Similar exposure to a tobacco-specific carcinogen in smokeless tobacco users and cigarette smokers.

Smokeless tobacco has been proposed as a reduced risk substitute for smoking, but no large studies have investigated exposure to the powerful carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in smokeless tobacco users versus smokers. The purpose of this study was to carry out such a comparison. Levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL), a biomarker of NNK exposure, and cotinine, a biomarker of nicotine exposure, were quantified in the urine of 420 smokers and 182 smokeless tobacco users who were participants in studies designed to reduce their use of these products. The measurements were taken at baseline, before intervention. Levels of total NNAL per milliliter of urine were significantly higher in smokeless tobacco users than in smokers (P < 0.0001). When adjusted for age and gender, levels of total NNAL per milligram of creatinine were also significantly higher in smokeless tobacco users than in smokers (P < 0.001). Levels of cotinine per milliliter of urine and per milligram of creatinine were significantly higher in smokeless tobacco users than in smokers (P < 0.001). These results show similar exposures to the potent tobacco-specific carcinogen NNK in smokeless tobacco users and smokers. These findings do not support the use of smokeless tobacco as a safe substitute for smoking.     

Association of COMT Val108/158Met genotype with smoking cessation in a nicotine replacement therapy randomized trial.

We investigated the association of catechol O-methyltransferase (COMT) genotype with abstinence following a smoking cessation attempt among a large cohort of smokers who attempted to quit using either the nicotine transdermal patch or placebo and were followed up over an 8-year period following their initial cessation attempt. In addition, we examined the possible moderating influence of sex on any association. The genotype x treatment interaction effect at 12-week follow-up indicated a greater benefit of active nicotine replacement treatment compared with placebo on likelihood of abstinence in the COMT Met/Met genotype group (33% versus 12%), in comparison to the Met/Val + Val/Val group (22% versus 16%). Our results indicate that COMT genotype may moderate the effect of active transdermal nicotine patch compared with placebo, with reduced relative benefit of nicotine replacement therapy in individuals with Met/Val or Val/Val genotype. Our data follow an emerging pattern of results suggesting that genetic variation in the dopamine pathway may provide a future basis for tailored smoking cessation therapies, but indicate that different genes influencing various components of this pathway may have different effects on response to smoking cessation pharmacotherapy.     

Perspectives: the possible influence of assisted reproductive technologies on transgenerational reproductive effects of environmental endocrine disruptors.

Demasculinization by environmental endocrine-disrupting chemicals (EDCs) is observed in many animal species but less evident in humans. Rodent studies with gestational exposure to either the fungicide vinclozolin or the insecticide methoxychlor demonstrate impaired male fertility with abnormal DNA methylation patterns in spermatozoa. Once established, these epigenetic changes may be permanent and thus paternally passed to subsequent generations. Conclusive evidence of a similar phenomenon in humans has not been established, but several observations bring up the possibility. Some, but not all, studies show an increase in male genital abnormalities after prenatal EDC exposure. Other studies demonstrate sperm abnormalities in males with EDC contact, although it is unclear as to whether this is due to prenatal or postnatal exposure. Although not examined in males with EDC exposure, one study shows gamete DNA methylation abnormalities in males with severe oligospermia. A subsequent study failed to corroborate these findings. The use of assisted reproductive techniques including intracytoplasmic sperm injection has removed natural selection barriers thus enabling reproduction in males that would otherwise be sterile. This review explores the hypothesis that prenatal EDC exposure results in transgenerational male reproductive abnormalities propagated by the use of assisted reproductive technologies.     

Australian Infection Control Association members' use of skills and resources that promote evidence-based infection control

BACKGROUND: To adopt an evidence-based approach, professionals must be able to access, identify, interpret, and critically appraise best evidence. Critical appraisal requires essential skills, such as computer literacy and an understanding of research principles. These skills also are required for professionals to contribute to evidence. METHODS: In 1996, members of the Australian Infection Control Association were surveyed to establish a profile including the extent to which they were reading infection control publications, using specific documents for policy and guideline development, developing and undertaking research, publishing research, and using computers. The relationships between demographics, computer use, and research activity were examined. RESULTS: The response rate was 63. 4% (630/993). The study group comprised mostly women (96.1%), and most (66.4%) were older than 40 years of age. Median infection control experience was 4 years (mean, 5.4 years; range, <12 months to 35 years). When developing guidelines and policies (92.7%; 584/630), infection control professionals reviewed State Health Department Infection Control Guidelines and Regulations. Research relating to infection control was undertaken by 21.5% (135/628) of the sample, and 27.6% (37/134) of this group published their research findings. Of the respondents (51.1%; 318/622) who used a computer to undertake infection control tasks, the majority (89.0%) used a personal computer for word processing. CONCLUSION: Regardless of infection control experience, Australian infection control professionals must be adequately prepared to contribute to, access, appraise, and where appropriate, apply best evidence to their practice. We suggest that computer literacy, an understanding of research principles, and familiarity with infection control literature are three essential skills that infection control professionals must possess and regularly exercise.     

Antibody-mediated resolution of light chain-associated amyloid deposits

Primary light-chain-associated (AL) amyloidosis is characterized by the deposition in tissue of monoclonal light chains as fibrils. With rare exception, this process is seemingly irreversible and results in progressive organ dysfunction and eventually death. To determine whether immune factors can effect amyloid removal, we developed an experimental model in which mice were injected with amyloid proteins extracted from the spleens or livers of patients with AL amyloidosis. Notably, the resultant amyloidomas were rapidly resolved, as compared to controls, when animals received injections of an anti-light-chain monoclonal antibody having specificity for an amyloid-related epitope. The reactivity of this monoclonal antibody was not dependent on the V(L) or C(L) isotype of the fibril, but rather seemed to be directed toward a beta-pleated sheet conformational epitope expressed by AL and other amyloid proteins. The amyloidolytic response was associated with a pronounced infiltration of the amyloidoma with neutrophils and putatively involved opsonization of fibrils by the antibody, leading to cellular activation and release of proteolytic factors. The demonstration that AL amyloid resolution can be induced by passive administration of an amyloid-reactive antibody has potential clinical benefit in the treatment of patients with primary amyloidosis and other acquired or inherited amyloid-associated disorders.     

The relation of religious belief and practices, depression, and hopelessness in persons with clinical depression

Religious belief and practices have been associated with lower levels of depression in persons dealing with stressful situations. In this study, researchers examined this relationship in 271 persons diagnosed with clinical depression. It was hypothesized that religious belief and practices would be associated with lower depression and that this relationship would be mediated by hopelessness. Religious belief, but not religious behavior, was a significant predictor of lower levels of hopelessness and depression beyond demographic variables. Through the relation of religious belief to lower levels of hopelessness, religious belief was indirectly related to less depression. There was also a small direct positive association of belief with depression, pointing to the complexity of the role belief plays for religious persons. Further study is needed for a better understanding of different ways religion affects depressed persons.