Applications of bispectral index monitoring in the pediatric intensive care unit

The bispectral index (BIS) monitor is an electroencephalographic recording device that generates a single numeric value. It has traditionally been used to measure anesthetic depth and avoid awareness in the operating room setting. In this report, the authors present different scenarios in the pediatric intensive care unit that demonstrate the potential applications of the BIS monitor outside of the operating room setting. The scenarios presented include use of the BIS monitor during titration of barbiturate coma, procedural sedation, sedation assessment during mechanical ventilation, and sedation while administering potentially confounding medications. Previous reports regarding the use of the BIS monitor in such scenarios and potential future applications are reviewed     

Fatty acids differentially influence phosphatidylinositol 3-kinase signal transduction in endothelial cells: impact on adhesion and apoptosis

In contrast to n-6 fatty acids like arachidonic acid (AA), the anti-inflammatory potential of n-3 fatty acids such as docosahexaenoic acid (DHA) has been demonstrated. We examined the phosphatidylinositol (PI)3-kinase dependent effects of AA versus DHA on monocyte rolling, adhesion and transmigration through inflammatory activated human umbilical venous endothelial cells (HUVEC) as well as on apoptosis, to investigate the impact on vascular inflammation. HUVEC were pre-incubated with AA, DHA or sham, and stimulated with VEGF, TNF-alpha or staurosporine. Rolling and adhesion were investigated by means of a parallel flow chamber; transmigration was performed in a static assay. Activation of PI3-kinase was measured as phosphorylation of protein kinase B (Akt). Apoptosis was determined by caspase-3 activity and annexin-V analysis. Pre-incubation of HUVEC with DHA markedly decreased TNF-alpha-induced monocyte rolling, adhesion, and transmigration, although expression of endothelial adhesion molecules was unchanged. In contrast, AA increased TNF-alpha-induced rolling. Both fatty acids did not alter TNF-alpha-mediated upregulation of the adhesion molecules ICAM-1, VCAM-1, and E-selectin. The divergent effects of AA and DHA were abrogated with PI3-kinase inhibitors. After pre-incubation with DHA, VEGF-, TNF-alpha- and staurosporine-induced phosphorylation of Akt was decreased when compared to AA. DHA pre-incubation significantly increased staurosporine-induced apoptosis. In addition, DHA in comparison to AA augmented staurosporine-mediated increase in caspase-3 activity. In conclusion, DHA-induced a reduction in rolling, adhesion and transmigration of monocytes through inflammatory activated HUVEC that is in part PI3-kinase dependent. PI3-kinase driven phosphorylation of Akt and apoptosis of HUVEC as contribution to the resolution of inflammation is differentially modulated by DHA versus AA.     

Prognostic factors and selection for clinical studies of patients with kidney cancer

Over the past 2 decades, a greater understanding of the basic biology and genetics of kidney cancer has occurred. Surgical techniques have also evolved, and technological advances have made possible new methods of managing renal tumors. The most extensively used system to provide prognostic information for renal cell carcinoma (RCC) is currently the tumor, nodes, metastasis (TNM) staging system. Emerging data over the last few years has questioned whether further revisions are needed and if improvements can be made with the introduction of new, more accurate and predictive prognostic factors. The recent discovery of molecular tumor biomarkers are expected to revolutionize the staging of RCC and potentially lead to the development of new therapies based on molecular targeting. This review will examine the current staging modalities and prognostic factors associated with RCC as well as the selection of patients most likely to benefit from clinical trials.     

Concentrations of lysosomal cysteine proteases are decreased in renal cell carcinoma compared with normal kidney

Renal cell carcinoma contains significantly lower concentrations of the lysosomal cysteine proteases, cathepsins B, C, H, L and S, than does normal kidney, as shown by several methods, such as activity determination, enzyme-linked immunosorbent assay, immunoblotting and immunohistochemistry. The same low levels of enzyme activity and concentration have been determined in renal cell carcinoma metastases in the lung. Our results on the decreased concentration of cysteine peptidases at the protein level would seem to conflict with earlier results on an increased concentration of the cathepsin L mRNA in renal cell carcinoma.Abbreviations ELISA enzyme-linked immunosorbent assay - FCS fetal calf serum - NHMec 7-(4-methyl)coumarylamide - NHNap 2-naphthylamide - Z benzyloxycarbonyl     

Renal insufficiency and long-term mortality and incidence of myocardial infarction in patients undergoing coronary artery bypass grafting.

AIMS: To evaluate the impact of renal insufficiency (RI) on long-term mortality and incident myocardial infarction (MI) in patients undergoing coronary artery bypass grafting (CABG). METHODS AND RESULTS: All patients (n = 6575) without dialysis-dependent RI undergoing a first isolated CABG during 1980-1995 at the Karolinska hospital who survived 30 days post-operatively were included. Estimated glomerular filtration rate (eGFR) was related to the incidence of MI and all-cause mortality within 5 years. There were 628 deaths and 496 incident MIs during follow-up. After multivariable adjustment, patients with mild (eGFR 60-90 mL/min), moderate (eGFR 30-60 mL/min), and severe (eGFR <30 mL/min) RI had an increased mortality within 5 years post-CABG; hazard ratio (HR) 1.2 [95% confidence interval (CI) 1.0-1.6], HR 1.8 (95% CI 1.3-2.4), and HR 5.2 (95% CI 3.1-8.6), respectively, compared with patients with normal renal function (eGFR >90 mL/min). In patients with moderate and severe RI, there was an increased incidence of MI; HR 1.5 (95% CI 1.1-2.1) and HR 3.5 (95% CI 1.8-6.8), respectively. There were no gender differences. CONCLUSION: Already mild RI predicts late all-cause mortality after coronary artery bypass grafting (CABG), and moderate and severe RI is associated with an increased long-term incidence of MI post-CABG.     

Contact force and impedance decrease during ablation depends on catheter location and orientation: insights from pulmonary vein isolation using a contact force-sensing catheter

Journal of Interventional Cardiac Electrophysiology - Contact force (CF) sensing during radiofrequency (RF) ablation allows controlling lesion size. The aim of this study was to analyze the impact...     

Tyrphostin AG126 exerts neuroprotection in CNS inflammation by a dual mechanism

The putative protein tyrosine kinase (PTK) inhibitor tyrphostin AG126 has proven beneficial in various models of inflammatory disease. Yet molecular targets and cellular mechanisms remained enigmatic. We demonstrate here that AG126 treatment has beneficial effects in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. AG126 alleviates the clinical symptoms, diminishes encephalitogenic Th17 differentiation, reduces inflammatory CNS infiltration as well as microglia activation and attenuates myelin damage. We show that AG126 directly inhibits Bruton's tyrosine kinase (BTK), a PTK associated with B cell receptor and Toll‐like receptor (TLR) signaling. However, BTK inhibition cannot account for the entire activity spectrum. Effects on TLR‐induced proinflammatory cytokine expression in microglia involve AG126 hydrolysis and conversion of its dinitrile side chain to malononitrile (MN). Notably, while liberated MN can subsequently mediate critical AG126 features, full protection in EAE still requires delivery of intact AG126. Its anti‐inflammatory potential and especially interference with TLR signaling thus rely on a dual mechanism encompassing BTK and a novel MN‐sensitive target. Both principles bear great potential for the therapeutic management of disturbed innate and adaptive immune functions. GLIA 2015;63:1083–1099