Structural requirements of the oxytocin receptor in rat uterus

Published and newly calculated pA₂-values of 147 neurohypophyseal hormone analogues (7 positions varied) acting as inhibitors of oxytocin on isolated rat uterus in vitro have been subjected to fractionation according to the method by Free and Wilson which was slightly modified for this purpose. The computation was carried out in several steps. After each step, substances with outlying pA₂ -values were el minated. The reduced group containing 73–79% of the original substances displayed a high degree of additivity of side chain contributions (SCC). This group seems to follow the “participation” rule as formulated by Free and Wilson. Analysis of the group of eliminated substances and of the resulting SCC-spectrum (level diagram) enabled us to draw some conclusions concerning the structural requirements of receptor binding: i) The intact ring structure is necessary for the peptide-receptor interaction: linear peptides or peptides with an extended ring are always outliers; ii) Carba analogues (substitution with CH₂ in the disulfide ring) display better affinities than peptides with an S-S ring; d -Arg⁸ substitution decreases the binding affinity; iii) Considerably better additivity is achieved when peptides are divided into subgroups with vasopressin-like and oxytocin-like features; populations of receptors more specific for vasopressin and for oxytocin, respectively, can be assumed. Estimates of the “true” receptor-peptide dissociation constants can be obtained by summation of the corresponding SCC's in each investigated position. The value obtained for oxytocin is identical with the medium affinity binding site on myometrial cells, and not with the high affinity site. A nonlinear relationship exists between SCC's computed from pA₂-values for magnesium-free and magnesium-containing (0.5 mm ) media but no evidence speaks in favor of a Mg-potentiating effect on receptor binding.     

123I-metaiodobenzylguanidine scintigraphy in the detection of irregular regional sympathetic innervation in long QT syndrome

Twelve patients with the long QT syndrome were studied to determinethe usefulness of ¹²³I-metaiodobenzylguanidine (MIBG) single-photonemission tomography (SPECT) at 2 h and 6 h after injection;the results were compared to 10 healthy volunteers (controls).Uptake of MIBG in the left ventricle at 2 h after injectionwas significantly reduced in patients with the long QT syndrome(1.43±0.13) vs 1.66±0.15 in controls, heart-to-mediastinumratio, P <0.002) and washout after 6 h was faster on a planarview image. Decreased MIBG uptake could be observed preferentiallyin the anterior and lateral walls near the apex. The half-timevalues of MIBG washout from the left ventricle were significantlyreduced in the long QT syndrome (6.4±1.5 h) comparedto controls (16.7±15.3 h, P <0.002). In three cases,the same pattern of disturbed activity distribution was maintainedeven after surgical left cardiac sympathetic denervation. Thepresent results strongly support the hypothesis that an inhomogenousregional distribution of sympathetic nerve terminals accompaniedby an overall reduction in their absolute number may play animportant role in the pathogenesis of the long QT syndrome.Additional functional disturbances, possibly related to theuptake of catecholamines in the left ventricle may coexist withregional inhomogeneity of nerve terminals. The differences observedfrom one case to the other may be related to the variation inseverity of the disease. MIBG SPECT imaging seems an interestingnew tool for the quantitative assessment of presynaptic sympatheticnerve terminal disturbances in the left ventricle of patientswith the long QT syndrome.     

Intracranial aspergillosis in a non-immunocompromised patient treated for muscle-invasive bladder cancer

We report a case of intracerebral Aspergillosis in a patient undergoing radical cystectomy for the treatment of muscle-invasive bladder cancer who did not reveal any deterioration of the immune system. Aspergillus fumigatus is an ubiquitously present, airborne fungus that tends to infect the upper respiratory tract. However, the latter was not observed in the patient presented. Complications in the form of an involvement of the central nervous system are very rarely recognized as a result of an Aspergillus infection and primarily occur in patients who are not immunologically competent. To our knowledge, we present the first case of intracerebral invasive Aspergillosis in an otherwise healthy patient diagnosed with an urological malignancy.     

Clinical Evaluation of a Prototype Passive Fixation Dual Chamber Single Pass Lead For Dual Chamber ICD Systems

Dual chamber ICD systems use two separate leads for sensing. We developed and tested a new prototype of a single pass dual chamber passive fixation lead for dual chamber ICDs. Methods and Results: The prototype was a modification of the Guidant CPI Endotak DSP lead. The additional sensing electrode for the right atrium consisted of a side-mounted porous atrial ring electrode (AR). Atrial signals were recorded from the lead in patients during normal sinus rhythm (NSR), atrial fibrillation (AFib), and/or atrial flutter (AFl) with the AR in stable contact with the atrial wall or floating. During NSR, with the AR in contact with the atrial wall, an average P wave amplitude of 7.2 ± 1.5 mV (mean ± SD, n = 12) was measured. After induction of AFib/AFl, the single amplitude decreased to 3.6 ± 1.5 mV (n = 8) during AFib and 3.4 ± 1.7 mV (n = 9) during AFl. Amplitudes dropped between 53% and 75% when the AR lost atrial wall contact. The atrial pacing threshold was 1.0 ± 0.4 V (n = 16) when the AR was in contact with the atrial wall. Conclusions: In future dual chamber ICDs the signals from a passive fixation single pass lead could be used for atrial sensing and pacing as long as the sensing electrode for the right atrium remains in contact with the atrial wall. This system might lead to a simpler, less invasive implantation of dual chamber ICD systems.     

Real‐World Data on the Lifespan of Implantable Cardioverter‐Defibrillators Depending on Manufacturers and the Amount of Ventricular Pacing

Real‐World Data on the Lifespan of ICDs Introduction: Implantable cardioverter‐defibrillator (ICD) longevity is crucial for both patients and public health systems because it determines the number of surgical ICD replacements, which can generally be considered an additional risk factor for complications, and the cost‐effectiveness of ICD therapy. Our objective was to obtain insight into the “real‐world” longevities of implantable cardioverter‐defibrillators, which quite often differ from those stated in the manufacturers’ declarations. Methods and Results: On the basis of a prospective database, we analyzed all ICD implantations performed in our hospital from June 1988 to June 2009. We studied 980 patients (follow‐up 58 ± 51 months) with 1,502 ICDs and all respective data until August 2010. We compared the percentage of still operating ICDs at different points in time in relation to manufacturers, types of device (single chamber 623, dual chamber 588, cardiac resynchronization therapy ICDs [CRT‐D] 291), and amount of right ventricular pacing (VP). We found distinct differences between the mean lifespans of ICDs of different manufacturers (Biotronik 4.3 years, Sorin 4.5 years, Guidant/Boston Scientific 4.7 years, St. Jude Medical 5 years, Medtronic 5.8 years). CRT‐D devices (hazard ratio [HR] 1.778, P = 0.0005) were associated with an elevated annual relative risk for device replacement while a decrease in the proportion of VP (HR 0.934 for each 10% decrease in VP, P < 0.0001) and Medtronic ICDs were associated with a reduced risk of device replacement (HR 0.544, P < 0.0001). Conclusion: CRT‐Ds and an elevated percentage of VP are associated with a significantly elevated risk for device replacement, while Medtronic ICDs showed the longest lifespans. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1336‐1342, December 2012)     

A New Temporary Occlusion and Aspiration System for Prevention of Distal Embolization During Percutaneous Transluminal Renal Angioplasty

Cholesterol embolization has been described as a severe complication of percutaneous transluminal renal angioplasty (PTRA) and may lead to renal insufficiency with the need of transient or permanent hemodialysis. We describe a case of successful angioplasty of a renal artery in-stent restenosis utilizing a new temporary balloon occlusion and aspiration system for prevention of distal embolization. Histological examination of blood retrieved from the distally occluded vessel showed lipid-rich macrophages (foam cells) and an amorphic lipoid substance as markers of atherosclerotic plaque debris. Further studies are necessary to evaluate the clinical relevance of atheromatous microembolization and its renal function and clinical course following angioplasty.     

Three-Year Experience with a Stylet for Lead Extraction: A Multicenter Study

The extraction of chronically implanted and infected pacemaker and defibrillator leads is an important issue. This article describes the experience gathered between 1990 and 1994 by seven European centers regarding a locking stylet that is uniformly applicable for a wide variety of internal pacing coil diameters. This interventional locking stylet for lead extraction has an outer diameter of 0.4 mm (0.016 inches). The stylet consists of a hollow shaft in which an inner traction wire is embedded. At the tip of the inner traction wire an anchoring mechanism, which can be opened by retraction, is applied. Removal attempts were made for 150 leads, 110 in ventricular and 40 in atrial positions. Results : Complete removal was possible in 122 cases (81 %). Partial removal was possible in 18 cases (12%). Failure to remove the lead with the extraction stylet was experienced in 10 cases (7%). In seven patients, the leads were removed by cardiothoracic surgery; 3 defective leads were left in place. There were no serious complications associated with the procedure. None of the patients died. Conclusion : The experience with this extraction stylet for lead removal has shown good results. Despite a low complication rate thus far, each case for lead removal should be judged on the individual basis of benefit-to-risk ratio.