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Biomedical subjects

M K O'Rourke

Publications and source records attributed to M K O'Rourke.

At least 19 recordsLinked to original sources

Exposure apportionment: ranking food items by their contribution to dietary exposure.

This paper identifies and ranks food items by estimating their contribution to the dietary exposure of the US population and 19 subpopulation groups. Contributions to dietary exposures to arsenic, cadmium, chromium, lead, nickel, benzene, chlorpyrifos, and diazinon are estimated using either the Dietary Exposure Potential Model (DEPM) approach, the National Human Exposure Assessment Survey Arizona (NHEXAS-AZ) approach or the combination of the two. The DEPM is a computer model that uses several national databases of food consumption and residue concentrations for estimating dietary. The DEPM approach ranks the contribution of food items to the total dietary exposure using two methods, the direct method that ranks contributions by population exposure magnitude and the weighted method that ranks by subpopulation exposure magnitude. The DEPM approach identifies highly exposed subpopulations and a relatively small number of food items contributing the most to dietary exposure. The NHEXAS-AZ approach uses the NHEXAS-AZ database containing food consumption data for each subject and chemical residues of a composite of food items consumed by each subject in 1 day during the sampling week. These data are then modeled to obtain estimates of dietary exposure to chemical residues. The third approach uses the NHEXAS-AZ consumption data with residue values from the national residue database. This approach also estimates percent contributions to exposure of each ranked food item for the Arizona population. Dietary exposures estimated using the three approaches are compared. The DEPM results indicate groups with highest dietary exposures include Nonnursing Infants, Children 1-6, Hispanic, Non-Hispanic White, Western, Northeast and Poverty 0-130%. The use of the Combined National Residue Database (CNRD) identifies 43 food items as primary contributors to total dietary exposure; they contribute a minimum of 68% of the total dietary exposure to each of the eight chemical residues. The percent contribution of ranked food items estimated using the NHEXAS samples is smaller than those obtained from the western US population via the DEPM. This indicates differences in consumption characteristics of the two groups with respect to the ranked food items. Six of 15 food items consumed by the NHEXAS-AZ subjects per day are ranked food items contributing between 56% and 70% of the estimated NHEXAS-AZ dietary exposure to each of the eight chemical residues. The difference between total dietary exposure estimates from the DEPM and NHEXAS-AZ approaches varies by chemical residue and is attributable to differences in sampling and analytical methods, and geographic areas represented by the data. Most metal exposures estimated using the NHEXAS consumption data with the CNRD have lower values than those estimated via the other approaches, possibly because the NHEXAS-AZ residue values are higher than the CNRD values. In addition, exposure estimates are seemingly affected by the difference in demographic characteristics and factors that affect types and amounts of food consumed. Efficient control strategies for reducing dietary exposure to chemical residues may be designed by focusing on the relatively small number of food items having similar ingredients that contribute substantively to the total ingestion exposure.

Diet↗

Prevention of bone loss and fracture after lung transplantation: a pilot study.

BACKGROUND: Osteoporotic fracture is a significant source of morbidity after lung transplantation. Therapies to prevent posttransplant fracture are largely untested among lung transplant recipients. METHODS: In this prospective uncontrolled study, lung transplant referrals were assessed for bone health with metabolic, radiographic, and bone mineral density measurements. Transplant recipients were treated with an antiresorptive regimen that included a bisphosphonate starting before or after transplantation. One year after transplantation, the fracture rate and bone density of patients in each group were reassessed and compared to historical controls. Between January 1996 and August 1999, 45/50 (90%) lung transplant referrals underwent bone health assessment. Transplant candidates received calcium, vitamin D, and hormone replacement therapy as indicated for hypogonadism. After July 1998, bisphosphonate therapy was added for candidates with osteopenia or osteoporosis (T score <1). After transplantation, all patients received 90 mg of pamidronate i.v. every 12 weeks, regardless of pretransplant bone density. Radiologic evaluation was performed for clinical suspicion of fracture. Bone density was remeasured 1 year after transplantation. RESULTS: Most transplant referrals suffered from osteopenia or osteoporosis, and 29% of transplant referrals had prevalent vertebral compression fractures. Hypogonadism was untreated in 50% of men and 20% of women, and 15% of patients had hypovitaminosis D. Of the 21 patients assessed 1 year after transplantation, new fractures occurred in 4% of these patients. Lateral lumbar spine and hip bone density remained stable or improved in 65% and 86% of patients, respectively. Most of those who lost bone density had started bisphosphonate therapy after transplantation. CONCLUSIONS: Antiresorptive therapy with a bisphosphonate decreases the fracture rate and preserves bone mass 1 year after lung transplantation. In end-stage lung disease patients with osteopenia or osteoporosis, bisphosphonate therapy should be initiated before transplant surgery is contemplated.

Absorptiometry, Photon↗

The association of respiratory problems in a community sample with self-reported chemical intolerance.

This epidemiological study evaluated respiratory histories in those individuals reporting chemical intolerance (CI) in a community population sample. The subsample of 181 completed standard Respiratory Health Questionnaires. CI was determined from self-ratings of feeling 'moderately' to 'severely' ill from exposure to at least three of five common chemicals (paint, pesticides, car exhaust, new carpet, and perfume); the prevalence rate was 22.7%. The comparison group (CN) (31.5% of the sample) were selected from their reports of 'never' feeling ill from the same chemicals. The prevalence rate of CI in females was over twice that in males (28% vs 12.9%), a significant difference. There were no significant differences in smoking, age, or education between CI and CN. Prevalence rates for symptoms and Relative Risk Ratios (RR) indicated that the CI were significantly more likely to report chronic cough, phlegm, wheeze, chest tightness, exertional dyspnea, acute respiratory illnesses, hay fever, child respiratory trouble, and physician confirmed asthma. Several of these respiratory symptoms were significantly, though differentially, related to 'current' asthma and hay fever reports. Results suggest a potential vulnerability to and greater interference from respiratory illness for the CI, which have implications for women's health and quality of life.

Adolescent↗

Diurnal variation of PEF and its use in epidemiological studies.

Diurnal variability in peak expiratory flow (PEF) has been an accepted clinical method in the management of asthma and the evaluation of occupational asthma. In this paper, the basis for this usage together with other clinical and epidemiological applications is discussed. The measured characteristics of PEF diurnal variability are described in asthmatics and asymptomatic subjects, showing the greater variability in asthmatics, and the "morning dip" related to circadian rhythm. PEF measured by pneumotachograph and the mini-Wright meter are shown to be in good agreement, but PEF measured by the latter and other small PEF meters is different in terms of absolute values, and both intraindividual variability within test sets and diurnally. The use of PEF meters, and the daily diaries in which the subject or patient records PEF and related factors are described.

Adolescent↗

Methotrexate for lung transplant recipients with steroid-resistant acute rejection.

BACKGROUND: Steroid-resistant or recurrent acute rejection is a risk factor for the development of chronic graft failure in lung transplant recipients. The best treatment for these patients is not known. Methotrexate has been used successfully in heart transplant recipients with persistent or recurrent acute rejection. This study was performed to evaluate the efficacy of methotrexate in lung transplant recipients with steroid-resistant acute rejection. METHODS: From January 1991 to December 1995, 12 patients with steroid-resistant acute rejection were treated with methotrexate given weekly for 6 weeks and dose-adjusted according to laboratory data and clinical side effects. After completion of therapy, all patients underwent transbronchial biopsy to evaluate the efficacy of methotrexate treatment. RESULTS: Twelve patients underwent treatment with methotrexate for steroid-resistant acute rejection. Acute rejection resolved in all patients completing at least 4 weeks of therapy; 10 of 12 patients (83%) had no further episodes of acute rejection during a mean follow-up period of 12.5 months (range 1 to 42 months). Acute rejection recurred in two patients 6 and 16 months after methotrexate therapy. Both resolved with high-dose corticosteroid therapy. One patient had asymptomatic cytomegalovirus shedding 8 weeks after completion of methotrexate therapy. One patient had aseptic meningitis after her fourth dose of methotrexate. Neither infectious complication was associated with neutropenia. One patient had bone marrow suppression and neutropenic fevers after augmentation of her methotrexate dose. Two patients received shortened methotrexate courses because of gastrointestinal side effects. CONCLUSIONS: Methotrexate is efficacious in the treatment of lung transplant recipients with steroid-resistant acute rejection. Patients must be monitored for side effects during therapy and dosing must be individualized based on laboratory and clinical parameters.

Acute Disease↗

Recognition of pollen and other particulate aeroantigens by immunoblot microscopy.

Most grass-pollen types appear identical by normal light microscopy. Restricted antigenic cross-reactivity of Cynodon dactylon (Bermuda grass) pollen allowed development of a new method to identify antigens associated with grass-pollen grains. Pollen applied to the surface of an adhesive tape was blotted onto nitrocellulose, and the blots were identified by anti-Bermuda-grass antibodies, second antibody, and fluorescence microscopy. Of the 44 species of grass pollen studied for specificity of the method, the only species to demonstrate uniformly bright staining were Cynodon dactylon, Elymus triticoides, Elymus cinereus, and Koeleria cristata. Thirty-one species were negative, and nine other species demonstrated occasional brightly fluorescent spots, suggesting contamination. The immunoblotting method was used to study Tucson air collected continuously by a Burkard pollen and spore trap throughout April 1986. Each 2-hour transect of the adhesive tape from the trap was examined by immunoblotting and by normal light microscopy to compare antigen particle counts with grass-pollen counts. The mean antigen-particle concentration, 52.8/m3 of air, was higher than the mean grass-pollen concentration, 21.9/m3 of air, suggesting presence of amorphous Bermuda-grass antigens in air samples. Antigen-particle concentration, not grass-pollen concentration, correlated significantly with wind velocity, temperature, and time of day.

Air↗

Multivariate analysis of ambient environmental factors and respiratory effects.

Relationships between respiratory health and environmental conditions (pollen, pollution and meteorology) are investigated in 204 subjects in four symptom groups in four geographical clusters in Tucson. Techniques used are principal components, factor and path analysis. Daily respiratory symptoms and peak expiratory flows were recorded during a three-year period. Ambient pollutants, meteorological conditions and pollen types were monitored in or near the clusters. Factor-based scales, which are climate and season specific, are developed for the environmental variables. Three pollutant/meteorological scales represent 'Summer', 'Winter', and 'Humidity'. Four pollen scales represent early and late spring, summer and fall pollen types. Relationships between environmental variables, respiratory symptoms and peak expiratory flow are analyzed with path diagrams, after accounting for age, sex, smoking habits and stove type. The different effects of the environment on asthmatics, allergics and airways obstructive disease subjects have been demonstrated. Many relationships were found between environmental factors and respiratory responses. The pollutant and meteorological variables are related to respiratory symptoms and peak flow directly as well as through interactions with pollen types. Some of the largest positive coefficients are seen in association with seasonal pollen types, specifically, rhinitis and dyspnoea.

Adult↗

Residential environmental measurements in the national human exposure assessment survey (NHEXAS) pilot study in Arizona: preliminary results for pesticides and VOCs.

A major objective of the National Human Exposure Assessment Survey (NHEXAS) performed in Arizona was to conduct residential environmental and biomarker measurements of selected pesticides (chlorpyrifos, diazinon), volatile organic compounds (VOCs; benzene, toluene, trichloroethene, formaldehyde, 1,3-butadiene), and metals for total human exposure assessments. Both personal (e.g., blood, urine, dermal wipes, 24 h duplicate diet) and microenvironmental (e.g., indoor and outdoor air, house dust, foundation soil) samples were collected in each home in order to describe individual exposure via ingestion, inhalation, and dermal pathways, and to extrapolate trends to larger populations. This paper is a preliminary report of only the microenvironmental and dermal wipe data obtained for the target pesticides and VOCs, and provides comparisons with results from similar studies. Evaluations of total exposure from all sources and pathways will be addressed in future papers. The pesticides and VOCs all showed log-normal distributions of concentrations in the Arizona population sampled, and in most cases were detected with sufficient frequency to allow unequivocal description of the concentration by media at the 90th, 75th, and 50th (median) percentiles. Those combinations of pollutant and media, in which a large fraction of the measurements were below the detection limit of the analysis method used, included trichloroethene, 1,3-butadiene, and formaldehyde in outdoor air; chlorpyrifos and diazinon in outdoor air; and diazinon in dermal and window sill wipes. In general, indoor air concentrations were higher than outdoor air concentrations for all VOCs and pesticides investigated, and VOC levels were in good agreement with levels reported in other studies. In addition, the agreement obtained between co-located VOC samplers indicated that the low-cost diffusional badges used to measure concentrations are probably adequate for use in future monitoring studies. For the pesticides, the median levels found in indoor samples agreed well with other studies, although the levels corresponding to the upper 0.1-1% of the population were considerably higher than levels reported elsewhere, with indoor air levels as high as 3.3 and 20.5 microg/m3 for chlorpyrifos and diazinon, respectively. These data showed excellent correlation (Pearson and Spearman correlation coefficients of 0.998 and 0.998, respectively) between chlorpyrifos in indoor air and in the corresponding dermal wipes, and relatively poor correlation between chlorpyrifos in dust (microg/g or microg/ml) and dermal wipes (Pearson=0.055 microg/g and 0.015 microg/m2; Spearman=0.644 microg/g and 0.578 microg/m2). These data suggest the importance of dermal penetration of semi-volatiles as a route of residential human exposure.

Air Pollutants↗

Mass data massage: an automated data processing system used for NHEXAS, Arizona. National Human Exposure Assessment Survey.

Data entry and management are critical components of all large survey projects; data quality objectives must be met and data must be quickly and readily accessible. We developed a comprehensive system for data entry and management utilizing scannable forms with bubble fields and handwriting recognition. This 'Mass Data Massage' (MDM) system had three components: (1) form creation and database definition; (2) programming of data dictionaries for documentation and preliminary logic and range checks; and (3) data entry, management and documentation using the 'Mass Data Cleaning Program' (MDCP). Scannable forms were written in Teleform, where the data field definition, variable names and ranges were defined as the form was created. Completed forms were returned from the field, subjected to final field quality control (QC) checks, and transferred to the data management section. They were batched and coded as necessary. Once a batch of data was scanned and visually verified, the operator called up the menu for the MDCP. The MDCP had 31 program modules with 500-1200 lines of code each. The operator could select and run the appropriate dictionary on each data batch 'correcting' apparent errors in responses. This process was iterative until the data batch passed all dictionary checks. Proposed 'changes' were forwarded to the data coordinator (DC) for acceptance or rejection. After all errors had been resolved, each data batch was subjected to a 10% quality assurance (QA) check. The original data batch and associated file of applied changes were archived. Time expenditure using the scanning approach varied with the number of questions and the types of responses (handwritten or bubble fields). One-page forms took 42-60% of the time needed for hand entry; forms longer than 10 pages took 35-38% of the time. Use of faster machines will further speed the process. The main advantage of the system was the reduction of systematic errors. Scanning alone reduced errors found on 995 NHEXAS Baseline Questionnaires. Overall, the dictionary identified 0.55% errors on the scanned forms. Ten percent QC checks, performed on corrected batches ready for appendage to the master database, revealed an overall error rate of 0.02%. Similar checks on a laboratory form scanned from numeric handwriting detected 0.3% errors following dictionary application and 0.2% errors during the 10% QA check. This system was faster, more accurate, and more cost-effective than hand entry of data. A batch of data that took >1 week to process using the hand entry method was processed within 1 day using MDM. Human coding of specific answers and the final verification were the most time-consuming processes.

Arizona↗

Evaluations of primary metals from NHEXAS Arizona: distributions and preliminary exposures. National Human Exposure Assessment Survey.

NHEXAS AZ is a multimedia, multipathway exposure assessment survey designed to evaluate metals and other analytes. This paper reports the analyte-specific concentration distributions in each of the media examined (air, soil, house dust, food, beverage, and water), for various methodologies used (inductively coupled plasma-atomic emission spectroscopy and hydride generation-atomic absorption spectroscopy). Results are reported for the five primary metals (Pb, As, Cd, Cr, and Ni). Ingestion was the most important pathway of exposure. Metal concentrations in air were very low (ng/m3) and found only above the 90th percentile. Metals were commonly found in house dust and soil. Exposure transfer coefficients minimize the importance of this component for those over the age of 6 years. When ranked by exposure, food, beverage, and water appeared to be the primary contributors of metal exposure in NHEXAS AZ. For instance, at the 90th percentile, Pb was undetected in air, found at 131 and 118 microg/m3 in floor dust and soil, respectively, and measured at 16 microg/kg in food, 7.1 microg/kg in beverage, and 2.0 and 1.3 microg/l in drinking and tap water, respectively. We calculated preliminary estimates of total exposure (microg/day) for each participant and examined them independently by age, gender, and ethnicity as reported by the subjects in the NHEXAS questionnaire. At the 90th percentile for Pb, total exposures were 64 microg/day across all subjects (n=176); adult men (n=55) had the greatest exposure (73 microg/day) and children (n=35) the least (37 microg/day). Hispanics (n=54) had greater exposure to Pb (68 microg/day) than non-Hispanics (n=119; 50 microg/day), whereas non-Hispanics had greater exposure for all other metals reported. These results have implications related to environmental justice. The NHEXAS project provides information to make informed decisions for protecting and promoting appropriate public health policy.

Adolescent↗

Spatial distributions of arsenic exposure and mining communities from NHEXAS Arizona. National Human Exposure Assessment Survey.

Within the context of the National Human Exposure Assessment Survey (NHEXAS), metals were evaluated in the air, soil, dust, water, food, beverages, and urine of a single respondent. Potential doses were calculated for five metals including arsenic. In this paper, we seek to validate the potential dose calculations through spatial analysis of the data. Others report elevated arsenic concentrations in biological and environmental samples from residents of mining towns, particularly Ajo, Arizona. These reports led us to expect potential arsenic doses above the 90th percentile of the NHEXAS exposure distribution to be from residents of mining communities. Arsenic dose was calculated using media concentrations, time activity patterns, and published exposure factors. Of the 179 homes evaluated, 54 were in mining communities; 11 of these were considered separately for reasons of population bias. Of the 17 homes with the greatest potential arsenic doses, almost half (47%) were in mining communities. We evaluated the potential doses by media from nonmining and mining areas using the nonparametric Mann-Whitney U test. Statistically significant (p = 0.05) differences were found between mining (n = 43) and nonmining sites (n = 122) for total exposure and for each of the following media: house dust, yard soil, outdoor air, beverage consumed, and water consumed. No differences were found in either food or indoor air of mining and nonmining areas. We eliminated outliers and repeated the test for all media; significance increased. Dietary, organic arsenic from fish consumption contributed to elevated arsenic exposure among people from nonmining communities and acted as an initial confounder. When controlling for fish consumption, we were able to validate our potential dose model using arsenic, particularly in Ajo. Further, we identified three mining communities lacking elevated arsenic exposure. Additional work is needed speciating the arsenic and evaluating health risks. The utilization of Geographic Information System facilitated spatial this project and paves the way for more sophisticated future spatial analyses.

Adult↗

The National Human Exposure Assessment Survey (NHEXAS) study in Arizona--introduction and preliminary results.

The objective of the National Human Exposure Assessment Survey (NHEXAS) in Arizona is to determine the multimedia distribution of total human exposure to environmental pollutants in the classes of metals, pesticides, and volatile organic compounds (VOCs) for the population of Arizona. This was accomplished by studying a probability-based sample of the total population in Arizona with a nested design for the different stages of sampling (954 Stage I, 505 Stage II, and 179 Stage III participants). This report compares the study population demographics with those from the U.S. Census and provides preliminary data on the distributions of the example pollutant for each class, lead for metals, chlorpyrifos for pesticides, and benzene for metals. The probability-based sample age and gender demographics compare reasonably well with the Census data (1990 Census and 1996 Census Estimate). The race/ethnicity compared less well with 21% Hispanics in the 1996 Census Estimate and 42% Hispanics in the entire NHEXAS-Arizona sample and 30% Hispanics as Stage III participants for this study. The chemical analyses of the various media (yard soil, foundation soil, house dust, indoor air, outdoor air, drinking water, food, and beverage) show generally low levels of the representative pollutants. The 50th percentiles of the distributions are generally near or below the analytical detection limits, and applicable Federal action limits were rarely exceeded.

Adolescent↗

Pesticide exposure and creatinine variation among young children.

Pesticide exposure may differentially impact young children; they live closer to the ground and take in greater amounts of food relative to body mass than older children or adults. We are using an organophosphate (OP) urinary biomarker screen (gas chromatography with flame photometric detection, GC/FPD) to evaluate pesticide exposure among 154 children < or = 6 years of age living in a heavily farmed border (US-Mexico) community. The screen detects diethylphosphates (DEPs) and dimethylphosphates (DMPs) above a reference range of 1000 non-occupationally exposed individuals (DL=25 microg/g creatinine, Cr). At least one metabolite was detected for 33% of the subjects; many samples contained multiple biomarkers. DEP was detected in 5% of the subjects. DMP and DMTP were frequently measured (25% and 26%, respectively). Biomarker concentrations are adjusted by the body's metabolism of Cr as an indicator of urine dilution. Cr concentrations were examined separately to evaluate their effect on internal dose measures. Cr concentrations were significantly different by season (K-W=0.83, P=0.022). Significant differences exist between the autumn:spring (P=0.038) Cr concentrations and between summer:autumn (P=0.041) Cr concentrations based on Mann-Whitney U=1070.5, z=-2.041, (P=0.041). Our analysis of NHANES III data did not reflect seasonal Cr differences for 6 year olds. No younger children were included. Absorbed daily dose (ADD) estimates were calculated for children with the highest concentrations of metabolite. Calculations are theoretical values assuming that the entirety of a given metabolite was metabolized from a single pesticide. Several class appropriate pesticides were evaluated. For the children with the highest levels, almost all estimated ADDs exceeded the RfD. Although the actual metabolite concentrations dropped appreciably, ADD were still exceeded RfDs at the 95th percentile. The urinary OP screen was effective in identifying subjects with atypical internal doses. Daily Cr yield is a critical component in ADD calculations. Cr variability produces differences in internal dose measurement and estimates of ADD independent of exposure. Cr variability among young children needs to be examined, and caution should be applied when evaluating Cr adjusted internal doses for children.

Agriculture↗

Multipollutant exposures and health responses to particulate matter.

Epidemiological methods provide opportunities to study interactions of pollutants in complex environments. During the study of health and the environment and the evaluation of particulate matter in Tucson, we found that type, location, and temporality of particulate matter exposures were critical with respect to the various interactions that related to health effects. Indoor particulate matter interacted with other components of particulate matter found in tobacco smoke, as evidenced by lung function. The interaction of environmental tobacco smoke with indoor formaldehyde caused various symptoms. Other interactions occurred between indoor and outdoor forms of particulate matter, which caused symptoms in some of the subjects.

Air Pollutants↗

Odor sensitivity and respiratory complaint profiles in a community-based sample with asthma, hay fever, and chemical odor intolerance.

This is a community-based study of odor sensitivity and respiratory complaints for persons reporting asthma (n = 14/141), hay fever (n = 72/140), and chemical odor intolerance (CI) (n = 41/181). CI, a symptom of multiple chemical sensitivity (MCS), was determined from self-ratings of feeling 'moderately' to 'severely' ill using the Chemical Odor Intolerance Index (CII). Index odors included perfume, pesticide, drying paint, new carpet odor, and car exhaust. Six additional odors [natural gas, disinfectants, chlorinated water, room deodorizers, and environmental tobacco smoke (ETS)] were also assessed in the health and environment survey. Asthmatics reported feeling 'frequently' to 'almost always' ill from the CII index odors of drying paint, new carpet odor, perfume, and cleaning agents compared to nonasthmatics. People with hay fever documented feeling 'frequently' to 'almost always' ill from pesticides, drying paint, and car exhaust compared to individuals without hay fever. The CI cited illness from air freshener, natural gas and chlorinated water, in addition to the index odors of perfume, paint, pesticides, new carpeting and auto exhaust. All three groups were significantly more likely to report feeling ill from ETS. People with asthma were significantly more likely to report lower lung complaints, such as wheeze and dyspnea. People with hay fever cited more chest tightness. The CI were significantly more likely to report upper and lower respiratory symptoms. Given this overlap in respiratory complaints, it could be that CI may serve to amplify these traditional immune-related disorders and/or suggest that having asthma or hay fever could make one more vulnerable to CI.

Adolescent↗