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Biomedical subjects

A Dufresne

Publications and source records attributed to A Dufresne.

At least 37 records · Page 2Linked to original sources

Mineral fiber content of lungs in patients with mesothelioma seeking compensation in Québec.

Asbestos fibers (AF) and ferruginous bodies (FB) in lung parenchyma from 50 workers seeking compensation from the Workers' Compensation Board of Québec for pleural or peritoneal mesothelioma were analyzed using transmission electron microscopy (TEM) equipped with energy-dispersive spectrometer (EDS) and phase-contrast microscopy (PCM). These workers had been occupationally exposed in mining and milling activities (12 were from Asbestos Township and 11 from Thetford Mines) and 27 were from other types of industry (asbestos factory, shipyard, etc.). For comparison, analyses of lung tissue at autopsy were done in a group of 49 subjects from a reference population. A 95% confidence interval upper limit of 540 AF < 5 microns/mg and a 95% confidence interval upper limit of 161 AF > or = 5 microns/mg dried lung tissue were found for the reference population. Similarly, a concentration of FB of 142 FB/g constituted the upper limit of detectable FB in the lungs of the reference population. Forty-eight of the 50 workers with mesothelioma had either a ferruginous body or total asbestos fiber count greater than the 95% confidence interval for the reference population; the remaining two had amosite and/or crocidolite concentrations greater than the 95% confidence interval for the reference population. The fiber types were different in the three groups, with the lungs of workers from Thetford Mines containing only chrysotile and tremolite, those from Asbestos Township containing chrysotile, tremolite, amosite, and crocidolite, and those in other industries containing largely amosite and crocidolite. We conclude that in this population of workers seeking compensation for mesothelioma, fiber analysis confirmed occupational asbestos exposure in every case. The fiber types responsible for the tumors are probably different in the three different groups.

Aged↗

Transforming growth factor-beta (TGF-beta) in silicosis.

Silicosis is characterized by fibrosing nodular lesions that may eventually develop into progressive massive fibrosis (PMF). Cytokines (interleukin-1beta [IL-1beta], tumor necrosis factor-alpha [TNF-alpha] and growth factors insulin-like growth factor-1 [IGF-1] platelet-derived growth factor [PDGF]) have been implicated in the formation of these lesions. TGF-beta promotes extracellular matrix accumulation by upregulating collagen and fibronectin gene expression, and inhibits matrix degradation by decreasing secretion of proteases and increasing secretion of protease inhibitors. We hypothesized that TGF-beta is associated with matrix deposition and fibrosis in silicosis. To test this hypothesis we studied early and late nodular lesions and PMF (11 cases and two controls) with immunohistochemistry, using rabbit polyclonal antibody to the purified whole molecule of TGF-beta in Bouin's fixed lung tissue. This antibody is reactive with both intra- and extracellular forms of TGF-beta. In the control lungs, small amounts of TGF-beta were present in the bronchial epithelium, macrophages, bronchial and vascular smooth muscle, and bronchial glands. There was minimal to moderate staining in the early silicotic peribronchiolar lesions. In the nodular lesions of silicosis, central hyalinized areas contained the maximum staining for TGF-beta. Fibroblasts in the periphery of the nodular lesions were also positive. In acute silicosis, there was marked staining of hyperplastic alveolar epithelium. Macrophages were markedly positive. In the PMF lesions, large areas of scar tissue contained TGF-beta. These data suggest a major role for TGF-beta in silicosis, particularly in the formation of silicotic nodules and the development of PMF.

Adult↗

Fibers in lung tissues of mesothelioma cases among miners and millers of the township of Asbestos, Quebec.

Twenty cases of mesothelioma among miners of the township of Asbestos, Quebec, Canada, have been reported. To further explore the mineral characteristics of various fibrous material, we studied the fibrous inorganic content of postmortem lung tissues of 12 of 20 available cases. In each case, we measured concentrations of chrysotile, amosite, crocidolite, tremolite, talc-anthophyllite, and other fibrous minerals. The average diameter, length, and length-to-diameter ratio of each type of fiber were also calculated. For total fibers > 5 microns, we found > 1,000 asbestos fibers per mg tissue (f/mg) in all cases; tremolite was above 1,000 f/mg in 8 cases, chrysotile in 6 cases, crocidolite in 4 cases, and talc anthophyllite in 5 cases. Among cases with asbestos fibers, the tremolite count was highest in 7 cases, chrysotile in 3 cases, and crocidolite in 2 cases. The geometric mean concentrations of fibers > or = 5 microns were in the following decreasing order: tremolite > crocidolite > chrysotile > other fibers > talc-anthophyllite > amosite. For total fibers < 5 microns, we found > 1,000 fibers per mg tissue (f/mg) in all cases; tremolite was above 1,000 f/mg in 12 cases, chrysotile in 8 cases, crocidolite in 7 cases, and talc-anthophyllite in 6 cases. Tremolite was highest in 8 cases, chrysotile in 2 cases, and crocidolite and amosite in 2 cases. The geometric mean concentrations of fibers < 5 microns were in the following decreasing order: tremolite > other fibers > chrysotile > crocidolite > talc-anthophyllite > amosite. We conclude, on the basis of the lung burden analyses of 12 mesothelioma cases from the Asbestos township of Quebec, that the imported amphibole (crocidolite and amosite) were the dominant fibers retained in the lung tissue in 2/12 cases. In 10/12 cases, fibers from the mine site (chrysotile and tremolite) were found at highest counts; tremolite was clearly the highest in 6, chrysotile in 2, and 2 cases had about the same counts for tremolite and chrysotile. If a relation of fiber burden-causality of mesothelioma is accepted, mesothelioma would be likely caused by amphibole contamination of the plant in 2/12 cases and by the mineral fibers (tremolite and chrysotile) from the mine site in the 10 other cases.

Aged↗

Physico-chemical fate of chromium compounds in the sheep lung model.

Transmission electron microscopy (TEM) equipped with energy-dispersive x-ray analysis (EDX), electron spectroscopy for chemical analysis (ESCA), secondary ion mass spectrometry (SIMS), and laser microprobe for mass analysis (LAMMA) were used to follow the fate of chromium compounds deposited in the sheep tracheal lobe. Four chromium compounds were used: two chromium(VI) compounds (lead chromate and chromium trioxide) and two chromium(III) compounds (chronic oxide and chromium sulfate). Chromium trioxide is very soluble and the other three are slightly soluble. The compositions, concentrations, and sizes of particles were determined in the bronchoalveolar lavages (BAL) at d 2, 3, 5, and 30 after instillation and on the lung samples collected at d 31. The concentrations of particles in the BAL samples separated the chromium compounds in two groups where Cr2O3 and PbCrO4 (as Pb) were higher than Cr2(SO4)3, PbCrO4 (as Cr), and CrO3. The half-life for alveolar clearance of Cr2O3 and Cr2(SO4)3 has been calculated respectively at 11 and 80 d. Prismatic PbCrO4 particles break up in the lung and sustain a high concentration of isometric particles of lead chromate and another lead-containing compound in the BAL. The CrO3 instilled particles react with endogenous compounds or are transformed to insoluble hydroxyl complexes instead of diffusing very rapidly through the alveolar-capillary barrier. The alveolar clearance as measured in the BAL is not different from the control.

Animals↗

Pulmonary retention of ceramic fibers in silicon carbide (SiC) workers.

The fibrous inorganic content of post-mortem lung material obtained from 15 men who worked in the primary silicon carbide (SiC) industry was evaluated. Five men had neither lung fibrosis nor lung cancer (NFNC), six had lung fibrosis (LF), and four had lung fibrosis and lung cancer (LFLC). The workers had 23 to 32 years of exposure. Mean duration of exposure was 23.4 (SD 6.9) years in the NFNC group, 28.8 (SD 5.5) in the LF, and 32.3 (SD 9.0) in the LFLC group. Concentrations of SiC ceramic fibers and other fibrous minerals and angular particles were determined by transmission electron microscopy and energy dispersive spectroscopy. The geometric mean and geometric standard deviation lung concentrations of SiC ceramic fibers < 5 microns were not statistically different for the three groups (Mann-Whitney, p > 0.1). Pulmonary retention of SiC fibers > or = 5 microns showed an excess in LF and LFLC cases combined versus NFNC that approached statistical significance (Mann-Whitney, p = 0.06). There was a somewhat greater difference for lung retention of ferruginous bodies between NFNC and either LF or LFLC cases (Mann-Whitney, p = 0.02). SiC fibers > or = 5 microns and angular particles containing Si and especially ferruginous bodies were found at higher concentrations in LF and LFLC than in NFNC cases.

Air Pollutants, Occupational↗

Further information on aluminium inhalation in silicosis.

OBJECTIVES: In previous studies, a significant reduction in biological activity of quartz by the surface chemistry of aluminium was noted. Aluminium lactate inhalation one month after quartz exposure significantly suppressed silicosis. In a recent study, it was noted that aluminium inhalation failed to alter the silicosis process after disease was recognised by standard chest radiography in the first year after monthly treatment. METHODS: That study was extended with the same groups of sheep, the aluminium treated group received weekly aerosol of 100 mg of aluminium lactate for an additional two years. All sheep were evaluated at three-month intervals by chest radiography, lung function, and lung lavage. RESULTS: The sheep with silicosis had significantly reduced lung functions, increased cellularity, phospholipids, and hyaluronan. These changes persisted for several years without significant differences between the silicotic sheep with or without the aluminium aerosol treatment. CONCLUSION: Aluminium aerosol treatment of silicosis after radiographic recognition of disease and the end of exposure did not alter the disease process.

Administration, Inhalation↗

Does so-called interhemispheric transfer time depend on attention?

To our knowledge none of many past attempts to experimentally modulate the crossed-uncrossed differential (CUD) or so-called "interhemispheric transfer time" derived from appropriate visual reaction time experiments has ever succeeded. The present 4 experiments were designed to establish that (a) under normal attentional constraints, significant CUDs would be obtained, but that (b) lateral mobilization of attention by probabilistic (valid and invalid) cuing as to target location would significantly and systematically alter the CUDs. In a baseline experiment, a significant CUD was obtained. In Experiments 2-4, CUDs were rendered nonsignificant by probabilistic cuing. Specific experimental conditions generally did not significantly influence the CUD in a systematic direction. In only one of many analyses of those results did an experimental effect on the CUD reach significance: In Experiment 3 intrasubject mean reaction times yielded a significant complex dissociation of CUDs as a function of type of cuing (valid or invalid) and stimulus onset asynchrony. It was concluded that the CUD can be significantly modulated by target location cuing, but only under very specific conditions. The direction of the trends in all the experiments, and in the significant finding, suggests that the CUD component that is most markedly influenced by such cues is a postcallosal, motor component.

Adult↗

Cohort study of silicon carbide production workers.

Silicon carbide is produced by a chemical reaction at high temperature between free crystalline silica and petroleum coke. The process generates airborne fibers and fibrogenic dusts such as alpha-quartz and cristobalite, which are also potentially carcinogenic. The authors report that this is the first cohort study in this industry. The study was carried out among 585 Québec silicon carbide production workers who had worked at any time from 1950 to 1980. Follow-up was to December 31, 1989, and 167 deaths were observed. The standardized mortality ratio (SMR) for all causes of death was 1.05 (95% confidence interval (CI) 0.90-1.23); for nonmalignant respiratory diseases it was 2.03 (95% CI 1.21-3.22); and for lung cancer it was 1.69 (95% CI 1.09-2.52). Controlling for smoking status using a Cox regression analysis, the risk for nonmalignant respiratory diseases and for lung cancer increased with exposure to total dust; in the highest exposure category, rate ratios (RR) were 4.08 (95% CI 1.11-14.96) for nonmalignant respiratory diseases and 1.67 (95% CI 0.57-4.83) for lung cancer. Results were in the expected direction, but the power of the study was low, because of small sample size and use of cumulative total dust as the exposure variable, which may be a poor indicator of lung irritants and other potential carcinogens in this industry, notably silicon carbide ceramic fibers.

Adult↗

Lanthanide particles in the lung of a printer.

Lanthanides were extracted from the lung tissue of a subject with a history of potential exposure to carbon-arc lamp emissions in printing shops. The characterization of inorganic particles was performed by energy dispersive X-ray spectroscopy (EDS) on a transmission electron microscope (TEM) and laser microprobe mass analysis (LAMMA). Both techniques showed the presence of elemental Ce, La and Nd at concentrations higher than the average concentration measured in 41 other workers who had died of cancer at various sites. The lung content of other prismatic and compact particles did not show any statistically significant differences between the case and the control group.

Carcinoma, Squamous Cell↗

Relation between lung asbestos fibre burden and exposure indices based on job history.

Lung asbestos burden was compared with exposure indices derived from job history interviews in 42 male subjects originating from the Montréal Case-Control Study project, 12 of whom had documented asbestos exposed job histories. Job interview data consisting of a chronological timetable of job histories were translated into detailed exposure indices by an expert group of hygienists and chemists. Total and individual asbestos fibre type concentrations were quantified by transmission electron microscopy with fibre identification by energy dispersive chi ray spectrometry after deparaffinisation of tissue blocks and low temperature plasma ashing. Geometric mean or median asbestos content was higher in subjects with an asbestos exposed job history than those without for retained dose of amosite, total commercial amphiboles, and total asbestos fibre. Except for crocidolite fibre diameter, which was significantly less in the lungs of exposed workers, no consistent differences were found in measurements of fibre dimension for any fibre type. Subgroups of subjects exposed to silica, metals, or smokers and non-smokers without significant occupational exposure showed varying patterns of lung asbestos fibre type deficit compared with the asbestos exposed subgroup. There was an overall trend for higher lung asbestos content proportional to higher exposure indices for asbestos representing concentration, frequency, and reliability. These exposure indices as well as duration of exposure (in years) were independent predictors of total asbestos content in regression analyses when combined in a model with age. Stepwise regression indicated that exposure concentration was the most important variable, explaining 32% of the total variation in total asbestos content. Smoking, whether expressed in ever or never smoked dichotomy or in smoked-years, had no relation to lung asbestos content in this model.

Adult↗

Pulmonary dust retention in a silicon carbide worker.

This paper reports on pulmonary dust retention in a man who worked 42 years in the vicinity of an Acheson furnace of a silicon carbide plant and had a carborundum pneumoconiosis. Special attention is paid to the retained silicon carbide fibers in the lung parenchyma. The concentration of silicon carbide fibers longer than 5 microns is 39,300 fibers/mg dry lung. These fibers have a similar morphology to fibers observed in the working environment. The result is compared to pulmonary retention of workers exposed to asbestos.

Carbon↗

Measurement of metallic particles extracted from the lung parenchyma of two electricians and one electrotechnician.

This paper reports the chemical nature of particles extracted from the lung parenchyma of two electricians and one electrotechnician. Results indicate that these workers retained particles that are qualitatively representative of their work history. The concentration of nickel in the lung of these workers was statistically higher (Mann-Whitney, p < 0.013) than the concentrations measured in the lungs of 39 other workers who died of different types of cancers.

Electricity↗

The 1891-1920 birth cohort of Quebec chrysotile miners and millers: mortality 1976-88.

A cohort of some 11,000 men born 1891-1920 and employed for at least one month in the chrysotile mines and mills of Quebec, was established in 1966 and has been followed ever since. Of the 5351 men surviving into 1976, only 16 could not be traced; 2508 were still alive in 1989, and 2827 had died; by the end of 1992 a further 698 were known to have died, giving an overall mortality of almost 80%. This paper presents the results of analysis of mortality for the period 1976 to 1988 inclusive, obtained by the subject-years method, with Quebec mortality for reference. In many respects the standardised mortality ratios (SMRs) 20 years or more after first employment were similar to those for the period 1951-75--namely, all causes 1.07 (1951-75, 1.09); heart disease 1.02 (1.04); cerebrovascular disease 1.06 (1.07); external causes 1.17 (1.17). The SMR for lung cancer, however, rose from 1.25 to 1.39 and deaths from mesothelioma increased from eight (10 before review) to 25; deaths from respiratory tuberculosis fell from 57 to five. Among men whose exposure by age 55 was at least 300 million particles per cubic foot x years (mpcf.y), the SMR (all causes) was elevated in the two main mining regions, Asbestos and Thetford Mines, and for the small factory in Asbestos; so were the SMRs for lung cancer, ischaemic heart disease, cerebrovascular disease, and respiratory disease other than pneumoconiosis. Except for lung cancer, however, there was little convincing evidence of gradients over four classes of exposure, divided at 30, 100, and 300 mpcf.y. Over seven narrower categories of exposure up to 300 mpcf.y the SMR for lung cancer fluctuated around 1.27 with no indication of trend, but increased steeply above that level. Mortality form pneumoconiosis was strongly related to exposure, and the trend for mesothelioma was not dissimilar. Mortality generally was related systematically to cigarette smoking habit, recorded in life from 99% of survivors into 1976; smokers of 20 or more cigarettes a day had the highest SMRs not only for lung cancer but also for all causes, cancer of the stomach, pancreas, and larynx, and ischaemic heart disease. For lung cancer SMRs increased fivefold with smoking, but the increase with dust exposure was comparatively slight for non-smokers, lower again for ex-smokers, and negligible for smokers of at least 20 cigarettes a day; thus the asbestos-smoking interaction was less than multiplicative. Of the 33 deaths from mesothelioma in the cohort to date, 28 were in miners and millers and five were in employees of a small asbestos products factory where commercial amphiboles had also been used. Preliminary analysis also suggest that the risk of mesothelioma was higher in the mines and mills at Thetford Mines than in those at Asbestos. More detailed studies of these differences and of exposure-response relations for lung cancer are under way.

Aged↗

Aluminium inhalation in sheep silicosis.

In prior studies, we and others have documented a significant reduction by surface chemistry modification in the biological activity of quartz. We further documented that aluminium lactate inhalation one month after quartz exposure significantly suppressed the silica-induced alveolitis, reduced the pathological process and decreased the retention of quartz in the lung tissue. In the present study, we evaluated the efficacy of aluminium inhalation in altering the silicosis process after disease was recognized by standard chest radiography. Twenty-four sheep were enrolled in the study. The 14 silica exposed sheep had an abnormal chest radiograph of the ILO category 1 or above after 3 years of 100 mg Minusil-5 in 100-ml saline intratracheal injections. Ten control sheep were exposed to saline intratracheal injections. All sheep were evaluated at 3-month intervals by chest radiography, lung function and lung lavage. At month 36 of the study, all 14 sheep had an abnormal chest radiograph while the radiographs of controls remained normal. The sheep with silicosis had significantly reduced lung functions and increased cellularity, phospholipids and hyaluronan. These changes persisted during the next 12 months without exposure or treatment. At month 48 and at monthly intervals after, for 12 months, aerosol inhalations were carried out with saline alone for control and seven silicotic sheep and with 100 mg of aluminium lactate in 10 ml saline generated with a Bird Mark 8 pressure ventilator for the other seven silicotic sheep. All sheep were evaluated at 3-month intervals by chest radiography, lung function and lung lavage.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Ferruginous body counts in sputum as an index of past exposure to mineral fibres.

Previous work by our group among vermiculite miners exposed to fibrous tremolite demonstrated that asbestos body counts in sputum closely reflected intensity and duration of past exposure. In the present project sputum samples from nearly 600 volunteers from 11 cohorts of workers exposed to asbestos and other mineral fibres were found to contain much lower numbers of asbestos bodies than had been observed in vermiculite workers and these counts did not reliably reflect past levels of exposure. No evidence was found that occupational exposure to man-made mineral fibres led to any ferruginous body formation. Asbestos body counts appeared to differentiate between mesothelioma cases and controls and between levels of radiological asbestosis, but in both comparisons, based on small numbers, the power of discrimination was low. Substantial variation was found both in asbestos body and in macrophage counts in daily sampling of vermiculite workers but it was not sufficient to invalidate comparison between groups for epidemiological study. In individual subjects, however, little reliance can be put on results from a single sputum sample, particularly if negative.

Adult↗

Pulmonary clearance of fibrous and angular SiC particulates in the sheep model of pneumoconiosis.

Both angular and fibrous SiC (carborundum) particulates can be emitted by SiC production operations. Carborundum pneumoconiosis is now recognized as an occupational lung disease with specific pathological features. These were previously reproduced in the sheep model of pneumoconiosis with fibrous SiC but not with angular SiC. To further document this question, the pulmonary retention in the sheep of the two morphological types was studied. Animals were injected in the tracheal lobe with equal mass (100 mg) of particulates prepared from SiC materials taken in the field. Particles were measured by analytical transmission electron microscopy in samples of bronchoalveolar lavage fluids (BAL) obtained at months 2, 4, 6 and 8 after the injection. They were also measured in samples of lung parenchyma obtained at month 8. Measurements in BAL and in lung samples both indicated a much lower retention for fibrous than for angular SiC. The retention rate in lung parenchyma at month 8 was 30 times lower for fibrous SiC. The half-life of decrease of concentrations was 3.4 times shorter for fibrous SiC. Other data in the literature support the notion that fine fibres are cleared more effectively than coarser angular particles.

Animals↗

Silicon carbide pneumoconiosis: a radiographic assessment.

Interstitial lung disease and airflow limitation have been reported in silicon carbide workers but it is uncertain whether these recent observations reflect past working conditions alone (30 years ago) or both past and present conditions even if the latter have improved. To investigate this, we analyzed pairs of chest radiographs obtained in 1977 and 1984 in 128 silicon carbide plant workers. Three indices, related to density of small opacities, profusion of opacities, and presence of pleural plaques, were obtained. Student t-tests on results obtained in each time period showed the mean density (1.02 in 1977 and 0.56 in 1984) and profusion (4.27 in 1977 and 2.13 in 1984) indices to be significantly different. However, the pleural plaque index was not different in 1984 (0.34) as compared with 1977 (0.32). There was no deterioration of the radiographic image even in groups with density ratios equal or greater than 1/1. We concluded that the actual environmental working conditions did not influence the integrity of the lung radiographic image in these workers within a time span of 6 or 7 years.

Adolescent↗

Enzyme activities of lung lavage in silicosis.

The cytotoxic effect of quartz on lung cells has been well documented by in vitro and animal studies, but the pertinence of these findings to humans has not yet been documented. We measured lactate dehydrogenase (LDH) activities in the lung lavage of 24 long-term workers in the Québec granite industry and 25 control subjects. We found significant increases in LDH activities in the workers' lung lavage, even in the absence of established silicosis (9 subjects). We looked at a similar observation in the sheep model of early silicosis, measured quartz content of lung lavage, and found significant correlation with LDH levels (R = 0.64, p less than 0.001). All of the quartz particles in human and sheep lung lavage were in the alveolar macrophages. To test further the relationship of macrophage damage (cytotoxicity of quartz) we measured the release of LDH by sheep alveolar macrophage in 24 h cell culture under control conditions, exposure to inert dust, titanium, minusil-5 quartz, or aluminum-treated quartz. The LDH release was at control levels during titanium exposure and showed a significantly dose-related increase during quartz exposure. The latter cytotoxic effect was largely attenuated by aluminum treatment of quartz. These in vitro data agreed with previous reports. This study presents evidence of a cytotoxic effect of quartz inhalation in humans. The effect is related to the intensity of quartz retention in the lung macrophages; it is not a nonspecific dust exposure effect and can be attenuated by surface modification of the quartz.

Adult↗