Myokardiale Beteiligung des Eosinophilie-Syndroms bei einer Fadenwurminfektion Nachweis regionaler Myokardrestriktion mittels Pulswellen-Gewebe-Doppler-Echokardiographie

Zusammenfassung Fallbericht: Wir berichten über eine 57jährige Patientin, die zur Abklärung vermehrter eosinophiler Granulozyten aufgenommen worden war. Diagnostik: Die ausführliche Diagnostik ergab zunächst ein Eosinophilie-Syndrom mit Infiltrationen in das Knochenmark und in die Lunge. Klinisch imponierten zunehmend pektanginöse Beschwerden mit Zeichen einer Myokardinsuffizienz. Die daraufhin durchgeführte invasive Diagnostik ergab einen unauffälligen Koronarstatus. Deshalb wurden unter dem Verdacht einer myokardialen Beteiligung Endomyokardbiopsien entnommen, die histologisch das Bild einer Endokarditis parietalis fibroplastica Löffler ergaben. Serologische Untersuchungen nach Parasiten erbrachten schließlich im ELISA-Test positive Titer für eine Fadenwurminfektion durch Toxocara, die im Verlauf noch anstiegen. Die weiterführende Diagnostik mittels Pulswellen-Gewebe-Doppler-Echokardiographie verifizierte die myokardiale Beteiligung im Sinne einer restriktiven Füllungsstörung. Schlußfolgerung: Eine myokardiale Beteiligung durch Eosinophilie, hervorgerufen durch Toxocara, wurde bisher nicht beschrieben. Die Diagnostik mittels Pulswellen-Gewebe-Doppler-Echokardiographie erlaubt die regionale Differenzierung restriktiver Füllungsstörungen, wodurch die Bedeutung dieser neuen diagnostischen Möglichkeit bei myokardialen Erkrankungen dokumentiert werden konnte. Abstract Case Report: The case of a 57-year-old woman is reported who was admitted for peripheral hypereosinophilia. Diagnosis: Detailed investigations revealed first of all a hypereosinophilic syndrome with infiltration of bone marrow and lung. The patient suffered more and more from angina pectoris with signs of heart failure. Coronary angiography was therefore carried out which showed normal coronary arteries. With suspicion of myocardial involvement endomyocardial biopsies were performed which revealed the presence of Löfflers endocarditis parietalis fibroplastica. Finally, serological studies for parasites disclosed a positive ELISA test for Toxocara, confirmed later to be rising. Conclusion: Myocardial involvement of hypereosinophilia, caused by Toxocara is not described until now. Further diagnostic by means of pulsed wave tissue Doppler echocardiography provided regional differentiation of a restrictive filling pattern which documented the importance of this new diagnostic tool in myocardial illness.     

Properties and function of KCNQ1 K+ channels isolated from the rectal gland of Squalus acanthias

KCNQ1 (KVLQT1) K+ channels play an important role during electrolyte secretion in airways and colon. KCNQ1 was cloned recently from NaCl-secreting shark rectal glands. Here we study the properties and regulation of the cloned sKVLQT1 expressed in Xenopus oocytes and Chinese hamster ovary (CHO) cells and compare the results with those obtained from in vitro perfused rectal gland tubules (RGT). The expression of sKCNQ1 induced voltage-dependent, delayed activated K+ currents, which were augmented by an increase in intracellular cAMP and Ca2+. The chromanol derivatives 293B and 526B potently inhibited sKCNQ1 expressed in oocytes and CHO cells, but had little effect on RGT electrolyte transport. Short-circuit currents in RGT were activated by alkalinization and were decreased by acidification. In CHO cells an alkaline pH activated and an acidic pH inhibited 293B-sensitive KCNQ1 currents. Noise analysis of the cell-attached basolateral membrane of RGT indicated the presence of low-conductance (<3 pS) K+ channels, in parallel with other K+ channels. sKCNQ1 generated similar small-conductance K+ channels upon expression in CHO cells and Xenopus oocytes. The results suggest the presence of low-conductance KCNQ1 K+ channels in RGT, which are probably regulated by changes in intracellular cAMP, Ca2+ and pH.     

Transgenic pigs as models for translational biomedical research

The translation of novel discoveries from basic research to clinical application is a long, often inefficient, and thus costly process. Accordingly, the process of drug development requires optimization both for economic and for ethical reasons, in order to provide patients with appropriate treatments in a reasonable time frame. Consequently, “Translational Medicine” became a top priority in national and international roadmaps of human health research. Appropriate animal models for the evaluation of efficacy and safety of new drugs or therapeutic concepts are critical for the success of translational research. In this context rodent models are most widely used. At present, transgenic pigs are increasingly being established as large animal models for selected human diseases. The first pig whole genome sequence and many other genomic resources will be available in the near future. Importantly, efficient and precise techniques for the genetic modification of pigs have been established, facilitating the generation of tailored disease models. This article provides an overview of the current techniques for genetic modification of pigs and the transgenic pig models established for neurodegenerative diseases, cardiovascular diseases, cystic fibrosis, and diabetes mellitus.     

External beam radiotherapy as postoperative treatment of diffuse pigmented villonodular synovitis

PURPOSE: Diffuse pigmented villonodular synovitis is a rare proliferative disorder of synovial membranes with invasive and expansive growth patterns. Radical synovectomy is regarded as the treatment of choice. However, because of the high recurrence rates, additive treatment might be useful. Radiotherapy (RT) has been evaluated with positive results, but the optimal treatment schedules are vague. We have reviewed our experience with postoperative RT in cases of suspected or proven residual disease. METHODS AND MATERIALS: Between December 1996 and January 2006, 7 diffuse pigmented villonodular synovitis patients underwent RT at our institution. The most common location was the knee joint (5 patients). All patients underwent radical surgery and were treated subsequently with 6-MV photon RT. The total doses applied were 30-50 Gy, depending on the resection status and estimated risk of relapse. For analysis, we retrospectively reviewed all patients in April 2006. RESULTS: The mean follow-up time was 29 months (range, 3-112 months). RT had no acute adverse effects. At the assessment, no evidence was found of recurrent or persisting disease in any patient. Of the 7 patients, 6 reported asymptomatic limb function and excellent quality of life; 1 patient had persistent restriction of joint movement after repeated surgery. No radiotherapeutic late effects were seen. CONCLUSION: The results of our series have confirmed the efficacy and safety of postoperative RT for diffuse pigmented villonodular synovitis. Hence, this treatment should be considered for patients with suspected or proven residual disease.     

In silico model-driven assessment of the effects of single nucleotide polymorphisms (SNPs) on human red blood cell metabolism

The completion of the human genome project and the construction of single nucleotide polymorphism (SNP) maps have lead to significant efforts to find SNPs that can be linked to pathophysiology. In silico models of complete biochemical reaction networks relate a cell's individual reactions to the function of the entire network. Sequence variations can in turn be related to kinetic properties of individual enzymes, thus allowing an in silico model-driven assessment of the effects of defined SNPs on overall cellular functions. This process is applied to defined SNPs in two key enzymes of human red blood cell metabolism: glucose-6-phosphate dehydrogenase and pyruvate kinase. The results demonstrate the utility of in silico models in providing insight into differences between red cell function in patients with chronic and nonchronic anemia. In silico models of complex cellular processes are thus likely to aid in defining and understanding key SNPs in human pathophysiology.     

Right insula for our sense of limb ownership and self-awareness of actions

Normally, we are aware that our arms and legs belong to us and not to someone else. However, some stroke patients with hemiparesis/-plegia after right-sided stroke show a disturbed sensation of limb ownership and a disturbed self-awareness of actions and such patients with anosognosia for hemiparesis/plegia typically deny their paresis/-plegia and are convinced that their limbs function normally. They may experience their limb(s) as not belonging to them and may even attribute them to other persons. Modern lesion analyses techniques in such patients and recent neuroimaging results in healthy subjects suggest a prominent role of the right insula for our sense of limb ownership as well as for our feeling of being involved in a movement—our sense of agency. We thus hypothesize that the right insular cortex constitutes a central node of a network involved in human body scheme representation.