Search PubMed⌕ Search

Biomedical subjects

M R Cullen

Publications and source records attributed to M R Cullen.

At least 37 records · Page 2Linked to original sources
PubMed1997

Sick-building syndrome.

Sick-building syndrome (SBS) is an increasingly common problem. Although objective physiological abnormalities are not generally found and permanent sequelae are rare, the symptoms of SBS can be uncomfortable, even disabling, and whole workplaces can be rendered non-functional. In assessment of patients with SBS complaints, specific building-related illnesses suggested by history or physical examination should be ruled out. On-site assessment of buildings is extremely useful. Treatment involves both the patient and the building. Whenever possible, changes such as ventilation improvements and reduction of sources of environmental contamination should be initiated even if specific aetiological agents have not been identified.

Air Pollution, Indoor↗
PubMed1997

Occupational exposure to machining fluids and laryngeal cancer risk: contrasting results using two separate control groups.

This death certificate-based case-control study linked Connecticut Tumor Registry and Connecticut Division of Vital Statistics death data to determine whether machining fluid exposure is associated with laryngeal cancer risk. Laryngeal cancer cases were compared with oral cancer controls and general population controls. Level of exposure to machining fluids was imputed from the usual occupation and industry on the death certificate. Because exposure was infrequent among females, analysis was limited to males. When cases were compared to oral cancer controls, high exposure to machining fluids was associated with laryngeal cancer (odds ratio = 1.48; 95% confidence interval = 1.01-2.16), with a p-value for trend of 0.08. When cases were compared to population controls, no association between machining fluid exposure and laryngeal cancer was observed. A possible reason for the contrasting results, other than chance, is that exposure data quality for the cases and oral cancer controls may have differed from that of the population controls.

Case-Control Studies↗
PubMed1997

The CARET asbestos-exposed cohort: baseline characteristics and comparison to other asbestos-exposed cohorts.

The Carotene and Retinol Efficacy Trial (CARET) was a double-blind, placebo-controlled trial of the daily administration of 25,000 IU vitamin A and 30 mg beta-carotene for the prevention of lung cancer. Of close to 18,500 participants, more than 4,000 were asbestos-exposed men recruited from shipyard and construction trades at five study centers in the United States. While the primary endpoint of the trial was the incidence of lung cancer, a number of questions about the natural history of asbestos-related disease will also be addressed. The mean age at entry into the trial was 57 years and the mean duration of follow-up on active intervention was 4 years. With the exception of 133 never-smoker pilot participants (3%), all subjects recruited were by intention current (38%) or ex-smokers (58%), with a mean cumulative smoking exposure at entry of 43 pack-years. Mean years from first asbestos exposure were 35, and mean duration of asbestos exposure in a high-risk trade was 19 years. The distribution of radiographic abnormalities was as follows: normal, 34%; parenchymal opacities (ILO profusion score > 1/0) alone, 18%; pleural thickening alone, 27%; both parenchymal opacities and pleural thickening, 21%. The CARET cohort, when compared to previously reported asbestos-exposed cohorts, is characterized by substantial asbestos exposure and high proportion of asbestos-related radiographic findings. The active intervention was halted in 1996, after a mean duration of 40 years. Passive follow-up of the cohort will continue until the year 2000.

Asbestos↗
PubMed1997

Airway isocyanate-adducts in asthma induced by exposure to hexamethylene diisocyanate.

OBJECTIVES: The clinical features, airway histology, and detection of hexamethylene diisocyanate (HDI) protein adducts in endobronchial biopsies from a patient with HDI asthma are described. METHODS: Isocyanate asthma was diagnosed by history, methacholine challenge, and workplace HDI challenge. Bronchoscopy was performed 24 h after challenge and immunohistochemical staining was performed. RESULTS: Airway biopsies obtained at bronchoscopy demonstrated inflammatory changes typical for asthma, including increased airway eosinophils and T cells. Immunohistochemical staining with specific anti-HDI antibodies demonstrated the presence and localization of HDI adducts in human bronchial biopsies. CONCLUSIONS: These studies confirm epithelial exposure to HDI following workplace challenge and demonstrate the feasibility of detecting and localizing isocyanate adducts in human lung tissue. Identifying and characterizing the airway macromolecules to which isocyanates bind in vivo are probably crucial to the understanding of how isocyanates cause sensitization and asthma. The ability to detect isocyanate adducts may also help characterize isocyanate exposure patterns and exposure-disease relationships.

Adult↗
PubMed1996

Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial.

BACKGROUND: Evidence has accumulated from observational studies that people eating more fruits and vegetables, which are rich in beta-carotene (a violet to yellow plant pigment that acts as an antioxidant and can be converted to vitamin A by enzymes in the intestinal wall and liver) and retinol (an alcohol chemical form of vitamin A), and people having higher serum beta-carotene concentrations had lower rates of lung cancer. The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate (vitamin A) taken daily against placebo in 18314 men and women at high risk of developing lung cancer. The CARET intervention was stopped 21 months early because of clear evidence of no benefit and substantial evidence of possible harm; there were 28% more lung cancers and 17% more deaths in the active intervention group (active = the daily combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate). Promptly after the January 18, 1996, announcement that the CARET active intervention had been stopped, we published preliminary findings from CARET regarding cancer, heart disease, and total mortality. PURPOSE: We present for the first time results based on the pre-specified analytic method, details about risk factors for lung cancer, and analyses of subgroups and of factors that possibly influence response to the intervention. METHODS: CARET was a randomized, double-blinded, placebo-controlled chemoprevention trial, initiated with a pilot phase and then expanded 10-fold at six study centers. Cigarette smoking history and status and alcohol intake were assessed through participant self-report. Serum was collected from the participants at base line and periodically after randomization and was analyzed for beta-carotene concentration. An Endpoints Review Committee evaluated endpoint reports, including pathologic review of tissue specimens. The primary analysis is a stratified logrank test for intervention arm differences in lung cancer incidence, with weighting linearly to hypothesized full effect at 24 months after randomization. Relative risks (RRs) were estimated by use of Cox regression models; tests were performed for quantitative and qualitative interactions between the intervention and smoking status or alcohol intake. O'Brien-Fleming boundaries were used for stopping criteria at interim analyses. Statistical significance was set at the .05 alpha value, and all P values were derived from two-sided statistical tests. RESULTS: According to CARET's pre-specified analysis, there was an RR of 1.36 (95% confidence interval [CI] = 1.07-1.73; P = .01) for weighted lung cancer incidence for the active intervention group compared with the placebo group, and RR = 1.59 (95% CI = 1.13-2.23; P = .01) for weighted lung cancer mortality. All subgroups, except former smokers, had a point estimate of RR of 1.10 or greater for lung cancer. There are suggestions of associations of the excess lung cancer incidence with the highest quartile of alcohol intake (RR = 1.99; 95% CI = 1.28-3.09; test for heterogeneity of RR among quartiles of alcohol intake has P = .01, unadjusted for multiple comparisons) and with large-cell histology (RR = 1.89; 95% CI = 1.09-3.26; test for heterogeneity among histologic categories has P = .35), but not with base-line serum beta-carotene concentrations. CONCLUSIONS: CARET participants receiving the combination of beta-carotene and vitamin A had no chemopreventive benefit and had excess lung cancer incidence and mortality. The results are highly consistent with those found for beta-carotene in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study in 29133 male smokers in Finland.

Anticarcinogenic Agents↗
PubMed1996

Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease.

BACKGROUND: Lung cancer and cardiovascular disease are major causes of death in the United States. It has been proposed that carotenoids and retinoids are agents that may prevent these disorders. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers, former smokers, and workers exposed to asbestos. The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day on the primary end point, the incidence of lung cancer, were compared with those of placebo. RESULTS: A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up (mean length of follow-up, 4.0 years). The active-treatment group had a relative risk of lung cancer of 1.28 (95 percent confidence interval, 1.04 to 1.57; P=0.02), as compared with the placebo group. There were no statistically significant differences in the risks of other types of cancer. In the active-treatment group, the relative risk of death from any cause was 1.17 (95 percent confidence interval, 1.03 to 1.33); of death from lung cancer, 1.46 (95 percent confidence interval, 1.07 to 2.00); and of death from cardiovascular disease, 1.26 (95 percent confidence interval, 0.99 to 1.61). On the basis of these findings, the randomized trial was stopped 21 months earlier than planned; follow-up will continue for another 5 years. CONCLUSIONS: After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.

Aged↗
PubMed1996

Feasibility study of respiratory questionnaire and peak flow recordings in autobody shop workers exposed to isocyanate-containing spray paint: observations and limitations.

Diisocyanates, highly reactive monomers which cross-link polyurethane, are the most widely recognized causes of occupational asthma. Many exposed workers are end-users, including autobody spray painters who form a large population at risk. Neither the factors which determine incidence rate nor strategies for control have been adequately studied in this setting. We have conducted a cross-sectional survey of 23 (about one in five) autobody shops in the New Haven area to determine the feasibility of clinical epidemiological studies in this population. Among 102 workers, there was a high rate of airway symptoms consistent with occupational asthma (19.6%). Symptoms were most prevalent among those with the greatest opportunity for exposure (dedicated spray painters) and least among office workers; part-time painters had intermediate rates. Atopy was not associated with risk while smoking seemed to correlate with symptoms. Regular use of air-supplied respirators appeared to be associated with lower risk among workers who painted part- or full-time. We were unable to validate the questionnaire responses with peak expiratory flow record data attempted on a 1/3 sample of the workers. Despite intensive training and effort, subject compliance was limited. Among those who provided adequate data (24 of 38), only two demonstrated unequivocal evidence of labile airways; two others demonstrated lesser changes consistent with an occupational effect on flow rates. There was no clear association between these findings and either questionnaire responses or exposure classification. Overall, the survey suggests that there is a high prevalence of airway symptoms among workers in autobody shops, at least in part due to work-related asthma. However, there is need for both methodological and substantive research in this setting to document rates of occupational asthma and to develop a scientific basis for its effective control.

Asthma↗
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↗
PubMed1995

Screening for lead poisoning by fingerstick in suburban pediatric practices.

OBJECTIVE: To assess the false-positive rate of blood lead determinations on samples obtained by fingerstick from children screened in private suburban and rural practices. METHODS: Screening capillary lead samples were obtained by fingerstick; children with capillary lead levels of 0.7 mumol/L (15 micrograms/dL) or greater were recalled for a confirmatory venous lead test that served as the criterion standard. Parents completed a five-question risk assessment questionnaire at the time of initial screening. SETTING: Four private suburban to rural practices that serve predominantly white, middle-class populations. PARTICIPANTS: Children seen for routine care between August 1992 and February 1993 (N = 1085; 98% between 6 months and 6 years of age). RESULTS: Capillary lead level was 0.7 mumol/L (15 micrograms/dL) or greater in 35 children (3% of total sample); venous lead samples were obtained in 30 patients. Nine of the elevated capillary lead results were true-positives (venous lead = 0.7, 0.8, 0.8, 0.9, 0.9, 0.9, 1.1, 1.1, and 1.7 mumol/L [15, 17, 17, 18, 18, 18, 22, 22, and 35 micrograms/dL]); parents of only two of these children answered yes to any question on the risk assessment questionnaire. Although the false-positive rate of the capillary lead screening test was 70% (21/30) in this setting, only 2% of the total sample had a false-positive screening test (an average of fewer than one false-positive per month per practice). Screening by fingerstick allowed phlebotomy to be avoided for 97% of the children. CONCLUSION: Fingerstick screening for lead poisoning is a reasonable alternative to direct venous testing within private suburban and rural practices, provided that care is taken to avoid specimen contamination, that appropriate caution is used in the interpretation of screening test results, and that medical and environmental interventions are based on the results of confirmatory venous testing.

Blood Specimen Collection↗
PubMed1995

Significance of individual sensitivity to chemicals: elucidation of host susceptibility by use of biomarkers in environmental health research.

Biomarker research has become the predominant theme for study of human dose-host-response relations to environmental chemicals. Increasing interest has been focused on identifying markers for host susceptibility, with mixed results. Efforts to identify markers for host variability in carcinogenic risk, on the basis of theoretical knowledge of carcinogen metabolism, have been disappointing. New work in the area of acquired risk modifiers, such as nutritional status, is theoretically attractive, but results have been limited. Impressive achievements have been made in the area of immunological variability, which may elucidate the molecular basis of as well as provide practical biomarkers for several diseases. The problem of multiple chemical sensitivities, on the other hand, has proved refractory to biomarker research, reflecting inadequate knowledge of the mechanism and inappropriate application of biomarker methods.

Biomarkers↗
PubMed1994

The beta-carotene and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high risk populations: smokers and asbestos-exposed workers.

CARET is a multicenter, two-armed, double-masked randomized chemoprevention trial in Seattle, Portland, San Francisco, Baltimore, Connecticut, and Irvine, to test whether oral administration of beta-carotene (30 mg/day) plus retinyl palmitate (25,000 IU/day) can decrease the incidence of lung cancer in high risk populations, namely, heavy smokers and asbestos-exposed workers. The intervention combines the antioxidant action of beta-carotene and the tumor suppressor mechanism of vitamin A. As of April 30, 1993, CARET had randomized 1,845 participants in the 1985-1988 pilot phase plus 13,260 "efficacy" participants since 1989; of these, 4,000 are asbestos-exposed males and 11,105 are smokers and former smokers (44% female). Accrual is complete everywhere except Irvine, which was the last center added (1991), and the safety profile of the regimen to date has been excellent. With 14,420 smokers, 4,010 asbestos-exposed participants, and 114,100 person-years through February 1998, we expect CARET to be capable of detecting a 23% reduction in lung cancer incidence in the two populations combined and 27, 49, 32, and 35% reductions in the smokers, female smokers, male smokers, and asbestos-exposed subgroups, respectively. CARET is highly complementary to the alpha-tocopherol-beta-carotene study in Finland and the Harvard Physicians Health Study (beta-carotene alone) in the National Cancer Institute portfolio of major cancer chemoprevention trials.

Aged↗
PubMed1994

The private funding of public research. New directions in the administration of occupational and environmental health research.

Dr. Cullen: The experience with the new research models, starting with the prototypic experience of the rubber industry studies of the 1970s and expanding to diverse sectors of American industry in the 1980s, has yielded some important lessons for the future. In closing this symposium I shall try to summarize these briefly. Certain strengths of the evolving process seem common to each of the models. Alone and collectively, the new research arrangements have quite apparently served to increase substantially the pool of funds available to the academic sector for the study of occupational health and safety problems. As a consequence, a larger pool of investigators has participated in the research process, greatly strengthening the future academic capability and experience of our fragilely supported teaching centers. Combined with the involvement of the academic centers in the review process, there has been an undeniable broadening and deepening of the nation's research output and long-term capability in occupational health. On the side of the private sector, the new relationships have led to marked progress in the knowledge base about health and safety problems, with a heavily directed focus on those of greatest relevance to the industries involved. The credibility of the knowledge acquired has been enhanced, an important achievement in a society in which perception of truth is often as important as the truth itself! Because of the requirements of the process for broad involvement by the organizations which undertake these activities, health and safety have achieved far greater visibility and attention by corporate and union leaders who may have previously had no involvement in issues of health and safety.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1994

Screening for lead poisoning in an urban pediatric clinic using samples obtained by fingerstick.

OBJECTIVE: To assess the false positive rate of blood lead (BPb) determinations on samples obtained by fingerstick from children screened in an urban clinic. METHOD: From a single fingerstick (N = 1573), blood was collected in a capillary tube for determining lead concentration (CPb) by graphite furnace and an additional sample was absorbed onto a filter paper for determining lead concentration (FPb) by atomic absorption spectrophotometry with Delves cup. Zinc protoporphyrin (ZPP) was measured immediately and a confirmatory venous lead (VPb) specimen was obtained at the same visit if the ZPP was > or = 35 micrograms/dL (0.6 mumol/L); children with either a CPb or FPb > or = 15 micrograms/dL (0.7 mumol/L) were later recalled for determining VPb. RESULTS: For the 172 children who had a VPb on the same day as the screening tests, the false positive rates (95% confidence intervals) at a lead threshold of 15 micrograms/dL (0.7 mumol/L) were: CPb, 13.5% (6.7-20.3); FPb, 19.1% (11.8-26.4). Analyses using all 679 screens with a paired venous specimen (mean delay between screen and venous testing = 30 days) yielded much higher false positive rates (CPb, 31.3%; FPb, 46.0%). CONCLUSIONS: Screening for lead poisoning is feasible within an urban pediatric clinic by direct measurement of lead concentration in blood samples obtained by fingerstick. The false positive rate that can be obtained is acceptable given the precision of measuring BPb concentration. Practitioners using a staged screening protocol may incorrectly attribute a higher false positive rate to the screening tests, when much of the error may be due to the temporal variability of BPb resulting from both biologic variability in BPb concentration and intermittent exposures.

Child↗
PubMed1993

An information sources map for Occupational and Environmental Medicine: guidance to network-based information through domain-specific indexing.

This paper describes a prototype information sources map (ISM), an on-line information source finder, for Occupational and Environmental Medicine (OEM). The OEM ISM was built as part of the Unified Medical Language System (UMLS) project of the National Library of Medicine. It allows a user to identify sources of on-line information appropriate to a specific OEM question, and connect to the sources. In the OEM ISM we explore a domain-specific method of indexing information source contents, and also a domain-specific user interface. The indexing represents a domain expert's opinion of the specificity of an information source in helping to answer specific types of domain questions. For each information source, an index field represents whether a source might provide useful information in an occupational, industrial, or environmental category. Additional fields represent the degree of specificity of a source in individual question types in each category. The paper discusses the development, design, and implementation of the prototype OEM ISM.

Abstracting and Indexing↗