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Biomedical subjects

D R Budman

Publications and source records attributed to D R Budman.

106 records · Page 6Linked to original sources
PubMed1980

Phase I evaluation of divided-dose vinblastine sulfate.

The known pharmacokinetics of vinblastine sulfate given by intermittent bolus dictate alternate dose schedules for prolonging the therapeutic levels. Herein, we have tested a divided dose schedule which shows out-patient feasibility, manageable toxicity, and encouraging responses.

Dose-Response Relationship, Drug↗
PubMed1979

Immunofluorescence studies of anti-T cell antibodies and T cells in systemic lupus erythematosus. Selective loss of brightly staining T cells in active disease.

Peripheral blood T cells from patients with systemic lupus erythematosus (SLE) and age- and sex-matched controls were studied by flow microfluorometry by using SLE anti-cell antibodies and fluorescein conjugated antibody to human IgM. Brightly staining cells were reduced in a number of patients with active SLE. Analysis of SLE T cells separated on a discontinuous stractin gradient indicated a preferential loss of cells, especially brightly staining cells, from one fraction. Quantitation of this phenomenon indicated that an average of greater than 90% of the brightly staining T cells from that fraction was lost in active SLE. This preferential loss of a subpopulation of T cells in patients with active SLE may be responsible for many of their immunologic abnormalities.

Antilymphocyte Serum↗
PubMed1979

Massive lymphadenopathy mimicking lymphoma in leukemic reticuloendotheliosis.

Leukemic reticuloendotheliosis is increasingly noted to have a spectrum of laboratory findings suggestive of both lymphocytes and monocytes. However, previous reports have not noted a clinical presentation which may be confused with lymphoma. This report documents a case of leukemic reticuloendotheliosis in a 29 year old man with clinical findings of diffuse lymphadenopathy, organomegaly and cutaneous involvement. As cytotoxic agents may be dysfunctional in leukemic reticuloendotheliosis, the ability to distinguish between the disorder and a lymphomatous process may be critical to the patient's management. Both morphologic examination of the "hairy-cell" and cytochemistry may not give an unequivocal differentiation between these two diseases. However, functional studies of the neoplastic cell, such as cell-marker analysis, phagocytic function and ultrastructural morphology, can define by noninvasive methods the correct diagnosis in the atypical presentation of leukemic reticuloendotheliosis.

Adult↗
PubMed1978

Increased risk of lymphoma in sicca syndrome.

The risk of cancer was ascertained in 136 women with sicca syndrome followed at the National Institutes of Health (NIH). Seven patients developed non-Hodgkin's lymphoma from 6 months to 13 years after their first admission to NIH. This was 43.8 times (P less than 0.01) the incidence expected from the rates of cancer prevailing among women of the same age range in the general population during this time. In addition, three cases of Waldenström's macroglobulinemia occurred in this study group. Eight patients developed cancers other than lymphoma, similar to the number expected based on the rates prevailing in the general population. Patients with a history of parotid enlargement, splenomegaly, and lymphadenopahy had an increased risk of lymphoma. These clinical conditions did not appear to be early manifestations of undiagnosed lymphoma but rather seemed to identify a subgroup of patients with sicca syndrome with marked lymphoid reactivity, who had a particularly high risk of subsequently developing lymphoma.

Adult↗
PubMed1977

Ribavirin: efficacy in the treatment of murine autoimmune disease.

Ribavirin, a drug with known antiviral activity, was given to mice with established lupus nephritis. Ribavirin was effective in prolonging survival, reducing the titer of antibodies to DNA, and reversing proteinuria. Other antiviral agents were not effective in the dosages used.

Acetates↗
PubMed1977

Increased spontaneous activity of antibody-forming cells in the peripheral blood of patients with active SLE.

Thirty-seven patients with criteria for systemic lupus erythematosus (SLE) and 18 normal controls were studied for their spontaneous background IgM antibody plaque-forming clell number to specific chemical haptens. Active SLE patients had significantly more plaque-forming cells in their peripheral blood to a total of five chemical determinants than did patients with inactive disease or controls. This increased number of plaque forming-cells correlated with depressed serum C3 levels by Spearman rank-order analysis. The finding of elevated numberof spontaneous IgM plaque-forming cells to defined chemical haptens supports the concept that active SLE demonstrates a generalized increase in B-cell activity toward a variety of antigens.

Adult↗
PubMed1977

Hematologic aspects of systemic lupus erythematosus. Current concepts.

Anemia occurs in more than one half of patients with systemic lupus erythematosus and is usually attributed to "chronic disease." Approximately 10% of patients with a positive Coombs' test manifest clinically significant hemolysis. Leukopenia affects both granulocytic and lymphocytic lines and may be caused by autoantibodies. Nevertheless, enhancement of B lymphocyte function occurs in active disease, perhaps due to a loss of regulatory T cells. Most patients have increased production and increased peripheral destruction of thrombocytes, with a normal circulation platelet count. Thrombocytopenia is usually caused by increased destruction. Qualitative abnormalities of platelet aggregation also occur. Circulation anticoagulants are not rare; however, spontaneous bleeding is uncommon. The anticoagulants, immunoglobulins directed against clotting factors, assume importance for invasive procedures. Most clinically significant hematopoietic abnormalities can be suppressed by corticosteroids; however, splenectomy, or immunosuppressive agents, or both, may be indicated for patients who respond inadequately to corticosteroids.

Agglutinins↗
PubMed1976

Study of lymphocyte subpopulations in normal humans and patients with systemic lupus erythematosus by fractionation of peripheral blood lymphocytes on a discontinuous Ficoll gradient.

Peripheral blood lymphocytes of thirty normal volunteers and fifty-two patients with systemic lupus erythematosus were fractionated using a discontinuous (5-30 percent) Ficoll gradient. Such fractionation permitted the isolation, identification of study of null cells, T cells and B cells. Patients with inactive SLE were found to have a cell distribution and responsiveness to PHA, Con A and Pokeweed mitogen (PWM) similar to controls. In contrast, patients with active SLE showed a significant decrease in T-cell fractions as well as a relative increase in null cells, a normal distribution of B cells, a marked reduction in responsiveness to Con A, a lesser reduction to PHA and only a minor reduction to PWM. With increasing disease activity, the number of null cells increased despite lymphopenia. Spontaneous lymphocyte transformation was observed in patients with SLE. This occurred predominantly in the fractions enriched in B cells and was observed both early (0-16 hr) and late (68-72 hr) in the lymphocyte cultures. The method of discontinuous Ficoll gradients is both versatile and reproducible with good correlations between isolated lymphoid subpopulations and disease activity.

B-Lymphocytes↗
PubMed1976

Hypertension and renal disease in systemic lupus erythematosus.

A retrospective analysis of 235 patients at the National Institutes of Health who met at least five criteria for systemic lupus erythematosus (SLE) indicated that 45% were hypertensive. Approximately two thirds of these hypertensive patients had creatinine clearances of more than 60 ml/min and nonnephrotic range proteinuria. Only 16% of normotensive patients had creatinine clearances of less than 60 ml/m9n. A subgroup of 36 patients with SLE and with biopsy-proved diffuse renal disease were studied. For these patients, the presence of hypertension could not be correlated with the degree of proteinuria or hematuria, with the level of serum complement, or with the presence of casts, focal necrosis, crescent formation, or interstitial inflammation. Hypertensive patients had a median age of 24.5 years; the majority had creatinine clearances of more than 60 ml/min. In SLE, hypertension is not necessarily associated with advanced renal disease, and high blood pressure may occur relatively early in the course of the disease.

Adult↗
PubMed1967

Thymidine and thymine incorporation into deoxyribonucleic acid: inhibition and repression by uridine of thymidine phosphorylase of Escherichia coli.

Thymidine is poorly incorporated into deoxyribonucleic acid (DNA) of Escherichia coli. Its incorporation is greatly increased by uridine, which acts in two ways. Primarily, uridine competitively inhibits thymidine phosphorylase (E.C.2.4.4), and thereby prevents the degradation of thymidine to thymine which is not incorporated into normally growing E. coli. Uridine also inhibits induction of the enzyme by thymidine. It prevents the actual inducer, probably a deoxyribose phosphate, from being formed rather than competing for a site on the repressor. The inhibition of thymidine phosphorylase by uridine also accounts for inhibition by uracil compounds of thymine incorporation into thymine-requiring mutants. Deoxyadenosine also increases the incorporation of thymidine, by competitively inhibiting thymidine phosphorylase. Deoxyadenosine induces the enzyme, in contrast to uridine. But this is offset by a transfer of deoxyribose from deoxyadenosine to thymine. Thus, deoxyadenosine permits incorporation of thymine into DNA, even in cells induced for thymidine phosphorylase. This incorporation of thymine in the presence of deoxyadenosine did not occur in a thymidine phosphorylase-negative mutant; thus, the utilization of thymine seems to proceed by way of thymidine phosphorylase, followed by thymidine kinase. These results are consistent with the data of others in suggesting that wild-type E. coli cells fail to utilize thymine because they lack a pool of deoxyribose phosphates, the latter being necessary for conversion of thymine to thymidine by thymidine phosphorylase.

DNA, Bacterial↗
PubMedDate not supplied

Phase I trial of vinzolidine.

Vinzolidine is a new, orally active, semisynthetic vinca alkaloid which shows broad anti-tumor activity against murine tumor test systems. This phase I study established a 1 day every 2 week schedule of 35 mg/m2 in good-risk patients and of 30 mg/m2 in poor-risk patients. Maximal tolerated dose was 45 mg/m2 with severe neutropenia, syndrome of inappropriate antidiuretic hormone, and paralytic ileus. Significant antitumor responses were seen in two patients with lymphoma and in one with squamous cell cancer of the lung.

Aged↗