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M Edelstein

Publications and source records attributed to M Edelstein.

At least 37 records · Page 2Linked to original sources
PubMed1991

Danazol treatment of myelodysplastic syndromes.

Peripheral cytopenias are common in patients with myelodysplastic syndromes. We previously successfully treated three such patients with improvement of some cytopenias with the impeded androgen danazol. To confirm this finding and elucidate the mechanism of response, we treated an additional 22 patients with myelodysplasia with oral danazol (600-800 mg daily) for 3-12 months. Eleven of 22 evaluable patients taking danazol met our criteria for improvement of peripheral counts, mainly thrombocytopenia. Chromosome analysis, marrow culture studies and serial bone marrow biopsies revealed no alteration of the abnormal clone or normal haematopoiesis in patients on danazol therapy. This suggested that improvement in blood counts was not related to modulation of ineffective haematopoiesis. Investigation of the thrombocytopenia in these patients revealed that most patients presented with markedly elevated platelet associated IgG (PAIgG), elevated plasma platelet-bindable IgG (PBIgG), and an elevated number of monocyte Fc gamma receptors. Treatment with danazol was associated with a decline in monocyte Fc gamma receptor number without significantly altering the elevated PAIgG or PBIgG levels. These results are similar to our observations in patients treated with danazol for chronic idiopathic thrombocytopenia purpura (ITP). Our data suggest that a component of the thrombocytopenia occurring in patients with myelodysplasia may be due to enhanced peripheral blood cell destruction by abnormal macrophages. Danazol may modulate cytopenia by decreasing the number of monocyte Fc gamma receptors. Danazol treatment was associated with minimal toxicity, but clinically meaningful responses were rare.

Adult↗
PubMed1989

In vivo DNA cross-linking by cyclophosphamide: comparison of human chronic lymphatic leukemia cells with mouse L1210 leukemia and normal bone marrow cells.

Alkaline elution was done on a variety of cells following cyclophosphamide (CY) treatment in vivo. Cells used were L1210 leukemia, normal mouse bone marrow, and peripheral blood cells obtained from a patient with chronic lymphatic leukemia (CLL). Endpoints used were determination of single strand breaks, DNA-DNA interstrand and DNA-protein cross-links. After treatment of mice with CY (4 mg/mouse), low levels of single strand breaks were observed in both L1210 leukemia and CDF1 normal bone marrow. When a patient with CLL was treated with CY (750 mg/m2), no evidence of single strand breaks could be demonstrated. Maximum levels of DNA-DNA interstrand cross-links were observed in mice 2 h after injection of CY for the L1210 leukemia cells [175 +/- 25 rad-equivalents (req)] and at 4 h for the CDF1 normal bone marrow cells (47 +/- 9 req). In human CLL, maximum levels were observed 12 h after injection of CY. Peak levels of DNA-DNA interstrand cross-links were approximately 4-fold lower in CDF1 normal bone marrow cells than in L1210 leukemia. The frequencies measured in human CLL cells were relatively low at any timepoint (mean at 12 h = 36 req). Maximum levels of DNA-protein cross-links were observed 4 h after injection of CY (4 mg/mouse) for both L1210 leukemia [123 req (mean)] and normal bone marrow cells [50 req (mean)]. DNA-protein cross-links were measurable in CLL at timepoints later than 4 h after the start of injection of CY. In order to obtain equitoxicity between L1210 leukemia and CDF1 normal bone marrow cells, about 18-fold higher doses of CY had to be given than in the case of the normal bone marrow cells. In contrast, only 4-fold higher doses had to be given to the normal bone marrow to obtain equivalent peak levels of DNA-DNA interstrand cross-links.

Animals↗
PubMed1989

Endogenous Aeromonas hydrophila endophthalmitis.

Aeromonas hydrophila as the etiologic agent of endophthalmitis is rare, having only been reported in association with a perforating injury of the eye. We describe a case of isolated spontaneous, endogenous endophthalmitis due to this agent, with no apparent source.

Aeromonas↗
PubMed1985

Recombinant interferon-gamma (immuneron): results of a phase I trial in patients with cancer.

Recombinant DNA-produced interferon-gamma (rIFN-gamma) was administered intravenously to patients with solid tumors in a Phase I study. The rIFN gamma was prepared from Escherichia coli and purified to greater than 95% with a specific activity of greater than or equal to 30 X 10(6) units/mg protein. Twenty patients received intravenous bolus injections once weekly for 4 consecutive weeks. They were assigned to one of six dose groups ranging from 1 to 81 X 10(6) units/m2 body surface area; intrapatient dose escalation was not allowed. Patients were monitored intensively for toxicity, but no dose-limiting toxicity was demonstrated. Fever was the predominant side effect, occurring in all patients treated, and usually reached 38-40 degrees C. Short-term somnolence and fatigue were also observed, but no chronic fatigue was seen. Decreases in white blood cell and platelet counts, generally within the normal range, were observed; however, the counts rose again after intervals of 2-5 days. There was no firm evidence of a relationship between adverse effects and dose. No life-threatening side effects were noted and no antibodies developed to either rIFN gamma or E. coli proteins. The pharmacokinetics of rIFN gamma did not appear to alter from week 1 to week 4. Calculated half-lives were from 0.8 to 3.5 h. Doses greater than 9 X 10(6) units/m2 gave measurable serum levels for at least 12 h. A partial response of 8 weeks' duration was observed in a patient with hepatoma.

Adult↗
PubMed1983

In vivo studies on the regeneration kinetics of haemopoietic spleen colony-forming cells from long-term bone marrow cultures.

Production of murine haemopoietic progenitor cells, capable of forming colonies on the spleens of irradiated recipients (CFU-s), can be maintained in vitro for up to several months. We have examined the properties of the suspension (SUSP) and adherent (ADH) CFU-s from these long-term marrow cell cultures in the spleen colony assay system. The numbers of colonies formed was linear with the numbers of SUSP or ADH cells injected, although the concentrations were only 20-25% of that found in normal bone marrow (NBM). The seeding efficiencies for SUSP and ADH CFU-s, measured in spleen and femur 24 hr after transplantation, were not significantly different from those for CFU-s from NBM. The results demonstrate that the CFU-s assay can give valid estimates of colony-forming cell numbers in the cultured cell populations. We therefore used the CFU-s assay to study the regeneration of SUSP, ADH and NBM CFU-s in spleen and femur at various times after transplantation. The growth of the cultured cells appeared to be delayed by 36-48 hr compared to the regeneration of CFU-s from NBM. Thereafter, ADH CFU-s grew at the same rate as NBM CFU-s, whereas the rate of SUSP CFU-s regeneration was slightly, but not significantly, slower. This similarity in growth rates indicates that the CFU-s from long-term marrow cultures have similar self-renewal probabilities to normal CFU-s.

Animals↗
PubMed1981

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Holistic Health↗
PubMed1977

Resolution of small G1 and G2 populations of L1210 leukemia by flow microfluorometric analysis aided by velocity sedimentation.

L1210 leukemic cells grown in vitro were subjected to kinetic analysis using a flow microfluorometer. A single broad peak was found for the DNA content distribution if unfractionated cells were used; prior fractionation using lg velocity sedimentation allowed the separation of small peaks with smaller (G1) and larger (G2) DNA contents from the dominant S phase peak with intermediate DNA content.

Animals↗
PubMed1977

Cellular quantitation of in vivo effects of 1-beta-D-arabinofuranosylcytosine on leukemia L1210.

We derived a cellular model for the use of the cytidine analogue 1-beta-D-arabinofuranosylcytosine (ara-C) against L1210 leukemia in vivo from dose- and time-survival studies. We employed a quantitative assay for leukemia colony-forming cells to construct dose- and time-survival curves for single, divided, and infused doses of ara-C. Time-survival curves for a large dose range of ara-C indicated not only cell killing but also progression delay effects in vivo. Divided dose studies showed the extent of cell killing (optimum effect) to be dependent upon both the dose and the interval of time between administration of the drugs. When the drug was given as an infusion, the extent of cell killing was as great as that produced by the best fractionation schedule, an effect which was verified in terms of therapeutic efficacy in leukemic mice.

Animals↗
PubMed1976

Combined effect of cytosine arabinoside and thiopurines.

Dose and time survival for leukemic colony-forming units (LCFU) and normal hematopoietic colony-forming units (NCFU) were obtained after the administration of either 6-mercaptopurine (6-MP) or 6-thioguanine (TG). Survival decreased to a plateau level with increasing doses as expected with phase-specific agents. Time survival curves demonstrated increased killing of LCFU after administration of 2 mg of 6-MP/mouse or 0.1 mg of TG/mouse reaching a minimum by 3-8 hours with repopulation therafter. Cytosine arabinoside (Ara-C) (1 mg/mouse) was combined with each agent, and the effects of sequence and interval were examined in terms of LCFU and NCFU survival. When Ara-C and either thiopurine were administered together, fractional survival was less than additive. However, as the interval was increased for either sequence and for both combinations, survival decreased to synergistic levels. Variation in dose of Ara-C and TG showed an inhibitory effect to be dependent upon the Ara-C dose. A correlation between results from the colony assay for for LCFU and survival of treated tumor-bearing mice was demonstrated for Ara-C plus TG. The results of these experiments are interpreted in terms of the proliferation kinetics of L1210 and the cellular effects of the agents; their clinical implications are discussed.

Animals↗