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I Magrath

Publications and source records attributed to I Magrath.

87 records · Page 5Linked to original sources
PubMed1981

NIH conference. A multidisciplinary approach to non-hodgkin's lymphomas.

Epidemiologic studies show that non-Hodgkin's lymphomas tend to develop after prolonged antigenic stimulation, after loss of normal regulation of lymphoid proliferation, or especially after both processes. Study of these tumors in vitro has greatly increased understanding of their pathophysiology and has provided a conceptual framework for their morphologic diversity. Lymphomas are now understood to be expanded clones of their normal counterparts. The anatomic location, phenotypic characteristics, proliferative capacity, and functional capabilities of the neoplasm often reflect those of the equivalent normal cells. If neoplastic transformation can occur at any stage of lymphoid differentiation, then it is theoretically possible that neoplastic lymphocytes may respond, or could be induced, to normal regulatory influences. Further study of selective cytotoxicity may reveal exploitable differences among lymphocytic subpopulations and permit more rational choices of therapy. Of major aid to future clinical trials should be the recent consensus on nomenclature by an international panel of experts.

Adolescent↗
PubMed1981

Induction of complement receptor expression in cell lines derived from human undifferentiated lymphomas. II. Characterization of the induced complement receptors and demonstration of the simultaneous induction of EBV receptor.

We have studied the specificity of complement receptors induced by theophylline in 2 cell lines derived from undifferentiated lymphomas, one of Burkitt's type, and compared it to that of complement receptors in other cell types. Both C3b and C3d receptors were induced. The induced C3b receptor differed from the C3b receptor of mature normal lymphocytes, polymorphonuclear leukocytes and the cells of a nodular lymphoma in 2 respects. Firstly, it bound C3b much less avidly (by a factor of several hundred-fold) and secondly, we were unable to demonstrate C4b binding. EBV receptors were induced at the same time as complement receptors, and permitted the conversion of a greater fraction of cells to EBNA positivity after experimental infection with EBV. The induction of receptors was not associated with a change in the fluidity of the plasma membranes and our data do not favor a different orientation of induced receptors within the membrane as compared to receptors of other cell types--a potential explanation for the different specificities. Our findings are consistent with the possibility that the complement receptors of lymphocyte precursors differ from these of mature lymphocytes.

Binding, Competitive↗
PubMed1980

Prognostic factors in Burkitt's lymphoma: importance of total tumor burden.

In 42 patients with African Burkitt's lymphoma, we have studied biochemical and clinical correlations with prognosis. Clinical stage and anti-EA titer were the best predictive factors, but lactic dehydrogenase (LDH) and uric acid (UA) concentrations also correlated with stage and prognosis, whereas lactic acid (LA), which was significantly elevated in Stage D, did not significantly correlated with prognosis or with LDH and UA levels. All of these factors with the possible exception of LA reflect the total body burden of tumor. We conclude that the tumor burden is the single most important prognostic factor in Burkitt's lymphoma, and that this is reflected directly by LDH and UA concentrations, and probably indirectly by anti-EA titer.

Adolescent↗
PubMed1979

Activation of suppressor T cells during Epstein-Barr-virus-induced infectious mononucleosis.

Infectious mononucleosis is caused by the Epstein-Barr virus (EBV), an unusual human pathogen because it preferentially infects B lymphocytes and consequently activates them to produce immunoglobulins. When cultures of lymphocytes from patients with infectious mononucleosis were stimulated with polyclonal activators, unseparated cells failed to produce immunoglobulins, whereas purified B cells responded normally. Cocultures demonstrated profound suppressor T-cell activity in blood from patients with infectious mononucleosis. Early in this disease, circulating immunoglobulin-secreting cells were elevated, but during the second week their number was strikingly depressed. These data indicate that during infectious mononucleosis, EBV causes polyclonal activation of B cells, reflected by hypergammaglobulinemia and increased circulating immunoglobulin-secreting cells. Next, suppressor T cells become activated and inhibit further B-cell activation. Thus, activation of suppressor T cells in infectious mononucleosis provides a unique additional mechanism of host defense because these T cells inhibit the activation and proliferation of an important target of the causative virus.

Adolescent↗
PubMed1978

Childhood Hodgkin's disease in Uganda: a ten year experience.

Between 1967 and 1977, 48 patients with Hodgkin's disease under 16-years-old were treated with MOPP chemotherapy alone at the Uganda Cancer Institute because radiotherapy facilities are not available. Thirty-eight percent had early stage disease (stages I-IIIA). Prolonged first remissions were achieved in 74% of 42 complete responders. Of 11 patients who relapsed, 5 had prolonged second remissions induced by MOPP. Three patients were lost to follow-up and 15 of the remaining 45 died: 12 of these from progressive Hodgkin's disease, 2 from unrelated causes and 1 from Burkitt's lymphoma after 4 months remission from Hodgkin's disease. Acturial survival for all patients is 67% (75% for stages I-IIIA and 60% for stages IIIB-IV). Treatment complications included Herpes zoster and gynaecomastia. The latter is probably related to gonadal dysfunction. All stages of childhood Hodgkin's disease can be successfully managed with MOPP chemotherapy alone.

Adolescent↗
PubMed1978

Hypercalcemia with suppressed parathyroid hormone in Burkitt's lymphoma.

Two patients with Burkitt's lymphoma presented with severe hypercalcemia, a previously unreported complication of this tumor. Roentgenograms and radionuclide scans showed multiple osteolytic lesions in both patients. Plasma parathyroid hormone (PTH) was undetectable during the hypercalcemia phase. Chemotherapy was followed by rapid tumor lysis, hyperphosphatemia, phosphaturia and hypocalcemia. The hypocalcemic phase persisted for two weeks despite rapid normalization of serum phosphorus and renal function. Measurement of urinary cyclic AMP, an index of PTH action, indicated that parathyroid function had been suppressed by the hypercalcemia and remained suppressed for almost one week despite marked hypocalcemia.

Adult↗
PubMed1978

Drug-induced changes in DNA fluorescence intensity detected by flow microfluorometry and their implications for analysis of DNA content distributions.

Chicken erythrocytes, which contain less DNA than mammalian diploid cells, were used as an internal standard to control instrumental and staining variables during flow microfluorometric analysis. With the DNA stain, mithramycin, and with an EPICS II flow microfluorometer, ratios between the modal G1 fluorescence of experimental cells and that of chicken erythrocytes were determined. The results indicate that unperturbed cell populations of L1210 and HeLa cells in vitro and L1210 ascites cells in vivo have relatively stable fluorescence ratios, although there is a significant difference between the ratios of one L1210 cell line in vitro and another in vivo. In contrast, L1210 ascites treated in vivo with different schedules of cyclophosphamide and Adriamycin showed wide fluctuations in the fluorescence intensity ratios for 96 hr after treatment. Also, differences in the fluorescence ratios were observed between less advanced and more advanced L1210 ascites after treatment with the same schedule. These effects indicate an alteration in DNA staining with mithramycin, brought about by drug treatment that could seriously affect the interpretation of DNA histogram data. Nevertheless, changes in mithramycin staining may prove to be a very important probe to detect persistent drug effects.

Animals↗
PubMed1976

Childhood Kaposi's sarcoma: clinical features and therapy.

Twelve cases of childhood Kaposi's sarcoma seen at the Uganda Cancer Institute over the last 7 years are reported. The disease presents mainly as generalized lymphadenopathy, with sparsely and anomalously distributed cutaneous nodules, and has a higher proportion of females with the disease than in the adult form. The histology is usually of mixed cell type. If not treated, childhood Kaposi's sarcoma runs a fulminating course, but disease control with chemotherapy is associated with prolonged survival.

Adolescent↗
PubMedDate not supplied

Ifosfamide in the treatment of high-grade recurrent non-Hodgkin's lymphomas.

We report the results of two phase II trials of ifosfamide in very high risk patients with either partially responsive or recurrent non-Hodgkin's lymphomas. In the first study, in which patients were extremely heavily pretreated (50 per cent had received a very intensive salvage regimen containing very high dose cyclophosphamide), there were two complete responses, two partial responses and one objective (minimal) response among 14 patients treated. Toxicity was acceptable even in this end-stage patient group. We concluded that ifosfamide is an active agent even in patients with tumours resistant to cyclophosphamide. The second trial was a pilot study in 13 patients of a regimen incorporating VP16, ifosfamide/mesna, and high dose ara-C (VIPA). There were four complete responses, five partial responses and two objective responses. Two patients died in complete remission from toxic complications, while a third, with a stably regressed mediastinal mass died after completion of the protocol. While very toxic, we considered that this regimen was highly effective, and have since incorporated a slightly less intensive combination of the same drugs into the primary therapy of high risk patients. Since the primary toxicity of the VIPA combination was myelosuppression, the use of a modified protocol incorporating colony stimulating factors to ameliorate the side-effects and possibly increase dose rate is worthy of further exploration in patients with recurrent B cell tumours.

Adolescent↗
PubMedDate not supplied

Prolonged disease-free survival in pediatric non-Hodgkin's lymphoma using ifosfamide-containing combination chemotherapy.

Pediatric non-Hodgkin's lymphoma (NHL) constitutes 16 per cent of pediatric malignancies reported to the National Cancer Institute (NCI) in Cairo. The adopted treatment for these cases was, from 1982 to July 1985, a modified St Jude's regimen consisting of: vincristine, cyclophosphamide, adriamycin, prednisone and intrathecal methotrexate for the first 6 weeks for induction, followed by cranial irradiation for cranial prophylaxis. Patients in remission received maintenance therapy for 18 months. Of 32 patients complete remission (CR) was achieved in 24 patients (75 per cent); partial remission (PR) in one patient (3 per cent); five patients showed no response (15 per cent) while two patients died during the induction phase. At 60+ months follow-up, 60 per cent of cases are still alive, disease-free, and overall survival is 66 per cent. A new protocol was adopted in 1985, consisting of alternating cycles: A and B, for 4-8 cycles. Cycle A: cyclophosphamide, high dose ara-C, adriamycin, and vincristine. Cycle B: ifosfamide, methotrexate, VP 16, with intrathecal methotrexate. The response in 39 cases is: CR in 31 cases (82 per cent); PR in four cases (10 per cent); no response in three cases (8 per cent). At 60+ months, the disease-free survival is 60 per cent, and overall survival 80 per cent. This new protocol has the advantage of: short duration of therapy and so better patient compliance, no maintenance therapy or cranial irradiation with its sequelae in the future. Moreover, it has a better overall survival.

Adolescent↗
PubMedDate not supplied

Report of an International Network of Cancer Treatment and Research workshop on non-Hodgkin's lymphoma in developing countries.

The International Network of Cancer Treatment and Research (INCTR) recently organized a workshop on non-Hodgkin lymphomas (NHLs) in selected developing countries with the purpose of examining existing information relating to the pathology and management of these neoplasms, and identifying potential areas for research. This report provides a summary of the information presented and is focused primarily on the pathology of NHLs in children and adults. In most countries, the WHO classification of lymphomas was used and most participating centers included immunohistochemistry using a wide array of lymphoid antibodies as part of routine diagnosis. Some of the series had been reviewed by an external panel of experts. B-cell lymphomas accounted for 82-88% of all NHLs. The proportions of chronic lymphatic leukemia (4-6%), mantle cell lymphoma (MCL, 3-5%), and plasmacytoma (2-4%) were similar in the series presented. However, there was a significant variation in the proportion of follicular lymphoma (FL), which accounted for 15% and 11% in India and Kuwait, but less than 5% in Pakistan and Egypt. All of these frequencies are significantly lower than those reported in Western series. Diffuse large B-cell lymphoma accounted for about 35% of cases in India but for more 50% in other countries, but this difference was not accounted for by an increased incidence in a single lymphoma subtype in India, but rather an apparent paucity of several subtypes (such as mantle cell and marginal zone lymphomas (MZL)) in other series. There were relatively high frequencies of Burkitt lymphoma in Egypt (7%) and precursor T-cell lymphoblastic lymphoma in India (6-7%). Peripheral T-cell lymphomas (PTCLs) (not otherwise specified and angioimmunoblastic subtypes) accounted for 3-5% of NHLs, and extranodal lymphoma of T/NK cell type was rare (<1%). These differences in the relative proportions of NHL subtypes among developing countries and between developing countries and the rest of the world presumably arise from differences in environmental and genetic factors that influence lymphomagenesis and strongly suggest that more research in developing countries would provide valuable insights into the pathogenesis of lymphoid neoplasms.

Adult↗