are apple juice, chicken and/or beef broth or bouillon, lemon-lime soda, lemonade, sports drink, and water. It is important that the patient remains hydrated. Sports drinks contain electrolytes which are depleted during the purging of the bowel. Drinks containing fiber such as prune and orange juice should not be consumed, nor should liquids dyed red, purple, orange, or sometimes brown; however, cola is allowed. In most cases, tea or coffee taken without milk are allowed.The day before the colonoscopy, the patient is either given a laxative preparation (such as bisacodyl, phospho soda, sodium picosulfate, or sodium phosphate and/or magnesium citrate) and large quantities of fluid, or whole bowel irrigation is performed using a solution of polyethylene glycol and electrolytes. The procedure may involve both a pill-form laxative and a bowel irrigation preparation with the polyethylene glycol powder dissolved into any clear liquid, such as a sports drink that contains electrolytes. A typical procedure regimen then would be as follows: in the morning of the day before the procedure, a 238 g bottle of polyethylene glycol powder should be poured into 1.9 litres (64 oz.) of the chosen clear liquid, which then should be mixed and refrigerated. Two bisacodyl 5 mg tablets are taken 3 pm; at 5 pm, the patient starts drinking the mixture (approx. 8 oz. (0.5 litres) each 15-30 min. until finished); at 8 pm, take two bisacodyl 5 mg tablets; continue drinking/hydrating into the evening until bedtime with clear permitted fluids. The procedure may be scheduled early in the day so the patient need not go without food and only limited fluids until later.The goal of the preparation is to clear the colon of solid matter, and the patient may be advised to spend the day at home with ready access to toilet facilities. The patient may also want to have at hand moist towelettes or a bidet for cleaning the anus. A soothing salve such as petroleum jelly applied after cleaning the anus will reduce discomfort. The patient may be asked not to take aspirin or similar products such as salicylate, ibuprofen, etc. for up to ten days before the procedure to avoid the risk of bleeding if a polypectomy is performed during the procedure. A blood test may be performed before the procedure. Investigation During the procedure the patient is often given sedation intravenously, employing agents such as fentanyl or midazolam. Although meperidine (Demerol) may be used as an alternative to fentanyl, the concern of seizures has relegated this agent to second choice for sedation behind the combination of fentanyl and midazolam. The average person will receive a combination of these two drugs, usually between 25 and 100 µg IV fentanyl and 1–4 mg IV midazolam. Sedation practices vary between practitioners and nations; in some clinics in Norway, sedation is rarely administered.Some endoscopists are experimenting with, or routinely use, alternative or additional methods such as nitrous oxide and propofol, which have advantages and disadvantages relating to recovery time (particularly the duration of amnesia after the procedure is complete), patient experience, and the degree of supervision needed for safe administration. This sedation is called "twilight anesthesia". For some patients it is not fully effective, so they are indeed awake for the procedure and can watch the inside of their colon on the color monitor. Substituting propofol for midazolam, which gives the patient quicker recovery, is gaining wider use, but requires closer monitoring of respiration. A meta-analysis found that playing music improves tolerability to patients of the procedure.The first step is usually a digital rectal examination, to examine the tone of the sphincter and to determine if preparation has been adequate. The endoscope is then passed through the anus up the rectum, the colon (sigmoid, descending, transverse and ascending colon, the cecum), and ultimately the terminal ileum. The endoscope has a movable tip and multiple channels for instrumentation, air, suction and light. The bowel is occasionally insufflated with air to maximize visibility (a procedure that gives the patient the false sensation of needing to take a bowel movement). Biopsies are frequently taken for histology. Additionally in a procedure known as chromoendoscopy, a contrast-dye (such as indigo carmine) may be sprayed through the endoscope onto the bowel wall to help visualise any abnormalities in the mucosal morphology. A Cochrane review updated in 2016 found strong evidence that chromoscopy enhances the detection of cancerous tumours in the colon and rectum.In most experienced hands, the endoscope is advanced to the junction of where the colon and small bowel join up (cecum) in under 10 minutes in 95% of cases. Due to tight turns and redundancy in areas of the colon that are not "fixed", loops may form in which advancement of the endoscope creates a "bowing" effect that causes the tip to actually retract. These loops often result in discomfort due to stretching of the colon and its associated mesentery. Manoeuvres to "reduce" or remove the loop include pulling the endoscope backwards while twisting it. Alternatively, body position changes and abdominal support from external hand pressure can often "straighten" the endoscope to allow the scope to move forward. In a minority of patients, looping is often cited as a cause for an incomplete examination. Usage of alternative instruments leading to completion of the examination has been investigated, including use of pediatric colonoscope, push enteroscope and upper GI endoscope variants.For screening purposes, a closer visual inspection is then often performed upon withdrawal of the endoscope over the course of 20 to 25 minutes. Lawsuits over missed cancerous lesions have recently prompted some institutions to better document withdrawal time as rapid withdrawal times may be a source of potential medical legal liability. This is often a real concern in clinical settings where high caseloads could provide financial incentive to complete colonoscopies as quickly as possible. Suspicious lesions may be cauterized, treated with laser light or cut with an electric wire for purposes of biopsy or complete removal polypectomy. Medication can be injected, e.g. to control bleeding lesions. The procedure typically takes 20–30 minutes, depending on the indication and findings; with multiple polypectomies or biopsies, procedure times may be longer. As mentioned above, anatomic considerations may also affect procedure times. After the procedure, some recovery time is usually allowed to let the sedative wear off. Outpatient recovery time can take an estimated 30–60 minutes. Most facilities require that patients have a person with them to help them home afterwards (depending on the sedation method used). One common after-effect from the procedure is a bout of flatulence and minor wind pain caused by air insufflation into the colon during the procedure. An advantage of colonoscopy over X-ray imaging or other less invasive tests is the ability to perform therapeutic interventions during the test. A polyp is a growth of excess of tissue that can develop into cancer. If a polyp is found, for example, it can be removed by one of several techniques. A snare device can be placed around a polyp for removal. Even if the polyp is flat on the surface it can often be removed. For example, the following shows a polyp removed in stages: Pain management The pain associated with the procedure is not caused by the insertion of the scope but rather by the inflation of the colon in order to do the inspection. The scope itself is essentially a long, flexible tube about a centimeter in diameter — that is, as big around as the little finger, which is less than the diameter of an average stool. The colon is wrinkled and corrugated, somewhat like an accordion or a clothes-dryer exhaust tube, which gives it the large surface area needed for water absorption. In order to inspect this surface thoroughly, the physician blows it up like a balloon, using air from a compressor or carbon dioxide from a gas bottle (CO2 is absorbed into the bloodstream through the mucosal lining of the colon much faster than air and then exhaled through the lungs which is associated with less post procedural pain), in order to get the creases out. The stomach, intestines, and colon have a so-called "second brain" wrapped around them, which autonomously runs the chemical factory of digestion. It uses complex hormone signals and nerve signals to communicate with the brain and the rest of the body. Normally a colons job is to digest food and regulate the intestinal flora. The harmful bacteria in rancid food, for example, creates gas. The colon has distension sensors that can tell when there is unexpected gas pushing the colon walls out—thus the "second brain" tells the person that he or she is having intestinal difficulties by way of the sensation of nausea. Doctors typically recommend either total anesthesia or a partial twilight sedative to either preclude or to lessen the patients awareness of pain or discomfort, or just the unusual sensations of the procedure. Once the colon has been inflated, the doctor inspects it with the scope as it is slowly pulled backward. If any polyps are found they are then cut out for later biopsy. Some doctors prefer to work with totally anesthetized patients inasmuch as the lack of any perceived pain or discomfort allows for a leisurely examination. Twilight sedation is, however, inherently safer than general anesthesia; it also allows the patients to follow simple commands and even to watch the procedure on a closed-circuit monitor. Tens of millions of adults annually need to have colonoscopies, and yet many dont because of concerns about the procedure.Colonoscopy can be carried out without any sedation and without problems with pain, which is practised in several institutions in many countries with the patients agreement. This allows the patient to shift the body position to help the doctor carry out the procedure and significantly reduces recovery time and side-effects. There is some discomfort when the colon is distended with air, but this is not usually particularly painful, and it passes relatively quickly. Unsedated patients can be released from the hospital on their own without any feelings of nausea, able to continue with normal activities, and without the need for an escort as recommended after sedation. Ultrasound Duodenography and colonography are performed like a standard abdominal examination using B-mode and color flow Doppler ultrasonography using a low frequency transducer — for example a 2.5 MHz — and a high frequency transducer, for example a 7.5 MHz probe. Detailed examination of duodenal walls and folds, colonic walls and haustra was performed using a 7.5 MHz probe. Deeply located abdominal structures were examined using 2.5 MHz probe. All ultrasound examinations are performed after overnight fasting (for at least 16 hours) using standard scanning procedure. Subjects are examined with and without water contrast. Water contrast imaging is performed by having adult subjects take at least one liter of water prior to examination. Patients are examined in the supine, left posterior oblique, and left lateral decubitus positions using the intercostal and subcostal approaches. The liver, gall bladder, spleen, pancreas, duodenum, colon, and kidneys are routinely evaluated in all patients. With patient lying supine, the examination of the duodenum with high frequency ultrasound duodenography is performed with 7.5 MHz probe placed in the right upper abdomen, and central epigastric successively; for high frequency ultrasound colonography, the ascending colon, is examined with starting point usually midway of an imaginary line running from the iliac crest to the umbilicus and proceeding cephalid through the right mid abdomen; for the descending colon, the examination begins from the left upper abdomen proceeding caudally and traversing the left mid abdomen and left lower abdomen, terminating at the sigmoid colon in the lower pelvic region. Color flow Doppler sonography is used to examine the localization of lesions in relation to vessels. All measurements of diameter and wall thickness are performed with built-in software. Measurements are taken between peristaltic waves. Economics Researchers have found that older patients with three or more significant health problems, like dementia or heart failure, had high rates of repeat colonoscopies without medical indications. These patients are less likely to live long enough to develop colon cancer. Gordon states, "At about $1,000 per procedure, theres clearly an economic incentive".The Hemoccult II FOBT (combined with follow-up colonoscopy if indicated by the test) is over 5 times as cost effective as other screening strategies, but is only about 85% as sensitive. Because of this relatively low sensitivity, US guidelines advocate the over 5 times more expensive procedures instead, because even the relatively small increase in lives saved and 5-fold cost increase is seen as worth choosing, given US living standards. History In the 1960s, Dr. Niwa and Dr. Yamagata at Tokyo University developed the device. After 1968, Dr. William Wolff and Dr. Hiromi Shinya pioneered the development of the colonoscope. Their invention, in 1969 in Japan, was an advance over the barium enema and the flexible sigmoidoscope because it allowed for the visualization and removal of polyps from the entire large intestine. Wolff and Shinya advocated for their invention and published much of the early evidence needed to overcome skepticism about the devices safety and efficacy. Colonoscopy with CCD invention and market is led by Fuji film, Olympus and Hoya in Japan. In 1982, Dr. Lawrence Kaplan of Aspen Medical Group in St. Paul, MN reported a series of 100 consecutive colonoscopies and upper endoscopies performed in a free-standing clinic miles from the nearest hospital, demonstrating the safety and cost effectiveness of these outpatient procedures. (Personal communication to the Joint Commission on Ambulatory Care, May 1983) Etymology The terms colonoscopy or coloscopy are derived from the ancient Greek noun κόλον, same as English colon, and the verb σκοπεῖν, look (in)to, examine. The term colonoscopy is however ill-constructed, as this form supposes that the first part of the compound consists of a possible root κολων- or κολον-, with the connecting vowel -o, instead of the root κόλ- of κόλον. A compound such as κολωνοειδής, like a hill, (with the additional -on-) is derived from the ancient Greek word κολώνη or κολωνός, hill. Similarly, colonoscopy (with the additional -on-) can literally be translated as examination of the hill, instead of the examination of the colon. In English, multiple words exist that are derived from κόλον, such as colectomy, colocentesis, colopathy, and colostomy among many others, that actually lack the incorrect additional -on-. A few compound words such as colonopathy have doublets with -on- inserted. See also References Further reading Gupta S, Lieberman D, Anderson JC, Burke CA, Dominitz JA, Kaltenbach T, et al. (March 2020). "Recommendations for Follow-Up After Colonoscopy and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer". Gastroenterology. 158 (4): 1131–1153.e5. doi:10.1053/j.gastro.2019.10.026. PMC 7672705. PMID 32044092. Gupta S, Lieberman D, Anderson JC, Burke CA, Dominitz JA, Kaltenbach T, et al. (March 2020). "Recommendations for Follow-Up After Colonoscopy and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer". Am J Gastroenterol. 115 (3): 415–434. doi:10.14309/ajg.0000000000000544. PMC 7393611. PMID 32039982. External links Colonoscopy. Based on public-domain NIH Publication No. 02-4331, dated February 2002. Patient Education Brochures. American Society for Gastrointestinal Endoscopy information Colorectal Cancer Incidence and Screening — United States, 2008 and 2010 Centers for Disease Control and Prevention

You function as a medical explainer. Your task is to convey the meanings of medical terms in a detailed, yet easy-to-understand manner.

I've encountered the term 'Malignant multiple sclerosis' while reading about medical topics. What does it refer to exactly?

Malignant multiple sclerosis is used to describe MS patients who reach significant level of disability in a short period of time. Malignant MS cases are not common, less than 5% of patients with MS experience this type of progression.The National MS Society Advisory Committee on Clinical Trials of New Agents consensus defined it as: disease with a rapid progressive course, leading to significant disability in multiple neurologic systems or death in a relatively short time after disease onset. Reaching Expanded Disability Status Scale of 6.0 or higher, which is equivalent of needing unilateral support to ambulate (or worse) is generally considered this significant disability level.Patients with severe forms of more common relapsing remitting or progressive MS subtypes, as well as rare Marburg variant and Balo concentric sclerosis, could be considered to have malignant MS. Patients should be carefully worked up to rule out Neuromyelitis optica (Devics disease) due to the distinctive pathophysiology and management strategies of this disease. Signs and symptoms Some common physical symptoms may include: "weakness in extremities, difficulties with coordination and balance, spasticity, paresthesia, speech impediments, tremors, dizziness, hearing loss, vision impairments, bowel and bladder difficulties" Diagnosis Earlier signs include an increase in mobility over a short period of time. Malignant MS happens in patients that already have or have been diagnosed with MS. There is not a specific test to detect malignant MS; it is often confused with acute disseminated encephalomyelitis. Malignant MS is diagnosed after clinical investigations. Doctors may access the symptoms and to rule out other disorders, a neurological exam is performed. Further diagnostics may include an analysis of the cerebrospinal fluid.Neurological testing may also be performed, such as "a magnetic resonance imaging (MRI), diffusion-tensor magnetic resonance imaging (DT-MRI), and computerized brain tomography are used to detect central nervous system lesions, myelin loss, white matter abnormalities, and other physical changes in the brain." Treatment Currently, there is no cure for malignant MS; however, "immunomodulatory therapy and other physical occupational therapies can help the management of symptoms and help them more easily perform everyday tasks such as handwriting, buttoning, and using eating utensils."Some mobility aids, such as canes, walkers, and wheelchairs may also be helpful as well for patients struggling with balance and walking. MOG antibody‐associated demyelinating pseudotumor Some anti-MOG cases satisfy the MS requirements (lesions disseminated in time and space) and are therefore traditionally considered MS cases. After the discovery of the anti-MOG disease this classification is into revision. Autologous stem cell transplantation Anecdotal evidence shows that autologous stem-cell transplantation, intensive immunosuppression combined with autologous stem cell therapy, may be an effective means for treating this life-threatening condition. The process of this therapy entails plasmapheresis or immunosuppression with mitoxantrone, cyclophosphamide, cladribine or bone marrow transplantation. In one study on a 17-year-old patient, researchers tried treating the patient with high-dose chemotherapy plus anti-thymocyte globulin followed by autologous stem cell transplantation. The findings of this study were positive. After being treated with a methylprednisolone (mPDN) i.v, the patient improved significantly. When the patient began to relapse/remit, they were treated again, resulting in improvement. After this, the patient remained stable for roughly 7 months before suffering their third relapse/remit.This therapy may be a therapy option for patients with malignant MS. See also Tumefactive multiple sclerosis Marburg acute multiple sclerosis Multiple sclerosis Autologous stem cell transplantation == References ==

You are an assistant in medical learning. Your role is to clarify medical terminology, ensuring the information is both accurate and accessible.

I'm not familiar with the medical term 'Edema.' Could you provide some insights?

Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the bodys tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight, the area may feel heavy, and joint stiffness. Other symptoms depend on the underlying cause.Causes may include venous insufficiency, heart failure, kidney problems, low protein levels, liver problems, deep vein thrombosis, infections, angioedema, certain medications, and lymphedema. It may also occur after prolonged sitting or standing and during menstruation or pregnancy. The condition is more concerning if it starts suddenly, or pain or shortness of breath is present.Treatment depends on the underlying cause. If the underlying mechanism involves sodium retention, decreased salt intake and a diuretic may be used. Elevating the legs and support stockings may be useful for edema of the legs. Older people are more commonly affected. The word is from the Greek οἴδημα oídēma meaning swelling. Signs and symptoms Specific area An edema will occur in specific organs as part of inflammations, tendinitis or pancreatitis, for instance. Certain organs develop edema through tissue specific mechanisms. Examples of edema in specific organs: Peripheral edema (dependent edema of legs) is extracellular fluid accumulation in the legs. This can occur in otherwise healthy people due to hypervolemia or maintaining a standing or seated posture for an extended period of time. It can occur due to diminished venous return of blood to the heart due to congestive heart failure or pulmonary hypertension. It can also occur in patients with increased hydrostatic venous pressure or decreased oncotic venous pressure, due to obstruction of lymphatic or venous vessels draining the lower extremity. Certain drugs (for example, amlodipine) can cause pedal edema. Cerebral edema is extracellular fluid accumulation in the brain. It can occur in toxic or abnormal metabolic states and conditions such as systemic lupus or reduced oxygen at high altitudes. It causes drowsiness or loss of consciousness, leading to brain herniation and death. Pulmonary edema occurs when the pressure in blood vessels in the lung is raised because of obstruction to the removal of blood via the pulmonary veins. This is usually due to failure of the left ventricle of the heart. It can also occur in altitude sickness or on inhalation of toxic chemicals. Pulmonary edema produces shortness of breath. Pleural effusions may occur when fluid also accumulates in the pleural cavity. Edema may also be found in the cornea of the eye with glaucoma, severe conjunctivitis or keratitis or after surgery. Affected people may perceive coloured haloes around bright lights. Edema surrounding the eyes is called periorbital edema (puffy eyes) . The periorbital tissues are most noticeably swollen immediately after waking, perhaps as a result of the gravitational redistribution of fluid in the horizontal position. Common appearances of cutaneous edema are observed with mosquito bites, spider bites, bee stings (wheal and flare), and skin contact with certain plants such as poison ivy or western poison oak, the latter of which are termed contact dermatitis. Another cutaneous form of edema is myxedema, which is caused by increased deposition of connective tissue. In myxedema (and a variety of other rarer conditions) edema is caused by an increased tendency of the tissue to hold water within its extracellular space. In myxedema, this is due to an increase in hydrophilic carbohydrate-rich molecules (perhaps mostly hyaluronin) deposited in the tissue matrix. Edema forms more easily in dependent areas in the elderly (sitting in chairs at home or on aeroplanes) and this is not well understood. Estrogens alter body weight in part through changes in tissue water content. There may be a variety of poorly understood situations in which transfer of water from tissue matrix to lymphatics is impaired because of changes in the hydrophilicity of the tissue or failure of the wicking function of terminal lymphatic capillaries. In lymphedema, abnormal removal of interstitial fluid is caused by failure of the lymphatic system. This may be due to obstruction from, for example, pressure from a cancer or enlarged lymph nodes, destruction of lymph vessels by radiotherapy, or infiltration of the lymphatics by infection (such as elephantiasis). It is most commonly due to a failure of the pumping action of muscles due to immobility, most strikingly in conditions such as multiple sclerosis, or paraplegia. It has been suggested that the edema that occurs in some people following use of aspirin-like cyclo-oxygenase inhibitors such as ibuprofen or indomethacin may be due to inhibition of lymph heart action. Generalized A rise in hydrostatic pressure occurs in cardiac failure. A fall in osmotic pressure occurs in nephrotic syndrome and liver failure.Causes of edema which are generalized to the whole body can cause edema in multiple organs and peripherally. For example, severe heart failure can cause pulmonary edema, pleural effusions, ascites and peripheral edema. Such severe systemic edema is called anasarca. In rare cases, a parvovirus B19 infection may cause generalized edemas.Although a low plasma oncotic pressure is widely cited for the edema of nephrotic syndrome, most physicians note that the edema may occur before there is any significant protein in the urine (proteinuria) or fall in plasma protein level. Most forms of nephrotic syndrome are due to biochemical and structural changes in the basement membrane of capillaries in the kidney glomeruli, and these changes occur, if to a lesser degree, in the vessels of most other tissues of the body. Thus the resulting increase in permeability that leads to protein in the urine can explain the edema if all other vessels are more permeable as well.As well as the previously mentioned conditions, edemas often occur during the late stages of pregnancy in some women. This is more common with those of a history of pulmonary problems or poor circulation also being intensified if arthritis is already present in that particular woman. Women who already have arthritic problems most often have to seek medical help for pain caused from over-reactive swelling. Edemas that occur during pregnancy are usually found in the lower part of the leg, usually from the calf down. Hydrops fetalis is a condition in a baby characterized by an accumulation of fluid in at least two body compartments. Cause Heart The pumping force of the heart should help to keep a normal pressure within the blood vessels. But if the heart begins to fail (a condition known as congestive heart failure) the pressure changes can cause very severe water retention. In this condition water retention is mostly visible in the legs, feet and ankles, but water also collects in the lungs, where it causes a chronic cough. This condition is usually treated with diuretics; otherwise, the water retention may cause breathing problems and additional stress on the heart. Kidneys Another cause of severe water retention is kidney failure, where the kidneys are no longer able to filter fluid out of the blood and turn it into urine. Kidney disease often starts with inflammation, for instance in the case of diseases such as nephrotic syndrome or lupus. This type of water retention is usually visible in the form of swollen legs and ankles. Protein Protein attracts water and plays an important role in water balance. In cases of severe protein deficiency, the blood may not contain enough protein to attract water from the tissue spaces back into the capillaries. This is why starvation often shows an enlarged abdomen. The abdomen is swollen with edema or water retention caused by the lack of protein in the diet.When the capillary walls are too permeable, protein can leak out of the blood and settle in the tissue spaces. It will then act like a magnet for water, continuously attracting more water from the blood to accumulate in the tissue spaces. Others Swollen legs, feet and ankles are common in late pregnancy. The problem is partly caused by the weight of the uterus on the major veins of the pelvis. It usually clears up after delivery of the baby, and is mostly not a cause for concern, though it should always be reported to a doctor. Lack of exercise is another common cause of water retention in the legs. Exercise helps the leg veins work against gravity to return blood to the heart. If blood travels too slowly and starts to pool in the leg veins, the pressure can force too much fluid out of the leg capillaries into the tissue spaces. The capillaries may break, leaving small blood marks under the skin. The veins themselves can become swollen, painful and distorted – a condition known as varicose veins. Muscle action is needed not only to keep blood flowing through the veins but also to stimulate the lymphatic system to fulfil its "overflow" function. Long-haul flights, lengthy bed-rest, immobility caused by disability and so on, are all potential causes of water retention. Even very small exercises such as rotating ankles and wiggling toes can help to reduce it.Certain medications are prone to causing water retention. These include estrogens, thereby including drugs for hormone replacement therapy or the combined oral contraceptive pill, as well as non-steroidal anti-inflammatory drugs and beta-blockers.Premenstrual water retention, causing bloating and breast tenderness, is common. Mechanism Six factors can contribute to the formation of edema: increased hydrostatic pressure; reduced colloidal or oncotic pressure within blood vessels; increased tissue colloidal or oncotic pressure; increased blood vessel wall permeability (such as inflammation); obstruction of fluid clearance in the lymphatic system; changes in the water-retaining properties of the tissues themselves. Raised hydrostatic pressure often reflects retention of water and sodium by the kidneys.Generation of interstitial fluid is regulated by the forces of the Starling equation. Hydrostatic pressure within blood vessels tends to cause water to filter out into the tissue. This leads to a difference in protein concentration between blood plasma and tissue. As a result, the colloidal or oncotic pressure of the higher level of protein in the plasma tends to draw water back into the blood vessels from the tissue. Starlings equation states that the rate of leakage of fluid is determined by the difference between the two forces and also by the permeability of the vessel wall to water, which determines the rate of flow for a given force imbalance. Most water leakage occurs in capillaries or post capillary venules, which have a semi-permeable membrane wall that allows water to pass more freely than protein. (The protein is said to be reflected and the efficiency of reflection is given by a reflection constant of up to 1.) If the gaps between the cells of the vessel wall open up then permeability to water is increased first, but as the gaps increase in size permeability to protein also increases with a fall in reflection coefficient.Changes in the variables in Starlings equation can contribute to the formation of edemas either by an increase in hydrostatic pressure within the blood vessel, a decrease in the oncotic pressure within the blood vessel or an increase in vessel wall permeability. The latter has two effects. It allows water to flow more freely and it reduces the colloidal or oncotic pressure difference by allowing protein to leave the vessel more easily.Another set of vessels known as the lymphatic system acts like an "overflow" and can return much excess fluid to the bloodstream. But even the lymphatic system can be overwhelmed, and if there is simply too much fluid, or if the lymphatic system is congested, then the fluid will remain in the tissues, causing swellings in legs, ankles, feet, abdomen or any other part of the body. Diagnosis Cutaneous edema is referred to as "pitting" when, after pressure is applied to a small area, the indentation persists after the release of the pressure. Peripheral pitting edema, as shown in the illustration, is the more common type, resulting from water retention. It can be caused by systemic diseases, pregnancy in some women, either directly or as a result of heart failure, or local conditions such as varicose veins, thrombophlebitis, insect bites, and dermatitis.Non-pitting edema is observed when the indentation does not persist. It is associated with such conditions as lymphedema, lipedema, and myxedema.Edema caused by malnutrition defines kwashiorkor, an acute form of childhood protein-energy malnutrition characterized by edema, irritability, anorexia, ulcerating dermatoses, and an enlarged liver with fatty infiltrates. Treatment When possible, treatment involves resolving the underlying cause. Many cases of heart or kidney disease are treated with diuretics.Treatment may also involve positioning the affected body parts to improve drainage. For example, swelling in feet or ankles may be reduced by having the person lie down in bed or sit with the feet propped up on cushions. Intermittent pneumatic compression can be used to pressurize tissue in a limb, forcing fluids—both blood and lymph—to flow out of the compressed area. References == External links ==

You are a facilitator of medical knowledge. Provide thorough and accessible explanations of medical terms, catering to both specialists and non-specialists.

Could you please explain the term 'Tramadol' in simple language?

Tramadol, sold under the brand name Ultram among others, is an opioid pain medication used to treat moderate to moderately severe pain. When taken by mouth in an immediate-release formulation, the onset of pain relief usually begins within an hour. It is also available by injection. It is available in combination with paracetamol (acetaminophen). As is typical of opioids, common side effects include constipation, itchiness, and nausea. Serious side effects may include hallucinations, seizures, increased risk of serotonin syndrome, decreased alertness, and drug addiction. A change in dosage may be recommended in those with kidney or liver problems. It is not recommended in those who are at risk of suicide or in those who are pregnant. While not recommended in women who are breastfeeding, those who take a single dose should not generally stop breastfeeding. Tramadol is converted in the liver to O-desmethyltramadol (desmetramadol), an opioid with a stronger affinity to the μ-opioid receptor. Tramadol is also a serotonin–norepinephrine reuptake inhibitor (SNRI).Tramadol was patented in 1963 and launched under the name "Tramal" in 1977 by the West German pharmaceutical company Grünenthal GmbH. In the mid-1990s, it was approved in the United Kingdom and the United States. It is available as a generic medication and marketed under many brand names worldwide. In 2020, it was the 35th most commonly prescribed medication in the United States, with more than 17 million prescriptions. Medical uses Tramadol (a schedule IV drug in the US) is used primarily to treat mild to severe pain, both acute and chronic. There is moderate evidence for use as a second-line treatment for fibromyalgia but it is not FDA approved for this use; however, its use is approved for treatment of fibromyalgia as a secondary painkiller by the NHS.Its analgesic effects take about one hour to come into effect and 2 to 4 h to peak after oral administration with an immediate-release formulation. On a dose-by-dose basis, tramadol has about one-tenth the potency of morphine (thus 100 mg is commensurate with 10 mg morphine but may vary) and is practically equally potent when compared with pethidine and codeine. For pain moderate in severity, its effectiveness is equivalent to that of codeine at low doses, and hydrocodone at very high doses; for severe pain it is less effective than morphine.These painkilling effects last about 6 h. The potency of analgesia varies considerably as it depends on an individuals genetics. People with specific variants of CYP2D6 enzymes may not produce adequate amounts of the active metabolite (desmetramadol) for effective pain control.Sleep medicine physicians sometimes prescribe tramadol (or other opiate medications) for refractory restless legs syndrome (RLS); that is, RLS that does not respond adequately to treatment with first-line medications such as dopamine agonists (like pramipexole) or alpha-2-delta (α2δ) ligands (gabapentinoids), often due to augmentation. Contraindications Tramadol may not provide adequate pain control for individuals with certain genetic variants of CYP2D6 enzymes as they metabolize tramadol to the inactive molecule. These genetic polymorphisms are not currently routinely tested for in clinical practice. Pregnancy and lactation Tramadols use in pregnancy is generally avoided, as it may cause some reversible withdrawal effects in the newborn. A small prospective study in France found, while an increased risk of miscarriages existed, no major malformations were reported in the newborn. Its use during lactation is also generally advised against, but a small trial found that infants breastfed by mothers taking tramadol were exposed to about 2.88% of the dose the mothers were taking. No evidence of this dose harming the newborn was seen. Labor and delivery Its use as an analgesic during labor is not advised due to its long onset of action (1 hour). The ratio of the mean concentration of the drug in the fetus compared to that of the mother when it is given intramuscularly for labor pains has been estimated to be 1:94. Children Its use in children is generally advised against, although it may be done under the supervision of a specialist. On 21 September 2015, the FDA started investigating the safety of tramadol in use in persons under the age of 17. The investigation was initiated because some of these people have experienced slowed or difficult breathing. The FDA lists age under 12 years old as a contraindication. Elderly The risk of opioid-related adverse effects such as respiratory depression, falls, cognitive impairment and sedation is increased. Tramadol may interact with other medications and increase the risk for adverse events. Liver and kidney failure The drug should be used with caution in those with liver or kidney failure, due to metabolism in the liver (to the active molecule desmetramadol) and elimination by the kidneys. Side effects The most common adverse effects of tramadol include nausea, dizziness, dry mouth, indigestion, abdominal pain, vertigo, vomiting, constipation, drowsiness, and headache. Other side effects may result from interactions with other medications. Tramadol has the same dose-dependent adverse effects as morphine including respiratory depression. Dependence and withdrawal Long-term use of high doses of tramadol causes physical dependence and withdrawal syndrome. These include both symptoms typical of opioid withdrawal and those associated with serotonin–norepinephrine reuptake inhibitor (SNRI) withdrawal; symptoms include numbness, tingling, paresthesia, and tinnitus. Psychiatric symptoms may include hallucinations, paranoia, extreme anxiety, panic attacks, and confusion. In most cases, tramadol withdrawal will set in 12–20 hours after the last dose, but this can vary. Tramadol withdrawal typically lasts longer than that of other opioids. Seven days or more of acute withdrawal symptoms can occur as opposed to typically 3 or 4 days for other codeine analogues. Overdose Recognised risk factors for tramadol overdose include respiratory depression, addiction, and seizures. Naloxone only partially reverses the toxic effects of tramadol overdose and may increase the risk of seizures.Deaths with tramadol overdose have been reported and are increasing in frequency in Northern Ireland; the majority of these overdoses involve other drugs including alcohol. There were 254 tramadol-related deaths in England and Wales in 2013, and 379 in Florida in 2011. In 2011, 21,649 emergency room visits in the United States were related to tramadol. Interactions Tramadol can interact with other medications with similar mechanisms of action. Tramadol acts as a serotonin-norephinephrine reuptake inhibitor and thus can interact with other serotonergic medications (selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, tricyclic antidepressants, triptans, cough and cold medications containing dextromethorphan, herbal products containing St. John’s wort, and medications that inhibit the metabolism of serotonin, such as monoamine oxidase inhibitors) and, in combination, may lead to serotonin syndrome. It may also make some serotonergic antagonist anti-emetic medications (ondansetron) less effective.Tramadol also acts as an opioid agonist and thus can increase the risk for side effects when used with other opioid analgesics (such as morphine, pethidine, tapentadol, oxycodone, and fentanyl).Tramadol is metabolized by CYP2D6 enzymes which contribute to the metabolism of approximately 25% of all medications. Any medications with the ability to inhibit or induce these enzymes may interact with tramadol.Tramadol increases the risk for seizures by lowering the seizure threshold. Using other medications that lower seizure threshold (such as antipsychotic medications or amphetamines), further increases this risk. Pharmacology Mechanism of action Tramadol induces analgesic effects through a variety of different targets on the noradrenergic system, serotoninergic system and opioid receptors system. Tramadol exists as a racemic mixture, the positive enantiomer inhibits serotonin reuptake while the negative enantiomer inhibits noradrenaline re-uptake, by binding to and blocking the transporters. Tramadol has also been shown to act as a serotonin releasing agent. Both enantiomers of tramadol are agonists of the μ-opioid receptor and its M1 metabolite, O-desmetramadol, is also a μ-opioid receptor agonist but is 6 times more potent than tramadol itself. All these effects work synergistically to induce analgesia. Tramadol has been found to possess these actions: Agonist of the μ-opioid receptor (MOR) and to a far lesser extent of the δ-opioid receptor (DOR) and κ-opioid receptor (KOR) Serotonin reuptake inhibitor (SRI) and norepinephrine reuptake inhibitor; hence, an SNRI Serotonin 5-HT2C receptor antagonist M1 and M3 muscarinic acetylcholine receptor antagonist α7 nicotinic acetylcholine receptor antagonist NMDA receptor antagonist (very weak) TRPA1 inhibitorTramadol acts on the opioid receptors through its major active metabolite desmetramadol, which has as much as 700-fold higher affinity for the MOR relative to tramadol. Moreover, tramadol itself has been found to possess no efficacy in activating the MOR in functional activity assays, whereas desmetramadol activates the receptor with high intrinsic activity (Emax equal to that of morphine). As such, desmetramadol is exclusively responsible for the opioid effects of tramadol. Both tramadol and desmetramadol have pronounced selectivity for the MOR over the DOR and KOR in terms of binding affinity.Tramadol is well-established as an SRI. In addition, a few studies have found that it also acts as a serotonin releasing agent (1–10 μM), similar in effect to fenfluramine. The serotonin releasing effects of tramadol could be blocked by sufficiently high concentrations of the serotonin reuptake inhibitor 6-nitroquipazine, which is in accordance with other serotonin releasing agents such as fenfluramine and MDMA. However, two more recent studies failed to find a releasing effect of tramadol at respective concentrations up to 10 and 30 μM. In addition to serotonergic activity, tramadol is also a norepinephrine reuptake inhibitor. It is not a norepinephrine releasing agent. Tramadol does not inhibit the reuptake or induce the release of dopamine.A positron emission tomography imaging study found that single oral 50-mg and 100-mg doses of tramadol to human volunteers resulted in 34.7% and 50.2% respective mean occupation of the serotonin transporter (SERT) in the thalamus. The estimated median effective dose (ED50) for SERT occupancy hence was 98.1 mg, which was associated with a plasma tramadol level of about 330 ng/ml (1,300 nM). The estimated maximum daily dosage of tramadol of 400 mg (100 mg q.i.d.) would result in as much as 78.7% occupancy of the SERT (in association with a plasma concentration of 1,220 ng/ml or 4,632 nM). This is close to that of SSRIs, which occupy the SERT by 80% or more.Peak plasma concentrations during treatment with clinical dosages of tramadol have generally been found to be in the range of 70 to 592 ng/ml (266–2,250 nM) for tramadol and 55 to 143 ng/ml (221–573 nM) for desmetramadol. The highest levels of tramadol were observed with the maximum oral daily dosage of 400 mg per day divided into one 100-mg dose every 6 hours (i.e., four 100-mg doses evenly spaced out per day). Some accumulation of tramadol occurs with chronic administration; peak plasma levels with the maximum oral daily dosage (100 mg q.i.d.) are about 16% higher and the area-under-the-curve levels 36% higher than following a single oral 100-mg dose. Positron emission tomography imaging studies have reportedly found that tramadol levels are at least four-fold higher in the brain than in plasma. Conversely, brain levels of desmetramadol "only slowly approach those in plasma". The plasma protein binding of tramadol is only 4 to 20%; hence, almost all tramadol in circulation is free, thus bioactive. Correspondence to effects Co-administration of quinidine, a potent CYP2D6 enzyme inhibitor, with tramadol, a combination which results in markedly reduced levels of desmetramadol, was found not to significantly affect the analgesic effects of tramadol in human volunteers. However, other studies have found that the analgesic effects of tramadol are significantly decreased or even absent in CYP2D6 poor metabolizers. The analgesic effects of tramadol are only partially reversed by naloxone in human volunteers, hence indicating that its opioid action is unlikely the sole factor; tramadols analgesic effects are also partially reversed by α2-adrenergic receptor antagonists such as yohimbine, the 5-HT3 receptor antagonist ondansetron, and the 5-HT7 receptor antagonists SB-269970 and SB-258719. Pharmacologically, tramadol is similar to tapentadol and methadone in that it not only binds to the MOR, but also inhibits the reuptake of serotonin and norepinephrine due to its action on the noradrenergic and serotonergic systems, such as its "atypical" opioid activity.Tramadol has inhibitory actions on the 5-HT2C receptor. Antagonism of 5-HT2C could be partially responsible for tramadols reducing effect on depressive and obsessive–compulsive symptoms in patients with pain and co-morbid neurological illnesses. 5-HT2C blockade may also account for its lowering of the seizure threshold, as 5-HT2C knockout mice display significantly increased vulnerability to epileptic seizures, sometimes resulting in spontaneous death. However, the reduction of seizure threshold could be attributed to tramadols putative inhibition of GABAA receptors at high doses (significant inhibition at 100 μM). In addition, desmetramadol is a high-affinity ligand of the DOR, and activation of this receptor could be involved in tramadols ability to provoke seizures in some individuals, as DOR agonists are well known for inducing seizures.Nausea and vomiting caused by tramadol are thought to be due to activation of the 5-HT3 receptor via increased serotonin levels. In accordance, the 5-HT3 receptor antagonist ondansetron can be used to treat tramadol-associated nausea and vomiting. Tramadol and desmetramadol themselves do not bind to the 5-HT3 receptor. Pharmacokinetics Tramadol undergoes hepatic metabolism via the cytochrome P450 isozyme CYP2B6, CYP2D6, and CYP3A4, being O- and N-demethylated to five different metabolites. Of these, desmetramadol (O-desmethyltramadol) is the most significant, since it has 200 times the μ-affinity of (+)-tramadol, and furthermore has an elimination half-life of 9 hours, compared with 6 hours for tramadol itself. As with codeine, in the 6% of the population who have reduced CYP2D6 activity (hence reducing metabolism), a reduced analgesic effect is seen. Those with decreased CYP2D6 activity require a dose increase of 30% to achieve the same degree of pain relief as those with a normal level of CYP2D6 activity.Phase II hepatic metabolism renders the metabolites water-soluble, which are excreted by the kidneys. Thus, reduced doses may be used in renal and hepatic impairment.Its volume of distribution is around 306 L after oral administration and 203 L after parenteral administration. Chemistry Tramadol is marketed as a racemic mixture of both R- and S-stereoisomers, because the two isomers complement each others analgesic activities. The (+)-isomer is predominantly active as an opiate with a higher affinity for the µ-opiate receptor (20 times higher affinity than the (-)-isomer). Synthesis and stereoisomerism The chemical synthesis of tramadol is described in the literature. Tramadol [2-(dimethylaminomethyl)-1-(3-methoxyphenyl)cyclohexanol] has two stereogenic centers at the cyclohexane ring. Thus, 2-(dimethylaminomethyl)-1-(3-methoxyphenyl)cyclohexanol may exist in four different configurational forms: (1R,2R)-isomer (1S,2S)-isomer (1R,2S)-isomer (1S,2R)-isomerThe synthetic pathway leads to the racemate (1:1 mixture) of (1R,2R)-isomer and the (1S,2S)-isomer as the main products. Minor amounts of the racemic mixture of the (1R,2S)-isomer and the (1S,2R)-isomer are formed as well. The isolation of the (1R,2R)-isomer and the (1S,2S)-isomer from the diastereomeric minor racemate [(1R,2S)-isomer and (1S,2R)-isomer] is realized by the recrystallization of the hydrochlorides. The drug tramadol is a racemate of the hydrochlorides of the (1R,2R)-(+)- and the (1S,2S)-(−)-enantiomers. The resolution of the racemate [(1R,2R)-(+)-isomer / (1S,2S)-(−)-isomer] was described employing (R)-(−)- or (S)-(+)-mandelic acid. This process does not find industrial application, since tramadol is used as a racemate, despite known different physiological effects of the (1R,2R)- and (1S,2S)-isomers, because the racemate showed higher analgesic activity than either enantiomer in animals and in humans. Detection in biological fluids Tramadol and desmetramadol may be quantified in blood, plasma, serum, or saliva to monitor for abuse, confirm a diagnosis of poisoning or assist in the forensic investigation of a sudden death. Most commercial opiate immunoassay screening tests do not cross-react significantly with tramadol or its major metabolites, so chromatographic techniques must be used to detect and quantitate these substances. The concentration of desmetramadol in the blood or plasma of a person who has taken tramadol is generally 10–20% those of the parent drug. Society and culture Formulations Available dosage forms include liquids, syrups, drops, elixirs, effervescent tablets and powders for mixing with water, capsules, tablets including extended-release formulations, suppositories, compounding powder, and injections. Patent history The U.S. Food and Drug Administration (FDA) approved tramadol in March 1995, and an extended-release (ER) formulation in September 2005. ER Tramadol was protected by US patents nos. 6,254,887 and 7,074,430. The FDA listed the patents expiration as 10 May 2014. However, in August 2009, US District Court for the District of Delaware ruled the patents invalid, a decision upheld the following year by the Court of Appeals for the Federal Circuit. Manufacture and distribution of generic equivalents of Ultram ER in the United States was therefore permitted prior to the expiration of the patents. Legal status Effective 18 August 2014, tramadol has been placed into Schedule IV of the federal Controlled Substances Act in the United States. Before that, some US states had already classified tramadol as a Schedule IV controlled substance under their respective state laws.Tramadol is classified in Schedule 4 (prescription only) in Australia, rather than as a Schedule 8 Controlled Drug (Possession without authority illegal) like most other opioids.Effective May 2008, Sweden classified tramadol as a controlled substance in the same category as codeine and dextropropoxyphene, but allows a normal prescription to be used.The UK classified tramadol as a Class C, Schedule 3 controlled drug on 10 June 2014, but exempted it from the safe custody requirement. Misuse Illicit use of the drug is thought to be a major factor in the success of the Boko Haram terrorist organization. When used at higher doses, the drug "can produce similar effects to heroin." Said one former member, "whenever we took tramadol, nothing mattered to us anymore except what we were sent to do because it made us very high and very bold, it was impossible to go on a mission without taking it." Tramadol is also used as a coping mechanism in the Gaza Strip. It is also abused in the United Kingdom, inspiring the title of the TV show Frankie Boyles Tramadol Nights (2010).From March 2019, the Union Cycliste Internationale (UCI) banned the drug, after riders were using the painkiller to improve their performance. Research Investigational uses Diabetic neuropathy Antidepressant Postherpetic neuralgia Premature ejaculation Adjunct to local anaesthesia False findings about sources in nature In 2013, researchers reported that tramadol was found in relatively high concentrations (1%+) in the roots of the African pin cushion tree (Nauclea latifolia). In 2014, however, it was reported that the presence of tramadol in the tree roots was the result of tramadol having been administered to cattle by farmers in the region: tramadol and its metabolites were present in the animals excreta, which contaminated the soil around the trees. Therefore, tramadol and its mammalian metabolites were found in tree roots in the far north of Cameroon, but not in the south where it is not administered to farm animals.A 2014 editorial in Lab Times online contested the notion that tramadol in tree roots was the result of anthropogenic contamination, stating that samples were taken from trees that grew in national parks, where livestock were forbidden; it also quoted researcher Michel de Waard, who stated that "thousands and thousands of tramadol-treated cattle sitting around a single tree and urinating there" would be required to produce the concentrations discovered.In 2015, radiocarbon analysis confirmed that the tramadol found in N.latifolia roots could not be plant-derived and was of synthetic origin. Veterinary medicine Tramadol may be used to treat post-operative, injury-related, and chronic (e.g., cancer-related) pain in dogs and cats as well as rabbits, coatis, many small mammals including rats and flying squirrels, guinea pigs, ferrets, and raccoons. See also Tramadol/paracetamol References Further reading Dean L (2015). "Tramadol Therapy and CYP2D6 Genotype". In Pratt VM, McLeod HL, Rubinstein WS, et al. (eds.). Medical Genetics Summaries. National Center for Biotechnology Information (NCBI). PMID 28520365. Bookshelf ID: NBK315950. External links "Tramadol". Drug Information Portal. U.S. National Library of Medicine. "Tramadol hydrochloride". Drug Information Portal. U.S. National Library of Medicine.

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I'm seeking clarification on the medical term 'Placentitis.' Could you explain it?

Placentitis is an inflammation of the placenta. The main forms of placentitis are: Villitis, inflammation of chorionic villi. Intervillositis, inflammation of the intervillous space.It may be caused by vertically transmitted infections. Because of the close proximity, placentitis often occurs simultaneously as funisitis (inflammation of the umbilical cord) and chorioamnionitis (inflammation of the fetal membranes). Chronic lymphocytic placental inflammation occurs in 5% to 15% of pregnancies, and are generally not associated with documented infection. Villitis of unknown etiology Villitis of unknown etiology (VUE), also known as chronic villitis, is a placental injury. VUE is an inflammatory condition involving the chorionic villi (placental villi). VUE is a recurrent condition and can be associated with intrauterine growth restriction (IUGR). IUGR involves the poor growth of the foetus, stillbirth, miscarriage, and premature delivery. VUE recurs in about 1/3 of subsequent pregnancies.VUE is a common lesion characterised by inflammation in the placental chorionic villi. VUE is also characterised by the transfer of maternal lymphocytes across the placenta.VUE is diagnosed in 7–10% placentas in pregnancies. Roughly 80% of the VUE cases are in term placentas (greater than 37 weeks of pregnancy). A case of VUE in a placenta less than 32 weeks old should be screened for infectious villitis. Chronic histiocytic intervillositis Chronic Histiocytic Intervillositis (CHI or CHIV) also known as Chronic Intervillositis of Unknown (A)etiology (CIUE) and Massive Chronic Intervillositis (MCI) is defined as a diffuse infiltration of mononuclear cells (histiocytes, lymphocytes, monocytes) of maternal origin into the intervillous space within the placenta. It often results in severe intrauterine growth restriction which can lead to miscarriage or stillbirth. Overall perinatal mortality rate is high: 41% to 77%. Recurrence rate is also high: 67% to 100%. See also Chorioamnionitis References External links CHI Support CHI Facebook Support Group

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I'm seeking clarification on the medical term 'Monoclonal gammopathy.' Could you explain it?

Monoclonal gammopathy, also known as paraproteinemia, is the presence of excessive amounts of myeloma protein or monoclonal gamma globulin in the blood. It is usually due to an underlying immunoproliferative disorder or hematologic neoplasms, especially multiple myeloma. It is sometimes considered equivalent to plasma cell dyscrasia. The most common form of the disease is monoclonal gammopathy of undetermined significance. Causes Causes of paraproteinemia include the following: Leukemias and lymphomas of various types, but usually B-cell non-Hodgkin lymphomas with a plasma cell component. Myeloma Plasmacytoma Lymphoplasmacytic lymphoma Idiopathic (no discernible cause): some of these will be revealed as leukemias or lymphomas over the years. AL amyloidosis Diagnosis These are characterized by the presence of any abnormal protein that is involved in the immune system, which are most often immunoglobulins and are associated with the clonal proliferation of lymphocytes.When a paraproteinemia is present in the blood, there will be a narrow band, or spike, in the serum protein electrophoresis because there will be an excess of production of one protein.There are two large classes of blood proteins: albumin and globulin. They are generally equal in proportion, but albumin is much smaller than globulin, and slightly negatively charged, which leads to an accumulation at the end of the electrophoretic gel. The globulins separate out into three regions on the electrophoretic gel, which are the α band, the β band, and the γ band. The α band can be separated into two components: α1 and α2. The α1 region consists mostly of α1-antitrypsin and α1-acid glycoprotein. The α2 region is mostly haptoglobin, α2-macroglobulin, α2-antiplasmin, and ceruloplasmin. The β band consists of transferrin, low-density lipoproteins, and complement system proteins. The γ band is where the immunoglobulins appear, which is why they are also known as gammaglobulins. The majority of paraproteins appear in this band. Types Paraproteinemias may be categorized according to the type of monoclonal protein found in blood: Light chains only (or Bence Jones protein). This may be associated with multiple myeloma or AL amyloidosis. Heavy chains only (also known as "heavy chain disease"); Whole immunoglobulins. If immunoglobulins tend to precipitate within blood vessels with cold, that phenomenon takes the name of cryoglobulinaemia.The three types of paraproteins may occur alone or in combination in a given individual. Note that while most heavy chains or whole immunoglobulins remain within blood vessels, light chains frequently escape and are excreted by the kidneys into urine, where they take the name of Bence Jones protein.It is also possible for paraproteins (usually whole immunoglobulins) to form polymers by aggregating with each other; this takes the name of macroglobulinemia and may lead to further complications. For example, certain macroglobulins tend to precipitate within blood vessel with cold, a phenomenon known as cryoglobulinemia. Others may make blood too viscous to flow smoothly (usually with IgM pentamer macroglobulins), a phenomenon known as Waldenström macroglobulinemia.The most common type of paraproteinemia is monoclonal gammopathy of undetermined significance (MGUS). Another form, monoclonal gammopathy of renal significance (MGRS) results in kidney damage and chronic kidney disease due to the effects of monoclonal immunoglobulins. References External links Paraproteinaemia at patient.info.

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I'm seeking clarification on the medical term 'Phantom pain.' Could you explain it?

Phantom pain is a perception that an individual experiences relating to a limb or an organ that is not physically part of the body, either because it was removed or was never there in the first place. However, phantom limb sensations can also occur following nerve avulsion or spinal cord injury. Sensations are recorded most frequently following the amputation of an arm or a leg, but may also occur following the removal of a breast, tooth, or an internal organ. Phantom limb pain is the feeling of pain in an absent limb or a portion of a limb. The pain sensation varies from individual to individual. Phantom limb sensation is any sensory phenomenon (except pain) which is felt at an absent limb or a portion of the limb. It has been known that at least 80% of amputees experience phantom sensations at some time of their lives. Some experience some level of this phantom pain and feeling in the missing limb for the rest of their lives. The term "phantom limb" was first coined by American neurologist Silas Weir Mitchell in 1871. Mitchell described that "thousands of spirit limbs were haunting as many good soldiers, every now and then tormenting them". However, in 1551, French military surgeon Ambroise Paré recorded the first documentation of phantom limb pain when he reported that, "For the patients, long after the amputation is made, say that they still feel pain in the amputated part". Signs and symptoms Phantom pain involves the sensation of pain in a part of the body that has been removed. The onset of phantom pain can occur within the first few days of amputation. The sensation may come and go, but can be continuous. While the sensation often affects the part of the limb farthest from the body, such as the foot of an amputated leg, other body parts closer to the brain, such as the arm or hand, can still experience similar sensations. Sensations can be described as shooting, stabbing, boring, squeezing, throbbing or burning. Sensations on smaller limbs and digits such as toes or fingers tend to be less severe. Sometimes the sensation feels as if the phantom part is forced into an uncomfortable position. Overall, the sensations may be triggered by pressure on the remaining part of the limb or emotional stress. Types There are various types of sensations that may be felt: Sensations related to the phantom limbs posture, length and volume e.g. feeling that the phantom limb is behaving just like a normal limb like sitting with the knee bent or feeling that the phantom limb is as heavy as the other limb. Sometimes, an amputee will experience a sensation called telescoping, the feeling that the phantom limb is gradually shortening over time. Sensations of movement (e.g. feeling that the phantom foot is moving). Sensations of touch, temperature, pressure and itchiness. Many amputees report of feeling heat, tingling, itchiness, and pain. In less severe cases where small digits are amputated, the sensation can be described as a tingling feeling as opposed to a painful sensation. Pathophysiology The neurological basis and mechanisms for phantom limb pain are all derived from experimental theories and observations. Little is known about the true mechanism causing phantom pains, and many theories highly overlap. Historically, phantom pains were thought to originate from neuromas located at the stump tip. Traumatic neuromas, or non-tumor nerve injuries, often arise from surgeries and result from the abnormal growth of injured nerve fibers. Although stump neuromas contribute to phantom pains, they are not the sole cause. This is because patients with congenital limb deficiency can sometimes, although rarely, experience phantom pains. This suggests that there is a central representation of the limb responsible for painful sensations. Currently, theories are based on altered neurological pathways and cortical reorganization. Peripheral mechanisms Neuromas formed from injured nerve endings at the stump site are able to fire abnormal action potentials, and were historically thought to be the main cause of phantom limb pain. Although neuromas are able to contribute to phantom pain, pain is not completely eliminated when peripheral nerves are treated with conduction blocking agents. Physical stimulation of neuromas can increase C fiber activity, thus increasing phantom pain, but pain still persists once the neuromas have ceased firing action potentials. The peripheral nervous system is thought to have at most a modulation effect on phantom limb pain. Spinal mechanisms In addition to peripheral mechanisms, spinal mechanisms are thought to have an influencing role in phantom pains. Peripheral nerve injury can lead to the degeneration of C fibers in the dorsal horn of the spinal cord, and terminating A fibers may subsequently branch into the same lamina. If this occurs, A fiber inputs could be reported as noxious stimuli. Substance P, involved in the transmission of pain signals, is usually expressed by Aδ and C fibers, but following peripheral nerve damage, substance P is expressed by Aβ fibers. This leads to hyperexcitability of the spinal cord, which usually occurs only in the presence of noxious stimuli. Because patients with complete spinal cord injury have experienced phantom pains, there must be an underlying central mechanism responsible for the generation of phantom pains. Central mechanisms Under ordinary circumstances, the genetically determined circuitry in the brain remains largely stable throughout life. For much of the twentieth century, it was believed that no new neural circuits could be formed in the adult mammalian brain, but experiments from the 1980s onward cast this into doubt. For instance, functional MRI studies in amputees have shown that almost all patients have experienced motor cortical remapping. The majority of motor reorganization has occurred as a downward shift of the hand area of the cortex onto the area of face representation, especially the lips. Sometimes there is a side shift of the hand motor cortex to the ipsilateral cortex. In patients with phantom limb pain, the reorganization was great enough to cause a change in cortical lip representation into the hand areas only during lip movements. It has also been found that there is a high correlation between the magnitude of phantom limb pain and the extent to which the shift of the cortical representation of the mouth into the hand area in motor and somatosensory cortical reorganization has occurred. Additionally, as phantom pains in upper extremity amputees increased, there was a higher degree of medial shift of the facial motor representation. There are multiple theories that try to explain how cortical remapping occurs in amputees, but none have been supported to a great extent. The neuromatrix The neuromatrix theory proposes that there is an extensive network connecting the thalamus and the cortex, and the cortex and the limbic system. It is a theory that extends beyond body schema theory and incorporates the conscious awareness of oneself. This theory proposes that conscious awareness and the perception of self are generated in the brain via patterns of input that can be modified by different perceptual inputs. The network is genetically predetermined, and is modified throughout one’s lifetime by various sensory inputs to create a neurosignature. It is the neurosignature of a specific body part that determines how it is consciously perceived. The input systems contributing to the neurosignature are primarily the somatosensory, limbic, and thalamocortical systems. The neuromatrix theory aims to explain how certain activities associated with pain lead to the conscious perception of phantom pain. The persistence of the neurosignature, even after limb amputation, may be the cause of phantom sensations and pain. Phantom pain may arise from abnormal reorganization in the neuromatrix to a pre-existing pain state.Opposition to the neuromatrix theory exists largely because it fails to explain why relief from phantom sensations rarely eliminates phantom pains. It also does not address how sensations can spontaneously end and how some amputees do not experience phantom sensations at all. In addition, a major limitation of the neuromatrix theory is that it too broadly accounts for various aspects of phantom limb perception. It is also likely that it is too difficult to be tested empirically, especially when testing painless phantom sensations. Management Various methods have been used to treat phantom limb pain. Doctors may prescribe medications to reduce the pain. Some antidepressants or antiepileptics have been shown to have a beneficial effect on reducing phantom limb pain. Often physical methods such as light massage, electrical stimulation, and hot and cold therapy have been used with variable results. There are many different treatment options for phantom limb pain that are actively being researched. Most treatments do not take into account the mechanisms underlying phantom pains, and are therefore ineffective. However, there are a few treatment options that have been shown to alleviate pain in some patients, but these treatment options usually have a success rate less than 30%. It is important to note that this rate of success does not exceed the placebo effect. It is also important to note that because the degree of cortical reorganization is proportional to phantom limb pains, any perturbations to the amputated regions may increase pain perception. Mirror therapy Mirror box therapy allows for illusions of movement and touch in a phantom limb by inducing somatosensory and motor pathway coupling between the phantom and real limb. Many patients experience pain as a result of a clenched phantom limb, and because phantom limbs are not under voluntary control, unclenching becomes impossible. This theory proposes that the phantom limb feels paralyzed because there is no feedback from the phantom back to the brain to inform it otherwise. Vilayanur S. Ramachandran believes that if the brain received visual feedback that the limb had moved, then the phantom limb would become unparalyzed.Although the use of mirror therapy has been shown to be effective in some cases there is still no widely accepted theory of how it works. According to 2017 paper that reviewed a wide range of studies of mirror therapy, "Research evidence suggests that a course of treatment (four weeks) of mirror therapy may reduce chronic pain. Contraindications and side effects are few. The mechanism of action of mirror therapy remains uncertain, with reintegration of motor and sensory systems, restored body image and control over fear-avoidance likely to influence outcome. The evidence for clinical efficacy of mirror therapy is encouraging, but not yet definitive. Nevertheless, mirror therapy is inexpensive, safe and easy for the patient to self-administer."Little research was published on MT before 2009, and much of the research since then has been of low quality. Out of 115 publications between 2012 and 2017 about using mirror therapy to treat phantom limb pain, a 2018 review, found only 15 studies whose scientific results should be considered. From these 15 studies, the reviewers concluded that "MT seems to be effective in relieving PLP, reducing the intensity and duration of daily pain episodes. It is a valid, simple, and inexpensive treatment for PLP." Medication Pharmacological techniques are often continued in conjunction with other treatment options. Doses of pain medications needed often drop substantially when combined with other techniques, but rarely are discontinued completely. Tricyclic antidepressants, such as amitriptyline, and sodium channel blockers, mainly carbamazepine, are often used to relieve chronic pain, and recently have been used in an attempt to reduce phantom pains. Pain relief may also be achieved through use of opioids, ketamine, calcitonin, and lidocaine. Deep-brain stimulation Deep brain stimulation is a surgical technique used to alleviate patients from phantom limb pain. Prior to surgery, patients undergo functional brain imaging techniques such as PET scans and functional MRI to determine an appropriate trajectory of where pain is originating. Surgery is then carried out under local anesthetic, because patient feedback during the operation is needed. In the study conducted by Bittar et al., a radiofrequency electrode with four contact points was placed on the brain. Once the electrode was in place, the contact locations were altered slightly according to where the patient felt the greatest relief from pain. Once the location of maximal relief was determined, the electrode was implanted and secured to the skull. After the primary surgery, a secondary surgery under general anesthesia was conducted. A subcutaneous pulse generator was implanted into a pectoral pocket below the clavicle to stimulate the electrode. It was found that all three patients studied had gained satisfactory pain relief from the deep brain stimulation. Pain had not been completely eliminated, but the intensity had been reduced by over 50% and the burning component had completely vanished. Epidemiology Phantom limb pain and phantom limb sensations are linked, but must be differentiated from one another. While phantom limb sensations are experienced by those with congenital limb deficiency, spinal cord injury, and amputation, phantom limb pain occurs almost exclusively as a result of amputation. Almost immediately following the amputation of a limb, 90–98% of patients report experiencing a phantom sensation. Nearly 75% of individuals experience the phantom as soon as anesthesia wears off, and the remaining 25% of patients experience phantoms within a few days or weeks. Of those experiencing innocuous sensations, a majority of patients also report distinct painful sensations. Age and gender have not been shown to affect the onset or duration of phantom limb pain. Although it has not been fully explored, one investigation of lower limb amputation observed that as stump length decreased, there was a greater incidence of moderate and severe phantom pain. See also Phantom limb Phantom eye syndrome References External links MacLachlan, Malcolm; McDonald, Dympna; Waloch, Justine (2004), "Mirror Treatment of Lower Limb Phantom Pain: A Case Study", Disability and Rehabilitation, 26 (14/15): 901–904, doi:10.1080/09638280410001708913, PMID 15497919, S2CID 36325980Richardson, Cliff; Glenn, Sheila; Horgan, Maureen; Nurmikko, Turo (October 2007), "A Prospective Study of Factors Associated with the Presence of Phantom Limb Pain Six Months After Major Lower Limb Amputation in Patients with Peripheral Vascular Disease", The Journal of Pain, 8 (10): 793–801, doi:10.1016/j.jpain.2007.05.007, PMID 17631056Targeted Muscle Reinnervation

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I'm curious about the meaning of the medical term 'Internuclear ophthalmoplegia.' Can you give me some insights?

Internuclear ophthalmoplegia (INO) is a disorder of conjugate lateral gaze in which the affected eye shows impairment of adduction. When an attempt is made to gaze contralaterally (relative to the affected eye), the affected eye adducts minimally, if at all. The contralateral eye abducts, however with nystagmus. Additionally, the divergence of the eyes leads to horizontal diplopia. That is if the right eye is affected the patient will "see double" when looking to the left, seeing two images side-by-side. Convergence is generally preserved. Causes The disorder is caused by injury or dysfunction in the medial longitudinal fasciculus (MLF), a heavily myelinated tract that allows conjugate eye movement by connecting the paramedian pontine reticular formation (PPRF)-abducens nucleus complex of the contralateral side to the oculomotor nucleus of the ipsilateral side. In young patients with bilateral INO, multiple sclerosis is often the cause. In older patients with one-sided lesions a stroke is a distinct possibility. Other causes are possible. Variants A rostral lesion within the midbrain may affect the convergence center thus causing bilateral divergence of the eyes which is known as the WEBINO syndrome (Wall Eyed Bilateral INO) as each eye looks at the opposite "wall". If the lesion affects the PPRF (or the abducens nucleus) and the MLF on the same side (the MLF having crossed from the opposite side), then the "one and a half syndrome" occurs, with paralysis of all conjugate horizontal eye movements other than abduction of the eye on the opposite side to the lesion. Diagnosis Can be seen in multiple sclerosis, stroke, and other pathologies. Accompanying symptoms include scanning speech, intention tremor, incontinence, and nystagmus. See also Multiple sclerosis One and a half syndrome References == External links ==

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Can you demystify the medical term 'Cyanide poisoning' for me?

Cyanide poisoning is poisoning that results from exposure to any of a number of forms of cyanide. Early symptoms include headache, dizziness, fast heart rate, shortness of breath, and vomiting. This phase may then be followed by seizures, slow heart rate, low blood pressure, loss of consciousness, and cardiac arrest. Onset of symptoms usually occurs within a few minutes. Some survivors have long-term neurological problems.Toxic cyanide-containing compounds include hydrogen cyanide gas and a number of cyanide salts. Poisoning is relatively common following breathing in smoke from a house fire. Other potential routes of exposure include workplaces involved in metal polishing, certain insecticides, the medication sodium nitroprusside, and certain seeds such as those of apples and apricots. Liquid forms of cyanide can be absorbed through the skin. Cyanide ions interfere with cellular respiration, resulting in the bodys tissues being unable to use oxygen.Diagnosis is often difficult. It may be suspected in a person following a house fire who has a decreased level of consciousness, low blood pressure, or high lactic acid. Blood levels of cyanide can be measured but take time. Levels of 0.5–1 mg/L are mild, 1–2 mg/L are moderate, 2–3 mg/L are severe, and greater than 3 mg/L generally result in death.If exposure is suspected, the person should be removed from the source of exposure and decontaminated. Treatment involves supportive care and giving the person 100% oxygen. Hydroxocobalamin (vitamin B12a) appears to be useful as an antidote and is generally first-line. Sodium thiosulphate may also be given. Historically cyanide has been used for mass suicide and by the Nazis for genocide. Signs and symptoms Acute exposure If hydrogen cyanide is inhaled it can cause a coma with seizures, apnea, and cardiac arrest, with death following in a matter of seconds. At lower doses, loss of consciousness may be preceded by general weakness, dizziness, headaches, vertigo, confusion, and perceived difficulty in breathing. At the first stages of unconsciousness, breathing is often sufficient or even rapid, although the state of the person progresses towards a deep coma, sometimes accompanied by pulmonary edema, and finally cardiac arrest. A cherry red skin color that darkens may be present as the result of increased venous hemoglobin oxygen saturation. Despite the similar name, cyanide does not directly cause cyanosis. A fatal dose for humans can be as low as 1.5 mg/kg body weight. Other sources claim a lethal dose is 1–3 mg per kg body weight for vertebrates. Chronic exposure Exposure to lower levels of cyanide over a long period (e.g., after use of improperly processed cassava roots, which are a primary food source in tropical Africa) results in increased blood cyanide levels, which can result in weakness and a variety of symptoms, including permanent paralysis, nervous lesions, hypothyroidism, and miscarriages. Other effects include mild liver and kidney damage. Causes Cyanide poisoning can result from the ingestion of cyanide salts; imbibing pure liquid prussic acid; skin absorption of prussic acid; intravenous infusion of nitroprusside for hypertensive crisis; or the inhalation of hydrogen cyanide gas. The last typically occurs through one of three mechanisms: The gas is directly released from canisters (e.g. as part of a pesticide, insecticide, or Zyklon B). It is generated on site by reacting potassium cyanide or sodium cyanide with sulfuric acid (e.g. in a modern American gas chamber). Fumes arise during a building fire or any similar scenario involving the burning of polyurethane, vinyl or other polymer products that required nitriles in their production.As potential contributing factors, cyanide is present in: Tobacco smoke. Many seeds or kernels such as those of almonds, apricots, apples, oranges, and flaxseed. Foods including cassava (also known as tapioca, yuca or manioc) and bamboo shoots.As a potential harm-reduction factor, Vitamin B12, in the form of hydroxocobalamin (also spelled hydroxycobalamin), might reduce the negative effects of chronic exposure; whereas, a deficiency might worsen negative health effects following exposure to cyanide. Mechanism Cyanide is a potent cytochrome c oxidase (COX, a.k.a Complex IV) inhibitor. As such, cyanide poisoning is a form of histotoxic hypoxia, because it interferes with oxidative phosphorylation.: 1475 Specifically, cyanide binds to the heme a3-CuB binuclear center of COX (and thus is a non-competitive inhibitor of it). This prevents electrons passing through COX from being transferred to O2, which not only blocks the mitochondrial electron transport chain but also interferes with the pumping of a proton out of the mitochondrial matrix which would otherwise occur at this stage. Therefore, cyanide interferes not only with aerobic respiration but also with the ATP synthesis pathway it facilitates, owing to the close relationship between those two processes.: 705 One antidote for cyanide poisoning, nitrite (i.e. via amyl nitrite), works by converting ferrohemoglobin to ferrihemoglobin, which can then compete with COX for free cyanide (as the cyanide will bind to the iron in its heme groups instead). Ferrihemoglobin cannot carry oxygen, but the amount of ferrihemoglobin that can be formed without impairing oxygen transport is much greater than the amount of COX in the body.: 1475 Cyanide is a broad-spectrum poison because the reaction it inhibits is essential to aerobic metabolism; COX is found in many forms of life. However, susceptibility to cyanide is far from uniform across affected species; for instance, plants have an alternative electron transfer pathway available that passes electrons directly from ubiquinone to O2, which confers cyanide resistance by bypassing COX.: 704 Diagnosis Lactate is produced by anaerobic glycolysis when oxygen concentration becomes too low for the normal aerobic respiration pathway. Cyanide poisoning inhibits aerobic respiration and therefore increases anaerobic glycolysis which causes a rise of lactate in the plasma. A lactate concentration above 10 mmol per liter is an indicator of cyanide poisoning, as defined by the presence of a blood cyanide concentration above 40 µmol per liter. Lactate levels greater than 6 mmol/L after reported or strongly suspected pure cyanide poisoning, such as cyanide-containing smoke exposure, suggests significant cyanide exposure.Methods of detection include colorimetric assays such as the Prussian blue test, the pyridine-barbiturate assay, also known as the "Conway diffusion method" and the taurine fluorescence-HPLC but like all colorimetric assays these are prone to false positives. Lipid peroxidation resulting in "TBARS," an artifact of heart attack produces dialdehydes that cross-react with the pyridine-barbiturate assay. Meanwhile, the taurine-fluorescence-HPLC assay used for cyanide detection is identical to the assay used to detect glutathione in spinal fluid. Cyanide and thiocyanate assays have been run with mass spectrometry (LC/MS/MS), which are considered specific tests. Since cyanide has a short half-life, the main metabolite, thiocyanate is typically measured to determine exposure. Other methods of detection include the identification of plasma lactate. Treatment Decontamination Decontamination of people exposed to hydrogen cyanide gas only requires removal of the outer clothing and the washing of their hair. Those exposed to liquids or powders generally require full decontamination. Antidote The International Programme on Chemical Safety issued a survey (IPCS/CEC Evaluation of Antidotes Series) that lists the following antidotal agents and their effects: oxygen, sodium thiosulfate, amyl nitrite, sodium nitrite, 4-dimethylaminophenol, hydroxocobalamin, and dicobalt edetate (Kelocyanor), as well as several others. Other commonly-recommended antidotes are solutions A and B (a solution of ferrous sulfate in aqueous citric acid, and aqueous sodium carbonate, respectively) and amyl nitrite. The United States standard cyanide antidote kit first uses a small inhaled dose of amyl nitrite, followed by intravenous sodium nitrite, followed by intravenous sodium thiosulfate. Hydroxocobalamin was approved for use in the US in late 2006 and is available in Cyanokit antidote kits. Sulfanegen TEA, which could be delivered to the body through an intra-muscular (IM) injection, detoxifies cyanide and converts the cyanide into thiocyanate, a less toxic substance. Alternative methods of treating cyanide intoxication are used in other countries. The Irish Health and Safety Executive (HSE) has recommended against the use of solutions A and B because of their limited shelf life, potential to cause iron poisoning, and limited applicability (effective only in cases of cyanide ingestion, whereas the main modes of poisoning are inhalation and skin contact). The HSE has also questioned the usefulness of amyl nitrite due to storage/availability problems, risk of abuse, and lack of evidence of significant benefits. It also states that the availability of kelocyanor at the workplace may mislead doctors into treating a patient for cyanide poisoning when this is an erroneous diagnosis. The HSE no longer recommends a particular cyanide antidote. History Fires The República Cromañón nightclub fire broke out in Buenos Aires, Argentina on 30 December 2004, killing 194 people and leaving at least 1,492 injured. Most of the victims died from inhaling poisonous gases, and carbon monoxide. After the fire, the technical institution INTI found that the level of toxicity due to the materials and volume of the building was 225 ppm of cyanide in the air. A lethal dose for rats is between 150 ppm and 220 ppm, meaning the air in the building was highly toxic. On 5 December 2009, a fire in the night club Lame Horse (Khromaya Loshad) in the Russian city of Perm took the lives of 156 people. Fatalities consisted of 111 people at the site and 45 later in hospitals. One of the main causes of death was poisoning from cyanide and other toxic gases released by the burning of plastic and polyurethane foam used in the construction of club interiors. Taking into account the number of deaths, this was the largest fire in post-Soviet Russia.On 27 January 2013, a fire at the Kiss nightclub in the city of Santa Maria, in the south of Brazil, caused the poisoning of hundreds of young people by cyanide released by the combustion of soundproofing foam made with polyurethane. By March 2013, 245 fatalities were confirmed. Gas chambers In early 1942, Zyklon B, which contains hydrogen cyanide, emerged as the preferred killing tool of Nazi Germany for use in extermination camps during the Holocaust. The chemical was used to murder roughly one million people in gas chambers installed in extermination camps at Auschwitz-Birkenau, Majdanek, and elsewhere. Most of the people who were murdered were Jews, and by far the majority of these murders took place at Auschwitz. Zyklon B was supplied to concentration camps at Mauthausen, Dachau, and Buchenwald by the distributor Heli, and to Auschwitz and Majdanek by Testa. Camps also occasionally bought Zyklon B directly from the manufacturers. Of the 729 tonnes of Zyklon B sold in Germany in 1942–44, 56 tonnes (about eight percent of domestic sales) were sold to concentration camps. Auschwitz received 23.8 tonnes, of which six tonnes were used for fumigation. The remainder was used in the gas chambers or lost to spoilage (the product had a stated shelf life of only three months). Testa conducted fumigations for the Wehrmacht and supplied them with Zyklon B. They also offered courses to the SS in the safe handling and use of the material for fumigation purposes. In April 1941, the German agriculture and interior ministries designated the SS as an authorized applier of the chemical, and thus they were able to use it without any further training or governmental oversight.Hydrogen cyanide gas has been used for judicial execution in some states of the United States, where cyanide was generated by reaction between potassium cyanide (or sodium cyanide) dropped into a compartment containing sulfuric acid, directly below the chair in the gas chamber. Suicide Cyanide salts are sometimes used as fast-acting suicide devices. Cyanide reacts at a higher level with high stomach acidity. On 26 January 1904, company promoter and swindler Whitaker Wright committed suicide by ingesting cyanide in a court anteroom immediately after being convicted of fraud. In February 1937, the Uruguayan short story writer Horacio Quiroga committed suicide by drinking cyanide in a hospital at Buenos Aires. In 1937, polymer chemist Wallace Carothers committed suicide by cyanide. In the 1943 Operation Gunnerside to destroy the Vemork Heavy Water Plant in World War II (an attempt to stop or slow German atomic bomb progress), the commandos were given cyanide tablets (cyanide enclosed in rubber) kept in the mouth and were instructed to bite into them in case of German capture. The tablets ensured death within three minutes. Cyanide, in the form of pure liquid prussic acid (a historical name for hydrogen cyanide), was the favored suicide agent of Nazi Germany. Erwin Rommel (1944), Adolf Hitlers wife, Eva Braun (1945), and Nazi leaders Heinrich Himmler (1945), possibly Martin Bormann (1945), and Hermann Göring (1946) all committed suicide by ingesting it. It is speculated that, in 1954, Alan Turing used an apple that had been injected with a solution of cyanide to commit suicide after being convicted of having a homosexual relationship, which was illegal at the time in the United Kingdom, and forced to undergo hormonal castration to avoid prison. An inquest determined that Turings death from cyanide poisoning was a suicide, although this has been disputed. Members of the Sri Lankan LTTE (Liberation Tigers of Tamil Eelam, whose insurgency lasted from 1983 to 2009), used to wear cyanide vials around their necks with the intention of committing suicide if captured by the government forces. On 22 June 1977, Moscow, Aleksandr Dmitrievich Ogorodnik, a Soviet diplomat accused of spying on behalf of the Colombian Intelligence Agency and the US Central Intelligence Agency, was arrested. During the interrogations, Ogorodnik offered to write a full confession and asked for his pen. Inside the pen cap was a cleverly hidden cyanide pill, which when bitten on, caused Ogorodnik to die before he hit the floor, according to the Soviets. On 18 November 1978, Jonestown. A total of 909 individuals died in Jonestown, many from apparent cyanide poisoning, in an event termed "revolutionary suicide" by Jones and some members on an audio tape of the event and in prior discussions. The poisonings in Jonestown followed the murder of five others by Temple members at Port Kaituma, including United States Congressman Leo Ryan, an act that Jones ordered. Four other Temple members committed murder-suicide in Georgetown at Jones command. On 6 June 1985, serial killer Leonard Lake died in custody after having ingested cyanide pills he had sewn into his clothes. On 28 June 2012, Wall Street trader Michael Marin ingested a cyanide pill seconds after a guilty verdict was read in his arson trial in Phoenix, AZ; he died minutes after. On 22 June 2015, John B. McLemore, a horologist and the central figure of the podcast S-Town, died after ingesting cyanide. On 29 November 2017, Slobodan Praljak died from drinking potassium cyanide, after being convicted of war crimes by the International Criminal Tribunal for the former Yugoslavia. Mining and industrial In 1993, an illegal spill resulted in the death of seven people in Avellaneda, Argentina. In their memory, the National Environmental Conscious Day (Día Nacional de la Conciencia Ambiental) was established. In 2000, a spill at Baia Mare, Romania, resulted in the worst environmental disaster in Europe since Chernobyl. In 2000, Allen Elias, CEO of Evergreen Resources was convicted of knowing endangerment for his role in the cyanide poisoning of employee Scott Dominguez. This was one of the first successful criminal prosecutions of a corporate executive by the Environmental Protection Agency. Murder John Tawell, a murderer who in 1845 became the first person to be arrested as the result of telecommunications technology. Grigori Rasputin (1916; attempted, later killed by gunshot) The Goebbels children (1945) Stepan Bandera (1959) Jonestown, Guyana, was the site of a large mass murder–suicide, in which over 900 members of the Peoples Temple drank potassium cyanide–laced Flavor Aid in 1978. Chicago Tylenol murders (1982) Timothy Marc OBryan (1966–1974) died on October 31, 1974 by ingesting potassium cyanide placed into a giant Pixy Stix. His father, Ronald Clark OBryan, was convicted of Tims murder plus four counts of attempted murder. OBryan put potassium cyanide into five giant Pixy Stix that he gave to his son and daughter along with three other children. Only Timothy ate the poisoned candy and died. Bruce Nickell (5 June 1986) Murdered by his wife who poisoned a bottle of Excedrin. Richard Kuklinski (1935–2006) Janet Overton (1942–1988) Her husband, Richard Overton was convicted of poisoning her, but Janets symptoms did not match those of classic cyanide poisoning, the timeline was inconsistent with cyanide poisoning, and the amount found was just a trace. The diagnostic method used was prone to false positives. Richard Overton died in prison in 2009. Urooj Khan (1966–2012), won the lottery and was found dead a few days later. A blood diagnostic reported a lethal level of cyanide in his blood, but the body did not display any classic symptoms of cyanide poisoning, and no link to cyanide could be found in Uroojs social circle. The diagnostic method used was the Conway diffusion method, prone to false positives with artifacts of heart attack and kidney failure. Autumn Marie Klein (20 April 2013), a prominent 41-year-old neuroscientist and physician, died from cyanide poisoning. Kleins husband, Robert J. Ferrante, also a prominent neuroscientist who used cyanide in his research, was convicted of murder and sentenced to life in prison for her death. Robert Ferrante is appealing his conviction. Mirna Salihin died in hospital on 6 January 2016, after drinking a Vietnamese iced coffee at a cafe in a shopping mall in Jakarta. Police reports claim that cyanide poisoning was the most likely cause of her death. Jolly Thomas of Kozhikode, Kerala, India, was arrested in 2019 for the murder of 6 family members. Murders took place over 14-year period and each victim ate a meal prepared by the killer. The murders were allegedly motivated by wanting control of the family finances and property. Mei Xiang Li of Brooklyn, NY, collapsed and died in April 2017, with cyanide later reported to be in her blood. However, Mei never exhibited symptoms of cyanide poisoning and no link to cyanide could be found in her life. Warfare or terrorism In 1988, between 3,200 and 5,000 people died in the Halabja massacre owing to unknown chemical nerve agents. Hydrogen cyanide gas was strongly suspected. In 1995, a device was discovered in a restroom in the Kayabacho Tokyo subway station, consisting of bags of sodium cyanide and sulfuric acid with a remote controlled motor to rupture them in what was believed to be an attempt by the Aum Shinrikyo cult to produce toxic amounts of hydrogen cyanide gas. In 2003, Al Qaeda reportedly planned to release cyanide gas into the New York City Subway system. The attack was supposedly aborted because there would not be enough casualties. Research Cobinamide is the final compound in the biosynthesis of cobalamin. It has greater affinity for the cyanide than cobalamin itself, which suggests that it could be a better option for emergency treatment. See also Anaerobic glycolysis Lactic acidosis List of poisonings Konzo References Explanatory notes Citations Sources Longerich, Peter (2010). Holocaust: The Nazi Persecution and Murder of the Jews. Oxford; New York: Oxford University Press. ISBN 978-0-19-280436-5. Hayes, Peter (2004). From Cooperation to Complicity: Degussa in the Third Reich. Cambridge; New York; Melbourne: Cambridge University Press. ISBN 978-0-521-78227-2. Piper, Franciszek (1994). "Gas Chambers and Crematoria". In Gutman, Yisrael; Berenbaum, Michael (eds.). Anatomy of the Auschwitz Death Camp. Bloomington, Indiana: Indiana University Press. pp. 157–182. ISBN 978-0-253-32684-3.

You function as a medical informant. Please provide in-depth yet accessible descriptions of medical terms, suitable for a broad audience.

Could you please explain the term 'Retiform parapsoriasis' in simple language?

Retiform parapsoriasis is a cutaneous condition, considered to be a type of large-plaque parapsoriasis. It is characterized by widespread, ill-defined plaques on the skin, that have a net-like or zebra-striped pattern. Skin atrophy, a wasting away of the cutaneous tissue, usually occurs within the area of these plaques. See also Parapsoriasis Poikiloderma vasculare atrophicans List of cutaneous conditions References == External links ==

You function as a medical explainer. Your task is to convey the meanings of medical terms in a detailed, yet easy-to-understand manner.

Could you provide a brief overview of 'Valve stenosis' in a medical context?

Valve stenosis may refer to: Pulmonary valve stenosis Aortic valve stenosis Mitral valve stenosis

You act as a mediator between medical professionals and the public. Provide comprehensive explanations of medical terms, ensuring they are both precise and easily understood.

Could you offer a clear explanation of the term 'Tillaux fracture' as used in the medical field?

A Tillaux fracture is a Salter–Harris type III fracture through the anterolateral aspect of the distal tibial epiphysis. It occurs in older adolescents between the ages of 12 and 15 when the medial epiphysis had closed but before the lateral side has done so, due to an avulsion of the anterior inferior tibiofibular ligament, at the opposite end to a Wagstaffe-Le Fort avulsion fracture Mechanism The fracture commonly results from an abduction-external rotation force, causing the anterior tibiofibular ligament to avulse the anterolateral corner of the distal tibial epiphysis resulting in a Salter Harris Type III fracture. Pathology It occurs in older children at the end of growth. Variability in fracture pattern is due to progression of physeal closure as anterolateral part of distal tibial physis is the last to close. When the lateral physis is the only portion not fused, external rotation may lead to Tillaux or Triplane fractures. Treatment If the displacement at fracture is less than 2 mm, it may be managed conservatively. However, displacement requires open reduction and internal fixation, especially when displacement is over 2 mm. Epidemiology It occurs commonly in adolescents and older children. However, it does occur rarely in adults though it may be under reported because of difficulty in diagnosis. Etymology This fracture pattern is named after Paul Jules Tillaux, a French Anatomist and Surgeon (1834-1904). See also Ankle fracture References == External links ==