Evaluation of progressive hepatic histopathology in long-term tamoxifen therapy

Tamoxifen (TAM) therapy is the better treatment for breast cancer and the drug use the prophylaxis of this disease in young premenopausal women. Yet, the effects associated with this therapy are unknown. To better understand the extension of this problem, we developed an animal model to mimic this therapy, aiming to evaluate its potential biochemical and histopathological changes in the liver. Young cycling female rats were treated with TAM for one, two and three months and toxicological biomarkers and liver histomorphometry were evaluated. Starting at two months, TAM-treatment prevented the normal age-dependent increase in body weight, without inducing changes in food intake. Serum levels of cholesterol and of the metabolic enzymes creatine kinase and aspartate aminotransferase were reduced in all TAM treatment periods. Serum levels of the metabolic enzymes alkaline phosphatase and lactate dehydrogenase were increased after the first month but returned to control levels upon 3 months of drug exposition. Moderate microvesicular steatosis, classified only at the first month of TAM treatment, was reduced afterwards. Our model showed an adaptive response of liver upon 3 months of treatment, suggesting that at the stated conditions, TAM will not promote hepatotoxicity. In this way, the present model may be useful in the study of possible key endocrine effects of TAM use and the search for better clinical outcomes.     

Evaluación formativa mediante el portafolio de 4 promociones de residentes de medicina de familia y comunitaria de la Unidad Docente de Murcia

ObjectiveTo evaluate the performance and quality of the 10 groups of training tasks envisaged in the portfolio training model undertaken by all residents of the Primary Care Teaching Unit in Murcia.DesignA cross-sectional study was conducted on the portfolios provided and completed by all residents in May 2011.ParticipantsAll residents who were in training at that time (131).MethodTen groups of training tasks were established from those recommended by the National Commission for the specialty. The performance of each one in each of the portfolios was evaluated, and the compliance for each training task was calculated. The quality of the performance of each of the tasks was given a score, 0 points (very poor) to 10 points (excellent).ResultsAs regards compliance, the tasks that were most performed were: filling in the Resident book correctly and using the resident skills guide, both with 99.24%, followed by reflection reports on the training visits. All tasks had a compliance rate higher than 67%. The mean percentage of compliance was 86.49%. All tasks obtained an average score greater than 7 (outstanding). The overall mean score was 7,8 points.ConclusionsThe level of perfomance of the tasks set out in the portfolio by the residents was very satisfying. It is necessary to continue working on improving the performance of the portfolio.     

Brain iron deposits are associated with general cognitive ability and cognitive aging

A novel analysis of magnetic resonance imaging (MRI) scans based on multispectral image fusion was used to quantify iron deposits in basal ganglia and microbleeds in 143 nondemented subjects of the generally healthy Lothian Birth Cohort, who were tested for general cognitive ability (intelligence) at mean ages of 11, 70, and 72 years. Possessing more iron deposits at age 72 was significantly associated with lower general cognitive ability at age 11, 70, and 72, explaining 4% to 9% of the variance. The relationships with old age general cognitive ability remained significant after controlling for childhood cognition, suggesting that iron deposits are related to lifetime cognitive decline. Most iron deposits were in the basal ganglia, with few microbleeds. While iron deposits in the general population have so far been dismissed in the literature, our results show substantial associations with cognitive functioning. The pattern of results suggests that iron deposits are not only a biomarker of general cognitive ability in old age and age-related cognitive decline, but that they are also related to the lifelong-stable trait of intelligence.     

Prognostic Value of Subdivisions of Nighttime Blood Pressure Fall in Hypertensives Followed Up for 8.2 Years. Does Nondipping Classification Need to Be Redefined?

J Clin Hypertens(Greenwich). 2010;12:508–515. © 2010 Wiley Periodicals, Inc. To evaluate the long-term prognostic significance of different ranges of the percentage fall in nighttime blood pressure (BP) of the nondipping pattern, 1200 hypertensive patients (645 women, age 51±12 years) underwent ambulatory BP monitoring under stabilized therapy. The occurrence of cardiovascular (CV) events was followed for 9833 patient-years and analyzed by the Cox hazard model. There were 152 CV fatal/nonfatal events (79 strokes, 51 coronary events, 22 others) during the 15.2 years of follow-up. According to nighttime BP fall (%) the authors noted: <0% (reverse-dippers [RD], n=83); 0%–4.9% (nondippers 1 [ND1], n=207); 5%–9.9% (nondippers 2 [ND2], n=311), 10%–19.9% (dippers [D], n=523); and ≥20% (extreme dippers [ED], n=76). After adjustment for confounding variables, hazard ratios (95% confidence interval) of CV event and stroke in RD vs D were 2.29 (1.31–3.99) and 2.46 (1.11–5.49); of ND1 vs D were 1.42 (1.12–1.79) and 1.62 (1.17–2.23); and of ND1 vs ND2 were 2.24 (1.33–3.75) and 2.30 (1.15–4.58). No differences were found in RD vs ND1 and ND2 vs D. Nondippers have a higher CV risk than dippers but only for a nighttime BP fall <5% suggesting that the limits for nondipping should be redefined for a stratification of CV risk.     

Respiratory syncytial virus pneumonia: mechanisms of inflammation and prolonged airway hyperresponsiveness

PURPOSE OF REVIEW: Respiratory syncytial virus is the leading viral pathogen associated with lower respiratory tract infection in young children worldwide. The pathogenesis of acute bronchiolitis and the mechanisms by which the virus induces long-term airway disease remain to be elucidated. This review highlights new findings reported in the English-language medical literature from January 2004 to January 2005. RECENT FINDINGS: Several studies have confirmed a strong association between respiratory syncytial virus infection in infancy and an increased risk for recurrent wheezing. Evidence indicates that the exaggerated immune response and abnormal neurogenic mechanisms induced by the virus play a significant role in the pathogenesis of the disease. Different genetic and immune markers have been correlated with acute disease severity and with increased risk of long-term pulmonary abnormalities. Recently, the application of real time polymerase chain reaction has demonstrated the persistence of respiratory syncytial virus RNA in the lungs of infected mice for months after inoculation. This unexpected observation has stimulated discussions as to whether the long-term presence of the virus could contribute to the long-term airway disease observed in children after respiratory syncytial virus lower respiratory tract infection. SUMMARY: Despite almost half a century of active research into the pathogenesis of respiratory syncytial virus-induced acute and chronic airway disease, many questions remain unresolved. Studies in animal models demonstrate that interventions reducing viral replication resulted in improvement of acute disease severity and long-term pulmonary abnormalities. The stage is ready for clinical studies to determine whether preventing or delaying the primary infection could reduce the incidence of recurrent wheezing in children.