1 The antithrombotic action of argatroban, a synthetic thrombin inhibitor, was studied in three models of thrombosis in the rat, and in the tail transection bleeding time test 20 tg kg', min-') had similar activity to that of heparin (180% increase at 25 jg kg-' min ') on a weight basis. Hoever, the antithrombotic effects of argatroban were accompanied by only moderate changes in the coagulation parameters (thrombin time and activated partial thromboplastin time, APTT), whereas, even at a subthreshold dose of heparin (12.5 pg kg' min-'), both the thrombin time and the APTT were greater than 150 s. 5 Infusions of both compounds caused dose-dependent increases in the tail transection bleeding time, with the dose of argatroban that doubles the bleeding time (11 I g kg-' min-') being five times greater than that of heparin (EDI, = 2.2 fig kg' min-').6 These data show that, when administered as an intravenous infusion, argatroban is a potent antithrombotic agent in rat models of venous 'mixed' and arterial thrombosis, this effect can be obtained with a lower degree of systemic anticoagulation than with heparin in the arterial model, and argatroban has a lower haemorrhagic potential than that of heparin.
This longitudinal study (1992-1994) was performed to determine the relation between accidental chlorine exposure and changes in lung function and airway responsiveness in 239 workers in a metal production plant. These workers had taken part in a cross-sectional survey in 1992. In both the initial and the follow-up surveys, history of exposure to chlorine ("puffs"), accidental chlorine inhalation reported to the first-aid unit (gassing incidents), and of chronic symptoms were documented; spirometry and methacholine challenge tests were performed. At follow-up, 211 workers (88.3%) were seen. In workers with 20 pack-years or more of cigarette smoking, the fall in FEV(1) was associated with having had a gassing incident during the follow-up period; the fall in FEV(1)/FVC (%) was predicted by the number of puffs causing mild symptoms between the two assessments. An increase in airway responsiveness (PC(20) decrease > 1.5-fold) was present in 19 workers; it was associated with accidents reported to the first-aid unit during the previous 2 yr (OR: 5.9, 95% CI: 1.1 to 32.3). These findings suggest: (1) an effect on airway function related to the estimated number of puffs with mild symptoms and gassing incidents, mostly among smokers; (2) a detectable increase in airway responsiveness associated with gassing incidents.
Background-To assess the frequency of chronic upper airways symptoms and to relate the presence of these symptoms to accidental exposure to chlorine and changes in lower airways symptoms, airway function, and bronchial responsiveness in a cohort of workers at risk of sporadic occupational exposure to high concentrations of chlorine Methods-Data were collected on symptom assessment, spirometry, and methacholine challenge tests from 211 workers seen twice at a 2 year interval (1992-4). Results-The proportion of workers reporting chronic rhinitis was 46.9% in 1992 and 42.2% in 1994. Chronic rhinitis reported in 1994 was significantly associated with acute exposure to chlorine (self reports, p=0.02; first aid reports, p=0.001). In a multivariate logistic regression analysis the presence of reported accidents at the first aid unit (one accident, odds ratio (OR) 3.1, 95% confidence interval (95% CI) 1.3 to 7.5; two or more accidents, OR 6.2, 1.1 to 35.8) and of personal atopy (OR 5.5, 2.2 to 10.8) were significant predictors of chronic rhinitis in 1994. Chronic lower airways symptoms were more frequent in 1994 among workers reporting chronic rhinitis on both assessments than in others (p=0.03) and changes in bronchial responsiveness were more pronounced in those with persistent rhinitis (p=0.09). Conclusions-These results suggest that persistent nasal symptoms in workers at risk of reactive airways dysfunction syndrome could be a useful marker of lower respiratory tract abnormalities. (Occup Environ Med 1999;56:334-338)
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