Longitudinal association of prepubertal urinary phthalate metabolite concentrations with pubertal progression among a cohort of boys.

BACKGROUND: Epidemiological studies have reported associations of anti-androgenic phthalate metabolite concentrations with later onset of male puberty, but few have assessed associations with progression. OBJECTIVES: We examined the association of prepubertal urinary phthalate metabolite concentrations with trajectories of pubertal progression among Russian boys. METHODS: At enrollment (ages 8-9 years), medical history, dietary, and demographic information were collected. At entry and annually to age 19 years, physical examinations including testicular volume (TV) were performed and spot urines collected. Each boy's prepubertal urine samples were pooled, and 15 phthalate metabolites were quantified by isotope dilution LC-MS/MS at Moscow State University. Metabolites of anti-androgenic parent phthalates were included: butylbenzyl (BBzP), di-n-butyl (DnBP), diisobutyl (DiBP), di(2-ethylhexyl) (DEHP) and diisononyl (DiNP) phthalates. We calculated the molar sums of DEHP, DiNP, and all AAP metabolites. We used group-based trajectory models (GBTMs) to identify subgroups of boys who followed similar pubertal trajectories from ages 8-19 years based on annual TV. We used multinomial and ordinal regression models to evaluate whether prepubertal log-transformed phthalate metabolite concentrations were associated with slower or faster pubertal progression trajectories, adjusting for covariates. RESULTS: 304 boys contributed a total of 752 prepubertal urine samples (median 2, range: 1-6) for creation of individual pools. The median length of follow-up was 10.0 years; 79% of boys were followed beyond age 15. We identified three pubertal progression groups: slower (34%), moderate (43%), and faster (23%) progression. A standard deviation increase in urinary log-monobenzyl phthalate (MBzP) concentrations was associated with higher adjusted odds of being in the slow versus faster pubertal progression trajectory (aOR 1.47, 95% CI 1.06-2.04). None of the other phthalate metabolites were associated with pubertal progression. CONCLUSIONS: On average, boys with higher concentrations of prepubertal urinary MBzP had a slower tempo of pubertal progression, perhaps attributable to the disruption of androgen-dependent biological pathways.

Human sperm sex chromosome disomy and sperm DNA damage assessed by the neutral comet assay.

STUDY QUESTION: Is there an association between human sperm sex chromosome disomy and sperm DNA damage? SUMMARY ANSWER: An increase in human sperm XY disomy was associated with higher comet extent; however, there was no other consistent association of sex chromosome disomies with DNA damage. WHAT IS KNOWN ALREADY: There is limited published research on the association between sex chromosome disomy and sperm DNA damage and the findings are not consistent across studies. STUDY DESIGN, SIZE, AND DURATION: We conducted a cross-sectional study of 190 men (25% ever smoker, 75% never smoker) from subfertile couples presenting at the Massachusetts General Hospital Fertility Clinic from January 2000 to May 2003. PARTICIPANTS/MATERIALS, SETTING, METHODS: Multiprobe fluorescence in situ hybridization for chromosomes X, Y and 18 was used to determine XX, YY, XY and total sex chromosome disomy in sperm nuclei using an automated scoring method. The neutral comet assay was used to measure sperm DNA damage, as reflected by comet extent, percentage DNA in the comet tail, and tail distributed moment. Univariate and multiple linear regression models were constructed with sex chromosome disomy (separate models for each of the four disomic conditions) as the independent variable, and DNA damage parameters (separate models for each measure of DNA damage) as the dependent variable. MAIN RESULTS AND THE ROLE OF CHANCE: Men with current or past smoking history had significantly greater comet extent (µm: regression coefficients with 95% CI) [XX18: 15.17 (1.98, 28.36); YY18: 14.68 (1.50, 27.86); XY18: 15.41 (2.37, 28.45); Total Sex Chromosome Disomy: 15.23 (2.09, 28.38)], and tail distributed moment [XX18: 3.01 (0.30, 5.72); YY18: 2.95 (0.24, 5.67); XY18: 3.04 (0.36, 5.72); Total Sex Chromosome Disomy: 3.10 (0.31, 5.71)] than men who had never smoked. In regression models adjusted for age and smoking, there was a positive association between XY disomy and comet extent. For an increase in XY disomy from 0.56 to 1.47% (representing the 25th to 75th percentile), there was a mean increase of 5.08 µm in comet extent. No other statistically significant findings were observed. LIMITATIONS, REASONS FOR CAUTION: A potential limitation of this study is that it is cross-sectional. Cross-sectional analyses by nature do not lend themselves to inference about directionality for any observed associations; therefore we cannot determine which variable is the cause and which one is the effect. A small sample size may be a further limitation. Comparison of these findings to other studies is limited due to methodological differences. WIDER IMPLICATIONS OF THE FINDINGS: Although consistent associations across sex chromosome disomies or DNA damage measures were not observed, this study highlights the need to explore etiologies of sperm DNA damage and sex chromosome disomy to better understand the potential mechanistic overlaps between the two. STUDY FUNDING/COMPETING INTERESTS: This work was supported by NIOSH Grant T42 OH008416, and NIH/NIEHS Grants ES 009718, ES 000002, and R01 ES017457. During the study M.E.M. was affiliated with the Department of Environmental Health at the Harvard School of Public Health. TRIAL REGISTRATION NUMBER: N/A.

The association between sperm sex chromosome disomy and semen concentration, motility and morphology.

STUDY QUESTION: Is there an association between sex chromosome disomy and semen concentration, motility and morphology? SUMMARY ANSWER: Higher rates of XY disomy were associated with a significant increase in abnormal semen parameters, particularly low semen concentration. WHAT IS KNOWN ALREADY: Although some prior studies have shown associations between sperm chromosomal abnormalities and reduced semen quality, results of others are inconsistent. Definitive findings have been limited by small sample sizes and lack of adjustment for potential confounders. STUDY DESIGN, SIZE AND DURATION: Cross-sectional study of men from subfertile couples presenting at the Massachusetts General Hospital Fertility Clinic from January 2000 to May 2003. PARTICIPANTS/MATERIALS, SETTING, METHODS: With a sample of 192 men, multiprobe fluorescence in situ hybridization for chromosomes X, Y and 18 was used to determine XX, YY, XY and total sex chromosome disomy in sperm nuclei. Sperm concentration and motility were measured using computer-assisted sperm analysis; morphology was scored using strict criteria. Logistic regression models were used to evaluate the odds of abnormal semen parameters [as defined by World Health Organization (WHO)] as a function of sperm sex chromosome disomy. MAIN RESULTS AND THE ROLE OF CHANCE: The median percentage disomy was 0.3 for XX and YY, 0.9 for XY and 1.6 for total sex chromosome disomy. Men who had abnormalities in all three semen parameters had significantly higher median rates of XX, XY and total sex chromosome disomy than controls with normal semen parameters (0.43 versus 0.25%, 1.36 versus 0.87% and 2.37 versus 1.52%, respectively, all P< 0.05). In logistic regression models, each 0.1% increase in XY disomy was associated with a 7% increase (odds ratio: 1.07, 95% confidence interval: 1.02-1.13) in the odds of having below normal semen concentration (<20 million/ml) after adjustment for age, smoking status and abstinence time. Increases in XX, YY and total sex chromosome disomy were not associated with an increase in the odds of a man having abnormal semen parameters. In addition, autosomal chromosome disomy (1818) was not associated with abnormal semen parameters. LIMITATIONS, REASONS FOR CAUTION: A potential limitation of this study, as well as those currently in the published literature, is that it is cross-sectional. Cross-sectional analyses by nature do not lend themselves to inference about directionality for any observed associations; therefore, we cannot determine which variable is the cause and which one is the effect. Additionally, the use of WHO cutoff criteria for dichotomizing semen parameters may not fully define fertility status; however, in this study, fertility status was not an outcome we were attempting to assess. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest study to date seeking to understand the association between sperm sex chromosome disomy and semen parameters, and the first to use multivariate modeling to understand this relationship. The findings are similar to those in the published literature and highlight the need for mechanistic studies to better characterize the interrelationships between sex chromosome disomy and standard indices of sperm health. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from NIOSH (T42 OH008416) and NIEHS (R01 ES009718, P30 ES000002 and R01 ES017457). The authors declare no competing interests. At the time this work was conducted and the initial manuscript written, MEM was affiliated with the Environmental Health Department at the Harvard School of Public Health. Currently, MEM is employed by Millennium: The Takeda Oncology Company. TRIAL REGISTRATION NUMBER: N/A.

Association of prenatal maternal perceived stress with a sexually dimorphic measure of cognition in 4.5-month-old infants.

Maternal prenatal stress can adversely impact subsequent child neurodevelopment, but little is known about its effect on cognitive development in infancy. This analysis of 107 infants from a prospective birth cohort assessed whether prenatal stress disrupts sexually dimorphic performance typically observed on a physical reasoning task. Maternal stress was assessed at 8-14 and 33-37 gestational weeks using the Perceived Stress Scale. Stress was defined as: low (scores below the median at both times), medium (scores above the median at one of the two times), and high (scores above the median at both times). At 4.5 months infants saw videos of two events: one impossible and the other possible. In the impossible event a box was placed against a wall without support underneath. In the possible event the box was placed against the wall, supported by the floor. Looking time at each event was recorded via infrared eye-tracking. Previous literature has shown that, at 4.5 months of age, girls typically look significantly longer at the impossible than at the possible event, suggesting that they expect the unsupported box to fall and are surprised when it does not. Boys tend to look equally at the two events suggesting that they do not share this expectation. This sex difference was replicated in the current study. General linear models stratified by sex and adjusted for household income, maternal education, mother's age at birth, infant's age at exam, and order of event presentation revealed that girls whose mothers reported high perceived stress during pregnancy had shorter looking time differences between the impossible and possible events than girls whose mothers reported low perceived stress (ß = -7.1; 95% CI: -12.0, -2.2 s; p = 0.006). Similar to boys, girls in the highest stress category spent about the same amount of time looking at each event. For boys, there were no significant looking time differences by maternal stress level. This finding suggests prenatal stress is associated with a delay in the development of physical reasoning in girls.

Arsenic exposure in relation to apple consumption among infants in the New Hampshire Birth Cohort Study.

Infants and young children commonly consume apple-based products, which may contain high concentrations of inorganic arsenic (iAs). As yet, iAs exposure from ingesting apple products has not been well-characterized in early childhood. Therefore, we investigated the association between urinary arsenic concentrations and intake of apple products in one-year-old infants participating in the New Hampshire Birth Cohort Study. A three-day food diary prior to collection of a spot urine sample was used to determine infant's consumption of apple products. The sum of urinary iAs, monomethylarsonic acid, and dimethylarsinic acid, referred to as ΣAs, was used to estimate iAs exposure. A total of 242 infants had urinary arsenic speciation analyzed without indication of fish/seafood consumption (urinary arsenobetaine < 1 µg/L) and with a completed three-day food diary. Of these, 183 (76%) infants ate apples or products containing apple. The geometric mean urinary ΣAs among the 59 infants who did not consume any type of apple product was 2.78 µg/L as compared to 2.38, 2.46, 2.28, and 2.73 µg/L among infants who exclusively consumed apple juice (n = 30), apple puree (n = 67), apples as whole fruit (n = 20) or products mixed with apples (n = 21), respectively. Differences in urinary ΣAs associated with apple consumption were not statistically significant in generalized linear models adjusted for urine dilution, rice consumption, and household water arsenic. Thus, while infants in our study frequently consumed apples and apple products, we did not find evidence that it increased iAs exposure.

Pancreatic cancer and serum organochlorine levels.

Occupational exposure to p,p'-dichlorodiphenyltrichloroethane (DDT) has been associated with increased pancreatic cancer risk. We measured organochlorine levels in serum obtained at the study enrollment from 108 pancreatic cancer cases and 82 control subjects aged 32-85 years in the San Francisco Bay Area between 1996 and 1998. Cases were identified using rapid case-ascertainment methods; controls were frequency-matched to cases on age and sex via random digit dial and random sampling of Health Care Financing Administration lists. Serum organochlorine levels were adjusted for lipid content to account for variation in the lipid concentration in serum between subjects. Median concentrations of p,p'-dichlorodiphenyldichloroethylene (DDE, 1290 versus 1030 ng/g lipid; P = 0.05), polychlorinated biphenyls (PCBs; 330 versus 220 ng/g lipid; P<0.001), and transnonachlor (54 versus 28 ng/g lipid; P = 0.03) were significantly greater among cases than controls. A significant dose-response relationship was observed for total PCBs (P for trend <0.001). Subjects in the highest tertile of PCBs (> or =360 ng/g lipid) had an odds ratio (OR) of 4.2 [95% confidence interval (CI) = 1.8-9.4] compared to the lowest tertile. The OR of 2.1 for the highest level of p,p'-DDE (95% CI = 0.9-4.7) diminished (OR = 1.1; 95% CI = 0.4-2.8) when PCBs were included in the model. Because pancreatic cancer is characterized by cachexia, the impact of this on the serum organochlorine levels in cases is difficult to predict. One plausible effect of cachexia is bioconcentration of organochlorines in the diminished lipid pool, which would lead to a bias away from the null. To explore this, a sensitivity analysis was performed assuming a 10-40% bioconcentration of organochlorines in case samples. The OR associated with PCBs remained elevated under conditions of up to 25% bioconcentration.

Association of DDT with spontaneous abortion: a case-control study.

PURPOSE: Spontaneous abortion (SAB), the most common adverse pregnancy outcome, affects approximately 15% of clinically recognized pregnancies. Except for advanced maternal age and smoking, there are not well-established risk factors for SAB. Animal models associate increased fetal resorption or abortion with exposure to the pesticide dichlorodiphenyl trichloroethane (DDT), but epidemiologic investigations of DDT and SAB are inconsistent. We undertook a pilot investigation of the hypothesized association of DDT with SAB. METHODS: Participants in this case-control study were selected from a longitudinal study of reproductive effects of rotating shifts among female Chinese textile workers who were married, ages 22-34, nulliparous without history of SAB or infertility, and planning pregnancy. From 412 pregnancies, 42 of which ended in SAB, 15 SAB cases and 15 full-term controls were randomly selected and phlebotomized. Serum was analyzed for p,p'-DDT, o,p'-DDT, their metabolites (DDE and DDD), and other organochlorines including polychlorinated biphenyls. RESULTS: Cases and controls were nonsmokers and did not differ in age (mean 25 years), body mass index (BMI), passive smoke exposure, or workplace exposures. Cases had significantly (p < 0.05) higher serum levels of p,p'-DDE (22 vs.12 ng/g) and o,p'-DDE (0.09 vs. 0.05 ng/g) than controls. After adjustment for age and BMI, each ng/g serum increase in p,p'-DDE was associated with a 1.13 (CI, 1.02-1.26) increased odds of SAB. With adjustment of serum DDE levels for excretion via breastfeeding, DDE-associated increased odds of SAB remained significant with up to 7% declines in maternal serum DDE levels for each month of breastfeeding. CONCLUSIONS: A potential increased risk of SAB is associated with maternal serum DDE levels.

High breast milk levels of polychlorinated biphenyls (PCBs) among four women living adjacent to a PCB-contaminated waste site.

As a consequence of contamination by effluents from local electronics manufacturing facilities, the New Bedford Harbor and estuary in southeastern Massachusetts is among the sites in the United States that are considered the most highly contaminated by polychlorinated biphenyls (PCBs). Since 1993, measures of intrauterine PCB exposure have been obtained for a sample of New Bedford area infants. Among 122 mother-infant pairs, we identified four milk samples with total PCB levels that were significantly higher than the rest, with estimated total PCBs ranging from 1,100 to 2,400 ng/g milk fat compared with an overall mean of 320 ng/g milk fat for the 122 women. The congener profile and history of one case was consistent with past occupational PCB exposures. Otherwise, the source of PCB exposures in these cases was difficult to specify. Environmental exposures including those from fish consumption were likely, whereas residence adjacent to a PCB-contaminated site was considered an unlikely exposure source. In all four cases, the infants were full-term, healthy newborns. Because the developing nervous system is believed to be particularly susceptible to PCBs (for example, prenatal PCB exposures have been associated with prematurity, decrements in birth weight and gestation time, and behavioral and developmental deficits in later infancy and childhood, including decrements in IQ), it is critical to ascertain if breast-feeding is a health risk for the women's infants. Despite the potential for large postnatal PCB exposures via breast milk, there is limited evidence of significant developmental toxicity associated with the transmission of moderate PCB concentrations through breast milk. Breast-feeding is associated with substantial health benefits including better cognitive skills among breast-fed compared with formula-fed infants. We conclude, based on evidence from other studies, that the benefits of breast-feeding probably outweigh any risk from PCB exposures via breast milk among the four New Bedford infants. In this case report, PCB analysis of breast milk and infant cord serum was a research tool. PCB analysis of milk is rarely done clinically, in part because it is difficult to use the results of such analyses to predict health risks. Substantial effort is needed to achieve a better understanding of the clinical and public health significance of PCB exposures, particularly among potentially susceptible groups such as infants and children. Such efforts are critical to improving the clinical and public health management of widespread and ongoing population exposures to PCBs.

Influence of bone resorption on the mobilization of lead from bone among middle-aged and elderly men: the Normative Aging Study.

Bone stores of lead accrued from environmental exposures and found in most of the general population have recently been linked to the development of hypertension, cognitive decrements, and adverse reproductive outcomes. The skeleton is the major endogenous source of lead in circulating blood, particularly under conditions of accelerated bone turnover and mineral loss, such as during pregnancy and in postmenopausal osteoporosis. We studied the influence of bone resorption rate on the release of lead from bone in 333 men, predominantly white, middle-aged and elderly (mostly retired) from the Boston area. We evaluated bone resorption by measuring cross-linked N-telopeptides of type I collagen (NTx) in 24-hr urine samples with an enzyme-linked immunosorbent assay. We used K-X-ray fluorescence to measure lead content in cortical (tibia) and trabecular (patella) bone; we used graphite furnace atomic absorption spectroscopy and inductively coupled plasma mass spectroscopy to measure lead in blood and urine, respectively. After adjustment for age and creatinine clearance, the positive relation of patella lead to urinary lead was stronger among subjects in the upper two NTx tertiles (beta for patella lead > or =0.015) than in the lowest NTx tertile (beta for patella lead = 0.008; overall p-value for interactions = 0.06). In contrast, we found no statistically significant influence of NTx tertile on the relationship of blood lead to urinary lead. As expected, the magnitude of the relationship of bone lead to urinary lead diminished after adjustment for blood lead. Nevertheless, the pattern of the relationships of bone lead to urinary lead across NTx tertiles remained unchanged. Furthermore, after adjustment for age, the relation of patella lead to blood lead was significantly stronger in the upper two NTx tertiles (beta for patella lead > or =0.125) than in the lowest NTx tertile (beta for patella lead = 0.072). The results provide evidence that bone resorption influences the release of bone lead stores (particularly patella lead) into the circulation.

Effects of ozone and other pollutants on the pulmonary function of adult hikers.

This study evaluated the acute effects of ambient ozone (O3), fine particulate matter (PM2.5), and strong aerosol acidity on the pulmonary function of exercising adults. During the summers of 1991 and 1992, volunteers (18-64 years of age) were solicited from hikers on Mt. Washington, New Hampshire. Volunteer nonsmokers with complete covariates (n = 530) had pulmonary function measured before and after their hikes. We calculated each hiker's posthike percentage change in forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), the ratio of these two (FEV1/FVC), forced expiratory flow between 25 and 75% of FVC(FEF25-75%), and peak expiratory flow rate (PEFR). Average O3 exposures ranged from 21 to 74 ppb. After adjustment for age,sex, smoking status (former versus never), history of asthma or wheeze, hours hiked, ambient temperature, and other covariates, there was a 2.6% decline in FEV1 [95% confidence interval (CI), 0.4-4.7; p = 0.02] and a 2.2% decline in FVC (CI, 0.8-3.5; p =0.003) for each 50 ppb increment in mean O3. There were consistent associations of decrements in both FVC (0.4% decline; CI,0.2-0.6, p = 0.001) and PEFR (0.8% decline; CI, 0.01-1.6; p = 0.05) with PM2.5 and of decrements in PEFR (0.4% decline; CI, 0.1-0.7; p = 0.02) with strong aerosol acidity across the interquartile range of these exposures. Hikers with asthma or a history of wheeze (n = 40) had fourfold greater responsiveness to ozone than others. With prolonged outdoor exercise, low-level exposures to O3, PM2.5, and strong aerosol acidity were associated with significant effects on pulmonary function among adults. Hikers with a history of asthma or wheeze had significantly greater air pollution-related changes in pulmonary function.

Measurement of PCBs, DDE, and hexachlorobenzene in cord blood from infants born in towns adjacent to a PCB-contaminated waste site.

There are limited data on the concentrations of common contaminants--polychlorinated biphenyls (PCBs), dichlorodiphenyl dichloroethene (pp'-DDE) and hexachlorobenzene (HCB)--in umbilical cord blood. Cord blood provides the primary direct measure of prenatal exposure to these contaminants, the key determinant of PCBs' neurodevelopmental toxicities. The objective of this study was to characterize cord blood levels of PCBs, pp'-DDE, and HCB among 751 infants who were born between 1993 and 1998 to mothers residing adjacent to a PCB-contaminated harbor in New Bedford, Massachusetts, and for whom the neurodevelopmental toxicities of these compounds are being studied. We refined standard analytic methods to optimize the sensitivity and precision of trace-level PCB, p,p'-DDE, and HCB measurements in blood. Using these methods, we measured the concentrations of 51 individual PCBs, their sum (sum(PCB)), p,p'-DDE, and HCB in cord serum. With correction for background contamination, the respective mean+/-SD cord serum concentrations of sum(PCB), p,p'-DDE, and HCB were 0.54+/-0.83, 0.48+/-0.94, and 0.03+/-0.04 ng/g serum. These concentrations were generally lower than those in most of the few published studies with congener-specific measures of PCBs in cord blood. However, for less-chlorinated PCB congeners (e.g., congeners 99 and 118), study samples had concentrations comparable to those in other populations, including groups at risk for high dietary PCB exposure. Of note, the contaminated harbor sediment has a relatively high proportion of less-chlorinated PCB congeners. Thus, although the sum(PCB) in study infants was not higher than concentrations in infants studied elsewhere, the relative predominance of less-chlorinated congeners was generally consistent with the characteristics of the contaminated site.

The relationship between bone lead and hemoglobin.

OBJECTIVE: To determine whether the concentration of lead in bone constitutes a biological marker that is more sensitive for chronic toxicity than blood lead levels. DESIGN: Survey. SETTING: A construction trade union with members who engage in carpentry, demolition, and other construction activities. PARTICIPANTS: Members of the construction trade union. MAIN OUTCOME MEASURES: We measured blood pressure, serum creatinine, hematocrit, and hemoglobin. We measured blood lead by anodic stripping voltametry and used a cadmium 109 K x-ray fluorescence instrument to make in vivo measurements of lead in the tibia (a heavily cortical bone) and the patella (a heavily trabecular bone). Information was also collected on medical history, smoking, and alcohol ingestion. RESULTS: Bone lead levels in the patella were found to be significantly correlated with a decrease in hemoglobin and hematocrit, even after adjusting for age, blood lead, body mass index, cigarette smoking, and alcohol ingestion and removing outliers. Blood lead levels were low (mean = 0.40 mumol/L [8.3 micrograms/dL]) and were not correlated with either hemoglobin or hematocrit. In the final multivariate regression model that corrected for measurement error, an increase in patella bone lead level from the lowest to highest quintile in this study population (37 micrograms/g) was associated with a decrease in hemoglobin and hematocrit of 11 g/L (95% confidence interval [CI], 2.7 to 19.3 g/L) and 0.03 (95% CI, 0.01 to 0.05), respectively. CONCLUSION: We conclude that patella bone lead levels are associated with decreased hematocrit and hemoglobin levels despite the presence of low blood lead levels. This conclusion may reflect a subclinical effect of bone lead stores on hematopoiesis and is the first epidemiological evidence that bone lead may be an important biological marker of ongoing chronic toxicity.

Use of state workers' compensation data for occupational carpal tunnel syndrome surveillance: a feasibility study in Massachusetts.

The purpose of this study was to determine the feasibility of using Massachusetts workers' compensation data for passive surveillance of occupational carpal tunnel syndrome (OCTS). Workers' compensation claims for OCTS (n = 358) and for possible cases of OCTS (n = 1,121) active during the first 6 months of 1989 were identified. The availability and distribution of demographic and employment descriptors were assessed. Medical records on a sample of the claims were reviewed to validate the diagnosis of OCTS. Age, gender, and occupation were available for less than 47% of the reported cases of OCTS. The majority (88%) of cases on whom medical record review was performed had a physician's diagnosis of carpal tunnel syndrome (CTS), and most of this group had confirmatory nerve conduction studies or electromyography. However, there were fundamental limitations to workers' compensation based disease surveillance in Massachusetts, including underascertainment of cases, potential ascertainment biases, delayed case reporting, limited access to specific diagnostic information, and incomplete and sometimes inaccurate information. These limitations are likely to be applicable in many, if not most, states and must be made clear in any analyses based on workers' compensation data.

Lead and hypertension in a sample of middle-aged women.

OBJECTIVES: The role of lead exposure as a risk factor for hypertension is less well defined among women than among men. This case-control study assessed the relation of blood and bone lead concentrations to hypertension in women. METHODS: Cases and controls were a subsample of women from the Nurses' Health Study. Hypertension was defined as a physician diagnosis of hypertension between 1988 and 1994 or measured systolic blood pressure > or = 140 mm Hg or diastolic blood pressure > or = 90 mm Hg. RESULTS: Mean (SD) blood lead concentration was 0.15 (0.11) mumol/L; mean tibia and patella lead concentrations by K-x-ray fluorescence were 13.3 (9.0) and 17.3 (11.1) micrograms/g, respectively. After adjustment for potentially confounding factors, an increase from the 10th to the 90th percentile of patella lead values (25 micrograms/g) was associated with approximately 2-fold (95% confidence interval = 1.1, 3.2) increased risk of hypertension. There was no association between hypertension and either blood or tibia lead concentrations. CONCLUSIONS: These findings support a potentially important role for low-level lead exposure as a risk factor for hypertension among non-occupationally exposed women.

Moderate alcohol consumption and bone density among postmenopausal women.

Chronic alcohol abuse is associated with low bone density and high risk of fracture. However, moderate alcohol consumption may help to maintain bone density in postmenopausal women by increasing endogenous estrogens or by promoting secretion of calcitonin. We conducted a prospective study among a sample of 188 white postmenopausal women (ages 50-74) from the Nurses' Health Study who participated in a health examination between 1993 and 1995 that included bone density assessments of the lumbar spine and proximal femur. Long-term alcohol intake was calculated as the average of the 1980 and 1990 measures from a food frequency questionnaire. Women who consumed 75 g or more of alcohol per week had significantly higher bone densities at the lumbar spine compared with non-drinking women (0.951 vs. 0.849 g/cm2, p = 0.002) after adjusting for age, body mass index (kg/m2), age at menopause, use of postmenopausal estrogens, and smoking status. Further adjustment for physical activity and daily intakes of calcium, vitamin D, protein, and caffeine did not alter the results. We also observed a linear increase in spinal bone density over increasing categories of alcohol intake (p = 0.002), suggesting that alcohol intakes of less than 75 g/week may also be of benefit. This positive association was observed among both current users and never users of postmenopausal estrogens. In contrast to the lumbar spine, femoral bone density was not higher among drinkers compared with nondrinkers, although density did increase among drinkers with increasing level of alcohol consumption. Further research is needed to determine whether moderate alcohol consumption can help to protect against spinal fractures in postmenopausal women. This finding must also be evaluated within a larger scope of the risks and benefits of alcohol on heart disease, breast cancer, and hip fractures.

Determination of the total arsenic concentration in human urine by inductively coupled plasma mass spectrometry: a comparison of the accuracy of three analytical methods.

Measurement of arsenic (As) in biological samples such as urine has important clinical applications and is being undertaken more frequently in epidemiologic studies because of concern about the carcinogenicity of low to moderate levels of As exposure. The objective of this study was to evaluate and improve the accuracy of As determination in urine by inductively coupled plasma mass spectrometry (ICP-MS). Determination of As in biological samples by ICP-MS is difficult for two reasons: the formation of the molecular ion 40Ar35Cl, which overlaps with monoisotopic As at a mass-to-charge ratio (m/z) of 75 (causing spectral interference), and signal enhancement due to organic matrix (nonspectral interference). Available procedures were examined, including the application of different correction procedures using 40Ar37Cl and 16O35Cl molecular-ion formation; the addition of N2 into plasma or nebulizer gas flows; and the addition of organic molecules to the sample and to calibration standards to eliminate or correct for interference due to molecular-ion formation. The accuracy and precision of determination of As [m/z 75, ionization potential (IP) 9.81 eV] with use of an internal standard was also investigated. Three elements were studied as candidate internal standards: germanium (Ge: m/z 74, IP 7.90 eV), indium (In: m/z 115, IP 5.79 eV), and tellurium (Te: m/z 128, IP 9.01 eV). It was found that these three elements performed more or less equally well with Ar-N2 plasma; it was also found that accuracy was significantly improved when Te was used as the internal standard instead of Ge or In for ethanol-added samples. Our results indicate that accurate and precise measurement of As in urine by ICP-MS can be obtained by either of two methods (< 5% error, approximately 2% RSD, limit of detection 0.1 ng ml-1): (1) the addition of 1% N2 to plasma gas flow or 3% N2 to nebulizer gas flow, along with use of any of the internal standards tested, or (2) the addition of ethanol to the sample and to calibration standards, with use of Te as the internal standard. The most accurate results (< 1% error) for National Institute of Standard and Technology Standard Reference Material (NIST SRM) 2670 (toxic elements in urine) were obtained with Ar-N2 plasma with either Te or In as the internal standard.

Determinants of bone and blood lead levels among community-exposed middle-aged to elderly men. The normative aging study.

Levels of lead in bone serve as a dosimeter for cumulative exposure to lead; moreover, lead in bone may serve as an internal source of circulating lead many years after environmental exposure has ceased. The authors measured lead in blood and used a K-x-ray fluorescence instrument to measure lead in the tibia (cortical) and patella (trabecular) bones in a cross-sectional survey of 719 middle-aged to elderly male participants in the Normative Aging Study who were without unusual occupational exposures to lead and who were healthy when enrolled in 1962-1965. Blood lead levels ranged from < 1 to 27.9 micrograms/dl, with a geometric mean of 5.7 micrograms/dl. Tibia and patella lead level ranges (geometric means) were < 1-51 (20.8) micrograms/g and 3-77 (29.8) micrograms/g, respectively. In backwards elimination multivariate regression models that considered age, race, education, retirement status, measures of both current and cumulative smoking, and alcohol consumption, the factors that remained significantly related to higher levels of both tibia and patella lead were higher age and measures of cumulative smoking, and lower levels of education. In the final model predicting blood lead that began with these same covariates and also included tibia and patella lead, the factor that accounted for the dominant portion of the variance in blood lead was patella lead. After adjustment for measurement error, a rise in patella lead from the median of the lowest to the median of the highest quintiles (13-56 micrograms/g) corresponded to a rise in blood lead of 4.3 micrograms/dl. The authors conclude that bone lead levels are substantial and comprise the major source of circulating lead in these men.

The relationship of bone and blood lead to hypertension. The Normative Aging Study.

OBJECTIVE: To test the hypothesis that long-term lead accumulation, as reflected by levels of lead in bone (as opposed to blood which reflects recent lead exposure), is associated with an increased odds of developing hypertension. DESIGN: Case-control study of participants in the Veterans Administration (now Department of Veterans Affairs) Normative Aging Study, a 30-year longitudinal study of men. PARTICIPANTS: Of 1171 active subjects who were seen between August 1991 and December 1994, 590 (50%) participated in this investigation and had data on all variables of interest. MAIN OUTCOME MEASURES: Hypertension was defined as taking daily medication for the treatment of hypertension or systolic blood pressure higher than 160 mm Hg or diastolic blood pressure of 96 mm Hg or higher during the time of examination. Levels of lead in the tibia (representing cortical bone) and the patella (representing trabecular bone) were measured in vivo with a K x-ray fluorescence (KXRF) instrument. Levels of lead in blood were measured by graphite furnace atomic absorption spectroscopy. RESULTS: Blood lead levels were low, ranging from less than 0.05 to 1.35 micromol/L (<1 to 28 microgram/dL), with a mean (SD) of 0.30 (0.20) micromol/L (6.3[4.1] microgram/dL). Bone lead levels were similar to those described in other general populations. In comparison to nonhypertensives, mean levels of lead in blood and both tibia and patella bone lead levels were significantly higher in hypertensive subjects. In a logistic regression model of hypertensive status that began with age, race, body mass index, family history of hypertension, history of ethanol ingestion, pack-years of smoking, dietary sodium intake, dietary calcium intake, blood lead, tibia lead, and patella lead, the variables that remained after backward elimination were body mass index, family history of hypertension, and level of lead in the tibia. An increase from the midpoint of the lowest quintile to the midpoint of the highest quintile of tibia lead from 3 to 37 micrograms per gram of bone mineral was associated with an increased odds ratio of hypertension of 1.5. CONCLUSION: Our findings suggest that long-term lead accumulation, as reflected by levels of lead in bone, may be an independent risk factor for developing hypertension in men in the general population.