Biomedical subjects

Matthew P Longnecker

Publications and source records attributed to Matthew P Longnecker.

30 records · Page 2Linked to original sources

PubMed2004

Associations between plasma DDE levels and immunologic measures in African-American farmers in North Carolina.

Experimental studies in rodents demonstrate evidence of immunosuppressive effects of dietary exposure to DDT [2,2-bis((italic)p(/italic)-chlorophenyl)-1,1,1-trichloroethane], but human data pertaining to immunomodulating effects of DDT exposure are limited. In this study we examined the association between the persistent organochlorine breakdown product 1,1-dichloro-2,2,bis(p-chlorophenyl)ethylene p,p'-DDE) and immunologic measures using blood samples in a relatively highly exposed population of farmers in the United States. Levels of serum immunoglobulin A (IgA) and IgG and the prevalence of antinuclear antibodies in relation to plasma p,p'-DDE levels were evaluated in samples from 137 African-American male farmers (30-88 years of age; median, 64 years). Participants were recruited through black churches in four rural counties in eastern North Carolina. Data collection included a telephone interview pertaining to farming practices and health history, and one blood sample was collected from each participant. Linear and logistic regression, adjusting for age, cholesterol, triglycerides, smoking status, and years of any kind of pesticide use, was used to assess the association between immunologic parameters and plasma levels of p,p'-DDE. The median plasma p,p'-DDE concentration was 7.7 microg/L (range, 0.6-77.4 microg/L). There was no association between p,p'-DDE and IgA in any of the models. IgG levels decreased with increasing p,p'-DDE levels, with a statistically significant decrease of approximately 50% in the highest two categories of exposure (greater than or equal to 6.0 microg/L) compared with values of < 3.0 microg/L. Sixteen (12%) were positive for antinuclear antibodies. The prevalence of antinuclear antibodies was somewhat elevated in the highest category of p,p'-DDE exposure (odds ratio, 1.9; 95% confidence interval, 0.32-11.3; for > or = 12.0 microg/L compared with < 3.0 microg/L p,p'-DDE), but this difference was not statistically significant. These analyses provide evidence that p,p'-DDE modulates immune responses in humans.

Adult↗

PubMed2004

Prenatal DDT exposure in relation to anthropometric and pubertal measures in adolescent males.

DDT (dichlorodiphenyltrichloroethane), a pesticide once used widely in agriculture and now limited to public health use, remains a controversial chemical because of a combination of benefits and risks. DDT or its breakdown products are ubiquitous in the environment and in humans. Compounds in the DDT family have endocrine actions and have been associated with reproductive toxicity. A previous study reported associations between prenatal exposure to p,p -DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene] and increased height and weight in adolescent boys. We examined a group with higher exposures to see whether similar associations would occur. Our study group was 304 males born in Philadelphia in the early 1960s who had participated in a previous study. Anthropometric and pubertal measures from one to six visits during their adolescent years were available, as were stored maternal serum samples from pregnancy. We measured p,p -DDE, p,p -DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane], and o,p -DDT [1,1,1-trichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)-ethane] in the maternal serum. Outcomes examined in the boys were height, ratio of sitting height to height, body mass index, triceps skinfold thickness, ratio of subscapular to the sum of triceps and subscapular skinfold thicknesses, skeletal age, serum testosterone, and serum dehydroepiandrosterone sulfate. No associations between prenatal exposure to any of the DDT compounds and any outcome measure were seen.

Adolescent↗

PubMed2003

Oral contraceptive use and risk of breast cancer by histologic type.

We examined the association between oral contraceptive use and risk of specific breast cancer histopathologies in a large, multi-center, population-based, case-control study. Women younger than age 75 with a new diagnosis of invasive breast cancer were identified from 4 statewide tumor registries. We compared women with lobular (n = 493) and ductal carcinoma (n = 5,510) to randomly selected controls (n = 9,311). Odds ratios (OR) and 95% confidence intervals (CI) for each histologic type were estimated using polytomous logistic regression, adjusted for other breast cancer risk factors. Current oral contraceptive use was associated with increased risk of lobular carcinoma (OR = 2.6, 95%CI = 1.0-7.1) and there was a significant trend (p = 0.017) of increased risk with more recent use. Oral contraceptive use was not clearly associated with ductal carcinoma (OR = 1.2, 95%CI = 0.8-1.9). These results suggest that the association between oral contraceptive use and risk of breast cancer may vary by histologic type.

Adult↗

PubMed2003

Prenatal exposure to low-level polychlorinated biphenyls in relation to mental and motor development at 8 months.

The relation between exposure to low levels of polychlorinated biphenyls (PCBs), a class of persistent organic pollutants, and cognitive and motor development in young children has been examined in several studies, and results have varied. The authors evaluated the association between prenatal exposure to PCBs and children's neurodevelopment using data from the Collaborative Perinatal Project. Pregnant women were enrolled from 1959 to 1965 from 12 sites across the United States. PCBs were measured in maternal serum taken during pregnancy. To measure children's mental and psychomotor development at 8 months of age, the authors administered the Bayley Scales of Infant Development (means, 87 (standard deviation, 15) and 88 (standard deviation, 18), respectively). Overall, they did not observe a relation between prenatal PCB exposure and children's mental or psychomotor scores (n = 1,207; multivariate adjusted beta = 0.1 point per micro g/liter increase of PCB, p = 0.71, and beta = 0.5, p = 0.14, respectively). The PCB-psychomotor score relation varied by study center (p < 0.05): The association was direct in some centers, inverse in others. This could not be attributed to variation in the timing or measurement of the child's neurodevelopment or analysis of PCBs because these were standardized across centers. The reasons for variation in results within this study and across other studies remain unclear.

Adult↗

PubMed2003

An unexpected distribution of sodium concentration in serum specimens stored for more than 30 years.

PURPOSE: Sera from over 50,000 pregnant women in the Collaborative Perinatal Project have been frozen at -20 degrees C since 1959 to 1966, and with the health data on their offspring constitute a resource that is still actively used. In two studies using these specimens, we measured sodium concentration to assess desiccation. METHODS: Sodium was measured in over 5,000 specimens by two different methods. For 10 specimens with unusually low sodium values, a substudy was done to investigate the cause. RESULTS: High sodium levels (>140 mmol/L) were present in more than 20% of specimens, and levels were unusually low (<130 mmol/L) in more than 40% of specimens. The substudy showed that filtering the specimens increased sodium levels and that about 14% of the sodium was trapped in particulate matter. CONCLUSIONS: High sodium levels in these specimens were probably due to desiccation and possibly to leaching of sodium from the glass containers. Low sodium levels were probably caused by the particulate matter, which clogged the analytical sampling devices and also trapped sodium. In serum specimens that have been stored for long periods, use of routine laboratory procedures for analysis can yield erroneous results. Furthermore, measured analyte levels can be affected by more than just degradation and desiccation.

Adult↗

PubMed2003

Postmenopausal hormone therapy and risk of breast cancer by histologic type (United States).

OBJECTIVE: Postmenopausal hormone use and risk of breast cancer by histopathology was examined in a large multi-centered population-based case-control study. METHODS: Women younger than 75 years newly diagnosed with invasive breast cancer between 1988 and 1991 were identified from statewide tumour registries in Wisconsin, Massachusetts, New Hampshire, and Maine. Only postmenopausal women were included in this analysis. Breast cancer cases (lobular (n = 219), ductal, NOS (n = 2172), and specific ductal subtypes (n = 242)) were compared with randomly selected population controls (n = 3179) using adjusted multi-variable polytomous logistic regression to estimate odds ratios (OR) and 95% confidence intervals (95%CI) for each histology. RESULTS: Lobular carcinoma was associated with recent (within 2 years) estrogen therapy (OR: 1.8, 95% CI: 1.0-3.4) and recent use of combined estrogen-plus-progestin therapy (OR:3.6, 95%CI: 1.8-7.6). Risk of ductal carcinoma was not associated with recent use of either estrogen alone (OR: 0.9, 95% CI: 0.7-1.2) or combined therapy (OR:0.9, 95% CI: 0.6-1.3). No associations were found with ductal subtypes. CONCLUSIONS: The association between postmenopausal hormone use and risk of breast cancer may depend on histopathology. Of particular interest is the association between combined hormone therapy and increased risk of lobular carcinoma. This lesion is increasingly common but, nonetheless, comprises fewer than 10% of invasive breast cancers.

Aged↗

PubMed2003

The National Children's Study of environmental effects on child health and development.

Increasing recognition that children may be more susceptible than adults to environmental exposures and that they experience potentially life-long consequences of such exposures has led to widespread support for a large new cohort study in the United States. In this article, we propose a framework for a new cohort study of children, with follow-up beginning before birth and continuing to age 21 years. We also describe the administrative structure that has been built to develop the proposal further. The structure includes a partnership between federal and nonfederal scientists and relies on a collaborative, interdisciplinary research effort of unprecedented scale in medical research. We discuss briefly how the proposed cohort could be used to examine, among many other things, the effect of chemical contaminants in breast milk on children's health and development.

Child↗

PubMed2003

Comparison of polychlorinated biphenyl levels across studies of human neurodevelopment.

Polychlorinated biphenyls (PCBs) are persistent pollutants that are ubiquitous in the food chain, and detectable amounts are in the blood of almost every person in most populations that have been examined. Extensive evidence from animal studies shows that PCBs are neurotoxins, even at low doses. Interpretation of human data regarding low-level, early-life PCB exposure and subsequent neurodevelopment is problematic because levels of exposure were not similarly quantified across studies. We expressed the exposure levels from 10 studies of PCB and neurodevelopment in a uniform manner using a combination of data from original investigators, laboratory reanalyses, calculations based on published data, and expert opinion. The mainstay of our comparison was the median level of PCB 153 in maternal pregnancy serum. The median concentration of PCB 153 in the 10 studies ranged from 30 to 450 ng/g serum lipid, and the median of the 10 medians was 110 ng/g. We found that (a)) the distribution of PCB 153 exposure in most studies overlapped substantially, (b)) exposure levels in the Faroe Islands study were about 3-4-fold higher than in most other studies, and (c)) the exposure levels in the two recent U.S. studies were about one-third of those in the four earlier U.S. studies or recent Dutch, German, and northern Québec studies. Our results will facilitate a direct comparison of the findings on PCBs and neurodevelopment when they are published for all 10 studies.

Chromatography, Gas↗

PubMed2003

An approach to assessment of endocrine disruption in the National Children's Study.

In this article we consider the importance of assessing endocrine disruption in a large new cohort that has been proposed, the National Children's Study (NCS). We briefly review evidence that endocrine disruption is a potentially important hypothesis for human studies and weigh the need to assess endocrine disruption in the NCS. We note the salient features of earlier, similar cohort studies that serve as reference points for the design of the NCS. Finally, we discuss features of the NCS that would allow or enhance assessment of endocrine disruption, even if endocrine disruption were not a primary hypothesis motivating the study. At this time, the evidence supporting endocrine disruption in humans with background-level exposures is not strong. Thus, a compelling rationale for the NCS will probably need to be based on core hypotheses that focus on other issues. Nonetheless, if properly designed, the NCS could serve as an excellent resource for investigating future hypotheses regarding endocrine disruption.

Adolescent↗

PubMed2002

Maternal serum level of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene and risk of cryptorchidism, hypospadias, and polythelia among male offspring.

1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) is a metabolite of the insecticide 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (DDT) and is a ubiquitous environmental contaminant. Nearly everyone in the United States has a detectable serum level of DDE. DDE was recently found to inhibit binding of androgen to its receptor and to block androgen action in rodents. Normal development of male genitalia in mammals depends on androgen action. The authors used stored serum samples to examine the relation between maternal DDE levels during pregnancy and adjusted odds of cryptorchidism (n = 219), hypospadias (n = 199), and polythelia (extra nipples) (n = 167) among male offspring, using a nested case-control design with one control group (n = 552). Subjects were selected from the Collaborative Perinatal Project, a US birth cohort study begun in 1959-1966, when DDE levels were much higher than they are at present. Compared with boys whose mother's recovery-adjusted serum DDE level was less than 21.4 microg/liter, boys with maternal levels greater than or equal to 85.6 microg/liter had adjusted odds ratios of 1.3 (95% confidence interval (CI): 0.7, 2.4) for crypt-orchidism, 1.2 (95% CI: 0.6, 2.4) for hypospadias, and 1.9 (95% CI: 0.9, 4.0) for polythelia. For cryptorchidism and polythelia, the results were consistent with a modest-to-moderate association, but in no instance was the estimate very precise. The results were inconclusive.

Adult↗

PubMed2002

DDT metabolite and androgens in African-American farmers.

BACKGROUND: The ubiquitous dichlorodiphenyltrichloroethane (DDT) metabolite 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) is an androgen receptor antagonist. Data on potential antiandrogenic activity of DDE in humans are limited. METHODS: The relations between concentrations of plasma DDE and several serum androgens (total testosterone, bioavailable testosterone, 5alpha-dihydrotestosterone, and free androgen index) were examined in 137 North Carolina black male farmers, using multiple linear regression. RESULTS: Participants ranged in age from 30 to 88 years (mean = 62 years). Most had farmed for about 30 years and 27% reported having used DDT. The median DDE level was 7.7 microg per liter (1213 microg per kg lipid), slightly higher than in other recent studies. Overall, concentrations of DDE and androgens were unrelated. Total testosterone decreased 2% (95% confidence limits [CL] = -9%, 5%) per increase in interquartile distance of lipid-adjusted DDE. The percentage change in other hormones was similarly negligible. However, among those whose DDE level was in the top tenth percentile, compared with all others, total testosterone and free androgen index were lower by 23% (CL= -40%, 1%) and 22% (CL =-41%, 4%) respectively. Plasma androgen levels decreased with age, a relation that has previously been studied only in whites. CONCLUSIONS: Studies of more highly exposed populations may be needed to evaluate effects, if any, of DDE.

Adult↗

PubMedDate not supplied

In utero exposure to polychlorinated biphenyls and sensorineural hearing loss in 8-year-old children.

Early-life exposure to polychlorinated biphenyls (PCBs), a ubiquitous environmental contaminant, increases the hearing threshold at selected frequencies in rats. Among humans from the Faroe Islands with unusually high early-life PCB exposure, exposure was directly associated with increased hearing thresholds at two frequencies, although the deficits were present in the left ear but not the right. We examined PCB levels in maternal pregnancy serum in relation with audiometrically determined hearing thresholds among offspring when they were of school age. Complete data were available for 195 children with sensorineural hearing loss (SNHL) and 615 children selected at random, all of whom were born in 1959-1966 in the Collaborative Perinatal Project (CPP) U.S. cohort. The median exposure among those selected at random, as reflected by the mother's third trimester serum total PCB concentration, was 2.8 microg/l, about twofold higher than recent background levels in the United States. Based on the average hearing threshold across the frequencies essential for speech recognition in the "worst ear," the maternal serum PCB level was unrelated to the adjusted odds of SNHL or to adjusted mean hearing threshold. Overall, an adverse effect of early-life, background-level PCB exposure on SNHL was not supported by these data.

Adult↗