Search PubMed⌕ Search

Biomedical subjects

D J Hunter

Publications and source records attributed to D J Hunter.

At least 163 records · Page 9Linked to original sources
PubMed1997

Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer.

Folate derivatives are important in experimental colorectal carcinogenesis; low folate intake, particularly with substantial alcohol intake, is associated with increased risk. The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5,10-methylenetetrahydrofolate, required for purine and thymidine syntheses, to 5-methyltetrahydrofolate, the primary circulatory form of folate necessary for methionine synthesis. A common mutation (677C-->T) in MTHFR reduces enzyme activity, leading to lower levels of 5-methyltetrahydrofolate. To evaluate the role of folate metabolism in human carcinogenesis, we examined the associations of MTHFR mutation, plasma folate levels, and their interaction with risk of colon cancer. We also examined the interaction between genotype and alcohol intake. We used a nested case-control design within the Physicians' Health Study. Participants were ages 40-84 at baseline when alcohol intake was ascertained and blood samples were drawn. During 12 years of follow-up, we identified 202 colorectal cancer cases and matched them to 326 cancer-free controls by age and smoking status. We genotyped for the MTHFR polymorphism and measured plasma folate levels. Men with the homozygous mutation (15% in controls) had half the risk of colorectal cancer [odds ratio (OR), 0.49; 95% confidence interval (CI), 0.27-0.87] compared with the homozygous normal or heterozygous genotypes. Overall, we observed a marginal significant increased risk of colorectal cancer (OR, 1.78; 95% CI, 0.93-3.42) among those whose plasma folate levels indicated deficiency (<3 ng/ml) compared with men with adequate folate levels. Among men with adequate folate levels, we observed a 3-fold decrease in risk (OR, 0.32; 95% CI, 0.15-0.68) among men with the homozygous mutation compared with those with the homozygous normal or heterozygous genotypes. However, the protection due to the mutation was absent in men with folate deficiency. In men with the homozygous normal genotype who drank little or no alcohol as reference, those with the homozygous mutation who drank little or no alcohol had an 8-fold decrease in risk (OR, 0.12; 95% CI, 0.03-0.57), and for moderate drinkers, a 2-fold decrease in risk (OR, 0.42; 95% CI, 0.15-1.20); no decrease in risk was seen in those drinking 1 or more drinks/day. Our findings provide support for an important role of folate metabolism in colon carcinogenesis. In particular, these results suggest that the 677C-->IT mutation in MTHFR reduces colon cancer risk, perhaps by increasing 5,10-methylenetetrahydrofolate levels for DNA synthesis, but that low folate intake or high alcohol consumption may negate some of the protective effect.

Adult↗
PubMed1997

Past use of oral contraceptives and the risk of developing systemic lupus erythematosus.

OBJECTIVE: To examine the relationship between past use of oral contraceptives (OCs) and development of systemic lupus erythematosus (SLE). METHODS: Prospective cohort study of 121,645 women who were followed up every 2 years between 1976 and 1990 as part of the Nurses' Health Study. Women were classified as never users or past users of OCs based on self-report. Incidence of SLE was defined by 1) strict American College of Rheumatology (ACR) classification criteria (> or = 4 ACR criteria), 2) > or = 4 ACR criteria and any physician's diagnosis, 3) > or = 4 ACR criteria and diagnosis by an ACR-certified rheumatologist, 4) > or = 3 ACR criteria, or 5) diagnosis by a physician even if the patient did not meet the ACR criteria. RESULTS: Compared with never users of OCs, and after adjusting for age and ever use of postmenopausal hormones, the relative risk (95% confidence interval [95% CI]) for the incidence of SLE in the women who had definite cases of SLE (> or = 4 ACR criteria) (n = 99) was 1.4 (0.9-2.1) for past users of OCs. Using the most stringent case definition (ACR criteria plus a diagnosis of SLE by an ACR member) (n = 58), the relative risk for past users compared with never users was 1.9 (95% CI 1.1-3.3). No relationship was observed between duration of OC use or time since first use and the risk of developing SLE. CONCLUSION: Past use of OCs was associated with a slightly increased risk of developing SLE. The decision to use hormonal contraception must be individualized, but the small absolute risk observed for the development of SLE in white women should not be a dominant factor in the decision.

Cohort Studies↗
PubMed1997

Reproducibility of oral contraceptive histories and validity of hormone composition reported in a cohort of US women.

Histories of oral contraceptive (OC) use were reported by 116,686 women aged 25 to 42 years in the Nurses' Health Study II on a self-administered questionnaire accompanied by a color photo booklet of all OC preparations ever marketed in the US. To evaluate the quality of this information, we compared the responses of a randomly selected sample of 215 participants with their data from a subsequent, detailed telephone interview using a structured life events calendar. Agreement for a history of ever having used OC was high between the two methods (exact agreement 99%). Reported durations of use were equivalent (mean duration 42.7 months by telephone interview and 44.6 months by questionnaire). The Spearman correlation for duration of use calculated from the two methods was 0.94 (p < 0.0001). For a subset of women for whom we were able to obtain OC prescription records, the medical record confirmed the use of an identical or equivalent brand in 75% of intervals of reported use. Acceptably valid OC histories were obtained with a self-administered questionnaire.

Adult↗
PubMed1997

Variation in the incidence of uterine leiomyoma among premenopausal women by age and race.

OBJECTIVE: To quantify the incidence of uterine leiomyoma confirmed by hysterectomy, ultrasound, or pelvic examination according to age and race among premenopausal women. METHODS: From September 1989 through May 1993, 95,061 premenopausal nurses age 25-44 with intact uteri and no history of uterine leiomyoma were followed to determine incidence rates of uterine leiomyoma. The self-reported diagnosis was confirmed in 93% of the medical records obtained for a sample of cases. Using pooled logistic regression, we estimated relative risks (RRs) of uterine leiomyoma according to race and examined whether adjustment for other potential risk factors could explain the variation in the race-specific rates. RESULTS: During 327,065 woman-years, 4181 new cases of uterine leiomyoma were reported. The incidence rates increased with age, and the age-standardized rates of ultrasound- or hysterectomy-confirmed diagnoses per 1000 woman-years were 8.9 among white women and 30.6 among black women. After further adjustment for marital status, body mass index, age at first birth, years since last birth, history of infertility, age at first oral contraceptive use, and current alcohol consumption, the rates among black women were significantly greater for diagnoses confirmed by ultrasound or hysterectomy (RR 3.25; 95% confidence interval [CI] 2.71, 3.88) and by hysterectomy (RR 1.82; 95% CI 1.17, 2.82) compared with rates among white women. We observed similar RRs when the cohort was restricted to participants who reported undergoing a screening physical examination within the 2 years before baseline. CONCLUSION: A higher prevalence of known risk factors did not explain the excess rate of uterine leiomyoma among premenopausal black women.

Adult↗
PubMed1997

Non-dietary factors as risk factors for breast cancer, and as effect modifiers of the association of fat intake and risk of breast cancer.

To assess more precisely the relative risks associated with established risk factors for breast cancer, and whether the association between dietary fat and breast cancer risk varies according to levels of these risk factors, we pooled primary data from six prospective studies in North America and Western Europe in which individual estimates of dietary fat intake had been obtained by validated food-frequency questionnaires. Based on information from 322,647 women among whom 4,827 cases occurred during follow-up: the multivariate-adjusted risk of late menarche (age 15 years or more compared with under 12) was 0.72 (95 percent confidence interval [CI] = 0.62-0.82); of being postmenopausal was 0.82 (CI = 0.69-0.97); of high parity (three or more births compared with none) was 0.72 (CI = 0.61-0.86); of late age at first birth (over 30 years of age compared with 20 or under) was 1.46 (CI = 1.22-1.75); of benign breast disease was 1.53 (CI = 1.41-1.65); of maternal history of breast cancer was 1.38 (CI = 1.14-1.67); and history of a sister with breast cancer was 1.47 (CI = 1.27-1.70). Greater duration of schooling (more than high-school graduation compared with less than high-school graduation) was associated significantly with higher risk in age-adjusted analyses, but was attenuated after controlling for other risk factors. Total fat intake (adjusted for energy consumption) was not associated significantly with breast cancer risk in any strata of these non-dietary risk factors. We observed a marginally significant interaction between total fat intake and risk of breast cancer according to history of benign breast disease; with fat intake being associated nonsignificantly positively with risk among women with a previous history of benign breast disease; no other significant interactions were observed. Risks for reproductive factors were similar to those observed in case-control studies; relative risks for family history of breast cancer were lower. We found no clear evidence in any subgroups of a major relation between total energy-adjusted fat intake and breast cancer risk.

Breast Neoplasms↗
PubMed1997

A prospective study of oral contraceptive use and risk of breast cancer (Nurses' Health Study, United States).

Results of previous epidemiologic studies have provided reassurance that there is little, if any, increase in risk of breast cancer with oral contraceptive (OC) use in general. However, in several studies, an increased risk of breast cancer has been observed in two subgroups, young women who used OCs for extended durations and in women who used OCs prior to a first-term pregnancy. We evaluated these relationships using data from the ongoing Nurses' Health Study cohort (United States). We documented 3,383 cases of breast cancer from 1976 to 1992 among 1.6 million person-years of follow-up. We observed no overall relationship between duration of OC use and breast cancer risk, even among women who reported using OCs for 10 or more years (multivariate relative risk [RR] = 1.11, 95 percent confidence interval [CI] = 0.94-1.32). Among women less than 45 years of age, the multivariate RR for using OCs for 10 or more years was 1.07 (CI = 0.70-1.65) compared with never-users. The risk associated with five or more years of OC use prior to a first full-term pregnancy compared with never-use was 0.96 (CI = 0.65-1.43). Among women less than 45 years of age, we observed no evidence of an increased risk with OC use before a first full-term pregnancy (use for five or more years: RR = 0.57, CI = 0.24-1.31). Because of the age distribution of our cohort, we were unable to evaluate these relationships among women less than 40 years of age. Our study provides considerable evidence that long-term past OC use, either overall or prior to a first full-term pregnancy, does not result in any appreciable increase in breast cancer risk in women over 40 years of age.

Adult↗
PubMed1997

Treatment-seeking behaviour and stated preferences for prostatectomy in Spanish men with lower urinary tract symptoms.

OBJECTIVES: To determine whether men in the community with lower urinary tract symptoms sought treatment, would choose to have a prostatectomy, and the factors that might influence their decision. SUBJECTS AND METHODS: The study was a cross-sectional population survey using interviewers in the autonomous community of Madrid and comprised 2002 men aged > or = 50 years. The main outcome measures were self-reported International Prostate Symptom Scores (IPSS), treatment-seeking behaviour and the patients' stated preference for prostatectomy. RESULTS: The response rate among eligible subjects was 68.1%; overall, 38.2% of men sought medical advice for their lower urinary tract symptoms. Whether a man sought medical advice was related to symptom severity, 'bothersomeness', interference in daily activities and his perception of the future; of these, bothersomeness and interference in activities were more likely to determine whether or not a man consulted his doctor. Most men in the sample (84.9%) reported that they would choose a prostatectomy, although this value depended on whether they had had a previous prostatectomy, were younger, and on the content of the information presented. Men were more likely to report that they would accept surgery if their doctor recommended it and less likely when presented with information on the outcomes of treatment. CONCLUSION: Many Spanish men with lower urinary tract symptoms do not seek medical advice for their symptoms, although most stated that they would accept a prostatectomy on the recommendation of their doctor. Further research should examine whether reported patient preferences correspond to actual behaviour and what is the most appropriate type of information to give to potential patients.

Aged↗
PubMed1997

Measurement of retinoids and carotenoids in breast adipose tissue and a comparison of concentrations in breast cancer cases and control subjects.

A case-control study of the associations of retinoids and specific carotenoids with breast cancer using concentrations of these nutrients in breast adipose tissue was conducted among women attending a breast clinic in the Boston area in 1989-1992. Breast adipose tissue was collected during breast biopsy. Cases (n = 46) were women whose biopsies revealed invasive or in situ breast cancer; control subjects (n = 63) were women whose biopsies revealed benign disease. We observed inverse associations between breast adipose concentrations of retinoids and carotenoids and risk of breast cancer, although not all were statistically significant. The multivariate-adjusted odds ratio comparing women above the median value of the control group for retinol with those below or equal to the median was 0.71 (95% CI: 0.26, 1.93; NS); corresponding odds ratios were 0.61 (95% CI: 0.23, 1.64; NS) for retinyl palmitate, 0.30 (95% CI: 0.11, 0.85) for beta-carotene, 0.32 (95% CI: 0.11, 0.94) for lycopene, and 0.68 (95% CI: 0.27, 1.73; NS) for lutein/zeaxanthin. There was a nonsignificant positive correlation (r = 0.23, P = 0.15) between breast adipose tissue concentrations of retinol and dietary intake of preformed vitamin A, including supplements measured by using a food-frequency questionnaire. No correlation was found between breast adipose concentrations of carotenoids and intake of dietary carotenoids. These data suggest that higher breast adipose concentrations of retinoids and some carotenoids may be associated with decreased risk of breast cancer and that further examination of these relations is warranted.

Adipose Tissue↗
PubMed1997

A prospective study of NAT2 acetylation genotype, cigarette smoking, and risk of breast cancer.

Polymorphisms in the N-acetyltransferase 2 (NAT2) gene are determinants of the rate of metabolic activation of carcinogenic compounds such as aryl aromatic amines. Homozygosity for any combination of three variant alleles in Caucasians defines 'slow' acetylators; presence of one or two wild-type alleles characterizes 'rapid' acetylators. Although most previous studies have not observed an overall elevation in risk of breast cancer among slow acetylators, a recent study observed that cigarette smoking was associated with a large increase in risk of breast cancer among slow acetylators. We assessed the relation between NAT2 acetylation status and breast cancer risk, and its interaction with smoking, in a prospective study of mainly Caucasian US women. Four hundred and sixty-six incident cases who were diagnosed with breast cancer after giving a blood specimen in 1989-90 were matched to 466 controls in a nested case-control study. NAT2 genotype was determined using PCR-RFLP assays. The multivariate relative risk (RR) comparing slow with rapid acetylators was 0.9 (95% CI 0.7-1.2). Among slow acetylators, current smoking immediately prior to diagnosis was not associated with a significant elevation in risk compared with never smoking rapid acetylators (RR = 1.4, 95% CI 0.7-2.6). No significant association was seen between pack-years of smoking and risk of breast cancer among either slow or fast acetylators. A non-significant elevation in risk was observed among women who smoked for > or = 5 years prior to first pregnancy and were rapid acetylators, compared with never smoking rapid acetylators (RR = 1.5, 95% CI 0.9-2.6). In analyses limited to 706 post-menopausal women, the elevated risks for current smokers immediately prior to diagnosis who were slow acetylators compared with never smokers who were fast acetylators were slightly stronger but still not statistically significant. In summary, we observed little evidence of an association between NAT2 genotype and breast cancer. In this prospective study, cigarette smoking was not appreciably associated with breast cancer among either slow or fast NAT2 acetylators.

Acetylation↗
PubMed1997

For debate. Local government and the National Health Service: the new agenda.

There are some interesting paradoxes in the relationship between local government and the National Health Service (NHS). Local government is responsible for a range of major services, many of which relate to health broadly defined. The NHS provides many services which are often popularly thought to be part of local government (and, indeed, in many countries are). Local government prides itself on its 'localness'; the NHS, with its services delivered in a very local fashion for the most part, cannot quite decide whether it is a national service or a local one. Yet these two major agencies of governance and public service provision often seem unable to work very well together. In the interests of good government, both agencies need to work together where their interests coincide or abut one another. Differences of perspective, priority, culture and style need to be recognized but resolved. Opportunities for joint working need to be grasped and the experience built on. The paper looks at a series of issues and opportunities which bring local government and the NHS together. They create an incentive to improve working relationships; at the same time they suggest an agenda of future possibilities.

Humans↗
PubMed1997

Limitations of epidemiologically based needs assessment. The case of prostatectomy.

OBJECTIVES: The aim of this study was to make epidemiologically based estimates of the prevalent and incident "need" for prostatectomy for lower urinary tract symptoms, defined as the numbers of men who would both benefit from and want the operation. METHODS: The methods involved a consensus panel, a two-stage postal survey of 1,480 men aged 55 years or older from eight general practices to the northwest of London, United Kingdom, and a multistate life table. RESULTS: The overall response rate was 69% (initial survey: 78%, follow-up survey: 88%). A trial-based estimate of number of candidates for prostatectomy (men with symptoms that were at least moderately severe and bothersome and who would probably or definitely want surgery) was 610 men in a population of 250,000. The corresponding incidence estimate (including men with symptoms recurring after spontaneous remission or surgery) was approximately 200 per year, including approximately 110 new cases. Consensus-based estimation, including categories of patients who have not yet been subject to a trial, gave much higher figures of approximately 3,000, 650, and 200 candidates, respectively. Adding the number of men who said they were "inclined to" choose surgery would almost double these figures. CONCLUSIONS: Estimates of need were highly sensitive to choice of indications and assumptions about patients' attitudes toward surgery. Population needs assessment for specific procedures will always involve judgment as well as epidemiological data and modeling.

Aged↗
PubMed1997

Fitness to practice in the 21st century. What will doctors be doing in the 21st century?

I am not a clinical doctor, therefore it would be highly presumptuous of me to speculate on what doctors will be doing in 20-30 years time. I suspect it would be a difficult task even for a medically qualified speaker. If you think of what has happened over the past 20-30 years, and of how difficult if not impossible it would have been to predict these developments, then you have some measure of the problem in thinking ahead 20-30 years. So, I'm not going to attempt such an exercise. What I aim to do is refocus the question in the title a little and sketch out some of the health policy and health care concerns which are likely to shape the environment and context in which doctors and other health care practitioners will ply their craft.

Delivery of Health Care↗
PubMed1997

Risk factors for sexually transmitted diseases among women attending family planning clinics in Dar-es-Salaam, Tanzania.

BACKGROUND: Identification of risk factors for sexually transmitted diseases (STDs) assists in development of treatment algorithms, which are potentially important components of STD control when microbiologic facilities are limited. METHODS: A cross-sectional study was performed to assess STD and HIV risk factors of 2285 women attending three family planning clinics in Dar-es-Salaam, Tanzania during 1991-92. Women were interviewed and examined for signs of STDs. Specimens were taken for laboratory diagnosis of HIV, other sexually transmitted organisms, and Candida albicans. RESULTS: The prevalence of gonorrhoea was found to be 4.2%, prevalence of trichomoniasis was 14.3%, and positive syphilis serology was found in 2.5% of women. Unmarried women were at increased risk of trichomoniasis (age-adjusted OR = 1.48 95% CI [1.12, 1.95]), gonorrhoea (age-adjusted OR = 1.81 95% CI [1.14, 2.86]) and syphilis (age-adjusted OR 1.5 [0.84, 2.68]). An increasing number of sexual partners in the past five years was associated with an increased risk of all STDs. Current use of the oral contraceptive pill was positively associated with gonorrhoea, multivariate OR = 1.75 95% CI [1.05, 2.93]. The prevalence of candidiasis was 11.5% and was not associated with any of the demographic or behavioural risk factors examined. Clinical diagnostic algorithms for STDs in this study population had relatively low sensitivity and low positive predictive value. CONCLUSION: Being unmarried and having a higher number of sexual partners were consistently associated with each STD, while the associations for other risk factors varied between STDs, emphasising the complexity of STD distribution. Further development of diagnostic algorithms and other methods for screening women for STDs are needed to reduce the impact of STDs and HIV in developing countries.

Adolescent↗
PubMed1997

A prospective study of oral contraceptives and NIDDM among U.S. women.

OBJECTIVE: To examine prospectively the association between modern oral contraceptives with low doses of estrogen and progestin and subsequent incidence of NIDDM. RESEARCH DESIGN AND METHODS: In a prospective cohort study, 98,590 U.S. female nurses aged 25 to 42 and free of diagnosed diabetes, coronary heart disease, stroke, and cancer at baseline in 1989 were followed for 4 years. Endpoint was incidence of confirmed NIDDM. Oral contraceptive use was reported on mailed questionnaires. RESULTS: During 352,067 person-years follow-up, we confirmed 185 incident cases of NIDDM. After adjusting for age, BMI, cigarette smoking, family history of diabetes, parity, physical activity, alcohol intake, ethnicity, history of diagnosis of infertility, elevated cholesterol, and hypertension, women currently using oral contraceptives had a relative risk (RR) of 1.6 (95% CI, 0.9-3.1). For past users, the multivariate RR was 1.2 (95% CI, 0.8-1.8). This association was attenuated after restricting the analysis to symptomatic cases of NIDDM. For current users, RR = 1.3 (95% CI, 0.6-2.8), and for past users, RR = 0.9 (95% CI, 0.6-1.4), suggesting that increased surveillance may explain at least part of any excess risk. CONCLUSIONS: In this large prospective study, we found no appreciable increase in the 4-year risk of NIDDM among current users of oral contraceptives. There was no apparent increase in risk among past users. The small number of cases reflect the low absolute risk of NIDDM in this population of young women.

Adult↗
PubMed1997

The audit society.

Explore the source record for details and available documents.

Management Audit↗
PubMed1997

Risk of breast cancer associated with atypical hyperplasia of lobular and ductal types.

Epidemiological studies using the histological classification of Page for benign breast disease consistently demonstrate a positive association between atypical hyperplasia and the subsequent development of breast cancer. However, atypical hyperplasia is of either lobular or ductal types, and breast cancer risk in relation to type of atypical hyperplasia has not been studied extensively. Thus, we investigated prospectively the risk of breast cancer associated with histological subtypes of benign proliferative breast disease, including the types of atypical hyperplasia, among participants in the Nurses' Health Study who had biopsy-confirmed benign breast disease. Women who subsequently developed breast cancer were matched by year of birth and year of biopsy to participants who were free from breast cancer. Benign biopsy slides were classified according to the criteria of Page. Odds ratios (ORs) of breast cancer and 95% confidence intervals (CIs), adjusted for the matching variables and other breast cancer risk factors, were computed using unconditional logistic regression with benign nonproliferative breast disease as the referent group. Atypical ductal hyperplasia (OR = 2.4; 95% CI, 1.3-4.5) or atypical lobular hyperplasia (OR = 5.3; 95% CI, 2.7-10.4) in a prior biopsy were associated with increased breast cancer risk. Atypical lobular hyperplasia was more strongly associated with the risk of premenopausal breast cancer (OR = 9.6; 95% CI, 3.3-27.8) than with the risk of postmenopausal breast cancer (OR = 3.7; 95% CI, 1.3-10.2). The association of atypical ductal hyperplasia and breast cancer risk varied little by menopausal status. The magnitude of breast cancer risk seems to vary according to the type of atypical hyperplasia present at biopsy.

Adult↗