The "atypical urothelial cell" cytologic category is nonstandardized. We subclassify atypical cases to "atypical, favor a reactive process" or "atypical, unclear if reactive or neoplastic." We evaluated the predictive significance of atypical cases by looking at their histologic follow-up. Among the 1,114 patients and 3,261 specimens included, 282 specimens had histologic follow-up. An atypical diagnosis did not carry a significant increased risk of urothelial neoplasia compared with the benign category. Although an "atypical unclear" diagnosis carried a higher rate of detection of high-grade cancer on follow-up biopsy in comparison with "atypical reactive" or "negative" diagnoses (26/58 [45%] vs 15/52 [29%] and 16/103 [15.5%], respectively), this difference was not statistically significant. These results suggest that dividing atypical cases into 2 categories based on the level of cytologic suspicion of cancer does not add clinically relevant information within the atypical category. They also raise the question of the significance of the atypical category altogether.

Although asbestos research has been ongoing for decades, this increased knowledge has not led to consensus in many areas of the field. Two such areas of controversy include the specific definitions of asbestos, and limitations in understanding exposure-response relationships for various asbestos types and exposure levels and disease. This document reviews the current regulatory and mineralogical definitions and how variability in these definitions has led to difficulties in the discussion and comparison of both experimental laboratory and human epidemiological studies for asbestos. This review also examines the issues of exposure measurement in both animal and human studies, and discusses the impact of these issues on determination of cause for asbestos-related diseases. Limitations include the lack of detailed characterization and limited quantification of the fibers in most studies. Associated data gaps and research needs are also enumerated in this review.

In an attempt to explain the much greater risk of respiratory cancer at the same cumulative exposure in asbestos textile workers in Charleston, South Carolina, than in Quebec miners and millers, both exposed to chrysotile from the same source, 161 lung tissue samples taken at necropsy from dead cohort members were analysed by transmission electron microscopy. Altogether 1828 chrysotile and 3270 tremolite fibres were identified; in both cohorts tremolite predominated and fibre dimensions were closely similar. Lung fibre concentrations were analysed statistically (a) in 32 paired subjects matched for duration ofemployment and time from last employment to death and (b) in 136 subjects stratified by the same time variables. Both analyses indicated that the Quebec/ Charleston ratios for chrysotile fibre concentration in lung tissue were even higher than the corresponding ratios of estimated exposure intensity (mpcf). After allowance for the fact that regression analyses suggested that the proportion oftremolite in dust was probably 2 5 times higher in Thetford Mines, Quebec, than in Charleston, the results from both matched pair and stratification analyses of tremolite fibre concentrations in lung were almost the same as for chrysotile. It is concluded that neither fibre dimensional differences nor errors in estimation of exposure can explain the higher risks of lung cancer observed in asbestos textile workers. The possible co-carcinogenic role of mineral oil used in the past in asbestos textile plants to control dust provides an alternative hypothesis deserving consideration. exposures of the past were seldom documented. This difficult exercise has been attempted in nine industrial populations.2 Among these were the chrysotile miners and millers of Quebec34 and the chrysotile textile workers of Charleston, South Carolina.5 Linear relations between excess mortality from respiratory cancer and cumulative exposure in these two populations (fig 1) illustrate the problem considered in the present report. In both cohorts cumulative exposures (mpcf.y) were calculated from impinger data, all that were available for the past. Cumulative exposures as high as 2000 mpcf.y were recorded in the Quebec cohort, 10 times higher overall than exposures in Charleston. Figure 1 shows that, for the same cumulative exposure, the risk of respiratory cancer was about 50 times higher in Charleston. These estimates of risk were essentially corroborated by independent studies in the Charleston plant' and in Quebec.9 Studies in two other textile plants, one in the United States and another in the United Kingdom, gave similar results.'1 "The large difference in risk between mining and 180

1 Using subtype-selective 5-HT 1 receptor agonists and/or the 5-HT 1 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). 2 Agonists with anity at the 5-HT 1B 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-HT 1 receptors in both species. In contrast, PNU-109291 and LY344864, selective agonists at 5-HT 1D and 5-HT 1F receptors, respectively, were devoid of any signi®cant vasocontractile activity in cerebral arteries, or did not aect the sumatriptan-induced vasocontraction. The rank order of agonist potency was similar in both species and could be summarized as 5-HT=alniditan4sumatriptan=IS-159444PNU-109291=LY344864. 3 In bovine cerebral arteries, the 5-HT 1 receptor antagonist GR127935 dose-dependently inhibited the vasoconstrictions elicited by both 5-HT and sumatriptan, with respective pA 2 values of 8.0 and 8.6. 4 RT ± PCR studies in human coronary arteries showed a strong signal for the 5-HT 1B receptor while message for the 5-HT 1F receptor was weak and less frequently detected. Expression of 5-HT 1D receptor mRNA was not detected in any sample.5 The present results demonstrate that the triptan-induced contraction in brain vessels is mediated exclusively by the 5-HT 1B receptor, which is also present in a majority of human coronary arteries. These results suggest that selective 5-HT 1D and 5-HT 1F receptor agonists might represent new antimigraine drugs devoid of cerebro-and cardiovascular eects.