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Zürich, Switzerland

Retterspitz M.F.,University of Cologne | Monig S.P.,University of Cologne | Schreckenberg S.,University of Cologne | Schneider P.M.,University Hospital Zuerich | And 3 more authors.
Anticancer Research

Previous studies on the immunoreactivity of β-catenin, MUC1 and c-met in gastric carcinomas regarding survival and clinico-pathological features led to contradictory results. Therefore, a series of 94 diffuse-type and mixed-type subcardial gastric carcinomas according to the Laurén classification were investigated to elucidate possible correlations with clinico-pathological and prognostic data. An immunohistochemical study was performed to detect the expression of β-catenin, MUC1 and c-met. Loss of membranous I cytoplasmic β-catenin expression in the tumour centre correlated with pT, loss at the invasion front with pTNM stage. MUC1 expression in the tumour centre correlated with lymph node metastasis and pTNM stage. c-Met did not show such associations. In multivariate survival analysis, loss of membranous/ cytoplasmic β-catenin expression as well as a strong MUC1 expression at the tumour invasion front represent independent predictors of a worse prognosis. On the other hand, c-met expression did not exhibit any prognostic value in this study. Source

Gruber C.,Medical University of Vienna | Nabecker S.,Medical University of Vienna | Wohlfarth P.,Medical University of Vienna | Ruetzler A.,Social Medical Center East | And 6 more authors.
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine

Introduction: Airway management is an important component of cardiopulmonary resuscitation (CPR). Recent guidelines recommend keeping any interruptions of chest compressions as short as possible and not lasting more than 10 seconds. Endotracheal intubation seems to be the ideal method for establishing a secure airway by experienced providers, but emergency medical technicians (EMT) often lack training and practice. For the EMTs supraglottic devices might serve as alternatives.Methods: 40 EMTs were trained in a 1-hour standardised audio-visual lesson to handle six different airway devices including endotracheal intubation, Combitube, EasyTube, I-Gel, Laryngeal Mask Airway and Laryngeal tube. EMTs performances were evaluated immediately after a brief practical demonstration, as well as after 1 and 3 months without any practice in between, in a randomised order. Hands-off time was pair-wise compared between airway devices using a repeated-measures mixed-effects model.Results: Overall mean hands-off time was significantly (p<0.01) lower for Laryngeal tube (6.1s; confidence interval 5.2-6.9s), Combitube (7.9s; 95% CI 6.9-9.0s), EasyTube (8.8s; CI 7.3-10.3s), LMA (10.2s; CI 8.6-11.7s), and I-Gel (11.9s; CI 10.2-13.7s) compared to endotracheal intubation (39.4s; CI 34.0-44.9s). Hands-off time was within the recommended limit of 10s for Combitube, EasyTube and Laryngeal tube after 1 month and for all supraglottic devices after 3 months without any training, but far beyond recommended limits in all three evaluations for endotracheal intubation.Conclusion: Using supraglottic airway devices, EMTs achieved a hands-off time within the recommended time limit of 10s, even after three months without any training or practice. Supraglottic airway devices are recommended tools for EMTs with lack of experience in advanced airway management. © 2013 Gruber et al; licensee BioMed Central Ltd. Source

Hornemann T.,University Hospital Zuerich | Worgall T.S.,Columbia University

The atherosclerotic lesion contains a high amount of sphingolipids, a large group of structurally diverse lipids that regulate distinct biological functions beyond their role as structural membrane components. Assessment of their role in atherogenesis has been enabled after genes that regulate their metabolism had been identified and facilitated by the more wide availability of mass spectrometry. Here we discuss recent mechanistic insights obtained in animal and epidemiological studies that have greatly enhanced our understanding of mechanisms how sphingolipids affect the atherosclerotic process. © 2012 Elsevier Ireland Ltd. Source

Stover J.F.,University Hospital Zuerich | Belli A.,University of Southampton | Boret H.,HIA Sainte Anne | Bulters D.,University of Southampton | And 6 more authors.
Journal of Neurotrauma

Traumatic brain injury (TBI) is an important cause of death and disability. Safety and pharmacodynamics of 4-amino-tetrahydrobiopterin (VAS203), a nitric oxide (NO)-synthase inhibitor, were assessed in TBI in an exploratory Phase IIa study (NOSynthase Inhibition in TRAumatic brain injury=NOSTRA). The study included 32 patients with TBI in six European centers. In a first open Cohort, eight patients received three 12-h intravenous infusions of VAS203 followed by a 12-h infusion-free interval over 3 days (total dose 15 mg/kg). Patients in Cohorts 2 and 3 (24) were randomized 2:1 to receive either VAS203 or placebo as an infusion for 48 or 72 h, respectively (total dose 20 and 30 mg/kg). Effects of VAS203 on intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain metabolism using microdialysis, and the therapy intensity level (TIL) were end points. In addition, exploratory analysis of the extended Glasgow Outcome Score (eGOS) after 6 months was performed. Metabolites of VAS203 were detected in cerebral microdialysates. No significant differences between treatment and placebo groups were observed for ICP, CPP, and brain metabolism. TIL on day 6 was significantly decreased (p<0.04) in the VAS203 treated patients. The eGOS after 6 months was significantly higher in treated patients compared with placebo (p<0.01). VAS203 was not associated with hepatic, hematologic, or cardiac toxic effects. At the highest dose administered, four of eight patients receiving VAS203 showed transitory acute kidney injury (stage 2-3). In conclusion, the significant improvement in clinical outcome indicates VAS203-mediated neuroprotection after TBI. At the highest dose, VAS203 is associated with a risk of acute kidney injury. © Mary Ann Liebert, Inc. Source

Wulfanger J.,Martin Luther University of Halle Wittenberg | Schneider H.,Martin Luther University of Halle Wittenberg | Wild P.,University Hospital Zuerich | Ikenberg K.,University Hospital Zuerich | And 5 more authors.

Aminopeptidase N (APN)/CD13 as ubiquitously expressed membrane peptidase exerts important functions in diverse cellular processes, such as proliferation, migration and differentiation. Previously, a role of APN in the invasiveness of melanoma cells has been demonstrated, but the underlying molecular mechanisms controlling APN expression are not understood. The present study demonstrates that lack of APN expression in primary and established melanoma cells was directly associated with a high-grade DNA methylation status of the myeloid APN promoter. Demethylation by 5-aza-2'-desoxycytidine not only induced constitutive and cytokine-regulated APN protein expression but also resulted in an increased APN-dependent migration of melanoma cells. Furthermore, its heterogeneous expression was inversely correlated to the expression of melanocytic marker proteins in established as well as in short-term cultured human melanoma cells. Staining of tissue microarrays generated from a large series of melanoma samples and control tissues demonstrated a higher APN expression in primary melanoma lesions when compared with nevi and metastases, which was neither associated with clinico-pathological parameters nor with the patients' outcome. Thus, the heterogeneous APN expression pattern in melanoma cells is epigenetically controlled and directly associated with an altered migration capacity but not of clinical significance in our study group. © The Author 2012. Published by Oxford University Press. All rights reserved. Source

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