Use of intravenous immunoglobulin in idiopathic membranous nephropathy.
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Biomedical subjects
Publications and source records attributed to Y Sherer.
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Israel is one of the Mediterranean countries in which Brucellosis is endemic. As recently there has been a Brucellosis outbreak in a kibbutz, the aim of this study is to identify asymptomatic infected Kibbutz members, and to delineate the manner of infection in this setting. Therefore, all the asymptomatic Kibbutz members were screened by the Rose Bengal test for Brucellosis, while both patients and healthy members were asked to fill in a questionnaire in order to pinpoint the manner of infection, and signs and symptoms of the disease. In addition to the 14 patients with Brucellosis, 2 other Kibbutz members were also found to be infected by the screening tests. Analysis of the data of the questionnaires from 142 healthy and 16 patients disclosed that almost all of the infected patients (15/16) worked in the cowshed, as opposed to only 24 out of 142 (16.9%) of the healthy members. The infected tended to participate more in calf deliveries, and had contact with cow's blood and placenta, compared with the healthy subjects (P<0.001), while there were no significant differences with respect to having cuts on hands, or working in the cowshed without gloves. In addition, 15 out of 16 (93.8%) infected persons also drank unpasteurized milk, as compared with only 17 of the 142 (12%) healthy members (P<0.001), and thus were exposed to 2 major risk factors (working in the cowshed and consumption of unpasteurized milk). As the cows of the Kibbutz's cowshed were affected by Brucella melitensis (which usually affects flocks of goats and sheep rather than cows), the microbe was probably transmitted to the cowshed from neighboring flocks by wandering dogs, and then to the infected humans.
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Splenic cysts are rarely found or diagnosed. Excluding cases of trauma, the events preceding their development have not been fully understood. We describe a 22-year-old woman in her 34th week of pregnancy in whom ultrasound revealed a cystic lesion 8 x 10 cm. in diameter in the left upper abdomen. Further imaging tests followed by laparotomy confirmed the splenic origin of the cyst. Splenectomy was performed and the lesion was histopathologically defined as an epidermoid cyst.
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OBJECTIVES: To determine whether malignant thymoma is associated with high rates of concomitantly occurring autoimmune diseases. METHODS: Sheba Medical Center computer records from 1966 to 1995 were reviewed to identify patients with malignant thymoma, either type I (invasive thymoma) or type II (thymic carcinoma). All patients who had malignant thymoma and autoimmune phenomena were analyzed. The diagnosis of thymic neoplasm was confirmed by two independent pathologists. The diagnosis of autoimmune diseases was based on both clinical and serological findings. RESULTS: Six of 22 (27%) cases of malignant thymoma had an autoimmune disease. Five patients had type I malignant thymoma and either myasthenia gravis (four patients) or Graves' disease (one patient). Only one patient had type II malignant thymoma with Sjögren's syndrome. The diagnosis of autoimmune disease preceded the diagnosis of thymic neoplasm in four cases, and was diagnosed simultaneously in two. CONCLUSIONS: Malignant thymomas are highly associated with autoimmune diseases, as are benign thymomas. To our knowledge, we report the first documented cases of a patient with thymic carcinoma and Sjögren's syndrome, and another with invasive thymoma and Graves' disease.
BMT can both transmit and eliminate autoimmune diseases, and hence it has been suggested as an optional treatment for severe autoimmune conditions. In this communication we deal with the question of whether chronic GVHD is an autoimmune disease in itself, review the literature reports of autoimmune diseases following BMT in humans, and describe the autoimmune nature of the post-BMT state. Chronic GVHD, which is a frequent complication post-BMT, has clinical and pathogenic characteristics similar to autoimmune diseases, such as scleroderma and Sjogren's syndrome. Although the pathogenesis of chronic GVHD is not yet clear, thymic damage induced by acute GVHD may contribute to both the immunodeficiency and autoimmunity characterising chronic GVHD. A similar phenomenon is syngeneic GVHD, which results from an imbalance between autoreactive and autoregulatory lymphocytes. Additionally, other autoimmune diseases have been reported in post-BMT patients, and among these the most common are hypothyroidism, hyperthyroidism, myasthenia gravis and immune cytopenias. Although these diseases also occur also outside the post-BMT setting, they are unique with respect to pathogenesis (no association between myasthenia gravis and thymic pathology), diagnosis (symptoms of hyperthyroidism may be inadvertently related to other conditions), and prognosis (post-BMT autoimmune cytopenias may be fatal and treatment non-responsive). Nevertheless, many other autoimmune diseases have been reported after BMT, and these are mainly presented as case reports. Regarding the mechanism of post-BMT autoimmunity, the minority of cases stem from donor-related transfer of pathogenic lymphocytes or their progenitors, while most of the cases (either chronic GVHD or specific diseases) can be attributed to the immunologic imbalances characterising the post-BMT setting. The factors that may expose an individual to autoimmunity development post-BMT include genetic predisposition, an environmental factor such as CMV, and the nature of the donor who may aid in creating microchimerism and subsequently chronic GVHD and its related autoimmune manifestations.
Cytokines play an important role in the progression of autoimmune diseases, and therefore it is not surprising that their levels may be altered in some of these diseases. Interleukin-3 (IL-3), which is an hematopoietic growth factor as well as an important factor that aids in embryo implantation and placental development, was found to be decreased both in pregnant women with antiphospholipid syndrome (APS) compared with a control group, and in animal models of APS. Treatment of animals having APS with IL-3 succeeded in prevention of disease manifestations. In this communication we review IL-3 and APS interrelationship, and discuss the role of aspirin and other commonly used drugs, with respect to IL-3 levels in APS.
Anti-phospholipid syndrome includes a variety of clinical manifestations, among which is recurrent pregnancy loss. Recently, it was suggested that anti-phospholipid antibodies might also have a role in infertility, mainly in unexplained infertility. Most of the studies report about an increased prevalence of these antibodies in infertile women; however, data regarding the implication of these antibodies on treatment outcome (mainly in in-vitro fertilization) and if there is a beneficial effect of treating these patients with aspirin, heparin and prednisone--remains still controversial. In this communication we review the literature reports of association of anti-phospholipid antibodies and infertility, and deal with the question whether they have a pathogenic role in these cases.
The various therapeutic modalities which are found to be beneficial in experimental antiphospholipid syndrome include: bone marrow transplantation, anti-CD4 monoclonal antibodies, bromocriptine, intravenous immunoglobulins and anti-idiotypes, interleukin-3, and various anti-coagulant and anti-aggregate agents. The advantage of animal models is the ability to evaluate experimental treatments that cannot be tested directly on patients. In this paper, we review the effect of these agents on animal models of antiphospholipid syndrome, their mechanisms of action, and their clinical implications.
The aim of this study was to determine whether treatment of patients with immune thrombocytopenic purpura (ITP) with intravenous immunoglobulin (IVIg) is associated with a modification in the antiplatelet glycoprotein (GP) antibodies (Abs). Fourteen patients with ITP (11 females and 3 males, mean age 36.6 years, range 18-72) received one to four IVIg treatment courses. The preparation used was ISIVEN that was given in a dose of 2 g/kg body weight in a 5-day schedule and in monthly intervals. Levels of IgG, IgM and IgA isotypes of Abs to GPs IIb/IIIa and Ib/IX were measured before the treatment, and before and after each treatment course. Two patients did not respond to IVIg, 6 had a temporary response, 5 had a sustained response and 1 patient responded well to the treatment but was lost to follow-up. The patients had a high prevalence of serum Abs directed against GPs IIb/IIIa and Ib/IX before the treatment, and the mean IgG isotype levels of both Abs increased after each treatment course, and decreased again before the following course began. Whenever high Ab levels of either isotype (> 10 U/ml) were detected before the treatment, they were significantly decreased before the last treatment course. The elevated levels of IgG Abs to IIb/IIIa and Ib/IX after every course are probably a result of displacement of these Abs from Fc receptors by the IVIg, rather than of exogenous infusion of these Abs contained within the IVIg, whereas the decrease in high Ab levels after a few treatment courses results from the immunomodulatory effects of IVIg: suppression of Ab formation, and the presence of anti-idiotypes.
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Community-acquired pneumonia is one of the most common infectious conditions that require hospitalization. When intravenous treatment is indicated, cefonicid is usually the drug of choice. The aim of this study was to find out if chloramphenicol, which is superior to the standard drugs from a financial point of view, could serve as an equally efficient treatment, especially in the elderly. The outcomes of 3 pneumonia patient groups who were either treated with cefonicid, chloramphenicol or penicillin-G (n = 59, 17, 24, respectively) were retrospectively compared. Data about demographic characteristics of the patients, clinical outcomes, rehospitalization rates, duration of improvement/treatment/ hospitalization and clinical laboratory tests were obtained from each patient's medical records. Only minor differences (even though occasionally significant) were found with respect to rehospitalization and improvement rates, duration of hospitalization, treatment and improvement, death rates and clinical laboratory tests. However, chloramphenicol patients were found to be significantly older than cefonicid patients. Moreover, no bone-marrow suppression was associated with chloramphenicol treatment. All 3 drugs tested seem to have the same efficacy. We conclude that since chloramphenicol is as safe as, and much cheaper than cefonicid, this antibiotic agent is not inferior to the others, its usage in older patients with pneumonia should be considered.
Factor XI deficiency is an hereditary coagulopathy that is usually associated with milder tendency to bleeding with comparison to hemophilia A. While the failure of stable fibrin clot formation may lead to bleeding, it is speculated that the same process may provide a protection against thrombosis of injured arteries due to atherosclerotic plaque rupture. Whereas 2 studies indicate that hemophiliacs have decreased mortality rate from cardiovascular diseases, there is no similar data regarding factor XI deficiency patients. In here we report about 3 patients with severe factor XI deficiency who have a long-standing history of thromboembolic phenomena: 2 patients with myocardial infarctions, and one patient with transient ischemic attacks. We discuss the possible role of factor XI in thrombosis, and whether its deficiency may protect patients from thromboembolic phenomena.
The antiphospholipid (APS) syndrome frequently includes severe pregnancy complications such as fetal wastage and recurrent spontaneous abortions. Animal models for APS in pregnancy can provide both an understanding of the pathogenic mechanisms of anti-phospholipid antibodies (aPL), and aid in the evaluation of various therapeutic modalities in APS. Animal models for APS include both spontaneously developed diseases, as is the case for secondary APS in mice with another autoimmune disease, and induced models of APS. The latter includes either passive induction of disease by antibodies infusion, or active induction via manipulation of the idiotypic network. This article summarizes the literature reports of animal models of APS in pregnancy, deal with the various possible mechanisms of action of aPL in pregnancy, and discuss the treatment options of women having pregnancy complications of APS.
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