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Biomedical subjects

R B Epstein

Publications and source records attributed to R B Epstein.

At least 55 records · Page 3Linked to original sources

Efficacy of granulocyte transfusions in the control of systemic candidiasis in the leukopenic host.

An experimental canine model was designed to evaluate the effect of granulocyte transfusions on systemic infection with Candida albicans in the granulocytopenic host. Each of a pair of dogs was rendered granulocytopenic with a single intravenous (i.v.) dose of cyclophosphamide (50 mg/kg body weight) and challenged with 10(6) Candida albicans organisms administered i.v. when granulocyte counts were less than or equal to 500/mm3. Granulocytes procured by leukofiltration were infused into six experimental dogs 1, 24, 48, and 72 hr after challenge with Candida. An average of 13 +/- 1.3 X 10(9) granulocytes were administered per infusion, producing an average 1-hr increment of 588 +/- 146 granulocytes/mm3 over the pretransfusion granulocyte count. Experimental and control dogs were killed 96 hr after challenge and organs examined grossly and by quantitative culture techniques to measure the extent of infection. All animals receiving granulocyte transfusions had significantly less tissue infection than nontransfused controls (p less than 0.05). It was concluded that granulocyte transfusions are effective in reducing the severity of infection by Candida albicans during periods of leukopenia.

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Intralesional Bacillus Calmette-Guérin immunotherapy of canine venereal tumors.

Canine transmissible venereal tumors were studied for response to intralesional Bacillus Calmette-Guérin (BCG) therapy. Six pairs of littermates, identical for the major histocompatibility complex, were evaluated. One member of each pair received intralesional BCG to one of two growing tumors. Lesions of control animals received 0.9% NaCl solution. Both injected and noninjected lesions of BCG-treated animals underwent regression within 63 days, as compared to an extended period of tumor growth (beyond 100 days) for controls (p less than 0.05). Serial in vitro assays during therapy included; (a) mixed lymphocyte-tumor culture, (b) phytohemagglutinin stimulation, and (c) assessment of lymphocyte surface markers. Lymphocytes from BCG-treated dogs were significantly more responsive to tumor cells in mixed lymphocyte-tumor culture assay than were those from controls (p less than 0.05). Maximal responses occurred during tumor regression. T- and B-lymphocyte levels as assayed by rosette formation and surface marker immunoglobulins were not influenced by BCG therapy. It was concluded that intralesional BCG therapy of canine venereal tumors was highly effective in causing regression of injected and noninjected lesions. This tumor model system may be useful for the evaluation of the effectiveness of new immunotherapeutic approaches on established neoplasms in large, randomly bred animals.

Animals↗

Demonstration of hemopoietic stem cells in the peripheral blood of baboons by cross circulation.

Baboons were given 1200 R total body irradiation from two opposing 60Co sources. Three animals were given supportive therapy only and died, as expected, within 8 days of irradiation with profound marrow hypoplasia. Five baboons were cross-circulated with unirradiated partners and died within 14 days with evidence suggestive of graft-versus-host disease. Their marrows were repopulated with hemopoietic precursor cells, and three of the five had rises in peripheral white blood cell counts to more than 1500/cu mm before death. These results are compatible with the presence of hemopoietic stem cells in the peripheral blood of a nonhuman primate, the baboon.

ABO Blood-Group System↗

Effect of bone marrow suppression on granulocyte opsonin levels.

Levels of serum opsonin for neutrophilic granulocytes were measured in dogs made neutropenic by cyclophosphamide administration. Heat-labile opsonin became elevated within 24 hr following cyclophosphamide (P less than 0.005) and remained elevated over the 4-5 day period of observation (P less than 0.005). In contrast, heat stable opsonin was not significantly effected. Bone marrow suppression by X-ray and busulfan also caused serum opsonin levels to increase. Changes in the levels of IgG, C3, and total hemolytic complement during the course of bone marrow suppression did not correlate with the granulocyte opsonin levels. These findings suggest that serum granulocyte opsonin levels respond to bone marrow suppression and may provide an improved environment for the function of transfused granulocytes.

Agranulocytosis↗

Combined pre-immunization and granulocyte transfusion therapy for treatment of pseudomonas septicemia in neutropenic dogs.

An experimental model was designed to evaluate a combined protocol of active immunization and granulocyte transfusions for treatment of Pseudomonas aeruginosa sepsis in the neutropenic host. One member of a pair of dogs was immunized with P. aeruginosa vaccine. Both dogs were then rendered transiently neutropenic with a single intravenous dose of cyclophosphamide (40 mg. per kilogram) and challenged with an intravenous inoculum of P. aeruginosa. Twenty-four and 48 hours after pseudomonas challenge each animal received granulocyte transfusions. Effectiveness of therapy was evaluated by observation of survival time, febrile response, and quantitative blood cultures. Results showed a significant increase in the survival period (P is less than 0.05), a lower febrile response (P is less than 0.025), negative blood cultures, and a greater recovery rate in the immune group. Immune dogs that died had negative blood cultures or less than or equal to 10 pseudomonas per milliliter of blood despite the presence of P. aeruginosa in tissues. In contrast, control dogs had septic deaths within 67 hours of pseudomonas challenge, marked febrile responses with 24 hours of infection, and positive blood cultures with 4,000 to 25,800 pseudomonas per milliliter of blood. These data show that combined therapy with immunization and granulocyte transfusions is effective in reducing the severity of P. aeruginosa infection and in preventing bacteremia during periods of leukopenia.

Agranulocytosis↗

Restoration of hematopoiesis in dogs by infusion of cryopreserved autologous peripheral white cells following busulfan-cyclophosphamide treatment.

Canine cryopreserved autologous peripheral buffy coat cells were infused after an otherwise lethal regime of busulfan and cyclophosphamide. In seven dogs so treated, restoration of hematopoiesis occurred within 7 days, and six dogs recovered completely. Comparable colony-forming unit in agar activity was present in freshly processed and cryopreserved buffy coat cells and proved to correlate with in vivo marrow recovery. It was concluded that the peripheral blood is a convenient source for obtaining cells for autologous marrow reconstitution in canines.

Animals↗

Hemopoietic colony forming units in fresh and cryopreserved peripheral blood cells of canines and man.

Colony forming units (CFUa) were assayed in the peripheral blood and separated mononuclear cells of canines and man. Fresh and cryopreserved samples were studied. By plating 3 x 10-5 canine buffy coat cells or 3 x 10-6 human buffy coat cells between 33 plus or minus 6.6 and 38 plus or minus 1.0 colonies were observed. A high degree of reproducibility was shown for duplicate plates and on repeated testing. Cryopreservation for a one-month period resulted in a minimal recovery of 80 per cent CFUa for canine cells and 96 per cent for human cells. In vivo correlation between peripheral blood CFUa and marrow repopulation was assessed indogs following supralethal whole body irradiation. Prompt repopulation of the marrow was observed and this correlated well with the CFUa assay following infusion of stored buffy coat cells. It was concluded that the peripheral blood of both man and dog have significant numbers of cells with CFUa capabilities that may be potentially useful for marrow grafting purposes.

Animals↗

Tumor-blocking and -inhibitory serum factors in the clinical course of canine venereal tumor.

An in vitro method for growing colonies of canine transplantable venereal tumor cells in a semisolid agar medium is described. Using autologous or pooled homologous normal dog sera as a feeder layer, 49.3 +/- 3.5 and 47.5 +/- 4.5 tumor colonies were obtained, respectively, when 2 X 10(4) tumor cells were plated. With this assay system, assessment of colony counts provided an accurate and rapid technique for monitoring serum factors in tumor-bearing dogs that inhibited colony formation, or blocked the inhibition of colony formation. In 52 dogs given tumor transplants, a direct correlation was demonstrated between serum activity tested in vitro and the in vivo growth characteristics of the tumor. Tumor cells preincubated with serum from dogs with active tumor growth consistently showed normal colony growth when cultured in agar containing colony-inhibitory sera (blocking effect). In vivo regression was characterized by loss of serum blocking and the development of serum colony-inhibitory activity in culture. In metastatic disease, only blocking activity could be identified, while persistent local invasive disease was characterized by low levels of both blocking and inhibitory serum activity. The sensitivity of this technique coupled with its in vivo predictive capabilities provides a model for monitoring serological responses to a naturally occurring neoplasm in a large, randomly bred animal.

Animals↗