Bruce W. Case

Mesothelioma and asbestos fiber type: evidence from lung tissue analyses

Lung tissue samples from 78 cases from autopsy of mesothelioma in Canada, 1980 through 1984, and from matched referents were examined by optical and analytical transmission electron microscopic study. Concentrations of amosite, crocidolite, and tremolite fibers, and of typical asbestos bodies discriminated sharply between cases and referents. The distributions of chrysotile and anthophyllite/talc fibers and of all other natural and man‐made inorganic fibers (≥8 μm) in the two series were quite similar. Relative risk was related to the concentration of long (≥8 μm) amphibole fibers with no additional information provided by shorter fibers. The proportion of long fibers was much higher for amphiboles than chrysotile and, except for chrysotile, systematically higher in cases than referents. Amphibole asbestos fibers could explain most mesothelioma cases in Canada and other inorganic fibers, including chrysotile, very few. Fibrous tremolite, contaminant of many industrial minerals including chrysotile, probably explained most cases in the Quebec mining region and perhaps 20% elsewhere.

Mesothelioma in Quebec chrysotile miners and millers: Epidemiology and aetiology

In a cohort of some 11,000 men born 1891-1920 and employed in the Quebec chrysotile production industry, including a small asbestos products factory, of 9780 men who survived into 1936, 8009 are known to have died before 1993, 38 probably from mesothelioma--33 in miners and millers and five in factory workers. Among the 5041 miners and millers at Thetford Mines, there had been 4125 deaths from all causes, including 25 (0.61%) from mesothelioma, a rate of 33.7 per 100,000 subject-years; the corresponding figures for the 4031 men at Asbestos were eight out of 3331 (0.24%, or 13.2 per 100,000 subject-years). At the factory in Asbestos, where all 708 employees were potentially exposed to crocidolite and/or amosite, there were 553 deaths, of which five (0.90%) were due to mesothelioma; the rate of 46.2 per 100,000 subject-years was 3.5 times higher than among the local miners and millers. Six of the 33 cases in miners and millers were in men employed from 2 to 5 years and who might have been exposed to asbestos elsewhere; otherwise, the 22 cases at Thetford were in men employed 20 years or more and the five at Asbestos for at least 30 years. The cases at Thetford were more common in miners than in millers, whereas those at. Asbestos were all in millers. Within Thetford Mines, case-referent analyses showed a substantially increased risk associated with years of employment in a circumscribed group of five mines (Area A), but not in a peripherally distributed group of ten mines (Area B); nor was the risk related to years employed at Asbestos, either at the mine and mill or at the factory. There was no indication that risks were affected by the level of dust exposure. A similar pattern in the prevalence of pleural calcification had been observed at Thetford Mines in the 1970s. These geographical differences, both within the Thetford region and between it and Asbestos, suggest that the explanation is mineralogical. Lung tissue analyses showed that the concentration of tremolite fibres was much higher in Area A than in Area B, a finding compatible with geological knowledge of the region. These findings, probably related to the far greater biopersistence of amphibole fibres than chrysotile, have important implications in the control of asbestos related disease and for wider aspects of fibre toxicology.

No contractile effect for 5-HT1D and 5-HT1F receptor agonists in human and bovine cerebral arteries: similarity with human coronary artery

Using subtype‐selective 5‐HT1 receptor agonists and/or the 5‐HT1 receptor antagonist GR127935, we characterized in vitro the 5‐HT receptor that mediates the contraction of human and bovine cerebral arteries. Further, we investigated which sumatriptan‐sensitive receptors are present in human coronary artery by reverse‐transcriptase polymerase chain reaction (RT–PCR). Agonists with affinity at the 5‐HT1B receptor, such as sumatriptan, alniditan and/or IS‐159, elicited dose‐dependent contraction in both human and bovine cerebral arteries. They behaved as full agonists at the sumatriptan‐sensitive 5‐HT1 receptors in both species. In contrast, PNU‐109291 and LY344864, selective agonists at 5‐HT1D and 5‐HT1F receptors, respectively, were devoid of any significant vasocontractile activity in cerebral arteries, or did not affect the sumatriptan‐induced vasocontraction. The rank order of agonist potency was similar in both species and could be summarized as 5‐HT=alniditan>sumatriptan=IS‐159>>>PNU‐109291=LY344864. In bovine cerebral arteries, the 5‐HT1 receptor antagonist GR127935 dose‐dependently inhibited the vasoconstrictions elicited by both 5‐HT and sumatriptan, with respective pA2 values of 8.0 and 8.6. RT–PCR studies in human coronary arteries showed a strong signal for the 5‐HT1B receptor while message for the 5‐HT1F receptor was weak and less frequently detected. Expression of 5‐HT1D receptor mRNA was not detected in any sample. The present results demonstrate that the triptan‐induced contraction in brain vessels is mediated exclusively by the 5‐HT1B receptor, which is also present in a majority of human coronary arteries. These results suggest that selective 5‐HT1D and 5‐HT1F receptor agonists might represent new antimigraine drugs devoid of cerebro‐ and cardiovascular effects.

Asbestos effects on superoxide production: an in vitro study of hamster alveolar macrophages

Inhaled asbestos induces accumulation of alveolar macrophages (AM) and polymorphonuclear leukocytes (PMN) in lung. Asbestos-enhanced production of superoxide anion (O2-) by AM and/or PMN may be involved in the pathogenesis of asbestos-induced fibrosis, either through direct effects on collagen synthesis or via mediation of tissue injury and repair. In in vivo experiments, bronchoalveolar lavage (BAL) 3 to 8 weeks following intratracheal asbestos injections showed increases in both PMN and AM, with AM representing 78 to 82% of cells recovered. Inhalation models, generally regarded as more analagous to human exposures, have confirmed AM as the predominant component of the cellular response to inhaled asbestos. In this study, the in vitro effects of asbestos fiber on O2- production by AM have been determined in cell populations derived from the Syrian golden hamster. AM for in vitro study were obtained by BAL. O2- production was monitored as superoxide dismutase (SOD) - inhibitable cytochrome c reduction. Significant rises in O2- release by AM were noted in the presence of 0.4 mg/ml crocidolite (2.53 +/- 0.33 nmole cytochrome c reduced/10(6) cells/30 min, 37 degrees C; controls 1.13 +/- 0.18 nmole; P less than 0.02). Chrysotile induced levels of O2- release in AM which were similar to those evoked by crocidolite.

Correlation of cytotechnologists' parameters with their performance in rapid prescreening of papanicolaou smears

Efficient quality control is essential to ensure high sensitivity of Papanicolaou (Pap) smears. For this purpose, rescreening of 10% random negative smears is increasingly felt to be ineffective. Rapid rescreening (RR) of all negative Pap smears is more practical and has received widespread acceptance, especially in Europe, although its sensitivity is difficult to monitor and its retrospective nature may influence the vigilance of the screeners. The method of rapid prescreening (RPS) overcomes these drawbacks because rapid review of Pap smears precedes full screening.

Parallel visual processing: Constant same-different decision latency with two to fourteen shapes

Fourteen Os were shown 2, 5, 8, 11, or 14 geometric shapes at a 200-msec exposure. The maximum visual extent was the same for all numbers of shapes. The stimulus conditions were: all shapes identical, 1 shape different from the rest, and, for 5 to 14 shapes, 3 shapes different (4 shapes in all). The number of shapes, the condition, and the shapes used varied randomly through the sequence of 160 exposures. Decision latency to correct same or different response was independent of the number of shapes presented. Correct same and three-different decisions were faster than one-different decisions, but with two shapes different decisions were faster than same. The results suggest that same-different decisions are made with information processed in parallel from many stimuli

Occupational exposure to asbestos and man-made vitreous fibers, and risk of lung cancer: evidence from two case-control studies in Montreal, Canada.

Objective: To examine the effects of occupational asbestos and man-made vitreous fibers (MMVF) on the risk of lung cancer in two population-based case-control studies entailing exposure at lower levels than in historic cohort studies. Methodology: Study I (1979 to 1986) comprised 857 cases and 1066 population and cancer controls. Study II (1996 to 2001) comprised 858 cases and 1295 population controls. A detailed job history was obtained to evaluate lifetime occupational exposure to 294 agents, including asbestos and MMVF. Results: We found increased risks for substantial exposure to asbestos (odds ratio = 1.78; 95% confidence interval: 0.94 to 3.36). The corresponding odds ratio for substantial exposure to MMVF was 1.10 (95% confidence interval: 0.37 to 3.22). Discussion: Low and moderate levels of exposure to asbestos, as encountered in this population, were associated with some excess risk of lung cancer. Results for MMVF were inconclusive.

Asbestos Fiber Type and Length in Lungs of Chrysotile Textile and Production Workers: Fibers Longer than 18 μm

Excess lung cancer risk for a cohort of chrysotile textile plant workers was many times the risk observed in a cohort of chrysotile miners/millers. The latter had greater exposure to chrysotile/tremolite. A previous lung burden study confirmed this excess exposure in miners/millers and showed little difference in fiber length. Selection of too short a fiber length cut-off (5 µm or more) in the previous study could have masked differences in lung-retained fiber length. In this follow-up, we counted only those intrapulmonary fibers exceeding 18 µm in length. Lung fiber concentration and dimension were assessed by transmission electron microscopy (TEM) and energy-dispersive x-ray spectrometry (EDS) for autopsy samples from 64 textile workers and 43 chrysotile miners and millers. These long fibers were significantly more concentrated in the lungs of chrysotile miners and millers, consistent with their greater exposure. However, when only these longest fibers were compared, there was a somewhat greater mean and median intrapulmonary fiber length for chrysotile textile workers (mean fiber length, all fiber types combined, 25.2 ± 10.2 µm vs. 22.9 ± 6.6 µm in miners/millers, < .001; medians 21.6 vs. 20, p < .05). Despite their lesser apparent lung cancer risk, chrysotile, tremolite, total amphibole, and total long fiber asbestos concentrations were all highest in the lungs of miners/millers. Twenty-two of 64 textile workers had lung content of crocidolite and/or amosite (32.5% of 508). These amosite/crocidolite fibers were present in the lungs of workers who ceased employment prior to the first use of such fibers recorded in this industry. The results suggest that (I) asbestos fiber length differences cannot explain the difference in lung cancer risk excess and slope between cohorts and (2) the experience of textile workers should not be used to assess risk of lung cancer in miners, cement workers, and friction product workers, regardless of fiber type.

Immunoblastic lymphosarcoma: a light, immunofluorescence, and electron microscopic study.

Immunoblastic lymphosarcoma (ILS) is a newly recognized malignant lymphoreticular neoplasm and is included in the recent W.H.O. classification of lymphomas. This report concerns six cases of ILS studied by light, immunofluorescence (IF), and electron microscopy (EM). Four patients were female and all except one were over 50 years of age. Four patients had some immunological abnormality. Light microscopy showed a monomorphic population of immunoblasts with pyroninophilic cytoplasm and variable plasmacytoid differentiation. Intracytoplasmic IgG was demonstrated by IF in four cases, and IgA in one. Large lymphoid cells with varying proportions of polysomes, rough endoplasmic reticulum, and Golgi apparatus were seen by EM in four cases. Mean survival was 4.8 months in five cases; death in four was due to disseminated ILS. We concluded that our cases of ILS are of B cell origin, are often associated with immunological abnormalities, and carry a poor prognosis. Immunofluorescence and EM are helpful in its diagnosis.

Risk of mesothelioma and occupational exposure to asbestos and man-made vitreous fibers: evidence from two case-control studies in Montreal, Canada.

Objective: To examine the effects of exposure to occupational asbestos and man-made vitreous fibers (MMVF) across a wide range of occupations on risk of mesothelioma. Methodology: Two population-based case–control studies (1979–1986 and 1996–2001) provided 35 histologically confirmed mesothelioma cases and 1965 controls. A detailed job history was obtained to evaluate occupational exposure to many agents, including asbestos and MMVF. Results: The mesothelioma odds ratio for exposure to any asbestos type was 3.7 (95% confidence interval = 1.7 to 7.8). The subset exposed to amphibole fibers experienced an odds ratio = 7.0 (95% confidence interval = 2.7 to 18.5). Effects of MMVF could not be disentangled from those of asbestos. Discussion: In workers with exposure levels lower than in most historical cohort studies and across a wide range of industries, a strong association was found between asbestos, especially when it was amphibole, and mesothelioma.