Time after a peak-pesticide use period and neurobehavior among ecuadorian children and adolescents: The ESPINA study.

BACKGROUND: Limited evidence exists regarding transient neurobehavioral alterations associated with episodic pesticide exposures or agricultural pesticide spray periods. We previously observed that children examined soon after a pesticide spray period (the Mother's Day flower harvest [MDH]) had lower neurobehavioral performance than children examined later. The present study builds on our previous work by incorporating longitudinal analyses from childhood through adolescence. METHODS: We examined participants in agricultural communities in Ecuador (ESPINA study) during three periods: July-August 2008 (N = 313, 4-9-year-olds); April 2016 (N = 330, 11-17-year-olds); July-October 2016 (N = 535, 11-17-year-olds). Participants were examined primarily during a period of low floricultural production. Neurobehavior was assessed using the NEPSY-II (domains: Attention/Inhibitory Control, Language, Memory/Learning, Visuospatial Processing, and Social Perception). Linear regression and generalized linear mixed models were used to examine cross-sectional and longitudinal associations between examination date (days) after the MDH and neurobehavioral outcomes, adjusting for demographic, anthropometric, and socio-economic variables. RESULTS: Participants were examined between 63 and 171 days after the MDH. Mean neurobehavioral domain scores ranged from 1.0 to 17.0 (SDrange = 2.1-3.1) in 2008 and 1.0 to 15.5 (SDrange = 2.0-2.3) in 2016. In cross-sectional analyses (2016 only; N = 523), we found significant or borderline positive associations between time after the MDH and Attention/Inhibitory Control (difference/10 days [ß] = 0.22 points [95% CI = 0.03, 0.41]) and Language (ß = 0.16 points [95% CI = -0.03, 0.34]). We also observed positive, longitudinal associations (2008-2016) with Attention/Inhibitory Control (ß = 0.19 points [95% CI = 0.04, 0.34]) through 112 days after the harvest and Visuospatial Processing (ß = 3.56, ß-quadratic = -0.19 [95% CI: -0.29, -0.09]) through 92 days. CONCLUSIONS: Children examined sooner after the harvest had lower neurobehavioral performance compared to children examined later, suggesting that peak pesticide spray seasons may transiently affect neurobehavior followed by recovery during low pesticide-use periods. Reduction of pesticide exposure potential for children during peak pesticide-use periods is advised.

Possible pro-carcinogenic association of endotoxin on lung cancer among Shanghai women textile workers.

BACKGROUND: Endotoxin (lipopolysaccharide) is a widespread contaminant in many environmental settings. Since the 1970s, there has been generally consistent evidence indicating reduced risks for lung cancer associated with occupational endotoxin exposure. METHODS: We updated a case-cohort study nested within a cohort of 267,400 female textile workers in Shanghai, China. We compared exposure histories of 1456 incident lung cancers cases diagnosed during 1989-2006 with those of a reference subcohort of 3022 workers who were free of lung cancer at the end of follow-up. We applied Cox proportional hazards modelling to estimate exposure-response trends, adjusted for age and smoking, for cumulative exposures lagged by 0, 10, and 20 years, and separately for time windows of ⩽15 and >15 years since first exposure. RESULTS: We observed no associations between cumulative exposure and lung cancer, irrespective of lag interval. In contrast, analyses by exposure time windows revealed modestly elevated, but not statistically significant relative risks (∼1.27) at the highest three exposure quintiles for exposures that occurred >15 years since first exposure. CONCLUSIONS: The findings do not support a protective effect of endotoxin, but are suggestive of possible lung cancer promotion with increasing time since first exposure.

Lung cancer and occupational exposures other than cotton dust and endotoxin among women textile workers in Shanghai, China.

OBJECTIVES: Numerous epidemiological studies of lung cancer among textile workers worldwide consistently indicate reduced risks related to cotton dust exposure, presumably due to endotoxin contamination. Our objective was to investigate associations with other exposures potentially related to lung cancer, including wool and synthetic fibre dusts, formaldehyde, silica, dyes and metals, that have only been studied to a limited extent in the textile industry. METHODS: We conducted a case-cohort study nested within a cohort of 267,400 women textile workers in Shanghai, China. We compared work assignments and exposure histories of 628 incident lung cancer cases, diagnosed during 1989-1998, with those of a reference subcohort of 3188 workers. We reconstructed exposures with a job-exposure matrix developed specifically for textile factories. Cox proportional hazards modelling was applied to estimate age/smoking-adjusted relative risks (hazard ratios) and risk gradients associated with job assignments and specific agents other than cotton dust and endotoxin. RESULTS: No associations were observed for lung cancer with wool, silk or synthetic fibre dusts, or with most other agents. However, increased risks, although statistically imprecise, were noted for ≥ 10 years' exposures to silica (adjusted HR 3.5, 95% CI 1.0 to 13) and ≥ 10 years' exposures to formaldehyde (adjusted HR 2.1, 95% CI 0.4 to 11). CONCLUSIONS: Exposures to silica and formaldehyde, although not widespread among the cohort, may have increased lung cancer risk. Silica is an established human lung carcinogen, whereas there is only weak prior evidence supporting an association with formaldehyde. Both exposures warrant consideration as potential lung carcinogens in textile manufacturing.

Occupational exposure to bisphenol-A (BPA) and the risk of self-reported male sexual dysfunction.

BACKGROUND: Animal studies have suggested that bisphenol-A (BPA) is a potential human endocrine disrupter; but evidence from human studies is needed. METHODS: We conducted an occupational cohort study to examine the effect of occupational exposure to BPA on the risk of male sexual dysfunction. Current workers from BPA-exposed and control factories were recruited. The exposed workers were exposed to very high BPA levels in their workplace. Male sexual function was ascertained through in-person interviews using a standard male sexual function inventory. RESULTS: BPA-exposed workers had consistently higher risk of male sexual dysfunction across all domains of male sexual function than the unexposed workers. After controlling for matching variables and potential confounders, exposed workers had a significantly increased risk of reduced sexual desire [odds ratios (OR) = 3.9, 95% confidence interval: 1.8-8.6), erectile difficulty (OR = 4.5, 95% CI 2.1-9.8), ejaculation difficulty (OR = 7.1, 95% CI 2.9-17.6), and reduced satisfaction with sex life (OR = 3.9, 95% CI 2.3-6.6). A dose-response relationship was observed with an increasing level of cumulative BPA exposure associated with a higher risk of sexual dysfunction. Furthermore, compared with the unexposed workers, BPA-exposed workers reported significantly higher frequencies of reduced sexual function within 1 year of employment in the BPA-exposed factories. CONCLUSIONS: Our findings provide the first evidence that exposure to BPA in the workplace could have an adverse effect on male sexual dysfunction.

Post hoc Parkinson's disease: identifying an uncommon disease in the Cardiovascular Health Study.

BACKGROUND: Although ongoing cohort studies offer a unique opportunity to apply existing information collected prospectively to further the scientific understanding of Parkinson's disease (PD), they typically have limited information for clinical diagnosis. METHODS: We used combinations of self-report, International Classification of Diseases - 9th edition codes and antiparkinsonian medications to identify PD in the Cardiovascular Health Study. To determine whether the expected inverse association between smoking and PD is evident using our outcome definitions, we assessed baseline smoking characteristics for various definitions of PD. RESULTS: We identified 60 cases with prevalent PD (1.0%; 95% confidence interval, CI = 0.8-1.3%) and 154 with incident PD by year 14. Clear associations were observed for current smokers (odds ratio, OR = 0.50; 95% CI = 0.26-0.95) and for those who smoked ≥50 pack-years (OR = 0.53; 95% CI = 0.29-0.96). Estimates for smoking were similar when ≥2 data sources were required. Estimates for self-report alone were attenuated towards null. CONCLUSIONS: Using multiple data sources to identify PD represents an alternative method of outcome identification in a cohort that would otherwise not be possible for PD research. Ongoing cohort studies can provide settings in which rapid replication and explorations of new hypotheses for PD are possible.

Future needs of occupational epidemiology of extremely low frequency electric and magnetic fields: review and recommendations.

The occupational epidemiological literature on extremely low frequency electric and magnetic fields (EMF) and health encompasses a large number of studies of varying design and quality that have addressed many health outcomes, including various cancers, cardiovascular disease, depression and suicide, and neurodegenerative diseases, such as Alzheimer disease and amyotrophic lateral sclerosis (ALS). At a 2006 workshop we reviewed studies of occupational EMF exposure with an emphasis on methodological weaknesses, and proposed analytical ways to address some of these. We also developed research priorities that we hope will address remaining uncertainties. Broadly speaking, extensive epidemiological research conducted during the past 20 years on occupational EMF exposure does not indicate strong or consistent associations with cancer or any other health outcomes. Inconsistent results for many of the outcomes may be attributable to numerous shortcomings in the studies, most notably in exposure assessment. There is, however, no obvious correlation between exposure assessment quality and observed associations. Nevertheless, for future research, the highest priorities emerge in both the areas of exposure assessment and investigation of ALS. To better assess exposure, we call for the development of a more complete job-exposure matrix that combines job title, work environment and task, and an index of exposure to electric fields, magnetic fields, spark discharge, contact current, and other chemical and physical agents. For ALS, we propose an international collaborative study capable of illuminating a reported association with electrical occupations by disentangling the potential roles of electric shocks, magnetic fields and bias. Such a study will potentially lead to evidence-based measures to protect public health.

Dust and chemical exposures, and miscarriage risk among women textile workers in Shanghai, China.

INTRODUCTION: To investigate possible associations between miscarriage and occupational exposures in the Shanghai textile industry. METHODS: A retrospective cohort study of miscarriages among 1752 women in the Shanghai textile industry was conducted. Reproductive history was self-reported by women and occupational work histories were collected from factory personnel records. Occupational exposures were assigned by linking work history information to an industry-specific job-exposure matrix informed by factory-specific textile process information and industrial hygiene assessments. Estimates of cotton dust and endotoxin exposure were also assigned. Odds ratios (OR) and 95% CI were estimated by multivariate logistic regression, with adjustment for age at pregnancy, educational level, smoking status of the woman and her spouse, use of alcohol, and woman's year of birth. RESULTS: An elevation in risk of a spontaneously aborted first pregnancy was associated with exposure to synthetic fibres (OR 1.89, 95% CI 1.20 to 3.00) and mixed synthetic and natural fibres (OR 3.31, 95% CI 1.30 to 8.42). No increased risks were observed for women working with solvents, nor were significant associations observed with quantitative cotton dust or endotoxin exposures. Associations were robust and similar when all pregnancies in a woman's reproductive history were considered. CONCLUSIONS: Occupational exposure to synthetic fibres may cause miscarriages, and this possibility should be the subject of further investigation.

Occupational risk factors for nasopharyngeal cancer among female textile workers in Shanghai, China.

AIMS: To investigate whether occupational exposure to dusts and chemicals in the Chinese textile industry are associated with risk of nasopharyngeal cancer. METHODS: Sixty seven nasopharyngeal carcinoma (NPC) cases identified during 1989-98 and a random sample (n = 3188) of women were included in a case cohort study nested in a cohort of 267,400 women textile workers in Shanghai, China. A complete occupational history of work in the textile industry was obtained for each woman. A job exposure matrix developed by experienced industrial hygienists was used to assess exposures to specific dusts and chemicals. RESULTS: Risk of NPC is associated with cumulative exposure to cotton dust. The hazard ratio for women cumulatively exposed to >143.4 mg/m3 x years of cotton dust was 3.6 (95% CI 1.8 to 7.2) compared with unexposed women. Trends of increasing risk were also found with increasing duration of exposure to acids and caustics (p = 0.05), and with years worked in dyeing processes (p = 0.06). Women who worked at least 10 years in dyeing processes had a 3.6-fold excess risk of NPC (95% CI 1.0 to 12.1). CONCLUSIONS: Occupational exposure to cotton dust, acids, and caustics, and work in dyeing and printing jobs in the textile industry may have increased risk of NPC in this cohort.

Occupational risk factors for pancreatic cancer among female textile workers in Shanghai, China.

OBJECTIVES: To investigate whether occupational exposures to dusts and chemicals in the Shanghai textile industry are associated with risk of pancreatic cancer. METHODS: A case cohort study nested in a cohort of 267,400 female textile workers in Shanghai, China was conducted among 180 incident pancreatic cancer cases and an age stratified randomly selected comparison subcohort (n = 3188). A complete occupational history of work in the textile industry was obtained for each woman, and was linked to a job exposure matrix developed for the textile industry to estimate exposures to specific dusts and chemicals. Cumulative exposures to cotton dust and endotoxin were reconstructed from historical and contemporaneous measurements. RESULTS: After adjusting for smoking status, a trend of decreasing risk of pancreatic cancer was observed for increasing cumulative exposures to cotton dust and endotoxin with a lag of 20 years. The hazard ratios for women cumulatively exposed to >143.4 mg/m3 x years of cotton dust and >3530.6 EU/m3 x years of endotoxin were 0.6 (95% CI 0.3 to 0.9) and 0.5 (95% CI 0.3 to 0.9), respectively, compared to unexposed women. There was little evidence that exposures to other textile dusts and chemicals were associated with risk of pancreatic cancer. CONCLUSIONS: Occupational exposure to cotton dust and endotoxin in the textile industry may have reduced risks of pancreatic cancer in this cohort. These associations should be replicated by others before making a firm conclusion of their possible effects on pancreatic cancer.

Prioritizing future resources for epidemiologic research on old and newly emerging occupational hazards.

BACKGROUND: Inevitably, occupational epidemiologists must decide when and how to shift research attention and resources from investigations of old, established health hazards to a focus on newly emerging potential risk factors. As yet unknown occupational health consequences of burgeoning worldwide technologies, such as the microelectronics industry, and increasing recognition of the importance of common, yet non-traditional occupationally-related health effects, such as musculoskeletal disorders in office workers, give strong impetus for embarking in new directions. However, there remains much to be learned from continued investigation of well-established occupational hazards, such as asbestos, benzene, and lead. OBJECTIVES: A rational strategy for planning future research will need to consider optimizing resources. CONCLUSIONS: The following suggestions are offered. 1) First and foremost, occupational risk factors are most directly, and arguably most validly, identified by studying workers in well-defined cohorts, ideally when exposures are adequately characterized. To this end, industry-based cohort studies should be given priority, at least for older hazards, over population-based case-control and surveillance designs. 2) Defined cohorts with extensive exposure and health outcome data should continue to be followed, as resources permit; 3) Launching cohort studies for potential new hazards should incorporate extensive exposure assessments at the outset, and should preferentially select inception cohorts of newly hired workers. Valid biomarkers of pre-clinical disease will be especially valuable in this regard. 4) Capitalizing on new technological advances in exposure assessment, clinical medicine, molecular genetics should be encouraged

Risk of lymphatic or haematopoietic cancer mortality with occupational exposure to animals or the public.

BACKGROUND: Occupational exposure to animals or the public could result in exposure to infectious agents, which may play a role in the aetiology of lymphohaematopoietic (LH) cancers. AIMS: To conduct a population based, case-control study of death certificate data from 1984 to 1998 in 24 US states in order to evaluate the risk of mortality from LH neoplasms associated with occupational exposure to animals or the public. METHODS: Cases were selected as those with an underlying cause of death of non-Hodgkin's lymphoma (NHL, n = 72,589), Hodgkin's disease (HD, n = 5479), multiple myeloma (n = 35,857), or leukaemia (n = 68,598); 912 615 controls were randomly selected from all remaining deaths, frequency matched on age, sex, race, and geographic region. RESULTS: Occupational exposure to animals was associated with modest increased risks of mortality from all four LH cancers; these associations varied by region. Occupational exposure to the public was associated with only negligible increased risk with LH cancer outcomes. Occupations involving animal exposure were predominantly agricultural, and the risks associated with employment in the livestock industry exceeded the corresponding risks associated with the crop industry for all outcomes except HD. CONCLUSIONS: Increased risks of NHL, HD, multiple myeloma, and leukaemia were associated with occupations that involved animal exposure. Regional differences in risk imply that the risks may be associated with exposure to specific livestock or farming practices. However, these associations may be confounded by other farming related exposures, such as pesticides. Because the use of death certificates to classify occupation may result in misclassification during aetiologically relevant time periods, these hypotheses should be further explored in studies with detailed information on lifetime occupation.

Human peripheral lymphocytes as indicators of microsomal epoxide hydrolase activity in liver and lung.

In this study, we have applied an improved assay for the determination of microsomal epoxide hydrolase activity to assess enzymatic levels in human lung, liver, and blood lymphocytes. The assay is fluorescence-based and monitors the epoxide hydrolase-mediated conversion of (+/-)-benzo[a]pyrene-4,5-epoxide to (+/-)-trans-benzo[a]pyrene-4,5-dihydrodiol, using a high pressure liquid chromatography separation system. Approximately a 40-fold range in microsomal epoxide hydrolase activities was detected in blood lymphocytes collected from 70 individual donors. In 38 individuals who were sampled twice after a 3-month interval, the repeatability of an individual's lymphocyte epoxide hydrolase activity was highly correlated (r = 0.80, p < 0.02). In addition, within the same individual there appeared to be a strong correlation between lymphocyte and liver epoxide hydrolase activity (r = 0.92, p = 0.02), and some correlation between liver and lung activity (r = 0.58, p = 0.05). Activities were assessed in lymphocytes from a styrene-exposed worker population but no significant associations between blood concentrations of styrene and epoxide hydrolase activity levels were observed. Neither were any correlations detected in these workers between epoxide hydrolase activities and age, years on the job, alcohol consumption, sex, or smoking status. The results of our study suggest that blood lymphocytes are a useful sentinel cell for epoxide hydrolase activity determinations in individuals, as these measures are relatively stable over time and appear to reflect activity levels in other target organs.

Genetic polymorphisms of microsomal and soluble epoxide hydrolase and the risk of Parkinson's disease.

Oxidative stress is hypothesized to play a major role in the destruction of dopaminergic neurons, which is associated with Parkinson's disease. Epoxides are potentially reactive intermediates formed through the oxidative metabolism of both exogenous and endogenous substances that contribute to cytotoxic damage mediated by oxidative stress. The microsomal (EPHX1) and soluble (EPHX2) epoxide hydrolases function to regulate the oxidation status of a wide range of xenobiotic- and lipid-derived substrates; therefore, interindividual variation in these pathways may mitigate epoxide-related cellular injury. In this investigation, we examined the potential association between the risk of Parkinson's disease and genetic variation within the EPHX1 and EPHX2 genes. Fluorescent 5' nuclease-based assays were developed to identify the allelic status of individuals with respect to specific single nucleotide polymorphisms in exons 3 and 4 of the EPHX1 gene and exons 8 and 13 of the EPHX2 gene. EPHX1 and EPHX2 genotype data were obtained from 133 idiopathic Parkinson's disease patients and 212 control subjects matched on age, gender and ethnicity. No statistically significant differences were found in the distribution of the reference and variant alleles between Parkinson's disease and control subjects, or when results were stratified by gender. Therefore, common polymorphisms within EPHX1 and EPHX2 do not appear to be important risk factors for Parkinson's disease.

Glutathione S-transferase M1, T1, and P1 polymorphisms as risk factors for renal cell carcinoma: a case-control study.

Renal cell carcinoma (RCC) has known environmental risk factors, notably smoking, and enzymes that biotransform carcinogens have high levels of activity in the kidney. However, a possible role of polymorphisms in these enzymes in RCC etiology has received little study. We investigated glutathione S-transferase (GST) polymorphisms in a population-based case-control study of RCC. Subjects completed a structured interview, and DNA was isolated from pathological material or buccal cells for 130 cases, and from blood for 505 controls. Genotypes for GSTM1 and GSTT1 were determined by multiplex PCR, and for GSTP1 by oligonucleotide ligation assay. The frequency of GSTM1 null genotype was 50.0% in cases and 50.5% in controls, with an adjusted odds ratio (OR) of 1.0 [95% confidence interval (CI), 0.6-1.6]. For GSTP1, the frequencies of genotypes AA, AG, and GG representing the Ile104Val variant were: cases, 44.6%, 43.1%, and 12.3%; controls, 43.4%, 44.0%, and 12.6%; OR for AG and GG, 1.0 (95% CI, 0.6-1.6). An excess of the GSTT1 null genotype was observed in cases compared with controls, 28.6% versus 18.5% (OR, 1.9; 95% CI, 1.1-3.4). The association with GSTT1 was present among both smokers and nonsmokers, but was modified by body mass index, a recognized risk factor for RCC; among subjects in the lowest tertile of body mass index, the OR for GSTT1 null was 4.8 (95% CI, 1.8-13.0). The association between GSTT1 null and increased RCC risk in this population-based study suggests that activity of the GSTT1 enzyme protects against RCC. This contrasts with a recent report of reduced risk of RCC associated with GSTT1 null in a cohort of trichloroethene-exposed workers and suggests that specific chemical exposures alter the effect of GSTT1 on cancer risk.

MAOB intron 13 and COMT codon 158 polymorphisms, cigarette smoking, and the risk of PD.

BACKGROUND: A polymorphism (G to A transition) in intron 13 of the mitochondrial enzyme monoamine oxidase B (MAOB) gene may modify, alone or by interacting with the catechol-O-methyltransferase (COMT(LL)) genotype (low enzymatic activity), the risk of idiopathic PD. Also, the association between never smoking and PD risk may be present only in people with the MAOB G allele. METHODS: The authors studied two ongoing prospective cohorts-the Nurses' Health Study (121,700 women aged 30 to 55 in 1976) and the Health Professionals' Follow-up Study (51,529 men aged 40 to 75 in 1986). They identified new PD cases through 1996, selected random control subjects matched on age and study cohort, and obtained DNA samples from blood or buccal smears from 85% of the eligible cases and 84% of the control subjects. They included genotypes from 214 cases and 449 control subjects, all Caucasian. RESULTS: The odds ratio of PD was 1.2 (95% CI 0.9, 1.7) for MAOB genotypes G/GG/GA compared with genotypes A/AA, and 1.1 (0.7, 1.8) for COMT genotypes LL compared with HH. The odds ratio (95% CI) was 1.7 (0.7, 3.9) for those with MAOB G/GG and COMT(LL) genotypes compared with those with MAOB A/AA and COMT(HH). There was a strong association between never smoking and PD risk in all groups defined by MAOB and COMT genotypes. CONCLUSION: The findings do not support a major role of the MAOB intron 13 polymorphism in the development of PD, either by itself or by interacting with smoking.

A genetic polymorphism of MAO-B modifies the association of cigarette smoking and Parkinson's disease.

In a population-based case-control study, we found a reversal of the association of cigarette smoking with Parkinson's disease (PD) in relation to the monoamine oxidase B intron 13 genetic polymorphism. A reduced PD risk related to pack-years of smoking was detected for persons with the G allele, whereas an opposite effect was found among persons with the A allele. These results indicate an unexplained interaction between cigarette smoking and this genetic polymorphism.

Interaction of blood lead and delta-aminolevulinic acid dehydratase genotype on markers of heme synthesis and sperm production in lead smelter workers.

The gene that encodes gamma-aminolevulinic acid dehydratase (ALAD) has a polymorphism that may modify lead toxicokinetics and ultimately influence individual susceptibility to lead poisoning. To evaluate the effect of the ALAD polymorphism on lead-mediated outcomes, a cross-sectional study of male employees from a lead-zinc smelter compared associations between blood lead concentration and markers of heme synthesis and semen quality with respect to ALAD genotype. Male employees were recruited via postal questionnaire to donate blood and urine for analysis of blood lead, zinc protoporphyrin (ZPP), urinary coproporphyrin (CPU), and ALAD genotype, and semen samples for semen analysis. Of the 134 workers who had ALAD genotypes completed, 114 (85%) were ALAD1-1 (ALAD1) and 20 (15%) were ALAD1-2 (ALAD2). The mean blood lead concentrations for ALAD1 and ALAD2 were 23.1 and 28.4 microg/dl (p = 0.08), respectively. ZPP/heme ratios were higher in ALAD1 workers (68.6 vs. 57.8 micromol/ml; p = 0.14), and the slope of the blood lead ZPP linear relationship was greater for ALAD1 (2.83 vs. 1.50, p = 0.06). No linear relationship between CPU and blood lead concentration was observed for either ALAD1 or ALAD2. The associations of blood lead concentration with ZPP, CPU, sperm count, and sperm concentration were more evident in workers with the ALAD1 genotype and blood lead concentrations >/= 40 microg/dl. The ALAD genetic polymorphism appears to modify the association between blood lead concentration and ZPP. However, consistent modification of effects were not found for CPU, sperm count, or sperm concentration.

Association of a polymorphism in intron 13 of the monoamine oxidase B gene with Parkinson disease.

Monoamine oxidase B (MAO-B) is an enzyme that has relevance for Parkinson disease (PD) because of its roles in catabolizing dopamine and potentially activating exogenous neurotoxicants. A polymorphism of the gene encoding MAO-B has been identified as a single base change (A or G) in intron 13 of the X chromosome. The A allele was previously associated with an approximately twofold risk of PD. The present study compared A and G allele frequencies between newly diagnosed idiopathic PD cases and a control group free of neurodegenerative diseases. All study subjects were Caucasian. Cases were 37 men and 25 women, age 37-80 years; controls were 50 men and 29 women, age 45-82 years. MAO-B genotype was determined by the allele-specific polymerase chain reaction on DNA extracted from peripheral lymphocytes. In complete contrast to previous studies, elevated risks were detected with the G allele. The age-adjusted odds ratio for the G allele in males was 1.87 ((95% confidence interval) 0.78-4.47). Among females the age-adjusted odds ratios were 5.00 ((95% confidence interval) 1.13-22.1) for the GA genotype and 5.60 ((95% confidence interval) 1.01-30.9) for the GG genotype. These findings, although of limited statistical precision, suggest that the G allele of this MAO-B polymorphism may relate to PD risk.

Predicting long-term functional limitations among back pain patients in primary care settings.

To identify predictors of back-related long-term functional limitations, 1213 adult enrollees of a Health Maintenance Organization (HMO) in Washington state were interviewed about a month after a consultation for back pain in a primary care setting in 1989-1990, and followed each year thereafter. Out of 100 factors documented at the one-month assessment, measures of somatization, depression, functional limitations, and pain were the strongest predictors of two-year modified Roland-Morris score among a random subsample of 569 subjects. A multiple regression model containing the Symptom Checklist Depression and Somatization scores, the one-month modified Roland-Morris score and the number of pain days in the past six months explained about 30% of the variance in the outcome. Using recursive partitioning, a very simple model was developed to identify patients at high risk of sustaining long-term significant functional limitations. The regression model and the recursive partitioning model were successfully tested in a fresh sample of patients (n = 644). Clinical application of the recursive partitioning model and methodological aspects of this study are discussed.