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• Professor Emeritus, Department of Cellular & Molecular Pharmacology, University of California, San Francisco

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Increasing travel to and immigration from areas with endemic infection have led to a need for increased vigilance in the United States purchase voltaren 50 mg visa arthritis in neck treatment exercises. The incidence of transfusion-associated malaria has decreased over the last 30 years in the United States cheap voltaren 100mg fast delivery arthritis in lower back. Most cases are attributed to infected donors who have immigrated to the United States rather than people born in the United States who traveled to areas with endemic infec tion voltaren 50 mg otc medication to ease arthritis. Prevention of transfusion-transmitted malaria relies on interviewing donors for risk factors related to residence in or travel to areas with endemic infection or previous treatment for malaria discount voltaren 50 mg with mastercard arthritis in fingers cream. Donation should be delayed until 3 years after either completing treatment of malaria or living in a country where malaria is found and 12 months after returning from a trip to an area where malaria is found. The immigration of millions of people from areas with endemic T cruzi infection (parts of Central America, South America, and Mexico) and increased international travel have raised concern about the potential for transfusion-transmitted Chagas disease. To date, fewer than 10 cases of transfusion-transmitted Chagas disease have been reported in North America. However, studies of blood donors likely to have been born in or to have trav eled to areas with endemic infection have found antibodies to T cruzi in as many as 0. Although recognized transfusion transmissions of T cruzi in the United States have been rare, in some areas of the United States, the prevalence of Chagas disease estimated by detection of antibodies appears to have increased in recent years. In the absence of treatment, seropositive people can remain potential sources of infection by blood trans fusion for decades after immigration from a region of the world with endemic disease. Screening for Chagas disease by donor history is not adequately sensitive or specifc to identify infected donors. In the frst 16 months of screen ing, more than 14 million donations were tested, yielding a seroprevalence of 1:27 500; the highest rates were in Florida (1:3800) and California (1:8300). However, more recent discussions have suggested that donors only be screened a limited number of times, depending on their risk of continued exposure. Babesiosis is the most commonly reported transfusion-associated tickborne infection in the United States. However, at least 4 cases have been associated with receipt of whole blood-derived Platelets, which often contain a small number of red blood cells. Although most infections are asymptomatic, Babesia infection can cause severe, life-threatening disease, particularly in the elderly and people without spleens. Severe infection can result in hemolytic anemia, thrombocytopenia, and renal failure. Surveys using indirect immunofuorescent antibody assays in areas of Connecticut and New York with highly endemic infection have revealed seropositivity rates for B microti of approxi mately 1% and 4%, respectively. Although people with acute illness or fever are not suitable to donate blood, people infected with Babesia species commonly are asymptomatic or experience only mild and nonspecifc symptoms. In addition, Babesia species can cause asymptomatic infection for months and even years in untreated, otherwise healthy people. Questioning donors about recent tick bites has been shown to be ineffective, in part because donors who are sero positive for antibody to tickborne agents are no more likely than seronegative donors to recall tick bites. The asymptomatic incubation periods in the clini cally ill recipients lasted from 6. Improving Blood Safety A number of strategies have been proposed or implemented to further decrease the risk of transmission of infectious agents through blood and blood products. Methods used for this include wet and dry heat and treatment with a solvent/detergent. Solvent/detergent-treated pooled Plasma for transfusion no longer is marketed in the United States, but methods of treating single donor Plasma are under study. Because of the fragility of Red Blood Cells and Platelets, pathogen inactivation is more diffcult. However, several methods have been developed, such as addition of pso ralens followed by exposure to ultraviolet A, which binds nucleic acids and blocks replica tion of bacteria and viruses. Leukoreduction, in which flters are used to remove donor white blood cells, is performed increasingly in the United States. Benefts of this process include decreasing febrile transfusion reactions related to white blood cells and their products and decreasing the immune modulation associated with transfusion. Established alternatives include recombinant clotting factors for patients with hemophilia and factors such as erythropoietin used to stimulate red blood cell production. These adverse safety outcomes and shortened time to tumor progression have been observed in certain patients with cancer who have chemotherapy-related anemia, such as people with advanced head and neck cancer receiving radiation therapy and metastatic breast cancer. Blood may be donated by the patient several weeks before a surgical procedure (preoperative autologous donation) or, alternatively, donated immediately before surgery and replaced with a volume expander (acute normovolemic hemodilution). Autologous blood is not completely risk free, because bacterial contamination may occur. During surgery, blood lost by the patient may be collected, processed, and reinfused into the patient. The National Healthcare Safety Network is a secure Internet-based surveillance system that collects data from voluntary participating health care facilities in the United States. A similar system has been established in several centers in the United States that treat patients with thalassemia who depend on frequent blood transfusions. For regulatory purposes, serious adverse reactions and product problems should be reported to the manufacturer (or, alternatively, to the sup plier for transmission to the manufacturer). The proliferation of these products also has increased the opportuni ties for transmission of infectious pathogens, including bacteria, viruses, and parasites. The Joint 1 Commission adopted some of these standards, which will apply to accredited organiza tions that store or use tissue. Solid organs are overseen by the Health Resources and Services Administration through the Organ Procurement and Transplant Network, which also compiles donor-derived disease reports. All suspected disease-transmission cases, notifable diseases, and clusters should be reported to public health agencies.

The diagnosis of Graves disease is based on clinical and biochemical manifestations of hyperthyroidism generic 100mg voltaren visa arthritis in neck shoulder pain. The hyperthyroidism is due to continuous stimulation of the thyroid-stimulating hormone receptor by auto antibodies discount voltaren 100mg with visa acute arthritis definition. Alternatively voltaren 50 mg on line diet during arthritis, the anti-thyroid-stimulating hormone receptor autoantibodies may be inhibitory instead of stimulating; the presence of these antibodies is associated with hypothyroidism purchase voltaren 100mg without prescription arthritis pain throughout body. The anti-thyroid-stimulating hor mone receptor autoantibodies are considered to be responsible for transient neonatal hyperthyroidism. Treatment is gener ally with either radioiodine therapy or antithyroid medication. This disease is found most commonly in the middle-aged and elderly, but it also occurs in children. The clinical disease is marked by initial thyrotoxicosis, which is invariably followed by progressive hypothyroidism and myxoedema. The clinical diagnosis of Hashi moto disease is based on the presence of a firm, rubbery, painless goitre with initially euthyroidism, but later clinical signs of hypo thyroidism are often apparent in combination with the presence of high titres of antithyroid peroxidase and/or antithyroglobulin anti bodies. The former autoantibodies are closely associated with overt thyroid dysfunction, and their presence tends to correlate with thyroidal damage and lymphocytic inflammation. Although these antibodies may be cytotoxic to thyrocytes, formal proof of their pathogenicity has not yet been obtained. Histopathology reveals infiltrates of T cells and plasma cells, often containing germinal centres, and eventual fibrosis. T cells are considered to play a criti cal role in thyroid destruction by interacting with the follicular cells as well as the extracellular matrix. T cells may destroy thyroid tissue by direct cytotoxicity or indirectly by cytokine secretion. Excess iodine ingestion has been impli cated in the induction and exacerbation of autoimmune thyroiditis in human populations. Iodine is a requisite substrate for the synthesis of the thyroid hormones, but in many countries the levels of iodine ingested in the food are far beyond the recommended level of 150 flg/day. The administration of pharmacological quantities of iodine, such as iodides for the treatment of pulmonary disease, organic iodine present in medications, and X-ray contrast dyes, and the ingestion of iodine-rich natural foods may result in goitre, hypothyroidism, or hyperthyroidism, especially in patients with underlying thyroid disease (Vagenakis & Braverman, 1975). An autoregulatory mechanism within the thyroid serves as the first line of defence against fluctuations in the supply of iodine. This mechanism also prevents induction of the Wolff-Chaikoff effect, 84 Clinical Expression of Human Autoimmune Diseases which is associated with inhibition of thyroid stimulating hormone synthesis that can result from exposure to a very large quantity of iodine. The pathological consequences of iodine excess, such as seen with the Wolff-Chaikoff effect, ensue only when thyroid auto regulation is defective or when autoregulation is absent (Woeber, 1991). When the source of iodine has been dissipated, the patho logical consequences of iodine excess will resolve. However, because the autoimmune component has not been identified or other pathogenetic mechanisms dominate disease progression, these diseases have not yet been accepted as true autoimmune diseases. Here, we only briefly discuss some apparent examples, with emphasis on the contribution of the auto immune response to these conditions. Sarcoidosis is a multisystem granulomatous disease of unknown origin that occurs most commonly in young adults. A sarcoidosis-like pulmonary disease has been clearly asso ciated with beryllium exposure. Alzheimer disease is a very heterogeneous disorder that is characterized by dementia due to plaque formation, with a central amyloid core, in frontal and temporal lobes. Nevertheless, secondary immune responses to, for instance, amyloid-fl peptides may contribute to the pathogenesis of the disease, but this has not been validated. Atherosclerosis is a chronic inflammation of the arterial vessel wall resulting in plaque formation that eventually may cause cardio vascular events, such as myocardial infarction or cerebral vascular accidents. Atherosclerotic plaques also contain some T cells that are con sidered to be autoreactive, although the respective autoantigens have not yet been identified. These T cells are probably not involved in the plaque formation as such, but they may cause plaque instability, rupture, and subsequent clinical events. The incidence of a disease is the number of new diagnoses that occur in a population in a given time period. The prevalence is the number of people who have the disease and so is determined by the incidence and duration of the illness. The criteria used to define a disease, methods used to identify people with a specific condition, study area, as well as secular changes in rates can contribute to the variability in rates for a specific disease that may be seen among studies. A recent review of epidemiological studies covering 24 specific autoimmune diseases estimated that approximately 3% of the population in the United States suffers from an autoimmune disease (Jacobson et al. This estimate is likely to be low, as for many diseases our knowledge of basic epidemiology is quite limited or based on studies conducted 30 or more years ago, and some diseases. A revised estimate of the prevalence of autoimmune diseases presented in a recent report of the United States National Institutes of Health (2000) is 5�8%. Many specific autoimmune diseases are relatively rare, with an estimated incidence of less than 5 per 100 000 persons per year or an estimated prevalence of less than 20 per 100 000 (Table 7). Diabetes mellitus type 1 rates are for children and adolescents (age <20 years); all other rates are for adult populations. Two autoimmune diseases, diabetes mellitus type 1 and myocarditis, are most commonly seen in children and adolescents. Addison disease, multiple sclerosis, and vitiligo occur most often in young adults (and teenagers, in the case of vitiligo) (Table 7).

The incubation period is variable; egg production begins approximately 8 weeks after ingestion of P westermani metacercariae order 100 mg voltaren amex arthritis diet for animals. Chest radiographs may appear normal or resemble radiographs from patients with tuberculosis buy 100mg voltaren with amex arthritis in feet help. Parainfuenza virus types 1 and 2 are the most com-1 mon pathogens associated with croup generic voltaren 100mg amex arthritis in knee and foot, and parainfuenza virus type 3 most commonly is associated with bronchiolitis and pneumonia in infants and young children discount 50mg voltaren mastercard arthritis neck pain treatment. Rarely, parotitis, aseptic meningitis, and encephalitis have been associated with type 3 infections. Parainfuenza virus infections can exacerbate symptoms of chronic lung disease and asthma in children and adults. Severe and persistent infections occur in immunodefcient children and are associated most commonly with type 3 virus. Infections with type 4 parainfuenza virus are not as well characterized, but studies using reverse transcriptase polymerase chain reaction assays suggest that they may be more common than previ ously appreciated. Parainfuenza infections do not confer complete protective immunity; therefore, reinfections can occur with all serotypes and at any age, but reinfections usually cause a mild illness limited to the upper respiratory tract. Four antigenically distinct types�1, 2, 3, and 4 (with 2 subtypes, 4A and 4B)�have been identifed. Parainfuenza virus infections can be sporadic or associated with outbreaks of acute respiratory tract disease. Type 1 virus tends to produce outbreaks of respiratory tract illness, usually croup, in the autumn of every other year. A major increase in the number of cases of croup in the autumn usually indicates a parainfuenza type 1 outbreak. Type 2 virus also can cause outbreaks of respiratory tract illness in the autumn, often in conjunction with type 1 outbreaks, but type 2 outbreaks tend to be less severe, irregular, and less common. Parainfuenza type 3 virus usually is prominent during spring and summer in temperate climates but often continues into autumn, especially in years when autumn outbreaks of parainfuenza virus types 1 or 2 are absent. Infections with type 4 parainfuenza virus are recognized less commonly and can be associated with mild to severe illnesses. Infection with type 3 virus more often occurs in infants and is a prominent cause of lower respiratory tract illnesses in this age group. Infections between 1 and 5 years of age are more commonly associated with type 1 and, to a lesser extent, type 2 parainfuenza viruses. Rates of parainfuenza virus hospitalizations for children younger than 5 years of age are estimated to be 1 per 1000, with the highest rates in infants 0 to 5 months of age (3 per 1000). Immunocompetent children with primary parainfuenza infection may shed virus for up to 1 week before onset of clinical symptoms and for 1 to 3 weeks after symptoms have disappeared, depending on serotype. Severe lower respiratory tract disease with prolonged shedding of the virus can develop in immunodefcient people. In these patients, infection may spread beyond the respiratory tract to liver and lymph nodes. Virus may be isolated from nasopharyngeal secretions usually within 4 to 7 days of culture inoculation or earlier by using centrifuga tion of the specimen onto a monolayer of susceptible cells with subsequent staining for viral antigen (shell vial assay). Serologic diagnosis, made retrospectively by a signifcant increase in antibody titer between serum specimens obtained during acute infection and convalescence, is less useful, because infection may not always be accompanied by a signifcant homotypic antibody response. Monitoring for hypoxia and hypercapnia in more severely affected children with lower respiratory tract disease may be helpful. Parenteral dexamethasone in high doses, oral dexamethasone, and nebulized corticosteroids have been demonstrated to lessen the severity and duration of symptoms and hospitalization in patients with moder ate to severe laryngotracheobronchitis. Antimicrobial agents should be reserved for documented secondary bacterial infections. Strict adherence to infection-control procedures, including prevention of environmental contamination by respiratory tract secretions and careful hand hygiene, should control health care-associated spread. Hospitalized immunocompromised patients with type 3 parainfuenza infection should be isolated to prevent spread to other patients. Parasitic Diseases Many parasitic diseases traditionally have been considered exotic and, therefore, frequently are not included in differential diagnoses of patients in the United States, Canada, and Europe. Nevertheless, a number of these organisms are endemic in indus trialized countries, and overall, parasites are among the most common causes of mor bidity and mortality in various and diverse geographic locations worldwide. Outside the tropics and subtropics, parasitic diseases particularly are common among tourists returning to their own countries, immigrants from areas with highly endemic infection, and immunocompromised people. Some of these infections disproportionately affect impoverished populations, such as black and Hispanic people living in the United States, and aboriginal people living in Alaska and the Canadian Arctic. Physicians and clini cal laboratory personnel need to be aware of where these infections may be acquired, their clinical presentations, and methods of diagnosis and should advise people how to prevent infection. Important human parasitic infections are discussed in individual chapters in section 3; the diseases are arranged alphabetically, and the discussions include recommenda tions for drug treatment. The facial rash can be intensely red with a slapped cheek appearance that often is accompanied by circumoral pallor. A symmetric, macular, lace-like, and often pruritic rash also occurs on the trunk, moving peripherally to involve the arms, buttocks, and thighs. The rash can fuctuate in intensity and recur with environmental changes, such as temperature and exposure to sunlight, for weeks to months. A brief, mild, non specifc illness consisting of fever, malaise, myalgia, and headache often precedes the characteristic exanthema by approximately 7 to 10 days. Arthralgia and arthritis occur in fewer than 10% of infected children but commonly occur among adults, especially women. Knees are involved most commonly in children, but a symmetric polyarthropathy of knees, fngers, and other joints is common in adults.

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Diseases

• CDG syndrome
• Vancomycin-resistant Enterococcus (Vancomycin-resistant enterococcal bacteremia)
• Congenital cardiovascular disorder
• Congenital cardiovascular malformations
• Hypophosphatemic rickets
• Hepatic fibrosis
• Boder syndrome
• Chlamydia