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Biomedical subjects

H Checkoway

Publications and source records attributed to H Checkoway.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2000

Genetic polymorphism of dopamine D2 receptors in Parkinson's disease and interactions with cigarette smoking and MAO-B intron 13 polymorphism.

Genetic polymorphisms of dopamine D2 receptors (DRD2) may be susceptibility factors for Parkinson's disease due to their influence on dopamine response and association with cigarette smoking, which is inversely related to risk of Parkinson's disease. Relations of TaqIA and TaqIB DRD2 genotypes with Parkinson's disease were investigated and tested for interactive effects with smoking and the monoamine oxidase B (MAO-B) intron 13 polymorphism previously found to be related to smoking. Study subjects were 152 cases of idiopathic Parkinson's disease and 231 controls. The smoking history of all genotyped subjects was known. Subjects of genotype B12 were more frequent among cases than controls (27% and 23.8%, respectively), and were more frequent among "ever smokers" than "never smokers", among controls (27.8% and 17.2%, respectively), although these associations were not statistically significant. Neither TaqIA or TaqIB genotypes modified the inverse relation of smoking and Parkinson's disease. When genotypes for DRD2 were considered in combination with genotypes for intron 13 of MAO-B, genotype combinations with high risk of Parkinson's disease were found; although the MAO-B/DRD2 interaction did not reach statistical significance after Bonferroni correction for multiple comparisons, these results are suggestive of a possible synergism between MAOB and DRD2 genes with respect to Parkinson's disease.

Adult↗
PubMed2000

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.

Adult↗
PubMed2000

Mitochondrial ND1 sequence analysis and association of the T4216C mutation with Parkinson's disease.

Mitochondrial dysfunction originating from mutations in Complex I genes may play a role in the pathogenesis of Parkinson's disease (PD). In this study, the entire ND1 coding sequence was sequenced in 84 newly diagnosed PD cases and 127 age/gender-matched controls. Numerous missense mutations were found at low frequency (<5%), whereas a thymidine to cytosine missense mutation at position 4216 that results in the replacement of tyrosine with histidine was found in 25% of the PD case samples and in 18% of the controls. When calculated according to gender, the 4216 mutation was observed in 26% of the male cases versus 16% of male controls (Odds Ratio [OR] = 1.85; 95% CI = 0.79-4.34). In contrast, females exhibited approximately equal frequencies among cases (22.5%) and controls (21%), yielding an OR of 1.08 (95% C.I. = 0.36-3.22). The findings indicate only a weak association of this genetic variant with PD.

Humans↗
PubMed1999

A comparison of pain, functional limitations, and work status indices as outcome measures in back pain research.

STUDY DESIGN: We conducted a prospective study with a 2-year follow-up. OBJECTIVE: To compare pain, functional limitations, and work status indices as measures of outcome among back pain patients. SUMMARY OF BACKGROUND DATA: Work status, pain, and functional limitations indices are often considered as interchangeable outcome measures in back pain research. This perspective has been criticized by several authors, who argue that each of these outcome measures reflects a different construct that may vary independently of the others. METHODS: The study was conducted on 720 patients, who sought care for back pain in primary care settings of a large health maintenance organization in 1989-90, and were interviewed one month and two years later. X2 analyses and receiver operating characteristic curves were used to compare the accuracy of a pain rating and a modified 16-item Roland-Morris score in classifying patients on work status and on the change in work status over time. RESULTS: Moderate agreement between the pain and functional limitations measures and work status was observed. Pain and functional limitations change scores agreed moderately with improvement in work status, but were poorly associated with decline in work status. CONCLUSIONS: Although the pain, functional limitations, and work status indices examined in this study are related, they are not equivalent and should not be regarded as interchangeable. These results argue for a clearer distinction of outcome measures in back pain research.

Adult↗
PubMed1999

Dietary factors in Parkinson's disease: the role of food groups and specific foods.

PURPOSE: The association between self-reported past food intake and Parkinson's disease (PD) was investigated in a case-control study of men and women aged 40-89 years. METHODS: Newly diagnosed idiopathic PD cases were ascertained from neurologists, and from outpatient and pharmacy computerized databases, at the Group Health Cooperative (GHC) clinics in the Puget Sound region of Washington state. Control subjects were chosen from the GHC patient roster and had no reported history of diagnosed neurodegenerative disease. Dietary data were obtained from structured questionnaires. RESULTS: An increase in PD risk with increasing intake was noted for foods that contain animal fat and foods containing vitamin D. Intake of fruits, vegetables, meats, bread and cereals, or foods containing vitamins A, C, E, or iron was not significantly related to PD risk. Vitamin use, in general, was also not found to be related to PD risk, although a significant trend of increasing risk of PD was noted for intake of vitamin A supplements. CONCLUSIONS: Although these data support previous findings of no association of past intake with most food groups and PD risk, they confirm an increased risk of PD associated with foods containing animal fat.

Adult↗
PubMed1999

Neuropsychological function in retired workers with previous long-term occupational exposure to solvents.

OBJECTIVES: It is plausible that neurodegenerative processes of aging might have a contributing role in the development of chronic effects of exposure to organic solvents. This study evaluated the risk for neuropsychological deficits among retired workers, relative to their histories of exposure to occupational solvents. METHODS: This cross sectional study evaluated retired male workers, 62-74 years of age, including 89 people with previous long-term occupational exposure to solvents (67 retired painters and 22 retired aerospace manufacturing workers), and 126 retired carpenters with relatively minimal previous exposure to solvents. Subjects completed a standardised neuropsychological evaluation and psychiatric interview, structured interviews for histories of occupational exposure and alcohol consumption, and questionnaires assessing neurological and depressive symptoms. RESULTS: By comparison with the carpenters, the painters on average reported greater cumulative alcohol consumption and had lower scores on the WAIS-R vocabulary subtest, usually presumed to reflect premorbid intellectual functioning. These findings, however, were not sufficient to account for the other study findings. Controlling for age, education, vocabulary score, and alcohol use, the painters had lower mean scores on test measures of motor, memory, and reasoning ability; and a subgroup of aerospace workers with moderate to high cumulative exposure to solvents (n = 8) had lower mean scores on measures of visuomotor speed, and motor, attention, memory, and reasoning ability. Subjects were more likely to have an increased number of relatively abnormal test scores (three or more outlier scores on 17 test measures) among both the painter group (odds ratio (OR), 3.1; 95% confidence interval (95% CI) 1.5 to 6.2) and the subgroup of aerospace workers with higher cumulative exposure (OR 5.6; 95% CI 1.0 to 38). The painters, but not the aerospace workers, reported significantly more neurological and depressive symptoms. CONCLUSIONS: The findings are consistent with residual central nervous system dysfunction from long-term exposure to organic solvents, persisting years after the end of exposure.

Aged↗
PubMed1999

Crystalline silica exposure, radiological silicosis, and lung cancer mortality in diatomaceous earth industry workers.

BACKGROUND: The role of silicosis as either a necessary or incidental condition in silica associated lung cancer remains unresolved. To address this issue a cohort analysis of dose-response relations for crystalline silica and lung cancer mortality was conducted among diatomaceous earth workers classified according to the presence or absence of radiological silicosis. METHODS: Radiological silicosis was determined by median 1980 International Labour Organisation system readings of a panel of three "B" readers for 1809 of 2342 white male workers in a diatomaceous earth facility in California. Standardised mortality ratios (SMR) for lung cancer, based on United States rates for 1942-94, were calculated separately for workers with and without radiological silicosis according to cumulative exposures to respirable crystalline silica (milligrams per cubic meter x years; mg/m3-years) lagged 15 years. RESULTS: Eighty one cases of silicosis were identified, including 77 with small opacities of > or = 1/0 and four with large opacities. A slightly larger excess of lung cancer was found among the subjects with silicosis (SMR 1.57, 95% confidence interval (CI) 0.43 to 4.03) than in workers without silicosis (SMR 1.19, 95% CI 0.87 to 1.57). An association between silica exposure and lung cancer risk was detected among those without silicosis; a statistically significant (p = 0.02) increasing trend of lung cancer risk was seen with cumulative exposure, with SMR reaching 2.40 (95% CI 1.24 to 4.20) at the highest exposure level (> or = 5.0 mg/m3-years). A similar statistically significant (p = 0.02) dose-response gradient was observed among non-silicotic subjects when follow up was truncated at 15 years after the final negative radiograph (SMR 2.96, 95% CI 1.19 to 6.08 at > or = 5.0 mg/m3-years), indicating that the association among non-silicotic subjects was unlikely to be accounted for by undetected radiological silicosis. CONCLUSIONS: The dose-response relation observed between cumulative exposure to respirable crystalline silica and lung cancer mortality among workers without radiological silicosis suggests that silicosis is not a necessary co-condition for silica related lung carcinogenesis. However, the relatively small number of silicosis cases in the cohort and the absence of radiographic data after employment limit interpretations.

Adult↗
PubMed1999

Epidemiologic approaches to the study of Parkinson's disease etiology.

The etiology of Parkinson's disease has been enigmatic to clinicians, epidemiologists, and basic scientists since the clinical syndrome was first described in 1817. Mendelian inheritance probably accounts for a small proportion of Parkinson's disease. Apart from an increasing risk with age, the most consistent epidemiologic observation has been an inverse relation with cigarette smoking. Neither selective survival of nonsmokers nor behavioral characteristics of smokers can explain this seemingly protective association. Interest in environmental exposures, particularly pesticides, metals, and industrial solvents, heightened substantially following the discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a street drug contaminant, as a cause of human parkinsonism. Epidemiologic and toxicologic research has since been guided to a great extent, although not exclusively, by mechanisms of MPTP toxicity. Efforts to characterize gene/environment interactions have also intensified in recent years. In this review, we evaluate recent evidence concerning the etiology of Parkinson's disease, with emphasis on environmental and lifestyle exposures and their potential interactions with genetic susceptibility traits. The most challenging aspects of epidemiologic research into Parkinson's disease causation include methodologic difficulties surrounding case definition, completeness of case ascertainment, selection of appropriate controls in case-control studies, and assessment of environmental exposures. We conclude with recommendations for future research directions.

Age Distribution↗
PubMed1998

Contrasting associations of blood and semen lead concentrations with semen quality among lead smelter workers.

While blood lead concentration has been inversely associated with indicators of reproductive health in occupationally exposed male workers, the utility of lead concentration in semen as an indicator of lead exposure to the male reproductive system has not been fully explored. Blood and semen lead concentrations from 81 lead smelter workers were examined in relation to semen quality and endocrine function parameters. Mean blood and semen lead concentrations were 22.8 micrograms/dl (range 5-58) and 1.9 micrograms/dl (range 0.1-17.6), respectively. Total sperm count and concentration decreased with increasing blood lead concentration; p for trend was 0.003 and 0.009, respectively. Semen lead concentration was inversely related to total sperm count (p = 0.05), ejaculate volume (p = 0.001), and serum testosterone (p = 0.004), but not to sperm concentration. The association between semen lead concentration and total sperm count was eliminated when volume was included in the model. Blood lead concentration was more consistently associated with indicators of sperm production than was semen lead. In contrast, semen lead concentration was negatively associated with circulating testosterone concentrations. Our findings indicate that measurement of semen lead may not be a valuable adjunct to conventional blood lead monitoring for investigations of male reproductive system toxicity.

Adult↗
PubMed1998

Thyroid function in lead smelter workers: absence of subacute or cumulative effects with moderate lead burdens.

OBJECTIVE: To evaluate the effect of low to moderate occupational lead exposure on thyroid function we conducted a cross-sectional study of 151 male lead smelter workers. METHODS: Parameters of thyroid function were assessed in relation to both subacute and cumulative lead exposure over a 10-year employment period. Blood lead levels, obtained from plant surveillance records, were used to establish four ordinal levels of current and cumulative exposure (< 15, 15-24, 25-39, and > or =40 microg/dl). RESULTS: Mean values for the lowest as compared with the highest current exposure group were similar for thyroxine (T4: 6.8 versus 6.1 microg/dl), estimated free thyroxine (EFT4: 1.6 ng/dl in both groups), and thyroid-stimulating hormone (TSH: 1.8 versus 1.7 mIU/l); there was no evidence of a significant trend for diminished thyroid function associated with increasing current lead exposure. Similarly, no significant difference was observed for T4, EFT4, or TSH in relation to the 10-year cumulative exposure or for adjusted analyses controlling for potential confounders, including age and alcohol use. CONCLUSION: In contrast to studies observing thyroid dysfunction in the setting of high lead exposure and related clinical poisoning, our findings weigh against a significant physiologic effect on thyroid function at lower levels (< 60 microg/dl) of occupational lead exposure.

Adult↗
PubMed1998

Assessment of occupational exposures in community-based case-control studies.

Assessing occupational exposures in community-based studies is a challenge for investigators because there are no standardized or validated approaches for collecting information regarding occupational history. The strengths and limitations of the methods available for assessing occupational exposures are reviewed. In community-based case-control studies, the prevalence of most chemical agents is low. The common sources of misclassification in these studies are addressed, as are strategies for dealing with misclassification bias. Methods to assess the presence and magnitude of differential reporting by cases and controls are outlined, together with analytic strategies to improve the classification of occupational exposures.

Bias↗
PubMed1998

Radiographic evidence of silicosis risk in the diatomaceous earth industry.

There is limited and conflicting evidence regarding the exposure-response relationship between exposure to crystalline silica and silicosis; the level of risk to current workers remains uncertain. We conducted an epidemiologic investigation of 1,809 workers in the diatomaceous earth industry, where exposures to crystalline silica are primarily to the cristobalite form. On the basis of the median of three independent readings, 81 (4.5%) workers were judged to have opacities on chest radiographs (small opacities, profusion >= 1/0, and/or large opacities). Age-adjusted relative risk of opacities increased significantly with cumulative exposure to crystalline silica. The concentration of respirable crystalline silica to which workers were exposed (highly correlated with period of hire) was an important determinant of risk after accounting for cumulative exposure. For workers with an average exposure to crystalline silica of <= 0.50 mg/m3 (or hired >= 1950), the cumulative risk of opacities for a cumulative exposure to crystalline silica of 2.0 mg/m3-yr was approximately 1.1%; for an average exposure > 0.50 mg/m3 (or hired < 1950), the corresponding cumulative risk was 3.7%. These findings indicate an exposure-response relationship between cumulative exposure to crystalline silica and radiographic opacities; moreover, the relationship was substantially steeper among workers exposed at the highest average concentrations of crystalline silica.

Adult↗
PubMed1998

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.

Adult↗
PubMed1998

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.

Adult↗
PubMed1998

Magnetic field exposure and neurodegenerative disease mortality among electric utility workers.

Several recent reports indicate that occupational exposure to electric and magnetic fields may be associated with increased risk of neurodegenerative diseases. To address that hypothesis, we analyzed data from a cohort study of electric utility workers. We examined exposure to magnetic fields, assessed as duration of work in exposed jobs and through an index of cumulative exposure based on magnetic field measurements, in relation to mortality from Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, considering both underlying and all mentioned causes of death. Adjusted mortality rate ratios based on Poisson regression models indicate no association between magnetic fields and Parkinson's disease and little support for an association with Alzheimer's disease mortality. Mortality from amyotrophic lateral sclerosis was positively associated with duration of work in exposed jobs [rate ratio = 2.0, 95% confidence interval (CI)= 0.7-6.0; and rate ratio = 3.1, 95% CI = 1.0-9.8, based on underlying cause for 5 - < 20 years and > or = 20 years vs < 5 years, respectively], as well as with cumulative magnetic field exposure with a > or = 20-year lag (rate ratio = 2.3, 95% CI = 0.8-6.6; and rate ratio = 3.0, 95% CI = 1.0-9.2, for exposure in the middle and upper intervals relative to the lowest interval, respectively).

Adult↗