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T L Bush

Publications and source records attributed to T L Bush.

At least 37 records · Page 2Linked to original sources
PubMed1998

Does comorbid disease interact with cancer? An epidemiologic analysis of mortality in a cohort of elderly breast cancer patients.

BACKGROUND: Although widely believed that co-occurring chronic diseases in elderly persons do not act independently in causing death, there has been little empirical research assessing prognostic interrelationships between comorbidities. METHODS: Nonconcurrent prospective follow-up of 3,549 Virginia-resident elderly women diagnosed with a first breast cancer and 2,114 elderly women with no breast cancer history admitted to Virginia hospitals with principal diagnoses of genital prolapse during 1986-1988 was conducted through linkage of cancer registry and Medicare administrative records. Aggregate comorbidity was measured from Medicare claims via the Charlson comorbidity index (CCI). Mortality rates and relative risks were estimated for the breast cancer and non-breast-cancer groups stratified by the presence and level of comorbidity. Proportional hazards models were used to estimate Rothman's synergy index (S) measure of additive interaction. RESULTS: Over full follow-up, the excess mortality rate for women with breast cancer and other comorbidity was 17% greater than expected under the null hypothesis that risks were additive and independent (S = 1.17, p = .12). Stratified analyses revealed a pattern of S estimates across cancer stage subgroups that was biologically sensible, but this pattern was not supported by strong statistical evidence. CONCLUSIONS: This study provides the first empirical estimates of statistical interaction between breast cancer and other chronic comorbidity. S index values tended to be small, but these small effects would translate into substantial numbers of deaths attributable to interaction between cancer and comorbidity. Interactions between breast cancer and comorbid disease should be explored further in large studies that can estimate these effects with increased precision.

Aged↗
PubMed1998

Effect of postmenopausal hormone therapy on glucose and insulin concentrations. PEPI Investigators. Postmenopausal Estrogen/Progestin Interventions.

OBJECTIVE: To characterize the long-term impact of four hormone therapy regimens on insulin and glucose concentrations measured during a standard oral glucose tolerance test. RESEARCH DESIGN AND METHODS: The Postmenopausal Estrogen/Progestin Intervention Study was a 3-year placebo-controlled randomized trial to assess effects of four hormone regimens on cardiovascular risk factors. This efficacy analysis describes glucose and insulin concentrations from 788 adherent women at baseline and at 1 and 3 years' postrandomization. RESULTS: When compared with women taking placebo, those taking conjugated equine estrogen (CEE) at 0.625 mg/day with or without a progestational agent had mean fasting insulin levels that were 16.1% lower, mean fasting glucose levels 2.2 mg/dl lower, and mean 2-h glucose levels 6.4 mg/dl higher (each nominal P < 0.05). No significant differences were apparent between women taking CEE only versus the three progestin regimens: medroxyprogesterone acetate (MPA) at 2.5 mg daily (continuous MPA), MPA at 10 mg on days 1-12 (cyclical MPA), and micronized progesterone (MP) (cyclical) at 200 mg on days 1-12. The impact of hormone therapy on insulin and glucose depended on baseline levels of fasting insulin and 1-h glucose (P < 0.05). However, the treatment effects on carbohydrate metabolism appeared to be consistent across participant subgroups formed by lifestyle, clinical, and demographic characteristics. CONCLUSIONS: Oral hormone therapy involving 0.625 mg/day of CEE may modestly decrease fasting levels of insulin and glucose. Postchallenge glucose concentrations are increased, however, which may indicate delayed glucose clearance.

Blood Glucose↗
PubMed1997

Comorbidity measurement in elderly female breast cancer patients with administrative and medical records data.

The inter-rater reliability, cross-source (Medicare claims versus medical record) agreement, and ability to predict all-cause mortality of three aggregate comorbidity indices were evaluated in a group of 404 elderly, incident breast cancer cases identified from the Virginia Cancer Registry and linked to Medicare administrative data files. Comorbidity was based on both medical records and Medicare claims data using indices from Charlson et al (1987), Satariano and Ragland (1994), and Kaplan and Feinstein (1974). Inter-rater agreement was good for all indices (kappas > or = 0.80). Agreement between comorbidity indices measured by claims and medical records was considerably poorer (kappas between 0.30 and 0.40). However, claims-based and medical records-based comorbidity indices were similarly associated with mortality. For the Charlson index, the index best predicting survival, the adjusted relative risk for an increase from a lower to higher comorbidity category was 1.48 (95% confidence interval 1.23, 1.78) based on medical records compared to 1.53 (95% confidence interval 1.23, 1.93) based on Medicare claims. The claims-based Charlson index score still appeared to be associated with survival (relative risk = 1.30; 95% confidence interval = 1.00, 1.70) after controlling for the medical records-based score. This suggests that both comorbidity data sources add valuable prognostic information and, conversely, that the use of either source alone will result in some misclassification of comorbidity.

Aged↗
PubMed1997

Decreased vascular endothelial growth factor expression associated with tumor regression induced by (E)-2'-deoxy-2'-(fluoromethylene)cytidine (MDL 101,731).

The effect of the antitumor drug MDL 101,731 [(E)-2'-deoxy-2'-(fluoromethylene)cytidine] on tumor growth and on steady-state vascular endothelial growth factor (VEGF) mRNA levels in MDA-MB-231, PC-3, MCF-7, and HT-29 human tumor xenografts grown in nude mice was examined, using quantitative in situ hybridization. MDL 101,731 caused regression of MDA-MB-231 and PC-3 tumor xenografts, but only inhibition of growth (without regression) of MCF-7 xenografts. The drug caused inhibition of growth of HT-29 xenografts at low doses, and regression at high doses. When treatment with MDL 101,731 led to tumor regression, VEGF mRNA levels were decreased. When treatment led only to inhibition of growth, there was no significant change in VEGF mRNA. Further examination of the tumor xenografts revealed that elevated VEGF mRNA was associated with hypoxic zones surrounding areas of necrosis in the tumors, and that the drop in VEGF mRNA observed in tumors from mice treated with MDL 101,731 correlated with a loss of zones of necrosis. In contrast, treatment with cisplatin led to either an increase (PC-3) or no change (MDA-MB-231) in VEGF mRNA levels, and no loss of necrotic zones. Quantitative analysis of changes in VEGF mRNA levels was supported by immunohistochemical analysis of VEGF protein in the same tumor specimens. In vitro, MDL 101,731 was a potent inhibitor of VEGF secretion in cells exposed to hypoxia, whereas there was no effect of cisplatin on VEGF secretion by three of the four cell lines tested. These findings suggest that inhibition of VEGF expression by MDL 101,731 may distinguish this compound from other classes of cytotoxic agents, such as cisplatin.

Animals↗
PubMed1996

In vitro and in vivo inhibition of glioblastoma and neuroblastoma with MDL101731, a novel ribonucleoside diphosphate reductase inhibitor.

We examined the effects of MDL101731, a novel ribonucleoside reductase inhibitor, against human glioblastomas and neuroblastoma, both in vitro and in xenograft models, to determine its activity against malignant brain tumors. MDL101731 produced a concentration-dependent inhibition of both glioblastoma cell lines (HS683 and J889H) and neuroblastoma (SK-N-MC) in nanomolar concentrations (IC50, 30-90 nM). s.c. xenografts of human glioblastoma (D54) in athymic mice increased to five times their initial volume at a median of 7.4 days in control animals, while tumor regression occurred in 12 of 12 animals treated with MDL101731 (100 mg/kg, i.p., two times/week) during 22 days of treatment (P < 0.0001). Intracerebral implants of D54 carried a median survival of 20 days in control animals, whereas animals receiving MDL101731 (100 mg/kg, i.p., two times/week, days 10-35) had a median survival of 46.5 days (P < 0.0001). Intracerebral xenografts of SK-N-MC in athymic mice resulted in a median survival of 23 days in control animals and 26 days in animals treated with carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea 20 mg/kg/week, i.v. x 2; difference not significant). There was 90% survival in animals treated with MDL101731 (200 mg/kg, i.v., two times/week, days 7-35) up to 90 days after implant. These studies indicate that MDL101731 has potent antiproliferative activity against human malignant brain tumors.

Animals↗
PubMed1996

Evidence for primary and secondary prevention of coronary artery disease in women taking oestrogen replacement therapy.

The increasing use of oestrogen replacement therapy in women has focussed attention on the cardioprotective properties it has demonstrated. Historically, it has been shown that women enjoy a certain protection from heart disease, a phenomenon, however, which has not been studied extensively. Women at every age have less coronary artery disease (CAD) than men, even when various risk factors are accounted for, although the presence of diabetes carries equal mortality for both sexes. However, women who do develop CAD have a greater risk of mortality than men with CAD. Other gender differences include a later age of onset of CAD for women, and a difference in the type of atherosclerotic lesions developed. Most striking is the fact that, in women, high-density lipoprotein (HDL) seems to be a more potent predictor of major cardiovascular events than low-density lipoprotein (LDL), or total cholesterol. The Postmenopausal Oestrogen and Progesterone Interventions (PEPI) Trial looked at changes in HDL, fibrinogen, blood pressure and serum insulin resulting from oestrogen use. Four regimens were compared against placebo in 875 women. The results showed that HDL was increased significantly, LDL decreased significantly, fibrinogen levels decreased significantly, and blood pressure and serum insulin levels were essentially unaffected by oestrogen and oestrogen/progestin interactions. The Heart and Oestrogen/Progestin Replacement (HERS) Study, currently underway, is a secondary prevention trial testing the protective effect of hormone therapy in women with documented CAD. This trial may definitively answer the question of whether hormones protect against CAD. After HERS, it may be unethical to continue conducting placebo-controlled trials in a therapy that has such documented cardioprotective benefit.

Coronary Disease↗
PubMed1995

Serum gonadotropins and steroid hormones and the development of ovarian cancer.

OBJECTIVE: To prospectively examine the association between endogenous hormones and development of ovarian cancer. DESIGN: Nested case-control study. SETTING: A population-based serum bank in Washington County, Maryland. PARTICIPANTS: Serum samples were collected in 1974 from 20305 county residents and stored at -70 degrees C. From 1975 through 1989, a total of 31 cases of ovarian cancer were identified in women who were not taking hormones at the time of blood collection. These cases were matched to 62 controls on age, menopausal status, and, for premenopausal women, number of days from the beginning of the last menstrual period. MAIN OUTCOME MEASURE: Prediagnostic endogenous hormone levels of cases and controls were compared. RESULTS: Mean follicle-stimulating hormone levels were lower among cases (43.3 IU/L) compared with controls (54.4 IU/L) (P = .04), and increasing levels were associated with significantly lower risk (P for trend = .01), particularly among postmenopausal women. Luteinizing hormone levels were 9% lower among cases than controls, but the difference was not statistically significant (P = .39). Compared with controls, cases had higher androstenedione levels (4.5 nmol/L vs 3.3 nmol; P = .03) and higher dehydroepiandrosterone (DHEA) levels (15.9 nmol/L vs 9.7 nmol/L; P = .02). The risk of ovarian cancer increased with higher levels of androstenedione and DHEA sulfate (P for trend = .008 and .11, respectively). These associations were not materially different between premenopausal and postmenopausal women. CONCLUSION: The results suggest that women with low serum gonadotropin levels or high androgen levels have an increased risk of ovarian cancer. These findings do not support the hypothesis that pituitary gonadotropins increase the risk of ovarian cancer. Replication of the study in other populations is highly desirable.

Adult↗
PubMed1995

Rationale, design, and conduct of the PEPI Trial. Postmenopausal Estrogen/Progestin Interventions.

There is growing and consistent evidence that estrogen use in postmenopausal women is associated with a substantial reduction in the occurrence of cardiovascular disease. However, remarkably little is known about the biological mechanisms by which estrogen therapy may influence risk. Even less information is available on the cardiovascular effects of combined estrogen-progestin use. PEPI was not designed to test whether estrogen and estrogen-progestin therapy is efficacious in the prevention of cardiovascular disease, as a much larger trial with clinical disease outcomes is needed to answer that question. However, PEPI will provide critical evidence regarding the potential effectiveness of the various estrogen and estrogen/progestin regimens ni altering risk factors for cardiovascular disease in women. Detailed information on factors such as adherence, side effects, and general patient acceptability will also be ascertained. The main results from PEPI will provide the scientific community with information on the basic actions of estrogen and estrogen/progestin therapy on four biological systems believed to be causally associated with cardiovascular disease occurrence. Further, since the trial is designed to continue for 3 years, PEPI will be able to provide information on longer term as well as short-term effects on these systems. Finally, the results from PEPI should enable women and their physicians to select an optimal hormonal regimen, i.e., one that is acceptable, safe, and provides the most beneficial and least deleterious changes in cardiovascular and other risk factors.

Bone Density↗
PubMed1995

Measurement of mRNA levels in tumor xenografts with quantitative autoradiography and in situ hybridization.

In situ methodologies allow qualitative and semi-quantitative analysis of spatial gene expression in whole organisms or tissues. We have applied quantitative autoradiography to in situ hybridizations of sections from human breast tumor xenografts to measure mRNA levels for ornithine decarboxylase, estrogen receptor, transforming growth factor alpha, and glyceraldehyde-3-phosphate dehydrogenase. Comparisons of control and tamoxifen-treated animals show significant decreases in MCF-7 tumor estrogen receptor mRNA levels in the drug-treated animals. Combining quantitative autoradiography with in situ hybridization allows measurement of absolute rather than relative mRNA levels for genes of interest, and to monitor effector-induced changes in these mRNAs in vivo.

Animals↗
PubMed1995

Distribution and correlates of plasma fibrinogen in middle-aged women. Initial findings of the Postmenopausal Estrogen/Progestin Interventions (PEPI) study.

Fibrinogen levels have been reported in cohort and case-control studies to be positively related to the development of coronary heart disease. This report presents the distribution and determinants of fibrinogen in women enrolling in a 3-year randomized trial of hormone replacement therapy (HRT), the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. Fasting plasma fibrinogen levels were measured in 874 postmenopausal women, aged 45 to 65 years, who had not used HRT for at least 3.5 months. Mean (+/- SD) fibrinogen level was 2.83 +/- 0.45 g/L. There was a significant positive association between fibrinogen and age (P = .03). Significantly higher (P < .005) fibrinogen levels were seen in current smokers versus nonsmokers (2.94 versus 2.81 g/L), in women who reported consuming fewer than 12 alcoholic drinks in the 12 months before the baseline visit versus higher consumption (2.90 versus 2.79 g/L), and in women who reported never versus ever having used HRT (2.90 versus 2.77 g/L). Self-reported leisure time physical activity (LTPA) was negatively associated (P = .0001) with fibrinogen levels as follows: inactive (2.84 g/L), light (2.89 g/L), moderate (2.80 g/L), and heavy (2.60 g/L), with significantly (P = .0001) lower levels in women who reported heavy LTPA versus each of the other categories and in women reporting moderate versus light LTPA. A strong positive correlation was found between fibrinogen and body mass index (BMI) (r = .32; P < .0001). In a model that included age, smoking, alcohol intake, prior HRT, LTPA, and BMI, LTPA was no longer a statistically significant predictor of fibrinogen level, while associations with other variables remained significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Macronutrient intakes among adult Hispanics: a comparison of Mexican Americans, Cuban Americans, and mainland Puerto Ricans.

OBJECTIVES: The purpose of this study was to compare energy and macronutrient intakes between adult Mexican Americans, Cuban Americans, mainland Puerto Ricans, and non-Hispanics. METHODS: Age-specific mean intakes were estimated based on 24-hour recalls from the Hispanic Health and Nutrition Examination Survey (HHANES) (1982 to 1984) and the Second National Health and Nutrition Examination Survey (NHANES II) (1976 to 1980) and were compared with the use of t tests. RESULTS: Mexican Americans had higher total fat, saturated fat, and monounsaturated fat intakes than did Puerto Ricans and older Cuban Americans. Cuban Americans and Puerto Ricans had similar intakes, except for younger Cuban Americans, who had higher total and saturated fat and lower carbohydrate intakes. Cholesterol intakes among Mexican American men and 60- to 74-year-old women were higher than those among other Hispanic groups. Carbohydrate and protein intakes were higher among Hispanic groups compared with those among non-Hispanics while total fat intakes were generally lower. CONCLUSIONS: Since macronutrient intakes differ between Hispanic groups, dietary research, recommendations, and interventions should be targeted to each group individually. Older Puerto Rican and Cuban American adults met population guidelines for reducing chronic disease risk for more macronutrients than any other group.

Adult↗
PubMed1995

Serological precursors of cancer: malignant melanoma, basal and squamous cell skin cancer, and prediagnostic levels of retinol, beta- carotene, lycopene, alpha-tocopherol, and selenium.

To determine the association between prediagnostic serum levels of retinol, beta-carotene, lycopene, alpha-tocopherol, and selenium and the subsequent risk of malignant melanoma, and basal and squamous cell skin cancer, a nested case-control study among residents of Washington County, MD, was performed. Cases with melanoma (n = 30), basal cell (n = 32), and squamous cell (n = 37) skin cancer who were admitted to hospital for treatment or biopsy of metastatic lesions were each matched by age, sex, and race with two controls. There were no significant associations between serum micronutrient levels and the risk of subsequent skin cancer.

Adult↗