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InAs quantum dots grown on a GaAs substrate have been one of the most successful semiconductor material systems to demonstrate single-photon-based quantum optical phenomena. In this context, we present the feasibility to extend the low-temperature photoluminescence emission range of In(Ga)As/GaAs quantum dots grown by metal-organic vapor-phase epitaxy from the typical window between 880 and 960 nm to wavelengths above 1.3 μm. A low quantum dot density can be obtained throughout this range, enabling the demonstration of single- and cascaded photon emission. We further analyze polarization-resolved micro-photoluminescence from a large number of individual quantum dots with respect to anisotropy and size of the underlying fine-structure splittings in the emission spectra. For samples with elevated emission wavelengths, we observe an increasing tendency of the emitted photons to be polarized along the main crystal axes.

Purpose An isolated perfused pig heart model has recently been proposed for the development of novel methods in standard clinical magnetic resonance (MR) scanners. The original set-up required the electrical system to be within the safe part of the MR-room, which introduced significant background noise. The purpose of the current work was to refine the system to overcome this limitation so that all electrical parts are completely outside the scanner room. Methods Four pig hearts were explanted under terminal anaesthesia from large white cross landrace pigs. All hearts underwent cardiovascular magnetic resonance (CMR) scanning in the MR part of a novel combined 3T MR and x-ray fluoroscopy (XMR) suite. CMR scanning included real-time k-t SENSE functional imaging, k-t SENSE accelerated perfusion imaging and late gadolinium enhancement imaging. Interference with image quality was assessed by spurious echo imaging and compared to noise levels acquired while operating the electrical parts within the scanner room. Results Imaging was performed successfully in all hearts. The system proved suitable for isolated heart perfusion in a novel 3T XMR suite. No significant additional noise was introduced into the scanner room by our set-up. Conclusions We have substantially improved a previous version of an isolated perfused pig heart model and made it applicable for MR imaging in a state of the art clinical 3T XMR imaging suite. The use of this system should aid novel CMR sequence development and translation into clinical practice.

Aims Clinical and electrocardiographic (ECG) presentation of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and idiopathic right ventricular outflow-tract tachycardia (RVOT) may be similar. The aim of the study was to assess the validity and utility of T-wave integral measurement as an ECG discriminator of patients with ARVC and RVOT using a body surface mapping (BSM). Methods and results A 120-channel BSM with quantitative signal analysis of the T-wave integral was performed in 10 patients with ARVC. Results were compared with those obtained from 13 patients with RVOT and a control group of 12 healthy subjects (controls). Age, body mass index, and QRS-axis on surface ECG were not significantly different between the groups. Arrhythmogenic right ventricular cardiomyopathy patients showed a significantly negative T-wave integral in the right lower anterior region of the torso when compared with RVOT ( P < 0.001). There was no statistically significant difference between RVOT patients and controls. At a cut-off level of −0.3 mV ms, sensitivity and specificity were 83% [area under curve (AUC) 0.85 ± 0.04 for the comparison of ARVC and RVOT]. These differences were pronounced in ARVC patients with a plakophlin-2 mutation ( P < 0.001). Conclusion Quantitative analysis of the BSM T-wave integral in distinct anatomical regions discriminates ARVC patients from RVOT patients and controls and may serve as an additional diagnostic tool.

Diabet. Med. 29, e241–e248 (2012) Abstract Aims To investigate the health-related quality of life of patients with diabetes mellitus in Singapore and its associations with diabetes-related characteristics and glycaemic control. Methods An interviewer-administered, cross-sectional survey was conducted in a sample of 301 adult diabetes patients under primary care. The survey questionnaire included both a generic health-related quality of life measure, the Euroqol 5-D and a diabetes-specific instrument, the Audit of Diabetes-dependent Quality of Life. Patients’ most recent HbA1c values were extracted from their medical records. Results After excluding patients who lacked the 90-day HbA1c test result, the final number of responses analysed was 282. Pain/discomfort was the most common complaint among the five Euroqol 5-D domains (by 28.0% of the respondents). Lack of freedom to eat was the Audit of Diabetes-dependent Quality of Life domain with the greatest negative average weighted impact (= −3.8, on a scale of −9 to 3). A significant association was observed between Audit of Diabetes-dependent Quality of Life average weighted impact and both duration of diabetes and use of insulin. A negative correlation was found between health-related quality of life and HbA1c values in both health-related quality of life measures (both r = −0.2, P = 0.001). Conclusions Patients with diabetes in primary-care settings frequently reported problems with pain/discomfort and restrictions in diet. Poorer health-related quality of life was found to be associated with higher HbA1c values. The chronicity of diabetes and insulin therapy may have a negative impact on patients’ diabetes-related health-related quality of life. This study indicates the importance of achieving better disease management to improve the health-related quality of life of patients with diabetes.

Background: The aims of the present study were to estimate the rate of progression from newly diagnosed impaired fasting glycemia (IFG) to type 2 diabetes mellitus (T2DM) in Singapore and to identify factors associated with the progression to T2DM in individuals with newly diagnosed IFG. Methods: The present study was a retrospective cohort study of newly diagnosed IFG from the National Healthcare Group Diabetes Registry between 1 January 2006 and 31 December 2007 to estimated the rate of progression to T2DM. Univariate survival analysis, followed by multivariate survival analysis, was performed and interactions were tested in the final model. Results: Over a mean follow-up period of 1.65 ± 0.13 years, 85 of 490 participants with newly diagnosed IFG developed T2DM, giving an annual progression rate of 6.8%. The factors associated with the development of T2DM were higher fasting plasma glucose level in the year of IFG diagnosis (hazard ratio [HR] = 14.6; 95% confidence interval [CI] 5.66–37.5), Chinese race (HR = 2.70; 95% CI 1.44–5.06), and body mass index (HR = 1.11; 95% CI, 1.06–1.15). Conclusions: The progression rate to T2DM is high in subjects with newly diagnosed IFG. Intensive lifestyle modification can be incorporated into their current yearly follow-up to prevent progression to T2DM, which is a growing problem in Singapore.

Objective We aim to determine whether healthcare costs for patients diagnosed with Type 2 Diabetes Mellitus (T2DM) are associated with the severity of diabetes complications as measured by the Diabetes Complication Severity Index (DCSI). Methods Retrospective cohort analysis was performed on a 2007 primary care cohort of T2DM patients. The DCSI is a 13-point scale, which comprises 7 categories of complications and their severity levels. Healthcare cost data from 2008 and 2009 were used as primary outcome. Inpatient and outpatient costs incurred for services consumed by patients within the provider network were included. Generalized linear model with log-link and gamma distribution was used to predict healthcare costs. Results Of the 59,767 T2DM patients, 2977 (5.0%) deaths occurred and 1336 (2.2%) were lost to follow up. Healthcare cost was strongly associated with increase in DCSI score. Compared to patients without complications, those with more complications (higher DCSI score) had an increased risk of higher healthcare costs. Risk ratio (RR) increased from 1.25 (95%CI: 1.19–1.32) for DCSI = 1 to 1.61 (1.51–1.72) for DCSI = 2; 2.10 (1.91–2.31) for DCSI = 3; 2.52 (2.21–2.87) for DCSI = 4 and 3.62 (3.09–4.25) for DCSI ≥ 5. As a continuous score, a one-point increase in the DCSI was associated with a cost increase of 27% (95%CI: 1.25–1.29). Conclusion The DCSI score is a useful tool for predicting direct healthcare costs. The DCSI can be used to triage high-risk patients for more focused secondary prevention interventions at primary care level, in a bid to lower overall healthcare costs.

Mit einem an alle verfugbaren Emailadressen von Fruhforderstellen in der BRD verschickten Fragebogen wurden strukturelle Gegebenheiten und inhaltliche Ausrichtung von Elterngesprachen erfasst. 357 Kolleginnen unterschiedlicher beruflicher Provenienz beteiligten sich. 39.9 % der Fruhfordertatigkeit wird in den Familien erbracht, 30 % ambulant in einer Einrichtung sowie 30 % in einer KiTa. Im Mittel bringen Padagoginnen in der allgemeinen Fruhforderung 15,5 Minuten je Besuch fur das Gesprach mit Eltern auf. 18,1 % der Padagoginnen fuhrten ein 30 bis 60 Minuten dauerndes, zusammenhangendes Elterngesprach einmal im Monat. Die Gesprache drehen sich am haufigsten um 'Erziehung' und 'Forderung'. Die Themen 'Behinderung', 'Bewaltigung' und 'Lebensqualitat' treten seltener auf. Hoheres Lebensalter und Berufserfahrung bestimmen diese Themen haufiger als der Arbeitsort mobil oder ambulant. Starkung von Gesprachsbereitschaft und Gesprachsfuhrung, um die Bereitschaft zu erhohen, emotional schwierige Themen anzusprechen, ergeben sich als Desiderate ebenso wie die Uberprufung der hier explorativ gewonnenen Befunde durch eine reprasentative Untersuchung.

Highlights ► Study the willingness to be vaccinated for H1N1 among Singapore healthcare workers. ► Only 39.4% of respondents were willing to be vaccinated against H1N1. ► Barriers to vaccination were “fear of side effects” and “unsure of effectiveness”. ► People with chronic conditions were not more likely to accept H1N1 vaccination. ► People wanted to know more about the vaccine's side effects and effectiveness., Introduction A novel H1N1 vaccine was manufactured in response to the pandemic in 2009. This study describes the willingness to be vaccinated for H1N1 among healthcare workers (HCWs) in primary healthcare clinics with and without chronic medical conditions, their reasons for refusing vaccination and whether they sought additional information to make an informed decision for the vaccination. Materials and methods An anonymous survey was conducted in November 2009 among all medical, nursing, allied health and operations HCWs in nine primary care clinics in Singapore. Participants were asked if they had any chronic medical conditions associated with influenza-related complications (example: asthma, stroke, heart disease, cancer, diabetes mellitus, renal disease), their perception towards vaccination for H1N1 and against seasonal influenza within the preceding 2 years. Results The initial response rate was 80%, of which 711 (54.7%) of the completed surveys were analysed. Among the 711 respondents, 16.6% reported having at least 1 chronic disease. Asthma (10.8%), hypertension (10.4%) and dyslipidaemia (9.8%) were the main chronic conditions. Only 39.4% of respondents were willing to be vaccinated against H1N1. Males were 2.07 (95% CI 1.19–3.62) times more likely than females to receive the H1N1 vaccination; the 45–54 and 55+ years old were 2.12 (95% CI 1.06–4.24) and 2.44 (95% CI 1.13–5.27) times more willing than those below 25 years old; and those who considered accepting the seasonal influenza vaccine were 7.0 times more likely than those who did not (95%CI 4.48–10.92). The 2 principal barriers were “fear of side effects” and “unsure of vaccine's effectiveness”. Although 78% attended some H1N1-related talks, only 7% of all HCWs felt that they had sufficient information. Most wanted more information about the vaccine's safety profile and contraindications. Conclusion Fewer than 40% of HCWs expressed willingness to receive the H1N1 vaccination, lower than past rates of influenza vaccine. HCWs in primary care clinics who had a chronic condition did not perceive themselves to be at higher risk of developing H1N1-related complications and were not more willing than the rest of the HCWs to accept H1N1 vaccination. Vaccine's side effects and effectiveness were the main concerns. Uptake of H1N1 vaccine may improve with targeted health information covering the vaccine's safety profile.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a nonischaemic cardiomyopathy and leading cause of sudden death in the young. It has been shown that microvascular dysfunction reflected by an impaired myocardial blood flow (MBF) response to stress is present in patients with other forms of nonischaemic cardiomyopathy, e.g. dilated cardiomyopathy, and that the reduced MBF may be related to a poor prognosis. Therefore, we quantified MBF, coronary flow reserve and coronary vascular resistance in patients with nonfailing ARVC using H 2 15 O and PET. In ten male patients with ARVC (mean age 49 ± 14 years), MBF was quantified at rest and during adenosine-induced hyperaemia using H 2 15 O PET. Results were compared with those obtained in 20 age-matched healthy male control subjects (mean age 46 ± 14 years). Resting MBF was not significantly different between patients with ARVC and controls (MBFrest 1.19 ± 0.29 vs. 1.12 ± 0.20 ml/min/ml). However, hyperaemic MBF was significantly lower in patients with ARVC than in controls (2.60 ± 0.96 vs. 3.68 ± 0.84 ml/min/ml; p = 0.005). Consequently, patients with ARVC had a significantly lower coronary flow reserve than control subjects (2.41 ± 1.34 vs. 3.39 ± 0.93; p = 0.030). In addition, hyperaemic coronary vascular resistance was increased in patients with ARVC (36.79 ± 12.91 vs. 26.31 ± 6.49 mmHg × ml-1 × min × ml; p = 0.007), but was found to be unchanged at rest. In this small well-characterized cohort of patients with nonfailing ARVC, we found a significantly reduced hyperaemic MBF and increased coronary vascular resistance. Further studies are necessary to corroborate this potential new functional aspect of the pathophysiological mechanisms underlying ARVC.

Objectives The aim of the present study was to assess the feasibility and safety of target-directed sampling of right ventricular (RV) endomyocardial biopsies (EMB) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Background EMB is an integral part of the diagnostic evaluation of ARVC. Due to safety concerns, EMB are often obtained from the RV septum, which is usually spared from characteristic alterations. At our institution, EMB in ARVC patients were sampled target-directed from predilection areas and areas with abnormal contraction. Methods Under fluoroscopic guidance, 3,777 EMB samples from 6 different RV sites were obtained in 482 patients who were evaluated for unclear cardiomyopathy (n = 280; 58%), assumed myocarditis (n = 59; 12%), or unexplained ventricular tachyarrhythmias (n = 143; 30%). Complication rates were compared with those from exclusively septal EMB procedures (n = 2,321) in 271 patients after heart transplantation (HTx). Results Overall, no procedure-related deaths or sustained ventricular tachyarrhythmias occurred. A pericardial effusion was reported in 6 of 161 patients with the final diagnosis of ARVC (3.7%) needing no further intervention in all but 1 patient (0.6%) who required pericardiocentesis. Among the non-ARVC patients (n = 321), the incidence of a minor pericardial effusion (3.9%) and cardiac tamponade (2.2%) was comparable to that in ARVC (p = NS) but was higher when compared with HTx (p Conclusions Multisite target-directed EMB sampling in ARVC is a safe procedure when performed by experienced interventionalists. The procedure-related complication rates were low and comparable to those in other cardiomyopathies.

Zusammenfassung. Mit der Konstruktion und Validierung eines Fragebogens zu kognitiven Prozessen bei 4- bis 6-jährigen Kindern (KOPKI 4-6) soll das diagnostische Inventar zur Erfassung kognitiver Funktionen bei Vorschulkindern ergänzt werden. Der KOPKI 4-6 erfasst mit 98 Items die sechs Bereiche Sprache, Gedächtnis, Visuell-räumliche Fähigkeiten, Allgemeine Kognition, Aufmerksamkeit und Selbständigkeit. Anhand von Normierungsstichproben (N = 522) wurden alters- und geschlechtsspezifische Normen abgeleitet. Die interne Konsistenz und die Split-Half-Reliabilitäten erwiesen sich als hoch. Signifikante Korrelationen zwischen der Skalen des KOPKI 4-6 und parallel durchgeführten Intelligenztests (n = 154) belegten Kriterienvalidität. Die differentielle Validität wurde anhand klinischer Gruppen mit Sprachentwicklungsstörungen, Aufmerksamkeitsstörungen und kombinierten Entwicklungsstörungen untersucht (n = 104). Eine multivariate Varianzanalyse zeigte signifikante Unterschiede zwischen den klinischen Gruppen. Der KOPKI 4-6 erweist sich damit als ein praktikables Verfahren, das zur Diagnose kognitiver Prozesse bei kleinen Kindern eingesetzt werden und Hinweise auf relevante Stärken oder Schwächen in Teilbereichen der kognitiven Entwicklung geben kann.

Background: In patients with Brugada syndrome (BrS), life-threatening ventricular tachyarrhythmias predominantly occur during vagal stimulation at rest or during sleep. Previous imaging studies displayed an impaired autonomic function in BrS patients. However, it remains unclear whether these alterations primarily stem from a reduction of synaptic release of norepinephrine (NE) or an enhanced presynaptic reuptake. Both conditions could lead to reduced NE concentrations in the synaptic cleft. Therefore, we analyzed key components of the sympathoadrenergic signaling pathways in patients with BrS. Methods and Results: Endomyocardial biopsies were obtained from eight BrS patients (seven male; age 49 ± 15 years) and five controls (three male; age 43 ± 13 years; P = ns). The concentrations of NE, epinephrine (Epi), NE transport (NET) carrier protein, cyclic adenosine 5′monophosphate (cyclic adenosine monophosphate [cAMP]), inhibitory G-proteins (Gi1,2α), troponin-I (TNI), and phosphorylated TNI were analyzed. Levels of NET, Gi1,2α, TNI, Epi, and phosphorylated TNI were comparable between the groups. Compared to controls, patients with BrS showed reduced cAMP and NE concentrations. Conclusions: The current findings expand the concept of adrenergic dysfunction in BrS: the reduction of NE in BrS could lead to an impaired stimulation of β-adrenoceptors resulting in a reduction of cAMP and alterations of the subsequent signaling pathway with potential implication for arrhythmogenesis. (PACE 2011; 34:1147–1153)

Due to the concern of equating correct pronunciation with comprehension and the differences in health care systems, existing health literacy (HL) instruments may not be appropriate for or applicable to English-speaking countries other than the USA. The purpose of this study was to develop and validate the Health Literacy Test for Singapore (HLTS), which is an adapted version of the Short-Test of Functional Health Literacy in Adults. Three hundred and two patients were interviewed and administered the HLTS, the Newest Vital Sign (NVS), a demographic questionnaire, and a knowledge test of chronic diseases. The convergent validity of HLTS was determined by examining the association between HLTS and NVS HL levels, whereas predictive validity was tested by examining the difference in knowledge of chronic conditions between the two HLTS HL (i.e. adequate and inadequate HL) groups. Bivariate correlation of HLTS HL levels with age and education was assessed to test a priori hypotheses that patients with inadequate HL were older and less educated. The results showed that HLTS displayed good internal reliability (Cronbach's alpha = 0.87). The correlation between HLTS and NVS was moderate (γ = 0.55; P = 0.005) and individuals with inadequate HL were older (P = 0.002) and less educated (P = 0.007). In addition, patients with adequate HL had a higher mean score on the chronic disease knowledge test (P = 0.036). In conclusion, the HLTS is a valid and reliable measure for assessing Singaporeans ability to read and comprehend health-related materials written in English.

Aims To evaluate whether the three-dimensional (3D) left atrial volume index (LAVI) and/or the presence of carotid plaques (CP) can predict the result of dobutamine stress echocardiography (DSE), thereby aiding interpretation. Methods and results We studied 130 patients (52 male, mean age 63 ± 11 years) with normal resting wall motion (WM) undergoing DSE. All patients had the end-systolic 2D and 3D LAVI measured, as well as bilateral carotid scanning. DSE was reported as abnormal in 50 (38.5%) patients. 3D end-systolic LAVI measurements were significantly higher (31.5 ± 8.2 vs 27.4 ± 7.4 mL/m2, P = 0.004) in those with an abnormal DSE. The two groups did not differ significantly on the 2D derived maximum LAVI measurements (36.2 ± 9.5 vs 34.2 ± 11.2, P = 0.299) and the presence of plaques in the carotid arteries (89.1 vs. 76.2%, P = 0.100). Receiver operating characteristic curves were created to define cut-offs that could predict the DSE result for the 3D LAVI. A 3D LAVI of >24.5 mL/m2 had a sensitivity of 80% for predicting an abnormal DSE, whereas a value of >36.0 mL/m2 had a specificity of 93% for the same cause. Intra-observer ( r = 0.997, P < 0.0001) and inter-observer ( r = 0.961, P < 0.0001) variability for 3D LAVI measurements was found to be excellent. Conclusion Three-dimensional (but not 2D) assessment of LAVI may offer additional information in predicting the result of DSE. Carotid scanning did not offer additional information for the same cause.

Aim The aim of this study was to investigate whether interventricular asynchrony (IVA) can be measured by electrocardiography. Methods Sixty-two patients (New York Heart Association heart failure functional class III: age, mean ± SD: 64 ± 9 years; ejection fraction, mean ± SD: 24% ± 8%; dilative cardiomyopathy/ischemic cardiomyopathy, n = 39/23) with left bundle branch block (QRS duration, mean ± SD: 165 ± 21 milliseconds) underwent a 120-channel body surface mapping. QRS integral was analyzed and compared with IVA (echo). Results Interventricular asynchrony was associated with significantly decreased QRS integrals 15 cm cranial and 6 cm lateral from V1 in patients with normal axis (n = 36): At a cutoff value of −26 milliseconds ⁎ mV, receiver operating characteristic analysis to predict IVA revealed a sensitivity of 89% and a specificity of 83% (area under curve, mean ± SEM: 0.9 ± 0.07; P < .001). In patients with left axis deviation (n = 26), IVA showed significantly decreased QRS integrals 10 cm caudal from V1: at a cutoff value of −89 milliseconds ⁎ mV, receiver operating characteristic analysis to predict IVA revealed a sensitivity of 83% and a specificity of 100% (area under curve, mean ± SEM: 0.9 ± 0.07; P < .002). Conclusions Interventricular asynchrony strongly correlates with QRS integral. Key lead positions, however, are axis dependent and outside standard leads.

Cardiomyopathies (diseases of the heart muscle) are a relevant but heterogeneous group of cardiac diseases. The underlying structural myocardial alterations, detectable with contemporary cardiac imaging modalities and also on twelve-lead surface ECG, embody both linkage and differentiation of the respective clinical forms. Most of these are defined to the heart, however, cardiac involvement is also known in the presence of specific metabolic or muscular systemic diseases. In many of the known cardiomyopathies, a genetic background has been elucidated thus indicating a potential familial disease. This, in turn, also harbors the risk that more family members may be affected besides the index patient.

Background— Brugada syndrome (BrS) is characterized by the presence of coved ST-segment elevations in the right precordial leads (so-called type I ECG) and additional clinical features. Caused by cardiac ion channel gene mutations, BrS may be associated with ventricular and atrial conduction disturbances as well as ventricular fibrillation. Recent studies have discussed whether BrS is merely a primary electric disorder or whether inflammatory or other histopathologic abnormalities in the right ventricle (RV) underlie the ECG phenotype. Methods and Results— We retrospectively analyzed BrS biopsy samples from 21 unrelated patients for histopathologic abnormalities (hypertrophy, fibrosis, inflammation, fatty tissue) together with the patients’ clinical, genetic, and imaging data. Eleven patients (52%) had normal RV imaging (by angiography, echocardiography, or cardiac MRI). Results of myocardial biopsies were normal in 3 patients (14%) and revealed mostly moderate abnormalities in the others. Four patients (19%) had predominant fatty tissue in the RV myocardium. Using immunohistochemistry and conventional tissue staining, we could not detect inflammatory tissue changes, an observation compatible with the clinical absence of signs for myocarditis. Conclusions— Imaging and histopathologic evaluation may detect moderate but uncharacteristic cardiac abnormalities in patients with BrS. None of the patients had arrhythmogenic RV cardiomyopathy or overt myocarditis. Only in a small subset did predominant histopathologic abnormalities in the biopsy samples of the RV outflow tract occur that could provide a link to the ECG phenotype. A variety of mechanisms, including genetic and structural RV alterations, may underlie the Brugada ECG phenotype.

We demonstrate resonance fluorescence from single In-GaAs/GaAs quantum dots embedded in a rib waveguide beamsplitter structure operated under pulsed laser excitation. A systematic study on the excitation laser pulse duration depicts that a sufficiently small laser linewidth enables a substantial improved single-photon-to-laser-background ratio inside a waveguide chip. This manifests in the observation of clear Rabi oscillations over two periods of the quantum dot emission as a function of laser excitation power. A photon cross-correlation measurement between the two output arms of an on-chip beamsplitter results in a g(2)(0)=0.18, demonstrating the generation, guiding and splitting of triggered single photons under resonant excitation in an on-chip device. The present results open new perspectives for the implementation of photonic quantum circuits with integrated quantum dots as resonantly-pumped deterministic single-photon sources.

Background We investigated whether multichannel ECG-recordings are useful to risk-stratify patients with congenital long-QT syndrome (LQTS) for risk of sudden cardiac death under optimized medical treatment. Methods In 34 LQTS-patients (11 male; age 31±13 years, QTc 478±51ms; LQT1 n = 8, LQT2 n = 15) we performed a standard 12-channel ECG and a 120-channel body surface potential mapping. The occurrence of clinical events (CE; syncope, torsade de pointes (TdP), sudden cardiac arrest (SCA)) was documented and correlated with different ECG-parameters in all lead positions. Results Seven patients developed TdP, four survived SCA and 12 experienced syncope. 12/34 had at least one CE. CE was associated with a longer QTc-interval (519±43ms vs. 458±42ms; p = 0.001), a lower T-wave integral (TWI) on the left upper chest (-1.2±74.4mV*ms vs. 63.0±29.7mV*ms; p = 0.001), a lower range of T-wave amplitude (TWA) in the region of chest lead V8 (0.10±0.08mV vs. 0.18±0.07mV; p = 0.008) and a longer T-peak-T-end time (TpTe) in lead V1 (98±23ms vs. 78±26ms; p = 0.04). Receiver-operating-characteristic (ROC) analyses revealed a sensitivity of 96% and a specificity of 75% (area under curve (AUC) 0.89±0.06, p = 0.001) at a cut-off value of 26.8mV*ms for prediction of CE by TWI, a sensitivity of 86% and a specificity of 83% at a cut-off value of 0.11mV (AUC 0.83±0.09, p = 0.002) for prediction of CE by TWA and a sensitivity of 83% and a specificity of 73% at a cut-off value of 87ms (AUC 0.80±0.07, p = 0.005) for prediction of CE by TpTe. Conclusions Occurrence of CE in LQTS-patients seems to be associated with a prolonged, low-amplitude T-wave.

Background Perfusion cardiovascular magnetic resonance (CMR) and fractional flow reserve (FFR) are emerging as the most accurate tools for the assessment of myocardial ischemia noninvasively or in the catheter laboratory. However, there is limited data comparing CMR and FFR in patients with multi-vessel disease. This study aims to evaluate the correlation between myocardial ischemia detected by CMR with FFR in patients with multivessel coronary disease at angiography. Methods and results Forty-one patients (123 vascular territories) with angiographic 2- or 3-vessel coronary artery disease (visual stenosis >50 %) underwent high-resolution adenosine stress perfusion CMR at 1.5 T and FFR measurement. An FFR value of On a per patient basis, CMR and FFR detected identical ischemic territories in 19 patients (46 %) (mean number of territories 0.7+/−0.7 in both (p = 1.0)). On a per vessel basis, 89 out of 123 territories demonstrated concordance between the CMR and FFR results (72 %). In 34 % of the study population, CMR resulted in fewer ischemic territories than FFR; in 12 % CMR resulted in more ischemic territories than FFR. There was good concordance between the two methods to detect myocardial ischemia on a per-patient (k =0.658 95 % CI 0.383-0.933) level and moderate concordance on a per-vessel (k = 0.453 95 % CI 0.294–0.612) basis. Conclusions There is good concordance between perfusion CMR and FFR for the identification of myocardial ischemia in patients with multi-vessel disease. However, some discrepancy remains and at this stage it is unclear whether CMR underestimates or FFR overestimates the number of ischemic segments in multi-vessel disease.

Determining the cause for the sudden death in young adults tends to be complex and difficult. Two cases of death of young people were autoptically investigated who died suddenly while carrying out their hobbies (a 22-year-old male musician and a 20-year-old female dancer). In both cases neither the police investigation, the autopsy, nor the toxicological investigations gave any relevant results. However, when investigating the histology fatty and fibrotic tissue in the right ventricle of the myocardium were found, whereas the myocytes proved to be degenerated—typical for arrhythmogenic right ventricular cardiomyopathy (ARVC). It is important to consider the possibility of heart rhythm failure if a clear reason for sudden death in young adults cannot be detected. Heart rhythm failure often involves the genetic background of the case, which suggests that genetic analysis should be carried out as a supportive means of diagnostics.

The aim of the present study was to forecast the prevalence and number of adult Singapore residents with prediabetes and diabetes in 2035.A dynamic Markov model with nine mutually exclusive states was developed based on the clinical course of diabetes using time-dependent rates and probabilities. A 1-year cycle over a 25-year time horizon from 2010 to 2035 was used in the model. With publicly available data and a chronic disease register, the model forecast annual disease burden by simulating transition of cohorts across different health states using prevalence rates, incidence rates, mortality rates, disease transition, disease detection, and complication rates. An aging index was used in the model in anticipation of population aging to minimize risks of underestimating disease burden.From 2010 to 2035, the number of Singapore residents with prediabetes and diabetes is projected to more than double, from 434 685 to 903 596 and from 373 104 to 823 802, respectively. The prevalence of prediabetes and diabetes will rise steadily from 15.5 % to 24.9 % and from 13.3 % to 22.7 %, respectively. By 2035, a further estimate of 733 174 and 100 250 patients with prediabetes and uncomplicated diabetes, respectively, will remain undiagnosed. The prevalence of detected and undetected complications is forecast to rise from 60.0 % in 2010 to 70.2 % by 2035.By 2035, the prevalence of prediabetes and diabetes among Singapore residents aged 21+ years is expected to be one in four and one in five, respectively. There is an impetus to adopt more aggressive interventions to contain disease progression.

Background Chronic urticaria is a common skin condition that causes significant impact on patient's quality of life. Objective The purpose of the study was to assess adherence to therapy and quality of life of patients with chronic urticaria. We also aimed to study the relationship of medication adherence and quality of life of patients with chronic urticaria. Methods A cross sectional study was conducted with 103 patients from the dermatology clinic of National University Hospital, Singapore. Patients with chronic urticaria were asked to fill out a questionnaire for assessment of adherence to therapy and quality of life. We used the Morisky 8-Item Medication Adherence Scale to categorize adherence as high, medium, low. For assessment of quality of life, we used the validated chronic urticaria quality of life questionnaire (CU-Q2oL) by Bairadani et al. Results The highest median scores for the items measuring quality of life were interference with sleep and pruritus. We also observed that the majority of patients (71.9%) had low adherence to medical therapy. No difference in adherence was noted in patients on once daily medication or more frequent dosing. There was no significant difference in the quality of life among patients with low and medium adherence to therapy. Conclusion Quality of life of patients with chronic urticaria does not depend on the patients' adherence to medications. Dosing frequency does not affect adherence in our study population. It is also important to recognize the symptoms and issues most affecting quality of life of patients with chronic urticaria, so as to improve overall management.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inheritable heart muscle disease that predominantly affects the right ventricle (RV) and predisposes to ventricular arrhythmias and sudden cardiac death (SCD).1–17 In the last three decades, there have been a significant number of studies defining the pathogenesis, genetic aspects, and clinical manifestations of the disease (See ‘Etiology, pathogenesis, diagnosis and natural history’ in the online-only Data Supplement). In 1994 and 2010, an International Task Force (ITF) document proposed guidelines for the standardized diagnosis of ARVC/D based on electrocardiographic (ECG), arrhythmic, morphological, histopathologic, and clinico-genetic factors.18,19 The growing knowledge regarding arrhythmic outcome, risk factors, and life-saving therapeutic interventions, make it particularly timely to critically address and place into perspective the issues relevant to the clinical management of ARVC/D patients. The present ITF consensus statement is a comprehensive overview of currently used risk stratification algorithms and approaches to therapy, either pharmacological or nonpharmacological, which often poses a clinical challenge to cardiovascular specialists and other practitioners, particularly those infrequently engaged in the management of ARVC/D. This document should be regarded as a guide to clinical practice where rigorous evidence is still lacking, because of the relatively low disease prevalence and the absence of controlled studies. Recommendations are based on available data derived from nonrandomized and observational studies and consensus within the conference panellists. When development of prognostic-therapeutic algorithms was controversial, management decisions were recommended to be individualized. Recommendation and level of evidence of specific management options were classified according to predefined scales, as outlined in Tables 1 and 2 (http://www.escardio.org/guidelines-surveys/esc-guidelines/about/Pages/rules-writing.aspx). Because randomized studies are not available, most consensus recommendations on treatment of ARVC/D are based on data derived from follow-up registries and/or experts opinions (ie, level of evidence B or C). View this table: Table 1. Classes of Recommendations View this table: Table 2. Levels of Evidence All members of …

To assess clinical efficacy of IV paracetamol 1 g and IV dipyrone 1 g on a 24-h dosing schedule in this randomised, double-blinded study of 40 ASA I-III (American Society of Anesthesiologists classification of physical status) patients undergoing surgery for breast cancer.General anaesthesia using remifentanil and propofol was performed for surgery. The patients were randomly allocated to two groups, receiving infusions of paracetamol 1 g/100 mL (Para Group) or of dipyrone 1 g/100 mL (Dipy Group) 30 min before arrival in the recovery area and every 6 h up to 24 h postoperatively. All patients had unrestricted access to opioid rescue medication via an IV patient-controlled analgesia (PCA) device.The primary variables for clinical equivalence were the differences between the mean values for pain scores at rest and pain scores on coughing over 30 h postoperatively. The equivalence margin was determined as +/-10 mm on the visual analogue scale (VAS).Regarding pain scores at rest, the 90% CI of the mean differences between the treatment groups over 30 h postoperatively was found to be within the predefined equivalence margin [+7.5/-6.2], and the CI values for pain scores on coughing [+7.3/-9.0] were similar. The two groups did not differ in cumulative opioid rescue consumption (Dipy-Group 14.8 +/- 17.7 mg vs. Para Group 12.1 +/- 8.8 mg, p = 0.54) nor in piritramide loading dose (Dipy Group 0.95 +/- 2.8 mg vs. Para Group 1.3 +/- 2.8 mg, p = 0.545). Five patients in the Dipy Group experienced hypotension in contrast to none in the Para Group (p = 0.047). There were no significant between-treatment differences for other adverse events, patient satisfaction scores (p = 0.4) or quality of recovery scores (p = 0.3).IV paracetamol 1 g is clinically equivalent to IV dipyrone 1 g for postoperative analgesia after surgery for breast cancer.

Aims We report three young patients presenting with life-threatening ventricular tachycardia (VT) or ventricular fibrillation (VF) and/or survived sudden cardiac arrest, who were admitted to our institution for further diagnostic evaluation. Methods and results In all patients, idiopathic left ventricular (LV) aneurysms were identified after a detailed non-invasive and invasive evaluation. Sustained VT/VF was inducible during programmed ventricular stimulation in two of the three patients. Left ventricular aneurysms were depicted and characterized by various imaging modalities (echocardiography, magnetic resonance imaging, LV angiography). To elucidate the pathogenesis further, both myocardial viability and regional sympathetic innervation were assessed by radionuclide imaging techniques. Defects of innervation and metabolism were documented in the area of the aneurysm but distal to the aneurysm there were no signs of downstream denervation. Conclusion Life-threatening arrhythmias may be the first manifestation of an idiopathic LV aneurysm, which can be reliably diagnosed with modern imaging techniques. Radionuclide imaging may yield additional information as to the involvement of the autonomic nervous system potentially associated with arrhythmogenesis. Management strategies in patients with an idiopathic LV aneurysm range from antiarrhythmic drug treatment, implantation of an automatic cardioverter–defibrillator to surgical aneurysmectomy.

Idiopathic ventricular fibrillation (IVF) is defined as VF in the absence of any identifiable structural or functional cardiac disease. The underlying pathophysiological mechanisms are unknown. This study was performed to investigate the potential impact of sympathetic dysfunction, assessed by 123I-meta-iodo-benzylguanidine scintigraphy (123I-MIBG SPECT), on the long-term prognosis of patients with IVF. 123I-MIBG SPECT was performed in 20 patients (mean age 37±13 years) with IVF. Mean follow-up of patients after study entry was 7.2±1.5 years (range 4.9–10.5 years). Ten patients (five men, five women; mean age 43±12 years; p=NS versus study group) with medullary carcinoma of the thyroid gland served as an age-matched control group. Abnormal 123I-MIBG uptake was observed in 13 patients (65%). During follow-up, 18 episodes of VF/fast polymorphic ventricular tachycardias occurred in four IVF patients with abnormal 123I-MIBG uptake whereas only two episodes of monomorphic ventricular tachycardia (and no VF) occurred in a single IVF patient with normal 123I-MIBG uptake. Impairment of sympathetic innervation may indicate a higher risk of future recurrent episodes of life-threatening ventricular tachyarrhythmias in patients with IVF. Studies in larger cohorts are required to validate the significance of 123I-MIBG SPECT during the long-term follow-up of these patients.

Antagonists of the serotonergic 5-hydroxytryptamine 3A receptor (5-HT(3A)R) and muscle nicotinic acetylcholine receptors (nAChR) are widely used in anesthesia practice. Both 5-HT(3A)R and nAChR are ligand-gated ion channels with known pharmacological overlap between some of their agonists and antagonists. We studied the actions of clinically used 5-HT(3A)R antagonist antiemetics and nondepolarizing muscle blockers on ionic currents elicited by the activation of mammalian 5-HT(3A)R and muscle nAChR, expressed in Xenopus laevis oocytes. Currents were recorded using a whole-cell two-electrode voltage clamp technique. Dolasetron, ondansetron, and granisetron reversibly inhibited 5-HT(3A)R function at nanomolar concentrations with 50% inhibitory concentrations (IC(50)) of 11.8, 6.4, and 0.2 nM; the rank order of inhibition correlated well with their clinical antiemetic potencies. The principal metabolite of dolasetron, hydrodolasetron, was 40 times more potent than the parent compound on 5-HT(3A)R (IC(50) = 0.29 nM). The potency of the nondepolarizing muscle blocker d-tubocurarine in blocking 5-HT(3A)R was similar to that of the antiemetics and significantly more than vecuronium and rapacuronium (IC(50) = 11.4 nM, 18.9 microM, 60.5 microM). Conversely, ondansetron, dolasetron, and granisetron also reversibly inhibited nAChR currents in a dose-dependent manner with IC(50)s of 14.2, 7.8, and 4.4 microM for the adult nAChR and 16.0, 18.6, and 13.9 microM for the embryonic nAChR. Again, hydrodolasetron showed significantly (10 times) more inhibitory potency on the adult nAChR than the parent compound dolasetron. These results indicate that drugs that target specific ligand-gated ion channels may also affect other ion channel types.

The synthesis of a novel amino-ON CPG support and its application in the synthesis of 3'-aminoalkylated oligonucleotides is reported. The release of oligonucleotides with free 3'-amino groups is accomplished by treatment with concentrated ammonia for 2 h at 55 degrees C.

Background— Life-threatening ventricular tachyarrhythmias can occur in young patients without structural heart disease (idiopathic forms). In many patients, these are typically triggered by an increased sympathetic tone, eg, by physical or mental stress. In contrast, in Brugada syndrome, ventricular tachyarrhythmias more often occur during rest or sleep when the vagal tone is predominant. Furthermore, adrenergic agonists can reduce the level of ST-segment elevation, whereas it is increased by parasympathetic agonists or adrenergic antagonists. The aim of this study was to investigate presynaptic and postsynaptic myocardial sympathetic function in patients with Brugada syndrome. Methods and Results— Nine patients with Brugada syndrome (6 male, 3 female; age, 41±13 years) were enrolled in this study. The cardiac autonomic nervous system was assessed noninvasively, quantifying myocardial presynaptic and postsynaptic sympathetic function by means of positron emission tomography with the norepinephrine analogue 11 C-Hydroxyephedrine ( 11 C-HED) and the nonselective β-blocker 11 C-CGP 12177 ( 11 C-CGP). Presynaptic sympathetic norepinephrine recycling, assessed by 11 C-HED, was globally increased in patients with Brugada syndrome compared with a group of age-matched healthy control subjects (92.9±16.2 mL/g versus 69.1±14.2 mL/g; P 11 C-CGP, was similar in patients and control subjects (10.4±6.7 pmol/g versus 10.2±2.9 pmol/g; P =NS). Conclusions— The present study on autonomic innervation in Brugada syndrome describes an enhanced presynaptic norepinephrine recycling with preserved β-adrenoceptor density, further supporting the hypothesis of an autonomic dysfunction in Brugada syndrome. This is a further step toward the understanding of the pathophysiology of the disease with potential future impact on therapeutic strategies.

We performed this study to assess the recovery period after neuromuscular blockade by electromyographic F-wave analysis, a method that supplies more information about more proximal parts of the motor system than conventionally used methods, e.g., mechanomyography (MMG). In 20 neurosurgical ASA physical status I or II patients anesthesia was induced and maintained with IV fentanyl and midazolam. Patients were randomly assigned to receive either 0.25 mg/kg mivacurium (MV group, n = 10) or 0.1 mg/kg pancuronium (PC group, n = 10) intraoperatively. MMG monitoring of the adductor pollicis muscle was performed continuously. F waves were recorded at the abductor pollicis muscle of the contralateral hand at train-of-four (TOF) ratios of 0.1, 0.25, 0.5, 0.7, 0.75, 0.8, 0.85, 0.9, and 0.95. Recovery of F-wave amplitudes after neuromuscular blockade with pancuronium was significantly slower compared with mivacurium (P = 0.004) during the clinically important recovery period defined by MMG TOF ratios from 0.7 to 0.95. This electrophysiologic finding suggests a differential recovery of the motor system after administration of pancuronium and mivacurium not detected by MMG.

Arrhythmien aus dem rechten Ventrikel treten bevorzugt bei jungen Patienten mit seltenen kardialen Erkrankungen auf. Wesentliche Grunderkrankungen sind die idiopathische rechtsventrikulare Ausflusstrakt-Tachykardie (RVOT-VT), die arrhythmogene rechtsventrikulare Kardiomyopathie (ARVC), das Brugada-Syndrom und angeborene Herzfehler (v. a. Fallot-Tetralogie). In Abhangigkeit von der zugrunde liegenden Erkrankung bestehen erhebliche Unterschiede in der Diagnostik, Therapie und Prognose, welche wesentlich durch den plotzlichen Herztod bestimmt wird. Fur die optimale Versorgung der Patienten ist eine detaillierte Diagnostik und Risikostratifikation erforderlich. Die individuelle Therapiestrategie richtet sich nach der Grunderkrankung, Arrhythmiecharakteristik und dem Risiko des plotzlichen Herztodes und beinhaltet die antiarrhythmische Pharmakotherapie, die Katheterablation und die Implantation eines Cardioverter-Defibrillators. Diese Ubersicht fasst das aktuelle Wissen uber die Pathogenese, Diagnostik, Therapie und Prognose der wesentlichen Erkrankungen zusammen, die mit Arrhythmien aus dem rechten Ventrikel einhergehen.

UNLABELLED Methadone is a strong opioid analgesic that is finding increasing use in chronic pain therapeutics. We explored its reported efficacy for inhibiting N-methyl-D-aspartate (NMDA) receptors in a functional electrophysiologic assay (Xenopus laevis oocyte expression). Racemic methadone inhibited all subtypes of rat NMDA receptors with derived 50% inhibitory concentrations in the low micromolar range. These concentrations overlap with clinically achievable concentrations reported in pharmacokinetic studies. In contrast, morphine inhibited these functional ion channels only at 8-16 times larger concentrations. The NR1/2A and NR1/2B subtype combinations were in general significantly more sensitive to inhibition by methadone and morphine compared with the NR1/2C and NR1/2D subtypes. In the presence of racemic methadone, the maximum NMDA-stimulated currents were markedly decreased, but the NMDA concentration producing 50% of maximal activation was altered only slightly, indicating that methadone blocks by a noncompetitive mechanism. Although stereoisomers of methadone showed minimal stereoselectivity in most subtypes, R(-) methadone was highly selective in its inhibition of the NR1/2A combination. These results provide further functional data describing the NMDA receptor inhibitory actions of methadone and support the hypothesis that methadone acts through both opioid and NMDA receptor mechanisms. IMPLICATIONS At clinically achievable concentrations, methadone inhibits functional N-methyl-D-aspartate receptors. These results indicate a unique mode of action by this opioid that may enhance its ability to treat chronic pain and to limit opioid tolerance.

A novel improved controlled pore glass (CPG) support based on the 2-(hydroxymethyl)-6-nitrobenzoyl (HMNB) protecting group was developed for the synthesis of 3′-aminoalkylated oligonucleotides. The release of oligonucleotides with free 3′-amino groups from the support is complete within 2 h at 55 °C in concentrated ammonia.

summary. This survey was designed to evaluate the use of autologous blood transfusion techniques in Germany in 2000 and to identify how the use of these techniques has changed over the past 5 years. Questionnaires were mailed to the chief anaesthesiologists of 400 randomly selected German hospitals with ≥25 surgical beds. Information was sought about the current and past use of preoperative autologous blood donation (PABD), acute preoperative haemodilution and peri-operative blood salvage. Data were requested for the calendar year 2000. Three hundred and forty-three (86%) completed questionnaires were returned. PABD, haemodilution and peri-operative blood salvage were used by 85, 54 and 67% of respondents, respectively. Thirty-seven per cent of PABD users reported that PABD use declined, 28% reported that it increased and 34% reported that it remained unchanged over the past 5 years. The proportions of those reporting declining vs. increasing use of PABD did not differ significantly (P = 0·09). Sixty per cent of users of haemodilution reported that its use declined, 10% reported that it increased and 29% reported that it remained unchanged over the past 5 years. Sixteen per cent of hospitals that were equipped with cell-washing devices reported that the use of these devices declined, 47% reported that it increased and 37% reported that it remained unchanged over the past 5 years. The results indicate that autologous blood transfusion techniques were widely used in Germany in 2000, with PABD being the most common technique. The use of PABD did not change significantly, the use of haemodilution declined markedly and the use of peri-operative cell salvage increased markedly during the past 5 years before the survey.

Summary We compared the pharmacokinetics, pharmacodynamics and safety profile of a new galenic formulation of propofol (AM149 1%), which does not contain soyabean oil, with a standard formulation of propofol (Disoprivan® 1%). In a randomised, double-blind, cross-over study, 30 healthy volunteers received a single intravenous bolus injection of 2.5 mg.kg−1 propofol. Plasma propofol levels were measured for 48 h following drug administration and evaluated according to a three-compartment model. The pharmacodynamic parameters assessed included induction and emergence times, respiratory and cardiovascular effects, and pain on injection. Patients were monitored for side effects over 48 h. Owing to a high incidence of thrombophlebitis, the study was terminated prematurely and only the data of the two parallel treatment groups (15 patients in each group) were analysed. Plasma concentrations did not differ significantly between the two formulations. Anaesthesia induction and emergence times, respiratory and cardiovascular variables showed no significant differences between the two treatment groups. Pain on injection (80 vs. 20%, p

Summary Background: Volume replacement with hydroxyethyl starch (HES), a synthetic colloid, is widely accepted in adults, but only few data exist regarding its use in children. The aim of this study was to assess the effect of a low molecular weight HES solution (HES 70/0.5) compared with lactated Ringer's solution (LR) on haemoglobin levels as an indirect measure of plasma expansion in infants and toddlers, and its perioperative safety. Methods: Sixty-four patients, aged 1–38 months, were allocated randomly to receive 20 ml·kg−1 body weight of either HES 70/0.5 or LR during the first hour of urological surgery lasting >2 h. Thereafter, only LR was infused to maintain haemodynamic stability. Intraoperative blood loss and administered fluid volumes were analysed. Haemoglobin levels were determined perioperatively and intraoperatively at completion of volume loading. Changes in body weight and the incidence of postoperative oedema were assessed 24 and 48 h after surgery. For the safety analysis, patients were monitored for 72 h. Results: Intraoperative haemoglobin levels decreased significantly more with HES 70/0.5 (30 ± 10 g·l−1) compared with LR (21 ± 12 g·l−1) (P

Wir berichten uber den Langzeitverlauf eines kombinierten fusiformen Aneurysmas der Arteria subclavia dexter sowie des Abgangs des Truncus thyreocervicalis (3,2×2,8×2,2cm (Breite×Hohe×Tiefe)) bei einem 33-jahrigen Patienten. Bereits perinatal wurde der klinische Verdacht auf das Vorliegen einer Aortenisthmusstenose geausert, allerdings zum damaligen Zeitpunkt kein Interventionsbedarf gesehen. Die weitere Entwicklung des Kindes verlief zunachst normal, bis im Alter von 11 Jahren der Patient erneut aufgrund nach sportlicher Aktivitat verspurten Schwindelgefuhls kardiologisch vorgestellt wurde. Bei klinisch evidenter Progression wurde eine Herzkatheterdiagnostik durchgefuhrt, die eine juxtaductale Aortenisthmusstenose zeigte. Diese wurde konsekutiv mittels End-zu-End-Anastomose 1981 operativ korrigiert. Daneben zeigte sich bereits eine aneurysmatisch veranderte Arteria subclavia dexter, wobei diesbezuglich ein konservatives Procedere vorgeschlagen wurde. Der Patient stellte sich in regelmasigen Abstanden zu einer Verlaufskontrolle in unserer Ambulanz vor und ist seitdem vollstandig asymptomatisch. Der vorliegende Bericht zeigt den nunmehr uber 20-jahrigen asymptomatischen Verlauf eines fusiformen Aneurysmas der Arteria subclavia dexter unter Einbeziehung des ebenfalls fusiform aneurysmatisch veranderten Abgang des Truncus thyreocervicalis und bietet einen Uberblick der Literatur zu diesem Thema.

Blockade of voltage-gated sodium (Na+) channels by local anesthetics represents the main mechanism for inhibition of impulse propagation. Local anesthetic-induced potassium (K+) channel inhibition is also known to influence transmission of sensory impulses and to potentiate inhibition. K+ channels involved in this mechanism may belong to the emerging family of background tandem pore domain K+ channels (2P K+ channels). To determine more precisely the effects of local anesthetics on members of this ion channel family, we heterologously expressed the 2P K+ channels TASK-2 (KCNK5), TASK-1 (KCNK3), and chimeric TASK-1/TASK-2 channels in oocytes of Xenopus laevis. TASK-2 cDNA-transfected HEK 293 cells were used for single-channel recordings. Local anesthetic inhibition of TASK-2 was dose-dependent, agent-specific, and stereoselective. The IC50 values for R-(+)-bupivacaine and S-(-)-bupivacaine were 17 and 43 micro M and for R-(+)-ropivacaine and S-(-)-ropivacaine, 85 and 236 micro M. Lidocaine (1 mM) inhibited TASK-2 currents by 55 +/- 4%, whereas its quaternary positively charged analog N-ethyl lidocaine (QX314) had no effect. Bupivacaine (100 micro M) decreased channel open probability from 20.8 +/- 1.6% to 5.6 +/- 2.2%. Local anesthetics [300 micro M R-(+)-bupivacaine] caused significantly greater depolarization of the resting membrane potential of TASK-2-expressing oocytes compared with water-injected control oocytes (15.8 +/- 2.5 mV versus 0.1 +/- 0.05 mV; p < 0.001). Chimeric TASK-1/TASK-2 2P K+ channel subunits that retained pH sensitivity demonstrated that the carboxy domain of TASK-2 mediates the greater local anesthetic sensitivity of TASK-2. These results show that clinically achievable concentrations of local anesthetics inhibit background K+ channel function and may thereby enhance conduction blockade.

Zusammenfassung. Eine Literaturübersicht erörtert Beiträge zur Wirksamkeit von Frühförderung für die Publikationsjahre 1995 bis 2002. Methodische Schwierigkeiten wie Definition von Fallgruppen, outcome-Kriterien und Kontrollgruppen schränken die Aussagekraft vorliegender Studien ein und ziehen die Angemessenheit von Effektivitätsprüfungen in Zweifel, die den komplexen interpersonalen Handlungsraum Frühförderung auf wenige Entwicklungsparameter reduzieren. Frühzeitigkeit und Intensität der Förderung scheinen sich zumindest kurzfristig günstig auf kognitive Merkmale wie etwa auch Sprachentwicklung auszuwirken. Für den motorischen Bereich gibt es derzeit keine Anzeichen für die Überlegenheit einer bestimmten Methode. Wenn auch Befunde für günstige Auswirkungen von Förderung positiver und responsiver Eltern-Kind-Interaktionen vorliegen, bilden sich für die Praxis bedeutsame umfassende Variablen wie familiäre Lebensqualität, Kompetenzgefühl und Befindlichkeit bislang kaum in der Forschung ab.

Inherited ventricular arrhythmias such as the long QT syndrome (LQTS), Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia (CPVT), idiopathic ventricular fibrillation (VF), and arrhythmogenic right ventricular cardiomyopathy (ARVC) account for a relevant proportion of sudden cardiac death cases in young patients cohorts. The detailed pathogenetic mechanisms of inherited ventricular arrhythmias are still poorly understood because systematic investigations are difficult to perform due to low patient numbers and the lack of appropriate experimental models. However, recent advances in research and science have identified a genetic background for many of these diseases. Present Knowledge: In LQTS, various mutations in different genes encoding for cardiac potassium and sodium channel proteins have been identified (“channelopathy”), and initial progress in genotype-phenotype correlation is made. Mutations in the cardiac sodium channel gene have also been identified in a subset of patients with Brugada syndrome, whereas a genetic background has not yet been demonstrated in idiopathic VF and right ventricular outflow-tract tachycardia (RVO-VT). Very recently, mutations in the cardiac ryanodine receptor gene have been identified in CPVT and in a subgroup of patients with ARVC. Although several chromosomal loci were suggested, no other responsible genes or mutations have been found in autosomal dominant forms of ARVC. However, in Naxos disease, a recessive form of ARVC with coexpression of palmoplantar keratoderma and woolly hair, a mutation in the plakoglobin gene has recently been discovered, thus underscoring the potential role of genetic alterations in cytoskeletal proteins in ARVC. Future Perspectives: In the next years, significant progress in the genetic diagnosis pathophysiologic understanding of disease mechanisms, genotype-phenotype correlation, and the development of gene- or target-directed treatment strategies can be expected in the field of inherited ventricular arrhythmias. Conclusion: This review summarizes the current knowledge of the molecular mechanisms, including aspects of pathoanatomy, autonomic innervation, genetics, and genotype-phenotype correlations with their potential implications for diagnosis and treatment of inherited ventricular arrhythmias.