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"text": "\n73424\nEnhanced plasma level of lipid peroxidation in Iranians could be improved by antioxidants supplementation.\n\nMeraji, S\n\nZiouzenkova, O\n\nResch, U\n\nKhoschsorur, A\n\nTatzber, F\n\nEsterbauer, H\n\nBeiträge in Fachzeitschriften\nISI:A1997WX71800007\n9152683.0\n10.1038/sj.ejcn.1600405\nNone\nTo study the influence of supplementation with antioxidants on factors, which might increase the risk of coronary heart disease (CHD) in Iranians.\n Twenty-one male volunteers enter the prospective, single-blind, randomized study.\n The supplementation was conducted at the Cardiovascular Center, University of Tehran, the biochemical analysis were carried out in the University of Graz.\n Twenty-one male medical students were recruited by advertisement. Five subjects were dropped out due to lack of the compliance.\n One group of Iranians received 30 mg/d beta-carotene and placebo for alpha-tocopherol; the other received beta-carotene plus 400 IU alpha-tocopherol for ten weeks. Concentrations of antioxidants in plasma and low density lipoproteins (LDL), plasma lipid profile, autoantibody against oxidized LDL (oLAb) and malondialdehyde (MDA) concentrations in plasma were measured. Oxidative resistance of LDL was estimated using conjugated diene assay.\n Iranians had a significantly lower plasma levels of total cholesterol (P < 0.002), LDL-cholesterol (P < 0.01) and high density lipoprotein-cholesterol (P < 0.002), compared to healthy Austrian subjects (n = 13). Although the baseline concentrations of alpha-tocopherol and beta-carotene were comparable with Austrians, lycopene, canthaxanthin and lutein were significantly higher in Iranians (P < 0.03-0.001). In vitro oxidative resistance of LDL, measured as lag-time, was slightly higher (P < 0.01) in Iranians comparing with Austrians. Plasma MDA and oLAb concentrations were significantly higher in Iranians (P < 0.001). Both dietary supplementations reduced plasma MDA concentrations (P < 0.001-0.001). A key finding was that a supplement combined with alpha-tocopherol caused also a significant increase of oLAb concentration (P > 0.01) as well as the significant increase of lag-time (P > 0.005).\n This study shows that high plasma MDA level of Iranians can be decreased by beta-carotene supplementation with or without alpha-tocopherol. However, alpha-tocopherol is a more powerful antioxidant, which can increase the resistance of LDL to oxidation, reduce the MDA concentrations in plasma and increase autoantibodies to oLDL.\n\nTatzber, Franz\n\n\n"
},
{
"text": "\n86878\nVariability of EWS chimaeric transcripts in Ewing tumours: a comparison of clinical and molecular data.\n\nZoubek, A\n\nPfleiderer, C\n\nSalzer-Kuntschik, M\n\nAmann, G\n\nWindhager, R\n\nFink, FM\n\nKoscielniak, E\n\nDelattre, O\n\nStrehl, S\n\nAmbros, PF\n\nBeiträge in Fachzeitschriften\nISI:A1994PP75600021\n7524604.0\n10.1038/bjc.1994.419\nPMC2033557\nEwing tumours (ET), including Ewing's sarcoma and peripheral primitive neuroectodermal tumour, are well characterised at the molecular level by a unique chromosomal rearrangement which fuses the EWS gene to one of two closely related ETS proto-oncogenes, FLI-1 or ERG. Expression of the resulting chimaeric transcripts can be readily detected by reversed transcriptase polymerase chain reaction (RT-PCR). This approach led to the identification of a number of different exon combinations at the junction site of coding sequences. The physiological consequences of the observed variability in the hinge region of EWS chimaeric proteins are not known. We have analysed tumour-derived material from 30 ET patients with well-documented clinical course (18 with localised and 12 with metastatic disease at diagnosis) for the presence of EWS/FLI-1 or EWS/ERG RNA. Karyotypes were obtained in 21 out of 27 cases and analysed by routine cytogenetics. A chromosome 22 rearrangement was demonstrated in 18 cases (67%). In contrast, RT-PCR revealed the presence of chimaeric transcripts in 28 tumours (93%), with fusions of EWS exon 7 to FLI-1 exons 6 (19/28), 5 (4/28) and 7 (1/28). In addition, EWS/FLI-1 exon combinations 10/5 and 9/4 were observed in one case each. In the last tumour, the presence of at least four additional splicing variants corresponding to fusion of EWS exon 7 to FLI-1 exons 4, 6, 8 and 9 was demonstrated. Two tumours expressed EWS/ERG fusion transcripts involving EWS exon 7 and ERG exon 6. In this study, EWS/FLI-1 exon combinations 7/6 (type I) predominated over 7/5 (type II) in localised ET (14 versus 1) and were more abundant in tumours affecting the long bones (9 versus 0), whereas in central axis tumours and metastatic disease there was only little difference in the frequency of the two types. So far, no correlations between different chimaeric EWS transcripts and any other clinical parameters have been identified.\n\n\n"
},
{
"text": "\n113729\nComparison of image quality and radiation dose of different pulmonary CTA protocols on a 128-slice CT: high-pitch dual source CT, dual energy CT and conventional spiral CT.\n\nDe Zordo, T\n\nvon Lutterotti, K\n\nDejaco, C\n\nSoegner, PF\n\nFrank, R\n\nAigner, F\n\nKlauser, AS\n\nPechlaner, C\n\nSchoepf, UJ\n\nJaschke, WR\n\nFeuchtner, GM\n\nBeiträge in Fachzeitschriften\nISI:000298651000002\n21874569.0\n10.1007/s00330-011-2251-y\nNone\nTo compare image quality and radiation dose of high-pitch dual-source computed tomography (DSCT), dual energy CT (DECT) and conventional single-source spiral CT (SCT) for pulmonary CT angiography (CTA) on a 128-slice CT system.\n Pulmonary CTA was performed with five protocols: high-pitch DSCT (100 kV), high-pitch DSCT (120 kV), DECT (100/140 kV), SCT (100 kV), and SCT (120 kV). For each protocol, 30 sex, age, and body-mass-index (mean 25.3 kg/m(2)) matched patients were identified. Retrospectively, two observers subjectively assessed image quality, measured CT attenuation (HU±SD) at seven central and peripheral levels, and calculated signal-to-noise-ratio (SNR) and contrast-to-noise-ratio (CNR). Radiation exposure parameters (CTDIvol and DLP) were compared.\n Subjective image quality was rated good to excellent in >92% (>138/150) with an interobserver agreement of 91.4%. The five protocols did not significantly differ in image quality, neither by subjective, nor by objective measures (SNR, CNR). By contrast, radiation exposure differed between protocols: significant lower radiation was achieved by using high-pitch DSCT at 100 kV (p < 0.01 in all). Radiation exposure of DECT was in between SCT at 100 kV and 120 kV.\n SCT, high-pitch DSCT, and DECT protocols techniques result in similar subjective and objective image quality, but radiation exposure was significantly lower with high-pitch DSCT at 100 kV.\n New CT protocols show promising results in pulmonary embolism assessment. High-pitch dual-source CT (DSCT) at 100 kV provides radiation dose savings for pulmonary CTA. High-pitch DSCT at 100 kV maintains diagnostic image quality for pulmonary CTA. Dual energy CT uses more radiation but also provides lung perfusion evaluation. Whether the additional perfusion data is worth the extra radiation remains undetermined.\n\nDejaco, Christian\n\n\n"
},
{
"text": "\n118053\nThe Austrian Tonsil Study 2010 - Part 2: Postoperative haemorrhage.\n\nSarny, S\n\nHabermann, W\n\nOssimitz, G\n\nStammberger, H\n\nBeiträge in Fachzeitschriften\nISI:000299987700005\n22222625.0\n10.1055/s-0031-1291309\nNone\nThe Austrian Tonsil Study 2010 - Part 2: Postoperative Haemorrhage Background: Postoperative haemorrhage is the most common and serious complication of tonsil and adenoid surgery. Definitions, frequency and risk factors of postoperative bleedings are however, controversially discussed in the literature. Patients and Methods: In a prospective multicenter cohort study all tonsillectomies (TE), adenotonsillectomies (TE+AE), tonsillotomies (TO), adenotonsillotomies (TO+AE) and adenoidectomies (AE) performed within 9 months from October 1st, 2009 - June 30th, 2010 were collected and evaluated. Postoperative haemorrhage was defined as any bleeding after extubation and was classified into 7 grades A1, A2, B1, B2, C, D and E depending on the therapy needed and the postoperative day. Results: Data from 9 405 patients of 32 ENT-departments in Austria were analysed. Overall postoperative haemorrhage rate for TE was 16.0%, for TE+AE 11.8%, for TO +/- AE 2.3% and for AE 0.8%. Surgical revision was necessary in almost one third of patients with a postoperative bleeding event (TE 5.3%, TE+AE 4.1%, TO 0.8% und AE 0.3%). Multiple haemorrhage occurred in every 5th patient, who experienced postoperative bleeding (1.7% of all patients). The frequency of haemorrhage depended on the type of surgery and the age of the individual. Severe bleedings requiring surgical revision were more frequent in children between 6 and 15 years and AE. 9 patients (1.2% of all patients with haemorrhage) experienced a dramatic haemorrhage (grade D), with the need of blood transfusions and difficult surgical control. No deaths occurred during the study period. Conclusions: Due to a new classification postoperative bleeding episodes could be precisely defined and postoperative risk factors were quantified. Considering all postoperative bleedings, including minor and anamnestic ones, the haemorrhage rate over all types of surgeries was 7.9% (2.7% of all patients required a surgical revision). Tonsillectomy (with or without adenoidectomy) carries the highest statistical risk of postoperative bleeding, with 4.9% of all patients requiring surgical intervention. 11 Patients who experience one - albeit minimal - postoperative haemorrhage, have a 5 times higher risk for further bleeding requiring surgical control, and should therefore be carefully monitored.\n\nHabermann, Walter\n\nSarny, Stephanie\n\n\n"
},
{
"text": "\n119286\nInfluence of Sex on the Survival of Patients With Esophageal Cancer.\n\nBohanes, P\n\nYang, D\n\nChhibar, RS\n\nLabonte, MJ\n\nWinder, T\n\nNing, Y\n\nGerger, A\n\nBenhaim, L\n\nPaez, D\n\nWakatsuki, T\n\nLoupakis, F\n\nEl-Khoueiry, R\n\nZhang, W\n\nLenz, HJ\n\nBeiträge in Fachzeitschriften\nISI:000305413200020\n22585694.0\n10.1200/JCO.2011.38.8751\nPMC3397720\nPurpose The prognostic value of sex for esophageal cancer survival is currently unclear, and growing data suggest that hormonal influences may account for incidence disparities between men and women. Therefore, moving from the hypothesis that hormones could affect the prognosis of patients with esophageal cancer, we investigated the primary hypothesis that sex is associated with survival and the secondary hypotheses that the relationship between sex and survival depends, at least in part, on age, histology, and race/ethnicity. Patients and Methods By using the SEER databases from 1973 to 2007, we identified 13, 03 patients (34%) with metastatic esophageal cancer (MEC) and 26, 48 patients (66%) with locoregional esophageal cancer (LEC). Cox proportional hazards model for competing risks were used for analyses. Results In the multivariate analysis, women had longer esophageal cancer-specific survival (ECSS) than men in both MEC (hazard ratio [ HR], 0.949; 95% CI, 0.905 to 0.995; P = .029) and LEC (HR, 0.920; 95% CI, 0.886 to 0.955; P < .001) cohorts. When age and histology were accounted for, there was no difference for ECSS between men and women with adenocarcinoma. In contrast, women younger than age 55 years (HR, 0.896; 95% CI, 0.792 to 1.014; P = .081) and those age 55 years or older (HR, 0.905; 95% CI, 0.862 to 0.950; P < .001) with squamous cell LEC had longer ECSS than men. In the squamous cell MEC cohort, only women younger than age 55 years had longer ECSS (HR, 0.823; 95% CI, 0.708 to 0.957; P = .011) than men. Conclusion Sex is an independent prognostic factor for patients with LEC or MEC. As secondary hypotheses, in comparison with men, women age 55 years or older with squamous cell LEC and women younger than age 55 years with squamous cell MEC have a significantly better outcome. These last two findings need further validation. J Clin Oncol 30:2265-2272. (c) 2012 by American Society of Clinical Oncology\n\nGerger, Armin\n\n\n"
},
{
"text": "\n138505\nThe role of the carbohydrate recognition domain of placental protein 13 (PP13) in pregnancy evaluated with recombinant PP13 and the DelT221 PP13 variant.\n\nSammar, M\n\nNisamblatt, S\n\nGonen, R\n\nHuppertz, B\n\nGizurarson, S\n\nOsol, G\n\nMeiri, H\n\nBeiträge in Fachzeitschriften\nISI:000339954800017\n25079598.0\n10.1371/journal.pone.0102832\nPMC4117483\nPlacental protein 13 (PP13), a placenta specific protein, is reduced in the first trimester of pregnancy in women who subsequently develop preeclampsia. A naturally occurring PP13 deletion of thymidine at position 221 (DelT221 or truncated variant) is associated with increased frequency of severe preeclampsia. In this study we compared the full length (wildtype) PP13 and the truncated variant.\n Full length PP13 or its DelT221 variant were cloned, expressed and purified from E-Coli. Both variants were administrated into pregnant rats at day 8 of pregnancy for slow release (>5 days) through osmotic pumps and rat blood pressure was measured. Animals were sacrificed at day 15 or day 21 and their utero-placental vasculature was examined.\n The DelT221 variant (11 kDA) lacked exon 4 and a part of exon 3, and is short of 2 amino acids involved in the carbohydrate (CRD) binding of the wildtype (18 kDA). Unlike the wildtype PP13, purification of DelT221 variant required special refolding. PP13 specific poly- clonal antibodies recognized both PP13 and DelT221 but PP13 specific monoclonal antibodies recognized only the wildtype, indicating the loss of major epitopes. Wildtype PP13 mRNA and its respective proteins were both lower in PE patients compared to normal pregnancies. The DelT221 mutant was not found in a large Caucasian cohort. Pregnant rats exposed to wildtype or DelT221 PP13 variants had significantly lower blood pressure compared to control. The wildtype but not the DelT221 mutant caused extensive vein expansion.\n This study revealed the importance of PP13 in regulating blood pressure and expanding the utero-placental vasculature in pregnant rats. PP13 mutant lacking amino acids of the PP13 CRD domain fails to cause vein expansion but did reduce blood pressure. The study provides a basis for replenishing patients at risk for preeclampsia by the full length but not the truncated PP13.\n\nHuppertz, Berthold\n\n\n"
},
{
"text": "\n147780\nDetection Accuracy of Collective Intelligence Assessments for Skin Cancer Diagnosis.\n\nKurvers, RH\n\nKrause, J\n\nArgenziano, G\n\nZalaudek, I\n\nWolf, M\n\nBeiträge in Fachzeitschriften\nISI:000367994700015\n26501400.0\n10.1001/jamadermatol.2015.3149\nNone\nIncidence rates of skin cancer are increasing globally, and the correct classification of skin lesions (SLs) into benign and malignant tissue remains a continuous challenge. A collective intelligence approach to skin cancer detection may improve accuracy.\n To evaluate the performance of 2 well-known collective intelligence rules (majority rule and quorum rule) that combine the independent conclusions of multiple decision makers into a single decision.\n Evaluations were obtained from 2 large and independent data sets. The first data set consisted of 40 experienced dermoscopists, each of whom independently evaluated 108 images of SLs during the Consensus Net Meeting of 2000. The second data set consisted of 82 medical professionals with varying degrees of dermatology experience, each of whom evaluated a minimum of 110 SLs. All SLs were evaluated via the Internet. Image selection of SLs was based on high image quality and the presence of histopathologic information. Data were collected from July through October 2000 for study 1 and from February 2003 through January 2004 for study 2 and evaluated from January 5 through August 7, 2015.\n For both collective intelligence rules, we determined the true-positive rate (ie, the hit rate or specificity) and the false-positive rate (ie, the false-alarm rate or 1 - sensitivity) and compared these rates with the performance of single decision makers. Furthermore, we evaluated the effect of group size on true- and false-positive rates.\n One hundred twenty-two medical professionals performed 16 029 evaluations. Use of either collective intelligence rule consistently outperformed single decision makers. The groups achieved an increased true-positive rate and a decreased false-positive rate. For example, individual decision makers in study 1, using the pattern analysis as diagnostic algorithm, achieved a true-positive rate of 0.83 and a false-positive rate of 0.17. Groups of 3 individuals achieved a true-positive rate of 0.91 and a false-positive rate of 0.14. These improvements increased with increasing group size.\n Collective intelligence might be a viable approach to increase diagnostic accuracy in skin cancer and reduce skin cancer-related mortality.\n\nZalaudek, Iris\n\n\n"
},
{
"text": "\n149138\nSeeking worldwide professional consensus on the principles of end-of-life care for the critically ill. The Consensus for Worldwide End-of-Life Practice for Patients in Intensive Care Units (WELPICUS) study.\n\nSprung, CL\n\nTruog, RD\n\nCurtis, JR\n\nJoynt, GM\n\nBaras, M\n\nMichalsen, A\n\nBriegel, J\n\nKesecioglu, J\n\nEfferen, L\n\nDe Robertis, E\n\nBulpa, P\n\nMetnitz, P\n\nPatil, N\n\nHawryluck, L\n\nManthous, C\n\nMoreno, R\n\nLeonard, S\n\nHill, NS\n\nWennberg, E\n\nMcDermid, RC\n\nMikstacki, A\n\nMularski, RA\n\nHartog, CS\n\nAvidan, A\n\nBeiträge in Fachzeitschriften\nISI:000343377600005\n25162767.0\n10.1164/rccm.201403-0593CC\nNone\nGreat differences in end-of-life practices in treating the critically ill around the world warrant agreement regarding the major ethical principles. This analysis determines the extent of worldwide consensus for end-of-life practices, delineates where there is and is not consensus, and analyzes reasons for lack of consensus. Critical care societies worldwide were invited to participate. Country coordinators were identified and draft statements were developed for major end-of-life issues and translated into six languages. Multidisciplinary responses using a web-based survey assessed agreement or disagreement with definitions and statements linked to anonymous demographic information. Consensus was prospectively defined as >80% agreement. Definitions and statements not obtaining consensus were revised based on comments of respondents, and then translated and redistributed. Of the initial 1, 83 responses from 32 countries, consensus was found for 66 (81%) of the 81 definitions and statements; 26 (32%) had >90% agreement. With 83 additional responses to the original questionnaire (1, 66 total) and 604 responses to the revised statements, consensus could be obtained for another 11 of the 15 statements. Consensus was obtained for informed consent, withholding and withdrawing life-sustaining treatment, legal requirements, intensive care unit therapies, cardiopulmonary resuscitation, shared decision making, medical and nursing consensus, brain death, and palliative care. Consensus was obtained for 77 of 81 (95%) statements. Worldwide consensus could be developed for the majority of definitions and statements about end-of-life practices. Statements achieving consensus provide standards of practice for end-of-life care; statements without consensus identify important areas for future research.\n\nMetnitz, Philipp\n\n\n"
},
{
"text": "\n150029\nLow-molecular-weight heparin for women with unexplained recurrent pregnancy loss: a multicenter trial with a minimization randomization scheme.\n\nSchleussner, E\n\nKamin, G\n\nSeliger, G\n\nRogenhofer, N\n\nEbner, S\n\nToth, B\n\nSchenk, M\n\nHenes, M\n\nBohlmann, MK\n\nFischer, T\n\nBrosteanu, O\n\nBauersachs, R\n\nPetroff, D\n\nETHIG II group\n\nBeiträge in Fachzeitschriften\nISI:000354119100004\n25938990.0\n10.7326/M14-2062\nNone\nA daily injection of low-molecular-weight heparin (LMWH) is often prescribed to women with unexplained recurrent pregnancy loss (RPL), although evidence suggesting a benefit is questionable.\n To determine whether LMWH increases ongoing pregnancy and live-birth rates in women with unexplained RPL.\n Controlled, multicenter trial with randomization using minimization conducted from 2006 to 2013. (ClinicalTrials.gov: NCT00400387).\n 14 university hospitals and perinatal care centers in Germany and Austria.\n 449 women with at least 2 consecutive early miscarriages or 1 late miscarriage were included during 5 to 8 weeks' gestation after a viable pregnancy was confirmed by ultrasonography.\n Women in the control group received multivitamin pills, and the intervention group received vitamins and 5000 IU of dalteparin-sodium for up to 24 weeks' gestation.\n Primary outcome was ongoing pregnancy at 24 weeks' gestation. Secondary outcomes included the live-birth rate and late pregnancy complications.\n At 24 weeks' gestation, 191 of 220 pregnancies (86.8%) and 188 of 214 pregnancies (87.9%) were intact in the intervention and control groups, respectively (absolute difference, -1.1 percentage points [95% CI, -7.4 to 5.3 percentage points]). The live-birth rates were 86.0% (185 of 215 women) and 86.7% (183 of 211 women) in the intervention and control groups, respectively (absolute difference, -0.7 percentage point [CI, -7.3 to 5.9 percentage points]). There were 3 intrauterine fetal deaths (1 woman had used LMWH); 9 cases of preeclampsia or the hemolysis, elevated liver enzyme level, and low platelet count (HELLP) syndrome (3 women had used LMWH); and 11 cases of intrauterine growth restriction or placental insufficiency (5 women had used LMWH).\n Placebo injections were not used, and neither trial staff nor patients were blinded.\n Daily LMWH injections do not increase ongoing pregnancy or live-birth rates in women with unexplained RPL. Given the burden of the injections, they are not recommended for preventing miscarriage.\n Pfizer Pharma.\n\nSchenk, Michael\n\n\n"
},
{
"text": "\n156641\nUse of ECG and Other Simple Non-Invasive Tools to Assess Pulmonary Hypertension.\n\nKovacs, G\n\nAvian, A\n\nForis, V\n\nTscherner, M\n\nKqiku, X\n\nDouschan, P\n\nBachmaier, G\n\nOlschewski, A\n\nMatucci-Cerinic, M\n\nOlschewski, H\n\nBeiträge in Fachzeitschriften\nISI:000391222000064\n28030578.0\n10.1371/journal.pone.0168706\nPMC5193419\nThere is a broad consensus that pulmonary hypertension (PH) is to be diagnosed by right heart catheterization (RHC) and that the most important non-invasive tool is echocardiography. However, the role of simple non-invasive tools in the work-up of PH is not clearly defined. We hypothesized that the use of simple non-invasive techniques may help to guide important decisions in the diagnostics of pulmonary hypertension.\n We aimed to develop an algorithm with the use of simple, non-invasive tools in order to identify patients with very high or very low likelihood of PH.\n We retrospectively analyzed all consecutive patients undergoing RHC between 2005 and 2010 in our center and performed logistic regression of simple non-invasive parameters regarding detection and exclusion of PH and derived a two-step algorithm. In a prospective study we evaluated this algorithm between 2011 and 2013.\n The retrospective cohort consisted of n = 394 patients of which 49% presented with PH. Right axis deviation in the ECG was present in 90/394 patients and had a positive predictive value (PPV) of 93% for PH. The combination of non-right axis deviation, N-terminal pro brain natriuretic peptide (NT-proBNP)<333pg/ml, arterial oxygen saturation (SO2)≥95.5% and WHO functional class I-II was present in 69/394 patients and excluded PH with a negative predictive value (NPV) of 96%. The prospective study confirmed these results in a cohort of n = 168 patients (PPV:92%, NPV:97%). Taken together, simple non-invasive tools allowed a prediction regarding the presence or absence of PH in 42% of patients with suspected PH.\n ECG, NT-proBNP, SO2 and WHO functional class may predict the presence or absence of PH in almost half of the patients with suspected PH, suggesting an important role for these variables in the work-up of patients at risk for PH.\n NCT01607502.\n\nAvian, Alexander\n\nBachmaier, Gerhard\n\nDouschan, Philipp\n\nForis, Vasile\n\nKovacs, Gabor\n\nOlschewski, Andrea\n\nOlschewski, Horst\n\n\n"
},
{
"text": "\n160324\nAutocapture(TM) and Capture Management(TM) Current concepts in pacing threshold and output management].\n\nAnelli-Monti, M\n\nMächler, H\n\nOberwalder, P\n\nDacar, D\n\nKnez, I\n\nSalaymeh, L\n\nStreinu, C\n\nRigler, B\n\nBeiträge in Fachzeitschriften\nNone\n27432388.0\n10.1007/s003990170003\nNone\nPacing threshold is not a stable value during the pacemaker's life. It is affected by many physiological, pharmacological and pathophysiological factors. A pacing system able to confirm capture and automatically adjust its output to the actual pacing threshold is highly desirable for a prolonged battery life and maximal patient safety. The Autocapture(TM) of St. Jude Medical and the Capture Management(TM) of Medtronic are currently available on the market. The key feature is the measurement of the evoked response (ER) signal by the pacemaker for capture confirmation. In case of loss of capture, the Autocapture(TM) System delivers a back up safety pulse of 4.5 Volt and 0.49 ms and starts a new threshold search. The pacemaker adapts its output to 0.3V/0.25V above the newly measured threshold. This system needs bipolar leads with low polarization for the first generation in Microny® and Regency® pacemakers; in the second generation with Affinity® and Integrity® pacemakers various bipolar leads are suitable. The Capture Management(TM) System of Medtronic, available in the Kappa® DR 700 series, performs a two point automatic threshold search once every day during rest. The output is determined by the programmed safety margin (nominal 1.5×voltage threshold). A backup pulse is only delivered during the threshold search. No special electrodes are necessary. These functions were shown to work safely and efficaciously in multicenter trials to decrease the current consumption with a prolongation of battery life up to 142%. The patients safety was increased by identifying changes of the capture threshold over time and adjusting the pacing stimulus. The conventional safety margins of 100% might not be safe for all patients. We also learned much about lead maturation and lead instability by the possibility of continuous follow-up of threshold changes in a larger group of leads in order to identify the risk group of about 10% of patients with late threshold increase and lead instability.\n\nAnelli-Monti, Michael\n\nKnez, Igor\n\nMächler, Heinrich\n\nOberwalder, Peter\n\n\n"
},
{
"text": "\n160703\nCatalytic competence, structure and stability of the cancer-associated R139W variant of the human NAD(P)H:quinone oxidoreductase 1 (NQO1).\n\nLienhart, WD\n\nStrandback, E\n\nGudipati, V\n\nKoch, K\n\nBinter, A\n\nUhl, MK\n\nRantasa, DM\n\nBourgeois, B\n\nMadl, T\n\nZangger, K\n\nGruber, K\n\nMacheroux, P\n\nBeiträge in Fachzeitschriften\nISI:000400358900009\n28236663.0\n10.1111/febs.14051\nPMC6250432\nThe human NAD(P)H:quinone oxidoreductase 1 (NQO1; EC1.6.99.2) is an essential enzyme in the antioxidant defence system. Furthermore, NQO1 protects tumour suppressors like p53, p33ING1b and p73 from proteasomal degradation. The activity of NQO1 is also exploited in chemotherapy for the activation of quinone-based treatments. Various single nucleotide polymorphisms are known, such as NQO1*2 and NQO1*3 yielding protein variants of NQO1 with single amino acid replacements, i.e. P187S and R139W, respectively. While the former NOQ1 variant is linked to a higher risk for specific kinds of cancer, the role, if any, of the arginine 139 to tryptophan exchange in disease development remains obscure. On the other hand, mitomycin C-resistant human colon cancer cells were shown to harbour the NQO1*3 variant resulting in substantially reduced enzymatic activity. However, the molecular cause for this decrease remains unclear. In order to resolve this issue, recombinant NQO1 R139W has been characterized biochemically and structurally. In this report, we show by X-ray crystallography and 2D-NMR spectroscopy that this variant adopts the same structure both in the crystal as well as in solution. Furthermore, the kinetic parameters obtained for the variant are similar to those reported for the wild-type protein. Similarly, thermostability of the variant was only slightly affected by the amino acid replacement. Therefore, we conclude that the previously reported effects in human cancer cells cannot be attributed to protein stability or enzyme activity. Instead, it appears that loss of exon 4 during maturation of a large fraction of pre-mRNA is the major reason of the observed lack of enzyme activity and hence reduced activation of quinone-based chemotherapeutics.\n © 2017 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.\n\nBourgeois, Benjamin Michel Rene\n\nMadl, Tobias\n\n\n"
},
{
"text": "\n162497\nHighly trabeculated structure of the human endocardium underlies asymmetrical response to low-energy monophasic shocks.\n\nConnolly, A\n\nRobson, MD\n\nSchneider, J\n\nBurton, R\n\nPlank, G\n\nBishop, MJ\n\nBeiträge in Fachzeitschriften\nISI:000412093600028\n28964115.0\n10.1063/1.4999609\nPMC5570597\nNovel low-energy defibrillation therapies are thought to be driven by virtual-electrodes (VEs), due to the interaction of applied monophasic electric shocks with fine-scale anatomical structures within the heart. Significant inter-species differences in the cardiac (micro)-anatomy exist, however, particularly with respect to the degree of endocardial trabeculations, which may underlie important differences in response to low-energy defibrillation protocols. Understanding the interaction of monophasic electric fields with the specific human micro-anatomy is therefore imperative in facilitating the translation and optimisation of these promising experimental therapies to the clinic. In this study, we sought to investigate how electric fields from implanted devices interact with the highly trabeculated human endocardial surface to better understand shock success in order to help optimise future clinical protocols. A bi-ventricular human computational model was constructed from high resolution (350 μm) ex-vivo MR data, including anatomically accurate endocardial structures. Monophasic shocks were applied between a basal right ventricular catheter and an exterior ground. Shocks of varying strengths were applied with both anodal [positive right ventricle (RV) electrode] and cathodal (negative RV electrode) polarities at different states of tissue refractoriness and during induced arrhythmias. Anodal shocks induced isolated positive VEs at the distal side of "detached" trabeculations, which rapidly spread into hyperpolarised tissue on the surrounding endocardial surfaces following the shock. Anodal shocks thus depolarised more tissue 10 ms after the shock than cathodal shocks where the propagation of activation from VEs induced on the proximal side of "detached" trabeculations was prevented due to refractory endocardium. Anodal shocks increased arrhythmia complexity more than cathodal shocks during failed anti-arrhythmia shocks. In conclusion, multiple detached trabeculations in the human ventricle interact with anodal stimuli to induce multiple secondary sources from VEs, facilitating more rapid shock-induced ventricular excitation compared to cathodal shocks. Such a mechanism may help explain inter-species differences in response to shocks and help to develop novel defibrillation strategies.\n\nPlank, Gernot\n\n\n"
},
{
"text": "\n166892\nImproved glycaemic control and treatment satisfaction with a simple wearable 3-day insulin delivery device among people with Type 2 diabetes.\n\nMader, JK\n\nLilly, LC\n\nAberer, F\n\nPoettler, T\n\nJohns, D\n\nTrautmann, M\n\nWarner, JL\n\nPieber, TR\n\nBeiträge in Fachzeitschriften\nISI:000445328800020\n29888811.0\n10.1111/dme.13708\nPMC6175230\nTo evaluate the PAQ® (CeQur SA, Horw, Switzerland), a wearable 3-day insulin delivery device that provides set basal rates and bolus insulin on demand, in people with Type 2 diabetes.\n Adults with Type 2 diabetes with HbA1c concentrations ≥53 and ≤97 mmol/mol (7.0 and 11.0%) while treated with ≥2 insulin injections/day were enrolled in two single-arm studies comprising three periods: a baseline (insulin injections), a transition and a PAQ treatment period (12 weeks). Endpoints included HbA1c , seven-point self-monitored blood glucose, total daily dose of insulin and body weight. Safety was assessed according to examination, hypoglycaemic episodes and adverse device effects.\n A total of 28 adults were enrolled (age 63 ± 7 years, 86% men, BMI 32.3 ± 4.3kg/m2 , Type 2 diabetes duration 17 ± 8 years, HbA1c 70 ± 12 mmol/mol (8.6 ± 1.1%), total daily insulin dose 58.7 ± 20.7 U), of whom 24 completed the studies. When transitioned to PAQ, 75% of participants continued on the first basal rate selected. After 12 weeks of PAQ wear, significant improvements from baseline were seen [HbA1c -16 ± 9 mmol/mol (95% CI -20, -12) or -1.5 ± 0.9% (95% CI -1.8, -1.1) P<0.0001], and at all seven self-monitored blood glucose readings time points (P ≤0.03). Total daily insulin dose increased by 12.1 ± 19.5 U (95% CI 3.9, 20.4; P=0.0058), the number of meal time boluses increased by 0.9 ± 1.5/day (95% CI 0.3, 1.5; P=0.0081) and body weight remained stable. Six participants had mild to moderate catheter site reactions and one mild skin irritation occurred. No participant experienced severe hypoglycaemia.\n Adults with Type 2 diabetes were safely transitioned from insulin injections to the PAQ and had significantly improved glycaemic control and treatment satisfaction with insulin therapy. (ClinicalTrials.gov identifiers: NCT02158078 & NCT02419859).\n © 2018 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.\n\nAberer, Felix\n\nMader, Julia\n\nPieber, Thomas\n\nPöttler, Tina\n\n\n"
},
{
"text": "\n167647\nEndoplasmic reticulum stress in bipolar disorder? - BiP and CHOP gene expression- and XBP1 splicing analysis in peripheral blood.\n\nBengesser, SA\n\nReininghaus, EZ\n\nDalkner, N\n\nBirner, A\n\nHohenberger, H\n\nQueissner, R\n\nFellendorf, F\n\nPlatzer, M\n\nPilz, R\n\nHamm, C\n\nRieger, A\n\nKapfhammer, HP\n\nMangge, H\n\nReininghaus, B\n\nMeier-Allard, N\n\nStracke, A\n\nFuchs, R\n\nHolasek, S\n\nBeiträge in Fachzeitschriften\nISI:000445713400013\n29843019.0\n10.1016/j.psyneuen.2018.05.029\nNone\nEndoplasmic Reticulum stress activates the Unfolded Protein Response, which is partially impaired in Bipolar Disorder (BD) according to previous in-vitro studies. Thus, BiP and CHOP gene expression and XBP1 splicing were analyzed in peripheral blood of study participants with BD and controls.\n RNA was isolated from fasting blood of study participants with BD (n = 81) and controls (n = 54) and reverse transcribed into cDNA. BiP and CHOP gene expression was analyzed with quantitative RT-PCR. Atypical splicing of XBP1 mRNA was measured by semi-quantitative RT-PCR, gel-electrophoresis and densitometry. ANCOVAs with the covariates age, BMI, sex, lithium and anticonvulsants intake were used with SPSS. Bonferroni correction was used to correct for multiple testing (adjusted p = 0.0083).\n BiP gene expression was significantly higher in BD than in controls (F(1/128) = 10.076, p = 0.002, Partial η2 = 0.073). Total XBP1 (F(1/126) = 9.550, p = 0.002, Partial η2 = 0.070) and unspliced XBP1 (F(1/128)= 8.803, p= 0.004, Patial η2 = 0.065) were significantly decreased in BD. Spliced XBP1 (F(1/126) = 5.848, p = 0.017, Partial η2 = 0.044) and the ratio spliced XBP1/ unspliced XBP1 did not differ between BD and controls (F(1/126) = 0.599, p = 0.441, Partial η2 = 0.005). Gene expression did not differ between euthymia, depression and mania.\n BiP gene expression was significantly higher in BD compared to controls. Total and unspliced XBP1 were significantly lower in BD than in the control group. Thus, both genes may be considered as putative trait markers. Nevertheless, XBP1 splicing itself did not differ between both groups.\n Copyright © 2018 Elsevier Ltd. All rights reserved.\n\nBengesser, Susanne\n\nBirner, Armin\n\nDalkner, Nina\n\nFellendorf, Frederike\n\nHamm, Carlo\n\nHolasek, Sandra Johanna\n\nKapfhammer, Hans-Peter\n\nMangge, Harald\n\nMeier-Allard, Nathalie\n\nPilz, Rene\n\nPlatzer, Martina\n\nQueissner, Robert\n\nReininghaus, Eva\n\nRieger, Alexandra\n\nStracke, Anika\n\n\n"
},
{
"text": "\n182538\nMinor Structural Differences in the Cervical Spine Between Patients With Cervical Dystonia and Age-Matched Healthy Controls.\n\nKatschnig-Winter, P\n\nEnzinger, C\n\nBohlsen, D\n\nMagyar, M\n\nSeiler, S\n\nHofer, E\n\nFranthal, S\n\nHomayoon, N\n\nKögl, M\n\nWenzel, K\n\nDeutschmann, H\n\nFazekas, F\n\nSchmidt, R\n\nSchwingenschuh, P\n\nBeiträge in Fachzeitschriften\nISI:000542188900001\n32547481.0\n10.3389/fneur.2020.00472\nPMC7272577\nBackground: Cervical dystonia is the most common form of focal dystonia. The frequency and pattern of degenerative changes of the cervical spine in patients with cervical dystonia and their relation to clinical symptoms remain unclear as no direct comparison to healthy controls has been performed yet. Here, we used magnetic resonance imaging (MRI) to investigate (1) whether structural abnormalities of the cervical spine are more common in patients with cervical dystonia compared to age-matched healthy controls, (2) if there are clinical predictors for abnormalities on MRI, and (3) to calculate the inter-rater reliability of the respective radiological scales. Methods: Twenty-five consecutive patients with cervical dystonia and 20 age-matched healthy controls were included in the study. MRI scans of the cervical spine were analyzed separately by three experienced raters blinded to clinical information, applying different MRI rating scales. Structural abnormalities were compared between groups for upper, middle, and lower cervical spine segments. The associations between scores differentiating both groups and clinical parameters were assessed in dystonia patients. Additionally, inter-rater reliability of the MRI scales was calculated. Results: Comparing structural abnormalities, we found minor differences in the middle cervical spine, indicated by a higher MRI total score in patients but no significant correlation between clinical parameters and MRI changes. Inter-rater reliability was satisfying for most of the MRI rating scales. Conclusion: Our results do not provide evidence for a role of MRI of the cervical spine in the routine work-up of patients with cervical dystonia in the absence of specific clinical signs or symptoms.\n Copyright © 2020 Katschnig-Winter, Enzinger, Bohlsen, Magyar, Seiler, Hofer, Franthal, Homayoon, Kögl, Wenzel, Deutschmann, Fazekas, Schmidt and Schwingenschuh.\n\nDeutschmann, Hannes\n\nEnzinger, Christian\n\nFazekas, Franz\n\nFranthal, Sebastian Othmar\n\nHofer, Edith\n\nHomayoon, Nina\n\nKatschnig-Winter, Petra\n\nMagyar, Marton\n\nSchmidt, Reinhold\n\nSchwingenschuh, Petra\n\nWenzel, Karoline\n\n\n"
},
{
"text": "\n186819\nCpG islands in MyD88 and ASC/PYCARD/TMS1 promoter regions are differentially methylated in head and neck squamous cell carcinoma and primary lung squamous cell carcinoma.\n\nŠutić, M\n\nBaranašić, J\n\nBilić, LK\n\nBilić, M\n\nJakovčević, A\n\nBrčić, L\n\nSeiwerth, S\n\nJakopović, M\n\nSamaržija, M\n\nZechner, U\n\nKnežević, J\n\nBeiträge in Fachzeitschriften\nISI:000622322000001\n33637109.0\n10.1186/s13000-021-01078-3\nPMC7913417\nPatients with head and neck squamous cell carcinoma (HNSCC) can develop lung squamous cell carcinoma (LuSCC), which could be the second primary tumor or HNSCC metastasis. Morphologically it is difficult to distinguish metastatic HNSCC from a second primary tumor which presents a significant diagnostic challenge. Differentiation of those two malignancies is important because the recommended treatments for metastatic HNSCC and primary LuSCC differ significantly. We investigated if the quantification of the promotor methylation status in HNSCC and LuSCC differs.\n Primary HNSCC (N = 36) and LuSCC (N = 17) were included in this study. Methylation status in the ASC/TMS1/PYCARD (apoptosis-associated speck-like protein containing a caspase recruitment domain; 8 CpG sites) and MyD88 (Myeloid differentiation primary response protein 88; 10 CpG sites) promoters was analyzed. Bisulfite converted DNA, isolated from tumor tissue was quantified using pyrosequencing. Results of pyrosequencing analysis were expressed as a percentage for each tested CpG site. Receiver-operating characteristic (ROC) curve analysis was used for the evaluation of the diagnostic properties of selected biomarkers.\n CpG sites located in the promoters of ASC/TMS1/PYCARD_CpG8 (- 65 upstream) and MyD88_CpG4 (- 278 upstream) are significantly hypermethylated in the HNSCC when compared with LuSCC (p ≤ 0.0001). By performing ROC curve analysis we showed that corresponding areas under the curve (AUC) were 85-95%, indicating that selected CpG sites are useful for a distinction between primary LuSCC and primary HNSCC.\n Results of the present study indicate that there is a significant difference in the methylation status of tested genes between primary HNSCC and LuSCC. However, to prove this approach as a useful tool for distinguishing second primary LuSCC from HNSCC metastasis, it would be necessary to include a larger number of samples, and most importantly, metastatic samples.\n\nBrcic, Luka\n\n\n"
},
{
"text": "\n186886\nAnterior bundle of ulnar collateral ligament: evaluation of anatomic relationships by using MR imaging, MR arthrography, and gross anatomic and histologic analysis.\n\nMunshi, M\n\nPretterklieber, ML\n\nChung, CB\n\nHaghighi, P\n\nCho, JH\n\nTrudell, DJ\n\nResnick, D\n\nBeiträge in Fachzeitschriften\nISI:000221585200029\n15105452.0\n10.1148/radiol.2313030560\nNone\nTo evaluate the gross and microscopic anatomy and the magnetic resonance (MR) imaging and MR arthrographic appearance of the anterior bundle of the ulnar collateral ligament (UCL) of the elbow.\n The origin and insertion of the anterior bundle of the UCL, the bundle's relationship to the overlying flexor tendons, and the presence of a layered configuration were assessed through inspection and dissection of an elbow specimen. T1-weighted spin-echo MR imaging and MR arthrography in standard imaging planes and a coronal oblique plane were performed in eight other elbow specimens. Additional MR arthrography was performed in four specimens by using the coronal plane with the elbow in 20 degrees of flexion. The specimens were then cut in planes corresponding to those of the MR images. Histologic analysis of two specimens was performed.\n The anterior bundle of the UCL appeared as a low-signal-intensity structure on T1-weighted spin-echo MR and MR arthrographic images. It consisted of a uniform layer of parallel collagen fibers attaching proximally to the base of the medial epicondyle of the humerus and distally to the medial aspect of the coronoid process of the ulna (sublime tubercle). A layer of synovium separated the anterior bundle from the more superficial tendon of the flexor digitorum superficialis muscle. MR imaging-anatomic comparison in four (50%) specimens revealed separation between the anterior bundle of the UCL and the sublime tubercle. Results of histologic analysis of two of these specimens confirmed insertion of the anterior bundle of the UCL 3 and 4 mm distal to the articular margin. Ligamentous degeneration was detected in only one of these specimens.\n There is variability in the distal insertion of the anterior bundle, and this suggests that caution should be exercised in the diagnosis of its partial detachment from the sublime tubercle of the ulna.\n Copyright RSNA, 2004\n\n\n"
},
{
"text": "\n3135\nPerioperative myocardial cell injury: the relationship between troponin T and cortisol.\n\nMahla, E\n\nTiesenhausen, K\n\nRehak, P\n\nFruhwald, S\n\nPürstner, P\n\nMetzler, H\n\nBeiträge in Fachzeitschriften\nISI:000087877900007\n10869919.0\n10.1016/S0952-8180(00)00150-1\nNone\nSTUDY OBJECTIVE: To investigate whether there is an association between Troponin T (TnT), reflecting myocardial cell injury, and cortisol, reflecting the degree of surgical trauma and associated stress, in light of our recent evaluation of TnT as a marker of perioperative myocardial cell injury.DESIGN: Prospective, cohort study.PATIENTS: 70 patients (67.4 +/- 8.7 yrs) with definite or at-risk coronary artery disease (CAD) undergoing elective noncardiac surgery (vascular n = 38, abdominal n = 21, orthopedic n = 8) with general (n = 63) or regional (n = 4) anesthesia with postoperative on-demand analgesia.MEASUREMENTS AND MAIN RESULTS: Morning blood samples for TnT (upper limit of normal: <0.2 ng/mL), CK-MB (reference range =12 U/L), and cortisol (normal morning range 7-25 mcg/dL) were taken on the day before surgery, on the morning of surgery before induction of anesthesia, and on the first 5 postoperative days. Data were compared by analysis of variance. Three patients were excluded from the study because of incomplete blood samples of TnT or cortisol. Preoperative mean cortisol levels (mcg/dL +/- SD) were within the normal range and equal in TnT positive (n = 13) and negative (n = 54) patients (16.1 +/- 4.5 vs. 15.6 +/- 5.8). On the 1st postoperative day, there was a substantial increase of cortisol in the TnT positive group (35.7 +/- 26.9). Cortisol remained high until the 5th postoperative day (24.7 +/- 9. 4). There was a significant difference in the cortisol concentration in TnT-positive compared to TnT-negative patients (p < 0.001), a significant difference in the perioperative cortisol concentration over time (p < 0.05), and a significant interaction (p < 0.001). But there was no consistent temporal relationship between the increase of TnT and the increase of cortisol.CONCLUSIONS: The significant relationship between a highly sensitive and specific marker of myocardial cell injury and a marker of stress suggests that cardiac-risk patients undergoing stressful surgical procedures might benefit from close perioperative TnT monitoring with early recognition of myocardial cell injury.\n\nFruhwald, Sonja\n\nMahla, Elisabeth\n\nMetzler, Helfried\n\nTiesenhausen, Kurt\n\n\n"
},
{
"text": "\n5375\nEvaluation of automated sample preparation and quantitative PCR LCx assay for determination of human immunodeficiency virus type 1 RNA.\n\nMuller, Z\n\nStelzl, E\n\nBozic, M\n\nHaas, J\n\nMarth, E\n\nKessler, HH\n\nBeiträge in Fachzeitschriften\nISI:000220963000009\n15070986.0\n10.1128%2FJCM.42.4.1439-1443.2004\nPMC387536\nEfforts have been made to achieve full automation of molecular assays for quantitative detection of human immunodeficiency virus type 1 (HIV-1). In the present study, the Abbott LCx HIV RNA Quantitative assay was evaluated in conjunction with automated HIV-1 RNA extraction on the MagNA Pure LC instrument and compared to the conventional LCx HIV RNA Quantitative assay, which uses a manual nucleic acid extraction protocol. Accuracy, linearity, and interassay and intra-assay variations were determined. The performance of the assay in a routine clinical laboratory was tested with a total of 105 clinical specimens. When the accuracy of the LCx HIV RNA Quantitative assay with the automated sample preparation protocol was tested, all results were found to be within +/- 0.5 log unit of the expected results. Determination of linearity resulted in a quasilinear curve over 3.5 log units. For determination of interassay variation, coefficients of variation were found to be between 21 and 66% for the LCx HIV RNA Quantitative assay with the automated sample preparation protocol and between 10 and 69% for the LCx HIV RNA Quantitative assay with manual sample preparation. For determination of intra-assay variation, coefficients of variation were found to be between 7 and 25% for the LCx HIV RNA Quantitative assay with the automated sample preparation protocol and between 7 and 19% for the LCx HIV RNA Quantitative assay with manual sample preparation. When clinical samples were tested by the LCx HIV RNA Quantitative assay with the automated sample preparation protocol and the results were compared with those of the LCx HIV RNA Quantitative assay with manual sample preparation, 95% of all positive results were found to be within +/- 0.5 log unit. In conclusion, the assay with automated sample preparation proved to be suitable for use in the routine diagnostic laboratory and required significantly less hands-on time.\n\nBozic, Michael\n\nHaas, Josef\n\nKessler, Harald\n\nMarth, Egon\n\nStelzl, Evelyn\n\n\n"
}
]
}