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D J Hunter

Publications and source records attributed to D J Hunter.

At least 145 records · Page 8Linked to original sources
PubMed1998

Predictors of dietary heterocyclic amine intake in three prospective cohorts.

Cooking meat creates heterocyclic amines (HCAs) through pyrolysis of amino acids and creatinine. Although recognized as mutagenic, the etiological role of HCA in human cancer is unclear, due to the lack of information on the effect of typical food cooking methods on HCA concentrations and on variation in HCA exposure in populations. We estimated overall daily dietary HCA intake and variation in intake between individuals, using recent data on HCA concentrations in various meats prepared by cooking methods, temperatures, and times common in United States in the 1990s. Random samples of 250 participants from each of three large prospective cohorts were mailed a questionnaire to assess frequency of consumption, cooking method, and typical outside appearance of pan-fried, broiled, and grilled or barbecued chicken, fish, hamburger, and steak; fried, microwaved, and broiled bacon; fried sausage; roast beef; and homemade gravy. The 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and 2-amino-3,4,8-trimethylimidazo[4,5,f]quinoxaline (DiMeIQx) concentrations, measured in composite samples by solid-phase extraction and high-performance liquid chromatography, were assigned to each food, cooking method, and doneness level. The dietary reports showed approximately 30-fold relative variation in 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline intake, 20-fold for 2-amino- -methyl-6-phenylimidazo[4,5-b]pyridine, and over 110-fold for 2-amino-3,4,8-trimethylimidazo[4,5,f]quinoxaline, when the 10th and 90th percentiles of HCA intake were compared (90th/10th percentile value). These reported variations in HCA exposure among participants in these three large cohorts indicates that estimation of HCA intake and determination of association with disease risk are feasible, if additional information on meat cooking methods is obtained.

Adult↗
PubMed1998

Use of toenail fluoride levels as an indicator for the risk of hip and forearm fractures in women.

The relation between fluoride intake and risk of osteoporotic fractures remains unclear. The lack of individual measures of long-term fluoride intake has limited epidemiologic studies. We used toenail fluoride in this study as a measure of long-term intake to evaluate the relation between fluoride intake and subsequent risk of hip and distal forearm fractures. Between 1982 and 1984, we collected toenail clippings from 62,641 women in the Nurses' Health Study who were free from cancer, heart disease, stroke, and previous hip or forearm fracture. We identified fracture cases (53 proximal femur and 188 distal forearm) through subsequent biennial mailed questionnaires and matched controls to cases on year of birth. The odds ratio of hip fracture among women in the highest quartile of toenail fluoride [ > 5.50 parts per million (ppm)], compared with those in the lowest quartile (> 2.00 ppm), was 0.8 (95% confidence interval = 0.2-4.0), with adjustment for menopausal status, postmenopausal hormone use, caffeine intake, and alcohol consumption. The corresponding adjusted odds ratio for forearm fracture was 1.6 (95% confidence interval = 0.8-3.1). Further adjustment for body mass index, smoking status, and calcium and vitamin D intake did not alter these results.

Adult↗
PubMed1998

Vitamins in HIV disease progression and vertical transmission.

Human immunodeficiency virus (HIV) infection is a major public health problem worldwide, but particularly in subsaharan Africa and Asia. Numerous observational studies report inverse associations between vitamin status, measured biochemically or as levels of dietary intake, and the risk of disease progression or vertical transmission. Evidence to support these findings has been obtained from a few randomized placebo-controlled trials. In this paper, we review studies that examined the role of vitamins A, B, C, D, and E in HIV disease progression and transmission, and we discuss the potential mechanisms of action of these vitamins. Adequate vitamin intake leads to enhancement of epithelial integrity and systemic immunity and could contribute to improved clinical condition among HIV-infected subjects and reduce vertical transmission by reducing the risk and severity of opportunistic infection and reducing viral load in blood. Adequate vitamin status may also reduce vertical transmission through the intrapartum and breastfeeding routes by reducing HIV viral load in lower genital secretions and breast milk, respectively. Vitamin supplements may be one of a few potential treatments that are inexpensive enough to be made available to HIV-infected persons in developing countries.

Adjuvants, Immunologic↗
PubMed1998

Risk of uterine leiomyomata among premenopausal women in relation to body size and cigarette smoking.

To investigate whether factors influencing ovarian function affect risk of uterine leiomyomata, we examined prospectively the association of new diagnoses confirmed by ultrasound or hysterectomy with body mass index, weight change, height, and cigarette smoking among 94,095 premenopausal women with intact uteri, who were ages 25-42 years at the start of follow-up in 1989. We assessed body mass index and cigarette smoking from responses on the study questionnaire completed just before diagnosis. During 322,775 person-years, 2,967 new cases of uterine leiomyomata confirmed by ultrasound or hysterectomy were reported. Risk among all cases confirmed by ultrasound or hysterectomy increased with increasing adult body mass index. The multivariate relative risks (RR) and 95% confidence intervals (CI) according to body mass index categories of <20.0, 20.0-21.9, 22.0-23.9, 24.0-25.9, 26.0-27.9, 28.0-29.9, and > or =30.0 were 0.90 (95% CI = 0.79-1.03), 1.00 (referent), 1.08 (95% CI = 0.97-1.21), 1.16 (95% CI = 1.03-1.31), 1.21 (95% CI = 1.05-1.40), 1.36 (95% CI = 1.16-1.59), and 1.23 (95% CI = 1.09-1.39), respectively. The RRs for hysterectomy-confirmed cases generally were higher. Similarly, risk was positively associated with weight gain since age 18 years. Body mass index at age 18 years, height, and cigarette smoking were unrelated to risk of uterine leiomyomata. Elevated adult body mass index is associated with a modest increased risk of uterine leiomyomata among premenopausal women.

Adult↗
PubMed1998

Vitamin D receptor genotype and the risk of bone fractures in women.

Several studies have confirmed an initial report of a relation between bone density and polymorphic forms of the calcitriol (vitamin D) receptor gene, whereas others have failed to find an association. We examined whether variants of the vitamin D receptor gene are associated with the risk of bone fracture, using a nested case-control analysis within the Nurses' Health Study cohort. The study women all were Caucasian and were 43-69 years of age when they provided a blood sample. Cases included the 54 proximal femur (hip) fractures and 163 distal radius (forearm) fractures that occurred subsequent to the blood draw. Cases and controls were genotyped by polymerase chain reaction for the BsmI polymorphism. The BB genotype, previously associated with lower bone density, was associated with a more than twofold increased risk of hip fracture compared with the bb genotype. Risk was greater for women who were older, leaner, or less physically active or who had a lower calcium intake. The heterozygous genotype was not associated with any increased risk of hip fracture, and we observed little association between vitamin D receptor genotype and forearm fracture. This study supports an association between vitamin D receptor genotype and hip fracture. It also implies that modification by other risk factors may have contributed to the conflicting results from previous studies of vitamin D receptor genotype and femoral bone density.

Adult↗
PubMed1998

Glutathione S-transferase GSTM1 and GSTT1 polymorphisms and colorectal cancer risk: a prospective study.

Glutathione S-transferase (GST) M1 and T1 genes encode GST enzymes, and are polymorphic in humans. These enzymes catalyze conjugation with glutathione, which is an important step in the detoxification of certain carcinogens. Several case-control studies have found associations of the homozygous null deletions in GSTM1 and GSTT1 with increasing the risk of colorectal and lung cancer. We prospectively examined the associations of the GSTM1 and GSTT1 polymorphisms with colorectal cancer risk in a nested case-control study (212 cases of colorectal cancer and 221 controls) within the Physicians' Health Study. Among controls, the prevalence of the GSTM1 homozygous null genotype was 53% and for GSTT1 homozygous null genotype, 23%. We found no increase in the risk of colorectal cancer for either GSTM1 null [odds ratio (OR) = 1.0; 95% confidence interval (CI), 0.7-1.5] or GSTT1 null (OR = 0.8; 95% CI, 0.5-1.2) genotypes. No differences were seen by site of colon cancer (proximal versus distal) or by age (< or = 60 years versus > 60 years). Current cigarette smokers with GSTM1 null genotype were not at an increased risk of colon cancer (OR = 1.2; 95% CI, 0.3-4.2) compared with current smokers without the null genotype; for the GSTT1 null genotype this OR was 1.1 = 95% CI (0.3-4.7). This lack of association persisted when we examined pack-years of smoking and age at starting smoking. Our results do not support an association of GSTM1 or GSTT1 polymorphisms with colorectal cancer or an interaction with cigarette smoking.

Adult↗
PubMed1997

Dual effects of weight and weight gain on breast cancer risk.

CONTEXT: Breast cancer is a major cause of mortality among women. It is important to identify modifiable risk factors for this disease. OBJECTIVE: To examine body mass index (BMI) at the age of 18 years and at midlife and adult weight change in relation to breast cancer incidence and mortality. DESIGN: Cohort study. SETTING: A cohort of 95256 US female nurses aged 30 to 55 years who were followed up for 16 years. MAIN OUTCOME MEASURE: Incident and fatal breast cancer. RESULTS: During 1203498 person-years, 2517 incident breast cancers (60% postmenopausal) were documented. Higher current BMI was associated with lower breast cancer incidence before menopause and was minimally associated with incidence after menopause. However, a stronger positive relationship was seen among postmenopausal women who never used hormone replacement (relative risk=1.59 for BMI >31 kg/m2 vs < or = 20 kg/m2; 95% confidence interval, 1.09-2.32; P for trend <.001). Higher BMI at the age of 18 years was associated with lower breast cancer incidence both before and after menopause. Weight gain after the age of 18 years was unrelated to breast cancer incidence before menopause, but was positively associated with incidence after menopause. This increased risk with weight gain was limited to women who never used postmenopausal hormones; among these women, the relative risk was 1.99 (95% confidence interval, 1.43-2.76) for weight gain of more than 20 kg vs unchanged weight (P for trend <.001). Current BMI and weight gain were even more strongly associated with fatal postmenopausal breast cancer. In this population, the percentage of postmenopausal breast cancer accounted for by weight gain alone was approximately 16% and by hormone replacement therapy alone was 5%, but when the interaction between these variables was considered, together they accounted for about one third of postmenopausal breast cancers. CONCLUSIONS: Avoiding adult weight gain may contribute importantly to the prevention of breast cancer after menopause, particularly among women who do not use postmenopausal hormones.

Adolescent↗
PubMed1997

Plasma organochlorine levels and the risk of breast cancer.

BACKGROUND: Exposure to "environmental estrogens" such as organochlorines in pesticides and industrial chemicals has been proposed as a cause of increasing rates of breast cancer. Several studies have reported higher blood levels of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and polychlorinated biphenyls (PCBs) in patients with breast cancer than in controls. METHODS: We measured plasma levels of DDE and PCBs prospectively among 240 women who gave a blood sample in 1989 or 1990 and who were subsequently given a diagnosis of breast cancer before June 1, 1992. We compared these levels with those measured in matched control women in whom breast cancer did not develop. Data on DDE were available for 236 pairs, and data on PCBs were available for 230 pairs. RESULTS: The median level of DDE was lower among case patients than among controls (4.71 vs. 5.35 parts per billion, P=0.14), as was the median level of PCBs (4.49 vs. 4.68 parts per billion, P=0.72). The multivariate relative risk of breast cancer for women in the highest quintile of exposure as compared with women in the lowest quintile was 0.72 for DDE (95 percent confidence interval, 0.37 to 1.40) and 0.66 for PCBs (95 percent confidence interval, 0.32 to 1.37). Exposure to high levels of both DDE and PCBs was associated with a nonsignificantly lower risk of breast cancer (relative risk for women in the highest quintiles of both DDE and PCBs as compared with women in the lowest, 0.43; 95 percent confidence interval, 0.13 to 1.44). CONCLUSIONS: Our data do not support the hypothesis that exposure to DDT and PCBs increases the risk of breast cancer.

Adult↗
PubMed1997

A prospective study of pregravid determinants of gestational diabetes mellitus.

CONTEXT: Gestational diabetes mellitus (GDM) affects 3% to 5% of pregnancies. Knowledge of risk factors for GDM is needed to identify possible preventive strategies. OBJECTIVE: To assess whether recognized determinants of noninsulin-dependent diabetes mellitus also may be markers for increased risk of GDM. DESIGN: Prospective cohort study. SETTING: The Nurses' Health Study II, which involves female US nurses aged 25 to 42 years at entry. PARTICIPANTS: The analyses included 14613 women without previous GDM or other known diabetes who reported a singleton pregnancy between 1990 and 1994. Of these women, 722 (4.9%) reported a new diagnosis of GDM. MAIN OUTCOME MEASURE: Self-report of GDM, validated by medical record review in a subset. RESULTS: In multivariate analyses including age, pregravid body mass index (BMI), and other GDM risk factors, the risk for GDM increased significantly with increasing maternal age (P for trend, <.01) and family history of diabetes mellitus (relative risk, 1.68; 95% confidence interval [CI], 1.39-2.04). Relative risks for GDM were 2.13 (95% CI, 1.65-2.74) for pregravid BMI of 25 to 29.9 kg/m2 and 2.90 (95% CI, 2.15-3.91) for BMI of 30 kg/m2 or more (vs BMI of <20 kg/m2). Risk for GDM increased with greater weight gain in early adulthood, and it also increased among nonwhite women. Pregravid current smokers had a relative risk for GDM of 1.43 (95% CI, 1.14-1.80), and pregravid vigorous exercise was associated with a nonsignificant reduction in GDM risk. CONCLUSIONS: Advanced maternal age, family history of diabetes mellitus, nonwhite ethnicity, higher BMI, weight gain in early adulthood, and cigarette smoking predict increased GDM risk. These observations may facilitate the identification of women at particular risk for GDM and suggest potential strategies for reducing this risk even before a woman becomes pregnant, such as avoiding substantial weight gain and smoking.

Adult↗
PubMed1997

Geographic variation in breast cancer incidence rates in a cohort of U.S. women.

BACKGROUND: Breast cancer mortality and incidence rates vary by geographic region in the United States. Previous analytic studies have measured mortality, not incidence, and have used regional prevalences to control for geographic variation in risk factors rather than adjusting for risk factors measured at the level of the individual. We prospectively evaluated regional variation in breast cancer incidence rates in the Nurses' Health Study and assessed the influence of breast cancer risk factors measured at the individual level. METHODS: The Nurses' Health Study cohort was established in 1976 when 121700 female nurses aged 30-55 years living in 11 U.S. states were enrolled. These states represent all four regions of the continental United States. We identified 3603 incident cases of invasive breast cancer through 1992 (1794565 person-years of follow-up). We calculated relative risks (RRs) adjusted for age and for age and established risk factors (i.e., multivariate-adjusted analysis), comparing California, the Northeast, and the Midwest with the South. RESULTS: For premenopausal women, there was little evidence of regional variation in breast cancer incidence rates, either in age-adjusted or in multivariate-adjusted analyses. For postmenopausal women in California, age-adjusted risk was modestly elevated (RR = 1.24; 95% confidence interval [CI] = 1.05-1.47); after adjusting for age and for established risk factors, the excess rate in California was attenuated by 25% (RR = 1.18; 95% CI = 1.00-1.40). No excess of breast cancer incidence was observed for postmenopausal women in either the Northeast or the Midwest. CONCLUSIONS: Little regional variation in age-adjusted breast cancer incidence rates was observed, with the exception of a modest excess for postmenopausal women in California. Adjustment for differences in the distribution of established risk factors explained some of the excess risk in California.

Adult↗
PubMed1997

Oral contraceptives and ovulatory causes of delayed fertility.

The return of fertility for women who discontinue oral contraceptives takes longer as compared with women who discontinue other methods of contraception. It remains unclear, however, whether subsequent fertility differs according to duration or age at first use. The authors performed a nested case-control study within a cohort of 116,686 female registered nurses residing in 14 US states. Baseline information was reported on mailed questionnaires in 1989. Cases comprised 1,917 married nurses without previous pregnancy who were unable to become pregnant for at least 1 year and were subsequently diagnosed with primary ovulatory infertility. Controls comprised 44,521 married parous nurses with no history of infertility and no pregnancies lasting less than 6 months. After allowing for 2 years of suppressed fertility following discontinuation of oral contraceptive use and excluding women with signs of menstrual or hormonal disorder, the authors found that the multivariate relative risk for ovulatory causes of delayed fertility was 1.2 (95% confidence interval 0.7-1.9) for ever users. There was no statistically significant trend of increasing risk with increasing duration of use and younger age at first use. The fact that 88 percent of cases reported an eventual pregnancy by 1993 suggests that absolute fertility was not impaired.

Adult↗
PubMed1997

EPR spectroscopy of Escherichia coli cytochrome bo which lacks CuB.

The spectroscopic and ligand-binding properties of a copper-deficient cytochrome bo3, a member of the haem-copper superfamily of terminal oxidases, are reported and contrasted with those of the native enzyme. The enzyme lacks the copper atom (CuB) which is normally an integral part of the catalytic site. The consequences of loss of the CuB are the loss of antiferromagnetic coupling to the high-spin haem and an inability to form any of the integer-spin derivatives of the enzyme. Low-spin compounds of the normally high-spin haem are still formed with appropriate ligands, although these are modified.

Azides↗
PubMed1997

Disease management.

The disease management approach to patient care seeks to coordinate resources across the healthcare delivery system. The growing interest in evidence based medicine and outcomes, and a commitment to integrated care across the primary, secondary, and community care sectors, all contribute to making disease management an attractive idea. A combination of patient education, provider use of practice guidelines, appropriate consultation, and supplies of drugs and ancillary services all come together in the disease management process. But its effectiveness is largely untested, so evaluation is essential.

Disease Management↗
PubMed1997

Leisure-time physical activity, body size, and colon cancer in women. Nurses' Health Study Research Group.

BACKGROUND: Physical inactivity and high body mass index (weight in kilograms divided by height in square meters) have been linked to increased risk of colon cancer. However, none of the few prospective studies in women has shown a statistically significant reduction in colon cancer incidence or mortality associated with increased leisure-time physical activity. PURPOSE: In this prospective study, we asked whether leisure-time physical activity, body mass index, or body fat distribution could significantly influence the risk of colon cancer in women. METHODS: The participants in this study were enrolled in the Nurses' Health Study, which began in 1976. Every 2 years, the women provided additional personal information and information on medical risk factors and major medical events. The time spent per week at a variety of leisure-time physical activities was determined, and the time spent at each activity was multiplied by its typical energy expenditure, expressed in terms of metabolic equivalents or METs. The resulting values for each woman were added to yield an MET-hours-per-week score. Reported diagnoses of colon cancer were confirmed by review of hospital records and pathology reports. Relative risks and associated 95% confidence intervals were calculated. RESULTS: In multivariate analyses that included body mass index, women who expended more than 21 MET-hours per week on leisure-time physical activity had a relative risk of colon cancer of 0.54 (95% confidence interval [CI] = 0.33-0.90) in comparison with women who expended less than 2 MET-hours per week. Women who had a body mass index greater than 29 kg/m2 had a relative risk of colon cancer of 1.45 (95% CI = 1.02-2.07) in comparison with women who had a body mass index less than 21 kg/m2. A tendency toward higher colon cancer risk was observed for increasing waist-to-hip ratio (relative risk = 1.48 [95% CI = 0.88-2.49] for comparison of the highest quintile ratio [>0.833] to the lowest [<0.728]). CONCLUSIONS AND IMPLICATIONS: The significant inverse association between leisure-time physical activity and incidence of colon cancer in women in this study is consistent with what has been found in men. Recommendations to increase physical activity and maintain lean body weight should receive greater emphasis as part of a feasible approach to the prevention of colon cancer.

Adult↗
PubMed1997

Implications of managed care for health systems, clinicians, and patients.

The rhetoric and realities of managed care are easily confused. The rapid growth of managed care in the United States has had many implications for patients, doctors, employers, state and federal programmes, the health insurance industry, major medical institutions, medical research, and vulnerable patient populations. It has restricted patients' choice of doctors and limited access to specialists, reduced the professional autonomy and earnings of doctors, shifted power from the non-profit to the for-profit sectors and from hospitals and doctors to private corporations. It has also raised issues about the future structuring and financing of medical education and research and about practice ethics. However, managed care has also accorded greater prominence to the assessment of patient satisfaction, profiling and monitoring of doctors' work, the use of clinical guidelines and quality assurance procedures and indicated the potential to improve the integration and outcome of care.

Choice Behavior↗
PubMed1997

Managed care. Origins, principles, and evolution.

Managed care has entered the lexicon of healthcare reform, but confusion and ignorance surround its meaning and purpose. It seeks to cut the costs of health care while maintaining its quality, but the evidence that it is able to achieve these aims is mixed. As well as raising awareness and understanding of the issues surrounding managed care, this series considers whether managed care is desirable for the NHS. Developed in the United States as a response to spiralling healthcare costs and dysfunctional fragmented services, managed care is not a discrete activity but a spectrum of activities carried out in a range of organisational settings. Due to its constantly changing nature, managed care is a slippery concept--but all its permutations have in common an attempt to influence and modify the behaviour and practice of doctors and other health professionals towards cost effective care. Whatever potential managed care may hold in this regard, careful appraisal of its implications is essential.

Europe↗
PubMed1997

Postmenopausal hormone therapy and mortality.

BACKGROUND: Postmenopausal hormone therapy has both benefits and hazards, including decreased risks of osteoporosis and cardiovascular disease and an increased risk of breast cancer. METHODS: We examined the relation between the use of postmenopausal hormones and mortality among participants in the Nurses' Health Study, who were 30 to 55 years of age at base line in 1976. Data were collected by biennial questionnaires beginning in 1976 and continuing through 1992. We documented 3637 deaths from 1976 to 1994. Each participant who died was matched with 10 controls alive at the time of her death. For each death, we defined the subject's hormone status according to the last biennial questionnaire before her death or before the diagnosis of the fatal disease; this reduced bias caused by the discontinuation of hormone use between the time of diagnosis of a potentially fatal disease and death. RESULTS: After adjustment for confounding variables, current hormone users had a lower risk of death (relative risk, 0.63; 95 percent confidence interval, 0.56 to 0.70) than subjects who had never taken hormones; however, the apparent benefit decreased with long-term use (relative risk, 0.80; 0.67 to 0.96, after 10 or more years) because of an increase in mortality from breast cancer among long-term hormone users. Current hormone users with coronary risk factors (69 percent of the women) had the largest reduction in mortality (relative risk, 0.51; 95 percent confidence interval, 0.45 to 0.57), with substantially less benefit for those at low risk (13 percent of the women; relative risk, 0.89; 95 percent confidence interval, 0.62 to 1.28). CONCLUSIONS: On average, mortality among women who use postmenopausal hormones is lower than among nonusers; however, the survival benefit diminishes with longer duration of use and is lower for women at low risk for coronary disease.

Adult↗