AIDS and preventive treatment in hemophilia.
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Biomedical subjects
Publications and source records attributed to J F Desforges.
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Using the technique of decision analysis to evaluate data on single-modality and combined-modality therapy in Hodgkin's disease, we have been able to determine which treatment gives the best chance for prolonged disease-free survival in given settings. Both the potential of combined-modality therapy for inducing secondary hematologic malignancies and the rate of salvage with MOPP following relapse after radiotherapy have been studied to observe the effect of different rates of these variables on the therapeutic decision. An analysis of patients with known pathologic stage endorsed the continued use of extended-mantle radiotherapy for Stages IA and IIA disease; under most of the conditions analyzed, combined-modality therapy appeared the best option for Stage IIIA disease. The results for Stages IB and IIB disease showed neither combined-modality therapy nor total nodal irradiation to have a conclusive advantage. We also analyzed management decisions for patients who had not had pathologic staging. For this, probabilities of each pathologic stage were derived from a large patient data base and were incorporated into the decision analysis. The results of this analysis indicated that, despite the mortality of laparotomy, treatment designated according to pathologic stage was more effective than immediate combined-modality therapy for most types of patients. For certain patients in whom the clinical features could be used to predict a high probability of advanced disease, the most effective management was immediate MOPP chemotherapy without staging laparotomy.
Using an accurate technique for staining and scoring soft agar cultures, this study defines the incidence of circulating CFUEOS in normal donors. With whole mononuclear cells as the source of colony stimulating factor (CSF) and fetal calf serum, 49.6% +/- 3.5 of the colonies were eosinophilic; with human placental conditioned media and fetal calf serum 33.2% +/- 12.9 of the colonies were eosinophilic, with AB serum and whole mononuclear cells in the feeder layer 58.6% +/- 9.1 of the colonies were eosinophilic. The percentage of mixed neutrophil/eosinophil colonies was similar under varying culture conditions suggesting the presence of circulating progenitor cells capable of producing both lines.
Myeloid progenitor cell cultures (CFU-C) were established in a double-layer agar system with peripheral blood mononuclear cells from 13 patients with the hypereosinophilic syndrome (HES). Normal controls produced 49% +/- 3.5% eosinophil colonies; results in 7 of the 13 HES patients were within the normal range, while in 5, the proportion of eosinophil colonies was greater than 3 standard deviations above the normal mean, and in 1 patient there was a low proportion of eosinophil colonies. The production of an increased proportion of eosinophil colonies correlated with more aggressive disease. Experiments in which normal progenitor cells were cultured over feeder layers of mononuclear cells demonstrated that cells of 3 of the 5 patients had an excess production of eosinophil colony-stimulating activity. When HES patients progenitor cells were cultured over normal feeder layers, 2 of the 5 patient samples continued to produce an increased proportion of eosinophil colonies, suggesting that these patients have an excess proportion of progenitor cells committed to eosinophil differentiation. Thus, the results demonstrated heterogeneity of growth characteristics for the HES patients. None, however, had the colony growth characteristic of acute or chronic myelogenous leukemia.
The presence of bound heme pigment was compared in membranes of AA and SS cells. Spectophotometric study of membranes prepared by hypotonic lysis and washed free of hemoglobin revealed the presence of an irreversibly oxidized hemoglobin derivative, HCh. SS cell membranes contained significantly more HCh than did the AA cell membranes. When red cells were separated into cohorts of various density on a discontinuous density gradient of Stractan, washed membranes from the highest-density AA cells had significantly more HCh than did the remainder. In contrast, when density-separated SS cells were studied, no significant difference could be demonstrated in the HCh content of membranes from various cohorts.
T cells stimulate the proliferation of BFUE (burst forming units-erythroid) from normal blood null cells in an in vitro culture system in the presence of erythropoietin. To determine whether abnormal BFUE proliferating effect of T cells could explain the pure red cell aplasia in chronic lymphocytic leukemia (CLL-PRCA), we investigated the erythropoietic function of T and null cells in four patients with CLL-PRCA and compared results to three patients with idiopathic pure red cell aplasia (I-PRCA) and normals. Sera from I-PRCA patients (P greater than 0.05) but not CLL-PRCA patients (P less than 0.1) inhibited erythroid stem cell proliferation in the presence of complement. BFUE in null cells of all PRCA patients were barely detectable or absent (P less than 0.0025). Normal or I-PRCA T cells increased BFUE proliferation from PRCA null cells of six patients (P less than 0.001). In contrast, CLL-PRCA T cells were poor stimulators of BFUE from autologous (P less than 0.001) or allogeneic null cells (P less than 0.02). Treatment with cyclophosphamide and prednisone induced reticulocytosis in all four CLL-PRCA patients. After treatment, in two cases, the burst promoting function of T lymphocytes was normal. Analysis of T cell subpopulations in two CLL-PRCA patients, suggested that the reduced burst promoting function was due to decreased numbers and/or function of T cells bearing Fc receptors for IgM (TM cells). These findings suggest that reduced generation of a burst promoting activity by CLL-PRCA T cells may contribute to the pathogenesis of PRCA in chronic lymphocytic leukemia.
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This study defines patients with symptomatic Hodgkin's disease for whom risks of staging laparotomy (LAP) outweigh benefits conferred by accurate knowledge of stage. From a database of more than 900 pathologically-staged patients, probabilities of pathological stage are calculated for combinations of basic findings and lymphangiogram results. Decision-making thresholds are defined at which results of treatment after LAP, taking operative mortality into account, are equivalent to immediate treatment appropriate to clinical stage. These thresholds are substantially altered by varying LAP mortality estimates, by assigning a false negative rate to LAP, and by considering uncertainty in treatment results. Fifty-four combinations of findings are described for which immediate therapy with MOPP is justified; total nodal irradiation (TNI) is never indicated in B patients without prior LAP staging. Analysing 94 B patients who had LAP showed an appreciable number might have been spared this, particularly when uncertainty in treatment results is considered. With 0.03 (=3%) uncertainty in treatment, and 1% LAP mortality, LAP was not indicated in one in seven patients; nearly one third of patients should have immediate treatment with 3% LAP mortality. Threshold analysis can define those patients for whom risks of LAP outweigh benefits.
To clarify the role of T lymphocytes or monocytes in the regulation of human peripheral blood erythroid burst forming unit proliferation, equal numbers of purified T cells, B cells or monocytes were cultured in vitro with null cells in the plasma clot system. BFUE proliferation was directly proportional to the T cell concentration and inversely proportional to monocyte concentration in culture. The effect of B cells was variable and dependent on the extent of T cell contamination. Addition of a highly specific anti-human thymocyte IgG preparation (ATG) to null cells, T cells + null cells or B cells + null cells significantly reduced or eliminated BFUE proliferation. A burst promoting activity (BPA) was found in the supernatants of T cell enriched mixed lymphocyte cultures and could oppose the inhibition of BFUE proliferation by ATG. A burst inhibitory activity was found in the supernatants of monocyte enriched cultures. These studies provide further evidence that BFUE proliferation is determined by opposing actions of stimulator T cells and inhibitor monocytes and/or their soluble products.
For the management of Hodgkin's disease, a number of decisions must be made in order to assure selection of the best treatment for the individual patient. Data can be organized so that one can approach the management of a cohort of patients using the technique of Decision Analysis to determine in an individual patient what degree of certainty is necessary to allow one to select the best treatment, and which tests will provide that information at minimal cost. Using the technique of Decision Analysis in approaching the management of Hodgkin's Disease, we have thus been able not only to deal-with problems for which adequate data are available but also to anticipate outcomes given variable data. The approach allows one to make the best decision possible within certain ranges of uncertainty.
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During the past two decades, new approaches to the diagnosis and treatment of Hodgkin's disease have contributed to improved rates of survival and probable cure. Currently, patients with Hodgkin's disease are treated according to the stage and symptoms of their disease. The degree of certainty necessary for determining stage depends on the potential effectiveness of the therapeutic options available in a given case. Certain cases have been identified where treatment with a single modality has been disappointing, and the use of both radiotherapy and chemotherapy may be considered for these. Such decisions can be made only by evaluating the effectiveness of salvage after relapse following single-modality treatment and assessing the added hazards of initial treatment with both modalities.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.