Repaglinide

By U. Tuwas. Emmanuel College.

The second step may involve transplanting stem cells purchase 1 mg repaglinide with visa, differentiated cells proven repaglinide 0.5 mg, tis- sues, or organs or restoring endogenous stem cell or progenitor function to repopulate damaged organs. Advances are being made in each of these areas, and effective combined approaches may one day be feasible. If any or all of this comes to fruition, if we are able to push back age-related diseases as a group and extend healthspan, and if this can be translated into clinical treatments, health care as we know it would be transformed with myriad economic and social consequences and benets. Research AfA (2012) The Silver Book: chronic disease and medical innovation in an aging nation. Anfossi G, Russo I, Bonomo K, Trovati M (2010) The cardiovascular effects of metformin: further reasons to consider an old drug as a cornerstone in the therapy of type 2 diabetes mel- litus. Lamanna C, Monami M, Marchionni N, Mannucci E (2011) Effect of metformin on cardio- vascular events and mortality: a meta-analysis of randomized clinical trials. A comparison of mortality in people initiated with metformin or sulphonylurea mono- therapy and matched, non-diabetic controls. Yamamoto M, Otsuki M (2006) Effect of inhibition of alpha-glucosidase on age-related glu- cose intolerance and pancreatic atrophy in rats. Viswanathan M, Guarente L (2011) Regulation of Caenorhabditis elegans lifespan by sir-2. Verges B, Walter T, Cariou B (2014) Endocrine side effects of anti-cancer drugs: effects of anti-cancer targeted therapies on lipid and glucose metabolism. Rockwood K, Mitnitski A (2011) Frailty dened by decit accumulation and geriatric medi- cine dened by frailty. Cover illustration: Cassava green mite filled with resting spores of the fungus Neozygites tanajoae. When in March 1985 the rst issue of the journal was published, Leo already acted as associate editor, at the side of editor-in-chief prof. The formal difference between the two was cancelled in 1993, when both were mentioned on the journal s cover as plain editor. Throughout his research and teaching career Leo has always been involved with pathogens, rst of insects, later of mites. Therefore, it should not come as a surprise that I was struck by the idea to honour Leo s editorial retirement with a special journal issue dedicated to the subject that he nds most interesting: acarine pathogens and pathology. I discussed the idea with Leo, and was very pleased to learn that he not only appreciated the token, but also that he was willing to lend his expertise to the enterprise. Next, we asked about all relevant researchers we could think of to participate, and much to my surprise almost all accepted the invitation. The 24 contributions provide a wide variety of aspects of acaro- pathogens, just as we had hoped for. There are numerous highlights, but one particularly worthy of mention because it is the rst time in the journal s history, and because it is yet another token of appreciation is the formal description of an acaropathogenic fungus, new to science: Hirsutella vandergeesti. Diseases of mites and ticks: from basic pathology to microbial control an introduction Leo P. This effect was ascribed to the presence of an acaropathogenic fungus that was later described by Fisher (1950)asHirsutella thompsonii. It would still take several decades before any compre- hensive research would be conducted on pathogens of Acari. The current collection of 24 papers is a mixture of primary research articles and lit- erature reviews, presenting a broad overview of the developments in about all possible aspects of acarine diseases, stretching from basic pathology to microbial pest control. The pathogens include fungi, bacteria, and protozoa (as well as an occasional virus and unidentied organism), the hosts are mites and ticks from a variety of taxa (e. With such variety the contributions can be ordered in a near innite number of coherent ways, and we had to pick just one. Individual ticks are frequently infected by more than one (type of) pathogen, which may interact in various possible ways. Ginsberg presents a literature review of the possible effects of coinfection of ticks, and a simple model linking the implications of coinfection with pathogen trans- mission. Very different, yet equally basic, is the intriguing case study of the association L. The genus Neozygites has a worldwide distribution and it is well known for its entomo-/acaropath- ogenicity. Inventories in Poland and several other Central-European countries show the presence of Neozygites spp. Still mainly descriptive, but increasingly applied, is the extensive review of fungi found in association with a variety of tick species in South America (Fernandes and Bittencourt). An isolate of Beauveria bassiana has previ- ously been found to induce the falling of Varroa destructor Anderson and Trueman from bees. Commercial products based on entomopathogenic fungi are being applied in a growing number of control programmes against plant pests, but their application against animal ectoparasites lacks behind, as Polar et al. Still, laboratory studies as well as pasture applications of several fungal products have shown great promise. Instead of treating large areas of eld, it could be much more cost effective if cattle were treated topically, but so far topical application has shown variable results.

The skin signs usually appear at the same time as the muscle symptoms but generic 2 mg repaglinide fast delivery, occasionally generic repaglinide 1 mg without prescription, appear months or even years earlier. Climbing stairs, getting up from important clues to systemic connective tissue disorders. The rash may become scaly and, rarely, itchy; In children the disorder is often self-limiting, but in eventually that on the light-exposed areas and overly- adults it may be prolonged and progressive. Myositis may lead to permanent weakness and immo- bility, and inammation to contractures or cutaneous calcinosis. Long-term and regular Other connective tissue disorders may look similar, follow-up is necessary. Myopathy can be In this disorder the skin becomes hard as connective a side-effect of systemic steroids, so weakness is not tissues thicken. In addition Investigations there is intimal thickening of arterioles and arteries. About 30% of adults with dermatomyositis also These processes are not conned to the skin, but involve have an underlying malignancy. Adult dermatomyositis or The cause of systemic sclerosis is unknown but polymyositis therefore requires a search for such an many, apparently unrelated, pieces of the complex underlying malignancy. Toxoplasmosis rapeseed oil in Spain and dimerised l-tryptophan for should be excluded by serology. Environmental factors may also be rel- evant in isolated cases; changes like those of systemic Treatment sclerosis have affected workers exposed to polyvinyl Systemic steroids, often in high doses (e. Fibrosis of the lungs leads to dyspnoea, and brosis of the heart to congestive failure. The kidneys are involved late, but this has a grave prognosis in chronic graft-vs. Complications Investigations Most complications are caused by the involvement of The diagnosis is made clinically because histological organs other than the skin, but ulcers of the ngertips abnormalities are seldom present until the physical and calcinosis are distressing (Fig. Barium studies are best avoided as obstruc- Differential diagnosis tion may follow poor evacuation. Other contrast media Other causes of Raynaud s phenomenon are given are available. The differential diagnosis includes of muscle enzymes and immunoglobulin levels, and chilblains (p. Changes like those of progressive systemic sclerosis Systemic steroids, salicylates, antimalarials and long- affect workers exposed to polyvinyl chloride mono- term penicillin are used, but are not of proven value. The mnemonic stands for Calcinosis, Raynaud s phenomenon, oEsophageal dysmotility, Sclerodactyly and Telangiectasia. Telan- giectasia is peri-ungual on the ngers and at, mat- like or rectangular on the face. Many patients with this syndrome develop a diffuse progressive systemic sclerosis after months or years. Localized areas of skin become indurated, sometimes after an upper respiratory tract infection or prolonged renal function. Recently, there have been sinophilia are present and a deep skin biopsy, which promising reports of the efcacy of ultraviolet A-1 includes muscle, shows that the fascia overlying the (340 400 nm) phototherapy for affected skin in muscle is thickened. The disease responds promptly to systemic steroids; the long-term prognosis is good but disability in the short term can be severe. In a young child this can lead to facial Morphoea is a localized form of scleroderma with hemiatrophy. Its prognosis is usu- condition may cause stenosis of the urethral meatus, ally good, and the brosis slowly clears leaving slight and adhesions between the foreskin and glans of the depression and hyperpigmentation. Alopecia is mild and the hair fall mimics Many think that this condition is related to morphoea, telogen efuvium. About 25% of non-indurated white shiny macules, sometimes with patients have a small vessel vasculitis with palpable obvious plugging in the follicular openings. Women purpura, leg ulcers and painful dermal nodules on the are affected far more often than men and, although hands or elbows. Many show Raynaud s phenomenon, any area of skin can be involved, the classical ivory- arthritis, serositis and myositis. The skin lesions (keratoderma blenorrhagicum) are psoriasis-like red scaling plaques, often studded with vesicles and pus- Investigations tules, seen most often on the feet. The toes are red and Patients with mixed connective tissue disease have anti- swollen, and the nails thicken. Psoriasiform plaques bodies in high titre directed against one or more extract- may also occur on the penis and scrotum, with redness able nuclear antigens.

An old-timer suggests putting a little turpentine around your ankles and one drop on your tongue repaglinide 0.5 mg otc, to discourage them generic 2mg repaglinide overnight delivery. Because this disease is now so prominent, and because it can occur so mysteriously, here are more detailed symptoms on its usual 3 stages (which not everyone goes through): 1 - Small raised bumps (and/or a rash) appear on the entire body for 1-2 days or several weeks and then fades. Frequently, enlargement of the spleen and lymph glands occurs and/or severe headaches, enlargement of the heart muscle, and abnormal heart rhythm. If treatment is postponed until more advanced symptoms develop (heart, brain, or joint problems), drug medications do not work as well. In California it is also transmitted by the black-legged tick, carried by wood rats. Both deer ticks and black-legged ticks are very tiny: An adult is less than 1/10th of an inch, and the nymph is a pinhead in size. Lyme disease most frequently occurs where the white-tailed deer is most abundant, which is the northeastern states. Dogs and cats can collect these special ticks out in the woods and bring them into your home. Tick bites are generally painless and unnoticed; so the symptoms may not at first, or later, be correctly diagnosed. But in advanced stages, when correct diagnosis finally occurs, the situation may have become critical. The symptoms are similar to those of multiple sclerosis, gout, and Epstein-Barr virus (chronic fatigue syndrome), all three of which see. A test now exists which can detect the bacteria (Borrelia burgdorferi) which causes Lyme disease. Lyme disease is treatable and almost always curable if correctly diagnosed in the early stages. You want the entire tick out, without leaving part of it in the skin or injecting bacteria from its broken body into the skin. Avoid going out in the woods in the summer months, when ticks are the most active (especially June to August). When the blood is pure and the body clean, there is far less likelihood of tick bites and lice infestation. A diet high in fiber and natural food will help keep the body clean and protect against infections. Herbs useful in preventing infections include: echinacea, goldenseal, garlic, and burdock. So, if you are being treated for Lyme disease and are not getting better, consider having a second test made. One study of nearly 800 people, diagnosed with Lyme disease, revealed that half of them did not have it! Buboes (swollen places) begin to appear the second day in the groin, under the arms, and in the neck. The disease causes great weakness, and death often occurs sometime between the third and sixth day. The bacteria are in its droppings, which it leaves in the food stuffs it has broken into and partly eaten. In earlier centuries, several outbreaks of the plague occurred; during one of which one-sixth of the people of Europe died. The symptoms are about the same as pneumonia, but it is transmitted through the air and is extremely contagious. If the tissues have been merely squeezed, then the matter is of little importance. There may be soreness and a black-and-blue appearance, but it will soon disappear. Then more extensive muscle spasms begin, and the victim gradually becomes maniacal. The final stages are depression, exhaustion and sometimes paralysis, coma, and death. If the symptoms of rabies have already begun to appear, the person will probably die. Rabies can also be transmitted by the bite of infected bats, foxes, skunks, and other animals. Do this even if, what appears to be, a rabid dog only licks a previous wound on you. If acid is not available, you may burn the wound with a magnifying glass in the sunlight. He also says to put hydrochloric acid on the wound, to neutralize the rabies poison in the saliva. Then, after discussing a number of herbal remedies to also use, he quotes a scientific paper by an M. By the time he discovered he had it, the disease was advanced and he knew he was soon to die. Kloss quotes a London newspaper which reported on the scientific paper: "Concluding from these various symptoms that he was suffering with hydrophobia, he [Buisson] resolved to make an end of himself by suffocating himself in a vapor [steam] bath.

In neurons purchase 0.5 mg repaglinide mastercard, ataxin-1 is predominantly nuclear buy 1 mg repaglinide visa, with some cytoplasmic staining in Purkinje cells and brainstem nuclei (Servadio et al. Another nuclear protein recently found to be capable of interacting with ataxin-1 is A1Up (Davidson et al. Analysis of the A1Up amino acid sequence identified a region in its N-terminal with substantial similarity to an ubiquitinlike domain. For example, one member of the ubiquitinlike family is Rad23, a protein important for nucleotide excision repair (Guzder et al. Rad23 and interacts with the 26S proteasome through its N-terminal ubiquitinlike domain (Schauber et al. The ataxin-1[82Q] transgenic mice developed severe ataxia and progressive Purkinje cell pathology. In contrast, mice expressing ataxin-1[30Q] failed to develop any signs of neurologic or pathological abnormalities and were indistinguishable from nontransgenic littermates (Clark et al. These studies demonstrated that Purkinje cell pathological changes are induced specific to the expression of ataxin-1 with an expanded polyglutamine tract. In transgenic mice from an ataxin-1[30Q] line, ataxin-1 localized to several approx 0. By 12 wk, the motor-skill impairment progressed to overt ataxia, which worsened over time. The first histologic change detected was the development of cytoplasmic vacuoles within Purkinje cell bodies at postnatal day 25; by 5 wk, loss of proximal dendritic branches and a decrease in the number of dendritic spines became apparent, indicating that ataxin-1[82Q] impairs the maintenance of dendritic arborization (Clark et al. By 12 15 wk, the complexity of the dendritic arborization of Purkinje cells was markedly reduced, the molecular layer atrophied, and there were several heterotopic Purkinje cells within the molecular layer (Fig. The Purkinje cells heterotopia was not detected in young animals and, thus, is not a developmental abnormality. Most likely it reflects an attempt to preserve synaptic function in the presence of severely reduced dendritic arborization. Importantly, Purkinje cell loss was minimal at the time of progressive gait abnormality. To ascertain whether ataxin-1 must be in the nucleus to cause disease, Klement et al. Ataxin-1 was diffusely distributed throughout the cytoplasm and formed no aggregates, even when the mice were a year old. Nuclear localization is clearly critical for pathogenesis and ataxin-1 aggre- gation. Cerebellar sections were examined for Purkinje cell morphological alter- ations using calbindin immunofluroesence. These mice developed ataxia and Purkinje cell pathology similar to the original ataxin-1[82Q] transgenic mice, but without detectable nuclear ataxin-1 aggregates at either the light or electron microscopic levels. Thus, although nuclear localization of ataxin-1 is necessary, nuclear aggregation of ataxin-1 appears not to be required for initiation of Purkinje cell pathogenesis in transgenic mice. It is important to note that the deletion of 122 amino acids might have compromised ataxin-1 in various ways (e. This seems unlikely because this truncated ataxin-1 retained its ability to produce all of the neurobehavioral and unique pathologic features observed in the ataxin-1[82Q] mice. The presence of nuclear aggregates of ataxin-1[82Q] were reduced significantly both in terms of their frequency and their size. Yet, the Purkinje cell pathology was markedly worse compared to that seen in the ataxin-1[82Q] mice. These studies demonstrated the importance of ataxin-1 ubiquitination for the formation of the nuclear aggregates. Further- more, they showed that pathology is not dependent on the formation of nuclear aggregates. Interestingly, a number of the genes found to be downregulated encoded proteins involved in neuronal calcium signaling. It is also worth noting that the same downregulation in gene expression was found in the mice expressing ataxin-1 [77Q] with amino acids deleted from the self-association region, lacking aggregates, as well as the ataxin-1[82] expressing mice, containing aggre- gates. This provides further evidence that the Purkinje cell disease process is the same with or without nuclear aggregates of ataxin-1. Within the nucleus, ataxin-1 associated with the nuclear matrix, and the mutant form caused redistribution of the promyelocytic oncogenic domain. Furthermore, the importance of the ubiquitin proteasomal pathway in the degradation of mutant ataxin-1 has also been demonstrated using a cell culture system (Cummings et al. Although both ataxin- 1[2Q] and ataxin-1[82Q] were ubiquitinated to a similar level in transfected cells, ataxin-1[82Q] was less susceptible to degradation than ataxin-1[2Q]. In addition, inhibition of the proteasomal pathway enhanced the aggrega- tion of ataxin-1 in transfected cells.

Affected calves had persistent neutrophil counts a neutrophilia in patients recovering from acute infec- exceeding 30 buy 2 mg repaglinide with mastercard,000/ l cheap repaglinide 0.5 mg free shipping, and some had counts exceeding tion. Lymphocyte counts may range from 30,000 to humans brought about further suspicion of an inher- 100,000 in such cases, and immature lymphocytes and ited disorder in leukemoid calves. Recessive homozygotes are expected as a result of parasite loads and other con- affected, and heterozygote carriers have intermediate ditions. Denitive diagnosis alongside identication migration into tissue sites of inammation. Infections thought to be clinically minor re- Treatment spond poorly or not at all to appropriate therapy. Recur- Treatment is only palliative, and most affected calves die rence of signs and multiple problems are typical. To date those that survive to develop chronic disease associated most affected calves studied have had greater than with poor growth are suspected to have the disease. Al- cause variable expression of the glycoprotein deciency though myelogenous leukemia is a consideration, is possible in homozygote recessives and in heterozy- neutrophil function tests differentiate these diseases gotes, it also is possible that mild forms of disease and because neutrophils in myelogenous leukemic patients prolonged survival occur. Affected calves must recessives bleed excessively or repeatedly following inju- be differentiated from calves with chronic abscessation ries or routine surgical procedures such as castration or of the thorax or abdomen and calves persistently in- dehorning. Thrombocytopenia is the most common cause of abnormal coagulation in dairy cattle. Thrombocytope- is most commonly observed in association with neonatal nia and leukopenia tend to be profound long before calf septicemia. Similar thrombocytopenia caused by usually affect platelet survival rather than production. Infec- bocytopenia has been reproduced experimentally, most tious diseases cause decreased platelet survival via sev- thrombocytopenia cases are sporadic and associated with eral mechanisms. The calf completely recovered following a fection show a return to normal platelet numbers in whole blood transfusion and replacement of the prop- conjunction with an increase in serum antibody titers tosed globe. Platelet count (usually less than 50,000/ l) pertains to cattle because, in general, specic reagents 2. Bleeding time and clot retraction occur from small vessels anywhere in the body typify are abnormal. Bleeding may occur from the skin at sites of Once the diagnosis of thrombocytopenia is conrmed injections or insect bites. Venipuncture causes bleeding, by laboratory studies, clues to the cause of this disorder hematoma formation, and possible venous thrombosis. Septicemia, endotoxemia, and recent Epistaxis is common in cattle with thrombocytopenia trauma may be clinically obvious, whereas ingested tox- and other signs of bleeding frequently accompanying ins or parenteral drugs may require careful historical data inammation or injury to specic sites. Melena and hematuria also are pos- ever the etiology of thrombocytopenia remains obscure, sible signs. Obviously stress, trauma, and bleeding requires therapy with a fresh whole blood hydration factors may affect the incidence of bleeding at transfusion and treatment of any primary condition. Blood transfusions are rst ized both by bleeding and excessive intravascular throm- aid for thrombocytopenia, and the success of transfu- bosis. This apparent contradiction leads to a dramatic sion completely depends on whether platelet loss or and usually fatal clinical appearance. Fibrinolysis is exces- Therefore they are near recovery, and humoral anti- sive, and localized or regional tissue hypoxia occurs as bodies are peaking at this same time. Subsequent major organ dys- transfusion and supportive care can save many of these function (liver, kidney, brain, gut) may ensue. Chronic bracken fern toxicity, Products of inammation (platelet activating factors) furazolidone toxicity in calves, and other conditions or infectious agents (endotoxin, clostridium toxin) that depress bone marrow are difcult to correct. The patient must be monitored with daily orrhages may be manifest as petechiae, ecchymoses, platelet counts and physical examination to deter- hematomas, or bleeding from body orices. Fecal occult frank blood clots in the feces may appear especially in blood, multistix evaluation of urine, and inspection cattle with enteritis. Microscopic or macroscopic hema- of mucous membranes are important means of moni- turia may be present. Further rapid venous thrombosis following venipuncture are whole blood transfusions are not indicated unless typical signs. Dexamethasone is preferable nous thrombosis may frustrate attempts to improve the in our experience and may be therapeutic at doses as systemic state. In all instances, a patient already seriously pected immune-mediated thrombocytopenia can be ill from a primary disease becomes sicker and has weaned off medication within 30 days and do not signs of thrombosis and bleeding. Other hepatocellular disease may cause hemorrhage result- causes of bleeding such as hepatic failure, warfarin ing from lack of liver origin clotting factors. Coumarin toxicosis, and inherited coagulopathies can only be competes with vitamin Kl, a precursor of clotting fac- ruled out by laboratory tests. Prolonged prothrombin time, activated partial lar decrease in liver production of the aforementioned thromboplastin time, and thrombin time clotting factors. For example, the prothrombin the earliest laboratory coagulation abnormality found time and activated partial thromboplastin time may or in patients with coumarin or dicoumarol toxicity.

Only a part of the eggs produced manages to reach the intestinal lumen or the bladder cavity; many others do not successfully accomplish the migration from veins to intestines and bladder repaglinide 2mg fast delivery. They die en route and are the cause of subsequent pathology at the predilection sites or elsewhere buy discount repaglinide 1 mg line. The adult worms are of a benign nature and do not normally cause any pathology [1]. It involves a denitive and an intermediate host, two free-living stages, responsible for the infection of humans (cercariae) and snails (miracidia), and both a sexual and an asex- ual multiplication. The population biology is characterized by the facts that the free-living stages are extremely short-lived (less than 48 hours), the egg production is low (no more than approximately 300 eggs per gram feces per day in S. On average, worms are believed to live for 3 5 years but some sur- vive for 30 years or even longer. There are four different phases of the life cycle, and each causes a char- acteristic type of pathology and disease: 1 The penetration of cercariae through the intact human skin may result in so-called cercarial-dermatitis or swimmers itch. The onset of this phase may be as early as 2 weeks postexposure; it normally subsides by the time egg excretion starts, 7 10 weeks after the infection. The symptoms and signs of infection during that stage are caused by the immunopathological host reaction to schistosome eggs that get stuck in the tissues. Sometimes eggs get astray and get stuck in unusual sites: ectopic schistosomiasis may be the result. Transmission of schistosomiasis is restricted to the tropics and even there the distribution is highly focal. It is dependent on ecological conditions favorable or unfavorable for the survival and multiplication of the inter- mediate host snails. Clinical features The most prominent clinical features and the cause of signicant morbidity of schistosomiasis in endemic areas are the presence of (sometimes bloody) diarrhea, hepatomegaly, and splenomegaly in S. These manifesta- tions are largely associated with the intensity of present or past infection, that is, the worm load. First-line lab- oratory diagnosis is complicated by the fact that eggs are not excreted yet in the rst two phases of infection. During the phases of established and late chronic infection egg excretion may be very low and eggs are easily missed. Serology is useful in travelers normally living in nonendemic areas but of little help in endemic regions due to the long persistence of antibod- ies after clinically successful treatment. Skin manifestations Skin manifestations are not normally part of the clinical picture in estab- lished infections. Yet, they are occasionally seen in infections with each of the three species of human schistosomes. In the early phase of infection they are caused by cercarial penetration of the human skin, or by the aller- gic reaction as a component of the Katayama syndrome. Later they may be due to eggs in the genital system or to eggs that get astray, in situations referred to as cases of ectopic schistosomiasis. Cercarial dermatitis The duration of passage through the dermis is normally short. The cercariae lose their tail and the so-called schistosomulae rapidly pass the dermis to be transported to deeper layers. The clinical picture of cercarial dermatitis develops in a matter of minutes, and mostly within 1 hour Schistosomiasis 229 after penetration. In less than a day, the schistosomulae pass the skin and reach the lungs; the dermatitis vanishes and symptoms disappear within 2 3 days. In a highly endemic area in Congo, I used to be told by the local people that in particular sites exposure to the surface water was unhealthy because it caused itching. In those sites snail and cercarial concentrations were shown to be very high (personal observations). Mostly, however, this phase of infection with the human parasite remains unnoticed by the local population. The situation may be different when previously uninfected adults get exposed to (high densities of) cercariae. Intense itching shortly after swimming is commonly described by European or American visitors to endemic countries who are later shown to be infected [3]. A history of cercarial dermatitis is reported in 10 36% of travelers later diagnosed with schistosomiasis [4]. Cercarial dermatitis is much more intense when the cercariae belong to schistosome species unable to successfully develop in humans, such as those of Ornithobilharzia ocellata of birds. The schistosomulae of this and related species penetrate the human skin and migrate through the skin but fail to continue further development to adult worms. There is no specic means of diagnosis as antibodies have not been formed yet and eggs can of course not be found either. These brothers, developed an intensely itchy rash immediately after swimming at a beach near Boston.

Serum androgens and genetic linkage analysis in early onset androgenetic alopecia buy repaglinide 1 mg without prescription. Insulin gene polymorphism and premature male pattern baldness in the general population cheap 1 mg repaglinide visa. Polymorphism of the androgen receptor gene is associated with male pattern baldness. Genetic variation in the human androgen receptor gene is the major determinant of common early-onset androgenetic alopecia. The E211 G>A androgen receptor polymorphism is associated with a decreased risk of metastatic prostate cancer and androgenetic alopecia. The psychosocial consequences of androgenetic alopecia: a review of the research literature. Psychological effects of androgenetic alopecia on women: comparisons with balding men and with female control subjects. Psychological characteristics of women with androgenetic alopecia: a controlled study. The reliability of horizontally sectioned scalp biopsies in the diagnosis of chronic diffuse telogen hair loss in women. Changes in hair weight and hair count in men with androgenetic alopecia, after application of 5% and2% topical minoxidil, placebo or no treatment. A randomized clinical trial of 5% topical minoxidil versus 2% topical minoxidil and placebo in the treatment of androgenetic alopecia in men. Five-year follow-up of men with androgenetic alopecia treated with topical minoxidil. The effects of nasteride on scalp skin and serum androgen levels in men with androgenetic alopecia. Use of nasteride in the treatment of men with androgenetic alopecia (male pattern hair loss). An open, randomized, comparative study of oral nasteride and 5% topical minoxidil in male androgenetic alopecia. The importance of dual 5alpha-reductase inhibition in the treatment of male pattern hair loss: results of a randomized placebo-controlled study of dutasteride versus nasteride. Quantitative assessment of spironolactone treatment in women with diffuse androgen-dependent alopecia. The diagnosis and treatment of iron deciency and its potential relationship to hair loss. The importance of adequate serum ferritin levels during oral cyproterone acetate and ethinyl oestradiol treatment of diffuse androgen-dependent alopecia in women. A randomized, placebo-controlled trial of 1% topical minoxidil solution in the treatment of androgenetic alopecia in Japanese women. Patients present with a complaint of increased shedding over normal levels and associated diffuse alopecia. The excessive shedding is the result of alterations of the hair-growth cycle with premature conversion of anagen follicles to telogen follicles, which represents a shift of 7 25% of anagen follicles to telogen (Fig. It presents as acute (<4 months), chronic (>4 months), and chronic-repetitive (Fig. The primary insult is to the dermal papillae of the anagen fol- licle, which induces an early shunt to telogen. Regeneration of the follicle is determined by the bulge area, so any damage, stress, or inammation that involves the bulge will affect regenera- tion (Fig. The shedding results in a diffuse loss with a more prominent central and frontal scalp loss. The patient usually relates loss of body hair and a diminished rate of hair growth, espe- cially of leg hair. When a trigger is identied and removed or treated, the patient experiences diminished shedding and later regrowth of hair (Table 3). The differential diagnosis of diffuse alopecia includes androgenetic alopecia, diffuse alopecia areata, and an inammatory alopecia such as central centrifugal cicatricial alopecia and lichen planopilaris, especially when the primary loss involves the central scalp. A light hair pull will extract loose hair, which can be then examined under 2x magnica- tion. If there are numerous dystrophic anagen hairs, the diagnosis is an anagen efuvium. Anagen efuviums are the result of severe insult to the dermal papillae, which produces 80% loss of scalp hair. A telogen efuvium represents a minor insult to some anagen dermal papillae with 7 25% loss of scalp hair. An anagen efuvium is observed in alopecia areata and as a result of a cytotoxic drug therapy. Also, a false-positive hair pull will be noted if the patient has not shampooed or combed for several days.