Pharmacokinetic and pharmacodynamic properties of atenolol in acute myocardial infarction.

A commonly used combined intravenous (i.v.) and oral dose regimen of atenolol was evaluated in 21 patients with acute myocardial infarction (MI). Atenolol 5-10 mg was administered i.v. and was followed by 50 mg twice daily during the first 24 h. Starting on the second day, 100 mg was administered as a single dose. Dose adjustments were made as necessary. The i.v. dose resulted in a rapid plasma peak concentration, but absorption of the first oral dose appeared to be delayed. The half-life (t1/2) was significantly prolonged on day 2 as compared with day 6, but the tmax, Cmax, and area under the curve (AUC) were all comparable to what has been reported in patients without MI. The change in heart rate (HR) or blood pressure (BP) was not related to the initial plasma level of atenolol. The interindividual variation was large, but most patients obtained plasma levels of atenolol which in studies of other diseases have been shown to be effective.     

Representative study for the evaluation of age- and gender-specific anthropometric parameters and blood pressure in an adolescent Hungarian population

BACKGROUNDS/AIMS: To assess the age- and gender-specific anthropometric parameters and blood pressure in Hungarian adolescents. METHODS: A cross-sectional study was performed between 1997 and 2000. Altogether 6,345 secondary school students (aged 15-18 years) were involved in the study. The representative sampling sites were selected randomly. In the capital city 3-stage and in the counties 4-stage stratified groups were assigned for the studies. Statistical analysis was performed using SPSS for Windows 9.0. RESULTS: The age- and gender-specific percentile distributions are given with regard to body weight, body height, body mass index (BMI), waist circumference, waist-to-hip ratio and arterial blood pressure values. Elevated blood pressure values were found at the first recording in 14.1% of the boys and in 2.5% of the girls. Since it is well known that the arterial blood pressure (ABP) may exhibit considerable intra- individual fluctuation with time, we therefore categorized normotensive and hypertensive students on the basis of the mean ABP values calculated from data obtained during the course of the three separate consecutive measurement periods at least 2 weeks apart. After that, the incidence of high blood pressure was 7.5% in boys and 1.1% in girls. CONCLUSION: The age- and gender-specific cutoff values thus formed may serve as reference values to assess the risk of developing nutrition-related noninfectious diseases in the future on the basis of the present percentile distribution of BMI. The present study also provides data on the prevalence of hypertension in the 15- to 18-year-old age group.     

Acetylation-defective mutants of Pparγ are associated with decreased lipid synthesis in breast cancer cells

In our prior publications we characterized a conserved acetylation motif (K(R)xxKK) of evolutionarily related nuclear receptors. Recent reports showed that peroxisome proliferator activated receptor gamma (PPARγ) deacetylation by SIRT1 is involved in delaying cellular senescence and maintaining the brown remodeling of white adipose tissue. However, it still remains unknown whether lysyl residues 154 and 155 (K154/155) of the conserved acetylation motif (RIHKK) in Pparγ1 are acetylated. Herein, we demonstrate that Pparγ1 is acetylated and regulated by both endogenous TSA-sensitive and NAD-dependent deacetylases. Acetylation of lysine 154 was identified by mass spectrometry (MS) while deacetylation of lysine 155 by SIRT1 was confirmed by in vitro deacetylation assay. An in vivo labeling assay revealed K154/K155 as bona fide acetylation sites. The conserved acetylation sites of Pparγ1 and the catalytic domain of SIRT1 are both required for the interaction between Pparγ1 and SIRT1. Sirt1 and Pparγ1 converge to govern lipid metabolism in vivo. Acetylation-defective mutants of Pparγ1 were associated with reduced lipid synthesis in ErbB2 overexpressing breast cancer cells. Together, these results suggest that the conserved lysyl residues K154/K155 of Pparγ1 are acetylated and play an important role in lipid synthesis in ErbB2-positive breast cancer cells.     

Post-examination analysis of objective tests

One of the key goals of assessment in medical education is the minimisation of all errors influencing a test in order to produce an observed score which approaches a learner's 'true' score, as reliably and validly as possible. In order to achieve this, assessors need to be aware of the potential biases that can influence all components of the assessment cycle from question creation to the interpretation of exam scores. This Guide describes and explains the processes whereby objective examination results can be analysed to improve the validity and reliability of assessments in medical education. We cover the interpretation of measures of central tendency, measures of variability and standard scores. We describe how to calculate the item-difficulty index and item-discrimination index in examination tests using different statistical procedures. This is followed by an overview of reliability estimates. The post-examination analytical methods described in this guide enable medical educators to construct reliable and valid achievement tests. They also enable medical educators to develop question banks using the collection of appropriate questions from existing examination tests in order to use computerised adaptive testing.     

Positioning, splinting, and contracture management

Whether a patient with burn injury is an adult or child, contracture management should be the primary focus of burn rehabilitation throughout the continuum of care. Positioning and splinting are crucial components of a comprehensive burn rehabilitation program that emphasizes contracture prevention. The emphasis of these devices throughout the phases of rehabilitation fluctuates to meet the changing needs of patients with burn injury. Early, effective, and consistent use of positioning devices and splints is recommended for successful management of burn scar contracture.     

The association between neighbourhoods and adverse birth outcomes: a systematic review and meta-analysis of multi-level studies

Many studies have examined the role of neighbourhood environment on birth outcomes but, because of differences in study design and modelling techniques, have found conflicting results. Seven databases were searched (1900-2010) for multi-level observational studies related to neighbourhood and pregnancy/birth. We identified 1502 articles of which 28 met all inclusion criteria. Meta-analysis was used to examine the association between neighbourhood income and low birthweight. Most studies showed a significant association between neighbourhood factors and birth outcomes. A significant pooled association was found for the relationship between neighbourhood income and low birthweight [odds ratio = 1.11, 95% confidence interval: 1.02, 1.20] whereby women who lived in low income neighbourhoods had significantly higher odds of having a low birthweight infant. This body of literature was found to consistently document significant associations between neighbourhood factors and birth outcomes. The consistency of findings from observational studies in this area indicates a need for causal studies to determine the mechanisms by which neighbourhoods influence birth outcomes.