Oxidative stress and apoptosis in cardiomyocyte induced by high-dose alcohol

Binge drinking of alcohol causes cardiac dysfunction in some people. The mechanism remains unclear. This study was designed to investigate high doses of alcohol-induced oxidative stress and apoptosis in cardiomyocytes and protective effects of antioxidants. Cardiomyocytes isolated from 1- to 2-day-old Sprague-Dawley rats were treated with ethanol at doses of 0 mM, 50 mM, 100 mM, and 200 mM for 24 hours. Vitamin E (1 mM) and vitamin C (0.2 mM) were added to medium 1 hour before addition of ethanol. Results showed typical apoptosis: chromatin condensation, membrane blebbing, shrinkage, and cytoplasm condensation. Apoptosis is concentration-dependent in the range of 0 to 100 mM ethanol (apoptosis rates were respectively 0.68%, 2.03%, and 9.66% at ethanol concentration of 0 mM, 50 mM, and 100 mM). Necrotic cells became greatly increased in the 200 mM ethanol-treated group. Intracellular production of reactive oxygen intermediates increased as mitochondrial membrane potential decreased after ethanol treatment. Cytochrome c was found to be greater in the cytosol of the ethanol-treated groups. Activity of caspase-3 was higher in ethanol-treated groups (P < 0.05). Both vitamin E and vitamin C inhibited oxidative stress and myocyte apoptosis in ethanol-treated groups (P < 0.05). In conclusion, our data indicated that acute high-dose ethanol treatment primarily induces cardiomyocyte apoptosis at concentration up to 100 mM while necrosis is predominate at 200 mM. The underlying mechanism appears to involve mitochondrial damage via an increase in oxidative stress and releasing cytochrome c, which activates caspases that initiate chromatin fragmentation and apoptosis. Antioxidants, to a large extent, inhibit oxidative stress and apoptosis induced by ethanol.     

Costs of illness due to typhoid fever in an Indian urban slum community: implications for vaccination policy

Data on the burden of disease, costs of illness, and cost-effectiveness of vaccines are needed to facilitate the use of available anti-typhoid vaccines in developing countries. This one-year prospective surveillance was carried out in an urban slum community in Delhi, India, to estimate the costs of illness for cases of typhoid fever. Ninety-eight culture-positive typhoid, 31 culture-positive paratyphoid, and 94 culture-negative cases with clinical typhoid syndrome were identified during the surveillance. Estimates of costs of illness were based on data collected through weekly interviews conducted at home for three months following diagnosis. Private costs included the sum of direct medical, direct non-medical, and indirect costs. Non-patient (public) costs included costs of outpatient visits, hospitalizations, laboratory tests, and medicines provided free of charge to the families. The mean cost per episode of blood culture-confirmed typhoid fever was 3,597 Indian Rupees (US$ 1=INR 35.5) (SD 5,833); hospitalization increased the costs by several folds (INR 18,131, SD 11,218, p<0.0001). The private and non-patient costs of illness were similar (INR 1,732, SD 1,589, and INR 1,865, SD 5,154 respectively, p=0.8095). The total private and non-patient ex-ante costs, i.e. expected annual losses for each individual, were higher for children aged 2-5 years (INR 154) than for those aged 5-19 years (INR 32), 0-2 year(s) (INR 25), and 19-40 years (INR 2). The study highlights the need for affordable typhoid vaccines efficacious at 2-5 years of age. Currently-available Vi vaccine is affordable but is unlikely to be efficacious in the first two years of life. Ways must be found to make Vi-conjugate vaccine, which is efficacious at this age, available to children of developing-countries.     

A pilot study to predict high cost patients in the pre-operative setting

Introduction: The National Surgical Quality Improvement Program (NSQIP) previously demonstrated that certain clinical variables predict surgical mortality and morbidity. We examined whether these clinical variables could also predict the cost of care in the private sector. Methods: All 1,008 patients enrolled into the NSQIP at our institution between October 2001 and June 2002 were tracked for cost incurred by the health system using our internal cost accounting database. The original data collection of clinical data and outcomes was via a trained nurse reviewer through direct chart review and patient interview. A model for predicting cost was created via multiple linear regression systematically testing 44 preoperative variables against log-transformed cost. This model was then recalculated using the statistically significant variables from the initial model with the inclusion of a variable denoting occurrence of a complication. Testing was also performed to fit the model to only those without post-operative complications as well as those that survived. Results: While 31 variables were significant when tested separately, after considering interaction, a single model was derived from the 15 statistically significant (p < 0.05) preoperative variables predicted 65% of the variation in hospital costs (adjusted R² = 0.650). Top predictors of increased costs included: operation requiring inpatient stay, high ASA classification, low albumin, use of general anesthesia, high surgical complexity, and high BUN. Though complications were significantly correlated with increased costs, including whether complications actually occurred only improved the best overall model’s predictive capability by an additional 2% of the variation in costs for the entire population (adjusted R² = 0.669). Testing the model’s output in the subset of patients that avoided complications yielded an R² of 0.438. Conclusions: High cost patients can be predicted in the preoperative setting. These factors predicted higher costs even cases that did not have complications as viewed after the fact. It may be feasible to create benchmarking studies that “risk-adjust” costs as they relate to specific patient populations, which will allow for comparisons across institutions of cost-effectiveness. Institutions treating higher risk patients should seek increased reimbursement for these populations in order to match costs with revenues.     

Intercostal nerve blockade versus thoracic epidural analgesia for post thoracotomy pain relief

Background Post thoractomy pain is a major source of concern in the postoperative period. The purpose of this study was to evaluate the effectiveness of intraoperative temporary intercostal nerve blockade versus thoracic epidural analgesia for control of post thoracotomy pain. Methods 40 patients undergoing elective pulmonary resection through a postero lateral thoractomy were randomly allocated to receive epidural analgesia using 0.25% bupivicaine (Group A, n=20) or temporary intercostal nerve blockade using 0.25% bupivicaine (Group B, n=20). Adequacy of analgesia was assessed over a period of 24 hours using a visual analogue score and an observer verbal ranking scale. Results Pain scores were similar in both the groups for the first 4 hours after surgery. Thereafter, the pain scores were significantly higher (p<0.05) in Group B as compared to Group A for the remainder of the observation period. There was significantly higher (p<0.01) usage, of nonsteroidal analgesic consumption in Group B. No neurological complications were encountered, in both the study groups. Conclusion We conclude that in the early postoperative period there is no significant difference in pain relief in both the techniques but there after, epidural analgesia significantly reduces post thoracotomy pain.     

Thoracic epidural infusions for post thoracotomy pain relief: a clinical study to compare the efficacy of fentanyl — bupivicaine mixtures versus fentanyl alone

Background: Optimum pain relief following thoracotomy is essential for patient comfort and to reduce the incidence of postoperative pulmonary complications. Methods: A randomized clinical trial was conducted on 90 patients scheduled for pulmonary resection. The patients were randomly divided into three groups. Group 1 received 0.125% bupivicaine with fentanyl 10μg.ml⁻¹, Group 2 received 0.25% bupivicaine with fentanyl 10μg.ml⁻¹ and Group 3 received only fentanyl 10μg.ml⁻¹ in a calculated dose as a continuous thoracic epidural infusion. Adequacy of anglesia was assessed at rest and during movement over 24 hours. Analgesic efficacy was assessed using a visual analogue score and an observer verbal ranking scale. Results: Pain scores were significantly higher in Group 3 during the assessment period. (p<0.01) as compared to the other groups. The use of intraoperative vasopressors was significantly higher (p<0.05) in Group 2 as compared to the other groups. No neurological complications were encountered in any of the study groups. Conclusion: We conclude that in the early postoperative period, the use of 0.125% bupivicaine improves fentanyl epidural analgesia in patients undergoing lung resection.     

Effect of micronutrient supplementation on linear growth of children

This review summarizes the results of published, randomized clinical trials that have examined the impact of administration of micronutrients, singly or in combination to infants, preschool and school children on linear growth. Supplementation of single micronutrients resulted in small or no benefits on linear growth. A meta-analysis of zinc supplementation trials confirmed that zinc has a significant but small impact (0.22 sd units) on length gain in children 0-13 years of age. However, a recent study reported a substantially greater benefit (>1 sd) in stunted and non-stunted breast-fed infants 6-12 months of age. With iron supplementation, a beneficial effect was found only in anemic children. Vitamin A supplementation trials have reported little or no benefit on linear growth. Data currently available suggest some impact in children with clinical or biochemical vitamin A deficiency, but this issue needs confirmation. Few studies could be identified where a combination of micronutrients was given as a supplement or as fortified food; in the latter set of studies energy availability was assured. The impact on length without multiple micronutrient supplementation was no greater than that observed with single micronutrients. In conclusion, zinc and iron seem to have a modest effect on linear growth in deficient populations. Vitamin A is unlikely to have an important effect on linear growth. Limited available evidence does not allow us to conclude whether a combination of micronutrients, with or without additional food, would have a greater impact than that seen with zinc alone.