The cost-of-illness for invasive meningococcal disease caused by serogroup B Neisseria meningitidis (MenB) in Germany

Introduction

Invasive meningococcal disease (IMD) is a severe disease mainly affecting infants and young children. The most common serogroup causing IMD in Germany is the serogroup type B Neisseria meningitidis (MenB). The aim of the present study is to estimate the economic burden of MenB-related IMD in Germany.

Reproducibility of Computerized Measurements of QT Interval from Multiple Leads at Rest and During Exercise

Background: Accurate measurement of the QT interval is important for diagnosing long QT syndrome (LQTS), and in research on determinants of ventricular repolarization time. We tested automatic analysis of QT intervals from multiple ECG leads on chest. Methods: Eleven healthy volunteers and 10 genotyped LQTS patients were tested at rest and during exercise with a bicycle ergometer twice 1–31 months apart. Electrocardiograms were recorded with the body surface potential mapping system, and 12 precordial channels were selected for analysis. Averaged QT peak and QT end intervals were determined with an automated algorithm, and the difference QT end minus QT peak (Tp‐e) was calculated. Repeatability was assessed by coefficient of variation (CV) between measurements. Results: Within one test at rest the QT end intervals were highly repeatable with CV 0.6%. In repeated tests CV was 4.4% for QT end interval and 3.5% when the QT interval was corrected for heart rate. In exercise test at specified heart rates, mean CV was 3.0% for QT end and 2.9% for QT peak interval. The CV of Tp‐e interval was 10.2% at rest, and 9.3% in exercise test. Reproducibility was comparable between healthy subjects and LQTS patients. Conclusions: The BSPM system with automated analysis produced accurate and highly repeatable QT interval measurements. Reproducibility was adequate also over prolonged time periods both at rest and in exercise stress test. The method can be applied in studying duration of ventricular repolarization time in different physiologic and pharmacologic interventions.     

Heart Rate Variability Predicts Severe Hypotension after Spinal Anesthesia

Background: Hypotension due to vasodilatation after spinal anesthesia (SA) may be harmful. Heart rate variability, an indirect measure of autonomic control, may predict hypotension.

Methods: One hundred patients were studied. Retrospectively, heart rate variability was analyzed in 30 patients, classified depending on the lowest systolic blood pressure (SBP) after SA. Seventy patients were studied prospectively, assigned to one of two groups by their low to high frequency ratio (LF/HF) before SA. Sensitivity and specificity of LF/HF for prediction of decrease of SBP greater 20% of baseline were tested.

Results: Retrospective analysis showed differences of LF/HF depending on the degree of hypotension after SA. Prospective analysis demonstrated significant differences of SBP after SA depending on baseline LF/HF (mean +/- SD): low LF/HF (1.3 +/- 0.7) = > SBP: 91 +/- 8% of baseline versus high LF/HF (5.5 +/- 2.4) = > SBP: 66 +/- 10% of baseline (P < 0.05). Baseline LF/HF as well as high frequency and proportional decrease of SBP after SA correlated significantly, in contrast to baseline hemodynamic parameters heart rate and SBP. A receiver operator curve characteristic analysis showed a sensitivity and specificity of LF/HF > 2.5 of 85% to predict SBP decrease of greater than 20% of baseline after SA.     

Analysis of surgical management of calvarial tumours and first results of a newly designed robotic trepanation system.

This study was performed to evaluate the surgical strategy in patients with calvarial tumours, in order to design and modify a robot-assisted trepanation system. A total of 75 patients underwent craniectomy for the treatment of calvarial tumours during the 10-year period from 1993 to 2002. The patients' complaints, the size, location and histology of the tumour, and the various cranioplasty techniques used were analysed retrospectively. In a second procedure several craniectomies at typical locations according to the study's results were performed in a laboratory setting using a hexapod robotic tool, constructed at the Helmholtz-Institute, RWTH Aachen University, and plastic model heads. The workflow was documented and the reproducibility and the accuracy of the procedure were registered. A total of 83 surgical procedures were performed on 75 patients. The majority (87 %) of lesions treated surgically were located in the frontal, temporal and anterior parts of the parietal region. Histological examination revealed benign lesions in 66 % of the patients and dural involvement in 46 %. According to these results craniectomies were performed using the robotic system. Mean positioning accuracy of the robotic system while milling was 0.24 mm, with a standard deviation of 0.04 mm, and maximum error under 1 mm. Craniectomies leaving a 1-mm layer of the tabula interna intact to ensure a healthy dura were performed in several regions successfully. The majority of calvarial tumours, requiring surgical treatment in our patients, were located in cosmetically relevant areas in which drilling can be carried out with the robotic trepanation system. Consequently, the surgical approach had to be planned carefully in order to achieve a good cosmetic outcome.     

An ex-vivo technic for the pharmacologic evaluation of potential antiphlogistics by ex-vivo determination of the rate of malondialdehyde (MDA) formation using rat platelets

Based on a standardized in-vitro method for quantifying the activity of prostaglandin-synthetase by means of coupling malondialdehyde with 2-thiobarbituric acid the possibility of using this method also as ex-vivo technique is described. By this, more favourable prerequisites to pharmacological valuation of the effects of potential antiinflammatory substances exists compared to the application of in-vitro results, only.     

Photodynamic therapy mediated induction of accelerated re-endothelialisation following injury to the arterial wall: implications for the prevention of postinterventional restenosis.

OBJECTIVE: Accelerated re-endothelialisation may inhibit the development of restenosis. Basic Fibroblast Growth Factor (bFGF) plays a key role for early proliferative activity in the artery following injury. Therefore, this study was devised to examine the effect of photodynamic therapy (PDT) on post-injury re-endothelialisation in vivo, and bFGF-mRNA expression in endothelial cells (EC) in vitro. MATERIALS AND METHODS: Rat carotid arteries were balloon-injured prior to PDT. Arteries were analysed after 1, 3, 5, 14 and 30 days. Morphometric measurements were undertaken following injection of 0.5% Evans Blue which stains non-endothelialised surfaces only. To identify EC, immunohistochemistry (CD-31) was performed. Proliferation was assessed by fluorescence cell counting. PCR quantification of bFGF-mRNA expression and proliferation were assessed in bovine aortic EC which were plated on isolated, PDT-treated EC-derived extracellular matrix at (12), 24, 48 (72 h). RESULTS: Three days following PDT, arteries displayed significantly increased endothelial lining (p = 0.02), which was more pronounced at 5 (p = 0.03) and 14 days (p = 0.02). At 30 days no relevant differences between PDT and control were noted. EC proliferation on PDT-treated matrix was significantly increased at 24, 48, and 72 h (p = 0.0004), whereas bFGF-mRNA expression was significantly increased at 24 h only (p = 0.007). CONCLUSION: Post-injury PDT appears to accelerate re-endothelialisation. Expression of bFGF-mRNA, however, although increased shortly after PDT, may not be responsible for a constant stimulation of EC proliferation.     

Tetanus: an uncommon cause of dysphagia

A 53-year-old woman was examined at our medical center because of progressive dysphagia of 14 days' duration and a severe inability to open her mouth and swallow saliva. A barium esophagogram showed no obstruction, but pooling of barium in the hypopharynx suggested a neuromuscular disorder. The clinical diagnosis of tetanus was confirmed by electromyography. With appropriate therapy, the patient recovered during a period of 6 weeks. This case illustrates both an uncommon cause of dysphagia and an uncommon initial manifestation of tetanus.     

Pathologische Anatomie (Sektionstechnik) und Physiologie

Ohne Zusammenfassung     

Mutant ryanodine receptors in catecholaminergic polymorphic ventricular tachycardia generate delayed afterdepolarizations due to increased propensity to Ca2+ waves.

AIMS: Mutations in cardiac ryanodine receptors (RyR2s) are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT), characterized by risk of polymorphic ventricular tachyarrhythmias and sudden death during exercise. Arrhythmias are caused by gain-of-function defects in RyR2, but cellular arrhythmogenesis remains elusive. METHODS AND RESULTS: We recorded endocardial monophasic action potentials (MAPs) at right ventricular septum in 15 CPVT patients with a RyR2 mutation (P2,328S, Q4,201R, and V4,653F) and in 12 control subjects both at baseline and during epinephrine infusion (0.05 microg/kg/min). At baseline 3 and during epinephrine infusion, four CPVT patients, but none of the control subjects, showed delayed afterdepolarizations (DADs) occasionally coinciding with ventricular premature complexes. In order to study the underlying mechanisms, we expressed two types of mutant RyR2 (P2,328S and V4,653F) causing CPVT as well as wild-type RyR2 in HEK 293 cells. Confocal microscopy of Fluo-3 loaded cells transfected with any of the three RyR2s showed no spontaneous subcellular Ca(2+) release events at baseline. Membrane permeable cAMP analogue (Dioctanoyl-cAMP) triggered subcellular Ca(2+) release events as Ca(2+) sparks and waves. Cells expressing mutant RyR2s showed spontaneous Ca(2+) release events at lower concentrations of cAMP than cells transfected with wild-type RyR2. CONCLUSION: CPVT patients show DADs coinciding with premature action potentials in MAP recordings. Expression studies suggest that DADs are caused by increased propensity of abnormal RyR2s to generate spontaneous Ca(2+) waves in response to cAMP stimulation. Increased sensitivity of mutant RyR2s to cAMP may explain the occurrence of arrhythmias during exercise or emotional stress in CPVT.