A platelet tetraspanin superfamily member, CD151, is required for regulation of thrombus growth and stability in vivo.

BACKGROUND: This study was designed to determine the role of CD151 in platelet thrombus formation in vivo and define the contribution of platelet vs. endothelial CD151 in regulating platelet thrombus formation in vivo. METHODS AND RESULTS: Using intravital microscopy and ferric chloride (FeCl(3)) injury of mesenteric arterioles, we found that thrombi formed in CD151(+/-) and CD151(-/-) mice were smaller and less stable, than those formed in CD151(+/+) mice, with a tendency for embolization. Similarly, in Folt's FeCl(3)-induced carotid injury model, both CD151(+/-) and CD151(-/-) mice showed more prolonged times to 95% vessel occlusion than CD151(+/+) mice. In addition, laser-induced injury of cremaster muscle arterioles showed that thrombi formed in CD151(+/-) and CD151(-/-) mice were smaller and less stable than those formed in CD151(+/+) mice. Following platelet depletion/reconstitution with ex vivo-labeled donor platelets, platelet-depleted CD151(+/+) mice that received reconstitution with CD151(-/-) platelets had smaller thrombi that were unstable and embolized. In contrast, platelet-depleted CD151(-/-) mice that received reconstitution with CD151(+/+) platelets had normal thrombi that were stable. CONCLUSIONS: These data provide evidence that platelet CD151 is required for regulating thrombus formation in vivo.

Laryngeal and hypopharyngeal cancer and occupational exposure to asbestos and man-made vitreous fibers: results of a case-control study.

BACKGROUND: The data from a case-control study performed in France between 1989 and 1991 were used to test whether exposure to either asbestos or to man-made vitreous fibers (MMVF) is a risk factor for cancer of the larynx or the hypopharynx. METHODS: This study involved 315 incident cases of laryngeal cancer, 206 cases of hypopharyngeal cancer, and 305 hospital-based controls with other types of cancer, all recruited in 15 hospitals in six French cities. The subjects' past occupational exposure to asbestos and to four types of MMVF (mineral wool, refractory ceramic fibers, glass filaments, and microfibers) was evaluated based on their job history, with the aid of a job-exposure matrix. Odds ratios were calculated with unconditional logistic regression, with adjustment for smoking and drinking levels. RESULTS: Exposure to asbestos resulted in a significant increase in the risk of hypopharyngeal cancer (OR = 1.80, 95% CI: 1.08-2.99) and a nonsignificant increase in the risk of laryngeal cancer (OR = 1.24, 95% CI: 0.83-1.90). Risk was highest for the epilarynx (highest cumulative level of exposure: OR = 2.22, 95% CI: 1.05-4.71). Exposure to mineral wools was of borderline significance for the risk of hypopharyngeal cancer (OR = 1.55, 95% CI: 0.99-2.41), and nonsignificantly associated with the risk of laryngeal cancer (OR-1.33, 95% CI: 0.91-1.95). The risk was again highest for the epilarynx (OR = 1.85, 95% CI: 1.08-3.17). No significant results were observed for the other MMVF. CONCLUSIONS: These results suggest that asbestos exposure increases the risk of epilaryngeal and hypopharyngeal cancers. It is difficult to reach a conclusion about the effects of mineral wools, because nearly all the exposed subjects were also exposed to asbestos. The possible effects of other MMVF were difficult to assess in this study, because of the paucity of exposed subjects.

Performance of population specific job exposure matrices (JEMs): European collaborative analyses on occupational risk factors for chronic obstructive pulmonary disease with job exposure matrices (ECOJEM).

OBJECTIVES: To compare the performance of population specific job exposure matrices (JEMs) and self reported occupational exposure with data on exposure and lung function from three European general populations. METHODS: Self reported occupational exposure (yes or no) and present occupation were recorded in the three general population surveys conducted in France, The Netherlands, and Norway. Analysis was performed on subjects, aged 25-64, who provided good forced expiratory volume in 1 second (FEV1) tracings and whose occupations were performed by at least two people, in the French (6217 men and 5571 women), the Dutch (men from urban (854) and rural (780) areas), and the Norwegian (395 men) surveys. Two population specific JEMs, based on the percentage of subjects who reported themselves exposed in each job, were constructed for each survey and each sex. The first matrix classified jobs into three categories of exposure according to the proportion of subjects who reported themselves exposed in each job (P10-50 JEM, low < 10%, moderate 10-49%, high > or = 50%). For the second matrix, a dichotomous variable was constructed to have the same statistical power as the self reported exposure--that is, the exposure prevalence (p) was the same with both exposure assessment methods (Pp JEM). Relations between occupational exposure, as estimated by the two JEMs and self reported exposure, and age, height, city, and smoking adjusted FEV1 score were compared. RESULTS: Significant associations between occupational exposure estimated by the population specific JEM and lung function were found in the French and the rural Dutch surveys, whereas no significant relation was found with self reported exposure. In populations with few subjects in most jobs, exposure cannot be estimated with sufficient precision by a population specific JEM, which may explain the lack of relation in the Norwegian and the Dutch (urban area) surveys. CONCLUSION: The population specific JEM, which was easy to construct and cost little, seemed to perform better than crude self reported exposures, in populations with sufficient numbers of subjects per job.

[Assessment of exposure to asbestos]. / Evaluation des expositions à l'amiante.

The aim of the study is to present the principles of assessing asbestos exposure in two different contexts: that of a patient suffering from pleuropulmonary pathology that could be attributed to asbestos and that of a group possibly exposed to asbestos. In the first case this evaluation concerns past exposure and depends typically on information obtained during the course of an interview with the patient. In the second case, the exposure is assessed by atmospheric analysis. Jobs in which occupational exposure to asbestos occurs should be examined, the tasks which entail this exposure and objects containing asbestos are discussed in the first part of the article. The accent is placed on the source of exposure, and the use of materials containing asbestos outside the asbestos industry. Some guidelines enabling the appreciation of the intensity of asbestos exposure as a function of the jobs involved and the objects handled are suggested. Regulations and the principle of quantifying asbestos in the atmosphere during direct exposure in the working environment on the one hand and during the course of passive exposure in the environment on the other are discussed in the second part of the article.

Pleural mesothelioma: dose-response relation at low levels of asbestos exposure in a French population-based case-control study.

A hospital-based case-control study of the association between past occupational exposure to asbestos and pleural mesothelioma was carried out in five regions of France. Between 1987 and 1993, 405 cases and 387 controls were interviewed. The job histories of these subjects were evaluated by a group of experts for exposure to asbestos fibers according to probability, intensity, and frequency. A cumulative exposure index was calculated as the product of these three parameters and the duration of the exposed job, summed over the entire working life. Among men, the odds ratio increased with the probability of exposure and was 1.2 (95% confidence interval (CI) 0.8-1.9) for possible exposure and 3.6 (95% CI 2.4-5.3) for definite exposure. A dose-response relation was observed with the cumulative exposure index: The odds ratio increased from 1.2 (95% CI 0.8-1.8) for the lowest exposure category to 8.7 (95% CI 4.1-18.5) for the highest. Among women, the odds ratio for possible or definite exposure was 18.8 (95% CI 4.1-86.2). We found a clear dose-response relation between cumulative asbestos exposure and pleural mesothelioma in a population-based case-control study with retrospective assessment of exposure. A significant excess of mesothelioma was observed for levels of cumulative exposure that were probably far below the limits adopted in most industrial countries during the 1980s.

[The assessment of asbestos exposure]. / Evaluation des expositions à l'amiante.

The aim of the study is to present the principles of assessing asbestos exposure in two different contexts: that of a patient suffering from pleuropulmonary pathology that could be attributed to asbestos and that of a group possible exposed to asbestos. In the first case this evaluation concerns past exposure and depends typically on information obtained during the course of an interview with the patient. In the second case, the exposure is assessed by atmospheric analysis. Jobs in which occupational exposure to asbestos occurs should be examined, the tasks which entail this exposure and objects containing asbestos are discussed in the first part of the article. The accent is placed on the source of exposure, and the use of materials containing asbestos outside the asbestos industry. Some guidelines enabling the appreciation of the intensity of asbestos exposure as a function of the jobs involved and the objects handled are suggested. Regulations and the principle of quantifying asbestos in the atmosphere during direct exposure in the working environment of the one hand and during the course of passive exposure in the environment of the other are discussed in the second part of the article.

Occupational exposures estimated by means of job exposure matrices in relation to lung function in the PAARC survey.

OBJECTIVES: The aim of this analysis of the French Cooperative PAARC (Pollution Atmosphérique et Affections Respiratoires Chroniques) survey, was to test whether occupational exposures to dusts, gases, or chemical fumes or to specific hazards, estimated by job exposure matrices, were related to a decrease in forced expiratory volume in one second (FEV1). METHODS: The most recent occupation was recorded in adults, aged 25-59, from non-manual worker households. Analysis was restricted to 10,046 subjects whose occupation was encountered at least 10 times in the study and who performed good FEV1 tracings. From occupational title, exposures to dusts, gases, and chemical fumes, and to specific hazards were classified in three categories (no, low, and high) with a British, a French, and an Italian job exposure matrix. Specific hazards were analysed for the British and French job exposure matrices for the same 42 specific dusts, gases, and chemical fumes. To limit spurious associations, a selection of seven hazard groups and 12 specific hazards was set before the start of the analysis. Based on the consistency of the relations according to sex and the British and French job exposure matrices, associations of age, height, city, and smoking adjusted FEV1 score with occupational exposures were classified as very likely, possible, or unlikely. RESULTS: For the three job exposure matrices and both sexes clear exposure-response relations between the level of exposure to dusts, gases, and chemical fumes, and a decrease in FEV1 were found. Associations with FEV1 were classified as very likely for known hazards such as organic dusts and textile dusts, and not previously recognised hazards such as polycyclic aromatic hydrocarbons (PAHs) and detergents, and as possible for solvents, waxes and polishes, and diesel fumes. Associations found for PAHs and solvents were confirmed by the Italian job exposure matrix. Associations remained significant in women, but not in men, after adjustment for educational level. CONCLUSIONS: Hypotheses have been generated for exposure to detergents, PAHs, and solvents, but they need to be interpreted with caution before replication. Significant associations found for known risk factors with a decrease in FEV1 are arguments for the validity of the matrices. Despite the expected limitations of job exposure matrices, these results encourage further work to improve exposure assessment by job exposure matrices.

Pleural plaques, asbestos exposure, and asbestos bodies in bronchoalveolar lavage fluid.

The profiles of occupational asbestos exposure were investigated in a series of 66 hospital patients in whom pleural plaques constituted the only asbestos-induced abnormality. The relationship between a radiological semiquantitative score of pleural plaques and indices of asbestos exposure was also examined. On the basis of a standardized occupational questionnaire, four classes of asbestos exposure were distinguished in our study population: no evidence of exposure, low-level exposure, sporadic exposure at higher levels, and a remaining group of individuals with substantial exposure. Asbestos body count in bronchoalveolar lavage fluid (BALF) was used as an objective indicator of cumulative lung retention of asbestos. Our results support the data indicating that pleural plaques may occur in subjects with low-level or sporadic asbestos exposure. Although it is admitted that pleural plaques are strongly associated with past asbestos exposure, our data suggest that the stage of pleural plaques was not correlated to the level, frequency, duration of exposure nor to the amount of asbestos bodies in the BALF in subjects free of any lung parenchymal abnormalities on high resolution computerized tomography.

Pleural mesothelioma and exposure to asbestos: evaluation from work histories and analysis of asbestos bodies in bronchoalveolar lavage fluid or lung tissue in 131 patients.

Exposure to asbestos was evaluated in 131 patients with pleural malignant mesothelioma in the Paris area between 1986 and 1992 using data from a detailed specific questionnaire and light microscopy analysis of the retention of asbestos bodies in bronchoalveolar lavage fluid or lung tissue. Probable or definite exposure to significant levels of asbestos dust was identified in only 48 (36.6%) subjects, and significant asbestos body counts (above 1 asbestos body/ml in bronchoalveolar lavage fluid or 1000 asbestos bodies/g of dry lung tissue) were found in only 45 (34.3%) subjects. Overall 50 subjects had experienced exposure to only low levels of asbestos or no exposure at all and showed no significant retention of asbestos bodies in the biological sample analysed. Previous studies have shown that light microscopy may be useful in the identification of subjects with previous exposure to asbestos. In this study, apart from cases with obvious exposure to asbestos, a large group of subjects seemed to have a history of exposure or lung retention of asbestos bodies suggestive of very low levels of cumulative exposure, similar to those described in the general population.

Retrospective assessment of asbestos exposure--I. Case-control analysis in a study of lung cancer: efficiency of job-specific questionnaires and job exposure matrices.

Retrospective assessment of asbestos exposure--I. Case-control analysis in a study of lung cancer: efficiency of job-specific questionnaires and job exposure matrices. International Journal of Epidemiology 1993; 22 (Suppl. 2): S83-S95. In a lung cancer study in Northern Germany the asbestos exposure assessment obtained from detailed supplementary questionnaires (SQ) was compared to the assessment obtained by the application of two job exposure matrices (JEM) to the job history. The study includes 391 incident male cases and the same number of controls from the general population, matched by sex, age, and region. Almost 16% of the subjects are considered as never having been exposed to asbestos and 24% are classified as certainly exposed according to both of the JEM, the corresponding percentages of the SQ-method being 68% and 32%. Sixty percent are considered by the JEM as having an intermediate probability of exposure. In general, the agreement between the different methods is better when the exposure definition is restricted to definite exposures, the corresponding Kappa statistic being 0.67 for the comparison between both JEM and 0.44/0.39 between the JEM and the SQ. The positive agreement between SQ and JEM (reference) increases from 12% and 17% for subjects with low probability of exposure to 61% and 69% for those with definite exposures. A ranking according to cumulative exposure shows some dose-response relationship for each of the three methods with a smoking-adjusted OR in the highest category of 1.85 (95% CI: 1.01-3.38) for the SQ method and 2.47 (95% CI: 1.40-4.37) and 2.94 (95% CI: 1.73-4.99) for the two JEM. The results are discussed with reference to the conceptual differences between the methods and their potential scope in future studies.

Retrospective assessment of asbestos exposure--II. At the job level: complementarity of job-specific questionnaire and job exposure matrices.

Retrospective assessment of asbestos exposure--II. At the job level: Complementarity of job-specific questionnaire and job exposure matrices. International Journal of Epidemiology 1993; 22 (Suppl. 2): S96-S105. The assessments of asbestos exposure by two a priori job exposure matrices (JEM) and by a job-specific questionnaire (SQ) are compared at job level. The data used for the comparison were generated by an ongoing case-control study on lung cancer in a region of northern Germany with a relatively high past prevalence of asbestos exposure. Among job periods assessed as unexposed by either JEM, 96% are recognized as such by the SQ. Discrepancies between the SQ and JEM were observed in jobs rated potentially exposed by the JEM. Despite varying estimates, the JEM and SQ were consistent as regards the relative classification of job periods by probability of exposure. The concordance of the methods, estimated by Kappa statistics, was stronger for the two JEM than for either of the JEM and the SQ. The identification of specific occupation/industry combinations in which discrepancies were most frequent and the comparison with expert ratings in some jobs yield insights into the sources of the disagreement between the methods. The misclassification of exposure by the JEM usually results in an overestimation of exposure. This is essentially related to loss of information due to the use of job codes as surrogates for job task descriptions and to the insufficiency of published data on asbestos exposure in different industries. As regards the SQ, two main sources of potential loss of sensitivity were identified: 1) possible omission of indirect sources of exposure by this method, 2) possible incompleteness of the SQ. The present comparison of methods of asbestos exposure assessment does not allow any one approach to be considered superior to another. Indeed, as proposed by Ahrens et al. in Part I of the study, both should be used to ensure optimal epidemiological performance.

Squamous cell carcinoma in epidermolysis bullosa. Treatment with systemic chemotherapy.

Dystrophic epidermolysis bullosa is associated with a high incidence of cutaneous squamous cell carcinoma. Despite aggressive surgical treatment, metastases occur frequently, and survival is generally poor. Chemotherapy for advanced disease has usually been avoided because of the potential for severe cutaneous toxicity. Two patients with autosomal recessive dystrophic epidermolysis bullosa and advanced squamous cell carcinoma are described. Both received cisplatin-based systemic chemotherapy without significant toxicity.

Hodgkin's disease with leptomeningeal involvement. Report of a case with long survival.

A 30-year-old white man with Stage IV B Hodgkin's disease, mixed cellularity type, developed leptomeningeal involvement shortly after relapsing on nitrogen mustard, Oncovin (vincristine), procarbazine, and prednisone (MOPP), and while receiving Adriamycin (doxorubicin), bleomycin, Velban (vinblastine), and dacarbazine (ABVD). Whole brain irradiation and intrathecal methotrexate were successfully incorporated into his treatment program. The patient has now been in complete remission for more than 40 months. A review of this rare complication of Hodgkin's disease is presented.

[Experimental comparison of the tuberculostatic activities of INH, INHG and INHG-Na (author's transl)]. / Experimentelle vergleichende Untersuchung der tuberkulostatischen Wirksamkeit und Toxizität von INH, INHG und INHG-Na

In a comparative experimental study the glucuronic acid derivatives of isonicotinoylhydrazone (INH), isonicotinoyl-hydrazone d-glucuronic acid lactone (INHG, Gluronazid) and INH-sodium glucuronid (INHG-N-A, Gluronazid pro infusione) were shown to have the same tuberculostatic activity as INH both in vitro and in vivo. As judged by the serum inhibitory activity the serum level shows a different temporal pattern. After the administration of INHG or INHG-Na, the inhibitory activity reaches its peak later than does INH but remains in the active range essentially longer. The most substantial and, with regard to therapy, most significant difference between INHG or INHG-Na and INH lies in the varying toxicological properties. Both the oral and intravenous LD50 increase in the sequence INH, INHG and INHG-Na. The i.v. LD50 of INHG-Na exceeds the oral LD50. As compared to INH the lower toxicity permits a higher dosage of gluronazide. Thus a continuously higher serum inhibitory activity can be achieved than with a corresponding INH therapy.