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Biomedical subjects

P A Stewart

Publications and source records attributed to P A Stewart.

At least 19 recordsLinked to original sources
PubMed2001

A novel strategy for NQO1 (NAD(P)H:quinone oxidoreductase, EC 1.6.99.2) mediated therapy of bladder cancer based on the pharmacological properties of EO9.

The indolequinone EO9 demonstrated good preclinical activity but failed to show clinical efficacy against a range of tumours following intravenous drug administration. A significant factor in EO9's failure in the clinic has been attributed to its rapid pharmacokinetic elimination resulting in poor drug delivery to tumours. Intravesical administration of EO9 would circumvent the problem of drug delivery to tumours and the principal objective of this study is to determine whether or not bladder tumours have elevated levels of the enzyme NQO1 (NAD(P)H:quinone oxidoreductase) which plays a key role in activating EO9 under aerobic conditions. Elevated NQO1 levels in human bladder tumour tissue exist in a subset of patients as measured by both immunohistochemical and enzymatic assays. In a panel of human tumour cell lines, EO9 is selectively toxic towards NQO1 rich cell lines under aerobic conditions and potency can be enhanced by reducing extracellular pH. These studies suggest that a subset of bladder cancer patients exist whose tumours possess the appropriate biochemical machinery required to activate EO9. Administration of EO9 in an acidic vehicle could be employed to reduce possible systemic toxicity as any drug absorbed into the blood stream would become relatively inactive due to an increase in pH.

Antineoplastic Agents↗
PubMed2001

Occupational exposure to pesticides and pancreatic cancer.

BACKGROUND: An increased risk of exposure to pesticides for pancreatic cancer has been suggested in a number of epidemiologic studies. METHODS: Cases (N = 484), aged 30-79 years, were diagnosed in 1986-1989. Controls (N = 2,095) were a random sample of the general population. Information on usual occupation and potential confounding factors was obtained. A job-exposure matrix (JEM) approach was used to estimate the level of occupational exposure to pesticides. RESULTS: A significant trend in risk with increasing exposure level of pesticides was observed, with ORs of 1.3 and 1.4 for low and moderate/high exposure levels, respectively. Excess risks were found for occupational exposure to fungicides (OR = 1.5) and herbicides (OR = 1.6) in the moderate/high level after adjustment for potential confounding factors. An increased risk for insecticide exposure was disappeared after adjustment for fungicide and herbicide exposures. Results of our occupation-based analysis were consistent with those from the JEM-based analysis. CONCLUSIONS: Our results suggest that pesticides may increase risk of pancreatic cancer, and indicate the need for investigations that can evaluate risk by specific chemical exposures. Published 2001 Wiley-Liss, Inc.

Adult↗
PubMed2001

Occupation and leukemia: a population-based case-control study in Iowa and Minnesota.

BACKGROUND: Studies have suggested that risk of leukemia may be associated with occupational or industrial exposures and risk may vary by the histological type of the disease. METHODS: A population-based case-control study was conducted in Iowa and Minnesota to evaluate the association between various occupations, industries, and occupational exposures and leukemia risk. A total of 513 cases and 1,087 controls was included in the study. A lifetime occupational history and other risk factor information were collected through in-person interviews, and a job-exposure matrix was used to assess possible risks associated with specific exposures. RESULTS: A significantly increased risk of leukemia was observed among agricultural service industries and among nursing and healthcare workers. Janitors, cleaners, and light truck drivers also experienced increased risk. Those employed in plumbing, heating and air conditioning industries, and sales of nondurable goods (such as paints and varnishes) had an increased risk. Printers, painters, and workers in the food and metal industries had a nonsignificantly increased risk of leukemia. Analyses by specific exposures and histology of leukemia showed that risk of leukemia associated with occupational or industrial exposures may vary by histological type of the disease. CONCLUSIONS: An increased risk of leukemia among workers employed in agricultural industries, nursing and healthcare workers, and in a few occupations with possible exposure to solvents is consistent with earlier studies. Associations of risk with occupations not observed previously deserve further assessment. Published 2001 Wiley-Liss, Inc.

Adult↗
PubMed2001

Determining the probability of pesticide exposures among migrant farmworkers: results from a feasibility study.

BACKGROUND: Migrant and seasonal farmworkers are exposed to pesticides through their work with crops and livestock. Because workers are usually unaware of the pesticides applied, specific pesticide exposures cannot be determined by interviews. We conducted a study to determine the feasibility of identifying probable pesticide exposures based on work histories. METHODS: The study included 162 farm workers in seven states. Interviewers obtained a lifetime work history including the crops, tasks, months, and locations worked. We investigated the availability of survey data on pesticide use for crops and livestock in the seven pilot states. Probabilities of use for pesticide types (herbicides, insecticides, fungicides, etc.) and specific chemicals were calculated from the available data for two farm workers. The work histories were chosen to illustrate how the quality of the pesticide use information varied across crops, states, and years. RESULTS: For most vegetable and fruit crops there were regional pesticide use data in the late 1970s, no data in the 1980s, and state-specific data every other year in the 1990s. Annual use surveys for cotton and potatoes began in the late 1980s. For a few crops, including asparagus, broccoli, lettuce, strawberries, plums, and Christmas trees, there were no federal data or data from the seven states before the 1990s. CONCLUSIONS: We conclude that identifying probable pesticide exposures is feasible in some locations. However, the lack of pesticide use data before the 1990s for many crops will limit the quality of historic exposure assessment for most workers.

Adolescent↗
PubMed2001

A method for assessing occupational pesticide exposures of farmworkers.

BACKGROUND: The health of farmworkers as related to pesticide exposure is of concern but assessing exposures for epidemiologic studies requires different techniques than approaches used for studies of industrial workers. METHODS: A review of the literature identified possible factors that affect exposure intensity. A model was developed to estimate an exposure score. Exposures in the literature were estimated using the model and compared to the measurements in the literature. RESULTS: Three studies were found with information appropriate for evaluation of the model. There was a statistical difference between the means of the scores corresponding to above and below the median of the measurements. The correlation coefficient between the scores and the measurements from the literature was 0.77. CONCLUSIONS: Although the evaluation was limited, the model appeared to work well, but more testing is needed. More research is also needed to increase understanding of what affects the exposures of these workers.

Agriculture↗
PubMed2001

Prenatal diagnosis of ventriculocoronary fistula.

BACKGROUND: Cardiac anomalies may be associated with abnormal coronary vascular connections. We report the prenatal diagnosis of ventriculocoronary fistula in three fetuses with associated cardiac anomalies. MATERIALS AND METHODS: Fetal echocardiography was performed in three patients referred for suspected cardiac anomaly. Two-dimensional fetal echocardiography was complemented by color Doppler flow imaging and spectral Doppler in all cases. RESULTS: A ventriculocoronary fistula was diagnosed in three patients referred at 22, 23 and 32 weeks. The first patient had hypoplastic left heart associated with transposition of the great arteries and pulmonary atresia with an intact interventricular septum. The coronary fistula arose from the transposed aorta to the left ventricle. In two patients ventriculocoronary fistula was found in association with pulmonary atresia and an intact interventricular septum. In all cases there was bidirectional flow within the fistula (diastolic blood flow towards the ventricle with reversal during ventricular systole). The pregnancy with hypoplastic left heart with transposition, and one of those with pulmonary atresia resulted in neonatal death and stillbirth, respectively. In the third instance the ventriculocoronary fistula was verified by postpartum cardiac angiography. The infant initially received a Blalock-Taussig shunt, subsequently replaced by a bidirectional Glenn shunt, and was doing well at the time of writing. CONCLUSION: A ventriculocoronary fistula can be identified prenatally by color and spectral Doppler. This anomaly should be sought in fetuses with outflow tract obstructive cardiac lesions and an intact interventricular septum. Prenatal diagnosis allows early angiography postnatally. Delineation of coronary vascular regions may therefore facilitate preoperative planning.

Adult↗
PubMed2001

A pilot study to rate determinants of exposure from videotaped work activities of farmers' use of pesticides.

Industrial hygienists often observe workers to determine who should be measured based on a predicted exposure level. Such evaluations are usually based on real-time observation, yet surprisingly little research has been conducted on what determinants of exposure industrial hygienists use to rank workers and whether the ranking is accurate. Accuracy of the ranking may also be affected by the observation process, which is limited when conditions in the workers' immediate environment are rapidly changing. An alternative to real-time observation is videotaping workers and evaluating the tapes at a later date. A pilot study was conducted using previously collected data to determine if workers could be ranked by exposure level utilizing a scoring system to rate videotaped work practices. Six farmers had been videotaped and their dermal exposures measured as they applied insecticide to hogs. In this study, scores were developed to rate the farmers' working conditions by exposure level. Two types of determinants were used to describe exposure: touching and work practices. Touching included the number of times parts of the body had contact with surfaces possibly contaminated with insecticide. Work practices included the types of clothing and protective equipment worn as well as specific practices used by the farmer (e.g., application method). Two raters conducted independent assessments of the videotape using the same criteria. One rater reviewed the tape twice. Agreement between the raters for the "touching" score was weak (intra-class coefficient (ICC) = 0.28), but there was excellent agreement between the two raters (ICC = 0.92) for overall quality of work practices. As expected, a greater number of touches was moderately correlated with an increase in total exposure (rs = 0.60) and there was a weak inverse relationship between protective work practices and the exposure under the clothing (rs = -0.26). All other relationships with exposure level were contrary to what was expected. Since videotapes provide the industrial hygienist with a record of work events and can capture details that might otherwise be missed or not considered they may play a useful role in exposure assessment, especially if carefully developed procedures are followed to overcome the limitations found by this pilot study.

Agriculture↗
PubMed2000

Endothelial vesicles in the blood-brain barrier: are they related to permeability?

1. Macromolecules cross capillary walls via large vascular pores that are thought to be formed by plasmalemmal vesicles. Early hypotheses suggested that vesicles transferred plasma constituents across the endothelial wall either by a "shuttle" mechanism or by fusing to form transient patent channels for diffusion. Recent evidence shows that the transcytotic pathway involves both movement of vesicles within the cell and a series of fusions and fissions of the vesicular and cellular membranes. 2. The transfer of macromolecules across the capillary wall is highly specific and is mediated by receptors incorporated into specific membrane domains. Therefore, despite their morphological similarity, endothelial vesicles from heterogeneous populations in which the predominant receptor proteins incorporated in their membranes define the functions of individual vesicles. 3. Blood-brain barrier capillaries have very low permeabilities to most hydrophilic molecules. Their low permeability to macromolecules has been presumed to be due to an inhibition of the transcytotic mechanism, resulting in a low density of endothelial vesicles. 4. A comparison of vesicular densities and protein permeabilities in a number of vascular beds shows only a very weak correlation, therefore vesicle numbers alone cannot be used to predict permeability to macromolecules. 5. Blood-brain barrier capillaries are fully capable of transcytosing specific proteins, for example, insulin and transferrin, although the details are still somewhat controversial. 6. It has recently been shown that the albumin binding protein gp60 (also known as albondin), which facilitates the transcytosis of native albumin in other vascular beds, is virtually absent in brain capillaries. 7. It seems likely that the low blood-brain barrier permeability to macromolecules may be due to a low level of expression of specific receptors, rather than to an inhibition of the transcytosis mechanism.

Animals↗
PubMed2000

Early prenatal ultrasound diagnosis of cleidocranial dysplasia.

A woman was referred in the first trimester of her third pregnancy because of a family history of cleidocranial dysplasia. An ultrasound examination at 14 weeks 4 days revealed a fetus with appropriate biometric measurements. However, the clavicles were noted to be hypoplastic and the cranium appeared less well ossified than expected for gestational age, suggesting the diagnosis of cleidocranial dysplasia. On subsequent examination at 21 weeks, the findings were essentially unchanged. Induced vaginal delivery owing to decreased amniotic fluid volume occurred at 37 weeks, and a female weighing 3200 g was delivered. The infant had clinical and X-ray signs of cleidocranial dysplasia.

Adult↗
PubMed2000

Occupational exposure to formaldehyde and wood dust and nasopharyngeal carcinoma.

OBJECTIVES: To investigate whether occupational exposures to formaldehyde and wood dust increase the risk of nasopharyngeal cancer (NPC). METHODS: A multicentered, population based case-control study was carried out at five cancer registries in the United States participating in the National Cancer Institute's SEER program. Cases (n=196) with a newly diagnosed NPC between 1987 and 1993, and controls (n=244) selected over the same period from the general population through random digit dialing participated in structured telephone interviews which inquired about suspected risk factors for the disease, including a lifetime history of occupational and chemical exposure. Histological type of cancer was abstracted from clinical records of the registries. Potential exposure to formaldehyde and wood dust was assessed on a job by job basis by experienced industrial hygienists who were blinded as to case or control status. RESULTS: For formaldehyde, after adjusting for cigarette use, race, and other risk factors, a trend of increasing risk of squamous and unspecified epithelial carcinomas was found for increasing duration (p=0.014) and cumulative exposure (p=0.033) but not for maximum exposure concentration. The odds ratio (OR) for people cumulatively exposed to >1.10 ppm-years was 3.0 (95% confidence interval (95% CI) 1.3 to 6.6) compared with those considered unexposed. In analyses limited to jobs considered definitely exposed, these trends became stronger. The associations were most evident among cigarette smokers. By contrast, there was no association between potential exposure to formaldehyde and undifferentiated and non-keratinising carcinomas. There was little evidence that exposure to wood dust increased risk of NPC, as modest crude associations essentially disappeared after control for potential exposure to formaldehyde. CONCLUSIONS: These results support the hypothesis that occupational exposure to formaldehyde, but not wood dust, increases risk of NPC. This association seems to be specific to squamous cell carcinomas. Established cohorts of workers exposed to formaldehyde and wood dust should continue to be monitored for NPC and other respiratory cancers. Future studies of NPC should take into account histological type in assessing risk from environmental and host factors.

Adolescent↗
PubMed2000

Comparison of industrial hygienists' exposure evaluations for an epidemiologic study.

OBJECTIVES: A study was conducted to determine what level of information is required by industrial hygienists before they can develop exposure estimates comparable with those developed from a more in-depth evaluation. METHODS: Three industrial hygienists evaluated formaldehyde exposures of 300 jobs selected from an earlier epidemiologic study. The jobs were evaluated over the following 6 cycles: (i) job title and industry; (ii) job title, industry, dates; (iii) job and department title and industry; (iv) cycle 3 information with dates; (v) cycle 3 information with a plant report; and (vi) job and department title, industry, dates, and the report. Each hygienist assigned jobs to 1 of 4 exposure categories, which were compared with the categories in the original epidemiologic study. RESULTS: Overall, the mean differences between the hygienists' evaluations and the standard, although small, changed little over the cycles. The kappa statistic was poor to moderate for all the cycles, but the agreement was greater than expected due to chance. There was moderate improvement in overall agreement over the cycles using the weighted kappa statistic, but little improvement in the intraclass correlation coefficients of the hygienists' evaluations, which ranged from 0.4 to 0.5. Department information improved the agreement with the standard by 5--10%, but dates did not the improve agreement. There were some differences by type of plant, job function, exposure level, and date of the estimate. Using a hypothetical exposure-response scenario, this level of misclassification would have resulted in missing an association. CONCLUSIONS: Although there was slight improvement with increasing levels of information, these findings suggest that the subjective categorical assessment of exposures by industrial hygienists will not produce exposure estimates comparable to more in-depth evaluations of exposure.

Epidemiologic Methods↗
PubMed1999

Exposure of farmers to phosmet, a swine insecticide.

OBJECTIVES: The goal of this study was to measure dermal and inhalation exposures to phosmet during application to animals and to identify what determinants of exposure influence the exposure levels. METHODS: Ten farmers were monitored using dermal patches, gloves, and air sampling media during normal activities of applying phosmet to pigs for insect control. Exposures were measured on the clothing (outer), under the clothing (inner), on the hands, and in the air. Possible exposure determinants were identified, and a questionnaire on work practices was administered. RESULTS: The geometric mean of the outer exposure measurements was 79 microg/h, whereas the geometric mean of the inner exposure measurements was 6 microg/h. The geometric mean for hand exposure was 534 microg/h, and the mean air concentration was 0.2 microg/m3. Glove use was associated with the hand and total dermal exposure levels, but no other determinant was associated with any of the exposure measures. The average penetration through the clothing was 54%, which dropped to 8% when the farmers wearing short sleeves were excluded. The farmers reported an average of 40 hours a year performing insecticide-related tasks. CONCLUSIONS: Farmers who applied phosmet to animals had measurable exposures, but the levels were lower than what has been seen in other pesticide applications. Inhalation exposures were insignificant when compared with dermal exposures, which came primarily from the hands. Clothing, particularly gloves, provided substantial protection from exposures. No other exposure determinant was identified.

Animal Husbandry↗
PubMed1998

The impact of initial job assignment on formaldehyde exposure among African-American and white formaldehyde industry workers.

We compared initial job assignments of African-American and white employees at eight worksites that used formaldehyde between 1940 and 1979. Unexposed workers were excluded. Median, ambient air formaldehyde, 8-hour, time-weighted average (TWA8) exposure estimates were determined for each worksite. Job assignments with TWAs above the worksite's median TWA8 were called high formaldehyde exposed (HFE). Job assignments with TWAs less than or equal to the worksite's median TWA8 for the same period were called lower formaldehyde exposed (LFE). Two worksites assigned black workers to HFE jobs in significantly higher proportions than white workers in some decades. One worksite assigned white workers in significantly higher proportions than black workers to HFE jobs in some decades. One worksite assigned racial groups in nearly equal proportions from 1940 to 1969. The remaining sites showed insignificant assignment disproportions (alpha = 0.05; Chi-square < or = 3.841, 1 degree of freedom) for any period. No major trend was apparent across all plants and decades.

Black or African American↗
PubMed1998

Risk for prostate cancer by occupation and industry: a 24-state death certificate study.

Current knowledge of the etiology of prostate cancer is limited. Numerous studies have suggested that certain occupations and industries may be associated with the occurrence of prostate cancer. Information on occupation and industry on death certificates from 24 states gathered from 1984 to 1993 was used in case control study on prostate cancer. A total of 60,878 men with prostate cancer as underlying cause of death was selected and matched with controls who died of all other causes except cancer. Similar to the findings of our parallel large case control study of prostate cancer, we observed excess risks in some white-collar occupations, such as administrators, managers, teachers, engineers, and sales occupations. However, some blue-collar occupations, such as power plant operators and stationary engineers, brickmasons, machinery maintenance workers, airplane pilots, longshoreman, railroad industry workers, and other occupations with potential exposure to PAH also showed risk of excess prostate cancer. Risk was significantly decreased for blue-collar occupations, including farm workers, commercial fishermen, mechanics and repairers, structural metal workers, mining, printing, winding, dry cleaning, textile machine operators, cooks, bakers, and bartenders. Although we observed excess risks of prostate cancer among some low socioeconomic status (SES) occupations, the overall results suggest that the effects of higher SES cannot be ruled out in associations between occupational factors and the risk of prostate cancer.

Adult↗
PubMed1998

Questionnaires for collecting detailed occupational information for community-based case control studies.

In case control studies, collection of information on the workplace environment has generally been limited to self-reports of exposures or to job title, type of employer, and the dates the jobs were held, supplemented sometimes by work activities. This information, however, may be insufficient to assess the potential and level of exposure accurately due to recall difficulties and the variability of exposures within a job. A solution to this problem is to use job-specific questionnaires. The organization of a series of such questionnaires developed for a case control study of brain tumors is described. Three types of questionnaires, or modules, were developed, task-based, industry-based, and modules based on jobs with nonspecific types of tasks (e.g., laborer). The format of these modules starts with questions on the general work environment (type of employer) and proceeds to questions on tasks. More detailed information is then gathered on materials and equipment used, sensory descriptions, dermal exposure, work practices, engineering controls, and personal protective equipment use. The questionnaires cover a wide variety of exposures including solvents, heavy metals, polycyclic aromatic hydrocarbons, machining fluids, electromagnetic frequency fields, and many other exposures and, therefore, can be used in other case control studies.

Brain Neoplasms↗
PubMed1998

Mortality and cancer incidence of aircraft maintenance workers exposed to trichloroethylene and other organic solvents and chemicals: extended follow up.

OBJECTIVES: To extend the follow up of a cohort of 14,457 aircraft maintenance workers to the end of 1990 to evaluate cancer risks from potential exposure to trichloroethylene and other chemicals. METHODS: The cohort comprised civilians employed for at least one year between 1952 and 1956, of whom 5727 had died by 31 December 1990. Analyses compared the mortality of the cohort with the general population of Utah and the mortality and cancer incidence of exposed workers with those unexposed to chemicals, while adjusting for age, sex and calendar time. RESULTS: In the combined follow up period (1952-90), mortality from all causes and all cancer was close to expected (standardised mortality ratios (SMRs) 97 and 96, respectively). Significant excesses occurred for ischaemic heart disease (SMR 108), asthma (SMR 160), and cancer of the bone (SMR 227), whereas significant deficits occurred for cerebrovascular disease (SMR 88), accidents (SMR 70), and cancer of the central nervous system (SMR 64). Workers exposed to trichloroethylene showed non-significant excesses for non-Hodgkin's lymphoma (relative risk (RR) 2.0), and cancers of the oesophagus (RR 5.6), colon (RR 1.4), primary liver (RR 1.7), breast (RR 1.8), cervix (RR 1.8), kidney (RR 1.6), and bone (RR 2.1). None of these cancers showed an exposure-response gradient and RRs among workers exposed to other chemicals but not trichloroethylene often had RRs as large as workers exposed to trichloroethylene. Workers exposed to solvents other than trichloroethylene had slightly increased mortality from asthma, non-Hodgkin's lymphoma, multiple myeloma, and breast cancer. CONCLUSION: These findings do not strongly support a causal link with trichloroethylene because the associations were not significant, not clearly dose-related, and inconsistent between men and women. Because findings from experimental investigations and other epidemiological studies on solvents other than trichloroethylene provide some biological plausibility, the suggested links between these chemicals and non-Hodgkin's lymphoma, multiple myeloma, and breast cancer found here deserve further attention. Although this extended follow up cannot rule out a connection between exposures to solvents and some diseases, it seems clear that these workers have not experienced a major increase in cancer mortality or cancer incidence.

Asthma↗
PubMed1998

Mortality of industrial workers exposed to acrylonitrile.

OBJECTIVES: This study was designed to evaluate the relationship between occupational exposure to acrylonitrile and cancer mortality. MATERIALS AND METHODS: Workers (18079 white men, 4293 white women, 2191 nonwhite men, and 897 nonwhite women) employed in acrylonitrile production or use in the 1950s through 1983 were followed through 1989 for vital status and cause of death. Exposure-response relationships were evaluated from quantitative estimates of historical exposures. Tobacco use was determined for a sample of workers to assess potential confounding. Mortality rates between the exposed and unexposed workers in the cohort were compared using the Poisson regression. RESULTS: Analyses by cumulative, average, peak, intensity, duration, and lagged exposure revealed no elevated risk of cancers of the stomach, brain, breast, prostate or lymphatic and hematopoietic systems. Mortality from lung cancer was elevated for the highest quintile of cumulative exposure. When the decile categories were used, the relative risk did not continue to increase at higher levels. Adjustment for cigarette use reduced the risk for lung cancer only slightly. Separate analyses for wage and salaried workers, long-term and short-term workers, fiber and nonfiber plants, and individual plants revealed no clear exposure-response patterns. CONCLUSIONS: The results indicate that exposure to acrylonitrile at the levels studied is not associated with an increased relative risk for most cancers of a priori interest. The excess of lung cancer in the highest quintile of cumulative exposure may indicate carcinogenic activity at the highest levels of exposure, but analyses of exposure-response do not provide strong or consistent evidence for a causal association.

Acrylonitrile↗