Coal smoke, gestational cadmium exposure, and fetal growth.

BACKGROUND: Gestational cadmium exposure may impair fetal growth. Coal smoke has largely been unexplored as a source of cadmium exposure. We investigated the relationship between gestational cadmium exposure and fetal growth, and assessed coal smoke as a potential source of airborne cadmium, among non-smoking pregnant women in Ulaanbaatar, Mongolia, where coal combustion in home heating stoves is a major source of outdoor and indoor air pollution. METHODS: This observational study was nested within the Ulaanbaatar Gestation and Air Pollution Research (UGAAR) study, a randomized controlled trial of portable high efficiency particulate air (HEPA) filter air cleaner use during pregnancy, fetal growth, and early childhood development. We measured third trimester blood cadmium concentrations in 374 out of 465 participants who had a live birth. We used multiple linear and logistic regression to assess the relationships between log2-transformed maternal blood cadmium concentrations and birth weight, length, head circumference, ponderal index, low birth weight, small for gestational age, and preterm birth in crude and adjusted models. We also evaluated the relationships between log2-transformed blood cadmium concentrations and the density of coal-burning stoves within 5000 m of each participant's apartment as a proxy of coal smoke emissions from home heating stoves. RESULTS: The median (25th,75th percentile) blood cadmium concentration was 0.20 (0.15, 0.29) µg/L. A doubling of blood cadmium was associated with a 95 g (95% CI: 34, 155 g) reduction in birth weight in adjusted models. An interquartile range increase in coal stove density (from 3.4 to 4.9 gers/hectare) surrounding participants' apartments was associated with a 12.2% (95% CI: 0.3, 25.6%) increase in blood cadmium concentrations. CONCLUSIONS: Gestational cadmium exposure was associated with reduced birth weight. In settings where coal is a widely used fuel, cadmium may play a role in the putative association between air pollution and impaired fetal growth.

A gender-specific association of the polymorphism Ile197Met in the kininogen 1 gene with plasma irbesartan concentrations in Chinese patients with essential hypertension.

This study was conducted to explore interactions in the association of the kininogen (KNG1) Ile197Met polymorphism and gender with plasma concentrations of irbesartan in Chinese patients with essential hypertension. A total of 1100 subjects with essential hypertension received a daily oral dose of 150 mg irbesartan for twenty-eight consecutive days. High-performance liquid chromatography-fluorescence (HPLC) was used to detect plasma irbesartan concentrations on day 28. The KNG1 Ile197Met gene polymorphism was determined using high-throughput TaqMan technology. The frequency distribution of KNG1 Ile197Met genotype conformed to the Hardy-Weinberg equilibrium. After 28 days of treatment, patients with the GG genotype had significantly lower irbesartan concentrations (P = 0.033) compared to homozygous TT genotype carriers. After stratifying by gender, male G allele carriers had significantly lower irbesartan concentrations (GG, P = 0.015; TG, P = 0.015, respectively) relative to TT genotype after adjusting for age, region, body mass index (BMI), smoking, and alcohol consumption. However, there was no significant difference in female subjects. A further test for a multiplicative interaction between the KNG1 Ile197Met polymorphism and gender in association with ln-plasma irbesartan concentrations in a multiple linear regression model was also significant (P for interaction = 0.033). This is the first study to suggest that gender may influence the association of the Ile197Met variant of KNG1 with ln-plasma irbesartan concentration. This finding may indicate that the interaction of gender and the KNG1 Ile197Met gene polymorphism can influence plasma trough irbesartan concentrations, which may contribute to a better development of personalized hypertensive treatment in Chinese patients.

Associations of the SLCO1B1 Polymorphisms With Hepatic Function, Baseline Lipid Levels, and Lipid-lowering Response to Simvastatin in Patients With Hyperlipidemia.

Our goal was to examine the associations of the 388A>G and 521T>C polymorphisms in the solute carrier organic anion transporter 1B1 (SLCO1B1) gene with hepatic function, baseline lipid levels, and the lipid-lowering efficiency of simvastatin. We recruited 542 patients with hyperlipidemia. The 388A>G and 521T>C polymorphisms were genotyped. Serum alanine aminotransferase (ALT) and aspartate transaminase (AST), Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured before and after an oral 20-mg dose of simvastatin. Individuals with the 388AA genotype had higher ALT and AST levels than those with the 388AG or 388GG genotypes (P = .037 and P = .002, respectively). Individuals with both the 388AA and the 521TT genotypes had the highest levels of ALT and AST (P = .001 and P = .001, respectively). Moreover, we divided all patients into normal and abnormal subgroups based on elevated ALT and AST values (≥ 40 U/L), participants in the abnormal subgroup had a higher frequency of the 388A/521T haplotype and a lower frequency of the 388G/521T haplotype compared to those in the normal subgroup. In addition, compared to 388G allele and 521C allele carriers, individuals with the 388G allele and 521TT genotype carriers had greater TC and LDL-C reduction in response to simvastatin after 4 weeks of treatment. Our conclusion suggests that the interaction between the SLCO1B1 388A>G and 521T>C polymorphisms could be an important genetic determinant of hepatic function and the therapeutic efficiency of simvastatin in Chinese patients with hyperlipidemia.

The effect of portable HEPA filter air cleaner use during pregnancy on fetal growth: The UGAAR randomized controlled trial.

BACKGROUND: Fine particulate matter (PM2.5) exposure may impair fetal growth. AIMS/OBJECTIVES: Our aim was to assess the effect of portable high efficiency particulate air (HEPA) filter air cleaner use during pregnancy on fetal growth. METHODS: The Ulaanbaatar Gestation and Air Pollution Research (UGAAR) study is a single-blind randomized controlled trial conducted in Ulaanbaatar, Mongolia. Non-smoking pregnant women recruited at ≤18 weeks gestation were randomized to an intervention (1-2 air cleaners in homes from early pregnancy until childbirth) or control (no air cleaners) group. Participants were not blinded to their intervention status. Demographic, health, and birth outcome data were obtained via questionnaires and clinic records. We used unadjusted linear and logistic regression and time-to-event analysis to evaluate the intervention. Our primary outcome was birth weight. Secondary outcomes were gestational age-adjusted birth weight, birth length, head circumference, gestational age at birth, and small for gestational age. The study is registered at ClinicalTrials.gov (NCT01741051). RESULTS: We recruited 540 participants (272 control and 268 intervention) from January 9, 2014 to May 1, 2015. There were 465 live births and 28 losses to follow up. We previously reported a 29% (95% CI: 21, 37%) reduction in indoor PM2.5 concentrations with portable HEPA filter air cleaner use. The median (25th, 75th percentile) birth weights for control and intervention participants were 3450 g (3150, 3800 g) and 3550 g (3200, 3800 g), respectively (p = 0.34). The intervention was not associated with birth weight (18 g; 95% CI: -84, 120 g), but in a pre-specified subgroup analysis of 429 term births the intervention was associated with an 85 g (95% CI: 3, 167 g) increase in mean birth weight. CONCLUSIONS: HEPA filter air cleaner use in a high pollution setting was associated with greater birth weight only among babies born at term.

The effect of portable HEPA filter air cleaners on indoor PM2.5 concentrations and second hand tobacco smoke exposure among pregnant women in Ulaanbaatar, Mongolia: The UGAAR randomized controlled trial.

BACKGROUND: Portable HEPA filter air cleaners can reduce indoor fine particulate matter (PM2.5), but their use has not been adequately evaluated in high pollution settings. We assessed air cleaner effectiveness in reducing indoor residential PM2.5 and second hand smoke (SHS) exposures among non-smoking pregnant women in Ulaanbaatar, Mongolia. METHODS: We randomized 540 participants to an intervention group receiving 1 or 2 HEPA filter air cleaners or a control group receiving no air cleaners. We followed 259 intervention and 253 control participants to the end of pregnancy. We measured one-week indoor residential PM2.5 concentrations in early (~11weeks gestation) and late (~31weeks gestation) pregnancy and collected outdoor PM2.5 data from centrally-located government monitors. We assessed blood cadmium in late pregnancy. Hair nicotine was quantified in a subset (n=125) to evaluate blood cadmium as a biomarker of SHS exposure. We evaluated air cleaner effectiveness using mixed effects and multiple linear regression models and used stratified models and interaction terms to evaluate potential modifiers of effectiveness. RESULTS: The overall geometric mean (GM) one-week outdoor PM2.5 concentration was 47.9µg/m3 (95% CI: 44.6, 51.6µg/m3), with highest concentrations in winter (118.0µg/m3; 110.4, 126.2µg/m3). One-week indoor and outdoor PM2.5 concentrations were correlated (r=0.69). Indoor PM2.5 concentrations were 29% (21, 37%) lower in intervention versus control apartments, with GMs of 17.3µg/m3 (15.8, 18.8µg/m3) and 24.5µg/m3 (22.2, 27.0µg/m3), respectively. Air cleaner effectiveness was greater when air cleaners were first deployed (40%; 31, 48%) than after approximately five months of use (15%; 0, 27%). Blood cadmium concentrations were 14% (4, 23%) lower among intervention participants, likely due to reduced SHS exposure. CONCLUSIONS: Portable HEPA filter air cleaners can lower indoor PM2.5 concentrations and SHS exposures in highly polluted settings.

Associations of the ABCA1 and LPL Gene Polymorphisms With Lipid Levels in a Hyperlipidemic Population.

We conducted a cross-sectional study to investigate the effects of the adenosine triphosphate-binding cassette transporter 1 (ABCA1) I883M and lipoprotein lipase (LPL) HindIII polymorphisms on lipid levels in patients with hyperlipidemia. A total of 533 patients were enrolled. Serum lipid parameters were determined by an automatic biochemistry analyzer. Genotyping of the ABCA1 I883M and LPL HindIII was carried out using the polymerase chain reaction-restriction fragment length polymorphism technique. Multiple linear regression analysis was used to estimate the associations between serum lipid levels and the genetic polymorphisms. The frequency distribution of the ABCA1 I883M and LPL HindIII polymorphisms did not deviate from Hardy-Weinberg equilibrium. The major finding of our regression analysis showed that neither the ABCA1 I883M nor the LPL HindIII polymorphism was associated with baseline serum lipid levels in the total population. However, among patients with elevated alanine aminotransferase (ALT) levels (ALT ≥ 40 U/L), carriers of the M allele of the ABCA1 gene had lower levels of high-density lipoprotein cholesterol (HDL-C) and higher levels of low-density lipoprotein cholesterol (LDL-C) after adjusting for age, sex, smoking status, alcohol consumption, education level, occupation, and work intensity ( P < .05 for both). A test on interaction terms between the ABCA1 I833M polymorphism and ALT on HDL-C and LDL-C levels also remained significant ( P = .001 and P = .014, respectively). Our data suggest that there are significant interactive effects between ABCA1 I883M and ALT levels on HDL-C and LDL-C levels. However, the LPL HindIII polymorphism did not influence lipid levels.

Interactive Effect of the KCNJ11 Ile337Val Polymorphism and Cigarette Smoking on the Antihypertensive Response to Irbesartan in Chinese Hypertensive Patients.

OBJECTIVE: This study was designed to detect the association of the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene polymorphism with antihypertensive therapeutic response to irbesartan in a large-scale Chinese hypertensive population. METHODS: A total of 1,099 patients with essential hypertension were enrolled to receive a daily dose of 150 mg irbesartan for 27 days. Pretreatment baseline blood pressure (BP) and posttreatment BP on the 28th day were measured. Plasma irbesartan concentrations were measured by high-performance liquid chromatography-fluorescence. The KCNJ11 I337V gene polymorphism was determined using high-throughput TaqMan technology. RESULTS: The HapMap data in the Han Chinese population showed that the I337V was used as a representative for 4 common functional polymorphisms. Our results showed that the association of antihypertensive response to irbesartan and the KCNJ11 genetic variant in the total sample was not significant. However, in nonsmokers, relative to the GG genotype, subjects with the homozygous AA genotype had a significantly higher therapeutic response to irbesartan (adjusted beta ± SE: 4.7±1.9 mm Hg, P = 0.015). In smokers, the subjects with the homozygous AA genotype had a significantly lower therapeutic response to irbesartan (adjusted beta ± SE: -5.6±2.5 mm Hg, P = 0.026). A multivariate linear regression model confirmed that there was a significant interactive effect between the KCNJ11 gene and smoking on irbesartan treatment (interaction P = 0.001). CONCLUSION: The interactive effect of smoking status and the KCNJ11 genotype may influence the antihypertensive effects of irbesartan, which indicates a consideration for future individualized antihypertensive drug treatment.

Elevation in Total Homocysteine Levels in Chinese Patients With Essential Hypertension Treated With Antihypertensive Benazepril.

OBJECTIVE: To investigate the effect of benazepril on plasma homocysteine (Hcy) levels and to analyze the correlation between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and changes in Hcy levels in response to benazepril. METHODS: A total of 231 patients with mild to moderate essential hypertension were enrolled, and benazepril was orally administered at a dose of 10 mg/d for 2 weeks. Plasma Hcy levels were measured by high-performance liquid chromatography at baseline and after 2 weeks of treatment. Genotyping of the MTHFR C677T polymorphism was performed by TaqMan probe technique. RESULTS: There was no significant change in Hcy level after benazepril treatment for 2 weeks (P = .97). However, stratified by baseline Hcy levels, the patients with baseline Hcy <10 µmol/L had a significant increase in plasma Hcy levels (P = .003). The results from the multivariable linear regression analysis demonstrated a significant correlation between baseline Hcy levels and the changes in Hcy levels found in both the unadjusted (P = .002) and the adjusted model (P = .004). Strikingly, we found no significant effect modification by the MTHFR C677T polymorphism on the Hcy changes after benazepril treatment. There were also no statistically significant interactions of gene and environment factors (ie, gene smoking and drinking) on the changes in Hcy levels after benazepril treatment. CONCLUSION: Benazepril may cause an increase in plasma Hcy levels among patients with hypertension with low baseline Hcy levels, while effect modification by MTHFR C677T genotypes on the changes in Hcy levels in response to benazepril was not significant among patients with essential hypertension.

Antineoplastic drug contamination in the urine of Canadian healthcare workers.

PURPOSE: The purpose of this study was to quantify the urine concentration of non-metabolized cyclophosphamide (CP), a commonly administered antineoplastic drug, among potentially exposed Canadian healthcare workers and to identify factors associated with the drug concentration levels. METHODS: Participants were asked to provide two sets of 24-h urine samples (at two different sampling events), and the level of CP was quantified using high-performance liquid chromatography-tandem mass spectrometry. In addition to demographic information, participants were surveyed regarding their frequency of handling of antineoplastic drugs, safe drug handling training, and known contact with CP on their work shift. Descriptive and inferential statistical analyses were performed. A backward stepwise linear mixed effect model was conducted to identify the factors associated with urine concentration levels. RESULTS: We collected 201 urine samples, and 55 % (n = 111) had levels greater than the LOD of 0.05 ng/mL. The mean urinary CP concentration was 0.156 ng/mL, the geometric mean was 0.067 ng/mL, the geometric standard deviation was 3.18, the 75th percentile was 0.129 ng/mL, and the range was

Antineoplastic drug contamination on the hands of employees working throughout the hospital medication system.

We previously reported that antineoplastic drug contamination is found on various work surfaces situated throughout the hospital medication system (process flow of drug within a facility from initial delivery to waste disposal). The presence of drug residual on surfaces suggests that healthcare workers involved in some capacity with the system may be exposed through dermal contact. The purpose of this paper was to determine the dermal contamination levels of healthcare employees working throughout a hospital and to identify factors that may influence dermal contamination. We selected participants from six hospitals and wiped the front and back of workers' hands. Wipe samples were analyzed for cyclophosphamide (CP), a commonly used antineoplastic drug, using high-performance liquid chromatography-tandem mass spectrometry. Participants were asked about their frequency of handling antineoplastic drugs, known contact with CP on their work shift, gender, job title, and safe drug handling training. In addition, participants were surveyed regarding their glove usage and hand washing practices prior to wipe sample collection. We collected a total of 225 wipe samples. Only 20% (N = 44) were above the limit of detection (LOD) of 0.36ng per wipe. The average concentration was 0.36ng per wipe, the geometric mean < LOD, the geometric standard deviation 1.98, and the range < LOD to 22.8ng per wipe. Hospital employees were classified into eight different job categories and all categories had some dermal contamination levels in excess of the LOD. The job category with the highest proportion of samples greater than the LOD were those workers in the drug administration unit who were not responsible for drug administration (volunteer, oncologist, ward aide, dietician). Of note, the highest recorded concentration was from a worker who had no known contact with CP on their work shift. Our results suggest that a broader range of healthcare workers than previously believed, including those that do not directly handle or administer the drugs (e.g. unit clerks, ward aides, dieticians, and shipper/receivers), are at risk of exposure to antineoplastic drugs. A review of control measures to minimize antineoplastic drug exposure that encompasses a wide array of healthcare workers involved with the hospital medication system is recommended.

Associations of MTHFR and MTRR polymorphisms with serum lipid levels in Chinese hypertensive patients.

OBJECTIVE: To examine the effects of the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) gene polymorphisms and their interactions with environmental factors on serum lipid levels. METHODS: We investigated totally 340 patients with essential hypertension, from Dongzhi community, Anhui, China. High-throughput TaqMan allelic discrimination assay was used for the genotyping of MTHFR C677T (Ala222Val), MTHFR A1298C (Glu429Ala), MTRR A66G (Ile22Met), and MTRR His595Tyr. RESULTS: Compared with the MTRR 66AA genotype carriers, the GG genotype carriers had lower serum total cholesterol (TC) levels (adjusted ß ± standard error [SE]: -0.5 ± 0.2 mmol/L; P = .003) and low-density lipoprotein cholesterol (LDL-C) levels (adjusted ß ± SE: -0.4 ± 0.2 mmol/L; P = .005). Their false discovery rate (FDR)-adjusted P values were 0.056 and 0.056, respectively. We further found that there was a statistically significant interaction between 677TT genotype and sex in their associations with LDL levels (P interaction = .020), and significant interaction between 677TT genotype and smoking on LDL levels (P interaction = .036). A similar pattern of interaction was found between 66GG and drinking on levels of TC (P interaction = .034) and LDL (P interaction = .020). However, there were no significant interactions observed after FDR adjustment. CONCLUSION: Both MTHFR and MTRR gene polymorphisms could be important genetic determinants of serum lipid levels in Chinese patients with hypertension. These findings need to be replicated in a larger sample.

Antineoplastic drug contamination of surfaces throughout the hospital medication system in Canadian hospitals.

We previously reported that there is a potential for antineoplastic drug contamination throughout the hospital medication system (process flow of drug within a facility from delivery to waste disposal) due to the various surfaces contacted by health care workers. This article describes the contamination of these frequently contacted surfaces as well as identifies factors that may be associated with surface contamination. Surfaces which health care workers frequently contact were wiped and the concentration of cyclophosphamide (CP) was determined using high-performance liquid chromatography-tandem mass spectrometry. Descriptive and inferential statistical analyses were performed. A backward stepwise multiple linear regression was conducted to identify determinants associated with surface contamination. Overall, 229 surfaces were sampled, most on two occasions, for a total of 438 surface wipes. The mean CP concentration was 0.201 ng/cm(2), the geometric mean 0.019 ng/cm(2), and the geometric standard deviation 2.54, with a range of less than detection (LOD) to 26.1 ng/cm(2). (Method LOD was 0.356 ng/wipe; factoring in the surface area of the wiped surface, results in a sample LOD ranging from 0.00 to 0.049 ng/cm(2)). Our study found that frequently contacted surfaces at every stage of the hospital medication system had measureable levels of antineoplastic drug contamination. Two factors were statistically significant with respect to their association with surface contamination: (1) the stage of the hospital medication system, and (2) the number of job categories responsible for drug transport. The drug preparation stage had the highest average contamination. Those hospitals that had two or more drug transport job categories had higher levels of surface contamination. Neither the reported handling of CP prior to wipe sampling nor the cleaning of surfaces appeared to be associated with contamination.

Investigating maternal risk factors as potential targets of intervention to reduce socioeconomic inequality in small for gestational age: a population-based study.

BACKGROUND: The major aim of this study was to investigate whether maternal risk factors associated with socioeconomic status and small for gestational age (SGA) might be viable targets of interventions to reduce differential risk of SGA by socioeconomic status (socioeconomic SGA inequality) in the metropolitan area of Vancouver, Canada. METHODS: This study included 59,039 live, singleton births in the Vancouver Census Metropolitan Area (Vancouver) from January 1, 2006 to September 17, 2009. To identify an indicator of socioeconomic SGA inequality, we used hierarchical logistic regression to model SGA by area-level variables from the Canadian census. We then modelled SGA by area-level average income plus established maternal risk factors for SGA and calculated population attributable SGA risk percentages (PAR%) for each variable. Associations of maternal risk factors for SGA with average income were investigated to identify those that might contribute to SGA inequality. Finally, we estimated crude reductions in the percentage and absolute differences in SGA risks between highest and lowest average income quintiles that would result if interventions on maternal risk factors successfully equalized them across income levels or eliminated them altogether. RESULTS: Average income produced the most linear and statistically significant indicator of socioeconomic SGA inequality with 8.9% prevalence of SGA in the lowest income quintile compared to 5.6% in the highest. The adjusted PAR% of SGA for variables were: bottom four quintiles of height (51%), first birth (32%), bottom four quintiles of average income (14%), oligohydramnios (7%), underweight or hypertension, (6% each), smoking (3%) and placental disorder (1%). Shorter height, underweight and smoking during pregnancy had higher prevalence in lower income groups. Crude models assuming equalization of risk factors across income levels or elimination altogether indicated little potential change in relative socioeconomic SGA inequality and reduction in absolute SGA inequality for shorter height only. CONCLUSIONS: Our findings regarding maternal height may indicate trans-generational aetiology for socioeconomic SGA inequalities and/or that adult height influences social mobility. Conditions affecting foetal and childhood growth might be viable targets to reduce absolute socioeconomic SGA inequality in future generations, but more research is needed to determine whether such an approach is appropriate.

A common mutation in the defensin DEFB126 causes impaired sperm function and subfertility.

A glycosylated polypeptide, ß-defensin 126 (DEFB126), derived from the epididymis and adsorbed onto the sperm surface, has been implicated in immunoprotection and efficient movement of sperm in mucosal fluids of the female reproductive tract. Here, we report a sequence variant in DEFB126 that has a two-nucleotide deletion in the open reading frame, which generates an abnormal mRNA. The allele frequency of this variant sequence was high in both a European (0.47) and a Chinese (0.45) population cohort. Binding of the Agaricus bisporus lectin to the sperm surface glycocalyx was significantly lower in men with the homozygous variant (del/del) genotype than in those with either a del/wt or a wt/wt genotype, suggesting an altered sperm glycocalyx with fewer O-linked oligosaccharides in del/del men. Moreover, sperm from del/del carriers exhibited an 84% reduction in the rate of penetration of a hyaluronic acid gel, a surrogate for cervical mucus, compared to the other genotypes. This reduction in sperm performance in hyaluronic acid gels was not a result of decreased progressive motility (average curvilinear velocity) or morphological deficits. Nevertheless, DEFB126 genotype and lectin binding were correlated with sperm performance in the penetration assays. In a prospective cohort study of newly married couples who were trying to conceive by natural means, couples were less likely to become pregnant and took longer to achieve a live birth if the male partner was homozygous for the variant sequence. This common sequence variation in DEFB126, and its apparent effect of impaired reproductive function, will allow a better understanding, clinical evaluation, and possibly treatment of human infertility.

Occupational Exposure to Antineoplastic Drugs: Identification of Job Categories Potentially Exposed throughout the Hospital Medication System.

OBJECTIVES: Studies examining healthcare workers' exposure to antineoplastic drugs have focused on the drug preparation or drug administration areas. However, such an approach has probably underestimated the overall exposure risk as the drugs need to be delivered to the facility, transported internally and then disposed. The objective of this study is to determine whether drug contamination occurs throughout a facility and, simultaneously, to identify those job categories that are potentially exposed. METHODS: This was a multi-site study based in Vancouver, British Columbia. Interviews were conducted to determine the departments where the drugs travel. Subsequent site observations were performed to ascertain those surfaces which frequently came into contact with antineoplastic drugs and to determine the job categories which are likely to contact these surfaces. Wipe samples were collected to quantify surface contamination. RESULTS: Surface contamination was found in all six stages of the hospital medication system. Job categories consistently found to be at risk of exposure were nurses, pharmacists, pharmacy technicians, and pharmacy receivers. Up to 11 job categories per site may be at risk of exposure at some point during the hospital medication system. CONCLUSION: We found drug contamination on select surfaces at every stage of the medication system, which indicates the existence of an exposure potential throughout the facility. Our results suggest that a broader range of workers are potentially exposed than has been previously examined. These results will allow us to develop a more inclusive exposure assessment encompassing all healthcare workers that are at risk throughout the hospital medication system.

Serum folate and DDT isomers and metabolites are inversely associated in Chinese women: a cross-sectional analysis.

BACKGROUND: Vitamin nutritional status may influence some xenobiotic metabolism or vice versa. METHODS: This analysis examines the relationship between B-vitamin concentrations and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDT) isomers and metabolites in healthy women. Serum pp'DDT, pp'DDE, pp'DDD, op'DDT, op'DDE, and serum folate, cysteine, and vitamins B6 and B12 were measured in 296 nonsmoking female textile workers (21-34 yr) in Anhui, China. Mean (SD) age and body mass index of this cohort were 24.9 (1.5) y and 19.7 (2.0) kg/m(2), respectively. RESULTS: Median pp'DDT, pp'DDE, pp'DDD, op'DDT, and op'DDE were 1.5, 29.2, 0.22, 0.17, and 0.09 ng/g, respectively. Median folate and cysteine were 9.2 and 200.0 nmol/L, respectively. Folate was significantly inversely associated with pp'DDT and pp'DDE: beta (95% confidence interval [CI]) = -0.23 (-0.39, -0.07) and -0.20 (-0.36, -0.05), respectively, and it was marginally associated with pp'DDD. Cysteine was significantly inversely associated with pp'DDT, beta (95% CI) = -0.69 (-1.00, -0.37); pp'DDE, beta (95% CI) = -0.32 (-0.62, -0.02); pp'DDD, beta (95% CI) = -0.31 (-0.59, -0.03); and op'DDT, beta (95% CI) = -0.35 (-0.68, -0.02). CONCLUSIONS: Folate and cysteine are independently inversely associated with DDT isomers, adjusting for vitamins B6 and B12, age, and body mass index. These nutrients may play a role in DDT metabolism; however, it is also possible that DDT may exert a negative impact on folate and cysteine levels. Longitudinal studies are needed to ascertain the direction of this association.

Age and gender specific lung function predictive equations provide similar predictions for both a twin population and a general population from age 6 through adolescence.

BACKGROUND: There have been numerous studies of asthma in twins, but no study has evaluated whether lung function predictive models yield similar results between twin and general populations. We sought to evaluate this in late childhood and adolescent subjects. METHODS: We generated cross-sectional, sex- and age-specific regression models of FEV(1), and FVC, in a community-based cohort of 3140 healthy, non-smoking Chinese twins using generalized estimating equations to adjust for correlations within twin pairs. We applied the model to a healthy non-smoking general population cohort of 2187 subjects from the same region, and compared %predicted FEV(1) and FVC values between the two populations. RESULTS: Stratified by age and sex, the associations of height with FEV(1) or FVC varied by age group. During the adolescent growth spurt (age 13 for girls and ages 14-16 for boys), the associations of height with FEV(1) or FVC were nonlinear and greater than that seen at other ages. During adolescence, FEV(1) and FVC for a given height increased with age. The percent predicted values of FEV(1) and FVC in the twin population were similar to that of the general population. CONCLUSIONS: Twin and general populations have similar patterns of lung function change over middle childhood and adolescence. Similar equations may be used to estimate percent predicted values. Finally, a single prediction equation cannot completely describe patterns of lung function from childhood through adolescence due to puberty related changes.

A prospective study of serum DDT and progesterone and estrogen levels across the menstrual cycle in nulliparous women of reproductive age.

The authors explored whether exposure to 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and its isomers and metabolites affects female reproductive hormones characterized by urinary pregnanediol-3-glucuronide (PdG) and estrone conjugate (E(1)C) levels. During 1996-1998, 287 newly married Chinese women nonsmokers intending to conceive were prospectively studied. Serum for DDT measurement was collected at enrollment, and daily menstrual diaries and urine specimens were collected for 1 year or until a clinical pregnancy was achieved. More than 500 menstrual cycles were studied totaling over 8,000 days. Day of ovulation was determined for each cycle, and the association of serum DDT levels with daily PdG and E(1)C levels in a +/-10-day window around ovulation was analyzed. After adjustment for covariates including age, body mass index, and occupational exposures, consistent inverse associations of most DDT forms occurred with urine E(1)C during the periovulation phase and with urine PdG during the luteal phase of the menstrual cycle. For example, a 10-ng/g increase in serum p,p'-DDE was associated with a 0.05-log(E(1)C) decrease (p = 0.03) in the periovulation phase and a 0.06-log(PdG) decrease (p = 0.03) in the luteal phase. These results support the potential for DDT to be associated with decrements in estrogen and progesterone levels at times during the menstrual cycle that are critical for ovulation and early pregnancy maintenance.

Urinary estrogen and progesterone metabolite concentrations in menstrual cycles of fertile women with non-conception, early pregnancy loss or clinical pregnancy.

BACKGROUND: Knowledge is limited of how estrogen and progesterone variability in fertile women are associated with achieving pregnancy. METHODS: From 1996 to 1998, we enrolled 347 textile workers without hormone treatment in Anhui, China, who provided daily urine and data upon stopping contraception for up to 1 year until clinical pregnancy. Urinary hCG was assayed to detect conception and early pregnancy losses. We compared urinary concentrations of estrone conjugates (E(1)C) and pregnanediol-3-glucuronide (PdG) in 266 clinical pregnancies, 63 early pregnancy losses and 272 non-conception cycles from 347 women and also in 94 clinical pregnancy and 94 non-conception cycles from the same women. RESULTS: Using generalized estimating equations and relative to 266 clinical pregnancy cycles, log(E(1)C) was lower in 272 non-conception cycles [beta = -0.3 ng/mg creatinine (Cr); SE = 0.1; P < 0.0001]. On average, daily E(1)C was 18 ng/mg Cr lower in non-conception cycles than in clinical pregnancy cycles. Relative to 94 clinical pregnancy cycles, log(E(1)C) was lower in 94 non-conception cycles (beta = -0.4 ng/mg Cr; SE = 0.1; P < 0.0001) from the same women (average difference in daily E(1)C was 20 ng/mg Cr). The odds of E(1)C less than the 10th percentile (<30 ng/mg Cr) were higher in early pregnancy loss cycles [odds ratio (OR) = 4.8; P = 0.0027] than in clinical pregnancy cycles in the early luteal phase. Compared with clinical pregnancy cycles, log(PdG) concentrations were lower in non-conception cycles during the follicular phase, but this analysis lacked power for multiple testing. CONCLUSIONS: Estrogen concentrations varied from cycle to cycle, and higher estrogen was associated with achieving clinical pregnancy.

Body mass index and serum 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane in nulliparous Chinese women.

BACKGROUND: Basic health indicators, such as body mass index (BMI), have been associated with serum 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane/1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDT/DDE) levels; however, both positive and inverse associations of BMI with serum DDT/DDE have been reported. Given the association of BMI with a number of outcomes, it may confound studies of DDT/DDE-associated health effects. We investigated the relationship of BMI with serum DDT/DDE accounting for other determinants of exposure among women with relatively recent environmental exposures to DDT. METHODS: Serum DDT/DDE was analyzed in 466 nonsmoking, nulliparous women recruited from Anhui province in China between 1996 and 1998 as part of a reproductive health study of textile workers. The women in the sample were born between 1963 and 1977, 8 to 21 years before China's 1984 DDT ban. We used multivariate linear regression to investigate associations of BMI, age, and birth year with serum DDT/DDE. RESULTS: Mean (SD) serum total DDT concentration was 32 ng/g (17.8 ng/g). Birth year showed an inverse relationship with serum DDT independent of age. Despite limited variability in BMI, there was a consistent inverse relationship between BMI and serum DDT. Specifically, each kg/m(2) increase in BMI was associated with a -1.34 ng/g (95% confidence interval, -2.12 to -0.56 ng/g) decrease in serum total DDT. CONCLUSIONS: There were high total DDT levels in this sample of nulliparous Chinese women relative to Western populations, birth year was more strongly associated with serum DDT than age, and BMI was inversely related to serum DDT in this study.