NaV1.5 and interacting proteins in human arrhythmogenic cardiomyopathy

Evaluation of: Noorman M, Hakim S, Kessler E et al. Remodeling of the cardiac sodium channel, connexin43, and plakoglobin at the intercalated disk in patients with arrhythmogenic cardiomyopathy. Heart Rhythm 10(3), 412-419 (2013). Arrhythmogenic cardiomyopathy (AC) is a heart muscle disease characterized by a progressive replacement of the ventricular myocardium with adipose and fibrous tissue. This disease is often associated with mutations in genes encoding desmosomal proteins in the majority of patients. Based on results obtained from recent experimental models, a disturbed distribution of gap junction proteins and cardiac sodium channels may also be observed in AC phenotypes, secondary to desmosomal dysfunction. The study from Noorman et al. examined heart sections from patients diagnosed with AC and performed immunohistochemical analyses of N-cadherin, PKP2, PKG, Cx43 and the cardiac sodium channel NaV1.5. Altered expression/distribution of Cx43, PKG and NaV1.5 was found in most cases of patients with AC. The altered expression and/or distribution of NaV1.5 channels in AC hearts may play a mechanistic role in the arrhythmias leading to sudden cardiac death in AC patients. Thus, NaV1.5 should be considered as a supplemental element in the evaluation of risk stratification and management strategies. However, additional experiments are required to clearly understand the mechanisms leading to AC phenotypes.

Bullous pemphigoid: therapeutic algrorithm and practical management

Introduction: Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucosae. BP typically affects the elderly and manifests with severe itch, localised or generalised eczematous, urticated and/or bullous lesions. Its morbidity and impact on the quality of life are important. The disease is significantly associated with neurological disorders, such as stroke, Parkinson disease, major cognitive impairment and multiple sclerosis. Diagnosis of BP critically relies on immunopathologic examinations, particularly direct immunofluorescence microscopy studies. Areas covered: This paper looks at the evidence of therapies commonly used in bullous pemphigoid. Expert opinion: Treatment of BP has been a challenge, given the relative rarity of the disease, lack of good quality randomised controlled trials, the presence of co-morbidities in the affected elderly population and the high mortality rate. Recent controlled studies have indicated that potent topical corticosteroids constitute a more effective therapy for BP when compared to oral corticosteroids in terms of control of the disease, side effect profile and overall survival. Other therapies have been employed with varying success, but are not validated yet. Improved knowledge of the pathophysiology of BP will hopefully allow the development of new immunomodulatory treatments for this debilitating disease.

Das Geschlecht der Diplomatie. Geschlechterrollen in den Außenbeziehungen vom Spätmittelalter bis zum 20. Jahrhundert

Fürstinnen in Friedensverhandlungen, Botschaftergattinnen, die ihre Ehemänner in diplomatischen Verhandlungen unterstützen, eine Frau als erste offiziell akkreditierte Botschafterin der Sowjetunion, die Außenpolitik des wilhelminischen Deutschland unter dem Verdacht der Homosexualität: Der vorliegende Sammelband widmet sich der Frage, welche Rolle das Geschlecht und die mit ihm assoziierten Eigenschaften in der diplomatischen Praxis spielten. Unter welchen Umständen konnte die Geschlechtszugehörigkeit vor andere Kategorien wie Stand, Alter, Erfahrung oder Bildung treten, in welchen Kontexten wurde sie zur Nebensache? Ausgehend von Einzelfallstudien steckt der epochenübergreifend angelegte Sammelband ein neues Forschungsfeld ab und legt somit einen Grundstein für eine Geschlechtergeschichte von Außenpolitik.

Jospeh. Furttenbach. Lebenslauff (1652 – 1664)

Joseph Furttenbach (1591 1667) wirkte als Architekt, Ingenieur, Baumeister, Sammler, Chronist und Tagebuchschreiber in der ersten Hälfte des 17. Jahrhunderts. Seine autobiographischen Aufzeichnungen sind bisher unveröffentlicht geblieben. Sie werfen faszinierende Schlaglichter auf das Leben eines protestantischen Vermittlers italienischer Barockkultur im Süden des Alten Reiches, auf die kulturellen und sozialen Aktivi täten eines Kunstkammerbesitzers sowie den Alltag eines Stadtbaumeisters und frommen Lutheraners in der Reichsstadt Ulm.

State-of-the-art aortic imaging: part I - fundamentals and perspectives of CT and MRI

Over the last two decades, imaging of the aorta has undergone a clinically relevant change. As part of the change non-invasive imaging techniques have replaced invasive intra-arterial digital subtraction angiography as the former imaging gold standard for aortic diseases. Computed tomography (CT) and magnetic resonance imaging (MRI) constitute the backbone of pre- and postoperative aortic imaging because they allow for imaging of the entire aorta and its branches. The first part of this review article describes the imaging principles of CT and MRI with regard to aortic disease, shows how both technologies can be applied in every day clinical practice, offering exciting perspectives. Recent CT scanner generations deliver excellent image quality with a high spatial and temporal resolution. Technical developments have resulted in CT scan performed within a few seconds for the entire aorta. Therefore, CT angiography (CTA) is the imaging technology of choice for evaluating acute aortic syndromes, for diagnosis of most aortic pathologies, preoperative planning and postoperative follow-up after endovascular aortic repair. However, radiation dose and the risk of contrast induced nephropathy are major downsides of CTA. Optimisation of scan protocols and contrast media administration can help to reduce the required radiation dose and contrast media. MR angiography (MRA) is an excellent alternative to CTA for both diagnosis of aortic pathologies and postoperative follow-up. The lack of radiation is particularly beneficial for younger patients. A potential side effect of gadolinium contrast agents is nephrogenic systemic fibrosis (NSF). In patients with high risk of NSF unenhanced MRA can be performed with both ECG- and breath-gating techniques. Additionally, MRI provides the possibility to visualise and measure both dynamic and flow information.