The role of auxiliary dihydropyridine receptor subunits in muscle

The skeletal muscle dihydropyridine receptor is a slowly-activating calcium channel that functions as the voltage sensor in excitation-contraction coupling. In addition to the pore-forming α_1S subunit it contains the transmembrane α₂δ-1 and γ₁ subunits and the cytoplasmic β_1a subunit. Although the roles of the auxiliary subunits in calcium channel function have been intensively studied in heterologous expression systems, their functions in excitation-contraction coupling has only recently been elucidated in muscle cells of various null-mutant animal models. In this article we will briefly outline the current state of these investigations. * To whom correspondence should be addressed: Tel.: +43-512-507-3787; Fax: +43-512-507-2836; E-mail: bernhard.e.flucher@uibk.ac.at     

Some considerations on middle ear cholesteatoma in ‘foreign workers’*

The treatment of cholesteatoma in patients without a permanent residence or in medically underdeveloped countries presents a serious problem in middle ear surgery. Methods which erradicate disease safely and reduce the risk of recurrence to a minimum are necessary. We differentiate 3 clinical types of cholesteatoma: 1 Retraction of Shrapnell's membrane or in the postero-superior quadrant with very little cholesteatoma lateral to the ossicles. A transcanal technique is used to evert the cholesteatomatous pocket into the meatus intact, followed by reconstruction of the outer attic wall. 2 Circumscribed cholestatoma lateral and often also medial to the ossicles. Combined approach tympanoplasty is used in such cases. 3 Marginal perforations with large cholesteatomas, situated medial to the ossicular chain. For these ears, classical radical mastoidectomy is the method of choice. (Radical mastoidectomy also has to be performed in all cases of type II, where luxation of the matrix in toto has failed.) Results: No recurrence has been detected in cases where follow-up was possible.     

Exercise Induced Sympathetic Influences Do Not Change Interatrial Conduction Times in VDD and DDD Pacing

Using telemetry, right atrial electrogram (RA), and marker channel of atrial sense events (M_A) in combination with the left atrial electrogram (LA), recorded by a filtered bipolar esophageal lead, interatrial conduction during submaximal exercise and at rest was examined in 46 DDD pacemaker patients. The RA-LA and M_A-LA conduction times measured in the presence of atrial sensing (VDD) as well as the conduction time S_A-LA from atrial stimulus (S_A) to LA, determined during atrial pacing (DDD) were found to be individual constants independent of exercise induced sympathetic influences. Thus, having determined an optima! mechanical interval (LA-LV)_mech/opt from left atrium to ventricle by other methods, the optimal AV delay for DDD as well as for VDD operation can be calculated by the sum of the appropriate interatrial conduction time (S_A-LA, respectively M_A-LA) and the (LA-LV)_mech/opt interval. Due to the constant S_A-LA and M_A-LA, the difference between these two values (AV delay correction interval) is a constant as well, which remains unchanged during exercise. Therefore, in selecting the rate responsive AV delay, only hemodynamic and not electrophysiologica] measurements need to be considered.     

Polarity Reversal Improves Defibrillation Efficacy in Patients Undergoing Transvenous Cardioverter Defibrillator Implantation with Biphasic Sbocks

The purpose of this study was to determine the influence of polarity reversal on DFT in patients undergoing implantation of nonthoracotomy defibrillators with biphasic shocks. Previous studies have shown higher defibrillation efficacy with using the distal electrode as anode in implantation of nonthoracotomy defibrillators and monophasic shocks. However, it is as yet unclear whether biphasic shock defibrillation will also be influenced by polarity reversal. Using a transvenous lead system with a proximal electrode in the superior caval vein and a distal electrode in the RV apex, 27 patients undergoing defibrillator implantation were randomized to DFT testing with "initial" (distal electrode = cathode) or "reversed" polarity (distal electrode = anode). Defibrillation energy was reduced stepwise until defibrillation failure occurred. At this point, polarity was switched and testing continued until the lowest energy requirement was determined for both polarities. With reversed polarity, DFT was 11.1 ± 5.7 J versus 13.3 ± 5.8 J with initial polarity (P = 0.033). This means a 17% reduction of the DFT. In 10 patients, the threshold was lower with reversed, whereas in 3 patients it was lower with initial polarity. In conclusion, changing electrode polarity in transvenous implantable defibrillators with biphasic shocks may significantly influence defibrillation energy requirements. Therefore, polarity reversal should always be attempted before considering patch implantation.     

Pathogenesis of equine herpesvirus‐1 infection in the mouse model

Equine herpesvirus‐1 (EHV‐1) is a major equine pathogen causing respiratory diseases, abortions and severe neurological disorders. The basis of neurological disturbances is, as in other organs, infection of endothelial cells, followed by vasculitis, thrombosis and ischaemic damage of the parenchyma. Here, a murine model was used to explore the mechanism of entry to, and spread within the brain, the cell affinity of the agent and the modulating role of the immune defence, which are all factors governing the pathogenesis of the neurological disease. Because controversial views exist about these mechanisms, we undertook a neuropathological study with intranasally infected adult mice. EHV‐1 entered the brain through the olfactory neuroepithelium and along the olfactory nerves, and spread transsynaptically in rostro‐caudal direction, using olfactory and limbic neuronal networks. Exclusively neurons were infected. The cellular immune reaction exerted a restraining effect on virus dissemination. Following nasal infection, the olfactory route was the major pathway for virus entry and dissemination, involvement of the trigeminal nerve in virus spread seems much less probable. In the adult mouse brain EHV‐1 behaves as a typical neurotropic agent, using, similarly to other herpesviruses, the neuronal networks for dissemination. Vasculitis, the predominant type of lesion in natural infection, and endothelial cell positivity for EHV‐1 were detectable only in the lung. Thus, this agent exhibits in the mouse a dual affinity: it is neurotropic in the brain, and endotheliotropic in visceral organs. Consideration of pathogenetic aspects of equine and experimental murine EHV‐1 infections also helps a better understanding of human herpetic brain disease.     

Early diagnosis and straight forward surgery of an asymptomatic primary angiosarcoma of the kidney led to long-term survival

We report the first case of a diagnosis of an asymptomatic primary renal angiosarcoma. The patient underwent laparoscopic nephrectomy and is alive after long-term follow up. We provide the preoperative imaging studies and the histologic features of this exceedingly rare tumor.