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M Edelstein

Publications and source records attributed to M Edelstein.

At least 19 recordsLinked to original sources
PubMed1995

Prenatal stress prevents the desensitization of the corticosterone response to TFMPP by desmethylimipramine, but not by phenelzine, in adult male offspring.

Gravid female rats were subjected to one hour of restraint stress twice daily or left undisturbed from days 14-21 of gestation. Adult 105-day old male non-stressed (NS) and stressed (S) offspring were treated once daily with saline, desipramine (DMI) (10 mg/kg, sc) or phenelzine (5.0 mg/kg, sc) for 14 days. Twenty-four hours after the last injection, animals were challenged with saline or 1-(m-trifluoromethylphenyl)piperazine (TFMPP) (5.0 mg/kg, sc), a serotonin1B/2C (5-HT1B/2C) agonist, and plasma prolactin and corticosterone concentrations were measured one hour later. As compared to acute saline administration, TFMPP significantly increased prolactin and corticosterone concentrations in all groups. In NS offspring, both DMI and phenelzine treatment augmented the prolactin response, but blunted the corticosterone response, to TFMPP. In S offspring, the prolactin response to TFMPP also was augmented by phenelzine or DMI treatment, whereas the corticosterone response to TFMPP was blunted during phenelzine treatment. However, DMI treatment was not able to desensitize the corticosterone response to TFMPP in the S rats. The results indicate the adaptive capacity of 5-HT systems to DMI administration was compromised in adult animals exposed to stress in utero.

Adaptation, Physiological↗
PubMed1994

Exposure to threshold doses of nicotine in utero: I. Neuroendocrine response to restraint stress in adult male offspring.

Gravid female rats were injected subcutaneously with saline or nicotine (3.0 mg/kg and 0.05 mg/kg, bid) from day 4 to day 20 of gestation or were left undisturbed. In adult 120-day old male offspring, the ACTH, corticosterone and prolactin concentrations before, during (15, 30, 45 and 60 minutes) and after (30, 60, 90 and 120 minutes) one hour of restraint stress were studied. Baseline (non-stress) concentrations of each hormone were comparable among the groups. As compared to saline controls, ACTH concentrations were significantly higher during stress at 30 and 60 minutes in the high-dose nicotine (HN) animals, with the average ACTH concentration during stress also being significantly higher in the HN rats. Neither nicotine regimen affected the corticosterone response to stress at any time-point. The prolactin response to stress was significantly reduced in the HN group at 45 and 60 minutes as compared to saline controls, with the average prolactin concentration also reduced during stress. During recovery, average ACTH concentrations were significantly higher in the HN group, and significantly lower in the LN group, with no differences found for either corticosterone or prolactin. The results indicate that exposure to a high-dose of nicotine during gestation, and to a very low-dose as well, produced functional alterations in adult male offspring as manifested by abnormal neuroendocrine responses to restraint stress. However, the differences between the nicotine and saline controls were sometimes as great as between the non-injected controls and the saline controls. Thus, any conclusions drawn about the long-term effects of prenatal nicotine on neuroendocrine responsivity to stress must be tempered by the influence of the repeated injection procedure.

Adrenocorticotropic Hormone↗
PubMed1993

Myelodysplastic syndrome after cisplatin therapy.

Therapy-related myelodysplastic syndrome (tMDS) and acute nonlymphocytic leukemia (tANLL) are known late complications of cytotoxic drug therapy for hematologic malignancies, solid tumors, and nonmalignant conditions. The alkylating agents are often the causative agents, but a few reports have implicated cisplatin as an etiologic agent. Cisplatin has a significant impact on the treatment of a number of malignant neoplasms, including testicular and ovarian cancer, and is a part of several clinical trials for squamous cell carcinoma of the head and neck region. Given its increasing use, a complication as significant as tMDS is potentially important. In this article, the authors describe the case of a patient who had myelodysplastic syndrome develop after successful treatment for laryngeal cancer with cisplatin. The treatment included cisplatin in combination with 5-fluorouracil, followed by radiation therapy. The authors also present a review of articles in the literature regarding tMDS and tANLL occurrence after treatment with cisplatin-containing regimens. The authors conclude that cisplatin can be a leukemogenic agent. The drug may potentiate the leukemogenic effects of other alkylating agents and drugs that inhibit topoisomerase II action.

Anemia, Sideroblastic↗
PubMed1993

Autologous bone marrow transplant in acute myeloid leukemia in first remission.

PURPOSE: The Eastern Cooperative Oncology Group conducted a prospective study of postremission high-dose chemotherapy and autologous bone marrow transplantation (autoBMT) in a group of uniformly treated adults with de novo acute myeloid leukemia (AML) to evaluate whether intensive, myeloablative therapy in first complete remission (CR) could improve the disease-free survival. PATIENTS AND METHODS: After initial CR was induced by the combination of daunorubicin, cytarabine, and thioguanine, patients not eligible for allogeneic bone marrow transplantation (alloBMT) were offered autoBMT. Within a median of 2 months after CR, and without intervening postremission therapy, bone marrow was obtained, purged by exposure to 4-hydroperoxycyclophosphamide (4-HC), and cryopreserved. High-dose therapy consisted of oral busulfan over 4 days (16 mg/kg total) followed by intravenous (IV) cyclophosphamide 50 mg/kg daily for 4 days. The cryopreserved marrow was then reinfused. RESULTS: Of the 39 patients scheduled for autoBMT, four relapsed before transplantation. Two of the 35 (6%) transplant patients died of transplant-related complications, and 11 (33%) relapsed a median of 8 months after marrow reinfusion. No relapse has occurred after 24 months posttransplant. With a median follow-up of 31 months, the median disease-free survival period for all 39 patients has not been reached; however, 54% +/- 16% of patients are projected to be alive and disease-free at 3 years. CONCLUSION: Long-term, disease-free survival after autoBMT in AML seems to be better than the outcome after conventional-dose postremission therapy and rivals the results of alloBMT.

Adolescent↗
PubMed1992

Varying intensity of postremission therapy in acute myeloid leukemia.

The Eastern Cooperative Oncology Group (ECOG) conducted a randomized trial in patients less than or equal to 65 years old (median, 44 years) to determine whether increasing the intensity of postremission therapy in acute myeloid leukemia (AML) would improve the outcome. After uniform induction therapy, patients in complete remission (CR) who were less than 41 years old and who had a histocompatible sibling underwent allogeneic bone marrow transplantation (alloBMT) (54 patients). The remainder of patients in CR were randomized to receive either 2 years of continuous outpatient maintenance therapy with cytarabine and 6-thioguanine (83 patients) or a single course of inpatient consolidation therapy consisting of 6 days of high-dose cytarabine plus 3 days of amsacrine (87 patients). The median duration of follow-up is now 4 years, and patients are included in the analyses of outcome regardless of whether they relapsed before starting the intended treatment. Four-year event-free survival (EFS) was 27% +/- 10% for consolidation therapy versus 16% +/- 8% for maintenance therapy (P = .068) and 28% +/- 11% versus 15% +/- 9% (P = .047) in patients less than 60 years old. The outcome for patients receiving alloBMT was compared with the subset of patients less than 41 years old who received consolidation therapy (N = 29) or maintenance therapy (N = 21). Four-year EFS was 42% +/- 13% for alloBMT, 30% +/- 17% for consolidation therapy, and 14% +/- 15% for maintenance therapy. AlloBMT had a significantly better EFS (P = .013) than maintenance therapy, but was not different from consolidation therapy. In patients less than 41 years old, 4-year survival after alloBMT (42% +/- 14%) did not differ from consolidation therapy (43% +/- 18%), but both were significantly better than maintenance therapy (19% +/- 17%), P = .047 and .043, respectively. The mortality rate for maintenance therapy was 0%, consolidation therapy, 21%; and alloBMT, 36%. Consolidation therapy caused an especially high mortality rate in the patients greater than or equal to 60 years old (8 of 14 or 57%). The toxicity of combined high-dose cytarabine and amsacrine is unacceptable, especially in older patients, and alternative approaches to consolidation therapy such as high-dose cytarabine alone need to be tested. In AML, a single course of consolidation therapy or alloBMT after initial CR produces better results than lengthy maintenance therapy. Although EFS and survival of alloBMT and consolidation therapy do not differ significantly, a larger number of patients need to be studied before concluding that they are equivalent.

Acute Disease↗
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↗