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Ketamine may affect the reliability of electroencephalographic (EEG) depth-of-hypnosis indices as it affects power in high-frequency EEG components. The purpose of this study was to compare the effects of ketamine on three commonly-used depth-of-hypnosis indices by extending our EEG simulator to allow replay of previously-recorded EEG. Secondary analysis of previously-collected data from a randomized controlled trial of intravenous anesthesia with ketamine: Group 0.5 [ketamine, 0.5 mg kg−1 bolus followed by a 10 mcg kg−1 min−1 infusion], Group 0.25 [ketamine, 0.25 mg kg−1 bolus, 5 mcg kg−1 min−1 infusion], and Control [no ketamine]. EEG data were replayed to three monitors: NeuroSENSE (WAV), Bispectral Index (BIS), and Entropy (SE). Differences in depth-of-hypnosis indices during the initial 15 min after induction of anesthesia were compared between monitors, and between groups. Monitor agreement was evaluated using Bland–Altman analysis. Available data included 45.6 h of EEG recordings from 27 cases. Ketamine was associated with higher depth-of-hypnosis index values measured at 10 min (BIS, χ2 = 8.01, p = 0.018; SE, χ2 = 11.44, p = 0.003; WAV, χ2 = 9.19, p = 0.010), and a higher proportion of index values > 60 for both ketamine groups compared to the control group. Significant differences between monitors were not observed, except between BIS and SE in the control group. Ketamine did not change agreement between monitors. The ketamine-induced increase in depth-of-hypnosis indices was observed consistently across the three EEG monitoring algorithms evaluated. The observed increase was likely caused by a power increase in the beta and gamma bands. However, there were no lasting differences in depth-of-hypnosis reported between the three compared indices.

Background Risk factors for primary non-melanoma skin cancer (NMSC) in organ transplant recipients (OTR) have been well described. Data for subsequent NMSC and dynamics in their occurrence in OTR are limited. Objective To study long-term risks of primary and subsequent NMSC and associated risk factors in OTR. Methods A retrospective single-centre cohort study analysing medical records from a dermato-oncological specialty clinic. Results Of 464 OTR 110 (23.7%) developed at least one, 73 (15.7%) two and 51 (11%) three NMSC during a median follow-up of 9.6 years. Cumulative incidences at 5, 10 and 15 years were 14.7%, 23.5% and 34.5% for the first and 75.8%, 86.5% and 93.3% for the second. Median time-to-diagnosis declined from 22 years (95% CI 19-25) to 2 years (1-3) and about 1 year (0-2) for the first, second and third NMSC. Risk for subsequent NMSC only partially related to risk factors for the primary NMSC. Histologic type of the first NMSC predicted subtype and time-to-diagnosis of the subsequent NMSC. Conclusions A first post-transplant NMSC, particularly a SCC, confers a high risk for subsequent NMSC arising with accelerated dynamics. Risk-adapted dermato-oncologic surveillance is advisable for all OTR.

Ketamine may affect the reliability of electroencephalographic (EEG) depth-of-hypnosis indices as it affects power in high-frequency EEG components. The purpose of this study was to compare the effects of ketamine on three commonly-used depth-of-hypnosis indices by extending our EEG simulator to allow replay of previously-recorded EEG. Secondary analysis of previously-collected data from a randomized controlled trial of intravenous anesthesia with ketamine: Group 0.5 [ketamine, 0.5 mg kg

This paper contrasts the empirical features of financial and business cycles of 13 European Union countries, and discusses candidate theoretical mechanisms which could explain these differences. Relative to their business cycle counterparts, we show that financial cycles have a higher amplitude, a longer duration and exhibit far greater symmetry. Mostly owing to this difference in symmetry, we find that financial and business cycles synchronise on average only two-thirds of the time, exhibiting weaker concordance in countries having experienced very persistent financial downturns. We then relate our empirical results to the literature by reviewing five model mechanisms that could potentially underlie these facts. Overall, our results suggest that macroeconomic stabilization and financial stability objectives can, at times, be in conflict.

We operationalize the definition of systemic risk provided by the IMF, BIS, and FSB and derive a two-stage hierarchical hypothesis test to identify indicators of systemic risk. Applying the framework to a set of candidate variables for 45 countries, we detect two credit-based financial cycle variables that, by and large, pass our test. However, for many other variables, including the Basel III credit-to-GDP gap, we find that elevated systemic risk is signaled by high values in some countries and by low values in others. More generally, our results suggest that, ex ante, systemic risk can be clearly identified only once the turning points of indicators have been observed.

We propose and implement a method to identify shocks to transition risk. We identify transition risk shocks as instances where a strong differential valuation of green versus brown firms coincides with significant information on climate change. For that purpose, we combine information from long-short equity portfolios sorted on firms' carbon footprints with information from textual analysis of newspaper archives. We find that shocks increasing transition risk (negative abnormal returns of brown firms) induce a decline in aggregate and sectoral industrial production. Moreover, they significantly affect financial stability, as measured by the excess bond premium or credit conditions more generally. Finally, we document a pronounced asymmetry in the economy's response to shocks increasing or decreasing transition risk.

We show that one should not use the one-sided Hodrick-Prescott filter (HP-1s) as the real-time version of the two-sided Hodrick-Prescott filter (HP-2s): First, in terms of the extracted cyclical component, HP-1s fails to remove low-frequency fluctuations to the same extent as HP-2s. Second, HP-1s dampens fluctuations at all frequencies -- even those it is meant to extract. As a remedy, we propose two small adjustments to HP-1s, aligning its properties closely with HP-2s: (1) a lower value for the smoothing parameter and (2) a multiplicative rescaling of the extracted cyclical component. For example, for HP-2s with lambda = 1,600 (value of smoothing parameter), the adjusted one-sided HP filter uses lambda_star = 650 and rescales the extracted cyclical component by a factor of 1.1513. Using simulated and empirical data, we illustrate the relevance of the adjustments. For instance, financial cycles may appear 1.7 times more volatile than business cycles, where in fact volatilities differ only marginally.

Hamilton (2017) criticises the Hodrick and Prescott (1981, 1997) filter (HP filter) because of three drawbacks (i. spurious cycles, ii. end-of-sample bias, iii. ad hoc assumptions regarding the smoothing parameter) and proposes a regression filter as an alternative. I demonstrate that Hamilton's regression filter shares some of these drawbacks. For instance, Hamilton's ad hoc formulation of a 2-year regression filter implies a cancellation of two-year cycles and an amplification of cycles longer than typical business cycles. This is at odds with stylised business cycle facts, such as the one-year duration of a typical recession, leading to inconsistencies, for example, with the NBER business cycle chronology. Nonetheless, I show that Hamilton's regression filter should be preferred to the HP filter for constructing a credit-to-GDP gap. The filter extracts the various medium-term frequencies more equally. Due to this property, a regression-filtered credit-to-GDP ratio indicates that imbalances prior to the global financial crisis started earlier than shown by the Basel III creditto-GDP gap.

We study the international transmission of shocks to global financial conditions on macroeconomic tail risks in advanced and emerging economies. We show that contractionary financial and monetary policy shocks originating in the U.S. cause elevated downside risks to growth around the world. By tightening financial conditions globally, these shocks affect the left tail of the conditional output growth distribution disproportionately. This effect is particularly pronounced for countries with less flexible exchange rate arrangements, higher foreign currency exposures, and higher levels of private sector leverage. This suggests that policymakers face a trilemma, in which the exchange rate regime and macroprudential policies matter for downside risks to growth.

Die Fruherkennungsuntersuchungen auf Gebarmutterhals- und Brustkrebs fuhren zu einer deutlichen Reduktion der Sterblichkeit durch diese Erkrankungen. Neben dem Mammographiescreening sollen ab 2018 auch die Fruherkennungsmasnahmen fur das Zervixkarzinom im Rahmen eines organisierten Programms angeboten werden. Die Fruherkennungsuntersuchung des Gebarmutterhalskrebses wird in Zukunft mittels des HPV-Tests in 5‑jahrigen Intervallen vorgenommen werden. Als alternatives und erganzendes Verfahren wird die zytologische Untersuchung erhalten bleiben. Die Fruherkennung des Brustkrebses wird in Deutschland durch eine jahrliche Tastuntersuchung und das Mammographiescreening in 2‑jahrigen Intervallen im Alter von 50–69 Jahren ermoglicht. In Deutschland nahm in den letzten Jahren nur etwa die Halfte der eingeladenen Frauen die Untersuchung wahr. Zur Bewertung der Verfahren ist immer eine Abwagung des Nutzens und des Schadens notwendig.

The Basel III framework advises considering a reference indicator at the country level to guide the setting of the countercyclical capital buffer: the credit-to-GDP gap. In this paper, I provide empirical evidence suggesting that the credit-to-GDP gap is subject to spurious medium-term cycles, i.e. artificial boom-bust cycles with a maximum duration of around 40 years. This may impair its use as a reference indicator.

We operationalize the definition of systemic risk provided by the IMF, BIS, and FSB and derive testable hypotheses to identify indicators of systemic risk. We map these hypotheses into a two-stage hierarchical testing framework, combining insights from the early-warning literature on financial crises with recent advances on growth-at-risk. Applying this framework to a set of candidate variables, we find that the Basel III credit-to-GDP gap does not indicate systemic risk coherently across G7 countries. Credit growth and house price growth also do not pass our test in many cases. By contrast, a composite financial cycle signals systemic risk consistently for all countries except Canada. Overall, our results suggest that systemic risk may be consistently measured only once the turning points of indicators have been observed. Therefore, pre-emptive countercyclical macroprudential policy may smooth the financial cycle in boom phases, which then indirectly mitigates the amount of systemic risk in the future.

Hamilton (2017) criticises the HP filter because of three drawbacks (i. spurious cycles, ii. end-of-sample bias, iii. ad hoc assumptions regarding the smoothing parameter) which, moreover, apply to other popular time series filters as well. As an alternative filter, he proposes a regression filter. I demonstrate that Hamilton's regression filter is partially subject to the same drawbacks (i. and iii.). Furthermore, I illustrate that Hamilton's regression filter does not fulfil established criteria for the desired properties of filters. For instance, in contrast to the HP filter, Hamilton's filter does not approximate the ideal band pass filter, does not have constant cyclical properties across time series, and induces phase shifts. I discuss two refinements to bridge Hamilton's and the established view. For extracting business or financial cycles, I find that a one-sided HP filter and a 1-quarter regression filter can best reconcile both perspectives.

I propose a Bayesian quantile VAR to identify and assess the impact of uncertainty and certainty shocks, unifying Bloom's (2009) two identification steps into one. I find that an uncertainty shock widens the conditional distribution of future real economic activity growth, in line with a risk shock. Conversely, a certainty shock (a shock strongly decreasing uncertainty) narrows the conditional distribution of future real activity growth. In addition to the difference in signs, I show that the two shocks are different shocks. Each shock impacts the real economy uniquely. I support this with the underlying events: For instance, uncertainty shocks relate to events such as Black Monday and 9/11, but also to fears about future negative economic outcomes. In contrast, certainty shocks often link to phases of irrational exuberance. Commonly, no distinction is made between uncertainty and certainty shocks. I show that uncertainty shocks become more important if distinguished from certainty shocks.

Purpose Adjuvant endocrine therapy (ET) is indicated in patients with steroid hormone receptor (HR)-positive breast cancer. The aim of this study was to evaluate the quality of HR determination and adjuvant endocrine treatment of breast cancer patients in a large cohort of more than 7000 women by analyzing data from a population-based regional cancer registry. Methods Data from the Clinical Cancer Registry Regensburg (Bavaria, Germany) were analyzed. Female patients with primary, nonmetastatic invasive breast cancer who were diagnosed between 2000 and 2012 (n = 7421) were included. HR-status was available in 97.4 % (n = 7229) of the patients. This data set (n = 7229) was used for subsequent statistical analyses. Results Since 2009, almost a complete rate of 99.6 % of analyzed HR-status was achieved. In sum, 85.8 % of the patients (n = 6199) were HR-positive, whereas 14.2 % (n = 1030) were HR-negative. Overall, 85.3 % (n = 5285) of HR-positive patients received ET either alone or in combination with chemotherapy (CHT) and/or trastuzumab. The majority of premenopausal patients received CHT plus ET (716 patients, 52.3 %). In postmenopausal patients, the most frequent systemic therapy was ET alone (2670 patients, 55.3 %). Best overall survival (OS) was found in HER2-/HR-positive patients receiving CHT plus ET plus trastuzumab (7-year OS rate of 97.2 % in premenopausal patients versus 86.9 % in postmenopausal patients). Premenopausal patients had a reduced benefit from additional CHT than postmenopausal patients. Premenopausal patients receiving only ET had a 7-year OS rate of 95.3 % compared to 92.7 % of patients receiving CHT plus ET. In contrast, postmenopausal patients treated with CHT plus ET had a 7-year OS rate of 84.0 % in comparison with those patients receiving only ET with a 7-year OS rate of 81.7 %. Conclusions Analysis of HR in patients with early breast cancer achieved a very high quality in recent years. The vast majority of HR-positive patients received ET, and this guideline-adherent use improved OS. Inverse effects of the CHT plus ET combination in premenopausal versus postmenopausal patients and a still existing minority of patients not receiving guideline-adherent treatment should be further investigated in future studies.

We provide empirical evidence that US systemic financial stress shocks (US-SFSSs) are an important driver of economic dynamics and fluctuations in EMEs. Applying a structural vector autoregression, we analyze the international transmission of US-SFSSs to eight EMEs using monthly data from 1999 to 2012. US-SFSSs are identified as unexpected changes in the financial conditions index of the Federal Reserve Bank of Chicago. Findings indicate that a typical emerging market real economy experiences similar negative effects to those seen in the US real economy in response to US-SFSSs. For international transmission, our results emphasize that financial interconnectedness with the US is important relative to trade relations. The analyzed cases of Latin American economies suggest that indirect linkages are also important for transmitting the negative effects of US-SFSSs. In general, US-SFSSs act as a crucial driver of volatility in the emerging world; also at business cycle frequencies.

I show that the detrending of financial variables with the Hodrick and Prescott (1981, 1997) (HP) and band-pass filters leads to spurious cycles. I find that distortions become especially severe when considering medium-term cycles, i.e., cycles that exceed the duration of regular business cycles. In particular, these medium-term filters amplify the variances of cycles of duration around 20 to 30 years up to a factor of 204, completely cancelling out shorter-term fluctuations. This is important because it is common practice, and recommended under Basel III, to extract medium-term cycles using such filters; e.g., the HP filter with a smoothing parameter of 400,000. In addition, I find that financial cycle facts, i.e., differing amplitude, duration, and synchronisation of cycles in financial variables relative to cycles in GDP, are robust. For HP and band-pass filters, differences to GDP become marginal due to spurious cycles.

We demonstrate that financial cycles (identified as the common fluctuation in credit and asset prices, proxying balance-sheet leverage) differ across G-7 countries in terms of duration. This contradicts a similar-duration assumption inherent in the Basel III credit-to-GDP gap guiding countercyclical capital buffers. Against this backdrop, we propose an empirical methodology for constructing country-specific financial cycles that relaxes the similar-duration assumption and is based on the common fluctuation of several variables. Using credit and asset prices as inputs to our methodology, we show that constructed financial cycles significantly outperform the Basel III credit-to-GDP gap in predicting financial crises.

Die Rehabilitation des Sportlers nach einem operativen Eingriff aufgrund einer Schulterverletzung hat wesentliche Bedeutung fur die Erlangung der Sport- und Wettkampffahigkeit des Athleten. Bestimmung der adaquaten Rehabilitationskonzepte nach operativ versorgten Schulterverletzungen bei Sportlern. Selektive Literaturrecherche in der Datenbank PubMed unter Berucksichtigung eigener Erfahrungen sowie internationaler und nationaler Empfehlungen. Darstellung der Grundzuge der funktionellen Rehabilitation und der Prinzipien der kinetischen Kette sowie die Rehabilitationsphasen. Fur spezifische Verletzungsmuster (traumatische Erstluxation, Superior-labrum-anterior-to-posterior[SLAP]-Lasion, Rotatorenmanschettenverletzung) werden konkrete Rehabilitationskonzepte dargestellt und Kriterien zur Bestimmung der Sport- und Wettkampffahigkeit angegeben. Der Review zeigt aber auch, dass bis heute im Wesentlichen wissenschaftliche Untersuchungen auf hohem Evidenzniveau zur Behandlung dieser Patienten fehlen und klinische Erfahrung sowie Expertenmeinungen die Konzepte pragen. Die Rehabilitation des schulterverletzten Athleten erfordert ein abgestimmtes Vorgehen aller Beteiligten. Das Rehabilitationskonzept sollte unter Berucksichtigung operations- und patientenspezifischer Kriterien individuell erstellt werden. Weitere Studien sind dringend notwendig, um evidenzbasierte Empfehlungen abgeben zu konnen.

Ovarian epithelial cancer (OEC) is the most lethal gynaecological malignancy and the sixth most common cancer among women in industrialised countries. This review summarises the current knowledge on the role of reproductive factors for the development of OEC. Recent studies have shown that OECs represent a diverse group of cancers. This is partly reflected in the results of epidemiological and clinical studies which have investigated the impact of various reproductive factors on the risk of developing OEC. Fewer ovulatory cycles, parity and lactation were found to decrease the risk for OEC, whereas the association between infertility and ovarian cancer has not yet been fully elucidated and further investigation is required. None of the proposed hypotheses on the development of ovarian cancer fully explains the epidemiological and clinical findings of the association between reproductive factors and OEC development. Further research is warranted which would focus more on the clinical and genetic diversity of OECs to obtain a better understanding of the pathogenesis.

Der Aufnahmeprozess innerhalb einer Zentralen Notaufnahme versteht sich als ein Schnittstellenprozess. Die Einfuhrung eines Triageinstruments stellt einen Veranderungsprozess dar und wird ohne die Akzeptanz aller beteiligten Berufsgruppen nicht gelingen. Ziel dieser Studie ist es, den Aufnahmeprozess vor und nach Einfuhrung des Emergency-Severity-Index(ESI)-Triageinstruments zu analysieren und dessen klinische Akzeptanz retrospektiv aus drei verschiedenen Perspektiven zu evaluieren. 6 Monate nach Einfuhrung des ESI-Triageinstruments wurden Rettungsdienst (R), Arzte (A) und Pflegepersonen (P) mittels eines halbstandardisierten anonymisierten Fragebogens innerhalb der Zentralen Notaufnahme am Klinikum Furth befragt. Zur Auswertung wurde eine Mittelwertberechnung (x) der kategorisierten Antworten durchgefuhrt. Die beantworteten Thesen wurden ordinalskaliert von 0 (trifft nicht zu) bis 3 (trifft vollstandig zu) dargestellt. Vor Einfuhrung des ESI-Triageinstruments orientierte sich die Dauer der Wartezeit meist an der Reihenfolge des Eintreffens (xA1,9; xP2,0; xR2,3), was zu einer subjektiv empfundenen Unzufriedenheit der wartenden Patienten fuhrte (xP2,1). Der Aufnahmeprozess mit dem ESI-Triageinstrument wird berufsgruppenubergreifend positiv bewertet (xA2,2; xP2,7; xR2,5), da sich die interprofessionelle Zusammenarbeit und qualitative Erstversorgung verbessert hat (xA1,9; xP2,2; xR2,1). Wartende Patienten fuhlen sich wahrgenommen und wirken zufriedener (xP2,2). Das Schulungskonzept wird aus pflegerischer Sicht als sinnvoll und notwendig erachtet (xP2,7). Sowohl Rettungsdienst als auch Arzte sehen die fachliche Kompetenz, das ESI-Triageinstrument richtig anwenden zu konnen, bei den Pflegenden (xR2,2; xA2,3) und fuhlen sich dabei in ihrer Kompetenz nicht eingeschrankt (xA0,3; xR0,7). Durch die schrittweise Implementierung des ESI-Triageinstruments ist die erhoffte Prozessoptimierung im Aufnahmeprozess eingetreten, woraus eine Professionalisierung der interdisziplinaren Zusammenarbeit resultierte. Die berufsgruppenubergreifende klinische Akzeptanz des ESI-Triageinstruments war hierbei Prediktor der erfolgreichen Implementierung.

The European League Against Rheumatism (EULAR) and the European Federation of National Associations of Orthopaedics and Traumatology (EFORT) have recognised the importance of optimal acute care for the patients aged 50 years and over with a recent fragility fracture and the prevention of subsequent fractures in high-risk patients, which can be facilitated by close collaboration between orthopaedic surgeons and rheumatologists or other metabolic bone experts. Therefore, the aim was to establish for the first time collaborative recommendations for these patients. According to the EULAR standard operating procedures for the elaboration and implementation of evidence-based recommendations, 7 rheumatologists, a geriatrician and 10 orthopaedic surgeons met twice under the leadership of 2 convenors, a senior advisor, a clinical epidemiologist and 3 research fellows. After defining the content and procedures of the task force, 10 research questions were formulated, a comprehensive and systematic literature search was performed and the results were presented to the entire committee. 10 recommendations were formulated based on evidence from the literature and after discussion and consensus building in the group. The recommendations included appropriate medical and surgical perioperative care, which requires, especially in the elderly, a multidisciplinary approach including orthogeriatric care. A coordinator should setup a process for the systematic investigations for future fracture risk in all elderly patients with a recent fracture. High-risk patients should have appropriate non-pharmacological and pharmacological treatment to decrease the risk of subsequent fracture.

Screening programs for cervical cancer and breast cancer lead to a clear reduction of mortality. Starting in 2018 screening for cervical cancer will be structured as an organized program as already exists for breast cancer. In future screening for cervical cancer will be primarily performed by human papillomavirus (HPV) testing at intervals of 5 years while cytological examination (Pap smear) will also be available as an additional or alternative procedure. For breast cancer screening in Germany an annual clinical examination with palpation and mammography screening at 2‑year intervals is provided for women aged between 50 and 69 years. In Germany only approximately 50 % of invited women have used the opportunity to participate in screening in recent years. Weighing the benefits against the harms of cancer screening programs is always important in the process of evaluation of different strategies.

We investigate the interdependence of the default risk of several Eurozone countries (France, Germany, Italy, Ireland, the Netherlands, Portugal, and Spain) and their domestic banks during the period between June 2007 and May 2010, using daily credit default swaps (CDS). Bank bailout programs changed the composition of both banks’ and sovereign balance sheets and, moreover, affected the linkage between the default risk of governments and their local banks. Our main findings suggest that in the period before bank bailouts the contagion disperses from bank credit spreads into the sovereign CDS market. After bailouts, a financial sector shock affects sovereign CDS spreads more strongly in the short run. However, the impact becomes insignificant in the long term. Furthermore, government CDS spreads become an important determinant of banks’ CDS series. The interdependence of government and bank credit risk is heterogeneous across countries, but homogeneous within the same country.

Eine klinische Herausforderung ist die Behandlung klimakterischer Beschwerden bei Patientinnen mit gynakologischen Malignomen. Die Evidenz bezuglich der Hormontherapie (HT) in der Peri- und Postmenopause wurde fur die S3-Leitlinie „Hormontherapie in der Peri- und Postmenopause“ gepruft ( http://www.dggg.de/fileadmin/public_docs/Leitlinien/2-1-4-ht-lang-hp.pdf ), entsprechende Statements und Empfehlungen konnen dieser Leitlinie entnommen werden. Ziel dieser Ubersicht soll es sein, die heterogene Studienlage zur Fragestellung HT nach Malignomerkrankung darzustellen und dem Arzt sowie der Patientin eine Entscheidungsgrundlage zu geben. Ein nicht unwesentlicher Teil der Frauen leidet aufgrund einer onkologischen Therapie abrupt unter einer iatrogenen pramaturen Ovarialinsuffizienz und hat charakteristische Symptome, wie vasomotorische Beschwerden oder vaginale Atrophie. Andere befinden sich in der naturlichen Peri- bzw. Postmenopause und sind daher durch diese Beschwerden belastet. Einerseits muss eine potenzielle Forderung des Tumorwachstums durch eine HT berucksichtigt werden, andererseits die Moglichkeit einer effektiven Symptombehebung durch Hormonsubstitution.

A 57-year-old man, treated with immunosuppressive drugs for 3 months after a heart transplantation, developed a painful swelling of the left upper leg and fever. Needle biopsy of the lesion obtained pus from which Nocardia farcinica was cultured. Azathioprine treatment was discontinued and the dosage of cyclosporine reduced. Following antibiotic sensitivity tests, imipenem (4 g/d intravenously) and amikacin (1 g/d intravenously) were administered and the abscess split open. Although the fever responded and dissemination of the infection was excluded the response to treatment was not satisfactory. The drug dosages were repeatedly reduced in response to a rise in serum creatinine concentration to 3.4 mg/dl, deafness, double vision and generalized seizures: the local lesion got worse, but further surgical intervention then brought improvement. After 7 weeks of administration of the above antibiotics, treatment was changed to doxycycline (100 mg/d by mouth). 3 months later computed tomography could no longer demonstrate the lesion.

Serological tests for cytomegalovirus (CMV) after cardiac transplantation were performed at six to eight-week intervals on 26 patients (3 females and 23 males; mean age 46 [15-62] years) with angiographic or ultimately autopsy evidence of coronary atherosclerosis (group 1) and 24 patients (5 females and 19 males; mean age 45 [25-56] years) without coronary disease in the transplanted heart. A positive result meant an at least fourfold increase in CMV IgG titre, demonstration of CMV IgM or direct viral isolation from blood or other body fluid. In 20 patients of group 1 (77%) a CMV infection had occurred after the transplantation, but in only six patients (25%) in the group 2 (P less than 0.0001). These results are interpreted as demonstrating a relationship between CMV infection and rapidly progressive coronary atherosclerosis after cardiac transplantation.

Background Heart transplantation is an established tool for the treatment of terminal heart failure. Hyperlipidemia is a common problem following heart transplantation and has been implicated as an additional risk factor in the development of transplant coronary artery disease (TxCAD). Therefore, heart recipients are commonly treated with inhibitors of cholesterol synthesis (HMG-CoA reductase inhibitors). However, these patients have an increased risk of developing rhabdomyolysis due to elevated concentrations of HMG-CoA reductase inhibitors under co-administration with the immunosuppressive cyclosporin A (CsA). Aim of the study Aim of our study was to obtain pharmacokinetic data on pravastatin whilst monitoring the safety and efficiency of the lipid lowering therapy in heart-transplant recipients under immunosuppression with CsA and to compare these data to those of a healthy control group. Subjects, materials and methods Eleven patients (30.2 +/- 12.3 months after transplantation) receiving immunosuppressive therapy consisting of cyclosporin A, prednisone and azathioprine with LDL cholesterol (LDL-C) concentrations exceeding 3.9 mmol/l and 8 control subjects were included into the study. In addition to the immunosuppressive therapy, the patients received a daily dose of 40 mg/day pravastatin for the first 8 days which was then reduced to 10 mg/day administered until Day 29. Blood was sampled for pharmacokinetic profiling (maximum concentration of the drug (Cmax), time to reach Cmax (tmax), area under the concentration vs. time curve (AUC(0-24h)), elimination half-life time (tcl)) and measurement of the parameters of clinical chemistry on Days 1, 8 and 29. The control group received a single dose of 60 mg pravastatin and the values of Cmax and AUC(0-24h) were normalized for a dose of 10 mg. Results Pravastatin 40 mg/day for 1 week in the patient group caused a significant reduction in total cholesterol (C) and LDL-C from 8.11 +/- 1.20 mmol/l and 5.88 +/- 1.15 mmol/l to 6.91 +/- 1.01 mmol/l and 4.72 +/- 1.05 mmol/l, respectively (p = 0.005 and p = 0.003). Triglycerides and HDL cholesterol (HDL-C) concentrations did not change significantly. Mean values for Cmax of pravastatin were 384.2 ng/ml, 392.0 ng/ml and 115.1 ng/ml in patients on Days 1, 8 and 29, respectively. After normalization for a dose of 10 mg, the corresponding values of C(max-DN10mg) and Cmax were 96.0 ng/ml, 98.0 ng/ml and 115.1 ng/ml on study Days 1, 8 and 29. These values were 7-8 times higher than the normalized value of C(max-DN10mg) for the control group (13.7 ng/ml). The corresponding values of AUC(0-24h) were 1228.2 ng/ml x h, 1214.1 ng/ml x h and 345.9 ng/ml x h in the patient group on study Days 1, 8 and 29 as well as 157.5 ng/ml x h in the control group prior to normalization. After normalization for a dose of 10 mg, the values of AUC(0-24h-DN10mg) in the patient group were approximately 12 times higher than those of the control group. However, no significant differences between the 2 groups were observed in tmax and tcl. Within the patient group, no significant increase in Cmax or AUC was found on Day 1 to Day 8. The results of creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) showed also no significant increase during the observation period. Conclusion Heart-transplant recipients treated with the HMG-CoA reductase inhibitor pravastatin generally show higher plasma concentrations of this drug than control subjects. However, our data suggest that the HMG-CoA reductase inhibitor pravastatin can be used effectively in these patients receiving the immunosuppressive cyclosporin A. The pharmacokinetic data obtained indicate that there is no significant cumulation of the drug following multiple dosages in spite of increased drug concentrations after a single oral dosage.

Tailored scaling represents a principle of success that, both in nature and in technology, allows the effectiveness of physical effects to be enhanced. Mutation and selection in nature are imitated in technology, e.g. by model calculation and design. Proper scaling of dimensions in natural photonic crystals and our fabricated artificial 1D photonic crystals (DBRs, distributed Bragg reflectors) enable efficient diffractive interaction in a specific spectral range. For our optical microsystems we illustrate that tailored miniaturization may also increase the mechanical stability and the effectiveness of spectral tuning by thermal and electrostatic actuation, since the relative significance of the fundamental physical forces involved considerably changes with scaling. These basic physical principles are rigorously applied in micromachined 1.55-μm vertical-resonator-based devices. We modeled, implemented and characterized 1.55-μm micromachined optical filters and vertical-cavity surface-emitting laser devices capable of wide, monotonic and kink-free tuning by a single control parameter. Tuning is achieved by mechanical actuation of one or several air-gaps that are part of the vertical resonator including two ultra-highly reflective DBR mirrors of strong refractive index contrast: (i) Δn=2.17 for InP/air-gap DBRs (3.5 periods) using GaInAs sacrificial layers and (ii) Δn=0.5 for Si3N4/SiO2 DBRs (12 periods) with a polymer sacrificial layer to implement the air-cavity. In semiconductor multiple air-gap filters, a continuous tuning of >8% of the absolute wavelength is obtained. Varying the reverse voltage (U=0–5 V) between the membranes (electrostatic actuation), a tuning range of >110 nm was obtained for a large number of devices. The correlation of the wavelength and the applied voltage is accurately reproducible without any hysteresis. In two filters, tuning of 127 and 130 nm was observed for about ΔU=7 V. The extremely wide tuning range and the very small voltage required are record values to the best of our knowledge. For thermally actuated dielectric filters based on polymer sacrificial layers, Δλ/ΔU=-7 nm/V is found.

We showed recently that the 825T allele of the G-protein beta 3-subunit C825T polymorphism is associated with large inward rectifier K(+) currents I(K1) but low acetylcholine-activated K(+) current I(K,ACh) amplitudes. During chronic atrial fibrillation (AF), I(K1) and I(K,ACh) current densities were increased when compared to sinus rhythm (SR). It is unknown whether chronic AF and G beta 3 gene status are independent contributors to atrial K(+) current activity. We measured I(K1) and I(K,ACh) in tissue from AF patients with different G beta 3 genotypes and assessed the relation between the I(K1) and I(K,ACh) amplitudes and the incidence of postoperative AF.We measured the amplitudes of I(K1) and I(K,ACh) in atrial myocytes from 26 patients with sinus rhythm (SR) and from 16 patients with chronic AF (6 months). The K(+) currents were measured with standard patch-clamp techniques. The G beta 3 gene status of the patients was determined by PCR and restriction analysis.At -100 mV, the amplitude of I(K1) was larger in AF (10.9+/-1.0 pA/pF, n=49/16, cells/patients) than in SR (6.3+/-0.6 pA/pF, n=68/26, P0.05), whereas the amplitude of I(K,ACh) was smaller in chronic AF (2.9+/-0.7 pA/pF, n=49/16) than in SR (6.3+/-0.7 pA/pF, n=68/26, P0.05). These changes were independent of the patient G beta 3 gene status. Eight patients out of 26 in the SR group (31%) developed postoperative AF. When analysed based on incidence of postoperative AF, current amplitudes did not differ significantly.We provide evidence for up-regulation of I(K1) but down-regulation of I(K,ACh) in chronic AF which are independent of G beta 3 gene status. Atrial myocytes from patients who are in SR but later develop postoperative AF have no manifestation of altered I(K1) and I(K,ACh) at the time of cardiac surgery. Our results suggest that the AF-related changes of I(K1) and I(K,ACh) may be a consequence of or a contributory factor to chronic AF.

Als bosartige Tumoren des Herzens sind Leiomyosarkome im herzchirurgischen Alltag nur sehr selten zu finden, stellen jedoch ein hohes Risiko fur den betroffenen Patienten dar: nur eine fruhzeitige Diagnose sichert die Uberlebenschancen des Patienten, da sie aufgrund ihrer hohen Malignitat und raschen hamatogenen Metastasierung schnell zum Tode fuhren. Eine schnelle chirurgische Intervention mit radikaler Extirpation des Tumorgewebes ist daher umgehend notwendig. Eine erhohte Aufmerksamkeit, eine schnelle Diagnosesicherung und anschliesende radikale chirurgische Extirpation wird in Bezug auf das Krankheitsbild gefordert. Wir berichten uber einen 21-jahrigen Patienten mit der Verdachtsdiagnose Leiomyosarkom des Truncus pulmonalis. Eine operative Therapie erfolgte umgehend nach Abschluss der Diagnostik. Postoperativ bestatigte sich die Verdachtsdiagnose jedoch nicht. Es wurde ein seltener fibro-histiozytischer Tumor diagnostiziert. Im Hinblick auf die ungunstige Diagnose von Leiomyosarkomen ist schon bei Verdacht auf ein Leiomyosarkom eine radikale und rasche Therapie erforderlich.

Rehabilitation of athletes following surgical interventions for shoulder injuries is of utmost importance for recovery and return to sport.The aim was to determine adequate concepts for rehabilitation following shoulder surgery in athletes.A selective literature search was carried out in PubMed and a review of the available concepts is given taking personal experiences as well as national and international recommendations into consideration.This article presents the basic principles of functional rehabilitation, the kinetic chain and the different phases in rehabilitation. Specific rehabilitation concepts and return to sport strategies following traumatic dislocation, superior labrum anterior to posterior (SLAP) lesions and rotator cuff tears are presented. There is little high-level scientific evidence available for the treatment of these patients and most concepts are based on clinical experience and expert opinion.Rehabilitation of athletes with shoulder injuries requires a broad consensus strategy with respect to the next steps. Individual concepts for rehabilitation should take surgical and patient-specific criteria into consideration. Further research is urgently required to develop evidence-based recommendations.

Background Clinical and experimental evidence suggest that the parasympathetic nervous system is involved in the pathogenesis of atrial fibrillation (AF). However, it is unclear whether changes in G-protein-coupled inward rectifying K + current ( I K,ACh ) contribute to chronic AF. Methods and Results In the present study, we used electrophysiological recordings and competitive reverse-transcription polymerase chain reaction to study changes in I K,ACh and the level of the I K,ACh GIRK4 subunit in isolated human atrial myocytes and the atrial tissue of 39 patients with sinus rhythm and 24 patients with chronic AF. The density of I K,ACh was ≈50% smaller in myocytes from patients with AF compared with those in sinus rhythm, and this was accompanied by decreased levels of GIRK4 mRNA. The current density of the inward rectifying K + current ( I K1 ) was 2-fold larger during AF than in sinus rhythm, in correspondence with an increase in Kir2.1 mRNA. The larger I K1 in AF is consistent with more negative membrane potentials in right atrial trabeculae from AF patients. Moreover, action potential duration was reduced in AF, and the action potential shortening produced by muscarinic receptor stimulation was attenuated, indicating that the changes of I K1 and I K,ACh were functionally relevant. Conclusions Chronic human AF induces transcriptionally mediated upregulation of I K1 but downregulation of I K,ACh and attenuates the muscarinic receptor–mediated shortening of atrial action potentials. This suggests that atrial myocytes adapt to a chronically high rate by downregulating I K,ACh to counteract the shortening of the atrial effective refractory period due to electrical remodeling.

In this study we investigated whether a disturbance in microcirculation is detectable in heart recipients with cardiac allograft vasculopathy (CAV) and severe hypercholesterolemia (n = 11) and in 7 heart recipients without CAV in comparison to patients with severe coronary artery disease (n = 49) and age-matched apparently healthy subjects (n = 100). For this purpose, the flow velocity of erythrocytes through cutaneous capillaries at the nail fold of the finger was measured under resting conditions. In addition, reactive hyperemia in the same capillaries after a 3-min ischemia was determined. Patients with CAV and severe lipid disorder showed a pathological reduction in mean capillary erythrocyte velocity under resting conditions with v(RBC) = 0.10 +/- 0.07 mm/s. The latter was significantly and relevantly lower than in patients with coronary three-vessel disease (v(RBC) = 0.46 +/- 0.35 mm/s). It was notable that under resting conditions temporary cessation of flow occurred in 8 of the 11 patients which did not occur in healthy subjects and rarely in patients with three-vessel disease (1 of 49 patients). In comparison to age-matched healthy subjects (v(max) = 1.46 +/- 0.52 mm/s), the patients with three-vessel disease showed a significant reduction in postischemic maximum erythrocyte velocity (v(max) = 0.85 +/- 0.55 mm/s), with a considerable shortening of the duration of reactive hyperemia. Patients with CAV demonstrated a total loss of postischemic reactive hyperemia (only 1 of the 11 patients presented a weak reactive hyperemia). Since no macroangiopathy was detectable in the upstream arm arteries, primary cutaneous microangiopathy can be assumed in patients with cardiac allograft vasculopathy and severe hypercholesterolemia.