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J E Balow

Publications and source records attributed to J E Balow.

At least 19 recordsLinked to original sources
PubMed1992

Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis.

Pulse cyclophosphamide is more effective than prednisone alone in preventing renal failure in lupus nephritis. We undertook a randomised, controlled trial to find out whether pulse methylprednisolone could equal pulse cyclophosphamide in preserving renal function in patients with lupus nephritis, and whether there was a difference between long and short courses of pulse cyclophosphamide in preventing exacerbations. 65 patients (60 female, 5 male; median [range] age 29 [10-48] years) with severe lupus nephritis were assigned randomly to monthly pulse methylprednisolone for 6 months (25 patients), monthly pulse cyclophosphamide for 6 months (20), or monthly cyclophosphamide for 6 months followed by quarterly pulse cyclophosphamide for 2 additional years (20). Patients treated with pulse methylprednisolone had a higher probability of doubling serum creatinine than those treated with long-course cyclophosphamide (p less than 0.04). Risk of doubling creatinine was not significantly different between short and long course cyclophosphamide. However, patients treated with short-course cyclophosphamide had a higher probability of exacerbations than those treated with long-course cyclophosphamide (p less than 0.01). An extended course of pulse cyclophosphamide is more effective than 6 months of pulse methylprednisolone in preserving renal function in patients with severe lupus nephritis. Addition of a quarterly maintenance regimen to monthly pulse cyclophosphamide reduces the rate of exacerbations.

Adolescent↗
PubMed1992

NIH conference. Membranous nephropathy.

Membranous nephropathy is a worldwide problem that accounts for about 20% of the cases of the adult-onset nephrotic syndrome. This disease places many patients at risk for both end-stage renal failure and the complications of hyperlipidemia. Immune-mediated injury to the glomerular capillary wall in patients with membranous nephropathy is characterized by subepithelial immune complex formation and generation of the membrane attack complex of complement. Glomerular capillary hypertension, hyperlipidemia, and possibly cytokines could contribute to the glomerular sclerosis seen in the advanced stages of the disorder. In some cases, production of pathogenic antibody can be suppressed by treating the underlying condition. The mechanisms of action of immunosuppressive agents are being investigated and treatments are being tested in clinical trials to optimize the balance of efficacy and toxicity. Alternate-day treatment with corticosteroids is often recommended for nephrotic patients with idiopathic membranous nephropathy, but this approach has not been proved beneficial. Ongoing studies are evaluating whether cytotoxic drugs or cyclosporin A combined with prednisone is more effective than treatment with corticosteroids alone. Lipid-lowering drug therapy is warranted in cases of the persistent nephrotic syndrome to avert the cardiovascular sequelae of hyperlipidemia.

Animals↗
PubMed1979

Mortality in lupus nephritis.

The principal causes of death of 68 patients with lupus glomerulonephritis were reviewed. Renal failure (40%), vascular events (25%), and infections (16%) were the predominant causes. Diffuse proliferative glomerulonephritis was associated with an increased frequency of renal failure. A bimodal pattern of early deaths due to active lupus and sepsis and late deaths from vascular events was found superimposed on a constant rate of death from renal failure.

Acute Kidney Injury↗
PubMed1979

NIH conference. Systemic lupus erythematosus: evolving concepts.

Systemic lupus erythematosus, a disease of unknown cause and protean manifestations, continues to excite substantial investigational interest. These papers bring together recent advances in concepts of its immunopathogenesis, evidence for a major genetic role in the causation of the process, developing systems for the morphologic assessment of its often fatal nephritis, and data from ongoing trials of cytotoxic drugs in its management.

Adolescent↗
PubMed1978

Immune complex glomerulonephritis in sicca syndrome.

In three patients with the sicca syndrome (Sjögren's syndrome), who were followed for one to seven years, glomerulonephritis developed. None of these patients fulfilled the diagnostic criteria for systemic lupus erythematosus. All of these patients had circulating immune complexes as detected by the Clq binding assay. Glomerular histology by light and electron microscopy revealed changes compatible with membranoproliferative glomerulonephritis in two of the patients and membranous glomerulonephritis in the third. All patients showed rapid improvement in renal function following moderate doses of corticosteroids. In addition, the treatment decreased the level of circulating immune complexes in two patients who were followed for a sufficient period of time.

Adult↗
PubMed1977

Computed tomography in the diagnosis of subcapsular and perirenal hematoma.

Six patients are described in whom subcapsular and perirenal hematomas were demonstrated by computed tomography. This new diagnostic tool provided a rapid noninvasive means of visualizing the hematoma, its extent, location, and relationship to renal parenchyma. Serial examinations were used to follow progress of the hematomas toward resolution. Correlation is made with conventional rediography, angiography, and gray scale ultrasound.

Adolescent↗
PubMed1977

Corticosteroids in human lymphocyte-mediated cytotoxic reactions: effects on the kinetics of sensitization and on the cytolytic capacity of effector lymphocytes in vitro.

The present experiments tested the ability of hydrocortisone and methylprednisolone to alter the process of in vitro generation of cytotoxic T lymphocytes against specific alloantigens or to suppress the lytic phase of the subsequent cytotoxic reactions. The continuous presence of hydrocortisone in culture reduced the total number of cytotoxic lymphocytes recovered following their sensitization in mixed leukocyte cultures. However, corticosteroids had no direct effect on the processes required for generation of cytotoxic lymphocytes, since equal numbers of effector lymphocytes generated in the presence or absence of hydrocortisone produced equivalent, specific lympholysis. The addition of either hydrocortisone or methylprednisolone only during the cytolytic phase of cell-mediated lympholysis failed to significantly suppress the killing of lymphocyte targets. In contrast, parallel studies of the capacity of the same lymphocytes to serve as effector cells in antibody-dependent cellular cytotoxicity showed that both hydrocortisone and methylprednisolone directly inhibited the killing of Chang liver cells sensitized with low concentrations of antibody.

Adult↗
PubMed1977

Characterization of the direct effects of cyclophosphamide on cell-mediated immunological responses.

The direct immunosuppressive effects of cyclophosphamide were examined by incubating normal guinea-pig mononuclear cells with activated cyclophosphamide prepared from the serum of separate animals which were treated with cyclophosphamide in vivo. Treated cells were subsequently assayed in a panel of tests of cell-mediated immunity either immediately or following recovery during variable periods of incubation. It was found that cyclophosphamide (1) induces changes in lymphocyte functions which are not due simply to cell death; (2) is markedly antiproliferative in mitogen-induced blastogenesis; (3) depresses migration inhibitory factor production only after a delay of several hours and (4) depresses certain cytotoxicity reactions immediately following treatment, such responses are subsequently normalized when the cells are allowed to recover in culture.

Animals↗
PubMed1976

Successful renal transplantation in Wegener's granulomatosis.

Two patients with Wegener's granulomatosis, who were in complete remission secondary to cyclophosphamide therapy but who had end-stage renal failure, were treated with renal transplantation. Neither patient has clinical evidence of recurrent glomerulonephritis 10 and 28 months after receiving the renal transplants. Cytotoxic therapy has been proved to be highly effective in inducing and maintaining remission in patients with Wegener's granulomatosis; thus increasingly larger numbers of patients will be seen who, despite being maintained in complete remission, will have markedly impaired renal function due to previous acute damage. Renal transplantation can now be considered an acceptable alternative form of therapy in such patients.

Adult↗
PubMed1976

Cytotoxic effector capacity of bone marrow mononuclear cells.

Purified mononuclear cells from guinea pig bone marrow possess highly efficient cytotoxic effector cell capabilities in the phytohemagglutinin-induced cellular cytotoxity and antibody-dependent cellular cytotoxicity and antibody-dependent cellular cytotoxicity assays against chicken red blood cell targets. This cytotoxic activity is not removed by depletion of adherent cells by passage through rayon wool columns. Thus bone marrow lymphocytes themselves, depleted of adherent monocytes, possess this killer cell capacity. These effector cells may either arise de novo within the bone marrow parenchyma or arrive there as part of the recirculating lymphocyte pool. These studies lend further understanding of the development of functional capabilities of bone marrow lymphoid cells.

Animals↗
PubMed1976

Human bone marrow lymphocytes. Cytotoxic effector cells in the bone marrow of normal individuals.

This study was undertaken to determine the capability of lymphocytes in the bone marrow of normal individuals to mediate nonspecific killer cell functions in assays of phytohemagglutinin (PHA)-induced cellular cytotoxicity, and antibody-dependent cellular cytotoxicity (ADCC) against 51Cr-labeled chicken erythrocyte target cells. Relatively pure mononuclear cell suspensions were obtained from bone marrow aspirates in 30 normal volunteers by sucrose gradient centrifugations and from the peripheral blood of the same individuals by Hypaque-Ficoll density centrifugations. At an effector: target ratio of 10:1, the PHA-induced cellular cytotoxicity of peripheral blood was 78.8 +/- 1.3%, while that of bone marrow was not significantly less at 66 +/- 9% (P greater than 0.1). At low effector:target ratios, the ADCC of bone marrow was negligible, while at higher effector:target ratios (20:1) bone marrow ADCC was 69 +/- 3.7%, which was comparable to that of peripheral blood. The lymphocytes themselves in the mononuclear cell suspensions of both peripheral blood and bone marrow were capable of cytotoxicity activity since depletion of monocytes from the suspensions by adherence to rayon wool and G-10 Sephadex columns did not remove the cytotoxic activity. Blocking of the Fc receptor on the effector cells by the addition of aggregated gamma globulin to the cultures suppressed the ADCC but not the PHA-induced cellular cytotoxicity of both peripheral blood and bone marrow, indicating that ADCC is dependent on an Fc receptor on the effector cell in both compartments. These studies demonstrate that the bone marrow of normal humans contains populations of lymphoid cells which have highly efficient killer cell capacities. It is uncertain what portion of these cells arise in the bone marrow and what portion enter the bone marrow parenchyma as part of the recirculating lymphocyte pool. These findings have relevance in the clearer understanding of the killer cell potential of grafted human marrow, as well as the bone marrow sequestration of functionally capable lymphocyte subpopulations in disease states and during chemotherapy.

Adult↗
PubMed1976

Glucocorticosteroid therapy: mechanisms of action and clinical considerations.

The administration of glucocorticosteroids results in a wide range of effects on inflammatory and immunologically mediated disease processes. Glucocorticosteroids cause neutrophilic leukocytosis together with eosinopenia, monocytopenia, and lymphocytopenia. A principal mechanism whereby corticosteroids suppress inflammation is their impeding the access of neutrophils and monocytes to an inflammatory site. Granulocyte function is relatively refractory, whereas monocyte-macrophage function seems to be particularly sensitive to corticosteroids. Corticosteroid administration causes a transient lymphocytopenia of all detectable lymphocyte subpopulations, particularly the recirculating thymus-derived lymphocyte. The mechanism of this lymphocytopenia is probably a redistribution of circulating cells to other body compartments. There is considerable disagreement about the direct effects of corticosteroid administration on human lymphocyte function. The corticosteroid regimen should be adjusted to attain maximal therapeutic benefit with minimal adverse side effects. Often, alternate-day dosage regimens effectively maintain disease remission with minimization or lack of Cushingoid and infectious complications.

Animals↗
PubMed1975

Experimental disseminated candidiasis. II. Administration of glucocorticosteroids, susceptibility to infection, and immunity.

A model of experimental disseminated candidiasis in inbred guinea pigs was used for study of the effects of both short-acting and long-acting glucocorticosteroid administration on the susceptibility to infection, the development of in vivo and in vitro parameters of cell-mediated immunity, and the expression of already established Candida-specific, cell-mediated immunity. Results revealed that long-acting glucocorticosteroids markedly potentiated infection, increasing mortality and suppressing already established cellular immune parameters. The development of cellular immunity to Candida was not impaired. Short-acting glucocorticosteroids, however, did not potentiate infection, and they affected neither the development nor the expression of immune parameters.

Animals↗
PubMed1975

Cyclophosphamide suppression of established cell-mediated immunity. Quantitative vs. qualitative changes in lymphocyte populations.

The characteristics of cyclophosphamide-induced suppression of established ccll mediated immunity were studied in guinea pigs previously senstized to tuberculin. Cyclophosphamide treatment for 5 days produced a dose-dependent peripheral lymphoctopenia and disproportionatley greater neutrophenia which was particularly striking at high doses of 20 mg/kg per day(approximaetly 200 mg/kg-2 per day). Lymphoctes remianing in the circulation of cyclophosphamide treeated aniamls showed a doses-dependent reduction to both in vitro proliferactive and macrophage migration inhibitory factor responses to tuberculin compared to lymphocte responses of controls. Proliferative responses to phytohemaggultinin and concanavalin a were not significatly suppressed. Additional studies showed that cyclophosphamide suppressed the porliferactive and migration inhibitroy factor responses to tuberculin of lymph node and splenic as well as cirulating lymphocte populations. These studies showed that relatively short-term cyclophospamide administration produced immunosuppresion by quantitative as well as qualitative changes in lymphocyte populations. Significant suppresion of lymphocte function, howerver, was achived only with doses of cyclophoshamide which also produced a severe neutropenia.

Animals↗
PubMed1975

Immunosuppressive effects of glucocorticosteroids: differential effects of acute vs chronic administration on cell-mediated immunity.

The effects of acute vs. chronic glucocorticosteroid administration on established cellular immune responses were studied in guinea pigs previously sensitized to tuberculin. A greater than 50% reduction in circulating lymphocytes was observed 4 hr after injection of soluble hydrocortisone and 24 hr after daily subcutaneous injections of depot cortisone acetate. After a single dose of hydrocortisone, peripheral lymphocyte migration inhibitory factor (MIF) production and antigen and mitogen-induced proliferation were unchanged. However, the peripheral lymphocytes remaining in the circulation after chronic cortisone treatment showed a marked decrease in both antigen-induced MIF and proliferation, although mitogen responses remained normal. Although similar levels of lymphocytopenia were induced by acute and chronic glucocorticosteroid administration, only chronic treatment was associated with depression of certain cell-mediated lymphocyte functions. The available evidence suggests that these changes may depend on GCS-induced selective alterations in the circulation patterns of certain subpopulations of lymphocytes.

Animals↗