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Biomedical subjects

H Checkoway

Publications and source records attributed to H Checkoway.

At least 19 recordsLinked to original sources
PubMed2002

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.

Adult↗
PubMed2002

Exposure to crystalline silica, silicosis, and lung disease other than cancer in diatomaceous earth industry workers: a quantitative risk assessment.

OBJECTIVES: To estimate excess lifetime risk of (a) mortality from lung disease other than cancer (LDOC), and, (b) onset of radiographic silicosis, arising from occupational exposure to respirable crystalline silica dust. METHODS: Data from a cohort of California diatomaceous earth mining and processing workers exposed to crystalline silica dust (mainly as cristobalite) were reanalyzed with Poisson regression methods with internal and external adjustments for potential confounding by calendar time, age, smoking, Hispanic ethnicity, and time since first observation. Model fit was evaluated by comparing deviances and fitting cubic spline models. Lifetime risks of death from LDOC and radiographic silicosis were estimated up to age 85 with an actuarial approach accounting for competing causes of death. RESULTS: For deaths due to LDOC, a linear relative rate model gave the best fit in Poisson regression analyses. At the mean cumulative exposure of LDOC cases to silica, after adjustment for smoking, the estimated rate ratio was 4.2 (p<0.0001); at the maximum cumulative exposure of cases, the rate ratio was 18.4. The excess lifetime risk for white men exposed to respirable cristobalite dust for 45 years at the current permissible exposure limit (PEL; about 0.05 mg/m(3)) of the Occupational Safety and Health Administration was 54/1000 (95% confidence interval (95% CI) 17 to 150). For 70 incident cases of radiographic silicosis largely manifest before the end of employment, the best fit was also the linear relative rate model, predicting a rate ratio of 25.6 for silicosis at the mean cumulative exposure of the cases (p<0.0001). The excess lifetime risk for silicosis at the current PEL was 75/1000. CONCLUSION: Current occupational health standards for crystalline silica permit risks of lung disease other than cancer far in excess of what is usually considered acceptable by the Occupational Safety and Health Administration (a lifetime risk of less than one in a thousand deaths).

Adult↗
PubMed2002

Exposure-response analysis and risk assessment for silica and silicosis mortality in a pooled analysis of six cohorts.

AIMS: To study the relation between exposure to crystalline silica and silicosis mortality. Although mortality is an important endpoint for regulators, there have been no exposure-response studies for silicosis mortality, because of the relative rareness of silicosis as an underlying cause of death, and the limited availability of quantitative exposure estimates. METHODS: Data from six occupational cohorts were pooled with good retrospective exposure data in which 170 deaths from silicosis were reported. Standard life table analyses, nested case-control analyses, and risk assessment were performed. RESULTS: The rate of silicosis mortality in the combined data was 28/100 000 py, increasing in nearly monotonic fashion from 4.7/100 000 for exposure of 0-0.99 mg/m(3)-years to 233/100 000 for exposure of >28.1 mg/m(3)-years. The estimated risk of death up to age 65 from silicosis after 45 years of exposure at 0.1 mg/m(3) silica (the current standard in many countries) was 13 per 1000, while the estimated risk at an exposure of 0.05 mg/m(3) was 6 per 1000. Both of these risks are above the risk of 1 per 1000 typically deemed acceptable by the US OSHA. CONCLUSION: The findings from this pooled analysis add further support to the need to control silica exposure and to lower the occupational standards. Our estimates of lifetime silicosis mortality risk are probably underestimates as, in addition to exposure misclassification, our study might have suffered from outcome misclassification in that silicosis deaths might have been coded to other related causes, such as tuberculosis or chronic obstructive pulmonary disease.

Adult↗
PubMed2001

Comparison of self-report, video observation and direct measurement methods for upper extremity musculoskeletal disorder physical risk factors.

The prevention of work-related musculoskeletal disorders has become a national priority in many countries. Increasingly, attempts are made to quantify those exposures that increase risk in order to set exposure limit values. This study used commonly employed field measurement methods and tools in order to perform an inter-method comparison between three primary methods of risk factor exposure assessment: self-report questionnaires, observational video analysis and direct measurement. Extreme posture duration, repetition, hand force (estimated from electromyography) and movement velocity were assessed for 18 subjects while performing each of three jobs processing tree seedlings. Results indicated that self-reports were the least precise assessment method, which consistently overestimated exposures for each of the measured risk factors. However, adjustment of the reports as psychophysical scales may increase agreement on a group level. Wrist flexion/extension duration and repetition were best measured by electrogoniometer. Electrogoniometric measures of wrist deviation duration and frequency were less precise than video analysis. Forearm rotation duration and repetition, grip force and velocity appeared to be best quantified by direct measurement as measured by electrogoniometer and electromyography (EMG) (as root-mean-square amplitude). The results highlight the fact that it is as important to consider and report estimated measurement error in order to reduce potential exposure misclassification in epidemiologic studies.

Arm↗
PubMed2001

Genetic polymorphisms of superoxide dismutase in Parkinson's disease.

Oxidative stress reactions may contribute to the pathogenesis of Parkinson's disease (PD). The superoxide dismutases potentially play significant roles in PD by detoxifying superoxide radical. We developed genomic DNA and cDNA-based sequencing assays to identify genetic variants in the copper/zinc superoxide dismutase (SOD1) and manganese superoxide dismutase (SOD2) genes. No genetic variants were detected in the gene encoding SOD1 in DNA from 45 idiopathic PD cases and 49 controls from a population-based case-control study. However, we identified a previously described polymorphism of the mitochondrial targeting sequence consisting of a C47T in exon 2 of SOD2, which results in an alanine to valine substitution. We analyzed this SOD2 variant in DNA from 155 cases and 231 controls from the same study, using an allele-specific fluorogenic 5' nuclease assay, and found no differences in the distributions of allelic frequencies. These results indicate that SOD gene variants do not contribute to PD pathogenesis.

Adult↗
PubMed2001

Pooled exposure-response analyses and risk assessment for lung cancer in 10 cohorts of silica-exposed workers: an IARC multicentre study.

OBJECTIVES: Silica is one of the most common occupational exposures worldwide. In 1997 the International Agency for Research on Cancer (IARC) classified inhaled crystalline silica as a human carcinogen (group 1), but acknowledged limitations in the epidemiologic data, including inconsistencies across studies and the lack of extensive exposure-response data. We have conducted a pooled exposure-response analysis of 10 silica-exposed cohorts to investigate lung cancer. METHODS: The pooled cohort included 65,980 workers (44,160 miners, 21,820 nominees), and 1,072 lung cancer deaths (663 miners, 409 nonminers). Follow-up has been extended for five of these cohorts beyond published data. Quantitative exposure estimates by job and calendar time were adopted, modified, or developed to permit common analyses by respirable silica (mg/m3) across cohorts. RESULTS: The log of cumulative exposure, with a 15-year lag, was a strong predictor of lung cancer (p = 0.0001), with consistency across studies (test for heterogeneity, p = 0.34). Results for the log of cumulative exposure were consistent between underground mines and other facilities. Categorical analyses by quintile of cumulative exposure resulted in a monotonic trend with odds ratios of 1.0. 1.0, 1.3, 1.5, 1.6. Analyses using a spline curve also showed a monotonic increase in risk with increasing exposure. The estimated excess lifetime risk (through age 75) of lung cancer for a worker exposed from age 20 to 65 at 0.1 mg/m3 respirable crystalline silica (the permissible level in many countries) was 1.1-1.7%, above background risks of 3-6%. CONCLUSIONS: Our results support the decision by the IARC to classify inhaled silica in occupational settings as a carcinogen, and suggest that the current exposure limits in many countries may be inadequate. These data represent the first quantitative exposure-response analysis and risk assessment for silica using data from multiple studies.

Air Pollutants, Occupational↗
PubMed2001

Referent selection in case-crossover analyses of acute health effects of air pollution.

The case-crossover design was proposed for the study of a transient effect of an intermittent exposure on the subsequent occurrence of a rare acute-onset disease. This design can be an alternative to Poisson time series regression for studying the health effects of fine particulate matter air pollution. Characteristics of time-series of particulate matter, including long-term time trends, seasonal trends, and short-term autocorrelations, require that referent selection in the case-crossover design be considered carefully and adapted to minimize bias. We performed simulations to evaluate the bias associated with various referent selection strategies for a proposed case-crossover study of associations between particulate matter and primary cardiac arrest. Some a priori reasonable strategies were associated with a relative bias as large as 10%, but for most strategies the relative bias was less than 2% with confidence interval coverage within 1% of the nominal level. We show that referent selection for case-crossover designs raises the same issues as selection of smoothing method for time series analyses. In addition, conditional logistic regression analysis is not strictly valid for some case-crossover designs, introducing further bias.

Acute Disease↗
PubMed2001

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.

Adult↗
PubMed2001

Formal education and back pain: a review.

OBJECTIVES: To summarise the scientific evidence on the relation between educational status and measures of the frequency and the consequences of back pain and of the outcomes of interventions among back pain patients, and to outline possible mechanisms that could explain such an association if found. DESIGN: Sixty four articles published between 1966 and 2000 that documented the association of formal education with back pain were reviewed. MAIN RESULTS: Overall, the current available evidence points indirectly to a stronger association of low education with longer duration and/or higher recurrence of back pain than to an association with onset. The many reports of an association of low education with adverse consequences of back pain also suggest that the course of a back pain episode is less favourable among persons with low educational attainment. Mechanisms that could explain these associations include variations in behavioural and environmental risk factors by educational status, differences in occupational factors, compromised "health stock" among people with low education, differences in access to and utilisation of health services, and adaptation to stress. Although lower education was not associated with the outcomes of interventions in major studies, it is difficult, in light of the current limited available evidence, to draw firm conclusions on this association. CONCLUSION: Scientific evidence supports the hypothesis that less well educated people are more likely to be affected by disabling back pain. Further study of this association may help advance our understanding of back pain as well as understanding of the relation between socioeconomic status and disease as a general phenomenon.

Adolescent↗
PubMed2001

Crystalline silica exposure and lung cancer mortality in diatomaceous earth industry workers: a quantitative risk assessment.

OBJECTIVE: To use various exposure-response models to estimate the risk of mortality from lung cancer due to occupational exposure to respirable crystalline silica dust. METHODS: Data from a cohort mortality study of 2342 white male California diatomaceous earth mining and processing workers exposed to crystalline silica dust (mainly cristobalite) were reanalyzed with Poisson regression and Cox's proportional hazards models. Internal and external adjustments were used to control for potential confounding from the effects of time since first observation, calendar time, age, and Hispanic ethnicity. Cubic smoothing spline models were used to assess the fit of the models. Exposures were lagged by 10 years. Evaluations of the fit of the models were performed by comparing their deviances. Lifetime risks of lung cancer were estimated up to age 85 with an actuarial approach that accounted for competing causes of death. RESULTS: Exposure to respirable crystalline silica dust was a significant predictor (p<0.05) in nearly all of the models evaluated and the linear relative rate model with a 10 year exposure lag seemed to give the best fit in the Poisson regression analysis. For those who died of lung cancer the linear relative rate model predicted rate ratios for mortality from lung cancer of about 1.6 for the mean cumulative exposure to respirable silica compared with no exposure. The excess lifetime risk (to age 85) of mortality from lung cancer for white men exposed for 45 years and with a 10 year lag period at the current Occupational Safety and Health Administration (OSHA) standard of about 0.05 mg/m(3) for respirable cristobalite dust is 19/1000 (95% confidence interval (95% CI) 5/1000 to 46/1000). CONCLUSIONS: There was a significant risk of mortality from lung cancer that increased with cumulative exposure to respirable crystalline silica dust. The predicted number of deaths from lung cancer suggests that current occupational health standards may not be adequately protecting workers from the risk of lung cancer.

Adult↗
PubMed2001

Serum hepatic biochemical activity in two populations of workers exposed to styrene.

OBJECTIVE: To determine whether hepatic biochemical changes, as measured by routinely available tests indicative of hepatocellular necrosis, cholestasis, or altered hepatic clearance of bilirubin, occur in association with low to moderate exposure to styrene commonly experienced in industrial production. METHODS: Two independent cross sectional studies were performed comparing serum hepatic transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), cholestatic enzymes (alkaline phosphatase (AP) and gamma glutamyl transpeptidase (GGT)), and bilirubin in (a) 47 workers of fibreglass reinforced plastics who were exposed to styrene and (b) 21 boat and tank fabricators, with separate referent groups of unexposed workers. Exposure to styrene was assessed in air by dosimetry, and in venous blood by headspace analysis. Hepatic biochemical variables were assessed across strata of exposure to styrene defined as 25 ppm in air, or 0.275 mg/l in blood, adjusting for age, sex, body mass index, and ethanol consumption. RESULTS: A consistent and significant linear trend for increasing direct bilirubin and direct/total bilirubin ratio was found in association with increasing exposure to styrene, by both air and blood monitoring, in both studies. Mean direct bilirubin concentrations increased from 0.05-0.08 mg% in referents to 0.12-0.19 in workers exposed above 25 ppm, with a significant exposure-response trend (p<0.005). Significantly increased direct/total bilirubin ratios, ranging from 0.22 to 0.35 were associated with exposure to styrene (p<0.001), indicating diminished hepatic clearance of conjugated bilirubin. Also, a significant linear association between the hepatic transaminases ALT and AST and exposure to styrene was found in pooled regression analyses, with an increase in AP of about 10 IU/ml in workers exposed above 25 ppm air or 0.275 mg/l blood styrene in pooled analyses from both studies. CONCLUSIONS: The consistent finding of increased direct bilirubin and AP concentrations in these two independent studies provides evidence for diminished hepatic clearance of conjugated bilirubin with associated cholestasis in workers exposed to styrene. The finding of a significant linear association between hepatic transaminase concentrations and exposure to styrene in pooled analyses is consistent with mild hepatic injury and associated metabolic dysfunction.

Adult↗
PubMed2001

Parkinsonism and occupational exposure to pesticides.

OBJECTIVE: To examine the risk of parkinsonism related to lifetime occupational exposure to pesticides among a cohort of men, mostly orchardists, in Washington State. METHODS: All 310 subjects in this study had previously participated in a cohort study of men occupationally exposed to pesticides. Subjects were given a structured neurological examination and completed a self administered questionnaire which elicited detailed information on pesticide (insecticide, herbicide, and fungicide) use throughout their working careers. Demographic characteristics were also sought. Subjects had a mean age of 69.6 years (range 49-96, SD 8.1). There were 238 (76.8%) subjects who reported some occupational exposure to pesticides, whereas 72 (23.2%) reported none. Parkinsonism was defined by the presence of two or more of rest tremor, rigidity, bradykinesia, and impairment of postural reflexes in subjects not on antiparkinsonian medication, or the presence of at least one sign if they were on such medication. Parkinson's disease was not studied explicitly because of the difficulty in distinguishing it from other parkinsonian syndromes. A generalised linear model was used to estimate prevalence ratios (PRs) for parkinsonism relative to history of farming, pesticide use, and use of well water. RESULTS: A PR of 2.0 (95% confidence interval (95% CI) 1.0 to 4.2) was found for subjects in the highest tertile of years of exposure to pesticides; a similarly increased, non-significant, PR was found for the middle tertile (1.9 (95% CI 0.9 to 4.0)), although a trend test did not show a significant exposure-response relation. No increased risks were found associated with specific pesticides or pesticide classes, nor with a history of farming or use of well water. CONCLUSION: Parkinsonism may be associated with long term occupational exposure to pesticides, although no associations with specific pesticides could be detected. This finding is consistent with most of the publications on this topic.

Aged↗
PubMed2001

A case-crossover analysis of particulate matter air pollution and out-of-hospital primary cardiac arrest.

Numerous epidemiologic studies have reported increases in the daily incidence of cardiovascular mortality and morbidity associated with increases in daily levels of particulate matter air pollution. We studied the association between the incidence of primary cardiac arrest and two daily measures of particulate matter using a case-crossover study of 362 cases of out-of-hospital cardiac arrest. All cases were attended by paramedics and had no history of clinically recognized heart disease or life-threatening comorbidities. We compared particulate matter levels at index times with particulate matter levels from referent days matched on day of week within strata defined by month and year. The estimated relative risk at a lag of 1 day for an interquartile range (IQR) change in nephelometry (0.51 x 10(-1) km(-1)) was 0.893 (95% CI = 0.779-1.024). The estimated relative risk at a lag of 1 day for an IQR change in PM10 (19.3 microg m(-3)) was 0.868 (95% CI = 0.744-1.012). Other lag periods gave similar results. We did not find evidence of confounding by carbon monoxide or sulfur dioxide. Analysis of effect modification by individual-level variables did not reveal any susceptible subgroups. These findings do no support an association between particulate matter and increased risk of primary cardiac arrest among persons without clinically recognized heart disease. The null results of this study may result from several factors, including the highly selected nature of this case series and the relatively low particulate matter levels in the Seattle metropolitan area.

Adult↗
PubMed2000

The EcoRV genetic polymorphism of human monoamine oxidase type A is not associated with Parkinson's disease and does not modify the effect of smoking on Parkinson's disease.

We previously observed an association with Parkinson's (PD), and modification of the effect of smoking on PD, by a polymorphism of the monoamine oxidase B (MAO-B) gene. The A form of monoamine oxidase (MAO-A) shares with MAO-B many characteristics that could be relevant to PD, especially proneuroxicant bioactivation and dopamine metabolism. MAO-A is also inhibited by tobacco smoke, which bears an apparent protective effect on PD. We investigated the possibility that MAO-A genetic variants may also be involved in predisposition to PD and in modification of the effect of smoking. Three-hundred and seventy-one subjects--145 idiopathic PD cases and 226 age/gender-matched controls--were genotyped for the EcoRV polymorphism of MAO-A gene which has been related to increased enzyme activity. MAO-A EcoRV polymorphism was neither significantly associated with PD nor did it modify the inverse relationship with smoking. These results suggest that the EcoRV polymorphism of MAO-A is not an important biomarker of PD risk.

Adult↗
PubMed2000

Is silicosis required for silica-associated lung cancer?

BACKGROUND: Abundant epidemiologic and experimental evidence supports the 1997 International Agency for Research on Cancer classification of crystalline silica as a human lung carcinogen. Nonetheless, there remains uncertainty about whether excessive lung cancer occurs exclusively among workers with silicosis. METHODS: A review was performed of published occupational epidemiologic literature directly pertinent to the interrelations among silica exposure, silicosis, and lung cancer. RESULTS: The association between silica and lung cancer is generally, but not uniformly, stronger among silicotics than nonsilicotics. However, the existing literature is ambiguous due to incomplete or biased ascertainment of silicosis, inadequate exposure assessment, and the inherently strong correlation between silica exposure and silicosis which hinders efforts to disentangle unique contributions to lung cancer risk. CONCLUSIONS: Until more conclusive epidemiologic findings become available, population-based or individually-based risk assessments should treat silicosis and lung cancer as distinct entities whose cause/effect relations are not necessarily linked.

Environmental Exposure↗
PubMed2000

Cause-specific mortality risks of anesthesiologists.

BACKGROUND: The health-related effects of the operating room environment are unclear. The authors compared mortality risks of anesthesiologists to those of internal medicine physicians between 1979 and 1995. METHODS: The Physician Master File database, a listing of all US physicians, was used to identify anesthesiologists and general internists. The cohort of internists (n = 40,211) was a stratified random sample of all internists, frequency-matched to the cohort of anesthesiologists (n = 40,242) by gender, decade of birth, and US citizenship. The National Death Index was used to confirm death status and to determine specific causes of death. Mortality risks, adjusted for age, gender, and race, were compared using the Cox proportional hazards regression model. RESULTS: The standardized mortality ratios for all physicians were well below 1.0, except for suicide. The all-cause mortality ratios, and the risks of death caused by cancer and heart disease, did not differ between anesthesiologists and internists. Anesthesiologists had an increased risk of death from suicide (rate ratio [RR] = 1.45, 95% confidence interval [CI] = 1.07 - 1.97), drug-related death (RR = 2.79, 95% CI = 1.87 - 4.15), death from other external causes (RR = 1.53, 95% CI = 1.05 - 2.22), and death from cerebrovascular disease (RR = 1.39, 95% CI = 1.08 - 1.79). Male anesthesiologists had an increased risk of death from HIV (RR = 1.82, 95% CI = 1.09 - 3.02) and viral hepatitis (RR = 7.98, 95% CI = 1.0 - 63.84). Although the risk to anesthesiologists of drug-related deaths was highest in the first 5 years after medical school graduation, it remained increased over that of internists throughout the career. CONCLUSIONS: Substance abuse and suicide represent significant occupational hazards for anesthesiologists. New methods to combat substance abuse among anesthesiologists should be developed.

Anesthesiology↗