Anaesthetic considerations for interventional neuroradiology

In the past decade, the neuroradiological diagnosis and treatmentof cerebrovascular diseases has undergone significant advances.With the introduction of varying diagnostic and interventionalneuroradiological techniques and advances in the materials usedfor endovascular treatment, increasingly complex diagnosticand therapeutic neuroradiological procedures are being performedon extremely sick patients. As the interventional neuroradiologyfield expands, the neuroanaesthetist will become more involvedin management of patients undergoing neuroradiological procedures.This produces challenges for the neuroanaesthetist, and understandingthe anaesthetic implications of the current developments inneuroradiology is important in the management of these patients.This review provides an overview of diagnostic and therapeuticneuroradiological procedures, with special reference interventionalneuroradiology, and the anaesthetic management of patients undergoingthese procedures.     

Genomic complexity and AKT dependence in serous ovarian cancer

Effective oncoprotein-targeted therapies have not yet been developed for ovarian cancer. To explore the role of PI3 kinase/AKT signaling in this disease, we performed a genetic and functional analysis of ovarian cancer cell lines and tumors. PI3K pathway alterations were common in both, but the spectrum of mutational changes differed. Genetic activation of the pathway was necessary, but not sufficient, to confer sensitivity to selective inhibition of AKT and cells with RAS pathway alterations or RB1 loss were resistant to AKT inhibition, whether or not they had coexistent PI3K/AKT pathway activation. Inhibition of AKT1 caused growth arrest in a subset of ovarian cell lines, but not in those with AKT3 expression, which required pan-AKT inhibition. Thus, a subset of ovarian tumors are sensitive to AKT inhibition, but the genetic heterogeneity of the disease suggests that effective treatment with AKT pathway inhibitors will require a detailed molecular analysis of each patient's tumor. SIGNIFICANCE: A subset of ovarian cancers exhibits AKT pathway activation and is sensitive to selective AKT inhibition. Ovarian tumors exhibit significant genetic heterogeneity and thus an individualized approach based on real-time, detailed genomic and proteomic characterization of individual tumors will be required for the successful application of PI3K/AKT pathway inhibitors in this disease.     

Recommendations for the optimal care of patients with recent‐onset psychosis in the Asia‐Pacific region

Providing optimal care to patients with recent‐onset psychosis can improve outcomes and reduce relapse. However, there is a lack of consistency of the implementation of guidelines for such patients across the Asia‐Pacific region. We determined a pragmatic set of recommendations for use on a day‐to‐day basis to help provide optimal care at this crucial stage of illness. The recommendations were developed over a series of meetings by an international faculty of 15 experts from the Asia‐Pacific region, Europe, and South Africa. A structured search of the PubMed database was conducted. This was further developed based on the faculty's clinical experience and knowledge of the literature into 10 key aspects of optimal care for patients during the first five years of a diagnosis of a psychotic disorder, with particular relevance to the Asia‐Pacific region. Several common principles emerged: adherence to antipsychotic medications is crucial; substance abuse, psychiatric and medical comorbidities should be addressed; psychosocial interventions play a pivotal role; and family members can play a vital role in overall patient care. By following these recommendations, clinicians may improve outcomes for patients with recent‐onset psychosis.     

Computer‐assisted pathological immunohistochemistry scoring is more time‐effective than conventional scoring,but provides no analytical advantage

Ong C W, Kim L G, Kong H H, Low L Y, Wang T T, Supriya S, Kathiresan M, Soong R & Salto‐Tellez M
(2010) Histopathology 56 , 523–529 Computer‐assisted pathological immunohistochemistry scoring is more time‐effective than conventional scoring, but provides no analytical advantage Aims: Interpretation of immunohistochemistry is primarily done through human visual scoring while computer‐assisted scoring is relatively uncommon. This study aimed to examine (i) the level of agreement between human visual and computer‐assisted pathological scoring of immunoreactivity expression in colorectal cancers, (ii) whether computer‐assisted scoring affects the prognostic significance of biomarkers, and (iii) whether computer‐assisted pathological scoring provides any time‐saving or reproducibility advantages. Methods and results: Tissue microarray blocks were constructed from the primary colorectal adenocarcinoma specimens of 486 patients. Scoring of the six markers [cytokeratin (CK) 7, CK20, cyclooxygenase‐2, Ki67, p27 and p53] was done independently by a qualified pathologist, a trained scientist and the Ariol SL‐50 (Applied Imaging). Univariate analysis showed that human visual and computer‐assisted scoring were strongly correlated (all κ values >0.8). Both human visual and computer‐assisted pathological scoring identified the same set of biomarkers with significant association with survival. Computer‐assisted pathological scoring was shown to be a time‐effective means of scoring larger numbers of slides (for high‐throughput studies). Conclusions: Our results suggest that computer‐assisted pathological scoring can be a viable alternative to pathologist scoring in a manner that is more practical and time‐effective, but, interestingly, providing no analytical advantage.     

Regulation of alpha-fetoprotein by nuclear factor-kappaB protects hepatocytes from tumor necrosis factor-alpha cytotoxicity during fetal liver development and hepatic oncogenesis

Nuclear factor-kappaB (NF-kappaB) plays a critical role during fetal liver development and hepatic oncogenesis. Here, we have assessed whether NF-kappaB activity is required for murine hepatocellular carcinoma cell survival. We show that adenoviral-mediated inhibition of inhibitor of NF-kappaB kinase-beta (IKK-2) activity in hepatocellular carcinomas derived from transforming growth factor (TGF)-alpha/c-myc bitransgenic mice leads to inhibition of NF-kappaB and promotes tumor necrosis factor (TNF)-alpha-mediated cell death of malignant hepatocytes but not the surrounding peritumorous tissue. Induction of apoptosis is accompanied by inhibition of Bcl-X(L) and XIAP, two pro-survival NF-kappaB target genes. In addition, we have identified the alpha-fetoprotein (AFP) as a novel downstream target of NF-kappaB. We show that repression of IKK-2 activity in hepatocellular carcinomas promotes down-regulation of AFP gene expression. Likewise, genetic disruption of the RelA subunit results in reduced AFP gene expression during embryonic liver development, at a time in which fetal hepatocytes are sensitized to TNF-alpha-mediated cell killing. In this regard, we show that AFP inhibits TNF-alpha-induced cell death of murine hepatocellular carcinomas through association with TNF-alpha and inhibition of TNFRI signaling. Thus, NF-kappaB-mediated regulation of AFP gene expression during liver tumor formation and embryonic development of the liver constitutes a potential novel mechanism used by malignant and fetal hepatocytes to evade immune surveillance.