Oxidized Low-Density Lipoprotein Induces Macrophage Production of Prothrombotic Microparticles.

Background Activated vascular cells produce submicron prothrombotic and proinflammatory microparticle vesicles. Atherosclerotic plaques contain high levels of microparticles. Plasma microparticle levels increase during acute coronary syndromes and the thrombotic consequences of plaque rupture likely involve macrophage-derived microparticles (MΦMPs). The activation pathways that promote MΦMP production remain poorly defined. This study tested the hypothesis that signals implicated in atherogenesis also stimulate MΦMP production. Methods and Results We stimulated human primary MΦs with proinflammatory cytokines and atherogenic lipids, and measured MΦMP production by flow cytometry. Oxidized low-density lipoprotein (oxLDL; 25 µg/mL) induced MΦMP production in a concentration-dependent manner (293% increase; P<0.001), and these oxLDL MΦMP stimulatory effects were mediated by CD36. OxLDL stimulation increased MΦMP tissue factor content by 78% (P<0.05), and oxLDL-induced MΦMP production correlated with activation of caspase 3/7 signaling pathways. Salvionolic acid B, a CD36 inhibitor and a CD36 inhibitor antibody reduced oxLDL-induced MΦMP by 67% and 60%, respectively. Caspase 3/7 inhibition reduced MΦMP release by 52% (P<0.01) and caspase 3/7 activation increased MΦMP production by 208% (P<0.01). Mevastatin pretreatment (10 µM) decreased oxLDL-induced caspase 3/7 activation and attenuated oxLDL-stimulated MΦMP production and tissue factor content by 60% (P<0.01) and 43% (P<0.05), respectively. Conclusions OxLDL induces the production of prothrombotic microparticles in macrophages. This process depends on caspases 3 and 7 and CD36 and is inhibited by mevastatin pretreatment. These findings link atherogenic signaling pathways, inflammation, and plaque thrombogenicity and identify a novel potential mechanism for antithrombotic effects of statins independent of LDL lowering.

Roles and Responsibilities in the Provision of Accredited Continuing Medical Education/Continuing Professional Development.

The Cologne Consensus Conference 2015 has focused on "Providers in accredited CME[continuing medical education]/CPD [continuing professional development]". As an outcome of the CCC 2015, the authors of this paper, who were part of the faculty, propose a contemporary definition of the roles and responsibilities of stakeholders involved in the different stages of planning, delivery and evaluation of CME/CPD.

Electrocardiogram changes and wall motion abnormalities in the acute phase of Tako-Tsubo syndrome.

BACKGROUND: The Tako-Tsubo syndrome is still rarely diagnosed in patients presenting with symptoms of acute myocardial ischaemia. It is accompanied by wall motion abnormalities of the left ventricle but significant narrowings or occlusions of epicardial coronary arteries are absent. We investigated a potential relationship between electrocardiogram (ECG) changes, wall motion abnormalities and gender influence of Tako-Tsubo syndrome in an Austrian cohort of Tako-Tsubo syndrome patients. METHODS AND RESULTS: We were recently able to describe four different anatomical types of Tako-Tsubo syndrome in 153 patients of the Austrian Tako-Tsubo syndrome registry. In the present retrospective analysis we investigated ischaemia-related changes in the first diagnostic ECG for the different types of Tako-Tsubo syndrome: the apical and the combined apical-midventricular type showed most frequently a ST elevation (41.1% and 35.3%), whereas the midventricular type of Tako-Tsubo syndrome was more often accompanied by T wave inversion (60%). ECG changes in relation to the Tako-Tsubo syndrome type were similar in women and men. There was no difference in the prevalence of clinical complications among patients presenting with ST elevation or left bundle branch block (14.5%) compared with patients without ST elevation (10.4%) (p=0.476). CONCLUSION: Patients with Tako-Tsubo syndrome show characteristic ECG changes in the first diagnostic ECG which are associated to some extent with the anatomical type of Tako-Tsubo syndrome, but these ECG changes were not related to clinical outcome.

European Board for Accreditation in Cardiology (EBAC) 2015 CME/CPD Survey Summary.

In the spring of 2015, the European Board for Accreditation in Cardiology (EBAC) collaborated with International CME/CPD Consulting to design and administer a survey to approximately 1,171 professionals active in the field of European CME/CPD, with a focus on cardiology. With a nearly 5% response rate, the results herewith are non-representative, but do express current behaviours and attitudes of those active in European accredited CME/CPD.

Validation of the questionnaire for impulsive-compulsive disorders in Parkinson's disease (QUIP) and the QUIP-rating scale in a German speaking sample.

Impulsive-compulsive disorders are frequent in patients with Parkinson's disease (PD). Recently, a screening questionnaire and rating scale were developed for these disorders: the questionnaire for impulsive-compulsive disorders (QUIP) and QUIP-rating scale (QUIP-RS). We assessed the validity of these instruments in the German language in order to reevaluate the benefit and to obtain German screening tools in clinical practice. A convenience sample of 156 patients was assessed in Kiel and Vienna. The patients filled out the QUIP-current, the QUIP-anytime and the QUIP-RS. We validated the questionnaires against a gold standard diagnosis via receiver operating characteristic curves and determined optimal cut-off scores for the instruments. Excluding walkabout, which was not shown to be valid, sensitivities ranged from 60-92 % for the QUIP-current, 68-91 % for the QUIP-anytime, and 73-100 % for the QUIP-RS. Specificities were >71 % for QUIP-current, >69 % for QUIP-anytime and >62 % for QUIP-RS. With its very good sensitivities, the QUIP-RS is a valid instrument to assess impulsive-compulsive disorders and makes an early detection of behavioral disorders in PD possible. The QUIP-anytime was also shown to be a valid screening instrument. Both are expected to prove useful in scientific and clinical practice.

Stress-induced cardiomyopathy (Tako-Tsubo syndrome) in Austria.

BACKGROUND: Tako-Tsubo syndrome (TS) is a still rarely diagnosed clinical syndrome, which is characterized by acute onset of chest pain, transient cardiac dysfunction with (frequently) reversible wall motion abnormalities (WMAs), but with no relevant obstructive coronary artery disease. METHODS AND RESULTS: Among 179 consecutive patients with proven diagnosis of TS that were retrospectively analysed in this multicentre registry, women represented the majority of patients (94%) while only 11 men (6%) developed TS. Mean age was 69.1±11.5 years (range 35-88 years). Cardinal symptoms of TS, which led to admission, were acute chest pain (82%) and dyspnoea (32%), respectively. All patients demonstrated typical WMAs, whereby four different types of WMAs could be defined: (1) a more common apical type of TS (n=89; 50%); (2) a combined apical and midventricular form of TS (n=23; 13%); (3) the midventricular TS (n=6; 3%); and (4) an unusual type of basal WMAs of the left ventricle (n=3). Only in 101 patients (57%), a clear causative trigger for onset of symptoms could be identified. In-hospital cardiovascular complications occurred in 25 patients (14%) and consisted of cardiac arrhythmias in 10 patients (40%), cardiogenic shock in six patients (24%), cardiac decompensation in eight patients (32%) and cardiovascular death in one patient, respectively. Echocardiographic control of left ventricular function after the initial measurement was available in almost 70% of the patients: complete recovery of WMAs was found in 73 patients (58.87%); 49 patients (39.52%) showed persistent WMAs. Recurrences of TS were only seen in four patients. During the follow-up period, 13 patients died: three of cardiovascular causes and 10 of non-cardiac causes. In-hospital mortality was 0.6%, 30-day mortality was 1.3% and 2-year mortality was 6.7%. CONCLUSIONS: This study represents to date the largest series of patients suffering from TS in Austria and worldwide. Similar to others, in our series the prevalence of TS was significantly higher in women than in men, while in contrast to other studies, the apical type of TS was detected most frequently. The similar clinical presentation of TS patients to the clinical picture of acute myocardial infarction demonstrates the importance of immediate coronary angiography for adequate differential diagnosis of TS. TS is not necessarily a benign disease due to cardiovascular complications as well as persistent WMAs with delayed recovery.

Is left ventricular systolic dysfunction a risk factor for erectile dysfunction?

OBJECTIVES: To analyze erectile dysfunction (ED) in patients with left ventricular systolic dysfunction (LVSD). METHODS: A consecutive series of men aged 50-65 years undergoing an echocardiography (EC) at the Danube hospital in Vienna was analyzed. All patients completed the International Index of Erectile Function-5 (IIEF-5). LVSD was defined by EC as an ejection fraction (EF) below 55%. RESULTS: A total of 85 men (age, 58.5 years; standard deviation, 4.3) entered the analysis. Mean EF was 60.9% and mean IIEF-5 score 16.8. No ED (IIEF-5, 22-25) was present in 32 men (37.6%), mild ED (IIEF-5, 17-21) in 17 (20%), and 36 (42.4%) had moderate to severe ED (IIEF-5, 5-16). An EF below 55% was seen in 26 men (30.6%). Mean IIEF-5 in men with LVSD was 13.6 compared with 18.2 in those without LVSD (P = .005); the proportion of men with ED (IIEF-5 <22) was 76% in men with LVSD compared with 56.6% in those without LVSD (relative risk, 1.37; P = .05). In a logistic regression analysis adjusted for body mass index and age a declined IIEF-5 score was independently associated with a low EF (

Life-threatening pacemaker dysfunction associated with therapeutic radiation: a case report.

Reports about pacemaker (PM) dysfunction during irradiation (IR) are very rare, which is because of the extensive protective mechanisms that exist in these devices against electromagnetic interference (EMI). We report a case in which one of the most clinically relevant type of PM malfunctions, a runaway PM, occurred during radiation in a 76-year-old woman who was treated for inoperable esophageal cancer with a course of photon IR. The estimated IR dose of 0.11 Gy was the lowest in vivo dose ever reported. So a direct radiation effect as cause for this malfunction appears to be improbable. It could be concluded that the PM dysfunction was most likely induced by EMI during radiotherapy. The real reason of the device's software failure remains unclear.

Tissue factor-positive microparticles: cellular origin and association with coagulation activation in patients with colorectal cancer.

The pathogenesis of hypercoagulability in cancer is not entirely understood. We hypothesized that in cancer patients circulating tissue factor-positive microparticles (TF (+) MPs) are increased and associated with hemostatic system activation. In 20 patients with advanced colorectal cancer and in 20 age- and sex-matched controls, number and cellular origin of TF (+) MPs were determined in plasma by flow cytometry. D-dimer was determined as an indicator of hemostatic system activation. Compared to controls, the median (interquartile range) number of TF (+) MPs was two-fold higher in cancer patients: 25.9 (15.4 - 42.0) x 10 (3) /ml plasma versus 13.1 (11.9 - 19.7) x 10 (3) /ml plasma, p = 0.007. This was mainly due to a higher amount of TF (+) MPs from platelets (13.4 [5.0 - 17.4] x 10 (3) /ml plasma vs. 5.8 [4.5 - 7.5] x 10 (3) /ml plasma, p = 0.017). TF (+) MPs correlated with D-dimer ( ? = 0.48, p = 0.002). High levels of TF (+) MPs in cancer patients and their correlation with D-dimer suggest that TF (+) MPs might be involved in hemostasis activation in cancer patients.

Prevention of cardiovascular diseases and highly concentrated n-3 polyunsaturated fatty acids (PUFAs).

30 years ago the observation of a lower incidence of cardiovascular diseases in Inuits (Eskimos) was related to the higher fish consumption when compared to the residual Danish population. Clinical studies confirmed this finding. It was explained by the higher content of polyunsaturated fatty acids (PUFA) in fish, especially of omega-3 PUFAs. Experimental studies in cell cultures and also in animals with and without infarction models verified the anti-arrhythmic effect of omega-3 PUFAs among other possible contributing factors when compared to other fatty acids. In clinical studies a significant reduction (ca. 40%) of sudden cardiac deaths (SCD) could be found in patients after an acute myocardial infarction, if they were treated with at least 1 g omega-3 PUFAs daily, either by consumption of fish twice weekly or of a highly purified preparation omega-3 PUFAs in capsules. These findings led to recommendations of the American Heart Association and the European Society of Cardiology to a higher fish consumption and/or the daily intake of 1 g omega-3 PUFAs for primary and especially for secondary prevention of cardiovascular diseases. The much fewer side-effects, and the standardised dosage on one hand and the negative effect of the sometimes higher mercury content of fish make the intake of omega-3 PUFAs as capsules the better choice.

Generation of radially polarized beams in a Nd:YAG laser with self-adaptive overcompensation of the thermal lens.

Thermal effects such as lensing and birefringence negatively affect the beam quality and limit the power range of solid-state lasers. Self-adaptive overcompensation of the thermal lens is an answer to this problem. It provides a laser system with good beam quality and large stability range. Because the focal length of the thermally induced lens is different for the radial and the tangential polarization, overcompensation can be used to discriminate these two polarizations. Exploiting this method, we demonstrate the generation of radially polarized beams in a self-adaptively overcompensated high-power Nd:YAG laser with an output power of 155 W and an M2 of less than 10.

How safe is safe?--a case of Lactobacillus paracasei ssp. paracasei endocarditis and discussion of the safety of lactic acid bacteria.

We report a case of endocarditis due to Lactobacillus paracasei ssp. paracasei, which could be distinguished from Lactobacillus strains used for the fermentation of dairy products by randomly amplified polymorphic DNA-polymerase chain reaction. The safety of biotechnical lactic acid bacteria use is also discussed.

Cultivation of Mycobacterium bovis BCG in bioreactors.

The Mycobacterium bovis BCG vaccine for commercial use is classically produced as surface pellicles by culture on synthetic medium. Under these conditions, reproducibility of the cultures and quality assessment are hampered by slow growth of the bacilli, the formation of bacterial aggregates and a high proportion of dead bacilli after processing and final formulation of the vaccine. Here, we established dispersed cultures of M. bovis BCG in synthetic media in small-scale bioreactors. These cultures allow recording and adjusting of culture parameters and give rise to single bacilli with a high degree of live bacteria. In the murine model, bioreactor-grown M. bovis BCG exhibited slightly stronger replication and persistence than the vaccine produced under the classical conditions. The protective efficacy against challenge with M. tuberculosis was identical for both vaccine preparations.

Surgical conversion after endovascular grafting for abdominal aortic aneurysms.

PURPOSE: To analyze the indications, results, and technical problems associated with conversion after endoluminal repair of abdominal aortic aneurysms (AAA) based on a 6-year experience in endovascular grafting. METHODS: From August 1994 to May 2000, 520 patients with AAA were deemed candidates for endovascular therapy based on data from contrast-enhanced computed tomography and aortography. Any conversions were performed using an open operation modified according to the indication for conversion, elapsed time from the endoluminal repair, and type of endograft (tube, bifurcated, infra-/suprarenal fixation). RESULTS: Conversion to open repair was required in 37 (7.1%) cases: 23 tube grafts and 14 bifurcated devices. Seventeen (3.2%) conversions occurred at the original operation and 20 (3.8%) were performed secondarily. Indications for primary conversion were mainly device defects (n = 5) or access problems (n = 5), while secondary conversion was primarily owing to type I endoleak (n = 16). The conversion rate was significantly higher in modular devices (5.9%) than unibody designs (1.4%) (p = 0.003). The rate of primary conversions diminished from 10.9% in 1994-1995 to 2.4% between 1996 and 2000, as did the overall mortality rate, from 8.3% in the first time period to 0% in the second for elective conversions, but emergency operations had 40% mortality. CONCLUSIONS: Most AAAs require bifurcated devices for complete exclusion, and older model modular grafts have higher conversion rates. Primary conversion decreases as more experience in endoluminal grafting is acquired. Emergency open repair results in a high mortality rate.

Proton and gamma radiation tests on nonlinear crystals.

We report on the results of proton and gamma irradiation tests performed on nonlinear crystals for second- (SHG) and third-harmonic generation. Beta-barium borate (BBO), lithium triborate (LBO), and KTP crystals were exposed to three different energies of proton radiation (8, 70, and 300 MeV) and incremental doses of gamma radiation (up to 139 krad) in order to investigate the change in SHG performance and transmission spectra. BBO and LBO crystals turned out to be a suitable choice for SHG under radiative conditions.