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Assaf C.,Dermatologische Klinik | Assaf C.,Charit Universitatsmedizin Berlin
Aktuelle Dermatologie | Year: 2012

Transcription factors are DNA-binding proteins involved in transcription processes in eukaryotes, by binding parts of promoters or enhancers with high specificity. They can thus regulate genes or complex networks by themselves. On this basis, alteration of a solitary transcription factor may lead to various cellular changes and also to neoplasia. A network of transcription factors, such as E2a, ID-2, NOTCH and PAX5 regulates lymphocytic development into B-, T-, NK- or plasmocytoid dendritic cells. Alterations of these genes via mutation or activation of inhibitors my lead to developmental disorders and also to malignant transformation. In our own investigations we have shown that in Sezary's syndrome genomic deletion of transcription factor E2A may be detected in 70% of the cases, resulting in deregulation of a series of oncogenes and other transcription factors responsible for cell proliferation and transformation. © Georg Thieme Verlag KG Stuttgart.

Kadmon M.,Universitatsklinik Heidelberg | Busemann A.,Universitatsmedizin Greifswald | Euteneier A.,Klinik fur Unfallchirurgie und Orthopadie | Gawad K.,Hospital zum Heiligen Geist | And 2 more authors.
Zentralblatt fur Chirurgie - Zeitschrift fur Allgemeine, Viszeral- und Gefasschirurgie | Year: 2012

Background: The quality of postgraduate training is an important motivating factor for the career decisions of young doctors and has an impact on the satisfaction of postgraduate trainees. In Germany, we still lack a postgraduate training programme in surgery that defines the competency profile at the time of certification. This article describes the development of a national modular competency-based core curriculum for postgraduate surgery training as well as first experience and evaluation data from the initial period of implementation. Methods: The curriculum was developed in a group of highly motivated surgeons according to the "Kern-cycleo", a conceptual framework for curriculum development in medicine, and includs considerations from the "CanMEDSo"-competency framework for physicians. The curriculum follows a "blended learningo" concept with modular attendance courses and associated preparatory online courses. The didactics follows the principles of adult learning and are characterised by learner-centred, self-directed learning processes in small groups with feedback. The initial implementation phase was accompanied by a detailed evaluation of the general concept as well as the quality of content and didactics of the attendance courses. Results: Seven of the planned 12attendance courses have been designed, 6courses have been implemented2q1. Altogether 562participants from hospitals of all levels of patient care took part in the attendance courses, some of them in several courses. The gender distribution was almost balanced with a slight female surplus. The majority of participants were supported by their clinics through exemption from clinical work or financial sponsoring. 80 % of the participants completed the evaluation of the attendance courses. The data show a high degree of participant satisfaction with the content and didactic concept of the courses, as well as with the surrounding conditions and the commitment of the trainers. Conclusions: The evaluation data on the attendance courses implemented reveal a high acceptance among participants concerning the overall concept of the modular postgraduate training programme as well as the support of the programme by surgeons responsible for postgraduate training. © 2012 Georg Thieme Verlag KG Stuttgart • New York.

New oral anticoagulants (NOACs) such as the direct factor IIa inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban and apixaban demonstrate pharmacological characteristics that result in desirable and significant advantages in comparison to previous available antithrombotic treatment strategies. Thus, they allow oral application and show a rapid onset and offset of action. Amajor advantage results from their predictable pharmacokinetic and pharmacodynamic profile. Consequently, these NOACs can be administered at fixed doses without the need for routine coagulation monitoring. Nevertheless, when using these drugs some restrictions have to be considered, e.g. in patients with renal impairment and with regard to co-medications. Moreover, some aspects of their use in daily practice are not (well) established, such as monitoring of anticoagulatory effects in specific clinical situations, reversal of their effects and the potential use of antidotes in patients with major bleedings. In this regard, knowledge of the pharmacological characteristics of NOACs can provide an important and necessary basis for clinical decision making. © Georg Thieme Verlag KG Stuttgart · New York.

Papageorgiou A.-P.,Maastricht University | Papageorgiou A.-P.,Catholic University of Leuven | Swinnen M.,Catholic University of Leuven | Vanhoutte D.,Catholic University of Leuven | And 16 more authors.
Cardiovascular Research | Year: 2012

Aims: Thrombospondin-2 (TSP-2) modulates matrix integrity and myocyte survival in the hypertensive or ageing heart. Whether TSP-2 may affect cardiac inflammation and injury, in particular during acute viral myocarditis, is completely unknown. Methods and results: Therefore, mortality, cardiac inflammation, and function were assessed in TSP-2-null (KO) and wild-type (WT) mice in human Coxsackie virus B3 (CVB3)-induced myocarditis. TSP-2 KO had an increased mortality when compared with WT mice during viral myocarditis. The absence of TSP-2 resulted in increased cardiac inflammation and injury at 14 days, which resulted in depressed systolic function [fractional shortening (FS); 34 ± 2.6 in WT vs. 24 ± 1.8 in KO mice, P< 0.05] and increased cardiac dilatation (end-diastolic dimensions, mm; 3.7 ± 0.09 in WT vs. 4.8 ± 0.06 in KO mice, P< 0.05) 35 days post-infection. Lack of TSP-2 resulted in a decreased activation of the anti-inflammatory T-regulatory cells, as indicated by a lower number of CD25-positive T-cells, and significantly decreased gene expression of regulatory T-cell markers, Foxp3 and CTLA-4. Finally, overexpression of TSP-2 in WT hearts using cardiotropic vectors derived from adeno-associated virus serotype 9 (AAV9) inhibited cardiac inflammation and injury at 14 days and improved cardiac function at 35 days post-CVB3 infection when compared with control AAV9. Conclusion: TSP-2 has a protective role against cardiac inflammation, injury, and dysfunction in acute viral myocarditis. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2012.

Several new international recommendations have been published since the German Central Committee against Tuberculosis (DZK) published its recommendations for drug treatment of tuberculosis (TB) in 2001 and for chemoprevention of latent tuberculosis infection (LTBI) in 2004. These international publications have been integrated in the present new recommendations which describe both the treatment of active TB and preventive treatment, pointing out specific adaptations for Germany. Separate sections deal with the current management of mono-, poly-, and multiresistance or drug intolerance, of TB in children, of different forms of extrapulmonary TB, of LTBI and of special situations such as HIV infection, renal or hepatic insufficiency, infection following BCG instillation in bladder cancer or in case of adverse drug reactions. The following aspects differ from the previous recommendations: A three-drug regimen for the so-called fully susceptible minimal TB is no longer recommended in adults. A dosage of 15 mg/kg body weight of ethambutol for adults is regarded as sufficient. Four secondline drugs (supplemented by pyrazinamide, where appropriate) are recommended for multidrug-resistant tuberculosis (MDR-TB). MDR-TB should be treated over a period of at least 20 months, with an injectable drug administered for a minimum of 8 months (initial phase). Ciprofloxacine and ofloxacine are no longer used to treat TB. It is also recommended to offer an HIV test to all TB patients to complement antiretroviral therapy, if necessary, and to adapt the antituberculous therapy accordingly. © Georg Thieme Verlag KG Stuttgart - New York.

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