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Biomedical subjects

A Gottlieb

Publications and source records attributed to A Gottlieb.

At least 73 records · Page 4Linked to original sources

The treatment of patients with newly diagnosed poor prognosis acute myelogenous leukaemia: response to treatment and treatment failure.

The failure of poor prognosis patients with newly diagnosed AML to enter remission is usually due to two phenomena: a high mortality rate and resistance of the leukaemia to chemotherapy. We conducted a pilot study of a regimen designed to overcome these two types of treatment failure. Patients were carefully selected for therapy on the basis of their likelihood of surviving. Chemotherapy consisted of high dose cytosine arabinoside (HDaraC) with the doses modified on the basis of patient age so as to reduce the risk of toxicity. Finally, daunorubicin was administered only to those patients for whom HDaraC was not likely to produce sufficient antileukaemia effects to produce a remission. The median patient age was 67 years and 69/88 (78%) patients had a history of preleukaemia and/or toxic exposure. Only 11/84 (13%) patients died during remission induction therapy and 40/84 (48%) entered CR. Patients with only one risk factor had a higher CR rate than those with more than one risk factor (56% v. 30%, P = 0.02) and also had longer durations (222 d v. 113.5 d, P = 0.035). Two types of resistance to chemotherapy were observed: 'classical resistance' (the failure of chemotherapy to produce substantial killing of leukaemia cells) and the rapid regrowth of leukaemia cells subsequent to a level of cytoreduction which otherwise would have been sufficient to produce a CR.

Aged↗

A comparison of three clinic-based AIDS education programs on female adolescents' knowledge, attitudes, and behavior.

Health providers are becoming increasingly aware that adolescents are a population at risk for acquired immune deficiency syndrome (AIDS) and have identified education as essential for prevention. This study evaluates three clinic-based programs designed to determine the effects of education on knowledge and attitudes regarding AIDS and condom acquisition. Seventy-five sexually active females attending adolescent health clinics were randomly assigned to one of three groups: 1) controls (C) receiving no education; 2) education (E) alone consisting of a brief lecture on AIDS: and 3) enhanced education (EE) where the lecture was provided as well as a videotape describing the importance of condom use. All participants completed the AIDS Knowledge Questionnaire-Revised, the AIDS Attitude Survey, a self-report measure of condom use and received a coupon that could be exchanged for free condoms from the hospital pharmacy. A significant effect was found for knowledge, where both E and EE were superior to controls (p less than .001). No statistical differences were noted across groups regarding attitudes or condom acquisition. However, all adolescents in the EE group who reported prior condom use obtained condoms from the pharmacy as compared to the other groups (p less than .05). Our results suggest that educating adolescents in medical settings can improve their knowledge about AIDS. Didactic lectures in combination with videotape presentations on condom use appeared to be the best format for reinforcing an adolescent's existing behavior.

Acquired Immunodeficiency Syndrome↗

MDR1 transcript levels as an indication of resistant disease in acute myelogenous leukaemia.

The expression of the MDR1 gene was studied by Northern blot analysis in leukaemic cell specimens obtained from 74 patients with acute myelogenous leukaemia (AML). No relationship was found between MDR1 RNA levels and FAB type of leukaemia or patient age. Transcript levels tended to be highest in the leukaemic cells of patients with a history of toxic exposure or preleukaemia compared with 'standard risk' patients at diagnosis but the differences were not significant (P = 0.07). Patients whose leukaemic cells contained high MDR1 transcript levels were difficult to induce into remission and, if remission was induced, the remissions were short. Hence high levels of MDR1 expression may explain, at least in part, the ineffectiveness of anthracycline antibiotic containing treatment regimens in some patients with AML.

Adolescent↗

Postsecondary experiences of young adults with severe physical disabilities.

A need exists for follow-up information to determine how well the educational system is meeting the needs of young adults with severe physical disabilities. This study of the postsecondary experiences of 106 graduates of a special school for youth with severe physical disabilities examined the educational, employment, and community adjustment outcomes of these students. Findings suggest that young adults with physical disabilities should cultivate personal and family networks, continue their education, and use vocational rehabilitation agencies. Access to transportation was also found to be a key element in achieving employment and independence.

Adult↗

Disodium clodronate in the treatment of pain due to bone metastases.

Disodium clodronate (dichloromethylene bisphosphonate) a drug belonging to the class of bisphosphonates, inhibits osteoclastic bone resorption and therefore it may be used in the palliative treatment of patients affected by osteolytic bone metastases. The authors have evaluated the activity and tolerability of disodium clodronate in providing pain relief and improving the quality of life in patients with bone metastases, who were not improved by radiotherapy or chemotherapy. Out of 37 patients, 32 could be evaluated for pain relief. Of these, 62.5% had their pains improved by disodium clodronate administration without regard to the type of ongoing analgesic therapy, which had no implications on the outcome of the treatment.

Adult↗

Sodium naproxen versus sodium diclofenac in cancer pain control.

In a single-blind random study, simultaneously carried out by five Pain Therapy and Palliative Care Centres, the analgesic power and side-effects of sodium naproxen (CAS 26159-34-2) and sodium diclofenac (CAS 15307-86-5) by mouth were compared in a group of 100 advanced cancer patients. The patients complained of somatic and/or visceral pain and were treated with non-steroid anti-inflammatories as required. The dose administered amounted to 550 mg every 12 h for sodium naproxen and to 100 mg every 12 h for sodium diclofenac. The study stressed the similar analgesic effect of the two drugs--pain intensity and duration decreased by half in the first week of treatment--and a comparatively low morbidity rate.

Aged↗

Adolescents and AIDS. Female's attitudes and behaviors toward condom purchase and use.

Condom use has been advocated as a method to prevent human immunodeficiency virus (HIV) transmission. Although condoms are not uniformly popular with adolescent males, adolescent females' beliefs about condom use are unclear. To assess the specific health attitudes and behaviors as they relate to condom purchase by adolescents, we surveyed 99 adolescent females between 12 and 19 years of age (50 black, 49 white) who were attending a comprehensive adolescent health clinic. The respondents were from low to middle socioeconomic backgrounds and 85% were sexually active. A 41-item survey was developed and focused on four areas: comfort or embarrassment with menses (EM), basic knowledge of acquired immunodeficiency syndrome (AIDS) (KA); comfort in discussing contraception with partner (CC) and risk of contracting AIDS (AR). Chi-square analyses of the four factors determined that decreased EM was related to increased age (p less than 0.05), sexual activity (p less than 0.05), and CC (p less than 0.05). Older adolescents also demonstrated greater CC (p less than 0.05). Increased KA was related to contraceptive use (p less than 0.02) as well as CC (p less than 0.02). Descriptive analyses showed that 62% of the sample reported that a fear of AIDS had influenced their contraceptive behavior, but only 17% of the females reported purchasing or using a condom to prevent AIDS transmission. These findings suggest that although adolescent females have an awareness about AIDS, their behavior remains unchanged.

Acquired Immunodeficiency Syndrome↗

The role of prostacyclin in the mesenteric traction syndrome during anesthesia for abdominal aortic reconstructive surgery.

Mesenteric traction syndrome consists of sudden tachycardia, hypotension, and cutaneous hyperemia, and frequently occurs during mesenteric traction in patients undergoing abdominal aortic aneurysm (AAA) reconstructive surgery. The etiology and clinical impact of this phenomenon are unknown, but the symptoms suggest a release of vasoactive materials from the mesenteric vascular bed. Thirty-one patients who underwent AAA surgery were studied. Mesenteric traction was accompanied by a decrease in systolic (p = 0.005) and diastolic (p less than 0.05) blood pressures, and in systemic vascular resistance (p less than 0.005), and was accompanied by an increase in heart rate (HR) (p less than 0.005), and cardiac output (p = 0.01). These hemodynamic changes coincided with an increase (p less than 0.001) in plasma concentrations of 6-keto-prostaglandin F1 (6-K-PGF1). No apparent change was found in prostaglandin E2, thromboxane B2, and histamine concentrations. The concentration of 6-K-PGF1 was correlated with diastolic blood pressure (r = -0.52, p less than 0.005) and HR (r = 0.65, p less than 0.001). Cutaneous hyperemia was observed in 58% of the patients. In an additional six patients, who had taken aspirin daily before AAA surgery, no significant changes were observed in the hemodynamic measurements or 6-K-PGF1 concentrations. These data suggest that mesenteric traction syndrome may be mediated at least in part by a selective release of prostacyclin.

6-Ketoprostaglandin F1 alpha↗

T cell antigen receptors in autoimmunity.

Three mAb to variable region determinants of the alpha/beta-chain TCR were used to detect discrete populations of peripheral blood T cells. T cells sharing a TCR determinant defined by such an antibody presumably use the same or similar TCR V or J genes for their alpha- or beta-chains. Thus analysis with these mAb provides a tool to investigate TCR gene usage and expression. Since autoantigen specific T cells may play an important role in initiating autoimmune diseases, TCR were analyzed in different autoimmune diseases and control groups including rheumatoid arthritis, Graves disease, idiopathic thrombocytopenic purpura, psoriasis, SLE, insulin-dependent diabetes mellitus, and in nonautoimmune control diseases and normals. Purified T cells were stained by indirect immunofluorescence with three mAb to TCR variable regions: mAb S511 stains 1.8 +/- 0.9% (mean +/- 2 SD), mAb C37 stains 3.4 +/- 1.5% and mAb OT145 stains from 0 to 6% of T cells from normal donors. Several individuals were identified with expanded subsets of positive T cells. One patient with adult ITP followed during a 12-mo period consistently had elevated percentages of T cells staining with the mAb OT145 (15.9 to 24.5%). These cells were found to be exclusively CD8+. By Southern blotting DNA prepared from these OT145+, CD8+ cells, but not DNA from the patient's OT145- T cells, revealed a clonal rearrangement using a beta-chain C region probe. Thus this patient had a monoclonal expansion of CD8+, OT145+ cells. Hyperexpression of a TCR variable region, as defined by the available mAb, could not be associated with any of the diseases studied. Examination of T cells at the site of autoimmunity, such as T cells from rheumatoid arthritis synovial fluid, revealed normal percentages of cells staining with these mAb. Immunoperoxidase staining of psoriatic lesional skin showed no striking enrichment of T cells bearing one or the other TCR type.

Aged↗

Phase II trial of ifosfamide and mesna in previously treated patients with non-Hodgkin's lymphoma: Cancer and Leukemia Group B Study 8552.

Ifosfamide (1.25 g/m2 intravenously/day x 5) with mesna (20% of the ifosfamide dose x six doses on each day of ifosfamide therapy) was administered to 46 previously treated patients with non-Hodgkin's lymphoma of which 31 were eligible and evaluable. A 29% response rate (9/31) was observed (2 CR and 7 PR) with a median duration of response of 2.5 months. Myelosuppression was dose-limiting. Hemorrhagic cystitis was observed in three patients (10%). Nausea and vomiting was generally mild or moderate. One patient developed transient neurotoxic symptoms with confusion and disorientation. An additional patient developed an anaphylactic-type reaction with shortness of breath and respiratory strider during the fourth course of therapy. Ifosfamide, as a single agent, produces remissions of limited duration in non-Hodgkin's lymphoma in patients in second or third relapse.

Adolescent↗

Production of Biodispersan by Acinetobacter calcoaceticus A2.

Bacterial strains A2 and HE5, isolated by enrichment culture techniques, were shown to produce extracellular, nondialyzable materials which disperse limestone powders in water. These materials are referred to as biodispersans. Strains A2 and HE5 were classified as Acinetobacter calcoaceticus by physiological and genetic tests. An assay for limestone-dispersing activity was developed which is based on the settling time of a standard 10% limestone-in-water mixture. The assay was proportional to biodispersan concentration between 40 and 100 mug/ml. Dispersion was optimum between pH 9 and 12. Phosphate (2 mM) and magnesium (8 mM) ions caused a 50% inhibition of activity. An optimized medium for the production of biodispersan was developed with ethanol as the substrate. Biodispersan was produced only after the bacteria completed their exponential growth phase and continued during the stationary phase, reaching over 4 g of crude biodispersan per liter.

Journal Article↗

Intrathecal papaverine for the prevention of paraplegia after operation on the thoracic or thoracoabdominal aorta.

Eleven patients undergoing operation on the descending or thoracoabdominal aorta were administered papaverine intrathecally in an attempt to protect the spinal cord from ischemic damage. Concurrently, 19 patients, also undergoing operation on the thoracic or thoracoabdominal aorta, were operated on with a variety of conventional techniques, including distal aortic perfusion, but were not given intrathecal papaverine. No signs of early neurologic injury developed in any of the patients in the intrathecal papaverine group, although delayed paraparesis developed in one of the patients (9%; 70% confidence limits = 1% to 28%). On the other hand, eight of 19 patients undergoing operation with conventional techniques had either lower extremity paraparesis or paraplegia postoperatively (42%; 70% confidence limits = 29% to 57%; p = 0.058). Intrathecal papaverine appeared to provide spinal cord protection during thoracic aortic operations, particularly during prolonged periods of aortic cross-clamping. Papaverine was not associated with increased risk and may be superior to other conventionally used modalities. We conclude that continued evaluation of this technique is justified.

Adult↗

Combination trial of subcutaneous interferon alfa-2b and oral cyclophosphamide in favorable histology, non-Hodgkin's lymphoma.

Patients with follicular non-Hodgkin's lymphoma (NHL) respond well to chemotherapy but frequently relapse and progress with conversion to more aggressive histology lymphomas. In a prior Cancer and Leukemia Group B (CALGB) trial, oral cyclophosphamide, given as a single agent, was found to be equivalent to a five-drug regimen in remission induction in patients with follicular NHL who had not received prior chemotherapy. Recently, interferon alfa-2b (Intron A; Schering Plough) has been demonstrated to elicit complete or partial responses in up to 50% of patients with nodular NHL who had received prior chemotherapy. In the current CALGB pilot trial, oral cyclophosphamide (100 mg/m2 daily) combined with interferon alfa-2b (2 X 10(6) IU/m2 s.c. on alternate days) is being evaluated, both in previously treated and untreated patients with stage III or IV follicular NHL, for toxicity, safety and efficacy in remission induction. A total of 68 patients have been entered into this study. Four patients are ineligible on pathology review, and 60 have on-study data currently available. Forty-one (60%) had not received prior chemotherapy and 19 (32%) had previously received some form of chemotherapy. Leukopenia was found to be the single, most common toxicity experienced by all patients. Previously untreated patients experienced leukopenia of less than 2,000 WBC/microliter at a significantly higher rate (53% versus 14%) than a similar patient population receiving oral cyclophosphamide as a single agent in the prior CALGB trial. Leukopenia was found to be promptly reversible, however, by dose suspension or adjustment, and other toxicities were demonstrated to be mild and tolerable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Relationship between decay accelerating factor deficiency, diminished acetylcholinesterase activity, and defective terminal complement pathway restriction in paroxysmal nocturnal hemoglobinuria erythrocytes.

Paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes exhibit abnormalities in decay accelerating factor (DAF), acetylcholinesterase, and resistance to autologous C5b-9 attack. To investigate the nature of the lesion underlying PNH cells, we examined the relationship of these abnormalities to one another. Analyses of DAF in acetylcholinesterase-negative erythrocytes revealed that these two abnormalities involve functionally independent molecules, coincide precisely in the same cell populations, and are similarly expressed in PNH II and more complement-sensitive PNH III erythrocytes. The DAF and acetylcholinesterase deficiencies contrast with the C3b/C4b receptor (CR1) deficit, which is less profound and similarly distributed in complement-insensitive cell populations. Hemolytic studies showed that defective resistance to autologous C5b-9 attack is mediated by another mechanism. Whereas reconstitution of PNH II erythrocytes with DAF completely corrected their complement sensitivity, DAF reconstitution of PNH III erythrocytes restored their ability to circumvent C3b uptake but had no effect on their heightened susceptibility to reactive lysis. Assays of complement-insensitive (PNH I) erythrocytes surviving after reactive lysis disclosed partial DAF and acetylcholinesterase deficits. These findings indicate that the PNH lesion involves multiple membrane components and that PNH I erythrocytes are also abnormal.

Acetylcholinesterase↗

Limited efficacy of a four-day course of high-dose cytosine arabinoside in the treatment of poor-risk patients with acute nonlymphocytic leukemia.

High-dose cytosine arabinoside therapy was administered to 29 patients with poor-prognosis acute nonlymphocytic leukemia. In an attempt to reduce toxicity, therapy was divided into an initial 4-day course of therapy, followed by a 3-day course of the marrow aspirate examined 1 week after the end of treatment contained substantial numbers of leukemic cells. Of the 29 patients, 5 entered complete remission, 2 of them after the initial 4-day course of therapy. The toxicity of split-course therapy was the same as that of conventional 6-day high-dose cytosine arabinoside therapy. This study demonstrates that the modification of high-dose cytosine arabinoside therapy used in this study failed to reduce toxicity and produced a lower remission rate than that obtained with the 6-day course of therapy.

Acute Disease↗