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Maass N.,Universitatsfrauenklinik Aachen | Harbeck N.,Ludwig Maximilians University of Munich | Mundhenke C.,Universitatsklinikum Schleswig | Lerchenmuller C.,Gemeinschaftspraxis Dres. Wehmeyer | And 16 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2013

Purpose: Everolimus has shown to stop formation and activity of osteoclasts. Breast cancer patients with bone metastases only are candidates for effective but low toxic treatment. Patients and methods: We evaluated everolimus in a double-blind, placebo-controlled, phase II, randomized discontinuation study in breast cancer patients with HER2 negative breast cancer patients with bone metastases only. After being stable on 8 weeks of everolimus 10 mg/day, patients were randomized to everolimus-continuation or placebo. Primary outcome was time (from randomization) to progression (TTP). Seventy-six patients would have had to be randomized to show a hazard ration (HR) of 0.5 for everolimus-continuation. Results: Eighty-nine patients were enrolled in 4 years. Thirty-nine patients with SD after 8 weeks on everolimus were randomized to everolimus-continuation or placebo. TTP in patients with everolimus- continuation was 37.0 (95 % CI 16.7-40.3) versus 12.6 weeks (95 % CI 7.1-17.9) with placebo [HR 0.554 (95 % CI 0.282-1.09) p = 0.0818], adjusted for endocrine therapy [HR 0.464 (95 % CI 0.226-0.954) p = 0.037]. TTP in everolimus responders (n = 6) was 86 weeks. Conclusion: The RADAR study is mainly hypothesis generating. It suggests that everolimus has single-agent activity, and patients with bone metastases only may retrieve long-term benefit from everolimus if they do not progress within 8 weeks of treatment. © 2013 Springer-Verlag Berlin Heidelberg.

Lettau I.,University of Kiel | Hattermann K.,University of Kiel | Held-Feindt J.,Universitatsklinikum Schleswig | Brauer R.,Institute of Molecular Genetics | And 2 more authors.
Journal of Neuropathology and Experimental Neurology | Year: 2010

Glial tumors exhibit a high morbidity and mortality because of their invasive nature. Matrix metalloproteinase 19 (MMP19) is a secreted protease that together with epilysin (MMP28) forms a structural subgroup of MMPs. We analyzed their expression by quantitative reverse transcription polymerase chain reaction, Western blot, and immunohistochemistry in tumor and normal control brain tissues and in glioblastoma (GB) cells and performed MMP19 silencing functional assays. Matrix metalloproteinase 28 was transcribed to the same extent in normal brain samples and gliomas but was undetectable in GB cell lines. In contrast, MMP19 was detected by immunohistochemistry in normal brain samples only in endothelial cells but was found at high levels in astrocytomas of different World Health Organization grades in situ and in GB cells in vitro. Matrix metalloproteinase 19 was upregulated in GB cells after exposure to proinflammatory cytokines. In Transwell invasion assays, MMP19-silenced cells migrated more slowly through laminin-, basal lamina-, and brevican-coated membranes than controls. Matrix metalloproteinase 19-silenced GB cells also migrated into brain tissue slices compared with control cells. Brevican, a brain-specific proteoglycan and major component of brain extracellular matrix, was degraded by recombinant human MMP19. Taken together, these results indicate that MMP19 is highly expressed in proliferating astrocytoma/glioma cells, and that its expression may facilitate their invasion through brain extracellular matrix components. Copyright © 2010 by the American Association of Neuropathologists, Inc.

Reifferscheid F.,Universitatsklinikum Schleswig | Reifferscheid F.,Arbeitsgemeinschaft in Norddeutschland Tatiger Notarzte E.V. | Dorges V.,Universitatsklinikum Schleswig | Dorges V.,Arbeitsgemeinschaft in Norddeutschland Tatiger Notarzte E.V. | And 4 more authors.
Notarzt | Year: 2010

Due to a current shortage of doctors and an increasing number of emergency calls in an ageing population emergency physicians in Germany face new challenges. With the aim of providing a high level of quality nationwide a specialist designation in emergency medicine was introduced in 2003. While the curriculum regulates the contents of theoretical training, the duration and requirements to be met by physicians wishing to work in the field of pre-hospital emergency medicine differ between the various German State Chambers of Physicians. Also, there is no uniform regulation of training in the ambulance services. The specialist designation in emergency medicine is an attractive specialisation for the anaesthetist and raises the attractiveness of the speciality. However, further standardisation of specialist training is required. Uniform concepts for training and continuing medical education are needed to provide patients with life-threatening conditions with the highest level of medical care by a physician at the scene of the emergency. © Georg Thieme Verlag KG Stuttgart New York.

Reifferscheid F.,Universitatsklinikum Schleswig | Reifferscheid F.,Arbeitsgemeinschaft in Norddeutschland Tatiger Notarzte E.V. | Harding U.,Universitatsklinikum Munster | Harding U.,Arbeitsgemeinschaft in Norddeutschland Tatiger Notarzte E.V. | And 6 more authors.
Anasthesiologie und Intensivmedizin | Year: 2010

Background: With the aim of providing higher quality pre-hospital emergency care the German Medical Association reformed the specialist qualification programme in emergency medicine and defined a relevant curriculum. The present article analyses to what extend this new curriculum has been adopted by the 17 State Chambers of Physicians in Germany. Methods: All State Chambers of Physicians in Germany were invited to complete a standardised questionnaire regarding the requirements to be met by physicians wishing to work in the field of pre-hospital emergency medicine. Additional data was requested regarding the applicantś clinical experience, training in critical care, and the duration and requirements for practical training in emergency medicine. State Chambers that failed to return the questionnaire were contacted by telephone. Results: Eight State Chambers returned the completed questionnaire, and the relevant information from the other states was obtained by telephone interview as well as from a synopsis provided by the German Medical Association. Twelve State Chambers offer only the new curriculum whilst five offer both the old and new curriculum. Differences in the requirements for admission to the curriculum can be found with regard to the duration of clinical experience and practical training including the number of patients treated, and admission to the final exam. Conclusions: The new curriculum was introduced in order to create a uniform level of education for emergency physicians. However, in 2009 the qualification of emergency physicians remains heterogeneous: the new curriculum is mandatory only in some states, and official recognition of physicians who were trained in accordance with the old curriculum differs from state to state. © Anästh Intensivmed 2010.

Hanewinkel R.,Institute For Therapie Und Gesundheitsforschung Ift Nord | Hanewinkel R.,Universitatsklinikum Schleswig | Blohmke S.,Universitatsklinikum Schleswig | Sargent J.D.,Norris Cotton Cancer Center
Gesundheitswesen | Year: 2012

Aim: The aim of this study was to examine whether smoking in movies can predict established smoking in adolescence. Methods: A longitudinal study was conducted over a period of 13 months with 4112 German students. Adolescents exposure to smoking in movies was assessed by asking each student to indicate which film he or she had seen from a unique list of 50 movies, which was randomly selected for each individual survey from a sample of 398 popular contemporary movies. We calculated exposure to movie smoking for each respondent by summing the number of smoking occurrences for each movie that the respondent reported seeing. Results: At follow-up, a total of 272 young people had smoked more than 100 cigarettes during their lifetime. While 2.1% of the young people with the lowest exposure to movie smoking initiated established smoking, 13.4% of the group with the highest exposure to movie smoking initiated established smoking. The adjusted relative risk of initiation of established smoking was 2.05 times higher in the group with the highest movie smoking exposure compared to the group with the lowest exposure (95% confidence interval: 1.25-3.35). Conclusion: Our data indicate that smoking in movies can be regarded as an independent risk factor for the initiation of established smoking in adolescence. © Georg Thieme Verlag KG Stuttgart - New York.

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