Oral treatment with trimethoprim-sulfamethoxazole and zidovudine suppresses murine accessory cell-dependent immune responses.
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Trimethoprim-sulfamethoxazole (TMP-SMX), commonly used for prophylaxis of Pneumocystis carinii pneumonia (PCP) in AIDS patients, often produces a high incidence of treatment-limiting reactions. We investigated the effect of oral administration of TMP-SMX alone or in combination with the antiretroviral drug zidovudine (ZDV) on hematopoiesis and cellular immunity in BALB/c mice. Daily treatment for 28 days with TMP-SMX (160:800 mg/kg) had no effect on hematopoiesis or the ex vivo proliferative response of splenic T lymphocytes to allogeneic tumor cells (EL-4) or to concanavalin A (ConA), or that of splenic B cells to lipopolysaccharide (LPS). ZDV at 240 mg/kg/day was not immunosuppressive but caused a mild macrocytic anemia. Combined treatment produced severe pancytopenia, a significant drop in splenic cellularity, and a 61% decrease in the percentage of splenic macrophages. The percentage of splenic CD3+ lymphocytes increased 150% in the TMP-SMX + ZDV group, but the ratios of T-cell subsets and the frequency of B cells remained unchanged. Combined drug treatment did not impair the proliferative response of B cells to LPS or that of T cells to EL-4 cells. In concert with the reduction in the percentage of macrophages, the proliferative response of T lymphocytes to ConA decreased significantly. Optimal ConA-induced T-cell proliferation requires the participation of accessory cells (AC) (e.g., macrophages); EL-4 cells are able to function as AC. These data indicate that ZDV synergizes with TMP-SMX, causing severe hematotoxicity and suppressing AC-dependent immune function, and suggest that this therapeutic regimen may contribute to the immune deterioration in AIDS patients. (+info)
Hereditary hemochromatosis in a patient with congenital dyserythropoietic anemia.
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Herein is described the case of a young woman presenting with iron overload and macrocytosis. The initial diagnosis was hereditary hemochromatosis. Severe anemia developed after a few phlebotomies, and she was also found to have congenital dyserythropoietic anemia that, though not completely typical, resembled type II. Only genetic testing allowed the definition of the coexistence of the 2 diseases, both responsible for the iron overload. This report points out the need to consider congenital dyserythropoietic anemia in patients with hemochromatosis and unexplained macrocytosis and, conversely, to check for the presence of hereditary hemochromatosis in patients with congenital dyserythropoietic anemia and severe iron overload. To the authors' knowledge, this is the first report of homozygosity for the C282Y mutation of the HFE gene in a patient affected by congenital dyserythropoietic anemia. (+info)
Erythropoiesis in steel mutant mice: effects of erythropoietin in vitro.
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Adult SI/SI-d mutant mice have severe macrocytic, normochromic anemia. Moreover these animals are unresponsive to the stimulation of erythropoietin in vivo. By means of a bone marrow cell suspension culture system, the present investigation shows that in adult SI/SI-d marrow, there are cells capable of responding in vitro to erythropoietin in a normal fashion. Moreover, the erythropoietin present in SI/SI-d serum is biologically active in vitro without any prior biochemical modification. These observations support the suggestion that there is a defect in differentiation in the erythroid cell lines of SI/SI-d mice in vivo due to an abnormal hemopoietic microenvironment. (+info)
Depressed cell-mediated immunity in megaloblastic anemia due to folic acid deficiency.
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Cell-mediated immunity has been studied in patients with 1) megaloblastic anemia of folic acid deficiency, 2)megaloblastic anemia of pregnancy, or 3) iron-deficiency anemia. Using dinitrochlorobenzene skin tests, phytohemagglutinin-stimulated lymphocyte transformation, and rosette inhibition by antilymphocyte globulin, we have shown that cell-mediated immunity is depressed in megaloblastic anemia due to folate deficiency; this depression was reversed by folate treatment. Cell-mediated immunity was not impaired by iron-deficiency anemia. Suggested interactions between iron deficiency and folate metabolism were not clarified by these studies. (+info)
Arsenic intoxication as a cause of megaloblastic anemia.
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We have described a case of chronic arsenic intoxication associated with pancytopenia and megaloblastic erythropoiesis. The patient had the typical laboratory manifestations of effective erythorpoiesis due to a megaloblastic process, including macroovalocytes, mild pancytopenia, low reticulocyte index, increased marrow cellularity with erythroid hyperplasia, and morphologic evidence of megaloblastic maturation in the marrow. The patient's serum folate and vitamin B12 were normal, and the anemia regressed without therapy. Our case suggests that the combination of megaloblastosis with normoblastic or megaloblastic karyorrhexis,should raise the suspicion of arsenic intoxication in the mind of the observer. In addition, arsenic should be added to the list of agents causing a reversible megaloblastic anemia. (+info)
Unusual megaloblastic anaemia wiht multinucleate erythroblasts: two cases with septicaemia and acute renal failure.
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The case histories and blood pictures of two patients who had cardiac lesions, septicaemia, and renal failure and terminally developed a leucoerythroblastic anaemia with megloblastic features associated with multinucleate erythroblasts, are described. Though folate deficiency may have made a minor contribution to the blood abnormalities, it is considered that some other disturbance in erythropoiesis was responsible for the bizarre blood and bone marrow changes in these patients. Similar cases reported in the earlier literature are reviewed. (+info)
Erythrocyte volume distribution in normal and abnormal subjects.
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Size-frequency distribution curves of erythrocytes were generated with the Coulter Counter in 73 normal subjects and patients. Mean corpuscular volume (MCV) determined by routine calculation and MCV determined by size-frequency distribution were similar in all normal subjects and in patients with a single population of erythrocytes. Some patients with iron-deficiency anemia, folate deficiency, and vitamin B12 deficiency had two discrete erythrocyte populations. Some patients with microcytic anemia were shown to have a population of normocytes in addition to the predominant microcytic population. Reticulocytes and normocytes were identified in two patients recovering from macrocytic anemia. Transfused blood was identified as a separate population in a patient with microcytic anemia. In cases with two erythrocyte populations, the MCV of the principal population, as determined from size-distribution curves, differed from the MCV of the entire erythrocyte pool, as was determined by routine methods. Analysis of sequential erythrocyte size distributions in patients under treatment demonstrated the dynamics of erythrocyte subpopulations. Anisocytosis was quantified and shown to be associated frequently with hospitalized patients. (+info)
A new hematologic syndrome with a distinct karyotype: the 5 q--chromosome.
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Five patients, four women and one man, age 32-8- yr, all whites, had refractory anemia with the same abnormal bone marrow karyotype, i.e., a partial deletion of the long arm of the No. 5 chromosome. The hematologic syndrome was practically the same in these five cases. Examination of the blood revealed a moderate to severe, generally macrocytic anemia with slight leukopenia but normal or elevated platelet count. The bone marrow showed a depressed erythroid series and some abnormalities of the granulocytic series with an occasional excess of myeloblasts. Most of the megakaryocytes had a nonlobulated nucleus. These features, as well as cytogenetic, electron microscopic, isotopic, platelet function, and immunologic studies, are described in detail. The relationship of this newly established syndrome to other hematologic diseases is discussed. The syndrome constitutes another example of the association between a specific abnormal chromosome and a distinct hematologic disorder. (+info)