[Protective effects of d-chlorpheniramine maleate pre-treatment against acute side effects of Irinotecan(CPT- 11)].

It is wellknown that cholinomimetic side effects, such as sedation, abdominal pain, nasal flow and watery eyes, may develop in patients in the early stage of Irinotecan (CPT-11) administration; however, there have been no investigations concerning methods for preventing the development of these side effects. To assess the protective effects of pre-treatment with d-CM on cholinomimetic side effects in the early stage after Irinotecan (CPT-11) administration, we prescribed d- Chlorpheniramine maleate (d-CM) to a group of patients prior to Irinotecan (CPT-11) administration. Twenty members from the group of non-d-CM-treated patients (n=39) and 4 members from the group of treated patients (n=20) complained of side effects. The pre-administration of d-CM significantly reduced the number of patients with side effects (p<0.05). The relative risk (RR) for the frequency of side effects was 0.39 (95% CI; 0.15-0.98), demonstrating that the frequency of side effects was significantly reduced. Based on theses findings, we concluded that the pre-administration of d-CM had protective effects against side effects that might develop in the early stage after Irinotecan (CPT-11) administration.

Association between paraoxonase-1 Q192R polymorphism and lung function among Saskatchewan grain handlers.

INTRODUCTION: Paraoxonase-1 (PON1) is a high-density, lipoprotein-associated, multifunctional antioxidant enzyme that is detected in nonciliated bronchiolar epithelial cells, although its role in the lung has not yet been clarified. We therefore investigated the association between the PON1 Q192R polymorphism and lung function. PATIENTS & METHODS: A total of 216 male Saskatchewan grain handlers provided demographic, occupational and respiratory-symptom information by means of questionnaires, and thereafter underwent PON1 Q192R genotyping and lung-function testing. RESULTS: Mean lung-function values did not differ among the Q192R genotypes. However, current smokers with the Q/Q genotype had a higher mean percent predicted forced expiratory volume in the first second (FEV(1)), and absolute and percent predicted FEV(1) per forced vital capacity (FVC) compared with current smokers with at least one 192R allele (100.9 +/- 11.2% vs 92.0 +/- 15.1%, p = 0.01; 78.0 +/- 5.9% vs 74.1 +/- 6.8%, p = 0.03; and 96.8 +/- 7.1% vs 92.1 +/- 8.3%, p = 0.03; respectively). The incidence of subjects with FEV(1)/FVC less than 70% was significantly higher in current smokers with at least one 192R allele than in nonsmokers with the Q/Q genotype (odds ratio: 5.0; 95% confidence interval: 1.5-17.4). The protective effect of the Q/Q genotype was not found in nonsmokers. The FVC was not influenced by either PON1 genotype or smoking status. CONCLUSION: The results obtained from grain handlers suggest that PON1 may play some role in the protection of the airways against the toxicity of cigarette smoke, and the 192R allele may be a novel genetic risk factor for airway injury.

Tumor necrosis factor alpha and pulmonary function in Saskatchewan grain handlers.

OBJECTIVE: The objective of this study was to estimate the contribution of lifestyle (cigarettes) and tumor necrosis factor (TNF) alpha polymorphisms at position 308 of the tumor necrosis factor alpha gene promotor (TNF-308*1/*2) to pulmonary function among grain handlers. METHODS: Employed male grain handlers (157) provided occupational and respiratory symptom information, pulmonary function measurements, and DNA for genotyping. RESULTS: The genotypes of 101 were TNF-308*1/*1, 47 were *1/*2, and nine were *2/*2. Current smokers whose genotype was *2/*2 or *1/*2 had lower values compared with other combinations of genotype and smoking status. Among *1/*1 homozygotes, current smokers had better percent of predicted forced expiratory volume in 1 second (P = 0.04) mean values than nonsmokers and better percent of predicted forced vital capacity than exsmokers (P = 0.017) or nonsmokers (P = 0.008). CONCLUSIONS: These results indicate the complexity of determining which workers will develop acute and chronic adverse pulmonary conditions in response to exposure to grain dust and the toxins in cigarette smoke interacting with their genotype.