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Biomedical subjects

E Feldman

Publications and source records attributed to E Feldman.

At least 73 records · Page 4Linked to original sources
PubMed1992

Homoharringtonine in combination with cytarabine for patients with acute myelogenous leukemia.

Homoharringtonine (HHT) is one of several cephalotaxine alkaloids that has shown clinical efficacy in patients with acute myelogenous leukemia (AML). In a phase I trial we evaluated cytarabine 100 mg/m2 by continuous infusion daily for 7 days in combination with four dose levels of HHT ranging from 1.5-5 mg/m2 by continuous infusion daily for 7 days to see if an effective regimen could be developed. Twenty-two patients with relapsed and/or primary refractory AML were treated. Seventeen males and five females were treated, with a median age of 40 years (range 19-63). There were five remissions in 14 patients with relapsed AML and none of eight responders in patients with primary refractory AML. None of the three patients treated at 1.5 mg/m2 dose level of HHT responded. Of three patients treated at the 3 mg/m2 dose level, there was one complete remission. At both 4 mg/m2 and 5 mg/m2, two of eight patients achieved complete remission. Four of the five remissions occurred in patients with acute promyelocytic leukemia. Drug induced pancytopenia was universal, and hypotension and fluid retention were more common at the higher dose levels. Other toxicity was mild and included nausea, vomiting, diarrhea, and mucositis. No significant hepatic, renal, or cardiac toxicity was seen. We conclude that the dose of HHT 4 mg/m2 for 7 days by continuous infusion in combination with cytarabine is safe for patients with AML; and this combination is appropriate for a phase II evaluation.

Adult↗
PubMed1991

Modulation of erythropoiesis by novel human bone marrow cytochrome P450-dependent metabolites of arachidonic acid.

In the hematopoietic system the adherent stromal cells produce cytokines necessary for proliferation and differentiation of hematopoietic cells. In the present study, we showed the ability of adherent stromal cells to generate novel metabolites of arachidonic acid via the NADPH-cytochrome P450-dependent monooxygenase system. These metabolites were recovered in the incubation media, suggesting their release from cells. The formation of arachidonic acid metabolites was inhibited by 7-ethoxyresorufin and SKF-525A, but not by indomethacin or BW-755C. By using two-step high-pressure liquid chromatography (HPLC), bone marrow-adherent stromal cells and incubation media showed the presence of metabolites in a peak eluted at 19 to 20 minutes. The isolated HPLC peak was used to measure its effect on colony-forming unit-erythroid (CFU-E) growth and compare it with that of synthetic cytochrome P450 arachidonate metabolites, 19- and 20-hydroxyeicosatetraenoic (HETE) acid. These bone marrow cytochrome P450 arachidonic acid metabolites at picomolar concentration potentiated erythropoietin (Epo)-induced CFU-E growth by fourfold to sixfold. Addition of 19- and 20-HETE to the bone marrow culture resulted in a potentiating effect on CFU-E number in a dose-dependent manner. 20-HETE was much more potent in stimulating CFU-E growth than 19-HETE at a similar concentration of 10(-11) mol/L. The potentiating effect of 20-HETE resulted in a shifting to the left of the dose-response curve to Epo. To substantiate the finding of an active NADPH-dependent cytochrome P450-metabolizing system, we further examined the ability of adherent cells to metabolize exogenous pharmacologic compounds such as benzo(a)pyrene, a substrate for the heme-cytochrome P450 system, aryl hydrocarbon hydroxylase. The adherent stromal cytochrome P450 metabolizes benzo(a)pyrene at comparable levels to blood vessel endothelial cells. These novel observations underscore the importance of adherent stromal cytochrome P450 to metabolize endogenous substrates, including arachidonic acid, to compounds that may interact in a paracrine manner with Epodependent hematopoietic cells.

Arachidonic Acid↗
PubMed1991

Variables affecting long-term memory of learning that a food is inedible in Aplysia.

Long-term memory of learning that a food is inedible was studied in Aplysia. Seven days after a single training session, animals retained significant memory, as measured by a number of parameters. A 2nd experiment demonstrated savings 3 weeks after 2 training sessions. Long-term memory was also found after training procedures were altered to resemble those more likely to occur in nature, such as training for only 10 min or training with ad-lib access to inedible food, with no experimenter intervention. The effects were determined of bilaterally sectioning the esophageal nerves that innervate the gut. Denervation of the gut blocked the ability to learn that food is inedible but did not affect memory after the task had already been learned.

Animals↗
PubMed1991

Further thoughts on 'cell kill' in acute leukemia.

With traditional therapy of acute myelogenous leukemia, not more than 20% of patients achieve long-term survival. Efforts at intensifying postinduction chemotherapy have resulted in minor improvements only, but this limited progress has been hampered by increasing toxic-death rates. Eradication of the leukemia burden may be achieved by the introduction of more effective induction regimes and these may be rendered more effective by the application of 'enhancers'. With a lower tumor burden, and with more appropriate timing for supralethal therapy, it may be possible to achieve cure with greater frequency. Measurement of 'minimal residual disease' permits more logical selection of postinduction therapy.

Bone Marrow Transplantation↗
PubMed1991

Adding long-term care to Medicare: The Social HMO Experience.

The rancor accompanying the repeal of most of the 1988 Medicare Catastrophic Act reflects both the national need to improve health and long-term care benefits for the elderly and the political obstacles to finding new sources of financing for such benefits. Neither the need nor the obstacles will go away, but policymakers are now likely to look for lower-cost, efficient, and privately funded alternatives. The authors have developed and tested one such approach: the Social Health Maintenance Organization (SHMO). Operating since 1985, the SHMO model integrates community-based, long-term care services into the managed, prepaid HMO design. The four test sites are adding long-term care to Medicare at no extra cost to the government and only modest premiums for the 17,000 current members. Although the benefits offer limited protection for long-term nursing home care, they do cover long-term care in community settings, where people tend to prefer to stay. Also, integration of the acute and long-term care systems improves the ability to respond to the medical needs of frail members, who also have high acute-care use. The SHMO's model of front-end, community-oriented, long-term care benefits integrated with Medicare appears to be a practical, affordable, and clinically appropriate way to address the rising concern with the lack of coverage and services for long-term care.

Aged↗
PubMed1991

Psychiatric problems among medical admissions.

The prevalence, nature, associations and outcome of psychiatric morbidity among four hundred and fifty severe general medical admissions are described. Affective disorder was diagnosed in 13 percent of men and 17 percent of women. It was associated with a history of previous psychiatric disorder and current social problems. Persistent affective disorder after discharge was associated with continuing medical and social problems. Alcohol problems were common in men, especially in those with social problems, and often went unrecognized by medical staff. Cognitive impairment was confined to the elderly and was associated with longer hospital stay and high mortality. Patients with emotional and cognitive disorder make considerable demands on medical, social and psychiatric services during and following admission. The implications for improved recognition and management of psychiatric morbidity in general medical patients are discussed.

Adolescent↗
PubMed1991

Electrocortical mapping, MRI, and neuropsychological measures: evidence of Alzheimer's disease in the presence of vascular lesions.

We report here a case study of a 76-year-old woman with a high school education, whose presenting psychiatric symptomatology indicated dementia of unknown etiology. Neuropsychological test results were consistent with AD, but diagnosis was complicated by an MRI showing a large right hemisphere cortical infarct and scattered subcortical changes leading to a diagnosis of possible AD. Electrocortical mapping showed the right hemisphere infarct, and gave independent evidence suggestive of AD in the relatively intact left hemisphere. This case demonstrates the utility of multidimensional assessment as an aid to differential diagnosis.

Clinical Conference↗
PubMed1991

Effect of pharmacologically relevant concentrations of mitoxantrone on the in vitro growth of leukemic blast progenitors.

The inhibitory effects of a 1 h exposure to pharmacologically relevant concentrations of the anthracenedione mitoxantrone were assessed with respect to the in vitro clonogenic growth of leukemic myeloblasts obtained from patients with acute myelogenous leukemia (AML). A steep mitoxantrone dose-response curve was observed, and increases in drug concentrations at both low and high dose ranges were associated with a significant potentiation of anti-leukemic effects. In particular, mitoxantrone concentrations of 1 microM or greater were highly inhibitory to leukemic blast progenitor cell growth, and were also effective in reducing or eliminating leukemic cell self-renewal capacity in those samples assayed. These findings suggest that mitoxantrone mediated lethal effects towards leukemic cells are dose-related within a pharmacologically achievable range, and raise the possibility that an increase in plasma levels through dose escalation might lead to enhanced leukemic cell killing in vivo.

Cell Division↗
PubMed1991

Is childhood sexual abuse really increasing in prevalence? An analysis of the evidence.

One controversy regarding childhood sexual abuse is whether the increased rate of reported cases reflects a true increase in prevalence. In this report, data obtained in the 1970s and 1980s were compared with those of the 1940s. Using predetermined criteria for quality of information, commonality of definitions of childhood sexual abuse, and research design, the authors reviewed the Kinsey report published in 1953 and 19 prevalence studies reported in the last 10 years. Interrater reliability was .97 for each paper. In spite of differences in study designs and populations surveyed, where definitions of childhood sexual abuse were similar, the more recent studies with the strongest methodology reported prevalence figures similar to those of Kinsey in the 1940s, ie, 10% to 12% of girls younger than 14 years of age. Thus it would appear that increased reporting is due to changes in legislation and social climate rather than a true increase in prevalence. The absence of an increase in prevalence of childhood sexual abuse should not deter those interested in pursuing solid research in prevention and treatment because any childhood sexual abuse is too much.

Adolescent↗
PubMed1990

Phase II trial of fludarabine phosphate (F-Ara-AMP) in patients with advanced head and neck cancer.

Thirteen patients with advanced head and neck cancer were entered into a phase II study of fludarabine phosphate. Fludarabine phosphate was given by continuous infusion for 5 days, at a starting dose of 20 mg/m2 per day for patients previously treated with one regimen and 25 mg/m2 per day for previously untreated patients; therapy was repeated every 3-4 weeks. Of the 13 patients, 3 had undergone one prior regimen and 10 patients were previously untreated by chemotherapy. No responses were observed. Myelosuppression was the most common toxicity observed. Four patients developed mild nausea, vomiting and seven developed bleeding stomatitis that resolved in one week. In addition, four patients developed headaches which resolved spontaneously. No renal, hepatic, or neurotoxicity was observed. Our study demonstrates that in previously treated and untreated patients, fludarabine phosphate given on this schedule has little activity in patients with advanced head and neck cancer.

Aged↗
PubMed1990

Significance of psychiatric symptoms in general medical patients with mood disorders.

Little difference was found between the psychiatric symptoms of medical patients and general-population subjects with affective disorder, both groups having been assessed with the same procedure (Present State Examination). Discrimination between medical patients with and without affective disorder was best achieved when patients with depressive and anxiety disorders were considered separately. Depressed mood, morning depression, and hopelessness were the key symptoms in the depressives, and nervous tension, free-floating anxiety, panic attacks, and specific phobias in the patients with anxiety disorders. Symptom profile did not distinguish patients with persistent affective disorders from those whose disorders had resolved at a 4-month follow-up.

Adult↗
PubMed1990

Two separate differentiation inducing proteins for human myeloid leukemia cells and their isolation from normal lymphocytes.

Conditioned medium from mitogen stimulated normal peripheral blood lymphocytes (PBL) has been demonstrated to contain a maturation inducer activity mediating the differentiation of human myeloid leukemia cells to monocytes and macrophages. The maturation inducer activity was isolated by salt precipitation, Sepharose CL-6B ion exchange and affinity chromatographies and electrophoresis. Two separate activities with M.W. ranges of 52-56 and 32-35 kDa capable of mediating the terminal differentiation of leukemic HL-60 promyelocytes to monocytes and macrophages were detected. The higher molecular weight species was determined to be a 54 kDa single polypeptide and was found to be distinct from IL-3 and IL-6 by ELISA and differentiation blocking assay. The inducing activity of the 32-35 kDa material was largely neutralized after treatment with anti-IL-3, but not with other antibodies. Employing the immunofluorescent antibody technique, the 54 kDa protein was detected on the surface membranes of PBL. The proportions and number of maturation inducer bearing lymphocytes in patients with acute myelogenous leukemia (0.4% and 35/mm3, respectively) were significantly lower than that of healthy donors (7.9% and 178/mm3) The role of these physiological factors in leukemia cell differentiation is discussed.

Cell Differentiation↗
PubMed1990

Randomized multicenter trial of cytosine arabinoside with mitoxantrone or daunorubicin in previously untreated adult patients with acute nonlymphocytic leukemia (ANLL). Lederle Cooperative Group.

This phase III, randomized trial in previously untreated adults with ANLL compared mitoxantrone plus cytosine arabinoside with the CALGB "7 + 3" daunorubicin-based regimen. Two hundred evaluable patients (98 treated with the mitoxantrone-based regimen and 102 with the daunorubicin-based regimen) were included in the analysis of efficacy. The median age of the patients was 60 years. The induction regimen comprised cytosine arabinoside 100 mg/m2 by infusion daily for 7 days and mitoxantrone 12 mg/m2 or daunorubicin 45 mg/m2 daily for days 1-3. If needed, a second induction course was administered: cytosine arabinoside for 5 days and mitoxantrone or daunorubicin for 2 days. Postremission therapy consisted of two consolidation courses, identical to the second induction course. Sixty-three percent (62 of 98) of patients treated with mitoxantrone achieved complete remission (CR), compared to 53% (54 of 102) treated with daunorubicin. The median time to CR was 35 days in patients treated with mitoxantrone and 43 days for those treated with daunorubicin. Eighty-nine percent (55 of 62) of patients treated with mitoxantrone who entered complete remission achieved CR following one induction course, compared to 68% (37 of 54) of patients treated with daunorubicin who entered CR. The median duration of CR was 240 days in patients treated with mitoxantrone and 198 days in those treated with daunorubicin; the median length of survival was 328 days in patients who received mitoxantrone and 247 days in those who received daunorubicin. The toxicity profiles in patients treated with either of the two regimens were comparable in incidence and in severity. Patients treated with mitoxantrone required fewer median platelet units and were treated with fewer median days of intravenous antibiotics, compared to those who received daunorubicin. Mitoxantrone in combination with cytosine arabinoside is effective in previously untreated ANLL. complete remissions occur more frequently after a single induction course of the mitoxantrone-based regimen, compared to the standard Cancer and Acute Leukemia Group B regimen. This should be explored in further trials.

Adult↗
PubMed1989

Geographic origins of Jewish patients with inflammatory bowel disease.

Ulcerative colitis and Crohn's disease are more common among Jews than among non-Jews. Despite the existence of studies on the prevalence and incidence of inflammatory bowel disease in relation to the continent of residence or origin, there are no studies on the specific countries of origin of Ashkenazi Jewish patients. We report here the first analysis of 233 U.S. Jewish patients by defined world regions and subregions. Using two different sets of controls (a self-referred Jewish population for Tay-Sachs disease carrier detection and a sample of Jewish persons ascertained through unrelated studies from the same hospital as our patients), we found a significant excess of patients of middle European origin relative to those of Polish or Russian origin. These observations suggest that the inflammatory bowel disease gene(s) are more prevalent in the Jewish population that originated in middle Europe than in those from Poland and Russia. These results further suggest that Jewish patients with inflammatory bowel disease probably represent a nonrandom genetically predisposed subset of the Jewish population. This provides further evidence for the genetic contribution to inflammatory bowel disease in general, and to its higher risk in the Jewish population.

Colitis, Ulcerative↗
PubMed1989

Usefulness of a standard battery of laboratory tests in investigating chronic fatigue in adults.

Twenty-two adults with chronic fatigue were studied to determine the clinical usefulness of commonly applied laboratory tests. Subjects with the chief complaint of fatigue persisting for more than one year were followed for an average of seven months at a university family health centre. During this time a group of commonly recommended tests were carried out and the patients had repeated physical examinations. Physical diseases and laboratory abnormalities were few, and patients with abnormal values and active problems were followed until their fatigue resolved or their abnormalities reverted to normal following therapy. The study demonstrated that the presence of an abnormal laboratory result in a fatigued individual does not necessarily indicate the cause of fatigue. A psychiatric history was also performed and patients were tested with the symptom check list 90-R (SCL-90-R), a 90-item psychological symptom check list. Seven patients were receiving psychotherapy when they enrolled in the study. Two additional subjects entered therapy after the start of the study. Results on the symptom check list for the study group were largely abnormal, with a majority scoring in the highest quartile for depression, paranoid ideation and psychoticism. It is concluded that the investigation of patients with fatigue which has lasted for longer than one year should focus on psychological causes. In this group of patients laboratory abnormalities are not useful in guiding evaluation or treatment for their fatigue.

Adult↗