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Biomedical subjects

T L Bush

Publications and source records attributed to T L Bush.

At least 91 records · Page 5Linked to original sources
PubMed1989

Bis(benzyl)polyamine analogs inhibit the growth of chloroquine-resistant human malaria parasites (Plasmodium falciparum) in vitro and in combination with alpha-difluoromethylornithine cure murine malaria.

A number of bis(benzyl)polyamine analogs were found to be potent inhibitors of both chloroquine-resistant and chloroquine-sensitive strains of the human malaria parasite Plasmodium falciparum in vitro (IC50 values = 0.2-14 microM). Administration of one of the compounds, MDL 27695, which is N,N'-bis(3-[(phenylmethyl)amino]propyl)-1,7-diaminoheptane (C6H5CH2NH(CH2)3NH(CH2)7NH(CH2)3NHCH2C6H5), at 10-15 mg/kg i.p. three times per day for 3 days in combination with 2% alpha-difluoromethylornithine (DFMO; eflornithine) in drinking water effected cures of 47/54 mice infected with Plasmodium berghei. Cured mice were found to be immune upon rechallenge with the same P. berghei strain 4 months after the initial infection and drug-induced cure. MDL 27695 rapidly inhibited the incorporation of [3H]hypoxanthine into P. falciparum RNA and DNA, whereas the incorporation of [3H]isoleucine was not affected until much later. We conclude, therefore, that the major cytotoxic event may be direct binding of MDL 27695 to DNA with subsequent disruption of macromolecular biosynthesis and cell death. These compounds offer a lead in the search for new agents for chemotherapy of malaria.

Animals↗
PubMed1989

Self-report and medical record report agreement of selected medical conditions in the elderly.

This study assessed agreement between self- and medical record report of medical conditions in an elderly population. Medical charts of 120 participants in a screening program were abstracted, and the questionnaire report of eight major conditions was compared with the medical record. There was substantial or moderate agreement between self-report and medical record report for each condition, although strength of agreement varied by condition. Self-report by elderly individuals compares favorably with medical record report of medical conditions.

Aged↗
PubMed1988

Benefits and risks of menopausal estrogen and/or progestin hormone use.

Current evidence is reviewed here on risks and benefits of estrogen and progestin use by peri- and postmenopausal women in relation to the following conditions: endometrial cancer, breast cancer, osteoporosis, and coronary artery disease (CAD). On balance, estrogen therapy appears to be beneficial for menopausal women, as it probably reduces the risks of CAD and osteoporosis, two of the major causes of mortality and morbidity. Although unopposed estrogen therapy increases the risk of endometrial cancer, that cancer is relatively rare and is not fatal in the vast majority of cases associated with estrogen use. Definitive conclusions about the relation of menopausal estrogens to breast cancer cannot be drawn due to inconsistent evidence to date. Although evidence from randomized controlled trials is lacking, biochemical and clinical evidence suggest that progestin supplementation is associated with a reduction in endometrial cancer risk in women taking menopausal estrogens. Progestin supplementation also may augment the beneficial effects of estrogens in providing protection against osteoporosis, although this effect is not yet well established. There is little direct evidence bearing on the relation of menopausal progestins to breast cancer. Although studies of CAD per se are lacking at present, progestins probably unfavorably alter lipoprotein profiles, thereby increasing a user's risk of CAD. Given the relatively high incidence and mortality of CAD in postmenopausal women, any negative effects on CAD risk could potentially counterbalance beneficial effects on other causes. We conclude that estrogen replacement therapy is of potential benefit to postmenopausal women, but that the question of progestin supplementation requires further study, particularly for CAD risk.

Breast Neoplasms↗
PubMed1988

Physical activity and fracture risk in a free-living elderly cohort.

A prospective study to determine if regular leisure-time physical activity (including recreational walking) is associated with fracture risk was conducted in a large cohort (N = 3110) of free-living elderly men and women in the retirement community of Dunedin, Florida. Sixty-three percent of the cohort was female, all were white, and the average age was 73.0 years +/- 5.3 (SD). Participants in regular physical activity at baseline had a reduced risk of fracture; the risk ratio (RR) of fracture for men and women, respectively, was RR = 0.41, 95% CI = 0.17 to 1.01 and RR = 0.76, 95% CI = 0.50 to 1.15. Walking at least one mile 3 times/week appeared to offer a protective effect for both sexes. After controlling for potentially confounding variables including body mass and selected health conditions, the RR for regular physical activity on fracture incidence in men and women remained essentially unchanged. We conclude that regular physical activity such as walking may protect against fracture in older persons.

Aged↗
PubMed1988

Morbidity as a focus of preventive health care in the elderly.

The broad spectrum of preventive health concerns in the elderly ranges from incident disease to prevalent disease to the effect (sequelae) of disease. A major component of the burden of illness for the elderly derives from prevalent chronic disease. For a substantial impact on this burden, unique preventive health care strategies specific to the elderly need to be clearly formulated and tested. These strategies must include as a goal the prevention of disability and the maintenance of functioning. Current recommendations for periodic health examinations and for preventive health care for the elderly include only minimal components for a geriatric preventive health care approach. The specific content and impact of a full geriatric strategy is yet to be defined. A comprehensive geriatric periodic health examination will ultimately be based on epidemiologic definitions of the issues regarding risk factors, modifiers, and incident and prevalent disease as described above, melded with improved understanding of 1) the dynamics or models of illness in the elderly, 2) meaningful and important outcomes, 3) the points before which intervention will be most effective, and 4) further definition of the problems that contribute most to the burden of illness across the elderly population. The goals of prevention focused on prevalent disease will include attenuating the progression of morbidity, the development of disability, and the incidence of superimposed acute illness and injuries, and maximizing functional autonomy and quality of life in older persons. To accomplish these goals, epidemiology has major contributions to make in understanding the illness burden of an aging population, including 1) defining risk factors and effect modifiers for, and natural history of, disease and associated disability in older persons, 2) defining outcomes meaningful to older persons which express the burden of illness, and 3) identifying critical points before which intervention is efficacious in preventing disability.

Aged↗
PubMed1988

Cholesterol, lipoproteins, and coronary heart disease in women.

In the United States, coronary heart disease is the major cause of death and disability in women and in men. Despite this, little is known about the risk factors, including cholesterol and lipoprotein concentrations, for coronary disease in women. In this paper we review the determinants of cholesterol and lipoprotein concentrations in women, assess whether values for total cholesterol and lipoproteins (HDL and LDL) are associated with the occurrence of coronary heart disease in women, and evaluate the evidence that suggests that modifying the concentrations of lipids in women is associated with changing the risk of coronary disease. Besides genetic determinants, dietary cholesterol, dietary fat, total caloric intake, alcohol consumption, cigarette smoking, and physical activity are known to influence concentrations of lipids in women. Some of the strongest determinants of cholesterol and lipoprotein concentrations in women are sex hormones, including estrogen and progestin. Exogenous use of both of these hormones markedly influences HDL and LDL cholesterol; additional evidence suggests that endogenous sex hormones also influence lipid and lipoprotein concentrations. The few studies that have examined the association of total cholesterol with coronary heart disease occurrence and mortality in women have consistently shown that (a) women have much lower rates of coronary heart disease than men at the same values for cholesterol, and (b) clearly elevated risk for coronary heart disease in women is evident only at relatively high values of total cholesterol (i.e., greater than 260 mg/dL). There also appears to be an age effect, with total cholesterol concentrations being more predictive in older than in younger women.

Adult↗
PubMed1987

Cardiovascular mortality and noncontraceptive use of estrogen in women: results from the Lipid Research Clinics Program Follow-up Study.

A cohort of 2270 white women, aged 40-69 years at baseline, were followed for an average of 8.5 years in the Lipid Research Clinics Program Follow-up Study. There were 44 deaths due to cardiovascular disease among the 1677 nonusers of estrogens and six cardiovascular disease deaths among the 593 estrogen users. The age-adjusted relative risk (RR) of cardiovascular disease deaths in users compared with nonusers was 0.34 (95% confidence limits 0.12 to 0.81). After multivariable adjustment for potential confounding factors (age, blood pressure, and smoking), the estimated RR for estrogen use was 0.37 (95% confidence limits 0.16 to 0.88). Analyses were done to explore whether these results could be due to selection bias for estrogen use. However, the prevalence of cardiovascular disease at baseline was slightly higher in estrogen users (12%) than in nonusers (10%); furthermore, the exclusion of all women with prevalent cardiovascular disease at baseline did not alter the apparent protective effect of estrogen use on cardiovascular disease mortality (RR = 0.42, 95% confidence limits 0.13 to 1.10). Additional analyses examining the complex association between estrogen use, lipoprotein levels, and cardiovascular disease mortality suggest that the protective effect of estrogen is substantially mediated through increased high-density lipoprotein levels.

Adult↗
PubMed1986

The adverse effects of hormonal therapy.

Estrogen therapy must be cycled with progestin therapy in women with intact uteri in order to prevent uterine cancer. However, these women cannot be expected to benefit (with regard to cardiovascular disease) from any estrogen-induced changes in the lipoprotein profile, as progestins will either negate or overwhelm any estrogen effects. However, such women will definitely benefit from estrogen's effects with regard to menopausal symptoms and bone loss. These clearly beneficial effects of estrogen-progestin therapy are not outweighed by any known risks. However, in women without uteri (approximately 30 per cent of women), unopposed estrogen therapy in the menopause may protect against cardiovascular disease, as well as have beneficial effects on bone metabolism and menopausal symptoms. In this special case, the beneficial effects of unopposed estrogen therapy clearly outweigh any known risk.

Adult↗
PubMed1985

Noncontraceptive estrogen use and cardiovascular disease.

To summarize, estrogens have powerful effects on certain biologic parameters, the alteration of which could influence cardiovascular disease risk. Estrogens have long been known to influence lipid and lipoprotein levels by decreasing LDL (the atherogenic lipoprotein) and by increasing HDL (the protective lipoprotein). THese lipid alterations could favorably influence the risk of cardiovascular disease. Estrogens also temporarily increase glucose intolerance and lower fasting glucose levels; although the former event could adversely affect cardiovascular disease risk, the clinical significance of increased glucose intolerance with low fasting levels has not been determined. There is no consistent evidence that menopausal estrogens adversely affect coagulation or blood pressure levels, although both of these parameters could be affected in selected individuals. Overall, the estrogenic effects on lipid/lipoprotein levels appear to be the most consistent and the most powerful; given this assumption, estrogens should protect against cardiovascular disease. There is another interpretation of the biologic effect of estrogens on cardiovascular risk. It is possible that estrogens may increase the risk of a thromboembolic event due to an adverse influence on coagulation parameters and, at the same time, decrease the risk of an atherogenic event (via favorably altered lipid/lipoprotein levels). This proposed dual action of estrogens may explain the apparently conflicting results of increased risks of thromboembolism and decreased risks of atherosclerosis or myocardial infarction in men treated with high doses of estrogen (36, 196, 197). In women, there is some suggestion that (low-dose) postmenopausal estrogens may increase the risk of thromboembolism (79, 204), although the majority of studies report no such increase. The difference in risk of thromboembolism between men and women using estrogens may be due to several factors. First, the dose (potency) of the estrogen used by men is usually higher than that used by postmenopausal women, and the risk of estrogen-induced thrombus formation may be dose-dependent. Second, men tend to have more atherosclerotic lesions than women and thus would have more substrate available for thrombus formation. (This hypothesis is supported by the observation that the increased risk of thromboembolism was evident in men using estrogens for the secondary prevention of cardiovascular disease.) Indirect evidence supporting the hypothesis that endogenous estrogen levels are protective against cardiovascular disease is most consistent for women.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1984

Direct depletion and purification of monoclonal antibody defined cells from unfractionated human mononuclear leukocytes using antibody coated polystyrene Petri dishes.

Human peripheral blood mononuclear leukocytes were depleted or enriched in various monoclonal antibody-defined subsets using a simplification of the indirect " panning " technique. Unfractionated mononuclear leukocytes (MNL) were sensitized with appropriate dilutions of monoclonal antibodies to human Lyt3 , OKT4 and OKT8 antigens, and to a monocyte-myeloid line antigen. The sensitized cells were then placed on polystyrene Petri dishes coated with goat antimouse IgG to obtain a population of cells depleted and a population of cells enriched in each cell type. Direct separation of surface immunoglobulin-bearing cells was similarly achieved by coating the Petri dish with goat antihuman immunoglobulins. Results showed that MNL could be depleted to greater than 95% purity with these methods and that positively selected adherent cells could be enriched to at least 85% purity. The relative proportions of MNL subpopulations in various sorted cell populations is reported. Cells obtained by panning are functionally intact. As compared to complement lysis both marker positive and marker negative cells can be obtained and the technique requires less technical expertise than using fluorescence activated cell sorting. The modification reported here is simpler and less time consuming for human T cell subpopulation separations than previously reported panning methods since an initial sheep erythrocyte rosetting step was not used.

Animals↗
PubMed1983

Estrogen use and all-cause mortality. Preliminary results from the Lipid Research Clinics Program Follow-Up Study.

The association of exogenous estrogen use and hysterectomy status with all-cause mortality was examined in 2,269 white women, aged 40 to 69 years, who had been followed up for an average of 5.6 years in the Lipid Research Clinics Program Follow-up Study. A total of 72 deaths occurred during this period. The relative risk of death in estrogen users compared with nonusers was 0.54 in gynecologically intact women, 0.34 in hysterectomized women, and 0.12 in bilaterally oophorectomized women. The risk of death in estrogen users, irrespective of hysterectomy status, was 0.37 times that in nonusers (3.4/1,000 v 9.3/1,000). The significant negative association of estrogen use with mortality persisted after multivariate adjustment for confounding factors. Hysterectomy status alone was not a significant predictor of death. Some, but not all, of the lower risk of mortality in estrogen users can be accounted for by increased levels of high-density lipoprotein cholesterol.

Adult↗
PubMed1983

Smoking and cardiovascular mortality in women.

Smoking status and sociodemographic characteristics were recorded for 23,572 white women 25-74 years of age in a private census of Washington County, Maryland, done in 1963. Deaths from all causes, from total and sudden arteriosclerotic heart disease, and with stroke were recorded for the next 12 years. Smoking-specific mortality rates for women aged 25-44, 45-64, and 65-74 years at entry were calculated after adjustment for the effects of marital status, education, housing quality, and frequency of church attendance. Among women in the 65-74-year age group, smoking was not related to mortality. Among women in the two younger age groups, the risks of dying from any cause and from arteriosclerotic heart disease (total and sudden) were positively associated with cigarette smoking. For all arteriosclerotic heart disease deaths, the relative risks associated with smoking more than 20 cigarettes a day were 3.6 and 2.2 for women aged 25-44 and 45-64, respectively; for sudden deaths from arteriosclerotic heart disease, the relative risks were 6.5 and 2.7. The risk of dying with stroke was not associated with cigarette smoking.

Adult↗
PubMed1983

The potential role of respiratory therapy equipment in cross infection. A study using a canine model for pneumonia.

Experimental Pseudomonas aeruginosa pneumonia was induced in 8 dogs that had radiation-induced leukopenia. Three dogs were supported by mechanical ventilation (MV), 3 received continuous heated aerosol therapy (CHAT), and 2 did not receive respiratory therapy and served as control animals. The animals were studied in a carefully controlled environment until they succumbed to infection or they were killed at 24 h. An air sampler was used to collect exhaled P. aeruginosa aerosols at distances as far as 15 feet from the dogs at multiple time intervals. Water condensate in the tubing of MV and CHAT equipment was collected and cultured at the same intervals. Results showed that all dogs had multilobar P. aeruginosa pneumonia at necropsy. Control dogs did not exhale aerosols containing P. aeruginosa. Animals that were supported by MV, exhaled contaminated aerosols, but organisms could not be recovered at distances greater than 2 feet. In contrast, aerosols containing P. aeruginosa were recovered at distances as far as 15 feet from the animals receiving CHAT. Furthermore, as much as 1L of water condensate was collected in a 24-h period from tubing associated with MV and CHAT. Although the nebulizers and humidifiers remained sterile, tubing condensate was contaminated with as much as 10(7) colony-forming units per ml of P. aeruginosa in 5 of the 6 animals receiving either MV or CHAT. Contamination of tubing by P. aeruginosa was present as early as 8 to 12 h. This study identifies potential sources for cross infection through an airborne route for CHAT or from direct contact with contaminated tubing.

Aerosols↗
PubMedDate not supplied

Media coverage of women's health issues: is there a bias in the reporting of an association between hormone replacement therapy and breast cancer?

Media coverage of scientific research plays a major role in shaping public opinion and influencing medical practice. When an association is controversial, such as with hormone replacement therapy (HRT) and breast cancer, it is important that a balanced picture of the scientific literature be reported. The objective of this study was to assess whether scientific publications that do and do not support an HRT/breast cancer association were cited in the media in proportions similar to those with which they appear in the scientific literature. Scientific publications reporting on the HRT/breast cancer association published from January 1, 1995, to June 30, 2000, were identified through a systematic Medline search. Media reports from newspapers, magazines, television, and radio that reported on HRT and breast cancer were retrieved from an online database. Investigators independently recorded characteristics of the scientific publications and media reports. A total of 32 scientific publications were identified: 20 (62.5%) concluded there was an increased risk of breast cancer associated with HRT (positive publications), and 12 (37.5%) concluded there was no evidence for an association (null publications). Nearly half (47%) of the scientific publications were not cited by the media. There were 203 media citations of scientific publications: 82% were of positive publications and 18% were of null publications, representing a significant excess of citations of positive publications (p < 0.01). Media coverage of this controversial issue is based on a limited sample of the scientific publications. Moreover, the excess of media citations for positive scientific publications suggests a bias against null scientific publications.

Bias↗
PubMedDate not supplied

Response of human colon and prostate tumor xenografts to (E)-2'-deoxy-2'-(fluoromethylene) cytidine, an inhibitor of ribonucleotide reductase.

Daily oral or intravenous administration of the ribonucleoside diphosphate reductase inhibitor, (E)-2'-deoxy-2'-(fluoromethylene)cytidine (MDL 101,731), to nude mice caused rapid regression of colon and prostate xenografts. Studies were performed to optimize dosing schedule and route of administration. MDL 101,731 was tested against colon (HT-29) and prostate (PC-3) xenografts using twice weekly oral and intravenous administration. PC-3 tumors regressed almost completely with doses of 20 mg/kg. HT-29 xenografts regressed during intravenous administration of 100 mg/kg MDL 101,731, whereas oral administration was less effective. Based on these data it seems that MDL 101,731 is effective when administered intravenously, twice weekly and is an excellent candidate for clinical development against solid tumors.

Animals↗