Polymorphisms in the DNA repair gene XRCC1 and susceptibility to alcoholic liver cirrhosis in older Southeastern Brazilians

The population of Southeastern Brazil has a very high mortality rate from liver cirrhosis, a disease that is considered an irreversible pre-malignant condition. This is largely due to the high prevalence of alcohol abuse in the region, Chronic alcohol consumption is associated with the production of free radical intermediates that can cause several DNA lesions. Reduced repair of these DNA lesions would. therefore, constitute a significant risk factor for liver cirrhosis and subsequent cancer, Recently, a number of polymorphisms in several DNA repair genes have been discovered, and it is possible that these polymorphisms may affect DNA repair capacity and thus modulate susceptibility to the disease. In this study, we tested the hypothesis that polymorphisms in the DNA repair gene XRCC1 are associated with increased risk of liver cirrhosis in Southeastern Brazilians. We conducted a pilot case-control study of 97 liver cirrhosis cases and 96 controls (matched for age, sex, and ethnicity) to investigate the role of two allelic variants coding for amino acid changes in the XRCC1 gene (the Arg194Trp and the Arg399Gln polymorphisms). Overall, we observed a 1.8-fold increase in the relative risk of liver cirrhosis associated with the 399Gln allele (either the heterozygous ArglGln or the homozygous Gln/Gln genotypes). The adjusted odds ratio (OR) was 1.82 (95% confidence limit (CL) 1.10-3.30). The relative risk appears to be highest among the Mestiso ethnic group (OR 2.60. 95% CL 0.92-7.34). There was a significant association between the 399Gln polymorphism and the risk of liver cirrhosis in older individuals over the age of 45 years (OR 170 (95% CL 1.14-6.48) compared to an OR of 1,24 (95% CL 0.55-2.78) for those under 45 years of age. No association was observed between the XRCC1 194Trp polymorphism and risk of liver cirrhosis. These preliminary results suggest that the XRCCl 399Gln polymorphism may be a significant risk modifier for alcoholic liver cirrhosis and justifies additional studies in that direction. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.180217318

The practice of continuous sedation until death in nursing homes in Flanders, Belgium: a nationwide study

Objectives: To investigate how continuous sedation until death (CSD), the reduction or removal of consciousness of an incurably ill individual until death to relieve refractory suffering, is practiced in nursing homes. Design: Nationwide cross-sectional retrospective survey. Setting: Nursing homes in Flanders, Belgium. Participants: Palliative care nurses (N=660) in all nursing homes in Flanders. Measurements: Nurse reports of their most recent patient treated with CSD. Results: The response rate was 65.5%, and 249 nurses reported a case of CSD (57.6%). Most individuals had cancer (33.6%) or dementia (32.8%); lacked competence (65.7%); and had severe pain (71.2%), fatigue (62.3%), loss of dignity (59%), anxiety (58.4%), and longing for death (58.4%). Intractable pain (70.7%) and physical exhaustion (63.9%) were the most decisive symptoms for initiating CSD. Life expectancy was generally limited to 1week (64.9%), and 88.4% had insufficient nutritional oral intake before the start of CSD. CSD was rarely combined with artificial nutrition or hydration. Benzodiazepines were most frequently used (84.8%). Overall, according to the reporting nurses, CSD provided adequate symptom relief and good quality of dying. Conclusion: In nursing homes, CSD is typically used in residents with cancer or dementia and severe, intractable physical symptoms. Lack of competence prevents most residents from being involved in the decision-making process, which illustrates the importance of advance care planning in nursing homes in Flanders