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Sinn M.,ChariteUniversitatsmedizin Berlin
British Journal of Cancer | Year: 2014

Background:Previous investigations in pancreatic cancer suggest a prognostic role for α-smooth muscle actin (α-SMA) expression and stromal density in the peritumoural stroma. The aim of this study was to further validate the impact of α-SMA expression and stromal density in resectable pancreatic cancer patients treated with adjuvant gemcitabine compared with untreated patients.Methods:CONKO-001 was a prospective randomised phase III study investigating the role of adjuvant gemcitabine as compared with observation. Tissue samples of 162 patients were available for immunohistochemistry on tissue microarrays to evaluate the impact of α-SMA expression and stromal density impact on patient outcome.Results:High α-SMA expression in tumour stroma was associated with worse patient outcome (DFS: P=0.05, OS: P=0.047). A dense stroma reaction was associated with improved disease-free survival (DFS) and overall survival (OS) in the overall study population (DFS: P=0.001, OS: P=0.001). This positive prognostic impact was restricted to patients with no adjuvant treatment (DFS: P<0.001, OS: P<0.001). In multivariable analysis, α-SMA and stromal density expression were independently predictive factors for survival.Conclusions:Our data confirm the negative prognostic impact of high α-SMA expression in pancreatic cancer patients after curatively intended resection. In contrast to former investigations, we found a positive prognostic impact for a dense stroma. This significant influence was restricted to patients who received no adjuvant therapy.British Journal of Cancer advance online publication, 14 October 2014; doi:10.1038/bjc.2014.495 www.bjcancer.com. © 2014 Cancer Research UK

Tuvia S.,Chiasma | Atsmon J.,Tel Aviv University | Teichman S.L.,Chiasma | Katz S.,Chiasma | And 9 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: Oral administration of a novel octreotide formulation enabled its absorption to the systemic circulation, exhibiting blood concentrations comparable to those observed with injected octreotide and maintaining its biological activity. Objectives: The aim of the study was to determine oral octreotide absorption and effects on pituitary GH secretion compared to sc octreotide injection. Design: Four single-dose studies were conducted in 75 healthy volunteers. Intervention: Oral doses of 3, 10, or 20 mg octreotide and a single sc injection of 100-g octreotide were administered. Main Outcome Measure: We measured the pharmacokinetic profile of orally administrated octreotide and the effect of octreotide on basal and stimulated GH secretion. Results: Both oral and sc treatments were well tolerated. Oral octreotide absorption to the circulation was apparent within 1 h after dose administration. Escalating oral octreotide doses resulted in dose-dependent increased plasma octreotide concentrations, with an observed rate of plasma decay similar to parenteral administration. Both 20 mg oral octreotide and injection of 0.1 mg sc octreotide resulted in equivalent pharmacokinetic parameters [mean peak plasma concentration, 3.77 ± 0.25 vs. 3.97 ± 0.19 ng/ml; mean area under the curve, 16.2 ± 1.25 vs. 12.1 ± 0.45 hxng/ml); and median time ≥0.5 ng/ml, 7.67 vs. 5.88 h, respectively). A single dose of 20 mg oral octreotide resulted in basal (P < 0.05) and GHRH-stimulated (P < 0.001) mean GH levels suppressed by 49 and 80%, respectively. Conclusions: The results support an oral octreotide alternative to parenteral octreotide treatment for patients with acromegaly. Copyright © 2012 by The Endocrine Society.

Knecht S.,Universitatsklinikum Munster | Hesse S.,ChariteUniversitatsmedizin Berlin | Oster P.,Geriatrisches Zentrum
Deutsches Arzteblatt | Year: 2011

Background: Stroke is becoming more common in Germany as the population ages. Its long-term sequelae can be alleviated by early reperfusion in stroke units and by complication management and functional restoration in early-rehabilitation and rehabilitation centers. Methods: Selective review of the literature. Results: Successful rehabilitation depends on systematic treatment by an interdisciplinary team of experienced specialists. In the area of functional restoration, there has been major progress in our understanding of the physiology of learning, relearning, training, and neuroenhancement. There have also been advances in supportive pharmacotherapy and robot technology. Conclusion: Well-organized acute and intermediate rehabilitation after stroke can provide patients with the best functional results attainable on the basis of our current scientific understanding. Further experimental and clinical studies will be needed to expand our knowledge and improve the efficacy of rehabilitation.

Audebert H.J.,ChariteUniversitatsmedizin Berlin | Fiebach J.B.,ChariteUniversitatsmedizin Berlin
Current Neurology and Neuroscience Reports | Year: 2015

In acute stroke, imaging provides different technologies to demonstrate stroke subtype, tissue perfusion and vessel patency. In this review, we highlight recent clinical studies that are likely to guide therapeutic decisions. Clot length in computed tomography (CT) and clot burden in MR, imaging of leptomeningeal collaterals and indicators for active bleeding are illustrated. Imaging-based concepts for treatment of stroke at awakening and pre-hospital treatment in specialized ambulances offer new potentials to improve patient outcome. © 2015, Springer Science+Business Media New York.

Christen M.,University of Zurich | Muller S.,ChariteUniversitatsmedizin Berlin
Current Topics in Behavioral Neurosciences | Year: 2015

Understanding how the “brain produces behavior” is a guiding idea in neuroscience. It is thus of no surprise that establishing an interrelation between brain pathology and antisocial behavior has a long history in brain research. However, interrelating the brain with moral agency—the ability to act in reference to right and wrong—is tricky with respect to therapy and rehabilitation of patients affected by brain lesions. In this contribution, we outline the complexity of the relationship between the brain and moral behavior, and we discuss ethical issues of the neuroscience of ethics and of its clinical consequences. First, we introduce a theory of moral agency and apply it to the issue of behavioral changes caused by brain lesions. Second, we present a typology of brain lesions both with respect to their cause, their temporal development, and the potential for neural plasticity allowing for rehabilitation. We exemplify this scheme with case studies and outline major knowledge gaps that are relevant for clinical practice. Third, we analyze ethical pitfalls when trying to understand the brain–morality relation. In this way, our contribution addresses both researchers in neuroscience of ethics and clinicians who treat patients affected by brain lesions to better understand the complex ethical questions, which are raised by research and therapy of brain lesion patients. © Springer-Verlag Berlin Heidelberg 2014.

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