Warfarin dose and INR related to genotypes of CYP2C9 and VKORC1 in patients with myocardial infarction

Objectives

To analyse the effects of rosiglitazone administered at different times on neointimal formation in hypercholesterolemic rabbits following vascular injury.

Methods

Thirty-nine rabbits on a hypercholesterolemic diet were included. The animals underwent balloon catheter injury to the right iliac artery on day 14. They were divided into three groups as follows: control group, 13 rabbits without rosiglitazone; group I, 13 rabbits treated with rosiglitazone (3 mg/Kg body weight/day) for 28 days after the vascular injury; and group II, 13 rabbits treated with rosiglitazone (3 mg/Kg body weight/day) during all the experiment (42 days). Histological analysis was done by an experienced pathologist who was unaware of the rosiglitazone treatment. Histomorphometric parameters were performed by calculation of the luminal and intimal layer area, and intima/media layer area ratio (the area of the intimal layer divided by the area of the medial layer).

Results

Intimal area was significantly lower in group II vs. CG (p = 0.024) and group I (p = 0.006). Luminal layer area was higher in group II vs. CG (p < 0.0001) and group I (p < 0.0001). Intima/media layer area ratio was equal between CG and group I. Intima/media layer ratio area was significantly lower in group II vs. control group (p < 0.021) and group I (p < 0.003). There was a significant reduction of 65% and 71% in intima/media layer area ratio in group II vs. control group and group I, respectively.

Conclusion

Pretreatment with rosiglitazone in hypercholesterolemic rabbits submitted to vascular injury significantly reduces neointimal formation.     

Therapeutic hypothermia in neonates. Review of current clinical data, ILCOR recommendations and suggestions for implementation in neonatal intensive care units

Recent evidence suggests that the current ILCOR guidelines regarding hypothermia for the treatment of neonatal encephalopathy need urgent revision. In 2005 when the current ILCOR guidelines were finalised one large (CoolCap trial, n=235) and one small RCT (n=67), in addition to pilot trials, had been published, and demonstrated that therapeutic hypothermia after perinatal asphyxia was safe. The CoolCap trial showed a borderline overall effect on death and disability at 18 months of age, but significant improvement in a large subset of infants with less severe electroencephalographic changes. Based on this and other available evidence, the 2005 ILCOR guidelines supported post-resuscitation hypothermia in paediatric patients after cardiac arrest, but not after neonatal resuscitation. Subsequently, a whole body cooling trial supported by the NICHD reported a significant overall improvement in death or disability. Further large neonatal trials of hypothermia have stopped recruitment and their final results are likely to be published 2009-2011. Many important questions around the optimal therapeutic use of hypothermia remain to be answered. Nevertheless, independent meta-analyses of the published trials now indicate a consistent, robust beneficial effect of therapeutic hypothermia for moderate to severe neonatal encephalopathy, with a mean NNT between 6 and 8. Given that there is currently no other clinically proven treatment for infants with neonatal encephalopathy we propose that an interim advisory statement should be issued to support and guide the introduction of therapeutic hypothermia into routine clinical practice.     

The role of personality and self-efficacy in the selection and retention of successful nursing students: a longitudinal study

AIM: This paper is a report of a study to examine the role of personality and self-efficacy in predicting academic performance and attrition in nursing students. BACKGROUND: Despite a considerable amount of research investigating attrition in nursing students and new nurses, concerns remain. This particular issue highlights the need for a more effective selection process whereby those selected are more likely to complete their preregistration programme successfully, and remain employed as Registered Nurses. METHOD: A longitudinal design was adopted. A questionnaire, which included measures of personality and occupational and academic self-efficacy, was administered to 384 students early in the first year of the study. At the end of the programme, final marks and attrition rates were obtained from university records for a total of 350 students. The data were collected from 1999 to 2002. FINDINGS: Individuals who scored higher on a psychoticism scale were more likely to withdraw from the programme. Occupational self-efficacy was revealed to be a statistically significant predictor of final mark obtained, in that those with higher self-efficacy beliefs were more likely to achieve better final marks. Extraversion was also shown to negatively predict academic performance in that those with higher extraversion scores were more likely to achieve lower marks. CONCLUSION: More research is needed to explore the attributes of successful nursing students and the potential contribution of psychological profiling to a more effective selection process.     

Atypical early-onset Alzheimer's disease caused by the Iranian APP mutation

BACKGROUND: Approximately 1% of all cases of Alzheimer's disease are inherited autosomal dominantly, and to date, three causative genes have been found, the Presenilin 1 (PSEN1) gene, the Presenilin 2 (PSEN2) gene and the Amyloid precursor protein (APP) gene. We describe atypical phenotypic features in a family with a pathogenic APP gene mutation and discuss possible explanations for these atypical features. METHODS AND RESULTS: We report a family with a history of dementia compatible with autosomal dominant transmission. The disease course in the proband was not typical for Alzheimer's disease as the diagnosis was preceded by 8 years of an isolated amnesia. Further, the proband had epilepsy with complex partial seizures and central degenerative autonomic failure as determined by clinical physiology. Sequencing the three known causative Alzheimer genes revealed a pathogenic missense mutation, APP Thr714Ala (the Iranian mutation). CONCLUSIONS: The atypical clinical phenotype with long prodromal phase, autonomic failure and seizures in this new proband with the APP Thr714Ala mutation illustrates the clinical heterogeneity in families with identical pathogenic mutations.     

Reflexion on innovation diffusion factors: the case of Herceptin

New innovating cancer therapies are becoming available on the market. Because medical innovations put a serious financial burden on healthcare system, it is important to understand their diffusion. To analyze this process of diffusion, the molecule trastuzumab (Herceptin) provided by Roche Laboratories was chosen. Because Herceptin is commercialized since 1999 few data are available for this analysis. The objective of this study is to identify factors and brakes associated with the diffusion of the innovation Herceptin. By identifying these factors and brakes, one can notice that Herceptin is the perfect case to illustrate a successful diffusion. All factors mentioned in E. M. Rogers theory are verified with Herceptin: benefit, simplicity, triability, observability and compatibility. The tolerance is excellent and side effects minimized except for cardiac toxicity for patients previously treated with anthracyclines. The weakness concerning financing has been overcome since France changed the payment system to a prospective payment based on the hospital activity. The only problem left is that the fluorescence in situ hybridisation (FISH) test is still not reimbursed by the social security.     

Tumor-targeted enzyme/prodrug therapy mediates long-term disease-free survival of mice bearing disseminated neuroblastoma

Neural stem cells and progenitor cells migrate selectively to tumor loci in vivo. We exploited the tumor-tropic properties of HB1.F3.C1 cells, an immortalized cell line derived from human fetal telencephalon, to deliver the cDNA encoding a secreted form of rabbit carboxylesterase (rCE) to disseminated neuroblastoma tumors in mice. This enzyme activates the prodrug CPT-11 more efficiently than do human enzymes. Mice bearing multiple tumors were treated with rCE-expressing HB1.F3.C1 cells and schedules of administration of CPT-11 that produced levels of active drug (SN-38) tolerated by patients. Both HB1.F3.C1 cells and CPT-11 were given i.v. None of the untreated mice and 30% of mice that received only CPT-11 survived long term. In contrast, 90% of mice treated with rCE-expressing HB1.F3.C1 cells and 15 mg/kg CPT-11 survived for 1 year without detectable tumors. Plasma carboxylesterase activity and SN-38 levels in mice receiving both rCE-expressing HB1.F3.C1 cells (HB1.F3.C1/AdCMVrCE) and CPT-11 were comparable with those in mice receiving CPT-11 only. These data support the hypothesis that the antitumor effect of the described neural stem/progenitor cell-directed enzyme prodrug therapy (NDEPT) is mediated by production of high concentrations of active drug selectively at tumor sites, thereby maximizing the antitumor effect of CPT-11. NDEPT approaches merit further investigation as effective, targeted therapy for metastatic tumors. We propose that the described approach may have greatest use for eradicating minimum residual disease.