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Biomedical subjects

A Salama

Publications and source records attributed to A Salama.

At least 91 records · Page 5Linked to original sources
PubMed1993

[Detection of drug-induced antibodies to erythrocytes in the gel test].

Drug-induced immune hemolytic anemia is a serious hematological disorder which results from increased red blood cell destruction due to the production of autoantibodies, drug (metabolite)-dependent antibodies (DDAb) or both types of antibodies, even in one patient by the same drug. One of the major problems related to DDAb is that the causative drug (metabolite) usually does not bind tightly to target cells, and the antibodies are completely removed from the cells by conventional washing procedures, i.e. by the antiglobulin test. We have recently shown that the microtube geltest, by which the antiglobulin test is performed without washing the cells, is a highly sensitive and reliable alternative method for the detection of all kinds of DDAb. The results obtained with different DDAb are discussed.

Anemia, Hemolytic, Autoimmune↗
PubMed1992

[Rhesus(D)-IgG-antibodies in the treatment of autoimmune thrombocytopenia].

25 patients with confirmed chronic autoimmune thrombocytopenia (AITP) (20 women, 5 men; mean age 42 [17-75] years) were treated with anti-erythrocytic rhesus (D) antibodies. In the course of 5 days they each received three doses of 1200 micrograms of anti-D IgG antiserum by short-duration infusion. No adverse effects were noted. In 19 out of 25 (76%) the platelet counts (determined on the 6th day after the last infusion) rose by more than 30,000/microliters, in some by over 200,000/microliters. In 6 patients the maximal rise in platelets was below 30,000/microliters. There was little or no fall in haemoglobin concentration in 24 of the patients, although the direct antiglobulin test was clearly positive in all cases. Moderate transitory anaemia occurred in one case only (haemoglobin fell from 12.4 to 8.4 g/dl). The platelet counts gradually declined after treatment, taking several weeks or months to reach their original levels. The mechanism of anti-D therapy in AITP is not fully understood, but it probably depends on competitive inhibition of Fc receptors on phagocytic cells in the reticuloendothelial system.

Adolescent↗
PubMed1991

Treatment of aplastic anemia with antilymphocyte globulin and methylprednisolone with or without cyclosporine. The German Aplastic Anemia Study Group.

BACKGROUND AND METHODS: Immunosuppression is the most effective treatment for patients with aplastic anemia, except for bone marrow transplantation. The best results are achieved with antilymphocyte globulin or cyclosporine. Patients have been treated successfully with a combination of both agents, but there has been no controlled evaluation of its efficacy. We conducted a randomized, multicenter trial in 84 patients not eligible for bone marrow transplantation, comparing treatment with antilymphocyte globulin and methylprednisolone (41 patients--the control group) with antilymphocyte globulin, methylprednisolone, and cyclosporine (43 patients--the cyclosporine group). RESULTS: At three months significantly more patients in the cyclosporine group had a complete or partial remission in response to treatment than did patients in the control group (65 percent vs. 39 percent, P less than 0.03); this difference was confirmed at six months (70 percent vs. 46 percent, P less than 0.05). The superior results of the regimen including cyclosporine were most evident in the patients with severe or very severe aplastic anemia, whose response rate at six months was 65 percent, as compared with 31 percent of such patients in the control group (P less than 0.02). Granulocyte and hemoglobin levels became normal in most patients who responded, but platelet counts continued to be subnormal in 61 percent of the patients. Ten of 52 patients with responses (3 in the cyclosporine group and 7 in the control group) relapsed 4 to 37 months after treatment. The actuarial survival of all patients at 41 months is 64 percent in the cyclosporine group and 58 percent in the control group (P = 0.16); among the patients with severe or very severe disease, survival is 80 percent and 44 percent, respectively (P = 0.077). Cyclosporine had substantial but reversible side effects. CONCLUSIONS: Immunosuppressive treatment of aplastic anemia with antilymphocyte globulin, methylprednisolone, and cyclosporine appears to be more effective than a regimen of antilymphocyte globulin and methylprednisolone without cyclosporine and may thus represent a treatment of choice for patients who are not eligible for bone marrow transplantation.

Adult↗
PubMed1991

High-dose IgG for neutropenic patients with acquired immunodeficiency syndrome (AIDS).

Leukocytopenia and bacterial infections are common and serious complications in patients with AIDS. We report here on three patients in whom the administration of high IgG doses led to gradual (two patients) or prompt (one patient) increases in circulating leukocyte counts (from 200-600 to 2500-5900/microliters), inducing definite improvement in two patients; one patient died from Pneumocystis carinii pneumonia. Although the rise in leukocyte counts lasted for only approximately 3 weeks, high-dose IgG might be a useful therapeutic adjunct in such patients.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Antigenic determinants responsible for the reactions of drug-dependent antibodies with blood cells.

In an attempt to determine the antigenic combining sites of drug-dependent antibodies in patients with drug-related immune haemolysis, we have assessed the reactivity of 35 nomifensine-induced antibodies against human red blood cells (RBC) in the presence of 11 closely related compounds: nomifensine, its three main metabolites including their methoxylated analogues and diclofensine with its three main metabolites. Three types of antibody reactivity patterns could be differentiated: Firstly, antibodies most strongly reactive with nomifensine (n = 12); secondly, antibodies primarily directed against one of its main metabolites (n = 7), and thirdly, antibodies optimally reactive with its unknown metabolites (n = 16). The antibodies preferentially directed against nomifensine showed varying cross reactions with nomifensine-related compounds and in almost all cases also with diclofensine and/or its metabolites. Those antibodies which were optimally reactive with metabolites reacted only with nomifensine-derived compounds and only one of them was non-crossreactive. The third group of antibodies showed no (n = 12) or only weak (n = 4) cross reactions with nomifensine and/or its metabolites. Although none of the substances used bound firmly to RBC, certain blood groups have been identified in previous studies to be defined. RBC antigens were required for the reaction in approximately 40% of all antibodies, independent of their reactivity with the compounds. Thus, even when the specificity of some antibodies appeared to be predominantly controlled by certain structural features of the compounds, the actual antigenic combining site of each antibody was different and seemed to comprise parts of the drug-related determinants as well as different constituents on RBC membranes. These findings indicate firstly that RBCs function as 'carrier-like' macromolecules, since they are directly involved in the reaction; secondly, that the drugs and their metabolites act as 'pseudohaptens', in as much as they do not bind tightly to the cells; and, thirdly, that the determinants which govern the immune response appear to result from an accidental attachment rather than from a predetermined selection of antigenic membrane structures, since each antibody shows a unique reaction pattern.

Anemia, Hemolytic↗
PubMed1991

Autoantibodies and drug- or metabolite-dependent antibodies in patients with diclofenac-induced immune haemolysis.

Two patients with acute immune haemolytic anaemia caused by diclofenac are described. Both patients had developed IgG drug-independent autoantibodies and drug-dependent antibodies. The drug-dependent antibodies in one patient reacted with red blood cells (RBC) only in the presence of urine from patients receiving diclofenac (ex vivo antigen) but not in the presence of the drug itself or its known metabolites. This antibody appeared to recognize a trace metabolite which has not yet been identified. The drug-dependent antibodies in the second patient reacted with RBC in the presence of urine as ex vivo antigen as well as in the presence of the drug itself and its main metabolites. Incorrect diagnosis of such cases often is due to the occurrence of autoantibodies and/or unusual drug metabolism and excretion.

Aged↗
PubMed1991

Follow-up study on 24 patients with nomifensine-induced immune haemolytic anaemia.

There is as yet only scarce information regarding the natural history and long-term clinical sequelae of patients who survive the acute complications of severe drug-related immune haemolysis, the effect of the mode of drug administration for sensitization and possible alterations of serological characteristics of drug-dependent antibodies during the postsensitization period. We therefore followed 24 patients with nomifensine-induced haemolytic anaemia for up to 6 years after the haemolytic attack. All patients had suffered from a severe haemolytic episode. None of the patients showed any abnormal findings upon reinvestigation (complete history and physical examination; extended biochemical and haematological laboratory status), particularly with respect to renal function. Drug-dependent antibodies remained detectable in 19 of 21 sera, while drug-independent autoantibodies, demonstrable in six patients during the acute phase of haemolysis, could no longer be detected. With regard to the mode of drug administration, the majority of patients (15 out of 24) had developed the haemolysis at the beginning (immediately after a single dose) or during a second course of drug therapy (n = 8 and 7, respectively). The immune response did not appear to be dose- or time-dependent. This study confirms the benign long-term prognosis of patients who survive life-threatening complications in drug-induced immune haemolytic anaemia. In addition, it indicates that drug-dependent antibodies may remain detectable over long periods of time, and that irregular drug administration might be associated with a higher risk of drug sensitization.

Anemia, Hemolytic↗
PubMed1990

Autoimmune hemolytic anemia associated with an IgA autoanti-Gerbich.

A third patient with autoimmune hemolytic anemia due to autoantibodies against Gerbich antigens is described. The patient's serum contained strong hemagglutinating antibodies of the IgA plus IgG classes which reacted with all red blood cells (RBC) tested, but not with Gerbich-negative cells. Although the patient was typed as Gerbich positive, his serum failed to react with his own RBC, and the sensitization of his erythrocytes with autoantibodies was only demonstrable if eluates of his RBC were used. The failure of the autoantibodies to react with autologous RBC at the peak of hemolysis most likely reflects a weakening of Gerbich antigens during the course of autoimmune hemolytic anemia.

Adult↗
PubMed1990

Donath-Landsteiner autoimmune hemolytic anemia in children. A study of 22 cases.

During the last 4 years, we have studied a total of 531 adults and 68 children with clinically and serologically well-defined forms of immune hemolytic anemias. Among these, Donath-Landsteiner (DL) hemolysis was the underlying disease in 22 of the 68 children (32.4%), but was not observed in adults. All children with DL hemolysis suffered from acute infections presumably of viral origin. In none of the cases was the DL hemolysis suspected clinically. Boys were more often affected than girls. The hemolytic episodes were severe, but resolved within few weeks. Serologically, all patients had a strongly positive direct antiglobulin test (DAT) using anti-C3d reagents, but a weak (n = 6) or negative (n = 16) IgG-DAT. DL hemolysins were always weak and transient, detectable with enzyme-treated red blood cells (RBC) in all, with untreated RBC in 12 of 22 sera. To explore the reason why these weak antibodies can cause extensive hemolysis in vivo, we compared the action of DL antibodies and of cold agglutinins (anti-I) on RBC by several reincubations at 4 and at 37 degrees C. The data obtained from this experiment demonstrate a stronger aggravation of hemolysis by DL than by anti-I antibodies, presumably due to low-affinity interaction between the cells and DL antibodies.

Adult↗
PubMed1990

Role of glycine in the N-methyl-D-aspartate-mediated neuronal cytotoxicity.

Current evidence indicates that glutamate acting via the N-methyl-D-aspartate (NMDA) receptor/ion channel complex plays a major role in the neuronal degeneration associated with a variety of neurological disorders. In this report the role of glycine in NMDA neurotoxicity was examined. We demonstrate that NMDA-mediated neurotoxicity is markedly potentiated by glycine and other amino acids, e.g., D-serine. Putative glycine antagonists HA-966 and 7-chlorokynurenic acid were highly effective in preventing NMDA neurotoxicity, even in the absence of added glycine. The neuroprotective action of HA-966 and 7-chlorokynurenic acid, but not that of NMDA antagonists 3-(2-carboxypiperazine-4-yl)propylphosphonate and MK-801, could be reversed by glycine. These results indicate that glycine, operating through a strychinine-insensitive glycine site, plays a central permissive role in NMDA-mediated neurotoxicity.

Animals↗
PubMed1990

Effect of oxygen tension on catecholamine-induced formation of cAMP and on swelling of carp red blood cells.

We studied the effects of beta-adrenergic stimulation on the formation of adenosine 3',5'-cyclic monophosphate (cAMP) and on the cell volume in carp red blood cells in normoxia (PO2 = 150 mmHg) and hypoxia (PO2 = 8 mmHg). Accumulation of cAMP was the prerequisite for adrenergic cell swelling. Cell swelling was induced by beta-agonists, forskolin, and 8-bromo-cAMP. The amount of cAMP required for adrenergic swelling was minimal; swelling was observed at cAMP concentrations greater than 100 nM. Maximal increase in cell volume was observed at 200 nM cAMP. These values were independent of both the oxygen tension and the beta-agonist used. Norepinephrine caused the largest accumulation of cAMP, followed by isoproterenol and epinephrine. At hypoxic conditions, the cAMP concentrations obtained after stimulation with the natural catecholamines norepinephrine and epinephrine were greater than at normoxic conditions. The catecholamines caused appreciable cell swelling at lower concentrations in hypoxia than in normoxia. Thus the number of beta-adrenergic receptors, and their inherent ligand affinities, may be higher in hypoxic than in normoxic carp red blood cells. Oxygen tension had a pronounced effect on the magnitude of the adrenergic swelling. The maximal increase in cell volume was 5-7% in hypoxia, whereas in normoxia it was only approximately 2%. This was not due to differences in cAMP formation, but possibly to a greater activity of the Na(+)-H+ exchanger in hypoxic than in normoxic conditions.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1990

[Autoimmune hemolytic anemia with temporary weakening of Gerbich antigens].

A third patient with autoimmune hemolytic anemia due to autoantibodies against Gerbich antigens is described. The patient's serum contained strong hemagglutinating antibodies of the IgA plus IgG classes which reacted with all red blood cells (RBC) tested, but not with Gerbich-negative cells. Although the patient was typed as Gerbich-positive, his serum failed to react with his own RBC, and the sensitization of his erythrocytes with autoantibodies was only demonstrable if eluates of his RBC were used. The failure of the autoantibodies to react with autologous RBC at the peak of hemolysis most likely reflects a weakening of Gerbich antigens during the course of autoimmune hemolytic anemia.

Adult↗
PubMed1989

Acute treatment with clozapine blocks D1 dopamine receptor binding in discrete brain areas of the male rat.

The ability of acute treatment with clozapine in vivo to block D1 receptors in the rat telencephalon and midbrain was investigated using the irreversible inactivation of [125I]SCH 23982 binding sites by N-ethoxy-carbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ; 6 mg/kg, i.p., 24 h). As analyzed by quantitative autoradiography, clozapine (40 mg/kg, i.p., 15 min before EEDQ administration) was found to produce a partial protection of central D1 receptors in all brain areas investigated, including cerebrocortical regions. These data could perhaps explain the failure of clozapine to induce tardive dyskinesia upon chronic treatment.

Animals↗
PubMed1989

In vitro fixation of C3d and C5b-9 on platelets by human platelet reactive antibodies.

Most platelet-reactive autoantibodies and alloantibodies are not able to fix complement in vitro. However, exceptions have been found. These antibodies are usually characterized by the conventional platelet complement fixation test. A recently developed competitive enzyme immunoassay for quantitation of platelet-associated immunoglobulins and a modification thereof allowed the quantitative study of fixation of C3d and the membrane attack complex (C5b-9) on platelets by HLA antibodies, human platelet autoantibodies, and drug-dependent antibodies (ddab). The highest amounts of both complement products were fixed through ddabs, whereas autoantibodies only showed moderate complement fixation. This enzyme immunoassay is a valuable tool for the characterization of the complement-fixing properties of platelet-reactive antibodies.

Antibodies↗