Immunotoxic potential of N-ethyl, N-nitrosourea (ENU) in CD1 mice.

The immunotoxic potential of ENU, a potent and transplacental neurocarcinogen, was evaluated in male CD1 mice. The animals received i.p. injections of ENU--0, 2, 8 or 32 mg/kg body weight, in citrate-phosphate buffer, twice weekly for three weeks. Splenic lymphocytes were cultured in the presence of mitogens, lipopolysaccharide, pokeweed mitogen, concanavalin A and phytohaemagglutinin. Mixed lymphocyte cultures in the presence of allogeneic cells were also tested. Blastogenic response decreased in a dose-dependent manner, as measured by the 3H-thymidine uptake by splenocytes. Primary antibody production by splenic lymphocytes from animals challenged with a T-dependent antigen (sheep red blood cells) was stimulated at low doses but depressed at the highest dose group compared with the controls, whereas T-independent cell response showed no significant change. Our results suggest that exposure to repeated, low levels of ENU significantly alters the immune status of CD1 mice. The effects appear to be somewhat selective to T cell processes, based on in vivo responses to T-dependent and T-independent antigens.     

Epidemiology of Chronic Kidney Disease,With Special Emphasis on Chronic Kidney Disease of Uncertain Etiology,in the North Central Region of Sri Lanka

Background

The aim of the study was to identify the epidemiology of chronic kidney disease of uncertain etiology in Sri Lanka.

Methods

A cross-sectional study was carried out by analyzing health statistics, and three cohort studies were conducted (n = 15 630, 3996, and 2809) to analyze the demographic information, age-specific prevalence, etiology, and stage of presentation. We screened 7604 individuals for chronic kidney disease of uncertain etiology.

Results

The results showed that the male:female ratio was 2.4:1, the mean age of patients was 54.7 ± 8 years, 92% of the patients were farmers, and 93% consumed water from shallow dug wells. Familial occurrence was common (36%). The prevalence of chronic kidney disease in different age groups was 3% in those aged 30–40 years; 7% in those aged 41–50 years, 20% in those aged 51–60 years, and 29% in those older than 60 years. Chronic kidney disease of uncertain etiology was diagnosed in 70.2% of patients, while 15.7% and 9.6% were due to hypertension and diabetic mellitus, respectively. The majority of patients were stage 4 (40%) at first presentation, while 31.8% were stage 3 and 24.5% were stage 5. Stage 1 and 2 presentation accounted for only 3.4%.

Conclusions

Low prevalence of CKDU was noticed (1.5%) among those who consumed water from natural springs. Prevalence was highest among males, rice farming communities, and those presenting at later disease stages.Key words: chronic kidney disease, uncertain etiology, epidemiology, North Central Province, male farmers, natural spring water     

Traditional Cardiovascular Risk Factors and the Presence of Obstructive Coronary Artery Disease in Men and Women

Background

Extensive research has demonstrated the importance of traditional cardiovascular risk factors in predicting acute coronary events. Our main objective was to evaluate the relationship between traditional risk factors and the presence of obstructive coronary artery disease (CAD), and to explore potential differences in men vs women.

Methods

An observational study was conducted in a population-based cohort of stable patients who underwent cardiac catheterization in Ontario, Canada. We examined the relationship of diabetes, hypertension, hyperlipidemia, and smoking with the presence of obstructive CAD in men and women using multivariable logistic regression models.

Results

Of the 46,490 patients who were included in our study, 61.2% were men and 38.8% were women. We found that 97% of patients with obstructive CAD had at least 1 conventional cardiovascular risk factor. The adjusted odds ratios (ORs) for obstructive CAD in women with diabetes (OR, 1.51), hypertension (OR, 1.38), and smoking (OR, 1.39) were statistically significantly greater than in men (OR, 1.20 for diabetes; OR, 1.08 for hypertension; OR, 1.14 for smoking; P < 0.001). The sex difference was even greater for patients with multiple risk factors. For example, the association with obstructive CAD in women with 4 cardiac risk factors (OR, 4.30; 95% confidence interval, 3.49-5.28) was almost doubled compared with men (OR, 2.26; 95%confidence interval, 1.99-2.57; P < 0.001).

Conclusions

Almost all patients with stable CAD undergoing cardiac catheterization had at least 1 traditional cardiac risk factor. Importantly, the association between multiple cardiac risk factors and the presence of obstructive CAD is substantially stronger in women than men.     

Influence of Coronary Anatomy and SYNTAX Score on the Variations in Revascularization Strategies for Patients With Multivessel Disease

Background

The Variation in Revascularization Practice in Ontario (VRPO) project helped describe variations in revascularization across Ontario. Coronary anatomy was the most important predictor of revascularization strategy. We conducted a novel angiographic substudy of the VRPO cohort to: (1) validate “real-world” coronary angiographic reporting in the province of Ontario; and (2) understand the relationship between variability in revascularization and coronary anatomy complexity.

Methods

Seventeen hundred eighty-seven angiograms from 17 cardiac centres were randomly sampled from the VRPO cohort. The core lab assessment involved blinded interpretation of each angiographic film. A comparison of agreement in coronary anatomy and treatment strategy between abstracted chart data from the VRPO study and blinded film review was undertaken. Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) scores were calculated for all patients with multivessel disease.

Results

The weighted κ statistic for coronary anatomy was 0.75 (95% confidence interval, 0.72-0.77), suggesting substantial agreement between abstracted chart data and blinded film review. The weighted κ for revascularization strategy was 0.51 (95% confidence interval, 0.47-0.54) suggesting only moderate agreement. There were no significant differences in the mean/median SYNTAX scores across all 4 percutaneous coronary intervention: coronary artery bypass graft (CABG) groups.

Conclusions

Abstracted chart data in the VRPO project provides a valid assessment of coronary anatomy and furthermore serves as validation of “real-world” coronary angiographic reporting in the province of Ontario. The uniform distribution of coronary complexity across centres in Ontario, with respect to the SYNTAX score, suggests the variation of percutaneous coronary intervention: CABG ratio is not related to a difference in coronary anatomy complexity across sites, but rather a difference in management strategies for the same anatomy.     

Measuring breast cancer-specific health-related quality of life in South Asia: psychometric properties of the Sinhala version of the EORTC QLQ-BR23

OBJECTIVE: To evaluate the psychometric properties of the Sinhala version of the breast cancer-specific health-related quality of life (HRQL) module of the European Organization for Research and Treatment of Cancer (QLQ-BR23). METHODS: Psychometric testing assessed the hypothesized scale structure, internal consistency, construct validity and acceptability of the Sinhala version of the QLQ-BR23 in a consecutive series of 356 newly diagnosed breast cancer patients recruited from tertiary care oncology treatment centres in Sri Lanka. RESULTS: Compliance and self-completion rates were high (98% and 88%, respectively), and missing data low (0.06%). Multitrait scaling confirmed the scale structure of the QLQ-BR23 with excellent item convergence (95%), item discrimination (99%), and scaling success (99%) rates. The Cronbach's alpha coefficients of the scales for internal consistency reliability ranged from 0.68 to 0.93. Construct validity was confirmed with satisfactory results for interscale correlations and known-groups comparisons. QLQ-BR23 item-scale correlations met or exceeded the convergent validity criterion of 0.40 for all but one item. QLQ-BR23 interscale correlations met this criterion for three comparisons and for five comparisons with conceptually related QLQ-C30 scales. Correlations between QLQ-BR23 scales and QLQ-C30 functional scales were lower as expected. As expected, most dimensions of the QLQ-BR23 were able to discriminate clearly between pretreatment and current treatment patients. CONCLUSION: Overall psychometric results for the Sinhala version of the QLQ-BR23 confirmed it as a reliable and valid questionnaire for assessing breast cancer-specific HRQL in Sri Lanka.