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Heidelberg, Germany

Jox R.J.,Ludwig Maximilians University of Munich | Winkler E.C.,Universitatsklinik Heidelberg | Borasio G.D.,University of Lausanne
Deutsche Medizinische Wochenschrift

Background and objective: Deciding about treatment goals at the end of life is a frequent and difficult challenge to medical staff. As more health care institutions issue ethico-legal guidelines to their staff the effects of such a guideline should be investigated in a pilot project. Participants and methods: Prospective evaluation study using the pre-post method. Physicians and nurses working in ten intensive care units of a university medical center in Germany answered a specially designed questionnaire before and one year after issuance of the guideline. Results: 197 analyzable answers were obtained from the first (pre-guideline) and 251 from the second (post-guideline) survey (54 % and 58 % response rate, respectively). Initially the clinicians expressed their need for guidelines, advice on ethical problems, and continuing education. One year after introduction of the guideline one third of the clinicians was familiar with the guideline's content and another third was aware of its existence. 90% of those who knew the document welcomed it. Explanation of the legal aspects was seen as its most useful element. The pre- and post-guideline comparison demonstrated that uncertainty in decision making and fear of legal consequences were reduced, while knowledge of legal aspects and the value given to advance directives increased. The residents had derived the greatest benefit. Conclusion: By promoting the knowledge of legal aspects and ethical considerations, guidelines given to medical staff can lead to more certainty when making in end of life decision. © Georg Thieme Verlag KG Stuttgart · New York. Source

Berlit P.,Klinik fur Neurologie | Schonenberger S.,Universitatsklinik Heidelberg
Aktuelle Neurologie

There is an increased incidence of stroke during pregnancy of 25 to 34 per 100.000. Important causes include preeclampsia, eclampsia, sinus- and vein thrombosis as well as the reversible cerebral vasoconstriction syndrome (RCVS, post partum angiopathy). Thrombotic thrombocytopenic purpura (TTP) and sickle cell anemia are coagulopathies which often manifest during pregnancy for the first time. Important are the early diagnosis and a focused interdisciplinary management of these patients. Intravenous thrombolysis and endovascular thrombectomy are individual treatment options during pregnancy. © Georg Thieme Verlag KG Stuttgart • New York. Source

Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors worldwide with poor prognosis. Based on high-throughput screening technology, we and others have identified factors and pathways that are pivotal for tumor progression including trans- cription factors and microtubule-interacting proteins. In addition, aberrant activation of the IGF signalling pathway is frequently observed in HCCs which is predominantly based on high level expression of its ligand IGF-II. Because protumorigenic effects of IGF-II such as proliferation, anti-apoptosis, and migration are transmitted through its receptor IGF-1R, selective inhibition of this tyrosine kinase by small molecule compounds might reduce IGF-II-driven tumor growth. Indeed, administration of IGF-1R-selective inhibitors reduces IGF-II-induced effects and was associated with a significant reduction of tumor growth in a xenograft transplantation model. In conclusion, the IGF-II/IGF-1R signalling pathway is critically involved in the regulation of tumor growth and tumor cell dissemination, representing a promising therapeutic target structure in the treatment of HCC. © Springer-Verlag 2010. Source

Up to 5% of all bone fractures show impaired healing and the bridging of large bony defects still represents a challenge for the orthopedic surgeon. In recent years, methods to promote in-situ regeneration based on non-vital components like bone substitute materials and growth factors have found successful entrance to the clinic. However, the application of vital components such as in-vitro cultured cells in combination with supporting carriers and/or biomolecules, thus tissue-engineered products, is less common for the regeneration of bone. In contrast to cartilage, bone tissue represents a cell-rich and well-vascularized tissue. Consequently, a functional interplay of supporting osteoconductive bone graft substitutes, osteoinductive stimuli and osteogenic cells is important and necessary for the regeneration of large bone defects. The additional provision of high quantities of autologous stem cells for bone tissue engineering strategies may be promising for a steadily aging population as well as for high-performance sports, where fast regeneration and full load-bearing capacity of the reconstructed bone are required. The article summarizes donor-dependent aspects of human mesenchymal stem cells and their suitability for bone tissue engineering. Additionally, new approaches for the in-situ regeneration of bone and relevant regulatory statutes due to the classification of tissue-engineered products as pharmaceuticals in Europe will be discussed. Source

Zoller F.,German Cancer Research Center | Markert A.,German Cancer Research Center | Barthe P.,Montpellier University | Zhao W.,Universitatsklinik Heidelberg | And 5 more authors.
Angewandte Chemie - International Edition

Peptides are of growing interest as a non-immunoglobulin alternative for the development of new molecular entities. Disulfide-stabilized miniproteins are a class of peptides that represent an ideal template for the development of stable affinity reagents in drug design, molecular diagnostics, and targeted therapy. This is due to their outstanding proteolytic stability, their small size, and especially their tolerance to mutagenesis. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

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