Cognitions and alcohol-influenced performance: the impact of reinforcement contingencies

The effects of different reinforcement conditions on self-reported cognitions and task performance under the influence of alcohol were examined. Four groups of male university students attended a series of four drinking sessions. During the sessions, the groups performed a visual tracking task under different reinforcement conditions which influence the speed of acquisition of behavioural tolerance to the impairing effects of alcohol. At the end of each session, subjects completed a questionnaire intended to elicit any thoughts, feelings, ideas or images they experienced during the session. Their responses were scored in categories related to alcohol effects, task performance and motivation. The groups differed significantly on numbers of self-reported cognitions related to general alcohol effects and to alcohol effects on task performance; these differences corresponded to differences in the speed of tolerance development. In the group that acquired tolerance most rapidly, several aspects of task performance were significantly correlated with cognitions. These data provide support for the suggestion that cognitive activity may be an important factor in individuals' responses to alcohol and other drugs.     

Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity

With the development of targeted therapeutics, especially for small-molecule inhibitors, it is important to understand whether the observed in vivo efficacy correlates with the modulation of desired/intended target in vivo. We have developed a small-molecule inhibitor of all three vascular endothelial growth factor (VEGF) receptors (VEGFR), platelet-derived growth factor receptor, and c-Kit tyrosine kinases, pazopanib (GW786034), which selectively inhibits VEGF-induced endothelial cell proliferation. It has good oral exposure and inhibits angiogenesis and tumor growth in mice. Because bolus administration of the compound results in large differences in C(max) and C(trough), we investigated the effect of continuous infusion of a VEGFR inhibitor on tumor growth and angiogenesis. GW771806, which has similar enzyme and cellular profiles to GW786034, was used for these studies due to higher solubility requirements for infusion studies. Comparing the pharmacokinetics by two different routes of administration (bolus p.o. dosing and continuous infusion), we showed that the antitumor and antiangiogenic activity of VEGFR inhibitors is dependent on steady-state concentration of the compound above a threshold. The steady-state concentration required for these effects is consistent with the concentration required for the inhibition of VEGF-induced VEGFR2 phosphorylation in mouse lungs. Furthermore, the steady-state concentration of pazopanib determined from preclinical activity showed a strong correlation with the pharmacodynamic effects and antitumor activity in the phase I clinical trial.     

Endothelial dysfunction in hypertension in pregnancy: associations between circulating endothelial cells,circulating progenitor cells and plasma von Willebrand factor

Background  

Endothelial damage/dysfunction has been related to hypertension in pregnancy, with implications in pregnancy outcomes. We hypothesised abnormal levels of circulating endothelial cells (CECs), circulating progenitor cells (CPCs) and plasma von Willebrand factor (vWf, a marker of endothelial damage/dysfunction) in pregnant women with hypertension, when compared to pregnant normotensives and non pregnant healthy controls.     

Dermatofibrosarcoma protuberans of the scalp

Dermatofibrosarcoma protuberans is a rare entity. Due to its high propensity for local recurrence, knowledge of the appropriate management, both surgical and medical, is important for optimal patient outcomes.     

Enhancement characteristics of papillary renal neoplasms revealed on triphasic helical CT of the kidneys.

OBJECTIVE: The purpose of this study was to determine whether renal tumor enhancement or heterogeneity on triphasic helical CT scans is predictive of the papillary cell subtype or nuclear grade of renal cell carcinoma. MATERIALS AND METHODS: We reviewed the CT scans of 90 consecutive patients with renal masses who had undergone triphasic renal helical CT before a complete or partial nephrectomy (12 with papillary renal cell carcinomas, 66 with nonpapillary renal cell carcinomas, and 12 with benign lesions). Three radiologists who were unaware of the patients' diagnoses retrospectively and independently measured the attenuation of each patient's tumor, abdominal aorta, and normal renal parenchyma on the scans obtained during all three phases. Ratios of tumor-to-aorta enhancement and tumor-to-normal renal parenchyma enhancement were calculated for both of the phases performed after contrast material had been administered. Tumor heterogeneity was calculated as the difference between the highest and lowest attenuation values divided by the value of the enhancement of the aorta. Values were correlated with cell type and nuclear grade found at surgical pathology. RESULTS: Low tumor-to-aorta enhancement and low tumor-to-normal renal parenchyma enhancement ratios on the vascular phase scans significantly correlated (p < 0.001) with papillary renal cell type carcinoma. Homogeneity and tumor-to-parenchyma enhancement ratios on the parenchymal phase scans also significantly correlated (p < 0.001) with papillary renal cell type carcinoma. Heterogeneity and tumor enhancement ratios did not correlate with the nuclear grade of the carcinoma. CONCLUSION: Papillary renal cell carcinomas are typically hypovascular and homogeneous. A high tumor-to-parenchyma enhancement ratio (> or = 25%) essentially excludes the possibility of a tumor being papillary renal cell carcinoma. A low tumor-to-aorta enhancement ratio or tumor-to-normal renal parenchyma enhancement ratio is more likely to indicate papillary renal cell carcinoma.     

Calcineurin inhibitor minimization in pediatric liver allograft recipients

Abstract:  The use of CNI in pediatric LTx has dramatically improved the outcome for children with end-stage liver disease by significantly reducing the rate of acute and chronic rejection. Long-term concerns about CNI-induced nephrotoxicity and other adverse effects remain an issue, particularly as the emphasis moves from short-term survival to long-term quality of life. This review summarizes lessons learnt from pediatric and adult solid organ transplantation in minimizing CNI use in immunosuppression protocols in children following LTx. There are three models for CNI minimization: dose reduction, withdrawal or avoidance, supplemented by the use of IL-2 receptor blocking antibodies in the peri-transplant period, and early transition to alternate drugs such as MMF or SRL. Prospective studies evaluating reduction or withdrawal protocols in adult and pediatric LTx indicate that rejection rates are comparable with traditional CNI-based immunosuppression and that two and five yr patient and graft survival are similar, with recovery in renal function. There are few studies evaluating complete avoidance of CNI, apart from that in renal transplantation, although the benefits of long-term reduction in cardiovascular, metabolic, and possibly neoplastic side effects may justify this approach. It is not clear yet how CNI minimization will affect the development of tolerance but experimental and preliminary clinical studies indicate that CNI and steroid avoidance or minimization in the peri-operative period may favor the development of long-term graft tolerance. In summary, CNI minimization may be safe and effective in the short term but large-scale pediatric randomized studies are required to evaluate the long-term efficacy of these regimes in the development of chronic rejection, PTLD, and graft tolerance.     

Do sex-role appropriate materials influence the piagetian task performance of older adults?

The intent of this study was to assess the influence of sex-role appropriate materials on the utilization of logical competence among older persons, and to determine how such materials interact with subject's sex-role identity to affect cognitive performance. Thirty male and 30 female Ss (mean age = 71.3 years) were administered the Short Form of the Bern Sex-Role Inventory and either a male-oriented, a female-oriented, or a traditional version of two concrete operational and two formal operational Piagetian tasks. Gender was found to influence performance on one of the concrete tasks, task orientation influenced performance on one of the formal tasks, and sex-role classification interacted with task orientation to influence performance on both of the formal operational tasks. The pattern of results suggested that subjects may perform best on those versions of the formal operational tasks that do not match their own sex type. Possible explanations for these findings are discussed.     

Long-Term Health and Psychosocial Status of Youth who Received Substance Abuse Treatment in Adolescence

Alcohol and substance abuse in the adolescent population is a major health concern with a number of harms known to be associated with high levels of use. Few studies report on long-term health status of youth who have received treatment for a substance abuse problem during adolescence. This study aimed to describe the long-term status of a cohort of adolescents who received treatment in an intensive day treatment program situated in a tertiary care paediatric hospital. Youth participated in an interview that collected data using both standardized screening tools (GAIN-SS, AUDIT, CUDIT, DUI) as well as closed and open ended questions about education, employment, and physical and mental health status. Young adults in this sample continue to use alcohol and cannabis, with a proportion reporting problematic use. Their academic achievement is close to expected for their age group. They report concurrent mental health disorders; and as a cohort, access the health care system for both acute and chronic health conditions more than their contemporaries. These findings support the inclusion of academic, mental health and medical components in programs for adolescents with substance abuse, in order to address a broad range of determinants of health outcomes.