Polymorphisms in glutathione-S-transferase genes (GST-M1, GST-T1 and GST-P1) and susceptibility to prostate cancer among male smokers of the ATBC cancer prevention study.

Glutathione-S-transferase (GST) genes encode a family of detoxification enzymes that offer protection against endogenous and exogenous sources of reactive oxygen species (ROS). Germline variations in GST genes may alter the catalytic efficiency of GST isoenzymes leading to a potential increase in susceptibility to the genotoxic effects of ROS and electrophilic substances. A nested case-control study design was used to examine the association between the polymorphic GST genes and prostate cancer risk among Finnish male smokers of the ATBC Cancer Prevention Study. A case-case analysis was used to determine the association between these genetic polymorphisms and prostate cancer progression. Germline DNA was obtained from 206 prostate cancer cases and 194 controls frequency matched on age, intervention group and study clinic. Cases and controls were genotyped for three GST genes using MALDI-TOF mass spectrometry or multiplex polymerase chain reaction (PCR). Relative to the wild-type genotype, we observed a 36% reduction in prostate cancer risk associated with the GST-M1-null genotype (odds ratio (OR) 0.64, 95% confidence interval (CI) 0.43, 0.95). Unlike GST-M1, GST-T1-null (OR 0.74, 95% CI 0.42, 1.33) and GST-P1*B (OR 1.10, 95% CI 0.72, 1.69) were not strongly associated with prostate cancer risk. We did not observe any significant associations between the selected polymorphic GST genes and tumour grade or stage. In conclusion, we did not observe a direct association between polymorphic GST-T1 or GST-P1 and prostate cancer risk. Our observation of a relatively strong inverse association between the GST-M1-null genotype and prostate cancer risk needs to be confirmed in larger association studies.     

Role of birds of prey as carriers and spreaders of Cryptococcus neoformans and other zoonotic yeasts.

In the last 20 years, cases of human cryptococcosis, have increased in immunocompromised patients. In several instances, the cases have been associated with the exposure of the patients to bird droppings. In order to investigate birds of prey as potential carriers and spreaders of Cryptococcus neoformans and other yeasts of importance in human infections, 182 swab samples were collected from the cloacae of several species of birds of prey (Group I) and 32 faecal samples from aviaries in which the birds were housed (Group II). Samples were also taken from digestive tract of 60 dead birds (Group III). A total of 454 samples were cultured from which 215 colonies of yeastlike fungi were recovered and identified. Cryptococcusneoformans var. grubii was isolated from three cloacae samples (4.8%) collected from Falco tinnunculus and from one sample (3.1%) obtained from Buteo buteo, as well as from samples collected at the aviaries in which these birds were kept. Overall, 18 samples (9.9%) from Group I, 13 (40.6%) from Group II, 12 crops (20%), three proventriculi (5%) and 12 cloacae (20%) from Group III yielded positive cultures for yeasts. The results indicate that birds of prey and in particular, F. tinnunculus and B. buteo, may act as carriers and spreaders of C. neoformans and other zoonotic yeasts.     

Substituting human chorionic gonadotropin by gonadotropin-releasing hormone agonist to trigger final follicular maturation, during controlled ovarian hyperstimulation, results in less systemic inflammation.

BACKGROUND: To investigate the degree of systemic inflammation, as reflected by serum C-reactive protein (CRP) levels, associated with controlled ovarian hyperstimulation (COH) with human chorionic gonadotropin (hCG) or gonadotropin-releasing hormone (GnRH) agonist for the induction of final follicular maturation. DESIGN: Prospective, observational study. SETTING: An in vitro fertilization (IVF) unit of an academic medical center. PATIENTS: Twenty-four women undergoing COH and IVF with the flexible GnRH antagonist protocol were prospectively assigned to receive hCG or GnRH agonist for the induction of final follicular maturation. METHODS: Blood was drawn three times during COH for measurement of sex-steroid and CRP levels: the day on which adequate suppression was obtained (Day-0); the day of or prior to administration of hCG (Day-hCG); and (3) the day of ovum pick-up (Day-OPU). Levels were compared among the three time points in the two groups. RESULTS: No between-group differences were observed in terms of patient age, gonadotropin dosage, duration of stimulation or number of oocytes retrieved. Serum CRP levels were significantly higher on Day-OPU than on Day-hCG and Day-0, but the difference was significant only in the hCG group (p<0.03 for both). The percentage change in CRP levels after hCG administration (Day-OPU vs. Day-hCG) (96%) was higher than that after GnRH administration (23%). CONCLUSION: Administration of GnRH agonist in patients undergoing COH for IVF yields a lesser degree of systemic inflammation, as reflected by CRP levels, than hCG.     

Refined-sugar intake and the risk of colorectal cancer in humans

The relationship between sugar added to coffee and other hot beverages--as an indicator of taste for sugar and sugar intake outside main meals--and the risk of colorectal cancer was investigated using data from a case-control study conducted in Northern Italy on 953 cases of histologically confirmed colon cancer, 633 of rectal cancer and 2845 controls admitted to hospital for acute, non-neoplastic, non-digestive tract disorders. Compared with subjects who reported adding no sugar to their beverages, the multivariate relative risks (RR) of colon cancer were 1.4 for those adding one spoonful of sugar, 1.6 for those adding 2 spoonsful, and 2.0 for those adding 3 or more. The corresponding RRs for rectal cancer were 1.3, 1.5 and 1.4. For combination of colorectal cancer the RRs were 1.4, 1.5 and 1.8. All the trends in risk were significant, and the results were consistent across strata of study centre, sex and age, and were not appreciably modified by allowance for a number of major identified potential distorting factors, including an estimate of total calorie intake. These findings, if confirmed, would suggest that taste for sugar is a relevant indicator of colorectal cancer risk, and could be interpreted either in terms of a role of sugar in colorectal carcinogens, or of a specific influence of even limited amounts of sugar taken outside meals, which may stimulate the proliferation of the bowel epithelium, and hence enhance colorectal carcinogenesis.     

Les onze propositions issues des 3es États généraux des malades du cancer et de leurs proches de la Ligue contre le cancer

Sans résumé     

Obesity and beta-blockers: influence of body fat on their kinetics and cardiovascular effects

Beta-blockers are among the most widely used antihypertensive drugs. They differ from each other in regard to several factors such as: beta-agonist activity, beta 1-selectivity and solubility. Aim of this work was to evaluate the influence of obesity on the kinetics and the antihypertensive effect of two Beta-blockers with different solubility such as: the water-soluble, atenolol and the liposoluble, metoprolol. The study was carried out according to an open randomized cross-over design. Eight obese hypertensive patients, after a two week washout period, were randomly allocated to a four week treatment. After a two week intermediate washout period, each patient switched to the other treatment for an additional four week period. On the first and the last day of each treatment the subjects were hospitalized to collect blood samples for the assay of the two drugs and to measure cardiovascular parameters. Obesity does not exert any effect on the kinetics of the water-soluble beta-blocker, atenolol, while markedly interferes with that of the liposoluble, without any apparent influence on its anti-hypertensive effect. These findings extend to obese hypertensives the concept that the plasma concentrations of beta-blocking agents are not reliable predictors of their therapeutic effect.     

Dietary factors in the risk of bladder cancer

The relationship between selected dietary factors and the risk of bladder cancer was investigated in a case-control study conducted in northern Italy. The study included 163 cases and 181 controls who were hospitalized for acute, nonneoplastic or urinary tract diseases. The frequency of consumption of green vegetables and carrots was lower in the cases; thus, the estimated relative risks for the upper vs. the lower tertiles were 0.6 for green vegetables and 0.5 for carrots. Significant inverse trends in risk emerged with estimated carotenoid (as well as retinoid) intake. The apparent protection conveyed by vitamin A was stronger in current smokers. The risk of bladder cancer was not related to scores of fat and measures of alcohol consumption; the risk was elevated in coffee drinkers (although there was no tendency to rise with higher consumption), but it was reduced in tea drinkers. These findings were not explainable in terms of selection, information, or confounding bias. Thus, although available information is too uncertain for any precise definition of specific (micro)nutrients related to bladder cancer risk, the confirmation that several aspects of a less-affluent diet adversely affect the risk is still of interest in terms of a better understanding of bladder carcinogenesis.     

Intubating conditions after vecuronium and atracurium given in divided doses (the priming technique)

Intubating conditions have been assessed at 60 s following administration of vecuronium 0.1 mg kg-1 or atracurium 0.5 mg kg-1 given either as a single dose after induction of anaesthesia with thiopentone or in divided doses; vecuronium 0.015 mg kg-1 followed 4 or 6 min later by 0.085 mg kg-1, or atracurium 0.075 mg kg-1 followed 4 or 6 min later by 0.425 mg kg-1. In the divided dose groups the smaller initial (priming) dose was given prior to induction of anaesthesia. Onset and duration of clinical relaxation were assessed using a peripheral nerve stimulator. The intubating conditions at 60 s improved significantly, with the use of relaxants in divided doses being acceptable in 80 and 70% of patients, respectively, with vecuronium and atracurium, but the conditions are not as good as those commonly found using suxamethonium. Priming at 6 min has no advantage over priming at 4 min. The onset of complete block was accelerated with priming, but the difference was not significant. The duration of clinical relaxation of vecuronium was significantly prolonged by giving it in divided doses. Unpleasant awareness of muscle weakness was observed in 15 patients, requiring early induction of anaesthesia in five of them.