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David Hunter

Publications and source records attributed to David Hunter.

At least 37 records · Page 2Linked to original sources
PubMed2005

A network of investigator networks in human genome epidemiology.

The task of identifying genetic determinants for complex, multigenetic diseases is hampered by small studies, publication and reporting biases, and lack of common standards worldwide. The authors propose the creation of a network of networks that include groups of investigators collecting data for human genome epidemiology research. Twenty-three networks of investigators addressing specific diseases or research topics and representing several hundreds of teams have already joined this initiative. For each field, the authors are currently creating a core registry of teams already participating in the respective network. A wider international registry will include all other teams also working in the same field. Independent investigators are invited to join the registries and existing networks and to join forces in creating additional ones as needed. The network of networks aims to register these networks, teams, and investigators; be a resource for information about or connections to the many networks; offer methodological support; promote sound design and standardization of analytical practices; generate inclusive overviews of fields at large; facilitate rapid confirmation of findings; and avoid duplication of effort.

Databases, Genetic↗
PubMed2005

Selenium status, pregnancy outcomes, and mother-to-child transmission of HIV-1.

BACKGROUND: Among HIV-infected pregnant women, low selenium status may increase risk of mother-to-child transmission (MTCT) of HIV and poor pregnancy outcomes (low birthweight, small for gestational age, preterm birth, and fetal death) through several mechanisms, such as by promoting maternal HIV disease progression, viral shedding in the genital tract, and development of mastitis. However, there is no direct epidemiologic evidence on these relations among HIV-infected pregnant women. OBJECTIVE: To investigate the association between selenium status during pregnancy and pregnancy outcomes, MTCT of HIV, and child mortality. DESIGN: Baseline plasma selenium measurements from HIV-positive pregnant women (n = 670) were obtained between 12-27 weeks of gestation and mother-child pairs were followed prospectively until 24 months after delivery. RESULTS: Low plasma selenium levels were associated with increased risks of fetal death, child death, and HIV transmission through the intrapartum route. Low selenium status was not associated with risks of low birthweight or preterm birth but was associated with an apparently lower risk of small for gestational age. CONCLUSION: Adequate selenium status may be beneficial for some but not all pregnancy outcomes. Further studies are needed to better understand the role of selenium status in pregnancy outcomes, HIV transmission, and child health.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Peroxisome proliferator-activated receptor-gamma2 P12A polymorphism and risk of coronary heart disease in US men and women.

OBJECTIVE: Activation of the peroxisome proliferator-activated receptor-gamma (PPARgamma) improves insulin sensitivity and exerts antiatherogenic effects. A common alanine for proline substitution at codon 12 in the PPARG2 gene is related to lower receptor activity. Studies suggest that the A12 allele is associated with reduced risk of type 2 diabetes; however, data on the risk of coronary heart disease (CHD) are scarce and controversial. METHODS AND RESULTS: We examined the relationship between PPARG2 P12A and CHD risk in women (Nurses' Health Study) and men (Health Professionals Follow-Up Study) in nested case control settings. Among participants free of cardiovascular disease at baseline, 249 women and 266 men developed nonfatal myocardial infarction (MI) or fatal CHD during 8 and 6 years of follow-up, respectively. Using risk-set sampling, controls were selected 2:1 matched on age, smoking, and date of blood draw. The relative risk (RR) of nonfatal MI or fatal CHD of carriers compared with noncarriers of the A12 allele was 1.17 (95% CI, 0.82 to 1.68) among women and 1.44 (95% CI, 1.00 to 2.07) among men (pooled RR, 1.30 [95% CI, 1.00 to 1.67]). We found a significantly increased risk associated with the A12 allele among individuals with a body mass index > or =25 kg/m2 (women: RR, 1.88; 95% CI, 1.01 to 3.50; men: RR, 1.55; 95% CI, 0.92 to 2.60; pooled: RR, 1.68; 95% CI, 1.13 to 2.50) but not among those <25 kg/m2 (pooled RR, 0.86; 95% CI, 0.37 to 1.97; P heterogeneity overweight versus nonoverweight 0.16). CONCLUSIONS: These data do not support the hypothesis that the A12 allele is associated with a decreased risk of CHD. The potential interaction between PPARG2 P12A, overweight, and increased CHD risk needs further evaluation.

Adult↗
PubMed2005

Accounting for haplotype uncertainty in matched association studies: a comparison of simple and flexible techniques.

Population-based case-control studies measuring associations between haplotypes of single nucleotide polymorphisms (SNPs) are increasingly popular, in part because haplotypes of a few "tagging" SNPs may serve as surrogates for variation in relatively large sections of the genome. Due to current technological limitations, haplotypes in cases and controls must be inferred from unphased genotypic data. Using individual-specific inferred haplotypes as covariates in standard epidemiologic analyses (e.g., conditional logistic regression) is an attractive analysis strategy, as it allows adjustment for nongenetic covariates, provides omnibus and haplotype-specific tests of association, and can estimate haplotype and haplotype x environment interaction effects. In principle, some adjustment for the uncertainty in inferred haplotypes should be made. Via simulation, we compare the performance (bias and mean squared error of haplotype and haplotype x environment interaction effect estimates) of several analytic strategies using inferred haplotypes in the context of matched case-control data. These strategies include using only the most likely haplotype assignment, the expectation substitution approach described by Stram et al. ([2003b] Hum. Hered. 55:179-190) and others, and an improper version of multiple imputation. For relatively uncomplicated haplotype structures and moderate haplotype relative risks (</=2), all methods performed comparably well (small bias with appropriately-sized confidence intervals). For larger relative risks, the most likely haplotype and multiple imputation strategies showed noticeable bias towards the null; the expectation substitution strategy still performed well. When there was more uncertainty in the inferred haplotypes, the most likely and multiple imputation strategies showed even more bias towards the null, while the expectation substitution method had slightly smaller than nominal confidence intervals for larger relative risks (>/=5). An application to progesterone-receptor haplotypes and endometrial cancer further illustrates that the performance of all these methods depends on how well the observed haplotypes "tag" the unobserved causal variant.

Algorithms↗
PubMed2005

Apolipoprotein E, cardiovascular disease and cognitive function in aging women.

The apolipoprotein E (APOE) e4 allele increases risk of Alzheimer disease and cardiovascular diseases. We examined APOE genotypes alone or combined with cardiovascular conditions in relation to cognitive function in 4227 Nurses' Health Study participants, 70-80 years old. From 1995 to 2001, and again 2 years later, participants received telephone cognitive assessments of general cognition, category fluency, verbal memory and working memory. In biennial questionnaires since 1976, participants have provided extensive health information including cardiovascular conditions. Compared with women with the e3/3 genotype, e4 carriers performed worse at baseline across all tests (mean global composite score was lower by 0.10 points (95% confidence interval=-0.15, -0.05)) and declined more (mean change in global score was -0.07 points (95% CI=-0.12, -0.03)), with a strong allele dose-response trend (P-trend=0.0003). Among participants 75+ years, e2 carriers performed best. Women with an e4 allele and cardiovascular conditions such as transient ischemic attack or untreated hypertension had the worst cognition. Thus, APOE genotypes strongly influenced cognitive function and decline; prevention of cardiovascular disease may limit these effects.

Aged↗
PubMed2005

E-selectin genotypes and risk of type 2 diabetes in women.

Endothelial dysfunction increases risk for type 2 diabetes. We examined whether variation in the gene for E-selectin (SELE), a biomarker of endothelial dysfunction, was associated with levels of E-selectin or diabetes quantitative traits (including fasting levels of insulin and hemoglobin A(1c)) in 719 nondiabetic participants of the Nurses' Health Study or with risk of diabetes in 602 incident (over 10 years of follow-up) cases and 655 control women matched for age, race, and fasting status. Variation in three single nucleotide polymorphisms previously associated with cardiovascular disease risk and having effects on E-selectin function, S128R, G98T, and L554F, was not significantly (p > 0.05) associated with levels of E-selectin or diabetes quantitative traits, or with risk of incident diabetes in the primary analysis. Among women with low levels of subclinical inflammation (C-reactive protein levels below the population median), S128R R allele carriers had a diabetes risk factor-adjusted relative risk of incident diabetes of 1.71 (95% confidence interval, 1.04 to 2.81) relative to those with the SS genotype. Apart from an association in this subgroup, we conclude that the E-selectin variants we examined are not important genetic risk factors for type 2 diabetes in women.

Adult↗
PubMed2005

Trial of zinc supplements in relation to pregnancy outcomes, hematologic indicators, and T cell counts among HIV-1-infected women in Tanzania.

BACKGROUND: In observational studies, the zinc status of HIV-infected persons has been associated with both positive and adverse clinical outcomes. Such endpoints may affect the risk of adverse birth outcomes among HIV-infected women. OBJECTIVE: We examined the effects of zinc supplements on birth outcomes, hematologic indicators, and counts of T lymphocyte subsets among 400 HIV-infected pregnant women. DESIGN: Eligible women between 12 and 27 wk of gestation were randomly assigned to daily oral supplementation with either 25 mg Zn or placebo between recruitment and 6 wk after delivery. All women received iron, folic acid, and multivitamin supplements irrespective of the experimental assignment. RESULTS: We observed no significant differences in birth weight, duration of gestation, or fetal and neonatal mortality between women in the zinc and placebo groups. Hemoglobin concentrations increased between baseline and 6 wk postpartum in both groups. However, the rise in hemoglobin over this period was significantly lower (P = 0.03) in the zinc group (x +/- SD: 11.5 +/- 17.9 g/L) than in the placebo group (15.2 +/- 18.6 g/L). Similarly, the changes in red blood cell count and in packed cell volume over the same period were significantly lower in the zinc group (P < 0.01 and P = 0.01, respectively). Zinc had no effect on CD4(+), CD8(+), or CD3(+) cell counts during the follow-up period. CONCLUSION: Because of the lack of beneficial effects of zinc on adverse pregnancy outcomes and the likelihood of negative effects on hemoglobin concentrations, no compelling evidence exists to support the addition of zinc to prenatal supplements intended for pregnant HIV-infected women.

Adult↗
PubMed2005

Emergent autotransplantation of a renal allograft.

Renal autotransplantation is an acceptable treatment for a variety of renal pathology. Indications for autotransplantation include renal artery diseases, loin pain hematuria syndrome, repair of ureteral pathology, ex vivo tumor resection, and repair of traumatic injury. Long-term results confirm that autotransplantation is a safe and effective procedure. Renal allograft autotransplantation has also been described for repair of vascular disease, and relocation of an allograft. We describe the first case, to our knowledge of an emergent autotransplant of a renal allograft. The patient had undergone a simultaneous kidney-pancreas transplant 7 yr prior. During attempted stenting of a common iliac artery occlusion, the stent migrated, thus jeopardizing the renal allograft. The patient was taken emergently to the operating room for open repair. This included autotransplantation of the entire kidney. The patient recovered to baseline renal function. This article reviews the indications for renal autotransplantation and autotransplantation of a renal allograft. A case of emergent autotransplant of a renal allograft is described.

Adult↗
PubMed2005

Female sterilisation: a cohort controlled comparative study of ESSURE versus laparoscopic sterilisation.

OBJECTIVE: To compare patient satisfaction, discomfort, procedure time, success rate and adverse events of hysteroscopic (ESSURE, Conceptus Inc, San Carlos, USA) versus laparoscopic sterilisation. DESIGN: Cohort controlled comparative study. SETTING: The day surgery and outpatient unit of three large UK hospitals. POPULATION: Eighty-nine women requesting sterilisation were enrolled into the study. METHODS: A 2:1 ratio of ESSURE placement to laparoscopic sterilisation was undertaken. Laparoscopic sterilisation was carried out under general anaesthesia in the day surgery unit whereas all ESSURE procedures were carried out in a dedicated outpatient facility. All patients completed a self-assessment diary on days 7 and 90 post-operatively. Patient satisfaction, tolerance and discomfort were measured using an ordinal Likert style scale. Data were analysed using the chi(2) test for statistical significance. MAIN OUTCOME MEASURES: The primary outcome measure is patient satisfaction with ESSURE versus laparoscopic sterilisation. This included satisfaction with the decision to proceed with the relevant sterilisation method, recovery from the procedure and overall satisfaction following either ESSURE or laparoscopic sterilisation. Secondary outcome measures include successful completion of procedure, procedure time, tolerance, patient discomfort and post-operative adverse events. RESULTS: All women who underwent laparoscopic sterilisation had the procedure successfully completed whereas the overall bilateral device placement rate for ESSURE was 81%. Patient satisfaction with their decision to undergo either ESSURE or laparoscopic sterilisation was high with 94% of the ESSURE group being 'very' or 'somewhat' satisfied at 90 days post-procedure versus 80% in the laparoscopic sterilisation group. At 90 days post-procedure 100% of women in the ESSURE group were 'very satisfied' with their speed of recovery versus 80% in the laparoscopic sterilisation group. The procedure time (defined from the time of insertion of the hysteroscope or laparoscope to its removal) took significantly longer for ESSURE than laparoscopic sterilisation (mean = 13.2 vs 9.7 minutes, P= 0.045). However, the time required for insertion of a Verres needle and insufflation of the abdominal cavity is a necessary part of the laparoscopic sterilisation and had it been included would bring the procedures times more in line with each other. The mean time spent in hospital was significantly shorter for the ESSURE group than the laparoscopic group (188.7 vs 396.1 minutes, P < 0.005). Eighty-two percent of women in the ESSURE group described their tolerance of the procedure between 'good and excellent' compared with only 41% of the laparoscopic sterilisation group (P= 0.0002). Only 31% of the ESSURE group reported moderate or severe pain following the procedure compared with 63% of the laparoscopic sterilisation group (P= 0.08). Only 11% of patients had problems immediately post-operatively in the ESSURE group compared with 27% in the laparoscopy group. Finally, in the more medium term (three months post-operatively), patients still had an advantage in terms of post-procedure adverse events in the ESSURE group (21%vs 50%). CONCLUSIONS: This study provides evidence that ESSURE can be performed in the majority of women and, when successful, is associated with a greater overall patient satisfaction rate than laparoscopic sterilisation. Women also spend less time in hospital, have better tolerance of the procedure and describe less severe post-operative pain. However, the devices cannot be bilaterally placed in all cases and some women do not tolerate the procedure awake.

Adult↗
PubMed2005

HFE genetic variability, body iron stores, and the risk of type 2 diabetes in U.S. women.

To determine whether the HFE gene variants H63D and C282Y are associated with body iron stores and the risk of type 2 diabetes, we conducted a nested case-control study of 714 incident cases of type 2 diabetes and 1,120 matching control subjects in a prospective cohort, the Nurses' Health Study. In both healthy control and diabetic case subjects, H63D homozygosity, C282Y, and the compound heterozygotes were associated with significantly higher levels of plasma ferritin and significantly lower ratios of transferrin receptors to ferritin. Such effects were independent of age, BMI, and lifestyle factors. Overall, there were no significant differences in genotypes of H63D and C282Y between the case and control subjects. A meta-analysis of 4,245 case and 5,982 control subjects indicated a null association of C282Y with diabetes risk, whereas carriers of H63D or the compound heterozygotes had marginally increased risk (odds ratio [OR] 1.11 [95% CI 1.00-1.25] and 1.60 [0.99-2.60], respectively). In addition, we found a significant interaction between HFE variants and heme iron intake (P for interaction = 0.029). The ORs of type 2 diabetes across increasing quartiles of heme iron were 1.00, 1.21 (0.72-2.01), 1.72 (1.03-2.88), and 1.49 (0.91-2.46) among the participants with either the H63D or C282Y variant, whereas the ORs were 1.00, 0.71 (0.49-1.05), 1.12 (0.76-1.66), and 0.96 (0.65-1.42) among those with wild-type genotypes. Our data indicate significant effects of H63D and C282Y on body iron stores and suggest a potential interaction between HFE genotypes and heme iron intake in relation to the risk of type 2 diabetes.

Alcohol Drinking↗
PubMed2005

The +276 polymorphism of the APM1 gene, plasma adiponectin concentration, and cardiovascular risk in diabetic men.

Recently, the genetic variability at adiponectin locus (APM1) was associated with cardiovascular risk in patients with type 2 diabetes. We sought to examine the associations of five variants of APM1 gene (C-11365G, A-4034C, A-3964G, T45G, and G276T) with the risk of cardiovascular diseases (CVDs) in a larger cohort of diabetic patients. Of 879 diabetic men from the Health Professionals Follow-up Study, 239 participants developed coronary heart disease or stroke during 14 years of follow-up and 640 CVD-negative subjects were used as control subjects. The risk of CVD was significantly lower in TT homozygotes at locus +276 than in other genotypes under a recessive inheritance model after adjusting for age, BMI, smoking, alcohol consumption, physical activity, aspirin use, HbA1c, and history of hypertension or hypercholesterolemia (odds ratio 0.38 [95% CI 0.18-0.79]; P = 0.009). In the CVD-negative control subjects, the allele 276T was associated with significantly higher plasma adiponectin levels in a dose-dependent pattern (GG 14.8, GT 16.2, and TT 18.8 microg/ml) after adjusting for age, BMI, and other variables (P for trend = 0.0019). In conclusion, our study showed significant associations between APM1 G276T and decreased CVD risk and increased plasma adiponectin levels in diabetic men.

Adiponectin↗
PubMed2004

Fruit and vegetable intake and risk of major chronic disease.

BACKGROUND: Studies of fruit and vegetable consumption in relation to overall health are limited. We evaluated the relationship between fruit and vegetable intake and the incidence of cardiovascular disease and cancer and of deaths from other causes in two prospective cohorts. METHODS: A total of 71 910 female participants in the Nurses' Health study and 37,725 male participants in the Health Professionals' Follow-up Study who were free of major chronic disease completed baseline semiquantitative food-frequency questionnaires in 1984 and 1986, respectively. Dietary information was updated in 1986, 1990, and 1994 for women and in 1990 and 1994 for men. Participants were followed up for incidence of cardiovascular disease, cancer, or death through May 1998 (women) and January 1998 (men). Multivariable-adjusted relative risks were calculated with Cox proportional hazards analysis. RESULTS: We ascertained 9329 events (1964 cardiovascular, 6584 cancer, and 781 other deaths) in women and 4957 events (1670 cardiovascular diseases, 2500 cancers, and 787 other deaths) in men during follow-up. For men and women combined, participants in the highest quintile of total fruit and vegetable intake had a relative risk for major chronic disease of 0.95 (95% confidence interval [CI] = 0.89 to 1.01) times that of those in the lowest. Total fruit and vegetable intake was inversely associated with risk of cardiovascular disease but not with overall cancer incidence, with relative risk for an increment of five servings daily of 0.88 (95% CI = 0.81 to 0.95) for cardiovascular disease and 1.00 (95% CI = 0.95 to 1.05) for cancer. Of the food groups analyzed, green leafy vegetable intake showed the strongest inverse association with major chronic disease and cardiovascular disease. For an increment of one serving per day of green leafy vegetables, relative risks were 0.95 (95% CI = 0.92 to 0.99) for major chronic disease and 0.89 (95% CI = 0.83 to 0.96) for cardiovascular disease. CONCLUSIONS: Increased fruit and vegetable consumption was associated with a modest although not statistically significant reduction in the development of major chronic disease. The benefits appeared to be primarily for cardiovascular disease and not for cancer.

Adult↗
PubMed2004

Nutrition and physical activity and chronic disease prevention: research strategies and recommendations.

A shortage of credible information exists on practical dietary and physical activity patterns that have potential to reverse the national obesity epidemic and reduce the risk of major cancers and other chronic diseases. Securing such information is a challenging task, and there is considerable diversity of opinion concerning related research designs and priorities. Here, we put forward some perspectives on useful methodology and infrastructure developments for progress in this important area, and we list high-priority research topics in the areas of 1) assessment of nutrient intake and energy expenditure; 2) development of intermediate outcome biomarkers; 3) enhancement of cohort and cross-cultural studies; and 4) criteria for and development of full-scale nutrition and physical activity intervention trials.

Biomarkers↗
PubMed2004

Effect of prenatal vitamin supplementation on lower-genital levels of HIV type 1 and interleukin type 1 beta at 36 weeks of gestation.

Micronutrient status has been associated with shedding of human immunodeficiency virus type 1 (HIV-1) in the lower-genital tract in observational studies. We examined the effect of vitamin supplements on genital HIV-1 shedding and interleukin-1 beta (IL-1 beta ), a cytokine marker of vaginal inflammation and promotion of HIV-1 infection. Consenting HIV-1-infected pregnant women were randomized to receive daily supplementation with vitamin A and/or multivitamins B-complex, C, and E with use of a factorial design. Cervicovaginal lavage (CVL) specimens were obtained shortly before delivery. Significantly more women who received vitamin A had detectable levels of HIV-1 in CVL (74.8%), compared with those who did not receive vitamin A (65.1%) (P=.04, by multivariate analysis). Multivitamin B-complex, C, and E had no effect on the risk of viral shedding. Our results raise concern about the use of vitamin A supplements by HIV-1-infected women. Use of prenatal multivitamin supplements (including vitamins B-complex, C, and E) should be continued despite the lack of effect on HIV-1 transmission because of previously reported positive effects on maternal health and pregnancy outcomes.

Ascorbic Acid↗
PubMed2004

Dietary intake of Cruciferous vegetables, Glutathione S-transferase (GST) polymorphisms and lung cancer risk in a Caucasian population.

OBJECTIVE: To evaluate possible interactions between dietary intake of cruciferous vegetables and the glutathione s-transferase mu and theta (GSTM1 and GSTT1) genotypes in lung cancer risk. METHODS: Hospital-based case-control study of 716 Caucasian lung cancer cases and 939 spouse and friend controls conducted in Boston, Massachussetts between 1992 and 2000. Dietary intake was collected through a food frequency questionnaire and blood was obtained for genotyping. Logistic regression models were adjusted for age, gender, total calories and smoking variables. RESULTS: Higher intakes of cruciferous vegetables reduced lung cancer risk among GSTM1 present individuals (odds ratio (OR)highest versus lowest tertile = 0.61, 95% confidence interval (CI) = 0.39-0.95) but not among GSTM1 null individuals (OR(highest versus lowest tertile) = 1.15, 95% CI = 0.78-1.68). We observed statistically significant interactions between GSTM1 and cruciferous vegetable intake overall (likelihood ratio test (LRT): p = 0.05) and among current smokers (LRT: p = 0.01). No significant interactions were observed for GSTT1 or the combined GSTM1/T1 genotype. CONCLUSIONS: In our study, higher cruciferous vegetable intake reduced lung cancer risk only among individuals with the GSTM1 present genotype. Our findings differed from prior studies that specifically assessed isothiocyanates found in cruciferous vegetables or evaluated Asian study populations with higher levels of cruciferous vegetable consumption.

Aged↗