Biomedical subjects
Publications and source records attributed to M Moore.
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In order to identify the optimal configuration of HIV prevention programs, it is necessary to examine different theoretical models of behavior change. Cognitive/decision-making theories of human behavior change are compared to social learning theories vis-a-vis their influence on the structure of service delivery systems. Cognitive/decision-making theories ascribe behavior change to the provision of new information and favor the development of homogeneous interventions providing clients with information about risk behaviors. These interventions are easily standardized across delivery sites and various target populations. Social learning theories view behavior change as a series of stages and recognize the influence of sociocultural variables. They favor multiple heterogeneous interventions in a variety of settings, with the provision of skills training as well as information. Ongoing HIV prevention research indicates that social learning theories provide a more accurate paradigm of human behavior change for the complex behaviors related to HIV risk. Public health agencies must therefore continue to strengthen organizational and referral relationships with community-based organizations that can provide the specialized prevention interventions called for by social learning theory. This will require ongoing collaboration and technical assistance.
In a prospective study of 622 women with breast cancer, those with one to three histologically positive axillary lymph nodes were randomised after mastectomy to receive cyclophosphamide 100 mg/m2 orally on days 1-14, methotrexate 40 mg/m2 intravenously on days 1 and 8, and fluorouracil 600 mg/m2 intravenously on days 1 and 8 every 28 days for six cycles (CMF x six), or for twelve cycles of the same chemotherapy (CMF x 12). Those with > or = four positive nodes were randomised to one of these two groups or to 5000 cGy of postmastectomy regional radiotherapy (RT) followed by six cycles of the same chemotherapy (RT + CMF x six). With about 10 years median follow-up, there was no significant difference in survival or disease-free survival among the three groups. There was evidence of decreased locoregional recurrence in patients with > or = four nodes who received RT + CMF x six (relative risk 0.53, P = 0.067). Multivariate analysis indicated that the presence of > or = four positive nodes (negatively) and the percentage of ideal (full) dose of CMF received (positively) were the strongest factors predictive of survival. This study shows no advantage for 12 over six cycles of CMF chemotherapy in women with breast cancer and positive axillary nodes. There was a suggestion of decreased locoregional recurrence but no improvement in survival with radiotherapy for women with > or = four positive nodes.
Tumour-infiltrating lymphocytes from cervical carcinomas were cultivated in the presence of interleukin-2. The majority of bulk cultures were cytotoxic against K562, Mel 1 and Caski cells. CD8+ cells were the predominant subset in over 50% of cultures, with varying numbers of CD56+ and CD25+ cells. T cell clones were established from six tumour-infiltrating lymphocyte cultures and the majority exhibited non-MHC-restricted cytotoxicity. However, in one case cytotoxicity of several derived clones was limited to the autologous tumour and in another, to the autologous tumour and Caski cells. This study indicates that tumour-infiltrating lymphocytes can be amplified and cloned from cervical carcinoma biopsies in the presence of rIL2. Although the predominant cytolytic function is non-MHC-restricted, low autotumour cytotoxicity can be demonstrated at the clonal level. The nature of the antigen(s) recognised by T cells on autologous cervical carcinoma cells in unknown; the candidacy of human papillomavirus-related products requires investigation.
Seventeen patients with advanced melanoma and no prior exposure to chemotherapy were treated with brequinar sodium as first-line chemotherapy. Brequinar was given at a median weekly dose of 1200 mg/m2 intravenously. In 14 patients evaluable for efficacy, there were no objective responses. The toxicity was moderate. We conclude that, at this dose and schedule, brequinar has no activity in advanced melanoma.
Electroconvulsive therapy is usually accompanied by activation of the autonomic nervous system, which may be harmful in patients with cerebrovascular or ischaemic heart disease. We have compared this haemodynamic response in a series of 82 electroconvulsive treatments randomly assigned to receive either nitroglycerin 3 micrograms.kg-1, esmolol 2 mg.kg-1 or placebo. These drugs were given shortly after the suxamethonium and 2 min before the electroconvulsive therapy in all cases. Heart rate was significantly lower with esmolol 1 min after therapy as was blood pressure (systolic and diastolic). The pulse rate was higher following nitroglycerin than placebo, which in turn was higher than esmolol. The three groups did not differ with regard to seizure duration. The results demonstrate that esmolol is more effective than nitroglycerin in controlling the haemodynamic response to electroconvulsive therapy. With recent emphasis on stabilisation of heart rate in preference to blood pressure in at-risk cardiac patients, our study suggests that, in the doses selected, esmolol is preferred to nitroglycerin to control the heart rate response to electroconvulsive therapy.
Heart rate activity and computed tomographic measures of structural brain abnormalities were evaluated in 32 individuals with a genetic risk for schizophrenia (offspring of schizophrenic mothers). Heart rate activity was assessed in 1962 when the subjects were a mean age of 15.1 years. Diagnostic and computed tomography assessments were conducted in 1980. Compared to individuals with normal third ventricles, individuals with enlarged third ventricles evidenced significantly lower heart rate levels overall and significantly lower heart rate during rest and during the periods preceding conditioning and test for conditioning stimulus trials. These effects were independent of age, psychiatric diagnosis, and abnormalities in other brain regions. Difficulties in interpretation posed by the index of brain abnormality employed and by the 18-year time interval between the heart rate and computed tomography assessments are discussed. Together with prior evidence of a relationship between third ventricle enlargement and reduced electrodermal responsiveness in the same subjects, these findings provide a preliminary indication that enlargement of the third ventricle may involve damage to diencephalic structures involved in autonomic nervous system activity.
Many diverse tumors contain cells that select for mutations at the p53 gene locus. This appears to be the case because the p53 gene product can act as a negative regulator of cell division or a tumor suppressor. These mutations then eliminate this activity of the p53 gene product. The simian virus 40 (SV40) large T antigen binds to p53 and acts as an oncogene to promote cellular transformation and initiate tumors. If the binding of T antigen to the p53 protein inactivated its tumor suppressor activity, there would be no selection pressure for p53 mutants to appear in tumors. To test this idea, transgenic mice that carried and expressed the SV40 large T-antigen gene were created. Expression of the T antigen was directed to the liver, using the albumin promoter, and the choroid plexus, using the SV40 enhancer-promoter. A large number of papillomas (indicated in parentheses) of the choroid plexus (14), hepatocellular carcinomas (5), liver adenomas (10), and tumors of clear-cell foci (5) were examined for mutant and wild-type p53 genes and gene products. In all cases, the tumor extracts contained readily detectable T-antigen-p53 protein complexes. A monoclonal antibody specifically recognizing the wild-type p53 protein (PAb246) reacted with p53 in every tumor extract. A monoclonal antibody specifically recognizing mutant forms of the p53 protein (PAb240) failed to detect p53 antigens in these extracts. Finally, p53 partial cDNAs were sequenced across the regions of common mutations in this gene, and in every case only the wild-type sequence was detected. These results strongly support the hypothesis that T antigen inactivates the wild-type p53 tumor-suppressing activity and there is no need to select for mutations at the p53 locus.
This article describes a survey which investigated perception of alcoholism among Jewish, Moslem and Christian teachers in the north of Israel during the spring of 1991. Data were obtained from a sample of 553 teachers. The teachers were asked to agree or disagree with items associated with the disease concept or with the moral concept of alcoholism. The findings indicate differences in the perception of alcoholism among teachers of different religions, education levels, gender, and drinking practices. No differences were found among teachers of different ages or among those working in different types of schools.
This article summarizes the Christian, Druze, and Moslem part of an Israeli study which was carried out in 1988 in the framework of an international comparative project conducted simultaneously also in Australia and in the USA in order to compare the perception of a set of 64 magazine alcohol advertisements by youth from three nations and various cultural and religious groups within those nations. This study is a breakthrough in the Christian, Druze, and Moslem sectors, since it is the first project in the "alcohol domain" among high school students from those sectors. The article presents the results concerning Christian, Druze, and Moslem adolescents' attitudes toward magazine alcohol advertisements. The results have implications for prevention efforts among adolescents from those three religions.
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We performed a phase I trial of CI-937 (DUP937), an anthrapyrazole, with the following objectives: (a) to determine the maximally tolerated dose in humans; (b) to define the toxicity spectrum of this agent; (c) to describe the pharmacokinetics of the drug; (d) to test a pharmacokinetics based hypothesis of dose escalation; and (e) to relate drug pharmacokinetics to pharmacodynamics. CI-937 was administered as a single bolus injection every 3-4 weeks at doses ranging from 3.6 to 25.2 mg/m2. Thirty-two patients and 57 courses were evaluable for toxicity. Pharmacokinetic analysis was performed in 30 patients on the first course using a sensitive and selective radioimmunoassay. The maximally tolerated dose in patients with no prior therapy was 25.2 mg/m2 and dose-limiting toxicity was neutropenia. Thrombocytopenia, nausea, vomiting, stomatitis, and alopecia were mild. A partial response was recorded in a patient with mesothelioma. The area under the curve increased linearly with dose, and total body clearance of CI-937 was independent of dose. The mean total body clearance was 107 +/- 55.8 ml/min/m2, mean steady state volume of distribution was 492 +/- 469 liters/m2, and terminal half-life was 3.78 +/- 2.86 days. The extended factors of 2 methods of pharmacologically guided dose escalation were intended for use but ultimately were equivalent to that of the modified Fibonacci dose escalation method. Dose and the area under the curve were significant predictors of a percentage change in WBC and neutrophil count in a univariate analysis. Only dose and baseline neutrophil count predicted a percentage change in WBCs in a multifactor analysis. Dose and prior chemotherapy predicted percentage change in neutrophil count in a multifactor analysis. We conclude that the dose-limiting toxicity of CI-937 is neutropenia and that the recommended phase II starting dose is 22 mg/m2.
OBJECTIVE: To review published abstracts, journal articles, and presentations for evidence of the effects of human immunodeficiency virus (HIV) antibody counseling and testing on risk behaviors. Studies reviewed focused on homosexual men, intravenous drug users in treatment programs, pregnant women, and other heterosexuals. DATA SOURCES: Peer-reviewed journals (January 1986 through July 1990) and published abstracts and oral presentations from the second (1986) through the sixth (1990) International Conferences on AIDS. STUDY SELECTION: We identified 66 studies that included data on the behavioral effects of HIV antibody counseling and testing. By consensus of the authors, 16 of these were excluded because of small sample size or inadequate study design. DATA EXTRACTION: Studies were assessed by the authors according to methodological strength (sample selection, inclusion of appropriate comparison groups, and inclusion of statistical tests of significance). DATA SYNTHESIS: All longitudinal studies of homosexual men reported reductions in risky behavior among both tested and untested men, and a few reported greater decreases among seropositive men than among seronegative men and those untested or unaware of their serostatus. For intravenous drug users in treatment, we found reductions in intravenous drug use and sexual risk behaviors regardless of counseling and testing experience. We found little evidence for the impact of counseling and testing on pregnancy and/or pregnancy termination rates for either seropositive or seronegative high-risk women. We noted substantial risk reduction among heterosexual couples with one infected partner. Findings among other heterosexuals at increased risk were scanty and mixed. CONCLUSIONS: Further studies should specifically address the behavioral consequences of counseling and testing in various settings.
We report on 8 patients treated with subcutaneous methadone for cancer-related pain at 2 institutions. The success of other subcutaneous agents for pain control has been well demonstrated. It was felt that methadone would be useful due to its low cost. Unfortunately, 7 of the 8 patients experienced adverse reactions at the subcutaneous sites requiring cessation of subcutaneous methadone.
This article describes the Moslem and Druze parts of a survey conducted in the north of Israel during spring 1990 in order to investigate alcohol drinking habits of Moslem, Druze and Jewish high school students and to draw implications for prevention efforts. Of a general sample of 2763 students, 932 Moslem and 215 Druze adolescents were drawn from junior and senior high schools in a Druze village, several Moslem villages, an Arab town, and a mixed Arab-Jewish town. This is the first epidemiological study among students from those sectors in Israel. Involvement with alcohol was greatest among Druze males, lower by Moslem males from an Arab town and Moslem villages, and lowest by Moslem students in a mixed Arab-Jewish town. Druze students reported a higher rate of father's drinking than Moslem students did. Prevention efforts among these populations are discussed.