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Background The presence of glutathione transferase (GST) M1 null genotype (GSTM1-null) in end-stage renal disease (ESRD) patients is associated with lower overall survival rate in comparison to those with GSTM1-active variants. We examined association between GSTM1 and GSTT1 deletion polymorphisms as well as SNPs in GSTA1/rs3957357 and GSTP1/rs1695 genes with overall and cause-specific cardiovascular mortality in ESRD patients. Methods Total of 199 patients undergoing hemodialysis were included in the study. Median value of time elapsed from dialysis initiation until the death, or the end of follow-up was 8 ± 5 years. The effect of GSTM1, GSTT1, GSTP1 and GSTA1 gene polymorphisms on predicting overall and specific cardiovascular outcomes (myocardial infarction, MI or stroke) was analyzed using Cox regression model, and differences in survival were determined by Kaplan-Meier. Results GSTM1-null genotype in ESRD patients was found to be independent predictor of overall and cardiovascular mortality. However, after false discovery rate and Bonferroni corrections this effect was lost. The borderline effect modification by wild-type GSTA1"A/"A genotype on associations between GSTM1-null and analyzed outcomes was found only for death from stroke. Homozygous carriers of combined GSTM1"0/GSTA1"A genotype exhibited significantly shorter time to death of stroke or MI in comparison with carriers of either GSTM1-active or at least one GSTA1"B gene variant. The best survival rate regarding cardiovascular outcome was found for ESRD patients with combined GSTM1-active and mutant GSTA1"B/"B genotype. Conclusions Combined GSTM1"0/GSTA1"A genotypes might be considered as genetic markers for cardiovascular death risk in ESRD patients, which may permit targeting of preventive and early intervention. [ABSTRACT FROM AUTHOR]

OBJECTIVES The study aimed to evaluate the results following complete repair of tetralogy of Fallot (TOF) in relation to age at surgery and to assess the role of palliation in the current era. METHODS A retrospective review of 251 consecutive patients with TOF repaired between 2003 and 2011 at the Great Ormond Street Hospital was performed. Children were divided into two groups: Group A, younger than 6 months (n = 78) and B, older than 6 months (n = 173). Early clinical outcomes and reoperation/reintervention rates were studied as well as indication for a palliation. RESULTS There was 1 (0.4%) early and 1 (0.4%) late death after a median follow-up time of 4.5 years. Forty-three patients (17%) underwent repair after initial palliation with inter-stage mortality of 5%. Groups A and B were similar in terms of surgical approach, postoperative complications and length of stay. Significant differences were found in terms of more frequent use of a transannular patch (P = 0.05), longer surgeries (P = 0.02) and a greater proportion of palliated patients (P = 0.002) in older patients. There was no difference in rates of reoperation/reintervention between groups and following both primary and staged repair. Palliated patients were more symptomatic (duct-dependent pulmonary blood flow; P < 0.01, cyanotic spells; P < 0.01), had more extracardiac/genetic anomalies (P < 0.01), coronary anomalies (P = 0.015) and significantly smaller pulmonary annulus, right pulmonary artery (RPA) and left pulmonary artery (LPA) Z-scores (P < 0.01 for all). CONCLUSION Age at complete repair was not linked to early clinical outcome or reoperation/reintervention rate. Palliative procedures postponed the timing of complete repair, but did not increase the reintervention rate. [ABSTRACT FROM PUBLISHER]

There is increasing evidence that adiponectin has a critical role in the development of breast cancer, but factors that influence adiponectin concentrations have not been well studied. We conducted a cross-sectional study among Asian-American controls who participated in a population-based case-control study of breast cancer. Participants were interviewed in-person and donated a blood specimen. Using multivariate models, we investigated the relationships between serum adiponectin concentrations and lifestyle factors (including adiposity and dietary factors) and serum sex-hormones and growth factors among postmenopausal women who were nonhormone-users at blood draw (n = 196). Adiponectin concentrations were significantly positively associated with green tea intake (P trend = 0.03); levels were 31% higher among those who drank green tea 4 or more times per wk (14.5 ± 1.10 μg/mL) compared with nongreen-tea-drinkers (11.0 ± 1.09 μg/mL); this association remained after adjustment for body mass index (BMI) and waist/hip ratio (WHR), both of which were significantly and inversely associated with adiponectin. Adiponectin concentrations were positively associated with sex-hormone-binding globulin (P trend < 0.0001) and the ratios of total testosterone (T)/total estradiol (E2) (P trend <0.004) after adjustment for BMI and WHR. Confirmation of our findings on green tea and adiponectin is needed. [ABSTRACT FROM AUTHOR]

We prospectively investigated whether coffee consumption was associated with decreased risk of colorectal cancer and whether cigarette smoking and stage of disease modify the association in the Singapore Chinese Health Study. During the first 12 years of follow-up, 961 colorectal cancer cases occurred in the cohort of over 60,000 middle-aged or older Chinese men and women living in Singapore. Baseline dietary exposures were assessed through in-person interviews using a validated food frequency questionnaire. The relation between coffee consumption and colorectal cancer risk was assessed by proportional hazards (Cox) regression. No overall association between coffee intake and colorectal cancer was observed. However, in analysis by subsite and stage restricted to ever smokers, the coffee-colon cancer association became statistically significant for advanced disease (P for trend = 0.01). The hazard ratio was 0.56 (95% confidence interval = 0.35-0.90) for advanced colon cancer in drinkers of 2 or more cups per day compared with those who drank no coffee or less than 1 cup per day. Although there is a null association between coffee intake and risk of colorectal cancer overall, coffee may protect against smoking related advanced colon cancer. [ABSTRACT FROM AUTHOR]

Isothiocyanates, found in cruciferous vegetables, are anticarcinogenic. Racial differences in smoking do not fully account for the African-American excess lung cancer incidence. African Americans consume more cruciferous vegetables than U.S. Whites. Impact on lung cancer risk is unknown. The glutathione S transferase M1 (GSTM1) gene promotes urinary isothiocyanate excretion. We evaluated dietary isothiocyanates and lung cancer using a population-based case-control study of 933 African Americans and Caucasians (non-Hispanic U.S. White) from Los Angeles County, California (311 cases; 622 controls). Broccoli, cauliflower, greens, and cabbage food-frequency variables represented isothiocyanates. Isothiocyanates were protective for lung cancer risk. Adjusted odds ratio (OR) for the uppermost quartile > 80 μ mol isothiocyanates/wk, compared to lowest, was 0.65 [95% confidence interval (CI) = 0.41-1.00, trend P = 0.02]. Association was stronger among subjects with homozygous deletion of GSTM1 (OR = 0.52, 95% CI = 0.31-0.86) than subjects with at least one GSTM1 copy (OR = 0.77, 95% CI = 0.49-1.21). The difference was not statistically significant (P = 0.16). Despite African Americans consuming more cruciferous vegetables, the isothiocyanate association did not vary by race (P = 0.52). Reduced lung cancer risk with higher isothiocyanate intake may be slightly stronger among subjects with deletion of GSTM1. [ABSTRACT FROM AUTHOR]

Abstract: Background: Uncertainty exists on whether there is adjuvant benefit of percutaneous transluminal angioplasty (PTA) over supervised exercise and best medical therapy in the treatment of intermittent claudication. Methods: Patients with symptoms of stable mild to moderate intermittent claudication (MIMIC) were randomised in two multi-centre trials, for femoropopliteal and aortoiliac arterial disease, to receive either PTA or no PTA against a background of supervised exercise and best medical therapy and followed up for 24 months. Initial claudication distance (ICD) and absolute walking distance (AWD) on treadmill were compared between randomised groups adjusting for the corresponding measure at baseline. Secondary outcomes included ankle-brachial pressure index (ABPI) and quality of life. Findings: A total of 93 patients were randomised into the femoropopliteal trial (48 into PTA) and 34 into the aortoiliac trial (19 to PTA). The mean (standard deviation, SD) age was 66(9) years for the femoropopliteal trial (63% male) and 63(9) for the aortoiliac trial (65% male). At 24 months, there were significant improvements in both AWD and ICD in the PTA groups for both trials. The adjusted AWD was 38% greater in the PTA group for the femoropopliteal trial (95%; CI 1–90) (p =0.04) and 78% greater in the PTA group for the aortoiliac trial (95%; CI 0–216) (p =0.05). Further benefits were demonstrated for ABPI but not for quality of life. Interpretation: PTA confers adjuvant benefit over supervised exercise and best medical therapy in terms of walking distances and ABPI 24 months after PTA in patients with stable mild to moderate intermittent claudication. [Copyright &y& Elsevier]

Prospective data on environmental exposures, especially with respect to alcohol, tobacco, and diet, in relation to the risk of esophageal cancer in high-risk populations are sparse. We analyzed data from a population-based cohort of 18,244 middle-aged and older men in Shanghai to identify risk factors for esophageal cancer in this high-risk population. The cohort was followed through 2006, and 101 incident esophageal cancer cases were identified. Cox proportional hazards models were used to estimate hazard ratios (HR) and their corresponding 95% confidence intervals (CI) for associations between exposures and esophageal cancer risk. With adjustment for tobacco use and other potential confounders, regular drinkers vs. nondrinkers of alcoholic beverages had a twofold risk of developing esophageal cancer (HR = 2.02, 95% CI = 1.31-3.12). With adjustment for alcohol and other potential confounders, long-term smokers (40+ yr) vs. nonsmokers of cigarettes showed a twofold risk of developing esophageal cancer (HR = 2.06, 95% CI = 1.11-3.82). Increased consumption of fruits (including oranges/tangerines), seafood, and milk were found to be protective against the development of esophageal cancer; HRs were decreased by 40-60% for high vs. low consumers after adjustment for cigarette smoking, alcohol drinking, and other confounders. [ABSTRACT FROM AUTHOR]

Diet may be a modifier of smoking-related cancer risk, with protective effects of intake of fruits and vegetables and associated antioxidants found in many observational studies. We previously reported serum Beta-Cryptoxanthin levels being inversely associated with smoking-related lung cancer incidence in a cohort of Chinese men. We noted, however, that serum Beta-Cryptoxanthinn is negatively correlated with smoking. Since self-reports of smoking intensity undoubtedly contain errors, this negative correlation indicates a potential bias in assessing the effects of Beta-Cryptoxanthin, due to confounding with the unmeasured (residual) portion of cigarette exposure. We evaluated cotinine levels in pre-diagnostic spot urine samples to attempt to improve smoking assessment. We noted that urinary cotinine levels correlated significantly with cigarette consumption overall and that cotinine was strongly predictive of lung cancer risk. Urinary cotinine, however, was not as strong a predictor of lung cancer risk in current smokers as were self-reports of cigarette consumption and cotinine remained only a marginally significant predictor of lung cancer risk after adjustment for self-reports. An apparent benefit of Beta-Cryptoxanthin remained evident when including both urinary cotinine and self-reported cigarette consumption and cotinine in the statistical model. However, we conclude that cotinine measured from a single spot urine seems to have only limited value in augmenting self-reports of cigarette consumption so that, at present, the apparent protective effects of Beta-Cryptoxanthinn, as seen in our own study, should continue to be regarded as unproven. We believe that future epidemiological evaluation of the association between Beta-Cryptoxanthin (and other antioxidants) and reduced lung cancer risk must utilize improved biomarkers to augment smokers' own self-reports of smoking amount. [ABSTRACT FROM AUTHOR]

To identify kidney glutathione S-transferase (GST) isoenzyme, which does not bind to glutathione affinity column, biochemical characterization was performed by using an array of substrates and by measuring sensitivity to inhibitors. Immunological characterization was done by immunoblotting. Affinity flow-through GST exhibited activity towards 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole and cumene hydroperoxide, typical class α substrates and high sensitivity towards hematin, an α class inhibitor. It cross-reacted with antibodies against α class GST. Affinity flow-through GST in human kidney is an α class member. [ABSTRACT FROM AUTHOR]

Reduced glutathione (GSH) levels and glutathione reductase (GR) and glutathione S-transferase (GST) activities were investigated in the erythrocytes and lymphocytes of non-dialyzed patients with varying degrees of chronic renal insufficiency, and also of patients on regular hemodialysis treatment. GSH, GR and GST levels were higher in erythrocytes and lymphocytes of examined patients as compared to their corresponding age-matched healthy controls. A correlation was found between the degree of renal insufficiency and the above parameters tested. A routine hemodialysis did not significantly affect erythrocyte and lymphocyte GSH content and activities of its associated enzymes. The increased GSH levels as well as GSH-linked enzyme activities of blood cells in uremia may be a protective mechanism for the cells due to the accumulation of toxic, oxidizing, wastes in the blood as a result of the uremic state. This view is supported by the results of in vitro experiments, which have shown that GR and GST activities of normal human lymphocytes are increased when incubated with plasma from uremic patients. [ABSTRACT FROM AUTHOR]

Intraoperative anti-A/B immunoadsorption (ABO-IA) was recently introduced for ABO-incompatible (ABOi) heart transplantation. Here we report the first case of a patient transplanted with ABO-IA, that was of an age and weight that required two ABO-IA columns run in parallel, to enable the reduction in antibody titres to a sufficiently low level in the time available during implantation of the donor organ. [ABSTRACT FROM AUTHOR]

Objective(s): Modified ultrafiltration has gained wide acceptance as a powerful tool against cardiopulmonary bypass morbidity in pediatric cardiac surgery. The aim of our study was to assess the importance of modified ultrafiltration within conditions of contemporary cardiopulmonary bypass characteristics. Methods: Ninety–eight patients (overall cohort) weighing less than 12 kg undergoing surgical repair with cardiopulmonary bypass were prospectively enrolled in a randomized protocol to receive modified and conventional ultrafiltration (MUF group) or just conventional ultrafiltration (non-MUF group). A special attention was paid to forty-nine neonates and infants weighing less than 5 kg (lower weight (LW) cohort). Results: Post-filtration hematocrit was significantly higher in the MUF group for both cohorts (overall cohort p = 0.001; LW cohort p = 0.04), but not at other time points. During the postoperative course, patients in the MUF group received fewer packed red blood cells, (overall cohort p = 0.01; LW cohort p = 0.07), but required more fresh frozen plasma (overall cohort p = 0.04; LW cohort p = 0.05). There was no difference between groups in hemodynamic state, chest tube output, duration of mechanical ventilation, respiratory parameters, duration of intensive care unit, and hospitalization stay. Conclusions: If conventional ultrafiltration provides adequate hemoconcentration modified ultrafiltration does not provide additional positive benefits except for reduction in blood cell transfusion, This, however, comes at the cost of needing more fresh frozen plasma. Of particular importance is that this also applies to infants with weight bellow 5 kg where modified ultrafiltration was supposed to have the greatest positive impact. [ABSTRACT FROM AUTHOR]