PubMed Health⌕ Search

Biomedical subjects

M H Sweeney

Publications and source records attributed to M H Sweeney.

At least 19 recordsLinked to original sources
PubMed1998

An impediment to glutathione diffusion in older normal human lenses: a possible precondition for nuclear cataract.

Human age-related nuclear cataract is associated with progressive and widespread oxidation of proteins, particularly in the centre of the lens. The reasons for the onset of cataract and why this disease should take place only in the lenses of older individuals remain unclear. However, a common feature of nuclear cataract is the low concentration of reduced glutathione (GSH) in the centre of the lens. GSH is the principal lenticular antioxidant of the lens and it is synthesized and regenerated in the lens cortex. In this study we investigated the diffusion of glutathione within the human lens as a function of age. Normal human lenses were incubated in artificial aqueous humor containing [35S]cysteine and the label was metabolically incorporated into GSH. After 48-h incubation, lenses were sectioned and phosphorimaging was used to determine the distribution of 35S label. In young lenses, label appeared to diffuse uniformly throughout the whole lens. By contrast, in lenses over the age of 30, very little 35S had penetrated to the centre of the lens. A distinct zonal pattern of label distribution was noted in the older lenses after 48 h incubation, which had dimensions of approximately 7.2 mm (diameter) by 2.8 mm (axial). In some older lenses this pattern was noticeable even after 96-h incubation. Thus a barrier to the diffusion of GSH was observed in older normal lenses which was not present in younger lenses. Furthermore, the internal zone thus delineated has dimensions that coincide with those of the coloured and sclerotic zone present in nuclear cataract lenses. Since nuclear cataract is a disease of the elderly, and maintenance of GSH is known to be vital for lens clarity, we propose that the development of a barrier to the movement of GSH from its site of synthesis and regeneration in the cortex, into the nucleus in older normal lenses, may over time allow oxidative modification of protein to take place in the nucleus, resulting ultimately in nuclear cataract.

Adolescent↗
PubMed1998

Immunological markers among workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

OBJECTIVES: To examine the association of immune cell number and function with occupational exposure to substances contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). METHODS: A cross sectional medical survey. The exposed participants were employed at two chemical plants between 1951 and 1972 in the manufacture of 2,4,5-trichlorophenate and its derivatives. The reference group consisted of people with no occupational exposure to phenoxy herbicides who lived within the communities of the workers. Data from a total of 259 workers and 243 unexposed referents were included in the analysis of immune function. Laboratory tests for immune status included enumeration of circulating leukocyte and lymphocyte populations, proliferative responses of circulating lymphocytes to mitogens and antigens, and serum concentrations of the major immunoglobulins and complement factor C3. RESULTS: The workers had substantial exposure to substances contaminated with TCDD, as indicated by a lipid adjusted mean serum TCDD concentration of 229 ppt compared with a mean of 6 ppt in the unexposed referents. Workers were divided into categories based on their serum TCDD concentration. For all categories except the lowest, with values of serum TCDD comparable with the unexposed referents, there were increased odds of having lower counts of CD26 cells (activated T cells) (odds ratio (OR) 1.0, 95% confidence interval (95% CI) 0.5 to 1.8 for TCDD < 20 ppt; OR 1.6, 95% CI 0.8 to 3.2 for TCDD 20-51 ppt; OR 2.7, 95% CI 1.4 to 5.1 for TCDD 52-125 ppt; OR 2.6, 95% CI 1.4 to 4.9 for TCDD 125-297 ppt; OR 2.4, 95% CI 1.3 to 4.6 for TCDD 298-3389 ppt). A less consistent finding was decreased spontaneous proliferation of cultured lymphocytes. However, increases were found in proliferation of lymphocytes in response to concanavalin and pokeweed in workers in the high TCDD category. Age, cigarette smoking, and alcohol were significant predictors of several immunological outcomes. CONCLUSIONS: Associations between serum TCDD concentration and both a decrease in circulating CD26 cells and decreased spontaneous background proliferation were the major findings of this study. These results are unlikely to be of clinical importance but may reflect limited evidence for an association between immunological changes in workers and high serum concentrations of TCDD, or chance findings resulting from the evaluation of multiple immunological variables.

Adult↗
PubMed1998

Evaluation of cardiovascular outcomes among U.S. workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Some animal studies and some human studies suggest that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) may be associated with adverse effects on the cardiovascular system. As part of a cross-sectional medical study comparing workers employed 15 years earlier in the manufacture of 2,4,5-trichlorophenol or one of its derivatives at two U.S. chemical plants with an unexposed comparison group, we examined the association between TCDD exposure and various cardiovascular outcomes. A total of 281 workers and 260 unexposed referents participated. The workers had substantial exposure to TCDD, as demonstrated by significantly elevated mean serum TCDD concentration of 220 pg/g of lipid, compared with 7 pg/g of lipid among the referents. No significant association was found between TCDD exposure and any of the cardiovascular outcomes including myocardial infarction, angina, cardiac arrhythmias, hypertension, and abnormal peripheral arterial flow. Although our study had sufficient statistical power to detect an elevated risk for cardiac arrhythmias, hypertension, and abnormal peripheral arterial flow, it had low power (approximately 50%) to detect an elevated risk for myocardial infarction and angina. Our review of the literature suggests that our negative findings are consistent with those from other cross-sectional medical studies. Although several mortality studies of TCDD-exposed cohorts found significantly increased risks for cardiovascular disease mortality, similar increased risks were not observed in other mortality studies. The data available do not provide definitive conclusions but indicate that further examination of the association between TCDD exposure and cardiovascular disease should be pursued.

Aged↗
PubMed1997

Proportionate mortality among unionized construction ironworkers.

This report presents the results of proportionate mortality ratios (PMR) and proportionate cancer mortality ratios (PCMR) among 13,301 members of the International Union of Bridge, Structural, and Ornamental Ironworkers who had been members for a minimum of 1 year, were actively paying dues into the death beneficiary fund, and had died between 1984-1991. Using the United States proportionate mortality rates as the comparison population, statistically significant elevated risks, using 95% confidence intervals (CI), were observed for several types of injuries: falls (N = 259, PMR = 3.57, CI = 3.15-4.03), transportation injuries (N = 363, PMR = 1.22, CI = 1.10-1.35), and other types of injuries (N = 225, PMR = 1.63, CI = 1.43-1.86). The deaths due to falls were significantly elevated for each 10-year age group under age 60 (PMR > 7.00) and for those workers with < 20 years in the union (PMR > 6.00). Elevated mortality risks were also observed for all malignant neoplasms combined (N = 3,682, PMR = 1.09, CI = 1.06-1.13) as well as for site-specific malignant neoplasms of the lung (N = 1,523, PMR = 1.28, CI = 1.21-1.35), pleural mesothelioma (N = 7, PMR = 1.67, CI = 0.67-3.44) and "other and unspecified sites" (N = 307, PMR = 1.29, CI = 1.15-1.44). The category "pneumoconiosis and other respiratory diseases" was also significantly elevated (N = 690, PMR = 1.11, CI = 1.03-1.20); in this category, deaths due to asbestosis had the greatest elevated risk (N = 10, PMR = 3.56, CI = 1.70-6.54). No elevation in risk was found for kidney cancer or for chronic nephritis which were of interest because of Ironworkers' potential exposure to lead. The present study underscores the importance of fall protection and other injury prevention efforts in the construction industry, as well as the need to control airborne exposures to asbestos, welding fumes and other respirable disease hazards.

Accidents, Occupational↗
PubMed1996

Tradeswomen's perspectives on occupational health and safety: a qualitative investigation.

Qualitative research methods were used to determine the health and safety concerns of women employed in the construction trades. Major categories of concern were identified, including: 1) exposure to chemical and physical agents; 2) injuries from lifting/bending/ twisting, falling, and lacerations; 3) lack of proper education and training; and 4) the health and safety risks related specifically to tradeswomen. Many of the issues identified by the workers are amenable to change through either engineering, behavioral, or administrative interventions.

Accidents, Occupational↗
PubMed1995

Proportionate mortality among construction laborers.

This report presents the results of proportionate mortality ratio (PMR) analyses and proportionate cancer mortality ratio (PCMR) analyses among the 11,685 members of the Laborers' International Union of North America (LIUNA), who died between 1985-1988, using U.S. proportionate mortality rates as the comparison population. Statistically significant elevated mortality risks were observed for all malignant neoplasms (N = 3285, PMR = 1.13, CI = 1.09-1.17), as well as for site-specific neoplasms of the lung (N = 1208, PCMR = 1.06, CI = 1.00-1.12), stomach (N = 170, PCMR = 1.44, CI = 1.23-1.68), and thyroid gland (N = 10, PCMR = 2.24, CI = 1.07-4.12). The PCMRs for these malignant neoplasms were elevated among both white and non-white males, regardless of length of union membership, in most 10-year categories of age at death above 40 and for the three largest LIUNA regions examined. The study also observed 20 mesothelioma deaths, which indicated that some LIUNA members had been previously exposed to asbestos. Statistically significant elevated risks were also observed for deaths from transportation injuries (N = 448, PMR = 1.37, CI = 1.25-1.51), falls (N = 85, PMR = 1.34, CI = 1.07-1.66), and other types of injuries (N = 245, PMR = 1.61, CI = 1.42-1.83). The deaths due to injuries were most often observed among those members who had the shortest amount of time within the union, were younger, and first entered the union after 1955. This is the first study that has examined the general mortality experience limited to construction laborers only (Bureau of Census code 869).

Accidents, Occupational↗
PubMed1995

Induction of P-450 in workers exposed to dioxin.

OBJECTIVES: To examine the effects of occupational exposure to substances contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on cytochrome P-4501A2 activity in a cross sectional medical survey. METHODS: The exposed workers had been employed at two chemical plants > 15 years earlier in the manufacture of 2,4, 5-trichlorophenol and its derivatives. The control group consisted of people with no occupational exposure to phenoxy herbicides and who lived within the communities of the exposed workers. A total of 58 workers and 125 unexposed controls participated in the analysis. Cytochrome P-450 activity was assessed with test that measures caffeine metabolites in the urine. A ratio of metabolites of caffeine (CMR) constituted a measure of P-4501A2 activity. RESULTS: Compared with the control group in multivariate logistic regression, raised non-significant associations were found for three of four categories of TCDD in exposed workers (TCDD < 20 pg/g, odds ratio (OR) 1.7, 95% confidence interval (95% CI) 0.6 to 5.0, TCDD 20-66, OR 0.3, 95% CI 0.0 to 1.7; TCDD 67-147, OR 2.3, 95% CI 0.6 to 8.8; TCDD > or = 148, OR 3.1, 95% CI 0.8 to 12.5). We found a strongly significant association of CMR and urinary cotinine, a measure of smoking, and urinary free ethanol. We found weak non-significant associations between P-4501A2 activity and increased serum TCDD among workers. CONCLUSIONS: The absence of an association between serum TCDD and cytochrome P-4501A2 may be due to the size of the study, insensitivity of the CMR to assess cytochrome P-4501A2 activity, or inadequate levels of exposure, although these were among the highest in human groups tested.

Adult↗
PubMed1995

Ethical considerations, confidentiality issues, rights of human subjects, and uses of monitoring data in research and regulation.

Biomarkers are potentially powerful tools for use in research and regulation. Their derivation from biologic specimens collected from human subjects does, however, present many ethical implications. Ethical issues are relevant in almost each facet of human biomarker research studies: design, identification and recruitment of subjects, handling and use of the data, and interpretation and communication of results. Researchers also face a number of dilemmas when considering the use of human biologic specimens and new biomarkers. The mere fact that such markers are the result of measurements in human specimens gives the appearance of being more accurate than traditional sources of information such as questionnaires or environmental monitoring; yet, this may not always be the case. The meaning of the results of biomarker studies may be unclear because the purpose of the study is usually for research rather than clinical purposes. There generally are no established normal ranges for biomarkers and the interpretation of findings are often difficult. Researchers may not communicate these results to subjects or consider followup action because the task may be too difficult or undefined, or the reaction of the subject cannot be anticipated. A wide range of practices in this regard exists among researchers. Many questions remain unanswered about the use of biologic specimens. These include questions of ownership and access to specimens. Related to this is the question of whether specimens collected for one research purpose can be used for an entirely different research purpose. This is still an open question.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Specimen Banks↗
PubMed1994

Total serum testosterone and gonadotropins in workers exposed to dioxin.

Human reproductive endocrine data may be an important source of epidemiologic information in regard to the toxic potential of 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin). The association of serum dioxin with total serum testosterone, luteinizing hormone, and follicle-stimulating hormone was examined in 248 chemical production workers from New Jersey and Missouri plants and 231 nonexposed neighborhood referents who participated in a medical evaluation in 1987. In linear regression analyses, current serum dioxin was positively and significantly related to luteinizing hormone and follicle-stimulating hormone and inversely related to total testosterone after adjustment for potential confounders (p < 0.05). These trends were also apparent in logistic regression analyses, in which the authors examined the odds ratios of high luteinizing hormone (> 28 IU/liter), high follicle-stimulating hormone (> 31 IU/liter), and low testosterone (< 10.4 nmol/liter) by serum dioxin quartiles. There was a greater prevalence of high luteinizing hormone among workers in the second (odds ratio (OR) = 1.9, 95% confidence interval (CI) 0.7-5.5), third (OR = 2.5, 95% CI 0.9-7.3), and fourth (OR = 1.9, 95% CI 0.7-5.0) quartiles of serum dioxin compared with referents. For follicle-stimulating hormone, the authors observed a greater prevalence of high follicle-stimulating hormone among workers in the fourth quartile (OR = 2.0, 95% CI 0.7-5.6) compared with referents. Similarly, the prevalence of low testosterone was two to four times greater among workers in the second (OR = 3.9, 95% CI 1.3-11.3), third (OR = 2.7, 95% CI 0.9-8.2), and fourth quartiles (OR = 2.1, 95% CI 0.8-5.8) than among referents. The trends observed in these data offer human evidence of alterations in male reproductive hormone levels associated with dioxin exposure. The results support the animal literature in which dioxin-related effects have been observed on the hypothalamic-pituitary-Leydig-cell axis and on testosterone synthesis.

Adult↗
PubMed1994

Evaluation of porphyria cutanea tarda in U.S. workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

A cross-sectional medical study was performed to evaluate whether occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-contaminated substances is associated with porphyria cutanea tarda or porphyrinuria. The exposed participants were employed more than 15 years earlier in the manufacture of sodium trichlorophenol and its derivatives. The referent group consisted of individuals with no occupational exposure to phenoxy herbicides. A total of 281 workers and 260 referents participated. The pattern of urinary porphyrin excretion for each participant was assessed to determine if symptomatic or subclinical porphyria cutanea tarda was present. None of the participants were found to have symptomatic porphyria cutanea tarda. No difference was found between workers and referents in the prevalence of subclinical porphyria cutanea tarda (odds ratio [OR] = 0.93, 95% confidence interval [CI] 0.19, 4.54). There were also no differences in the risk between workers and referents for an out-of-range urinary uroporphyrin or coproporphyrin concentration. In conclusion, this study did not find an elevated risk for porphyria cutanea tarda or porphyrinuria among workers with high serum TCDD levels. Our review of the literature indicates that there is insufficient evidence available to convincingly support or refute an association in humans between TCDD exposure and porphyria cutanea tarda or porphyrinuria.

Adult↗
PubMed1993

Peripheral neuropathy after occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Reports of human exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) describe signs and symptoms consistent with exposure-related peripheral neuropathy. In a cross-sectional study, prevalence of peripheral neuropathy was measured in 265 workers exposed 15 years earlier to chemicals contaminated with TCDD and in 244 unexposed, age-, race-, gender- and community-matched comparisons. Cases of peripheral neuropathy were defined from examination, electrophysiologic and quantitative sensory tests, and symptoms. Exposure was assessed by measuring lipid-adjusted serum TCDD levels. The mean serum TCDD level for workers (220 parts per trillion (ppt)) was significantly higher than for referents (7 ppt) (p < .0001). Thirty-two percent of both worker and referent groups met the case definition for peripheral neuropathy. In the logistic regression analyses, serum TCDD level was not related to peripheral neuropathy. These data suggest that despite continued high serum TCDD levels, peripheral neuropathy is not a long-term sequela of high exposure to TCDD-contaminated chemicals. However, the study cannot preclude the occurrence and subsequent resolution of acute effects caused by high exposure, as experienced in Seveso and possibly by some workers, while exposed to high levels of TCDD-contaminated substances.

Adult↗
PubMed1993

Knowledge of medical history information among proxy respondents for deceased study subjects.

Proxy respondents were interviewed for 96 decedents in an occupational cohort. A second respondent was interviewed for 59 decedents. Medical records were reviewed to validate questionnaire information. The percentage of respondents who answered "don't know" (non-response) to questions about medical condition ranged from 5% (cancer and heart disease) to 17% (ulcers). Non-response rates were lowest among spouses, intermediate among children, parents, and siblings, and highest among other relatives and friends. Among 41-55 pairs, depending on the condition, agreement between paired respondents was excellent (kappa > 0.75) for ulcers, cancer, diabetes, and lung disease. A higher percentage of medical records was obtained for decedents with spouse respondents and for decedents with more recent dates of death. Sixty percent or more of the medical records were obtained for patients with cancer (n = 30), heart disease (n = 26), stroke (n = 9), and liver disease (n = 10). The positive predictive value of the proxy respondent information for these conditions was 93, 81, 78, and 60%, respectively.

Cerebrovascular Disorders↗
PubMed1991

Cancer mortality in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

BACKGROUND: In both animal and epidemiologic studies, exposure to dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, or TCDD) has been associated with an increased risk of cancer. METHODS: We conducted a retrospective cohort study of mortality among the 5172 workers at 12 plants in the United States that produced chemicals contaminated with TCDD. Occupational exposure was documented by reviewing job descriptions and by measuring TCDD in serum from a sample of 253 workers. Causes of death were taken from death certificates. RESULTS: Mortality from several cancers previously associated with TCDD (stomach, liver, and nasal cancers, Hodgkin's disease, and non-Hodgkin's lymphoma) was not significantly elevated in this cohort. Mortality from soft-tissue sarcoma was increased, but not significantly (4 deaths; standardized mortality ratio [SMR], 338; 95 percent confidence interval, 92 to 865). In the subcohort of 1520 workers with greater than or equal to 1 year of exposure and greater than or equal to 20 years of latency, however, mortality was significantly increased for soft-tissue sarcoma (3 deaths; SMR, 922; 95 percent confidence interval, 190 to 2695) and for cancers of the respiratory system (SMR, 142; 95 percent confidence interval, 103 to 192). Mortality from all cancers combined was slightly but significantly elevated in the overall cohort (SMR, 115; 95 percent confidence interval, 102 to 130) and was higher in the subcohort with greater than or equal to 1 year of exposure and greater than or equal to 20 years of latency (SMR, 146; 95 percent confidence interval, 121 to 176). CONCLUSIONS: This study of mortality among workers with occupational exposure to TCDD does not confirm the high relative risks reported for many cancers in previous studies. Conclusions about an increase in the risk of soft-tissue sarcoma are limited by small numbers and misclassification on death certificates. Excess mortality from all cancers combined, cancers of the respiratory tract, and soft-tissue sarcoma may result from exposure to TCDD, although we cannot exclude the possible contribution of factors such as smoking and occupational exposure to other chemicals.

Bronchial Neoplasms↗
PubMed1991

Evaluation of chronic bronchitis, chronic obstructive pulmonary disease, and ventilatory function among workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is produced as an undesirable contaminant in the manufacture of 2,4,5-trichlorophenol (TCP) and its derivatives. There is considerable concern about the health effects that may be associated with exposure to TCDD-contaminated substances. A cross-sectional medical study that included a comprehensive medical history, medical examination, and measurement of pulmonary function was conducted on workers employed more than 15 yr earlier in the manufacture of NaTCP and its derivatives at two chemical plants. The workers had substantial exposure to substances contaminated with TCDD, as evidenced by a mean serum TCDD level, lipid adjusted, of 200 ppt compared with a mean of 7 ppt in the unexposed reference group. The comparison group consisted of individuals with no occupational exposure to phenoxy herbicides who lived in the same communities as the workers. A total of 281 workers and 260 unexposed referents participated in the medical examination. Logistic and linear regression analyses, which contained categorical and continuous measures of TCDD exposure, were performed to control for important confounders, including cigarette and alcohol consumption. No difference was found between workers and referents in the risk for chronic bronchitis or COPD. Analysis of the ventilatory function data revealed no association between history of exposure to substances contaminated with TCDD and the forced expiratory volume at one second (FEV1), forced vital capacity (FVC), or the ratio of FEV1 to FVC (FEV1/FVC%).

Bronchitis↗