Biomedical subjects

H Checkoway

Publications and source records attributed to H Checkoway.

At least 55 records · Page 3Linked to original sources

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↗

PubMed1997

Occupational exposures and amyotrophic lateral sclerosis. A population-based case-control study.

This population-based case-control study was conducted in three countries in western Washington State to evaluate associations between workplace exposures and the risk of amyotrophic lateral sclerosis (ALS). Cases (n = 174) were all newly diagnosed with ALS by neurologists during 1990-1994, and controls (n = 348), who were matched according to age (+/-5 years) and sex, were identified via random-digit dialing or Medicare enrollment files. Four industrial hygienists blindly assessed detailed lifetime job histories for exposures to metals, solvents, and agricultural chemicals. Case-control comparisons were made for jobs held between 15 years of age and 10 years prior to the cases' dates of diagnosis. After adjustment for age and education, ever exposure to agricultural chemicals was associated with ALS (odds ratio (OR) = 2.0, 95% confidence interval (CI) 1.1-3.5); this association was observed separately in men (OR = 2.4, 95% CI 1.2-4.8) but not in women (OR = 0.9, 95% CI 0.2-3.8). Among men, the odds ratio for low exposure to agricultural chemicals (below the median level for exposed controls) relative to no exposure was 1.5 (95% CI 0.4-5.3), and for high exposure, it was 2.8 (95% CI 1.3-6.1) (p for trend = 0.03). Similar analyses based on the panel's assessment of exposures to metals and solvents showed no associations. These findings suggest an association between ALS and agricultural chemicals in men.

Adolescent↗

PubMed1997

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.

Adult↗

PubMed1997

Dose-response associations of silica with nonmalignant respiratory disease and lung cancer mortality in the diatomaceous earth industry.

The potential carcinogenicity of crystalline silica to humans remains a controversial issue. The authors conducted an historical cohort mortality study of 2,342 male workers exposed to crystalline silica, predominantly cristobalite, in a diatomaceous earth mining and processing facility in California. During the years 1942-1994, mortality excesses were detected for nonmalignant respiratory diseases (NMRD) (standardized mortality ratio = 2.01, 95% confidence interval (CI) 1.56-2.55) and lung cancer (standardized mortality ratio = 1.29, 95% CI 1.01-1.61). NMRD mortality rose sharply with cumulative exposure to respirable crystalline silica; allowing for a 15-year latency, the rate ratio for the highest exposure stratum (> or = 5.0 mg/m3-years) was 5.35 (95% CI 2.23-12.8). The rate ratio for lung cancer reached 2.15 (95% CI 1.08-4.28) in the highest exposure category. These associations were unlikely to have been confounded by smoking or asbestos exposure. The findings indicate a strong dose-response relation for crystalline silica and NMRD mortality. The lung cancer results, although less convincing, add further support to an etiologic role for crystalline silica.

Adult↗

PubMed1997

Pulmonary function and respiratory symptoms in forest firefighters.

This study evaluated effects on respiratory health of forest firefighters exposed to high concentrations of smoke during their work shift. This is the first study of cross-shift respiratory effects in forest firefighters conducted on the job. Spirometric measurements and self-administered questionnaire data were collected before and after the 1992 firefighting season. Seventy-six (76) subjects were studied for cross-shift and 53 for cross-season analysis. On average, the cross-season data were collected 77.7 days after the last occupational smoke exposure. The cross-shift analysis identified significant mean individual declines in FVC. FEV1, and FEF25 75. The preshift to midshift decreases were 0.089 L, 0.190 L, and 0.439 I/sec. respectively, with preshift to postshift declines of 0.065 L, 0.150 L, and 0.496 L/sec. Mean individual declines for FVC, FEV1 and FEF25 75 of 0.033 L, 0.104 L, and 0.275 I/sec. respectively, also were noted in the cross-season analysis. The FEV1 changed significantly (p < 0.05). The use of wood for indoor heat also was associated with the declines in FEV1. Although annual lung function changes for a small subset (n = 10) indicated reversibility of effect, this study suggests a concern for potential adverse respiratory effects in forest firefighters.

Adult↗

PubMed1997

Lobe of origin and histologic type of lung cancer associated with asbestos exposure in the Carotene and Retinol Efficacy Trial (CARET).

Lower lobe origin and histologic diagnosis of adenocarcinoma have been described as useful parameters for attributing lung cancer to prior asbestos exposure. To assess whether these characteristics differed between asbestos-exposed individuals and smokers, we evaluated lobe of origin and histologic type of tumors in 78 asbestos-exposed and 214 nonexposed heavy smokers developing lung cancer during the Carotene and Retinol Efficacy Trial (CARET), a prospective cancer chemoprevention trial. Most tumors in both cohorts, regardless of radiographic fibrosis at baseline, originated in upper lobes, representing 67% in asbestos-exposed and 80% in smokers, respectively (adjusted OR for lower lobe = 1.41; 95% CI = 0.69-2.91). Adenocarcinoma represented 32% of lung tumors in the asbestos cohort, and 30% in the smoking cohort (adjusted OR = 0.78; 95% CI = 0.40-1.55), and was inversely associated with radiographic fibrosis (adjusted OR = 0.19; 95% CI = 0.06-0.62). We conclude that neither anatomic site nor histologic cell type of tumors distinguishes effectively between smoking and asbestos as causal factors in development of lung cancer.

Adenocarcinoma↗

PubMed1997

Quantification of historical dust exposures in the diatomaceous earth industry.

Quantitative estimates of dust exposure in a diatomaceous earth (DE) mining and milling operation have been derived based on air sampling records for the period 1948-1988. A total of 6395 records was included in the analysis. Conversion of results obtained by particle counting, expressed as millions of particles per cubic feet (mppcf) of gravimetrically from a filter cassette and expressed as mg m-3 total, were converted to mg m-3 respirable dust using a conversion factor derived from data obtained during the same periods at the plant. Conversion factors were calculated as the average difference of means on the log scale in order to provide stable and consistent conversions and as a ratio of arithmetic means so that the results could be compared with similar studies. After converting the available data to mg m-3 respirable dust, geometric mean (geometric standard deviation) concentrations were 0.37 (2.43) during the 1950s and 0.17 (2.35) during later periods. Exposures were estimated using two linear models, one estimating the changes in concentration over time, and the other providing job-specific mean exposures during the more recent period. Extrapolation of the estimates to periods prior to the availability of any data was done using a subjectively-determined scaling factor. The average estimated respirable dust concentrations for 135 jobs were 3.55 (+/-1.25), 1.37 (+/-0.48), 0.47 (+/-0.16) and 0.29 (+/-0.10) mg m-3 prior to 1949, 1949-1953, 1954-1973 and 1974-1988, respectively. Despite the limitations of the available data, the estimation procedures used are expected to provide reasonable quantitative estimates of silica-containing dust exposure for subsequent exposure-response analyses.

California↗

PubMed1997

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.

Adult↗

PubMed1997

Surveillance of nasal and bladder cancer to locate sources of exposure to occupational carcinogens.

OBJECTIVE: To locate sources of occupational exposure to nasal and bladder carcinogens for surveillance follow up in British Columbia, Canada. METHODS: Incident cases of nasal cancer (n = 48), bladder cancer (n = 105), and population based controls (n = 159) matched for sex and age, were interviewed about their jobs, exposures, and smoking histories. Odds ratios (ORs) were calculated for 57 occupational groups with stratified exact methods to control for age, sex, and smoking. RESULTS: Occupational groups at increased risk of nasal cancer included: textile workers (six cases, OR 7.6); miners, drillers, and blasters (six cases, OR 3.5); welders (two cases, OR 3.5); pulp and paper workers (three cases, OR 3.1); and plumbers and pipefitters (two cases, OR 3.0). Nasal cancer ORs were not increased in occupations exposed to wood dust, possibly due to low exposures in local wood industries. Strongly increased risks of bladder cancer were found for sheet metal workers (four cases, OR 5.3), miners (19 cases, OR 4.5), gardeners (six cases, OR 3.7), and hairdressers (three cases, OR 3.2). Among occupations originally considered at risk, the following had increased risks of bladder cancer: painters (four cases, OR 2.8); laundry workers (five cases, OR 2.3); chemical and petroleum workers (15 cases, OR 1.8); machinists (eight cases, OR 1.6); and textile workers (three cases, OR 1.5). CONCLUSIONS: Occupational groups with increased risks and three or more cases with similar duties were selected for surveillance follow up. For nasal cancer, these included textile workers (five were garment makers) and pulp and paper workers (three performed maintenance tasks likely to entail stainless steel welding). For bladder cancer, these included miners (12 worked underground), machinists (five worked in traditional machining), hairdressers (three had applied hair dyes), and laundry workers (three were drycleaners).

Aged↗

PubMed1996

Cancer incidence among alachlor manufacturing workers.

A historical cohort study was conducted to evaluate cancer incidence among chemical workers with occupational and environmental exposure to alachlor, the active ingredient in a family of pre-emergent acetanilide herbicides. The study followed 943 workers with at least 1 year of cumulative employment at the Monsanto plant in Muscatine, Iowa, from startup of the alachlor manufacturing process in March 1968 through December 1990. Approximately 96% of all workers were successfully traced to determine their last known residence and cancer status. Eighteen workers were diagnosed with cancer during the follow-up period, based on pathology information from the statewide cancer registry maintained by the State Health Registry of Iowa. The standardized incidence ratio for all cancers was 1.5 (95% CI 0.9-2.4) for all workers exposed to alachlor, which was due primarily to elevated rates for colorectal cancer and chronic myeloid leukemia. Workers with 5 or more years in estimated high alachlor exposure jobs had elevated rates of colorectal cancer (3 cases, SIR = 5.2, 95% CI 1.1-15.1). Interpretation of the study results is limited by the small size of the study population, minimal length of follow-up, and current information concerning alachlor metabolism in primates and humans. Nonetheless, the findings suggest the need for continued evaluation of this and other alachlor-exposed cohorts.

Acetamides↗

PubMed1996

An updated mortality follow-up study of Florida phosphate industry workers.

We have added 14 years of mortality follow-up to a previously studied cohort of 18,446 white and 4,546 nonwhite male workers in the Florida phosphate industry. Follow-up was performed for the years 1949-1992. Based on comparisons with national rates, lung cancer standardized mortality ratios (SMR) were slightly elevated among white (SMR = 1.19; 354 observed) and nonwhite males (SMR = 1.13; 105 observed). However, no lung cancer excesses were found relative to local county rates (SMR = 0.98 for whites, SMR = 0.94 for nonwhites). Based on internal analyses of lung cancer mortality, using Poisson regression modeling, there were no associations of lung cancer with cumulative exposures to total dust, silica, or acid mists. There were weak trends of lung cancer risk with alpha and gamma radiation among white males, but no associations with radiation in nonwhites. No relation was found between acid mist exposures and laryngeal cancer. We conclude that there have not been large excesses of lung cancer or other diseases related to workplace exposures in this cohort.

Acids↗

PubMed1996

Investigating clandestine drug laboratories: adverse medical effects in law enforcement personnel.

A retrospective cohort study was conducted among an international group of 46 law enforcement chemists and 13 Washington State clandestine drug laboratory investigation team members with more than 2,800 combined investigations. Each participant completed a questionnaire concerning previous drug laboratory investigations and adverse health effects during response activities. Methamphetamine laboratories accounted for 81-97% of all responses. Total illness incident rates varied between 0.75-3.4% of responses. Most exposures were through inhalation, and many occurred in the years prior to use of personal protective equipment. Symptoms were primarily those of headache and respiratory, mucous membrane, and skin irritation. Most illness episodes occurred during the processing phase of laboratory responses, and none occurred during the entry phase. A majority of illness episodes occurred in laboratories with leak/spills, fire/explosion, or uncontrolled reactions. Responding to an active laboratory was associated with a 7 to 15-fold risk of becoming ill as compared with setup, in-transit, or former (equipment removed) laboratory responses. No other laboratories characteristics were consistently associated with a significantly elevated relative risk of adverse health effects.

Accidents, Occupational↗

PubMed1996

Selegiline and lymphocyte superoxide dismutase activities in Parkinson's disease.

Superoxide dismutases (SODs) are metalloenzymes that detoxify superoxide radicals, and occur in cytosolic (Cu,Zn-SOD) and mitochondrial (Mn-SOD) forms in multiple tissues, including brain. A neuroprotective effect against oxide stressor exposures may be provided by SOD, although excessive enzyme activity can produce cell injury by formation of hydroxyl radical from hydrogen peroxide. We measured Cu,Zn-SOD and Mn-SOD activities in peripheral lymphocytes of 43 newly diagnosed idiopathic Parkinson's disease (PD) cases and 62 age- and sex-matched controls free of neurodegenerative disorders. Significant excesses of both SOD forms were found among PD cases compared with controls; however, the excesses were found exclusively among PD patients treated with the monoamine oxidase inhibitor selegiline (L-deprenyl). Enzyme-linked immunosorbent assays (ELISAs) confirmed that the activity excesses were due to increased protein rather than more highly reactive enzymes in lymphocytes of PD cases. Our findings clearly indicate the importance of selegiline on measured Cu,Zn-SOD and Mn-SOD activity in peripheral lymphocytes. Characterizing a possible therapeutic value of SOD will require longitudinal assessments of SOD in relation to PD progression.

Antiparkinson Agents↗

PubMed1996

Lung cancer in chromate-exposed aerospace workers.

A retrospective cohort study evaluated the risk of lung cancer in aerospace workers with minimum of 6 months' employment in jobs with chromium [VI] exposure (n = 2429). Standardized incidence ratios (SIR) estimated the risk of lung cancer by duration of employment in chromate-exposure jobs and cumulative exposure based on industrial hygiene and work-history data. The overall SIR for lung cancer was 0.8 (observed [Obs] = 15). Lung cancer risk was inversely related to estimates of cumulative chromate exposure and duration of employment as a painter. Although based on few cases, an elevated lung cancer risk was found in subjects who had worked for 5 or more years as a chrome plater or surface processor tank tender (Obs = 2, SIR = 1.9) and sander/masker or polisher (Obs = 3, SIR = 2.7). A clear association was not observed between chromate exposure and the risk of lung cancer in this population of workers.

Adult↗

PubMed1996

Symptoms and cholinesterase activity among rural residents living near cotton fields in Nicaragua.

OBJECTIVES: To explore whether symptoms resulted from pesticide spray drift on residentially exposed populations in rural Nicaragua. METHODS: 100 residents, each 10 years of age or older, were randomly selected from a Nicaraguan community surrounded by actively sprayed cotton fields (the exposed community) and from a socioeconomically similar community far from agricultural spraying (the control community). Subjects working with pesticides were excluded, and the study was conducted at the end of the 1990 cotton spraying season (August-December). Demographic information, exposure questions, and prevalence of 11 acute symptoms and 17 chronic symptoms were gathered from a structured interview. Finger stick erythrocyte cholinesterase (AChE) was measured with a portable colorimeter. Acute symptoms were grouped according to their previously known associations with cholinesterase (ChE) inhibitors into four ordinal categories (asymptomatic, non-specific, possible, probable). RESULTS: Residents from the exposed community were significantly more likely to report recently sighting a spray plane near their community, exposure to pesticide from drift, crossing recently sprayed fields, eating home grown food, and feeling ill after drift exposure. The mean AChE value was significantly lower for residents of the exposed community (4.9 v 5.3 IU/dl). The proportion of subjects complaining of one or more chronic or acute symptoms was significantly higher for the exposed community (87%) than for the controls (53%). Odds ratios for residents in the exposed community, by symptom categories, were non-specific 1.6 (95% confidence interval (95% CI) 0-8 to 3.2), possible 4.1 (95% CI 1.7 to 10.2), and probable 9.93 (95% CI 2-9 to 34.4). CONCLUSION: These findings indicate a strong association between exposure to aerial pesticides and symptoms. This study should be replicated with more quantitative exposure measures, for if confirmed, the results have relevance for millions in rural communities worldwide.

Acute Disease↗

PubMed1996

Investigation of a cluster of pituitary adenomas in workers in the aluminum industry.

OBJECTIVE: Four cases of pituitary adenoma among employees at a primary aluminum production factory were identified over a five year period by a community physician. The objective of this investigation was to determine whether there has been a comparable high incidence in other aluminum factories, and if particular jobs, departments, or activities in the industry are associated with higher rates of the disease. METHOD: Pituitary adenoma in employees at all United States factories of the company for the years 1989-94 was assessed by a search of a health data information bank and an insurance data base covering present and past employees of the corporation. The incidence in the aluminum workers was estimated and compared with the workers in the index plant. A nested case control study was conducted to compare employment histories of identified cases with those of age and sex matched controls selected from the health information data base. RESULTS: 25 cases, including the index cases, were identified which had been diagnosed during the period 1989-94. The resulting rate of 10.4/100,000 person-years was much lower than that at the index plant. Case-control analysis showed no coherent pattern of location, department, or job significantly associated with risk. In particular, jobs and departments associated with exposures common to aluminum smelting-such as coal tar pitch volatiles and fluorides-were shown to be uncommon among cases compared with age and sex matched controls. CONCLUSION: Overall, despite the unprecedented cluster at a single plant, no strong evidence was found that the rate of pituitary adenoma is increased in aluminum workers generally. We found no association with any work activity or location in the industry to suggest a work related or exposure related cause for the disease.

Adenoma↗

PubMed1996

Semen quality of men employed at a lead smelter.

OBJECTIVE: To evaluate the effects of recent and long term occupational lead exposure on indicators of male reproductive health. METHODS: In a cross sectional study of male employees of a lead smelter (n = 2469), blood samples were obtained from 152 workers including 119 who also provided semen samples. Semen analysis and serum concentrations of testosterone, follicle stimulating hormone, and luteinising hormone were used as indicators of reproductive health. Semen and hormone variables were examined in relation to measures of current and long term body lead burden estimated from current blood lead concentrations and historical blood lead monitoring data. RESULTS: For current blood lead concentration groups of < 15, 15-24, 25-39, > 40 micrograms/dl, the geometric mean sperm concentrations were, respectively, 79.1, 56.5, 62.7, and 44.4 million cells/ml and geometric mean total sperm counts were 186, 153, 137, and 89 million cells (P for trend 0.04). Compared with workers with blood lead concentrations less than 15 micrograms/dl, workers with current blood lead concentrations of 40 micrograms/dl or more had an increased risk of below normal sperm concentration (odds ratio (OR) 8.2, 95% confidence interval (95% CI) 1.2-57.9) and total sperm count (OR 2.6, 95% CI 0.4-15.7), based on World Health Organisation standards. Independent of current lead exposure, sperm concentration, total sperm count, and total motile sperm count were inversely related to measures of long term lead exposure. No association was found between lead exposure and measures of sperm motility, sperm morphology, or serum concentrations of reproductive hormones. CONCLUSIONS: Blood lead concentrations below the currently accepted worker protection criteria seem to adversely affect spermatogenesis.

Adult↗