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Biomedical subjects

M Moore

Publications and source records attributed to M Moore.

At least 55 records · Page 3Linked to original sources

Tumour-infiltrating lymphocytes in cervical carcinoma.

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.

Adult

Multicenter phase II trial of brequinar sodium in patients with advanced melanoma.

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.

Adult

Circulatory responses during electroconvulsive therapy. The comparative effects of placebo, esmolol and nitroglycerin.

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.

Adrenergic beta-Antagonists

Third ventricle enlargement and lower heart rate levels in a high-risk sample.

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.

Adolescent

p53 mutations are not selected for in simian virus 40 T-antigen-induced tumors from transgenic mice.

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.

Animals

Perception of alcoholism among Jewish, Moslem and Christian teachers in Israel.

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.

Alcohol Drinking

Israeli Christian, Druze, and Moslem adolescents' attitudes toward magazine alcohol advertisements.

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.

Adolescent

Breastfed infants.

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Breast Feeding

Phase I pharmacokinetic and pharmacodynamic study of a new anthrapyrazole, CI-937 (DUP937).

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.

Adult

Evidence for the effects of HIV antibody counseling and testing on risk behaviors.

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.

Counseling

Local toxicity with subcutaneous methadone. Experience of two centers.

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.

Adult

Alcohol drinking among Moslem and Druze adolescents in Israel in 1990.

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.

Adolescent

Evaluation of a spring-loaded syringe driver for the subcutaneous administration of narcotics.

A simple spring-loaded syringe driver was tested for the subcutaneous administration of narcotic analgesics and antiemetics. With concentrations of 2 to 10 mg/mL of hydromorphone and 10 to 50 mg/mL of morphine, the infusion rate during preclinical testing was 1.01 +/- 0.1 mL/hr (range 0.70-1.2 mL/hr). The rate of infusion was not modified by the concentration of narcotic in solution. Clinical trials were performed with morphine in 17 patients, and with hydromorphone in 11 patients. The duration of the infusion was 21 +/- 11 days. The most frequent reason for discontinuation was death (22 cases). The average duration of the site of infusion was 6.3 +/- 4 days. When used subcutaneously, the rate of infusion of the device was 1 +/- 0.15 mL/hr (range 0.70-1.30 mL/hr). Patients and nurses were satisfied with the simplicity and safety of the device. Cost analysis shows that this device is significantly less expensive than currently available portable infusion devices. We conclude that the Medifuse Pump is an inexpensive, safe and effective device for the subcutaneous infusion of narcotics and antiemetics.

Adult

Structure of problem behaviors in preadolescence.

Earlier research suggests that diverse adolescent problem behaviors, such as substance use, school problems, early sexual intercourse, and delinquency, reflect a single underlying dimension of behavior. Data from an ongoing longitudinal study were used to examine this issue in a previously unexamined sample (N = 426) of preadolescent sixth-grade youth. Ss included boys and girls from diverse socioeconomic and racial/ethnic backgrounds, whose average ages were 11 and 12. By using confirmatory factor analyses to test competing models, multiple factor structures were detected, suggesting that earlier findings supporting a single factor conceptualization may not be generalizable to this age group. Implications of the finding that problem behaviors may be more differentiated in late childhood than in adolescence are discussed.

Antisocial Personality Disorder

Ventilatory function after exposure to various respirable hazards in a population of former coal miners.

The ventilatory function of 406 male former coal miners who had presented at the Cook County Hospital occupational medicine clinic between January 1976 and April 1987 was studied to determine whether subsequent exposure to respiratory hazards after leaving the coal mines adversely affected lung function. The miners were divided into five exposure groups based on their exposure to respirable hazards. These were coal dust only, coal dust plus asbestos dust, coal dust plus silica dust, coal dust plus another respirable hazard and coal dust plus two other respirable dust exposures. Duration of employment in coal mines, race, smoking history, and mean age were not significantly different between the various exposure groups. No significant difference was found in the per cent of predicted forced expiratory volume in one second (FEV1), per cent of predicted forced vital capacity (FVC), and FEV1/FVC when the coal dust only group was compared with each of the other four exposure groups using ANOVA. Among former coal miners who present for a respiratory disability determination, therefore, exposure to respirable hazards subsequent to employment in coal mines is not associated with a statistically significant deterioration in ventilatory function.

Coal Mining