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"text": "\n132287\nPersonalized management of atrial fibrillation: Proceedings from the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association consensus conference.\n\nKirchhof, P\n\nBreithardt, G\n\nAliot, E\n\nAl Khatib, S\n\nApostolakis, S\n\nAuricchio, A\n\nBailleul, C\n\nBax, J\n\nBenninger, G\n\nBlomstrom-Lundqvist, C\n\nBoersma, L\n\nBoriani, G\n\nBrandes, A\n\nBrown, H\n\nBrueckmann, M\n\nCalkins, H\n\nCasadei, B\n\nClemens, A\n\nCrijns, H\n\nDerwand, R\n\nDobrev, D\n\nEzekowitz, M\n\nFetsch, T\n\nGerth, A\n\nGillis, A\n\nGulizia, M\n\nHack, G\n\nHaegeli, L\n\nHatem, S\n\nGeorg Häusler, K\n\nHeidbüchel, H\n\nHernandez-Brichis, J\n\nJais, P\n\nKappenberger, L\n\nKautzner, J\n\nKim, S\n\nKuck, KH\n\nLane, D\n\nLeute, A\n\nLewalter, T\n\nMeyer, R\n\nMont, L\n\nMoses, G\n\nMueller, M\n\nMünzel, F\n\nNäbauer, M\n\nNielsen, JC\n\nOeff, M\n\nOto, A\n\nPieske, B\n\nPisters, R\n\nPotpara, T\n\nRasmussen, L\n\nRavens, U\n\nReiffel, J\n\nRichard-Lordereau, I\n\nSchäfer, H\n\nSchotten, U\n\nStegink, W\n\nStein, K\n\nSteinbeck, G\n\nSzumowski, L\n\nTavazzi, L\n\nThemistoclakis, S\n\nThomitzek, K\n\nVan Gelder, IC\n\nvon Stritzky, B\n\nVincent, A\n\nWerring, D\n\nWillems, S\n\nLip, GY\n\nCamm, AJ\n\nBeiträge in Fachzeitschriften\nISI:000326674600003\n23981824.0\n10.1093/europace/eut232\nNone\nThe management of atrial fibrillation (AF) has seen marked changes in past years, with the introduction of new oral anticoagulants, new antiarrhythmic drugs, and the emergence of catheter ablation as a common intervention for rhythm control. Furthermore, new technologies enhance our ability to detect AF. Most clinical management decisions in AF patients can be based on validated parameters that encompass type of presentation, clinical factors, electrocardiogram analysis, and cardiac imaging. Despite these advances, patients with AF are still at increased risk for death, stroke, heart failure, and hospitalizations. During the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association (AFNET/EHRA) consensus conference, we identified the following opportunities to personalize management of AF in a better manner with a view to improve outcomes by integrating atrial morphology and damage, brain imaging, information on genetic predisposition, systemic or local inflammation, and markers for cardiac strain. Each of these promising avenues requires validation in the context of existing risk factors in patients. More importantly, a new taxonomy of AF may be needed based on the pathophysiological type of AF to allow personalized management of AF to come to full fruition. Continued translational research efforts are needed to personalize management of this prevalent disease in a better manner. All the efforts are expected to improve the management of patients with AF based on personalized therapy.\n\n\n"
},
{
"text": "\n135736\nPlant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease\n\nGylling, H\n\nPlat, J\n\nTurley, S\n\nGinsberg, HN\n\nEllegard, L\n\nJessup, W\n\nJones, PJ\n\nLutjohann, D\n\nMaerz, W\n\nMasana, L\n\nSilbernagel, G\n\nStaels, B\n\nBoren, J\n\nCatapano, AL\n\nDe Backer, G\n\nDeanfield, J\n\nDescamps, OS\n\nKovanen, PT\n\nRiccardi, G\n\nTokgozoglu, L\n\nChapman, MJ\n\nBeiträge in Fachzeitschriften\nISI:000330582700040\n24468148.0\n10.1016/j.atherosclerosis.2013.11.043\nNone\nThis EAS Consensus Panel critically appraised evidence relevant to the benefit to risk relationship of functional foods with added plant sterols and/or plant stanols, as components of a healthy lifestyle, to reduce plasma low-density lipoprotein-cholesterol (LDL-C) levels, and thereby lower cardiovascular risk.\n Plant sterols/stanols (when taken at 2 g/day) cause significant inhibition of cholesterol absorption and lower LDL-C levels by between 8 and 10%. The relative proportions of cholesterol versus sterol/stanol levels are similar in both plasma and tissue, with levels of sterols/stanols being 500-/10, 00-fold lower than those of cholesterol, suggesting they are handled similarly to cholesterol in most cells. Despite possible atherogenicity of marked elevations in circulating levels of plant sterols/stanols, protective effects have been observed in some animal models of atherosclerosis. Higher plasma levels of plant sterols/stanols associated with intakes of 2 g/day in man have not been linked to adverse effects on health in long-term human studies. Importantly, at this dose, plant sterol/stanol-mediated LDL-C lowering is additive to that of statins in dyslipidaemic subjects, equivalent to doubling the dose of statin. The reported 6-9% lowering of plasma triglyceride by 2 g/day in hypertriglyceridaemic patients warrants further evaluation.\n Based on LDL-C lowering and the absence of adverse signals, this EAS Consensus Panel concludes that functional foods with plant sterols/stanols may be considered 1) in individuals with high cholesterol levels at intermediate or low global cardiovascular risk who do not qualify for pharmacotherapy, 2) as an adjunct to pharmacologic therapy in high and very high risk patients who fail to achieve LDL-C targets on statins or are statin- intolerant, 3) and in adults and children (>6 years) with familial hypercholesterolaemia, in line with current guidance. However, it must be acknowledged that there are no randomised, controlled clinical trial data with hard end-points to establish clinical benefit from the use of plant sterols or plant stanols.\n Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.\n\nMärz, Winfried\n\nSilbernagel, Günther\n\n\n"
},
{
"text": "\n136423\nPaley's multiplier method does not accurately predict adult height in children with bone sarcoma.\n\nGilg, MM\n\nWibmer, C\n\nAndreou, D\n\nAvian, A\n\nSovinz, P\n\nMaurer-Ertl, W\n\nTunn, PU\n\nLeithner, A\n\nBeiträge in Fachzeitschriften\nISI:000338997100031\n24777720.0\n10.1007/s11999-014-3636-4\nPMC4079875\nThe majority of patients with osteosarcoma and Ewing's sarcoma are diagnosed before skeletal maturity. Paley's multiplier is used for height prediction in healthy children, and has been suggested as a method to make growth predictions for children with osteosarcoma and Ewing's sarcoma when considering limb salvage options. To our knowledge, no evaluation of this method in this particular patient group has been performed, but a temporary growth deficit has been observed in children undergoing chemotherapy.\n We asked whether (1) Paley's formula reliably predicts growth in children who received polychemotherapy; (2) chemotherapy impairs growth velocity; and (3) final adult height is impaired in these patients.\n Retrospectively, data for 94 patients with osteosarcoma and Ewing's sarcoma were retrieved from databases of two sarcoma centers. Onset before 14 years of age in girls and 16 years in boys and a minimum followup until 18 years were required (mean, 67 months; range, 31-124 months) criteria. Exclusion criteria were the intake of growth hormones or no chemotherapy. Thirty-three patients (35%) fulfilled all inclusion criteria. Predicted adult heights were compared with actual adult height. The development of a growth deficit was evaluated for 23 children (without chemotherapy for recurrence) using age- and gender-specific standard deviation scores for height (WHO Z-scores).\n Height prediction using Paley's method showed a high percentage of false predictions (outside ± 1 SD, 70%; outside ± 2 SD, 61%). On average, the mean total height of the patients was overestimated (2.3 cm). The median absolute error of prediction was 5.0 cm (range, -17 to 8). Patients with osteosarcoma and Ewing's sarcoma showed a significant growth impairment during polychemotherapy. A catchup phase in growth before skeletal maturity was observed in patients with osteosarcoma but not with Ewing's sarcoma.\n Owing to its lack of reliability in this patient group, methods other than Paley's should be evaluated to predict adult height. Although limited by a small number of patients, our study results indicate a decreased adult height in patients with bone sarcoma after chemotherapy.\n Level III, therapeutic study. See the Instructions for Authors for complete description of levels of evidence.\n\nAvian, Alexander\n\nGilg, Magdalena Maria\n\nLeithner, Andreas\n\nMaurer-Ertl, Werner\n\nRitter-Sovinz, Petra\n\n\n"
},
{
"text": "\n179809\nProspective Cohort Study of Childhood-Onset Stargardt Disease: Fundus Autofluorescence Imaging, Progression, Comparison with Adult-Onset Disease, and Disease Symmetry.\n\nGeorgiou, M\n\nKane, T\n\nTanna, P\n\nBouzia, Z\n\nSingh, N\n\nKalitzeos, A\n\nStrauss, RW\n\nFujinami, K\n\nMichaelides, M\n\nBeiträge in Fachzeitschriften\nISI:000522799700019\n31812472.0\n10.1016/j.ajo.2019.11.008\nPMC7082771\nTo determine the reliability and repeatability of quantitative evaluation of areas of decreased autofluorescence (DAF) from fundus autofluorescence (FAF) images and track disease progression in children with Stargardt disease (STGD1), and to investigate clinical and genotype correlations, disease symmetry, and intrafamilial variability.\n Prospective cohort study.\n Children and adults with molecularly confirmed STGD1 (n = 90) underwent longitudinal FAF imaging with subsequent semiautomated measurement of the area of DAF and calculation of the annual rate of progression. The age of disease onset was recorded for all subjects, as well as the electroretinography (ERG) group at baseline (n = 86). Patients were grouped for analysis based on the age at baseline and age of onset, into children (n = 56), adults with childhood-onset STGD1 (n = 15), and adults with adult-onset (n = 19). Fifty FAF images were selected randomly and analyzed by 2 observers to evaluate repeatability and reproducibility. Differences between groups, interocular symmetry, genotype-phenotype correlations, and intrafamilial variability were also investigated both for baseline measurements as well as progression rates. We measured visual acuity, molecular genetics, ERG group, FAF metrics, and their correlations.\n The mean age of onset ± SD was 9.6 ± 3.4 years for childhood-onset (n = 71) and 28.3 ± 7.8 years for adult-onset STGD1 (n = 19). The intra- and interobserver reliability of DAF quantification was excellent (intraclass correlation coefficients 0.995 and 0.987, respectively). DAF area was symmetric between eyes and the mean rate of progression (SD) was 0.69 (0.72), 0.78 (0.48), and 0.40 (0.36) mm2/year for children, adults with childhood-onset, and adults with adult-onset disease, respectively. Patients belonging to a group 3 ERG phenotype (generalized cone and rod dysfunction) had a significantly greater progression rate. Limited intrafamilial variability was observed.\n This is the first large prospective study of FAF in a cohort of molecularly confirmed children with STGD1. DAF area quantification was highly reliable and may thereby serve as a robust structural endpoint. A high rate of progression was observed in childhood-onset disease, making this subtype of STGD1 ideally suited to be considered for prioritization in clinical trials.\n Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.\n\nStrauß, Rupert\n\n\n"
},
{
"text": "\n182828\nEvaluating infection prevention and control programs in Austrian acute care hospitals using the WHO Infection Prevention and Control Assessment Framework.\n\nAghdassi, SJS\n\nGrisold, A\n\nWechsler-Fördös, A\n\nHansen, S\n\nBischoff, P\n\nBehnke, M\n\nGastmeier, P\n\nBeiträge in Fachzeitschriften\nISI:000543525200003\n32571434.0\n10.1186/s13756-020-00761-2\nPMC7309981\nInfection prevention and control (IPC) is crucial for patient safety. The World Health Organization (WHO) has released various tools to promote IPC. In 2018, the WHO released the Infection Prevention and Control Assessment Framework (IPCAF) that enables acute care healthcare facilities to evaluate IPC structures and practices. Data regarding IPC implementation in Austria are scarce. To deliver insights into this topic and promote the IPCAF within the Austrian IPC community, we decided to invite all Austrian hospitals participating in the German nosocomial infection surveillance system to conduct a self-assessment using the WHO IPCAF.\n The IPCAF follows the eight WHO core components of IPC. A German translation of the IPCAF was sent to 127 Austrian acute care hospitals. The survey period was from October to December 2018. Participation in the survey, data entry and transfer to the German national reference center for surveillance of healthcare-associated infections was on a voluntary basis.\n Altogether, 65 Austrian hospitals provided a complete dataset. The overall median IPCAF score of all hospitals was 620 (of a possible maximum score of 800), which corresponded to an advanced level of IPC. Of the 65 hospitals, 38 achieved an advanced IPC level. Deeper analysis of the different core components yielded diverse results. Scores were lowest for core components on multimodal strategies for implementation of IPC interventions, and IPC education and training. Around 26% (n = 17) of hospitals reported that the local IPC team was not steadily supported by an IPC committee. Senior clinical staff was not present in the IPC committee in 23% (n = 15) of hospitals. Only 26% (n = 17) of hospitals reported employing at least one IPC professional per ≤250 beds. Surveillance for multidrug-resistant pathogens was not conducted in 26% (n = 17) of hospitals.\n Implementation of IPC key aspects is generally at a high level in Austria. However, potentials for improvement were demonstrated, most prominently with regard to staffing, IPC education and training, effective implementation of multimodal strategies, and involvement of professional groups. Our survey demonstrated that the IPCAF is a useful tool for IPC self-assessment and can uncover deficits even in a high-income setting like Austria.\n\nGrisold, Andrea\n\n\n"
},
{
"text": "\n1188\nHeterologous facilitation of G protein-activated K(+) channels by beta-adrenergic stimulation via cAMP-dependent protein kinase.\n\nMüllner, C\n\nVorobiov, D\n\nBera, AK\n\nUezono, Y\n\nYakubovich, D\n\nFrohnwieser-Steinecker, B\n\nDascal, N\n\nSchreibmayer, W\n\nBeiträge in Fachzeitschriften\nISI:000086820300002\n10779313.0\n10.1085%2Fjgp.115.5.547\nPMC2217221\nTo investigate possible effects of adrenergic stimulation on G protein-activated inwardly rectifying K(+) channels (GIRK), acetylcholine (ACh)-evoked K(+) current, I(KACh), was recorded from adult rat atrial cardiomyocytes using the whole cell patch clamp method and a fast perfusion system. The rise time of I(KACh ) was 0. 4 +/- 0.1 s. When isoproterenol (Iso) was applied simultaneously with ACh, an additional slow component (11.4 +/- 3.0 s) appeared, and the amplitude of the elicited I(KACh) was increased by 22.9 +/- 5.4%. Both the slow component of activation and the current increase caused by Iso were abolished by preincubation in 50 microM H89 (N-[2-((p -bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide, a potent inhibitor of PKA). This heterologous facilitation of GIRK current by beta-adrenergic stimulation was further studied in Xenopus laevis oocytes coexpressing beta(2)-adrenergic receptors, m(2 )-receptors, and GIRK1/GIRK4 subunits. Both Iso and ACh elicited GIRK currents in these oocytes. Furthermore, Iso facilitated ACh currents in a way, similar to atrial cells. Cytosolic injection of 30-60 pmol cAMP, but not of Rp-cAMPS (a cAMP analogue that is inhibitory to PKA) mimicked the beta(2)-adrenergic effect. The possibility that the potentiation of GIRK currents was a result of the phosphorylation of the beta-adrenergic receptor (beta(2)AR) by PKA was excluded by using a mutant beta(2)AR in which the residues for PKA-mediated modulation were mutated. Overexpression of the alpha subunit of G proteins (Galpha(s)) led to an increase in basal as well as agonist-induced GIRK1/GIRK4 currents (inhibited by H89). At higher levels of expressed Galpha(s), GIRK currents were inhibited, presumably due to sequestration of the beta/gamma subunit dimer of G protein. GIRK1/GIRK5, GIRK1/GIRK2, and homomeric GIRK2 channels were also regulated by cAMP injections. Mutant GIRK1/GIRK4 channels in which the 40 COOH-terminal amino acids (which contain a strong PKA phosphorylation consensus site) were deleted were also modulated by cAMP injections. Hence, the structural determinant responsible is not located within this region. We conclude that, both in atrial myocytes and in Xenopus oocytes, beta-adrenergic stimulation potentiates the ACh-evoked GIRK channels via a pathway that involves PKA-catalyzed phosphorylation downstream from beta(2)AR.\n\nSchreibmayer, Wolfgang\n\nSteinecker-Frohnwieser, Bibiane\n\n\n"
},
{
"text": "\n40114\nMRI criteria for dissemination in space in patients with clinically isolated syndromes: a multicentre follow-up study.\n\nKorteweg, T\n\nTintoré, M\n\nUitdehaag, B\n\nRovira, A\n\nFrederiksen, J\n\nMiller, D\n\nFernando, K\n\nFilippi, M\n\nAgosta, F\n\nRocca, M\n\nFazekas, F\n\nEnzinger, C\n\nMatthews, P\n\nParry, A\n\nPolman, C\n\nMontalban, X\n\nBarkhof, F\n\nBeiträge in Fachzeitschriften\nISI:000235632900016\n16488377.0\n10.1016/S1474-4422(06)70353-2\nNone\nBACKGROUND: The McDonald International Panel accepted the Barkhof/Tintoré criteria for providing MRI evidence of dissemination in space to allow a diagnosis of multiple sclerosis in patients with clinically isolated syndromes (CIS). We applied these criteria in a large cohort of patients with CIS, representative of those seen in a general diagnostic setting, to assess their accuracy in predicting conversion to definite multiple sclerosis and to identify factors that affect this risk. METHODS: In a collaborative study of seven centres, baseline MRI and clinical follow-up data for 532 patients with CIS were studied, with the development of a second clinical event used as the main outcome. All scans were scored for lesion counts and spatial lesion distribution to assess the fulfilment--ie, at least three out of four--of the Barkhof/Tintoré criteria. We used survival analysis and 2x2 tables to assess the test characteristics of the criteria at baseline. FINDINGS: Overall conversion rate was 32.5% with a median survival time of 85.3 months. Fulfilment of the criteria at baseline showed, after a survival time of 2 years, a conversion rate of about 45% (95% CI 37-53) versus about 10% (6-16) in those with no asymptomatic lesions at baseline (p<0.0001). For patients with a follow-up of at least 2 years, the fulfilment of the MRI criteria showed an accuracy of 68% (sensitivity 49%, specificity 79%) for predicting conversion and an increase in risk of nearly four times for conversion compared with those not fulfilling the criteria (odds ratio 3.7, 95% CI 2.3-5.9; p<0.0001). Cox proportional hazards regression analysis accorded with this increased risk. No effects were recorded on the performance of the criteria by sex, presenting symptoms, or centre. Age at baseline did have a small but significant effect as predictor (hazard ratio 0.97, 0.95-0.99; p=0.002), but did not affect the prognostic value of the MRI criteria. INTERPRETATION: MRI abnormalities have important prognostic value. The cut-off, based on the Barkhof/Tintoré criteria, as incorporated in the McDonald diagnostic scheme yields acceptable specificity, but could have lower sensitivity than previously reported.\n\nEnzinger, Christian\n\nFazekas, Franz\n\n\n"
},
{
"text": "\n107526\nCourse of thrombin activation markers in patients implanted with Palmaz-Schatz stents: first experiences with a post-interventional anticoagulation regimen.\n\nHaushofer, A\n\nHalbmayer, WM\n\nDittel, M\n\nPrachar, H\n\nMlczoch, J\n\nFischer, M\n\nBeiträge in Fachzeitschriften\nISI:A1994PT65200004\n7865675.0\n10.1097/00001721-199410000-00004\nNone\nFollowing implantation of coronary Palmaz-Schatz stents, 29 patients were anticoagulated with a combination of heparin, phenprocoumon and aspirin following a standard protocol. After removing the arterial and venous lines, post-interventional intravenous (i.v.) heparin treatment started with 1500 IU/h for patients > 80 kg and 1250 IU/h for patients < 80 kg. Heparin was monitored by the activated partial thromboplastin time (aPTT) and adjusted by increasing or reducing i.v. heparin by 250 IU/h to maintain the aPTT within the therapeutic range. Phenprocoumon therapy began the day after stent implantation (day 2) and lasted for 3 months. aPTT, Heptest, prothrombin fragment F1 and 2 (F1.2) and thrombin-antithrombin III complexes (TAT) were monitored at standard intervals for 10 days (mean monitoring time: 9.7 +/- 2.3 days). Anticoagulation was efficient with aPTT levels remaining within the therapeutic range on day 9 and the simultaneous, moderate-onset oral anticoagulation within the therapeutic range of the International Normalized Ratio (INR; 2.15-4.80) on day 8 on average, the mean INR being 2.43 +/- 0.76. On day 4, F1.2 levels were significantly higher than on the day of stenting (1.16 +/- 0.30 nmol/l vs 1.04 +/- 0.53 nmol/l; P < 0.005). F1.2 levels fell after day 5, the difference becoming significant from day 8 on (P < 0.05). F1.2 was negatively correlated with the Heptest (P < 0.05) and fell significantly as a function of the INR during phenprocoumon administration (P < 0.001). After phenprocoumon therapy was discontinued over 3 weeks, 25 patients were followed up by angiography. Despite adequate anticoagulation, mean F1.2 levels in patients showing restenosis at follow-up angiography were significantly higher (P < 0.005) than in those without restenosis. In one patient who developed subacute stent thrombosis, clotting factors were determined 20 min before stent occlusion. The levels of F1.2 and TAT were less than all other patients on this day (F1.2: 0.98 nmol/l vs 1.11 +/- 0.40 nmol/l; TAT: 2.7 micrograms/l vs 3.21 +/- 3.38 micrograms/l). Thus, neither F1.2 nor TAT predicted the occurrence of thrombotic stent failure in individuals. Efficient anticoagulation by a combination of anticoagulants is imperative for stent implantation. Using only current routine methods, this way of monitoring anticoagulation is effective for managing combined anticoagulation therapy.\n\n\n"
},
{
"text": "\n135937\nIntracoronary shunt insertion prevents myocardial stunning in a juvenile porcine MIDCAB model absent of coronary artery disease.\n\nDapunt, OE\n\nRaji, MR\n\nJeschkeit, S\n\nDhein, S\n\nKuhn-Régnier, F\n\nSüdkamp, M\n\nFischer, JH\n\nMehlhorn, U\n\nBeiträge in Fachzeitschriften\nISI:000080762600012\n10219550.0\n10.1016/S1010-7940(98)00290-5\nNone\nThe relevance of regional LV myocardial ischemia/reperfusion induced by temporary left anterior descending (LAD) coronary artery occlusion during minimally invasive direct coronary artery bypass (MIDCAB) grafting is controversial. The purpose of our study was (1) to determine the impact of conventional LAD occlusion during left internal thoracic artery (LITA)-LAD anastomosis on regional LV myocardial ischemia and function, and (2) to evaluate if intra-LAD shunt insertion during LITA-LAD anastomosis prevents potential regional LV ischemia and dysfunction in a pig model.\n In 20 anesthetized, mechanically ventilated pigs we performed LITA-LAD anastomosis on the beating heart without cardiopulmonary bypass during either 15 min LAD occlusion (occlusion-group; n = 10) or 15 min intra-LAD shunt insertion to maintain blood supply to the myocardium beyond the anastomosis (shunt-group; n = 10). Besides standard hemodynamics we determined the global and regional LV wall motion score index (WMSI) using epimyocardial echocardiography. To quantitate structural myocardial alteration we determined the inducible heat-shock protein-70 (HSP-70) in LV anterior wall myocardial biopsies. Data were recorded at baseline, at 15 min of LAD occlusion or shunt insertion, respectively, and at 30 min of reperfusion. At the end of the experiments we determined myocardial adenine nucleotide (ATP, ADP, AMP) and glycogen content.\n In both groups WMSI was not significantly different at 15 min LAD occlusion or shunt insertion, respectively, as compared to baseline. However, at 30 min reperfusion both global and regional WMSI demonstrated significant LV dysfunction in the occlusion-group, whereas LV function in the shunt-group remained normal. This was associated with higher myocardial HSP-70 expression in the occlusion-group (P < 0.05). Myocardial adenine nucleotide and glycogen contents were significantly better preserved in the shunt-group.\n Our data show that in a porcine MIDCAB model 15 min LAD occlusion and 30 min reperfusion result in significant myocardial stunning. In contrast, maintenance of LAD perfusion using intracoronary shunt insertion minimizes ischemia/reperfusion injury and prevents regional LV dysfunction. Although our experiments were conducted in healthy pig hearts absent from coronary artery disease, similar results may--at least partially--be expected in humans, and thus, intracoronary shunts could be a useful tool for myocardial protection during 'off-pump revascularization'.\n\n\n"
},
{
"text": "\n142784\nNonselective β blockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis.\n\nMandorfer, M\n\nBota, S\n\nSchwabl, P\n\nBucsics, T\n\nPfisterer, N\n\nKruzik, M\n\nHagmann, M\n\nBlacky, A\n\nFerlitsch, A\n\nSieghart, W\n\nTrauner, M\n\nPeck-Radosavljevic, M\n\nReiberger, T\n\nBeiträge in Fachzeitschriften\nISI:000336500900023\n24631577.0\n10.1053/j.gastro.2014.03.005\nNone\nNonselective β blockers (NSBBs) reduce portal pressure and the risk for variceal hemorrhage in patients with cirrhosis. However, development of spontaneous bacterial peritonitis (SBP) in these patients could preclude treatment with NSBBs because of their effects on the circulatory reserve. We investigated the effects of NSBBs in patients with cirrhosis and ascites with and without SBP.\n We performed a retrospective analysis of data from 607 consecutive patients with cirrhosis who had their first paracentesis at the Medical University of Vienna from 2006 through 2011. Cox models were calculated to investigate the effect of NSBBs on transplant-free survival time and adjusted for Child-Pugh stage and presence of varices.\n NSBBs increased transplant-free survival in patients without SBP (hazard ratio = 0.75; 95% confidence interval: 0.581-0.968; P = .027) and reduced days of nonelective hospitalization (19.4 days/year for patients on NSBBs vs 23.9 days/year for patients not taking NSBBs). NSBBs had only moderate effects on systemic hemodynamics at patients' first paracentesis. However, at the first diagnosis of SBP, the proportion of hemodynamically compromised patients with systolic arterial pressure <100 mm Hg was higher among those who received NSBBs (38% vs 18% of those not taking NSBBs; P = .002), as was the proportion of patients with arterial pressure <82 mm Hg (64% of those taking NSBBs vs 44% of those not taking NSBBs; P = .006). Among patients with SBP, NSBBs reduced transplant-free survival (hazard ratio = 1.58; 95% confidence interval: 1.098-2.274; P = .014) and increased days of nonelective hospitalization (29.6 days/person-year in patients on NSBBs vs 23.7 days/person-year in those not taking NSBBs). A higher proportion of patients on NSBBs had hepatorenal syndrome (24% vs 11% in those not taking NSBBs; P = .027) and grade C acute kidney injury (20% vs 8% for those not taking NSBBs; P = .021).\n Among patients with cirrhosis and SBP, NSBBs increase the proportion who are hemodynamically compromised, time of hospitalization, and risks for hepatorenal syndrome and acute kidney injury. They also reduce transplant-free survival. Patients with cirrhosis and SBP should not receive NSBBs.\n Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.\n\n\n"
},
{
"text": "\n167682\nFive-Year Outcomes with PCI Guided by Fractional Flow Reserve.\n\nXaplanteris, P\n\nFournier, S\n\nPijls, NHJ\n\nFearon, WF\n\nBarbato, E\n\nTonino, PAL\n\nEngstrøm, T\n\nKääb, S\n\nDambrink, JH\n\nRioufol, G\n\nToth, GG\n\nPiroth, Z\n\nWitt, N\n\nFröbert, O\n\nKala, P\n\nLinke, A\n\nJagic, N\n\nMates, M\n\nMavromatis, K\n\nSamady, H\n\nIrimpen, A\n\nOldroyd, K\n\nCampo, G\n\nRothenbühler, M\n\nJüni, P\n\nDe Bruyne, B\n\nFAME 2 Investigators\n\nBeiträge in Fachzeitschriften\nISI:000439063900008\n29785878.0\n10.1056/NEJMoa1803538\nNone\nWe hypothesized that fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) would be superior to medical therapy as initial treatment in patients with stable coronary artery disease.\n Among 1220 patients with angiographically significant stenoses, those in whom at least one stenosis was hemodynamically significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus medical therapy or to medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy and were entered into a registry. The primary end point was a composite of death, myocardial infarction, or urgent revascularization.\n A total of 888 patients underwent randomization (447 patients in the PCI group and 441 in the medical-therapy group). At 5 years, the rate of the primary end point was lower in the PCI group than in the medical-therapy group (13.9% vs. 27.0%; hazard ratio, 0.46; 95% confidence interval [CI], 0.34 to 0.63; P<0.001). The difference was driven by urgent revascularizations, which occurred in 6.3% of the patients in the PCI group as compared with 21.1% of those in the medical-therapy group (hazard ratio, 0.27; 95% CI, 0.18 to 0.41). There were no significant differences between the PCI group and the medical-therapy group in the rates of death (5.1% and 5.2%, respectively; hazard ratio, 0.98; 95% CI, 0.55 to 1.75) or myocardial infarction (8.1% and 12.0%; hazard ratio, 0.66; 95% CI, 0.43 to 1.00). There was no significant difference in the rate of the primary end point between the PCI group and the registry cohort (13.9% and 15.7%, respectively; hazard ratio, 0.88; 95% CI, 0.55 to 1.39). Relief from angina was more pronounced after PCI than after medical therapy.\n In patients with stable coronary artery disease, an initial FFR-guided PCI strategy was associated with a significantly lower rate of the primary composite end point of death, myocardial infarction, or urgent revascularization at 5 years than medical therapy alone. Patients without hemodynamically significant stenoses had a favorable long-term outcome with medical therapy alone. (Funded by St. Jude Medical and others; FAME 2 ClinicalTrials.gov number, NCT01132495 .).\n\nToth-Gayor, Gabor\n\n\n"
},
{
"text": "\n170258\nClinical Pharmacology of Fast-Acting Insulin Aspart Versus Insulin Aspart Measured as Free or Total Insulin Aspart and the Relation to Anti-Insulin Aspart Antibody Levels in Subjects with Type 1 Diabetes Mellitus.\n\nHaahr, H\n\nPieber, TR\n\nMathieu, C\n\nGondolf, T\n\nShiramoto, M\n\nErichsen, L\n\nHeise, T\n\nBeiträge in Fachzeitschriften\nISI:000463669700006\n30402720.0\n10.1007/s40262-018-0718-6\nPMC6451708\nFast-acting insulin aspart (faster aspart) is an ultra-fast-acting formulation of insulin aspart (IAsp). This post hoc analysis investigated the pharmacokinetics of faster aspart versus IAsp, measured as free or total IAsp, and the relationship between anti-IAsp antibodies and the pharmacokinetics/pharmacodynamics of faster aspart and IAsp.\n Free and total IAsp concentrations and anti-IAsp antibodies were determined in adults with type 1 diabetes mellitus receiving subcutaneous faster aspart and/or IAsp in four single-dose clinical pharmacology trials (n = 175) and a 26-week phase IIIa trial (n = 1040). Pharmacodynamics were assessed by euglycaemic clamp or meal test, respectively.\n The pharmacokinetic profile was left-shifted and early exposure was greater with faster aspart versus IAsp independent of free or total IAsp assay. The faster aspart-IAsp difference in the time to 50% of maximum IAsp concentration in the early part of the pharmacokinetic profile (tEarly 50 % Cmax) [95% confidence interval (CI)] was - 8.8 [- 10.0 to - 7.5] and - 7.6 [- 8.8 to - 6.4] min for free and total IAsp, respectively. The faster aspart/IAsp ratio for the area under the concentration-time curve (AUC) for IAsp from time zero to 30 min (AUCIAsp, -30 min) [95% CI] was 1.88 [1.74-2.04] and 1.77 [1.64-1.90] for free and total IAsp. Higher anti-IAsp antibody levels were associated with a lower ratio of free/total IAsp for the total AUC for IAsp (AUCIAsp, -t). Early glucose-lowering effect (AUC for the glucose infusion rate [GIR] from time zero to 60 min [AUCGIR, -60 min]) was greater by 25-44% for faster aspart versus IAsp independent of anti-IAsp antibody levels. Total glucose-lowering effect (total AUC for GIR [AUCGIR, -t]) in a clamp and 1-h postprandial glucose increment in a meal test appeared essentially unaffected by anti-IAsp antibodies.\n Faster aspart provides accelerated pharmacokinetics versus IAsp regardless if based on free or total IAsp assay. Higher anti-IAsp antibodies increase total IAsp concentrations but do not influence faster aspart nor IAsp pharmacodynamics. CLINICALTRIALS.\n NCT01618188, NCT02003677, NCT01934712, NCT02568280, NCT01831765.\n\nPieber, Thomas\n\n\n"
},
{
"text": "\n186690\nComplications, mobility, and quality of life in ankle sarcoma patients.\n\nSmolle, MA\n\nLeithner, A\n\nKapper, M\n\nDemmer, G\n\nTrost, C\n\nBergovec, M\n\nWindhager, R\n\nHobusch, GM\n\nBeiträge in Fachzeitschriften\nISI:000624134200021\n33641415.0\n10.1302/0301-620X.103B3.BJJ-2020-1308.R1\nNone\nThe aims of the study were to analyze differences in surgical and oncological outcomes, as well as quality of life (QoL) and function in patients with ankle sarcomas undergoing three forms of surgical treatment, minor or major limb salvage surgery (LSS), or amputation.\n A total of 69 patients with ankle sarcomas, treated between 1981 and 2017 at two tumour centres, were retrospectively reviewed (mean age at surgery: 46.3 years (SD 22.0); 31 females (45%)). Among these 69 patients 25 were analyzed prospectively (mean age at latest follow-up: 61.2 years (SD 20.7); 11 females (44%)), and assessed for mobility using the Prosthetic Limb Users Survey of Mobility (PLUS-M; for amputees only), the Toronto Extremity Salvage Score (TESS), and the University of California, Los Angeles (UCLA) Activity Score. Individual QoL was evaluated in these 25 patients using the five-level EuroQol five-dimension (EQ-5D-5L) and Fragebogen zur Lebenszufriedenheit/Questions on Life Satisfaction (FLZ).\n Of the total number of patients in the study, 22 (32%) underwent minor LSS and 22 (32%) underwent major LSS; 25 underwent primary amputation (36%). Complications developed in 26 (38%) patients, and were more common in those with major or minor LSS in comparison to amputation (59% vs 36% vs 20%; p = 0.022). A time-dependent trend towards higher complication risk following any LSS was present (relative risk: 0.204; 95% confidence interval (CI) 0.026 to 1.614; p = 0.095). In the prospective cohort, mean TESS was higher following minor LSS in comparison to amputation (91.0 vs 67.3; p = 0.006), while there was no statistically significant difference between major LSS and amputation (81.6 vs 67.3; p = 0.099). There was no difference in mean UCLA (p = 0.334) between the three groups (p = 0.334). None of the items in FLZ or EQ-5D-5L were different between the three groups (all p > 0.05), except for FLZ item "self-relation", being lower in amputees.\n Complications are common following LSS for ankle sarcomas. QoL is comparable between patients with LSS or amputation, despite better mobility scores for patients following minor LSS. We conclude that these results allow a decision for amputation to be made more easily in patients particularly where the principles of oncological surgery would otherwise be at risk. Cite this article: Bone Joint J 2021;103-B(3):553-561.\n\nBergovec, Marko\n\nLeithner, Andreas\n\nSmolle, Maria Anna\n\n\n"
},
{
"text": "\n1552\nL-type calcium current in human ventricular myocytes at a physiological temperature from children with tetralogy of Fallot.\n\nPelzmann, B\n\nSchaffer, P\n\nBernhart, E\n\nLang, P\n\nMächler, H\n\nRigler, B\n\nKoidl, B\n\nBeiträge in Fachzeitschriften\nISI:000074585800016\n9709403.0\n10.1016/S0008-6363(98)00002-9\nNone\nObjective: The aim was to investigate the electrophysiological properties of the L-type calcium current (I-Ca, -L) in ventricular myocytes at a physiological temperature (36-37 degrees C) isolated fl sm children undergoing surgical repair of tetralogy of Fallot, Methods: I-Ca, -L, was recorded with the patch-clamp technique in the single electrode whole-cell mode at a physiological calcium concentration(1.8 mmol/l) at 36-37 degrees C. Results: Under these conditions, maximum current density averaged -5.80 +/- 0.45 pA/pF. I-Ca, -L, showed a bell-shaped current-voltage relationship: the curl ent activated at - 37.7 +/- 1.36 mV. peaked at + 9.31 +/- 1.60 mV and reversed at + 57.7 +/- 2.17 mV (n = 17). At +10 mV. time to peak of I-Ca, -L, was 5.23 +/- 0.46 ms. membrane potentials for half-maximal steady-state activation and inactivation of I-Ca, -L were - 6.02 and - 20.4 mV, respectively, the slope factors were 7. 16 mV for steady-state activation and 6, 9 mV for steady-state inactivation. I-Ca, -L, did not completely inactivate and showed a big window current between:cen -45 and + 40 mV. The inactivation of I-Ca, -L showed a biexponential time course with a fast time constant ranging from 9.11 to 12.9 ms and a slow time constant ranging from 60.9 to 220 ms between - 30 and + 30 mV. Only the slow time constant showed a pronounced voltage dependency. The recovery from inactivation of I-Ca, -L was biphasic with a fast time constant of 60.7 ms and a slow time constant of 619 ms. beta-Adrenergic stimulation with isoprenaline (1 mu mol/l) increased the I-Ca, -L density from - 5.71 +/- 1.55 to - 13.8 +/- 1.96 pA/pF (142%; P < 0.05) at + 10 mV. Conclusions: The present study demonstrates that most of the electrophysiological properties of I-Ca, -L in ventricular myocytes isolated from children with tetralogy of Fallot resemble those of adult ventricular cells. The existence of a big calcium window current could be involved in the occurrence of early afterdepolarizations which could lead to the high incidence of arrhythmias after. surgical repair of tetralogy of Fallot. (C) 1998 Elsevier Science B.V. AII lights reserved.\n\nBernhart, Eva Maria\n\nKoidl, Bernd\n\nLang, Petra\n\nMächler, Heinrich\n\nPelzmann, Brigitte\n\nSchaffer, Peter\n\n\n"
},
{
"text": "\n3711\nDiffering beta-blocking effects of carvedilol and metoprolol.\n\nStoschitzky, K\n\nKoshucharova, G\n\nZweiker, R\n\nMaier, R\n\nWatzinger, N\n\nFruhwald, FM\n\nKlein, W\n\nBeiträge in Fachzeitschriften\nISI:000169189700011\n11378006.0\n10.1016/S1388-9842(01)00126-X\nNone\nBACKGROUND: Metoprolol is a beta(1)-selective beta-adrenergic antagonist while carvedilol is a non-selective beta-blocker with additional blockades of alpha(1)-adrenoceptors. Administration of metoprolol has been shown to cause up-regulation of beta-adrenoceptor density and to decrease nocturnal melatonin release, whereas carvedilol lacks these typical effects of beta-blocking drugs. AIMS: To compare beta-blocking effects of metoprolol and carvedilol when applied orally in healthy subjects. Methods: We investigated the effects of single oral doses of clinically recommended amounts of metoprolol (50, 100 and 200 mg) and carvedilol (25, 50 and 100 mg) to those of a placebo in a randomised, double-blind, cross-over study in 12 healthy male volunteers. Two hours after oral administration of the drugs heart rate and blood pressure were measured at rest, after 10 min of exercise, and after 15 min of recovery. RESULTS: Metoprolol tended to decrease heart rate during exercise (-21%, -25% and -24%) to a greater extent than carvedilol (-16%, -16% and -18%). At rest, increasing doses of metoprolol caused decreasing heart rates (62, 60 and 58 beats/min) whereas increasing doses of carvedilol caused increasing heart rates (62, 66 and 69 beats/min), 50 and 100 mg carvedilol failed to differ significantly from the placebo (71 beats/min). CONCLUSIONS: We conclude that clinically recommended doses of carvedilol cause a clinically relevant beta-blockade in humans predominantly during exercise where it appears to be slightly (although not significantly) less effective than metoprolol. On the other hand, the effects of carvedilol on heart rate at rest appear rather weak, particularly in subjects with a low sympathetic tone. This might be caused by a reflex increase on sympathetic drive secondary to peripheral vasodilation resulting from the alpha-blocking effects of the drug. These results might be helpful in explaining why carvedilol, in contrast to metoprolol, may fail to cause up-regulation of beta-adrenoceptor density and does not decrease nocturnal melatonin release. This, in turn, may be a reason for the weak side-effects of carvedilol resulting from the beta-blockade. In addition, our data might be of interest in the interpretation of the forthcoming results of the COMET trial, although it has to be emphasised that they were derived from healthy subjects and, therefore, cannot be directly extrapolated to patients with heart failure.\n\nFruhwald, Friedrich\n\nMaier, Robert\n\nWatzinger, Norbert\n\nZweiker, Robert\n\n\n"
},
{
"text": "\n148462\nCutaneous manifestations of angioimmunoblastic T-cell lymphoma: clinical and pathological characteristics.\n\nBotros, N\n\nCerroni, L\n\nShawwa, A\n\nGreen, PJ\n\nGreer, W\n\nPasternak, S\n\nWalsh, NM\n\nBeiträge in Fachzeitschriften\nISI:000351681700006\n25794369.0\n10.1097/DAD.0000000000000144\nNone\nAngioimmunoblastic T-cell lymphoma (AITL), an uncommon variant of peripheral T-cell lymphoma, affects the skin in approximately 50% of cases. Its protean clinical and histopathological cutaneous manifestations pose a challenge in diagnosis, particularly when these precede the diagnosis of AITL on a lymph node biopsy. In this retrospective study, we compared 11 cases of AITL with cutaneous manifestations (mean age 67 years; male:female ratio 1:0.8; 24 skin biopsies) with 20 control cases of inflammatory and non-AITL lymphomatous diseases (mean age 52 years; male:female ratio 1:1.5; 26 skin biopsies). Clinical, histopathological, immunohistochemical, and molecular data were documented. New insights into the clinical evolution of cutaneous involvement by AITL (C-AITL), from early macular, through papular to nodular stages, were observed. Microscopically, a parallel increment in the density of the dermal infiltrate and in the detection of lymphocyte cytological atypia was noted over time. Identification and quantification of follicular T-helper cells (Tfh), the neoplastic lineage, by immunohistochemistry helped to separate cases of C-AITL from inflammatory controls, offering promise as a useful diagnostic adjunct. The presence of T-cell clonality did not have discriminatory value between the 2 groups. Our work suggests that the early maculopapular phase of C-AITL eludes identification on pathological grounds alone and that features such as cytological atypia and high endothelial venules lack diagnostic specificity. In the context of (1) a rash that simulates a drug/viral exanthem or an acute manifestation of a connective tissue disorder, but proves recalcitrant, (2) constitutional abnormalities and/or lymphadenopathy that persist, and (3) a Tfh cell-rich perivascular dermatitis, the diagnosis of early C-AITL can be suspected, but not confirmed, without the benefit of a lymph node biopsy. The later nodular phase of C-AITL occurring in a similar constitutional background, can usually be discerned as lymphomatous, clinically and pathologically. Here a Tfh cell-rich infiltrate is a clue to the specific diagnosis, but confirmation by a nodal evaluation remains mandatory. Despite the difficulty in establishing a diagnosis of C-AITL in its early stages, and speculation that the initial eruptions might be reactive in nature, our sequential data support the concept that these are lymphomatous ab initio. To address the diagnostic challenge presented by this disease, meaningful integration of clinical and pathological data is imperative.\n\nCerroni, Lorenzo\n\n\n"
},
{
"text": "\n160602\nRepetitive use of levosimendan in advanced heart failure: need for stronger evidence in a field in dire need of a useful therapy.\n\nPölzl, G\n\nAltenberger, J\n\nBaholli, L\n\nBeltrán, P\n\nBorbély, A\n\nComin-Colet, J\n\nDelgado, JF\n\nFedele, F\n\nFontana, A\n\nFruhwald, F\n\nGiamouzis, G\n\nGiannakoulas, G\n\nGarcia-González, MJ\n\nGustafsson, F\n\nKaikkonen, K\n\nKivikko, M\n\nKubica, J\n\nvon Lewinski, D\n\nLöfman, I\n\nMalfatto, G\n\nManito, N\n\nMartínez-Sellés, M\n\nMasip, J\n\nMerkely, B\n\nMorandi, F\n\nMølgaard, H\n\nOliva, F\n\nPantev, E\n\nPapp, Z\n\nPerna, GP\n\nPfister, R\n\nPiazza, V\n\nBover, R\n\nRangel-Sousa, D\n\nRecio-Mayoral, A\n\nReinecke, A\n\nRieth, A\n\nSarapohja, T\n\nSchmidt, G\n\nSeidel, M\n\nStörk, S\n\nVrtovec, B\n\nWikström, G\n\nYerly, P\n\nPollesello, P\n\nBeiträge in Fachzeitschriften\nISI:000406038100076\n28571618.0\n10.1016/j.ijcard.2017.05.081\nNone\nPatients in the latest stages of heart failure are severely compromised, with poor quality of life and frequent hospitalizations. Heart transplantation and left ventricular assist device implantation are viable options only for a minority, and intermittent or continuous infusions of positive inotropes may be needed as a bridge therapy or as a symptomatic approach. In these settings, levosimendan has potential advantages over conventional inotropes (catecholamines and phosphodiesterase inhibitors), such as sustained effects after initial infusion, synergy with beta-blockers, and no increase in oxygen consumption. Levosimendan has been suggested as a treatment that reduces re-hospitalization and improves quality of life. However, previous clinical studies of intermittent infusions of levosimendan were not powered to show statistical significance on key outcome parameters. A panel of 45 expert clinicians from 12 European countries met in Rome on November 24-25, 2016 to review the literature and envision an appropriately designed clinical trial addressing these needs. In the earlier FIGHT trial (daily subcutaneous injection of liraglutide in heart failure patients with reduced ejection fraction) a composite Global Rank Score was used as primary end-point where death, re-hospitalization, and change in N-terminal-prohormone-brain natriuretic peptide level were considered in a hierarchical order. In the present study, we tested the same end-point post hoc in the PERSIST and LEVOREP trials on oral and repeated i.v. levosimendan, respectively, and demonstrated superiority of levosimendan treatment vs placebo. The use of the same composite end-point in a properly powered study on repetitive levosimendan in advanced heart failure is strongly advocated.\n Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.\n\nFruhwald, Friedrich\n\nvon Lewinski, Dirk\n\n\n"
},
{
"text": "\n114736\nExercise training improves exercise capacity and diastolic function in patients with heart failure with preserved ejection fraction: results of the Ex-DHF (Exercise training in Diastolic Heart Failure) pilot study.\n\nEdelmann, F\n\nGelbrich, G\n\nDüngen, HD\n\nFröhling, S\n\nWachter, R\n\nStahrenberg, R\n\nBinder, L\n\nTöpper, A\n\nLashki, DJ\n\nSchwarz, S\n\nHerrmann-Lingen, C\n\nLöffler, M\n\nHasenfuss, G\n\nHalle, M\n\nPieske, B\n\nBeiträge in Fachzeitschriften\nISI:000295883900010\n21996391.0\n10.1016/j.jacc.2011.06.054\nNone\nObjectives We sought to determine whether structured exercise training (ET) improves maximal exercise capacity, left ventricular diastolic function, and quality of life (QoL) in patients with heart failure with preserved ejection fraction (HFpEF). Background Nearly one-half of patients with heart failure experience HFpEF, but effective therapeutic strategies are sparse. Methods A total of 64 patients (age 65 +/- 7 years, 56% female) with HFpEF were prospectively randomized (2:1) to supervised endurance/resistance training in addition to usual care (ET, n = 44) or to usual care alone (UC) (n = 20). The primary endpoint was the change in peak V(O2) after 3 months. Secondary endpoints included effects on cardiac structure, diastolic function, and QoL. Results Peak V(O2) increased (16.1 +/- 4.9 ml/min/kg to 18.7 +/- 5.4ml/min/kg; p < 0.001) with ET and remained unchanged (16.7 +/- 4.7 ml/min/kg to 16.0 +/- 6.0 ml/min/kg; p = NS) with UC. The mean benefit of ET was 3.3 ml/min/kg (95% confidence interval [CI]: 1.8 to 4.8, p < 0.001). E/e' (mean difference of changes: -3.2, 95% CI: -4.3 to -2.1, p < 0.001) and left atrial volume index (milliliters per square meter) decreased with ET and remained unchanged with UC (-4.0, 95% CI: -5.9 to -2.2, p < 0.001). The physical functioning score (36-Item Short-Form Health Survey) improved with ET and remained unchanged with UC (15, 95% CI: 7 to 24, p < 0.001). The ET-induced decrease of E/e' was associated with 38% gain in peak V(O2) and 50% of the improvement in physical functioning score. Conclusions Exercise training improves exercise capacity and physical dimensions of QoL in HFpEF. This benefit is associated with atrial reverse remodeling and improved left ventricular diastolic function. (Exercise Training in Diastolic Heart Failure-Pilot Study: A Prospective, Randomised, Controlled Study to Determine the Effects of Physical Training on Exercise Capacity and Quality of Life [Ex-DHF-P]; ISRCTN42524037) (J Am Coll Cardiol 2011;58: 1780-91) (C) 2011 by the American College of Cardiology Foundation\n\n\n"
},
{
"text": "\n145434\nLipoprotein(a): when to measure and how to treat?\n\nChennamsetty, I\n\nScharnagl, H\n\nKleber, ME\n\nMarz, W\n\nKostner, GM\n\nBeiträge in Fachzeitschriften\nISI:000353132000001\nNone\n10.1515/labmed-2015-0002\nNone\nLipoprotein(a) [Lp(a)] is one of the most atherogenic lipoproteins consisting of a low-density lipoprotein particle and the specific glycoprotein apo(a). Apo(a) is homologous to plasminogen yet in contrast exhibits a specific size polymorphism. This polymorphism is due to the fact that the number of kringle-IV (K-IV) repeats ranges between two and approximately 50. Apo(a) is synthesized almost exclusively in the liver, and there is still some discussion going on whether the assembly of Lp(a) occurs intracellularly or in the circulating blood. The plasma Lp(a) concentration is markedly skewed to the right and extends from <1 mg/dL to more than 200 mg/dL. This concentration is up to more than 90% genetically determined and correlates inversely with the number of K-IV repeats. In the apo(a) promoter there are numerous response elements for transcription factors and nuclear receptors, whereby the hepatocyte nuclear factor 4 alpha (HNF4 alpha) binding sequence is the most important one. Activation of farnesoid-X receptor (FXR) causes the dissociation of HNF4 alpha from its response element and in turn a significant down regulation of apo(a) transcription. Recent large epidemiological studies document beyond any doubt that Lp(a) is an independent causal risk factor for coronary heart disease and myocardial infarction. Hence, novel approaches to correct elevated Lp(a) are under investigation. Among the established lipid-lowering drugs, only nicotinic acid lowers Lp(a) in a consistent and clinically relevant fashion, and we recently elucidated the molecular mechanism underlying this effect. Novel medicines in clinical trials include cholesterol ester transfer protein (CETP) inhibitors, proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies, the microsomal triglyceride transport protein (MTP) inhibitor lomitapide and antisense oligonucleotides. APO(a)(Rx)(R), an antisense oligonucleotide, which is specifically directed against the mRNA for apo(a), has the strongest effect on Lp(a). It offers the opportunity to examine the impact of selective Lp(a) lowering on clinical events. Lp(a) emerged as an important screening parameter to assess the risk for atherosclerosis. Its quantitation in the clinical laboratory had not been standardized for a long period of time. New commercial methods, in particular enzyme immunoassays with monoclonal antibodies that recognize single epitopes in apo(a), or nephelometric and turbidimetric assays hold the potential to warrant comparable results in different laboratories.\n\nKostner, Gerhard\n\nMärz, Winfried\n\nScharnagl, Hubert\n\n\n"
},
{
"text": "\n173702\nGalanin and Adrenomedullin Plasma Responses During Artificial Gravity on a Human Short-Arm Centrifuge.\n\nWinter, J\n\nLaing, C\n\nJohannes, B\n\nMulder, E\n\nBrix, B\n\nRoessler, A\n\nReichmuth, J\n\nRittweger, J\n\nGoswami, N\n\nBeiträge in Fachzeitschriften\nISI:000457396400001\n30774604.0\n10.3389/fphys.2018.01956\nPMC6367687\nGalanin and adrenomedullin plasma responses to head-up tilt and lower body negative pressure have been studied previously. However, to what extent short-arm human centrifugation (SAHC) affects these responses is not known. In this study, we assessed how the application of variable gradients of accelerations (ΔGz ) via shifting of the rotation axis during centrifugation affects selected hormonal responses. Specifically, we tested the hypothesis, that cardiovascular modulating hormones such as galanin and adrenomedullin will be higher in non-finishers (participants in whom at least one of the pre-defined criteria for presyncope was fulfilled) when compared to finishers (participants who completed the entire protocol in both sessions) during SAHC exposure. Twenty healthy subjects (10 women and 10 men) were exposed to two g-levels [1 Gz and 2.4 Gz at the feet (Gz_Feet)] in two positions (axis of rotation placed above the head and axis of rotation placed at the heart level). Elevated baseline levels of galanin appeared to predict orthostatic tolerance (p = 0.054) and seemed to support good orthostatic tolerance during 1 Gz_Feet SAHC (p = 0.034). In finishers, 2.4 Gz_Feet SAHC was associated with increased galanin levels after centrifugation (p = 0.007). For adrenomedullin, the hypothesized increases were observed after centrifugation at 1 Gz_Feet (p = 0.031), but not at 2.4 Gz_Feet, suggesting that other central mechanisms than local distribution of adrenomedullin predominate when coping with central hypovolemia induced by SAHC (p > 0.14). In conclusion, baseline galanin levels could potentially be used to predict development of presyncope in subjects. Furthermore, galanin levels increase during elevated levels of central hypovolemia and galanin responses appear to be important for coping with such challenges. Adrenomedullin release depends on degree of central hypovolemia induced fluid shifts and a subject's ability to cope with such challenges. Our results suggest that the gradient of acceleration (ΔGz ) is an innovative approach to quantify the grade of central hypovolemia and to assess neurohormonal responses in those that can tolerate (finishers) or not tolerate (non-finishers) artificial gravity (AG). As AG is being considered as a preventing tool for spaceflight induced deconditioning in future missions, understanding effects of AG on hormonal responses in subjects who develop presyncope is important.\n\nBrix, Bianca\n\nGoswami, Nandu\n\nRössler, Andreas\n\n\n"
}
]
}