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Biomedical subjects

M P Longnecker

Publications and source records attributed to M P Longnecker.

At least 19 recordsLinked to original sources
PubMed2006

Obesity and time to pregnancy.

BACKGROUND: Obesity may reduce fecundity. We examined the obesity-fecundity association in relation to menstrual cycle regularity, parity, smoking habits and age to gain insight into mechanisms and susceptible subgroups. METHODS: Data were provided by 7327 pregnant women enrolled in the Collaborative Perinatal Project at 12 study centres in the United States from 1959 to 1965. Prepregnancy body mass index (BMI) was analysed continuously and categorically [underweight (<18.5 kg/m2), optimal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2) and obese (>or=30.0 kg/m2)]. Adjusted fecundability odds ratios (FORs) were estimated using Cox proportional hazards modelling for discrete time data. RESULTS: Fecundity was reduced for overweight [OR=0.92, 95% confidence interval (95% CI): 0.84, 1.01] and obese (OR=0.82, 95% CI: 0.72, 0.95) women compared with optimal weight women and was more evident for obese primiparous women (OR=0.66, 95% CI: 0.49, 0.89). Fecundity remained reduced for overweight and obese women with normal menstrual cycles. Neither smoking habits nor age modified the association. CONCLUSIONS: Obesity was associated with reduced fecundity for all subgroups of women and persisted for women with regular cycles. Our results suggest that weight loss could increase fecundity for overweight and obese women, regardless of menstrual cycle regularity, parity, smoking habits and age.

Adult↗
PubMed2005

Maternal hormone levels among populations at high and low risk of testicular germ cell cancer.

Ethnic differences in maternal oestrogen levels have been suggested as explaining the significantly higher risk of testicular germ cell tumours (TGCT) of white men than black men in the United States. We therefore examined levels of maternal oestrogens, as well as testosterone and alphafetoprotein (AFP), in 150 black and 150 white mothers in the Collaborative Perinatal Project. Serum levels of estradiol (total, free and bioavailable), estriol, testosterone (total, free and bioavailable), sex hormone binding globulin (SHBG), and AFP were examined during first and third trimesters. We found that the black mothers, rather than the white mothers, had significantly higher estradiol levels in first trimester (P=0.05). Black mothers also had significantly higher levels of all testosterone (P<0.001) and AFP (P<0.001) in both trimesters. In addition, the ratios of sex hormones (estradiol/testosterone) were significantly lower among black mothers. These findings provide little support to the oestrogen hypothesis, but are consistent with higher levels of testosterones and/or AFP being associated with reduced risk of TGCT; alternatively, lower oestrogen/androgen ratios may be associated with reduced risk.

Adult↗
PubMed2002

A semiparametric empirical likelihood method for data from an outcome-dependent sampling scheme with a continuous outcome.

Outcome-dependent sampling (ODS) schemes can be a cost effective way to enhance study efficiency. The case-control design has been widely used in epidemiologic studies. However, when the outcome is measured on a continuous scale, dichotomizing the outcome could lead to a loss of efficiency. Recent epidemiologic studies have used ODS sampling schemes where, in addition to an overall random sample, there are also a number of supplemental samples that are collected based on a continuous outcome variable. We consider a semiparametric empirical likelihood inference procedure in which the underlying distribution of covariates is treated as a nuisance parameter and is left unspecified. The proposed estimator has asymptotic normality properties. The likelihood ratio statistic using the semiparametric empirical likelihood function has Wilks-type properties in that, under the null, it follows a chi-square distribution asymptotically and is independent of the nuisance parameters. Our simulation results indicate that, for data obtained using an ODS design, the semiparametric empirical likelihood estimator is more efficient than conditional likelihood and probability weighted pseudolikelihood estimators and that ODS designs (along with the proposed estimator) can produce more efficient estimates than simple random sample designs of the same size. We apply the proposed method to analyze a data set from the Collaborative Perinatal Project (CPP), an ongoing environmental epidemiologic study, to assess the relationship between maternal polychlorinated biphenyl (PCB) level and children's IQ test performance.

Biometry↗
PubMed2001

Association between maternal serum concentration of the DDT metabolite DDE and preterm and small-for-gestational-age babies at birth.

BACKGROUND: DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane) is highly effective against most malaria-transmitting mosquitoes and is being widely used in malaria-endemic areas. The metabolite, DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene), has been linked to preterm birth in small studies, but these findings are inconclusive. Our aim was to investigate the association between DDE exposure and preterm birth. METHODS: Our study was based on the US Collaborative Perinatal Project (CPP). From this study we selected a subset of more than 44000 eligible children born between 1959 and 1966 and measured the DDE concentration in their mothers' serum samples stored during pregnancy. Complete data were available for 2380 children, of whom 361 were born preterm and 221 were small-for-gestational age. FINDINGS: The median maternal DDE concentration was 25 mg/L (range 3-178)-several fold higher than current US concentrations. The adjusted odds ratios (OR) of preterm birth increased steadily with increasing concentrations of serum DDE (ORs=1, 1.5, 1.6, 2.5, 3.1; trend p<0.0001). Adjusted odds of small-for-gestational-age also increased, but less consistently (ORs=1, 1.9, 1.7, 1.6, 2.6; trend p=0.04). After excluding preterm births, the association of DDE with small-for-gestational-age remained. INTERPRETATION: The findings strongly suggest that DDT use increases preterm births, which is a major contributor to infant mortality. If this association is causal, it should be included in any assessment of the costs and benefits of vector control with DDT.

Adolescent↗
PubMed2001

Relation of serum tetrachlorodibenzo-p-dioxin concentration to diet among veterans in the Air Force Health Study with background-level exposure.

To examine the contribution of various foods to exposure to 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD) in a background-exposed U.S. population, serum TCDD levels were examined in relation to diet as assessed by a standard diet assessment instrument among men with no known unusual exposure to TCDD. Our subjects were male veterans aged 42-76 yr who were in the unexposed comparison group in the Air Force Health Study, a study of the health effects of exposure to Agent Orange and herbicides in Vietnam. Food consumption was assessed by a 126-item food frequency questionnaire. Two hundred and ninety veterans who had both TCDD levels and diet assessed in 1992 were included. In general, associations between serum TCDD and consumption of foods in specific groups or nutrients, that is, meats and fats, were not evident. Among younger men, fish and chicken intake were associated with higher serum TCDD levels. The results suggest that no single food group accounts for a large proportion of variation in TCDD exposure in older U.S. men.

Adult↗
PubMed2001

Serum dioxin and hepatic abnormalities in veterans of Operation Ranch Hand.

PURPOSE: We studied hepatic abnormalities and indices of hepatic function in relation to exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) in veterans of Operation Ranch Hand, the Air Force unit responsible for the aerial spraying of herbicides in Vietnam from 1962 to 1971. METHODS: The prevalence of ever having liver disease through March 1993, and level of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase (GGT), lactic dehydrogenase (LDH), alkaline phosphatase, and total bilirubin were examined according to serum dioxin levels. RESULTS: We found an increased risk of "other liver disorders" among veterans with the highest dioxin levels [adjusted odds ratio (OR) = 1.6, 95% confidence interval (CI) 1.2 to 2.1], due primarily to increased transaminases or LDH (adjusted OR = 2.7, 95% CI 1.4 to 5.1) and to other nonspecific liver abnormalities (adjusted OR = 1.4, 95% CI 1.0 to 2.0). CONCLUSIONS: Whether the associations observed were causal is unclear from these data.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed2001

Environmental contaminants as etiologic factors for diabetes.

For both type 1 and type 2 diabetes mellitus, the rates have been increasing in the United States and elsewhere; rates vary widely by country, and genetic factors account for less than half of new cases. These observations suggest environmental factors cause both type 1 and type 2 diabetes. Occupational exposures have been associated with increased risk of diabetes. In addition, recent data suggest that toxic substances in the environment, other than infectious agents or exposures that stimulate an immune response, are associated with the occurrence of these diseases. We reviewed the epidemiologic data that addressed whether environmental contaminants might cause type 1 or type 2 diabetes. For type 1 diabetes, higher intake of nitrates, nitrites, and N-nitroso compounds, as well as higher serum levels of polychlorinated biphenyls have been associated with increased risk. Overall, however, the data were limited or inconsistent. With respect to type 2 diabetes, data on arsenic and 2,3,7,8-tetrachlorodibenzo-p-dioxin relative to risk were suggestive of a direct association but were inconclusive. The occupational data suggested that more data on exposure to N-nitroso compounds, arsenic, dioxins, talc, and straight oil machining fluids in relation to diabetes would be useful. Although environmental factors other than contaminants may account for the majority of type 1 and type 2 diabetes, the etiologic role of several contaminants and occupational exposures deserves further study.

Diabetes Mellitus, Type 1↗
PubMed2001

Polychlorinated biphenyl serum levels in pregnant subjects with diabetes.

OBJECTIVE: Polychlorinated biphenyls (PCBs) are persistent pollutants that are ubiquitous in the food chain; detectable amounts are in the blood of nearly everyone. Their effect on humans at background levels of exposure is an area of active investigation. Increased blood levels of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin), a PCB-like compound, have recently been reported among subjects with diabetes, suggesting that PCB levels could be similarly elevated. To test this hypothesis, we examined a group of pregnant women whose serum PCB levels had been measured and whose diabetes status had been previously recorded. RESEARCH DESIGN AND METHODS: Using stored serum from a large birth cohort study, we conducted a cross-sectional study of 2,245 pregnant women, of whom 44 had diabetes (primarily type 1) and 2,201 were control subjects. RESULTS: The adjusted mean serum level of PCBs among the subjects with diabetes was 30% higher than in the control subjects (P = 0.0002), and the relationship of PCB level to adjusted odds of diabetes was linear. CONCLUSIONS: The possibility exists that PCBs and diabetes are causality related; alternatively, the pharmacokinetics of PCBs could be altered among patients with diabetes. At any event, if the association is replicated in other studies, increased serum levels of PCBs in subjects with diabetes or their offspring may put them at increased risk of PCB-induced changes in thyroid metabolism or neurodevelopment.

Adult↗
PubMed2000

Age at any full-term pregnancy and breast cancer risk.

The authors analyzed data from two multistate, population-based case-control studies to investigate the association between age at any full-term pregnancy (FP) and breast cancer risk. Study subjects included breast cancer cases aged 20-79 years identified from four statewide cancer registries and randomly selected controls interviewed from 1988 to 1996. Complete information on a comprehensive set of risk factors for breast cancer was available for 9,891 cases and 12,271 controls. The large number of subjects enabled simultaneous adjustment of the covariates and efficient application of various modeling approaches. Overall, each 5-year increase in age at first FP was associated with an odds ratio of 1.07 (95% confidence interval (CI): 1.01, 1.13) for breast cancer. The corresponding estimates were odds ratio = 1.02 (95% CI: 1.00, 1.05) for age at second through ninth FPs. For age at last FP, the effect estimate (odds ratio = 1.01, 95% CI: 0.97, 1.06) was indistinguishable from that for other FPs after the first. In this analysis, a modest and transient increase in breast cancer risk after childbirth was also observed. The relatively greater effect of age at first FP is consistent with the existence of a long-term effect of early first FP on the differentiation of mammary cells, causing them to become less susceptible to carcinogenesis.

Adolescent↗
PubMed2000

Risk of ovarian cancer in relation to use of phenolphthalein-containing laxatives.

We examined ovarian cancer risk in relation to use of phenolphthalein-containing laxatives in 410 epithelial ovarian cancer cases and 713 controls. Compared to women who never used a laxative, ever use of a phenolphthalein-containing laxative was not associated with an increased risk of ovarian cancer (odds ratio, OR, 1.1, 95% confidence interval, CI, 0.9-1.4). Risk was slightly, but not significantly, higher with more frequent use (OR 1.2 for 75 or more days of use). When women who used non-phenolphthalein containing laxatives was used as the reference group, the associations were slightly, but not significantly larger (OR 1.4 for any use of phenolphthalein-containing laxatives and OR 1.5 for 75 or more days of use)

Adult↗
PubMed2000

Serum dioxin level in relation to diabetes mellitus among Air Force veterans with background levels of exposure.

Data from several epidemiologic studies suggest that exposure to unusually high amounts of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) increases the risk of diabetes mellitus, and experimental data suggest that the mechanism for this is decreased cellular glucose uptake. To investigate the dose-response relation more closely, we examined the association of serum dioxin level with prevalence of diabetes mellitus and with levels of serum insulin and glucose among 1,197 veterans in the Air Force Health Study who never had contact with dioxin-contaminated herbicides and whose serum dioxin level was within the range of background exposure typically seen in the United States (< or =10 ng/kg lipid). Compared with those whose serum dioxin level was in the first quartile (<2.8 ng/kg lipid), the multivariate-adjusted odds of diabetes among those in the highest quartile (> or =5.2 ng/kg lipid) was 1.71 (95% confidence interval = 1.00-2.91). The association was slightly attenuated after adjustment for serum triglycerides. Whether adjustment for serum triglycerides was appropriate, however, cannot be determined with available data. The association of background-level dioxin exposure with the prevalence of diabetes in these data may well be due to reasons other than causality, although a causal contribution cannot be wholly dismissed.

Blood Glucose↗
PubMed2000

Polychlorinated biphenyl (PCB) exposure in relation to thyroid hormone levels in neonates.

Polychlorinated biphenyls (PCBs) are industrially produced environmentally persistent compounds. In developed countries all humans have detectable levels in blood and other tissues. PCBs alter thyroid hormone metabolism in animal experiments, and human data suggest background-level exposure may have similar effects in neonates. We evaluated this possible effect among 160 North Carolina children whose in utero PCB exposure was estimated on the basis of the mother's PCB levels in milk and blood, in 1978-1982 (estimated median PCB level in milk at birth, 1.8 mg/kg lipid). Their umbilical cord sera were thawed in 1998 and assayed for total thyroxine, free thyroxine, and thyroid stimulating hormone. We found that PCB exposure was not strongly related to any of the thyroid measures. For example, for a one unit change in milk PCB concentration (mg/kg lipid), the associated multivariate-adjusted increase in thyroid stimulating hormone level was 7% (95% confidence limits (CL) = -6, 21). Despite the possibility of sample degradation, these data suggest that within the range of background-level exposure in the United States, in utero PCB exposure is only slightly related to serum concentration of total thyroxine, free thyroxine, and thyroid stimulating hormone at birth.

Adult↗
PubMed2000

Eating frequency and risk of colorectal cancer.

Case-control studies have found elevated risk of colorectal cancer with higher eating frequency. The present analyses, the first to examine this association using prospectively collected information, utilized nationally representative data from the Epidemiologic Follow-Up Study of the First National Health and Nutrition Examination Survey (NHEFS). The study population included 9,978 subjects followed from 1982-84 to 1992. Colorectal cancer cases (n = 141) were identified by self-report, hospital records, and death certificates. Interviews conducted in 1982-84 provided information on meal and snack frequencies and covariates of interest. Relative risk (RR) of colorectal cancer and 95% confidence intervals (CI) were estimated using Cox proportional hazards models adjusted for age, gender, and race and energy, alcohol, total fat, and fiber intake. Compared with those eating < 3 times/day, those eating 3-4 times/day had an RR of 0.66 (95% CI = 0.42-1.03) and those eating > 4 times/day had an RR of 0.74 (95% CI = 0.41-1.32). The association was due to decreased risk with more meals rather than more snacks per day. Given limitations of previous studies as well as the possibility of a protective effect of higher eating frequency through improved glycemic control, the present findings suggest that the influence of eating frequency on colorectal cancer risk is more complex than has been previously supposed and merits additional study.

Adult↗
PubMed1999

Correlations among polychlorinated biphenyls, dioxins, and furans in humans.

BACKGROUND: Correlations among human levels of polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins, and polychlorinated dibenzofurans potentially complicate interpretation of studies of their individual health effects. Outcomes attributed to one may, in fact, be due to another. METHODS: We present correlations among dioxins, furans, and PCBs in blood collected in 1991-1992 from 44 American Vietnam veterans from Michigan. RESULTS: Correlations among specific dioxins and furans ranged from 0.26 to 0.80, with the higher-chlorinated congeners being more highly correlated. Correlations among PCBs ranged from 0.06 to 0.94, with those occurring at highest concentrations being more highly correlated. Correlations of PCBs with dioxins and furans ranged from -0.09 to 0.59. Correlations of individual chemicals with total dioxin toxic equivalents ranged from 0.31 to 0.76. DISCUSSION/CONCLUSIONS: If confirmed in other populations, such correlations may allow the use of simpler assays but may also raise issues of confounding and calibration.

Adult↗
PubMed1999

Calculation of population attributable risk for alcohol and breast cancer (United States).

OBJECTIVES: Because of increasing evidence that alcohol may be causally associated with breast cancer, we reconsider the population attributable risk (PAR) for alcohol and breast cancer for the US adult female population using an effect estimate from a meta-analysis and incorporating a revised perspective on measurement error correction. METHODS: To estimate PAR, we employed a formula appropriate to use with an adjusted effect estimate. To estimate intermediate quantities needed to apply that formula, we used adjusted relative risk estimates from a previously published meta-analysis, as well as SEER cancer statistics and general population data from the third National Health and Nutrition Examination Survey. We used relative risk estimates uncorrected for measurement error. RESULTS: The estimated age-adjusted PAR for alcohol and breast cancer was 2.1%. CONCLUSIONS: Because of the modest association between alcohol and breast cancer and the generally moderate level of alcohol intake among US women, the proportion of breast cancer attributable to alcohol intake is small. Widespread efforts to reduce alcohol consumption would not have a substantial impact on breast cancer rates in this population. While selected subgroups of women might benefit from decreasing alcohol consumption, specific profiles for such women have yet to be defined and defended.

Adult↗