HTTP 200 OK
Allow: GET, HEAD, OPTIONS
Content-Type: application/json
Vary: Accept
{
"count": 127182,
"next": "https://api-test.medunigraz.at/v1/research/search/publication/?format=api&limit=20&offset=124220",
"previous": "https://api-test.medunigraz.at/v1/research/search/publication/?format=api&limit=20&offset=124180",
"results": [
{
"text": "\n107873\nHistamine intolerance: lack of reproducibility of single symptoms by oral provocation with histamine: A randomised, double-blind, placebo-controlled cross-over study.\n\nKomericki, P\n\nKlein, G\n\nReider, N\n\nHawranek, T\n\nStrimitzer, T\n\nLang, R\n\nKranzelbinder, B\n\nAberer, W\n\nBeiträge in Fachzeitschriften\nISI:000287497700004\n21165702.0\n10.1007/s00508-010-1506-y\nNone\nOBJECTIVES: The term histamine intolerance stands for a range of symptoms involving various effector organs after the consumption of histamine-rich food. Our intention was to objectify and quantify histamine-associated symptoms and to analyse whether oral administration of the histamine-degrading enzyme diamine oxidase (DAO) caused a reduction of symptoms. PATIENTS AND METHODS: Four Austrian centres participated. Patients suspected to be histamine intolerant were recruited. The first step consisted in the open oral provocation of these patients with 75 mg of liquid histamine. Patients who developed symptoms were tested in a randomised double blind crossover provocation protocol using histamine-containing and histamine-free tea in combination with DAO capsules or placebo. Main and secondary symptoms (strongest and weaker symptoms based on a ten-point scale) were defined, the grand total of all symptoms of the individual provocation steps was determined and changes in symptoms after administration of DAO were measured. RESULTS: Thirty nine patients reacted to the open histamine provocation and were enrolled in the blinded part. Here, both the main and secondary symptoms were not reproducible. Subjects reacted sometimes unexpectedly and randomly. Regarding the total symptom scores, the differences between the three treatment groups were statistically significant. The intake of DAO demonstrated a statistically significant reduction of histamine-associated symptoms compared to placebo (P = 0.014). CONCLUSIONS: Oral provocation with 75 mg of liquid histamine failed to reproduce histamine-associated single symptoms in many patients. One may suggest that histamine-intolerant subjects reacted with different organs on different occasions. As a consequence, reproducibility of single symptoms alone may not be appropriate to diagnose histamine-intolerance whereas a global symptom score could be more appropriate. The fact, that the intake of DAO capsules compared to placebo led to a statistically significant reduction of total symptom scores, may indirectly point in the same direction.\n\nAberer, Werner\n\nKomericki, Peter\n\n\n"
},
{
"text": "\n112583\nThe effect of previous exposure to technology on acceptance and its importance in usability and accessibility engineering\n\nHolzinger, A\n\nSearle, G\n\nWernbacher, M\n\nBeiträge in Fachzeitschriften\nISI:000293020500003\nNone\n10.1007/s10209-010-0212-x\nNone\nIn Usability and Accessibility Engineering, metric standards are vital. However, the development of a set of reciprocal metrics-which can serve as an extension of, and supplement to, current standards-becomes indispensable when the specific needs of end-user groups, such as the elderly and people with disabilities, are concerned. While ISO 9126 remains critical to the usability of a product, the needs of the elderly population are forcing the integration of other factors. Familiarity and recognisability are not relevant to someone with no experience and therefore no referent; however, acceptance becomes a major factor in their willingness to learn something new and this acceptance requires trust based on association. Readability and legibility are of less relevance to a blind person than to someone with failing eyesight. This paper describes some usability metrics ascertained on the basis of experiments made with applications for elderly people throughout the summer term of 2007. The factors that influence the older users' acceptance of software, including the extent of their previous exposure to technology, are evaluated in order to provide short guidelines for software developers on how to design and develop software for the elderly. The evaluation of the expectations, behavior, abilities, and limitations of prospective end-users is considered of primary importance for the development of technology. A total of N = 31 participants (22 women/9 men) took part in various tests. The participants' ages ranged from 49 to 96 years with an average age of 79. Five of the tests were designed for a PDA or cellular phone, one test was designed for a laptop PC. Of the total of 55 tests, 52 tests provided sufficient data to evaluate the results. In 23 of the tests, all tasks were completed. As a main outcome, it can be experimentally proved that the acceptance is related to a factor, which is this paper is called PET (Previous Exposure to Technology). This is discussed in light of the aforementioned metrics.\n\nHolzinger, Andreas\n\n\n"
},
{
"text": "\n115252\nLow-dose 5-fluorouracil in combination with salicylic acid as a new lesion-directed option to treat topically actinic keratoses: histological and clinical study results.\n\nStockfleth, E\n\nKerl, H\n\nZwingers, T\n\nWillers, C\n\nBeiträge in Fachzeitschriften\nISI:000297318700027\n21517801.0\n10.1111/j.1365-2133.2011.10387.x\nNone\nBACKGROUND: Actinic keratoses (AKs) arise after chronic sun exposure. Because long-term ultraviolet (UV) damage may induce proliferation of atypical keratinocytes, treatment of AKs is recommended. OBJECTIVES: To compare 5-fluorouracil 0·5%/salicylic acid 10·0% [low-dose 5-FU/SA (Actikerall®)] with diclofenac 3% in hyaluronic acid (diclofenac HA) and vehicle for the treatment of AKs. METHODS: This was a randomized, placebo-controlled, double-blind, parallel-group, multicentre trial. Patients received topical low-dose 5-FU/SA once daily, its vehicle or diclofenac HA twice daily for a maximum of 12 weeks. The final evaluation was at week 20. The primary objectives were to demonstrate the histological clearance rate of one predefined lesion. The secondary objectives were the improvement of treated lesions, tolerability and safety. RESULTS: There were 470 patients with 4-10 AK lesions each (grade I or II) on the face/forehead or bald scalp included in the study. Low-dose 5-FU/SA was superior to diclofenac HA (P < 0·01) and vehicle (P < 0·0001) for histological clearance of one representative lesion 8 weeks post-treatment. In 72·0%, 59·1% and 44·8% of patients in the low-dose 5-FU/SA, diclofenac HA and vehicle groups, respectively, the week-20 biopsy revealed no AKs. Significantly more lesions were cleared with low-dose 5-FU/SA (74·5%) compared with diclofenac HA (54·6%; P < 0·001) or vehicle (35·5%; P< 0·001). Low-dose 5-FU/SA was superior in terms of complete clinical clearance: 55·4%, vs. diclofenac HA (32·0%, P < 0·001) and vehicle (15·1%P < 0·001). Application-site disorders (mainly burning and inflammation) were more frequent with low-dose 5-FU/SA but mainly of mild to moderate intensity. CONCLUSIONS: Topical low-dose 5-FU/SA demonstrated higher histological and clinical clearance rates vs. diclofenac HA or vehicle. Low-dose 5-FU/SA is an effective lesion-directed treatment for AKs. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.\n\nKerl, Helmut\n\n\n"
},
{
"text": "\n117429\nInterference with bile salt export pump function is a susceptibility factor for human liver injury in drug development.\n\nMorgan, RE\n\nTrauner, M\n\nvan Staden, CJ\n\nLee, PH\n\nRamachandran, B\n\nEschenberg, M\n\nAfshari, CA\n\nQualls, CW\n\nLightfoot-Dunn, R\n\nHamadeh, HK\n\nBeiträge in Fachzeitschriften\nISI:000284432600015\n20829430.0\n10.1093/toxsci/kfq269\nNone\nThe bile salt export pump (BSEP) is an efflux transporter, driving the elimination of endobiotic and xenobiotic substrates from hepatocytes into the bile. More specifically, it is responsible for the elimination of monovalent, conjugated bile salts, with little or no assistance from other apical transporters. Disruption of BSEP activity through genetic disorders is known to manifest in clinical liver injury such as progressive familial intrahepatic cholestasis type 2. Drug-induced disruption of BSEP is hypothesized to play a role in the development of liver injury for several marketed or withdrawn therapeutics. Unfortunately, preclinical animal models have been poor predictors of the liver injury associated with BSEP interference observed for humans, possibly because of interspecies differences in bile acid composition, differences in hepatobiliary transporter modulation or constitutive expression, as well as other mechanisms. Thus, a BSEP-mediated liver liability may go undetected until the later stages of drug development, such as during clinical trials or even postlicensing. In the absence of a relevant preclinical test system for BSEP-mediated liver injury, the toxicological relevance of available in vitro models to human health rely on the use of benchmark compounds with known clinical outcomes, such as marketed or withdrawn drugs. In this study, membrane vesicles harvested from BSEP-transfected insect cells were used to assess the activity of more than 200 benchmark compounds to thoroughly investigate the relationship between interference with BSEP function and liver injury. The data suggest a relatively strong association between the pharmacological interference with BSEP function and human hepatotoxicity. Although the most accurate translation of risk would incorporate pharmacological potency, pharmacokinetics, clearance mechanisms, tissue distribution, physicochemical properties, indication, and other drug attributes, the additional understanding of a compound's potency for BSEP interference should help to limit or avoid BSEP-related liver liabilities in humans that are not often detected by standard preclinical animal models.\n\n\n"
},
{
"text": "\n118285\nPrognostic factors in upper urinary tract urothelial carcinomas: a comprehensive review of the current literature.\n\nLughezzani, G\n\nBurger, M\n\nMargulis, V\n\nMatin, SF\n\nNovara, G\n\nRoupret, M\n\nShariat, SF\n\nWood, CG\n\nZigeuner, R\n\nBeiträge in Fachzeitschriften\nISI:000304487900031\n22381168.0\n10.1016/j.eururo.2012.02.030\nNone\nContext: The heterogeneity of upper tract urothelial carcinoma (UTUC) biology and prognosis, as well as the presence of different treatment options, makes the clinical decision-making process extremely challenging. Objective: Provide an overview of the currently available prognostic factors for UTUC, focusing on clinical and pathologic characteristics, as well as on molecular markers. Evidence acquisition: A systematic literature search was conducted using the PubMed, Scopus, and Embase databases to identify original articles, review articles, and editorials regarding prognostic factors in patients with UTUC. Keywords included urothelial carcinoma, renal pelvis, ureter, upper urinary tract urothelial carcinoma, upper urinary tract transitional cell carcinoma, prognosis, prognostic factors, markers, and survival. Articles published between 2000 and 2011 were reviewed and selected with the consensus of all the authors. Evidence synthesis: Prognostic factors can be divided into four different categories: preoperative/clinical factors, intraoperative/surgical factors, postoperative/pathologic factors, and molecular markers. Because of the rarity of the disease, only a small amount of level 1 evidence information from prospective randomized trials is available. Conversely, several single-institutional and multi-institutional studies have been published providing level 3 evidence information on various prognostic factors. Tumor stage and grade represent the best-established predictors of prognosis in patients with UTUC, but controversies still exist regarding the prognostic impact of tumor location and tumor necrosis. Several promising biomarkers have also been evaluated, but further studies evaluating their prognostic role are still needed. Finally, few prognostic models have been developed to provide clinicians with accurate estimates of the outcome of interest. Conclusions: In the past few years, several prognostic factors have been identified to help clinicians dealing with patients with UTUC in the decision-making process. However, well-designed multi-institutional studies are still needed to provide stronger evidence and to promote the use of these prognostic factors in clinical practice. (C) 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.\n\nZigeuner, Richard\n\n\n"
},
{
"text": "\n124131\nInfluence of PEGylation and RGD loading on the targeting properties of radiolabeled liposomal nanoparticles.\n\nRangger, C\n\nHelbok, A\n\nvon Guggenberg, E\n\nSosabowski, J\n\nRadolf, T\n\nPrassl, R\n\nAndreae, F\n\nThurner, GC\n\nHaubner, R\n\nDecristoforo, C\n\nBeiträge in Fachzeitschriften\nISI:000311479400001\n23226020.0\n10.2147/IJN.S36847\nPMC3512544\nPurpose: Liposomes have been proposed to be a means of selectively targeting cancer sites for diagnostic and therapeutic applications. The focus of this work was the evaluation of radiolabeled PEGylated liposomes derivatized with varying amounts of a cyclic arginyl-glycyl-aspartic acid (RGD) peptide. RGD peptides are known to bind to alpha(v)beta(3) integrin receptors overexpressed during tumor-induced angiogenesis.\nMethods: Several liposomal nanoparticles carrying the RGD peptide targeting sequence (RLPs) were synthesized using a combination of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, cholesterol, diethylenetriaminepentaacetic acid-derivatized lipids for radiolabeling, a polyethylene glycol (PEG) building block, and a lipid-based RGD building block. Relative amounts of RGD and PEG building blocks were varied. In vitro binding affinities were determined using isolated alpha(v)beta(3) integrin receptors incubated with different concentrations of RLPs in competition with iodine-125-labeled cyclo-(-RGDyV-). Binding of the indium-111-labeled RLPs was also evaluated. Biodistribution and micro single photon emission computed tomography/computed tomography imaging studies were performed in nude mice using different tumor xenograft models.\nResults: RLPs were labeled with indium-111 with high radiochemical yields. In vitro binding studies of RLPs with different RGD/PEG loading revealed good binding to isolated receptors, which was dependent on the extent of RGD and PEG loading. Binding increased with higher RGD loading, whereas reduced binding was found with higher PEG loading. Biodistribution showed increased circulating time for PEGylated RLPs, but no dependence on RGD loading. Both biodistribution and micro single photon emission computed tomography/computed tomography imaging studies revealed low, nonspecific tumor uptake values.\nConclusion: In this study, RLPs for targeting angiogenesis were described. Even though good binding to alpha(v)beta(3) integrin receptors was found in vitro, the balance between PEGylation and RGD loading clearly requires optimization to achieve targeting in vivo. These data form the basis for future development and provide a platform for the investigation of multimodal approaches.\n\nPrassl, Ruth\n\n\n"
},
{
"text": "\n128587\nApixaban versus enoxaparin for thromboprophylaxis in medically ill patients.\n\nGoldhaber, SZ\n\nLeizorovicz, A\n\nKakkar, AK\n\nHaas, SK\n\nMerli, G\n\nKnabb, RM\n\nWeitz, JI\n\nADOPT Trial Investigators\n\nBeiträge in Fachzeitschriften\nISI:000297731400002\n22077144.0\n10.1056/NEJMoa1110899\nNone\nBACKGROUND The efficacy and safety of prolonging prophylaxis for venous thromboembolism in medically ill patients beyond hospital discharge remain uncertain. We hypothesized that extended prophylaxis with apixaban would be safe and more effective than short-term prophylaxis with enoxaparin. METHODS In this double-blind, double-dummy, placebo-controlled trial, we randomly assigned acutely ill patients who had congestive heart failure or respiratory failure or other medical disorders and at least one additional risk factor for venous thromboembolism and who were hospitalized with an expected stay of at least 3 days to receive apixaban, administered orally at a dose of 2.5 mg twice daily for 30 days, or enoxaparin, administered subcutaneously at a dose of 40 mg once daily for 6 to 14 days. The primary efficacy outcome was the 30-day composite of death related to venous thromboembolism, pulmonary embolism, symptomatic deep-vein thrombosis, or asymptomatic proximal-leg deep-vein thrombosis, as detected with the use of systematic bilateral compression ultrasonography on day 30. The primary safety outcome was bleeding. All efficacy and safety outcomes were independently adjudicated. RESULTS A total of 6528 subjects underwent randomization, 4495 of whom could be evaluated for the primary efficacy outcome - 2211 in the apixaban group and 2284 in the enoxaparin group. Among the patients who could be evaluated, 2.71% in the apixaban group (60 patients) and 3.06% in the enoxaparin group (70 patients) met the criteria for the primary efficacy outcome (relative risk with apixaban, 0.87; 95% confidence interval [CI], 0.62 to 1.23; P = 0.44). By day 30, major bleeding had occurred in 0.47% of the patients in the apixaban group (15 of 3184 patients) and in 0.19% of the patients in the enoxaparin group (6 of 3217 patients) (relative risk, 2.58; 95% CI, 1.02 to 7.24; P = 0.04). CONCLUSIONS In medically ill patients, an extended course of thromboprophylaxis with apixaban was not superior to a shorter course with enoxaparin. Apixaban was associated with significantly more major bleeding events than was enoxaparin. (Funded by Bristol-Myers Squibb and Pfizer; ClinicalTrials.gov number, NCT00457002.)\n\nPilger, Ernst\n\n\n"
},
{
"text": "\n135048\nPresynaptic alpha2-adrenoceptors control excitatory, but not inhibitory, transmission at rat hippocampal synapses.\n\nBoehm, S\n\nBeiträge in Fachzeitschriften\nISI:000082768700012\n10457061.0\n10.1111/j.1469-7793.1999.0439m.x\nPMC2269514\n1. The effects of noradrenaline on neurotransmission at rat hippocampal synapses were investigated by recording autaptic currents in single neurons isolated on glial microislands. Noradrenaline reduced excitatory, but not inhibitory, autaptic currents in a pertussis toxin-sensitive manner, but the amine did not affect glutamate-evoked currents. 2. The inhibition of excitatory autaptic currents by noradrenaline was half-maximal at 0. 11 +/- 0.06 microM. The alpha2-adrenoceptor agonists UK 14 304 and clonidine were equipotent to noradrenaline in reducing these currents, whereas the alpha1-adrenoceptor agonist methoxamine and the beta-adrenoceptor agonist isoprenaline (isoproterenol) were ineffective. The reduction of excitatory autaptic currents by noradrenaline was not altered by the alpha1-adrenergic antagonist urapidil or the beta-antagonist propranolol, but reduced by the alpha2-antagonist yohimbine. The subtype-preferring antagonists rauwolscine and phentolamine (both at 0.3 microM) caused 9-fold and 36-fold rightward shifts in the concentration-response curve for the noradrenaline-dependent reduction of excitatory autaptic currents, respectively. Prazosine (1 microM) did not affect this concentration-response curve. 3. Noradrenaline reduced voltage-activated Ca2+ currents in excitatory, but not in inhibitory, microisland neurons. For comparison, the GABAB agonist baclofen reduced both excitatory and inhibitory autaptic currents and diminished voltage-activated Ca2+ currents in both types of neurons. The inhibition of Ca2+ currents by noradrenaline was half-maximal at 0.17 +/- 0.05 microM, and UK 14 304 and clonidine were equipotent to noradrenaline in reducing these currents. The noradrenaline-induced reduction of Ca2+ currents was antagonized by yohimbine, but not by urapidil or propranolol; the subtype-preferring alpha2-adrenergic antagonists displayed the following rank order of activity: phentolamine > rauwolscine > prazosine. 4. Noradrenaline did not affect K+ currents and failed to alter the frequency of miniature excitatory postsynaptic currents measured in mass cultures of hippocampal neurons. 5. These results show that noradrenaline regulates transmission at glutamatergic, but not at GABAergic, hippocampal synapses via presynaptic alpha2-adrenoceptors of the alpha2A/D subtype. This inhibitory action involves an inhibition of voltage-activated Ca2+ currents, but no modulation of spontaneous vesicle exocytosis or of voltage-activated K+ currents.\n\n\n"
},
{
"text": "\n135065\nFinal results of the HEALING IIB trial to evaluate a bio-engineered CD34 antibody coated stent (Genous™Stent) designed to promote vascular healing by capture of circulating endothelial progenitor cells in CAD patients.\n\nden Dekker, WK\n\nHoutgraaf, JH\n\nOnuma, Y\n\nBenit, E\n\nde Winter, RJ\n\nWijns, W\n\nGrisold, M\n\nVerheye, S\n\nSilber, S\n\nTeiger, E\n\nRowland, SM\n\nLigtenberg, E\n\nHill, J\n\nWiemer, M\n\nden Heijer, P\n\nRensing, BJ\n\nChannon, KM\n\nSerruys, PW\n\nDuckers, HJ\n\nBeiträge in Fachzeitschriften\nISI:000296587200037\n21763653.0\n10.1016/j.atherosclerosis.2011.06.032\nNone\nObjective: To assess the safety and efficacy of the Genous (TM) endothelial progenitor cell (EPC) capturing stent in conjunction with HmG-CoA-reductase inhibitors (statins) to stimulate EPC recruitment, in the treatment of patients with de novo coronary artery lesions. Methods and results: The HEALING IIB study was a multi-center, prospective trial, including 100 patients. The primary efficacy endpoint was late luminal loss by QCA at 6-month follow-up (FU). Although statin therapy increased relative EPC levels by 5.6-fold, the angiographic outcome at 6 month FU was not improved in patients with an overall in-stent late luminal loss of 0.76 +/- 0.50mm. The composite major adverse cardiac events (MACE) rate was 9.4%, whereas 6.3% clinically justified target lesion revascularizations (TLRs) were observed. 2 Patients died within the first 30 days after stent implantation due to angiographically verified in-stent thrombosis. At 12 month FU, MACE and TLR increased to 15.6% and 11.5% respectively and stabilized until 24 month FU. 18 Month angiographic FU showed a significant decrease in late luminal loss (0.67 +/- 0.54, 11.8% reduction or 10% by matched serial analysis, P = 0.001). Conclusion: The HEALING IIB study suggests that statin therapy in combination with the EPC capture stent does not contribute to a reduction of in-stent restenosis formation for the treatment of de novo coronary artery disease. Although concomitant statin therapy was able to stimulate EPC recruitment, it did not improve the angiographic outcome of the bio-engineered EPC capture stent. Remarkably, angiographic late loss was significantly reduced between 6 and 18 months. (C) 2011 Elsevier Ireland Ltd. All rights reserved.\n\n\n"
},
{
"text": "\n151540\nEosinophils Contribute to Intestinal Inflammation via Chemoattractant Receptor-homologous Molecule Expressed on Th2 Cells, CRTH2, in Experimental Crohn's Disease.\n\nRadnai, B\n\nSturm, EM\n\nStančić, A\n\nJandl, K\n\nLabocha, S\n\nFerreirós, N\n\nGrill, M\n\nHasenoehrl, C\n\nGorkiewicz, G\n\nMarsche, G\n\nHeinemann, Á\n\nHögenauer, C\n\nSchicho, R\n\nBeiträge in Fachzeitschriften\nISI:000385135400011\n26928963.0\n10.1093/ecco-jcc/jjw061\nPMC4892354\nProstaglandin [PG] D2 activates two receptors, DP and CRTH2. Antagonism of CRTH2 has been shown to promote anti-allergic and anti-inflammatory effects. We investigated whether CRTH2 may play a role in Crohn's disease [CD], focusing on eosinophils which are widely present in the inflamed mucosa of CD patients and express both receptors.\n Using the 2, , -trinitrobenzenesulfonic acid [TNBS]-induced colitis model, involvement of CRTH2 in colitis was investigated by pharmacological antagonism, immunohistochemistry, Western blotting, immunoassay, and leukocyte recruitment. Chemotactic assays were performed with isolated human eosinophils. Biopsies and serum samples of CD patients were examined for presence of CRTH2 and ligands, respectively.\n High amounts of CRTH2-positive cells, including eosinophils, are present in the colonic mucosa of mice with TNBS colitis and in human CD. The CRTH2 antagonist OC-459, but not the DP antagonist MK0524, reduced inflammation scores and decreased TNF-α, IL-1β, and IL-6 as compared with control mice. OC-459 inhibited recruitment of eosinophils into the colon and also inhibited CRTH2-induced chemotaxis of human eosinophils in vitro. Eosinophil-depleted ΔdblGATA knockout mice were less sensitive to TNBS-induced colitis, whereas IL-5 transgenic mice with lifelong eosinophilia were more severely affected than wild types. In addition, we show that serum levels of PGD2 and Δ(12)-PGJ2 were increased in CD patients as compared with control individuals.\n CRTH2 plays a pro-inflammatory role in TNBS-induced colitis. Eosinophils contribute to the severity of the inflammation, which is improved by a selective CRTH2 antagonist. CRTH2 may, therefore, represent an important target in the pharmacotherapy of CD.\n Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.\n\nGorkiewicz, Gregor\n\nGrill, Magdalena\n\nHeinemann, Akos\n\nHoegenauer, Christoph\n\nJandl, Katharina\n\nMarsche, Gunther\n\nSchicho, Rudolf\n\nSturm, Eva\n\n\n"
},
{
"text": "\n160259\nEarly biomarkers of brain injury and cerebral hypo- and hyperoxia in the SafeBoosC II trial.\n\nPlomgaard, AM\n\nAlderliesten, T\n\nAustin, T\n\nvan Bel, F\n\nBenders, M\n\nClaris, O\n\nDempsey, E\n\nFumagalli, M\n\nGluud, C\n\nHagmann, C\n\nHyttel-Sorensen, S\n\nLemmers, P\n\nvan Oeveren, W\n\nPellicer, A\n\nPetersen, TH\n\nPichler, G\n\nWinkel, P\n\nGreisen, G\n\nBeiträge in Fachzeitschriften\nISI:000399094700019\n28328980.0\n10.1371/journal.pone.0173440\nPMC5362210\nThe randomized clinical trial, SafeBoosC II, examined the effect of monitoring of cerebral oxygenation by near-infrared spectroscopy combined with a guideline on treatment when cerebral oxygenation was out of the target range. Data on cerebral oxygenation was collected in both the intervention and the control group. The primary outcome was the reduction in the burden of cerebral hypo- and hyperoxia between the two groups. In this study we describe the associations between the burden of cerebral hypo- and hyperoxia, regardless of allocation to intervention or control group, and the biomarkers of brain injury from birth till term equivalent age that was collected as secondary and explorative outcomes in the SafeBoosC II trial.\n Cerebral oxygenation was continuously monitored during the first 72h of life in 166 extremely preterm infants. Cranial ultrasound was performed at day 1, , , 4, and 35 and at term. Electroencephalogram (EEG) was recorded at 64h. Blood-samples taken at 6 and 64 hours were analysed for the brain injury biomarkers; S100beta, brain-fatty-acid-binding-protein, and neuroketal. All analyses were conducted post hoc.\n Significantly more infants with a cerebral burden of hypoxia within the 4th quartile versus infants within quartile 1-3 were diagnosed with severe intracranial haemorrhage (11/39 versus 11/117, p = 0.003), had low burst rate on EEG (12/28 versus 21/103, p = 0.015), or died (14/41 versus 18/123, p = 0.006), whereas none of these events were significantly associated with cerebral hyperoxia. The blood biomarkers were not significantly associated with the burden of cerebral hypo- or hyperoxia.\n The explorative analysis showed that early burden of cerebral hypoxia, but not hyperoxia was significantly associated with low brain electrical activity and severe intracranial haemorrhage while none of the three blood biomarkers were associated with the burden of either cerebral hypo- or hyperoxia.\n\nPichler, Gerhard\n\n\n"
},
{
"text": "\n163225\nFic Proteins of <i>Campylobacter fetus</i> subsp. <i>venerealis</i> Form a Network of Functional Toxin-Antitoxin Systems.\n\nSprenger, H\n\nKienesberger, S\n\nPertschy, B\n\nPöltl, L\n\nKonrad, B\n\nBhutada, P\n\nVorkapic, D\n\nAtzmüller, D\n\nFeist, F\n\nHögenauer, C\n\nGorkiewicz, G\n\nZechner, EL\n\nBeiträge in Fachzeitschriften\nISI:000413105000001\n29089929.0\n10.3389/fmicb.2017.01965\nPMC5651007\nEnzymes containing the FIC (filamentation induced by cyclic AMP) domain catalyze post-translational modifications of target proteins. In bacteria the activity of some Fic proteins resembles classical toxin-antitoxin (TA) systems. An excess of toxin over neutralizing antitoxin can enable bacteria to survive some stress conditions by slowing metabolic processes and promoting dormancy. The cell can return to normal growth when sufficient antitoxin is present to block toxin activity. Fic genes of the human and animal pathogen Campylobacter fetus are significantly associated with just one subspecies, which is specifically adapted to the urogenital tract. Here, we demonstrate that the fic genes of virulent isolate C. fetus subsp. venerealis 84-112 form multiple TA systems. Expression of the toxins in Escherichia coli caused filamentation and growth inhibition phenotypes reversible by concomitant antitoxin expression. Key active site residues involved in adenylylation by Fic proteins are conserved in Fic1, Fic3 and Fic4, but degenerated in Fic2. We show that both Fic3 and the non-canonical Fic2 disrupt assembly and function of E. coli ribosomes when expressed independently of a trans-acting antitoxin. Toxicity of the Fic proteins is controlled by different mechanisms. The first involves intramolecular regulation by an inhibitory helix typical for Fic proteins. The second is an unusual neutralization by heterologous Fic-Fic protein interactions. Moreover, a small interacting antitoxin called Fic inhibitory protein 3, which appears unrelated to known Fic antitoxins, has the novel capacity to bind and neutralize Fic toxins encoded in cis and at distant sites. These findings reveal a remarkable system of functional crosstalk occurring between Fic proteins expressed from chromosomal and extrachromosomal modules. Conservation of fic genes in other bacteria that either inhabit or establish pathology in the urogenital tract of humans and animals underscores the significance of these factors for niche-specific adaptation and virulence.\n\nGorkiewicz, Gregor\n\nHoegenauer, Christoph\n\n\n"
},
{
"text": "\n166739\nAntifungal Prophylaxis with Posaconazole Delayed-Release Tablet and Oral Suspension in a Real-Life Setting: Plasma Levels, Efficacy, and Tolerability.\n\nLenczuk, D\n\nZinke-Cerwenka, W\n\nGreinix, H\n\nWölfler, A\n\nPrattes, J\n\nZollner-Schwetz, I\n\nValentin, T\n\nLin, TC\n\nMeinitzer, A\n\nHoenigl, M\n\nKrause, R\n\nBeiträge in Fachzeitschriften\nISI:000433240200047\n29581116.0\n10.1128/AAC.02655-17\nPMC5971564\nWe continuously determined posaconazole plasma concentrations (PPCs) in 61 patients with hematological malignancies receiving posaconazole (PCZ) delayed-release tablets (DRT; 48 patients; median duration of intake, 92 days) and PCZ oral solution (OS; 13 patients; median duration of intake, 124 days). PCZ DRT and OS antifungal prophylaxis was efficient and well tolerated. Thirty-four of 48 patients (71%) receiving DRT always had PPCs of >0.7 mg/liter, while 14 of 48 patients (29%) had at least one PPC of ≤0.7 mg/liter. In patients receiving OS, 4 of 13 patients (31%) always had PPCs of >0.7 mg/liter, 6 of 13 patients (46%) had at least one PPC of ≤0.7 mg/liter, and 3 (23%) patients never reached a PPC of 0.7 mg/liter. In patients with at least one determined PPC, the mean proportion of all PPCs of >0.7 mg/liter was 91% for PCZ DRT, whereas it was 52% for PCZ OS (P = 0.001). In the per sample analysis, PPCs were significantly more likely to be >0.7 mg/liter in patients receiving DRT than in patients receiving OS (PPCs were >0.7 mg/liter in 91.4% [297/325] of patients receiving DRT versus 70.3% [85/121] of patients receiving OS; P < 0.001). Patients receiving PCZ DRT had higher proportions of PPCs of >0.7 mg/liter than patients receiving OS both in the per patient and in the per sample analyses. Two patients (3%) had side effects during PCZ prophylaxis, and one (2%) had fungal breakthrough infection. Therapeutic drug monitoring enables detection of extended periods of PPCs of ≤0.7 mg/liter (e.g., due to nonadherence or graft-versus-host disease), which may also be associated with the loss of protective intracellular PCZ concentrations, regardless of the PCZ formulation.\n Copyright © 2018 American Society for Microbiology.\n\nGreinix, Hildegard\n\nHönigl, Martin\n\nKrause, Robert\n\nMeinitzer, Andreas\n\nPrattes, Jürgen\n\nValentin, Thomas\n\nWoelfler, Albert\n\nZollner-Schwetz, Ines\n\n\n"
},
{
"text": "\n174364\nMagnetic resonance imaging of focal liver lesions. Comparison of the superparamagnetic iron oxide resovist versus gadolinium-DTPA in the same patient.\n\nVogl, TJ\n\nHammerstingl, R\n\nSchwarz, W\n\nKümmel, S\n\nMüller, PK\n\nBalzer, T\n\nLauten, MJ\n\nBalzer, JO\n\nMack, MG\n\nSchimpfky, C\n\nSchrem, H\n\nBechstein, WO\n\nNeuhaus, P\n\nFelix, R\n\nBeiträge in Fachzeitschriften\nISI:A1996VQ95300004\n8915751.0\n10.1097/00004424-199611000-00004\nNone\nThe authors assess the efficacy of static and dynamic magnetic resonance (MR) imaging using the superparamagnetic iron oxide SHU-555A (Resovist) versus standard dose of gadolinium (Gd)-DTPA in patients with focal liver lesions.\n Magnetic resonance imaging was performed in 30 patients suffering from histopathologically verified malignant (n = 22) and benign (n = 8) liver lesions. T2-weighted conventional and fat-suppressed as well as T1-weighted sequences were used before, during, and after fast intravenous administration of Resovist (1 mL/minute) at three doses of 4, 8, and 16 mumol/kg body weight. One week before the Resovist-enhanced MR imaging study 20 patients underwent Gd-DTPA-enhanced MR imaging.\n Detection rate was improved for metastatic lesions revealing 36 lesions unenhanced versus 53 focal lesions using Resovist-enhanced MR imaging. Gadolinium-DTPA-enhanced scans showed no additional lesion versus unenhanced and Resovist-enhanced MR imaging. Static and dynamic imaging demonstrated no measurable percentage signal intensity loss (PSIL) using Resovist-enhanced MR imaging versus a percentage enhancement of 79.7% in Gd-DTPA enhanced scans. In the dynamic T2-weighted sequences, hepatocellular carcinoma nodules (n = 4) showed a rapid decrease in signal intensity starting at 44 seconds. Postinfusion of Resovist followed by a low, constant increase in signal intensity. Gadolinium-DTPA enhanced scans showed a percentage enhancement of 73.4 focal nodular hyperplasia (FNH) and hemangioma revealed a strong and early dose-dependent PSIL 44 to 60 seconds postinfusion with a prolonged signal loss for the FNH in the late study. Statistical evaluation revealed a statistically significant superiority of Resovist-enhanced MR imaging concerning the detection and delineation of focal liver lesions compared with unenhanced and Gd-DTPA enhanced scans (P < 0.05).\n The fast infusion of the new superparamagnetic contrast agent Resovist shows advantages for dynamic and static MR imaging of focal liver lesions.\n\nSchrem, Harald Heinrich\n\n\n"
},
{
"text": "\n175831\nDisturbed Cardiorespiratory Adaptation in Preeclampsia: Return to Normal Stress Regulation Shortly after Delivery?\n\nLackner, HK\n\nPapousek, I\n\nSchmid-Zalaudek, K\n\nCervar-Zivkovic, M\n\nKolovetsiou-Kreiner, V\n\nNonn, O\n\nLucovnik, M\n\nPfniß, I\n\nMoertl, MG\n\nBeiträge in Fachzeitschriften\nISI:000477041100037\n31252672.0\n10.3390/ijms20133149\nPMC6651868\nWomen with pregnancies complicated by preeclampsia appear to be at increased risk of metabolic and vascular diseases in later life. Previous research has also indicated disturbed cardiorespiratory adaptation during pregnancy. The aim of this study was to follow up on the physiological stress response in preeclampsia several weeks postpartum. A standardized laboratory test was used to illustrate potential deviations in the physiological stress responding to mildly stressful events of the kind and intensity in which they regularly occur in further everyday life after pregnancy. Fifteen to seventeen weeks postpartum, 35 women previously affected by preeclampsia (19 mild, 16 severe preeclampsia), 38 women after uncomplicated pregnancies, and 51 age-matched healthy controls were exposed to a self-relevant stressor in a standardized stress-reactivity protocol. Reactivity of blood pressure, heart rate, stroke index, and systemic vascular resistance index as well as baroreceptor sensitivity were analyzed. In addition, the mutual adjustment of blood pressure, heart rate, and respiration, partitioned for influences of the sympathetic and the parasympathetic branches of the autonomic nervous system, were quantified by determining their phase synchronization. Findings indicated moderately elevated blood pressure levels in the nonpathological range, reduced stroke volume, and elevated systemic vascular resistance in women previously affected by preeclampsia. Despite these moderate abnormalities, at the time of testing, women with previous preeclampsia did not differ from the other groups in their physiological response patterns to acute stress. Furthermore, no differences between early, preterm, and term preeclampsia or mild and severe preeclampsia were observed at the time of testing. The findings suggest that the overall cardiovascular responses to moderate stressors return to normal in women who experience a pregnancy with preeclampsia a few weeks after delivery, while the operating point of the arterial baroreflex is readjusted to a higher pressure. Yet, their regulation mechanisms may remain different.\n\nCervar-Zivkovic, Mila\n\nKolovetsiou-Kreiner, Vassiliki\n\nLackner, Helmut Karl\n\nMörtl, Manfred Georg\n\nNonn, Olivia\n\nPfniß, Isabella\n\nSchmid-Zalaudek, Karin\n\n\n"
},
{
"text": "\n177164\nFactors Promoting Conduction Slowing as Substrates for Block and Reentry in Infarcted Hearts.\n\nCampos, FO\n\nWhitaker, J\n\nNeji, R\n\nRoujol, S\n\nO'Neill, M\n\nPlank, G\n\nBishop, MJ\n\nBeiträge in Fachzeitschriften\nISI:000503173400013\n31521328.0\n10.1016/j.bpj.2019.08.008\nPMC6990374\nThe development of effective and safe therapies for scar-related ventricular tachycardias requires a detailed understanding of the mechanisms underlying the conduction block that initiates electrical re-entries associated with these arrhythmias. Conduction block has been often associated with electrophysiological changes that prolong action potential duration (APD) within the border zone (BZ) of chronically infarcted hearts. However, experimental evidence suggests that remodeling processes promoting conduction slowing as opposed to APD prolongation mark the chronic phase. In this context, the substrate for the initial block at the mouth of an isthmus/diastolic channel leading to ventricular tachycardia is unclear. The goal of this study was to determine whether electrophysiological parameters associated with conduction slowing can cause block and re-entry in the BZ. In silico experiments were conducted on two-dimensional idealized infarct tissue as well as on a cohort of postinfarction porcine left ventricular models constructed from ex vivo magnetic resonance imaging scans. Functional conduction slowing in the BZ was modeled by reducing sodium current density, whereas structural conduction slowing was represented by decreasing tissue conductivity and including fibrosis. The arrhythmogenic potential of APD prolongation was also tested as a basis for comparison. Within all models, the combination of reduced sodium current with structural remodeling more often degenerated into re-entry and, if so, was more likely to be sustained for more cycles. Although re-entries were also detected in experiments with prolonged APD, they were often not sustained because of the subsequent block caused by long-lasting repolarization. Functional and structural conditions associated with slow conduction rather than APD prolongation form a potent substrate for arrhythmogenesis at the isthmus/BZ of chronically infarcted hearts. Reduced excitability led to block while slow conduction shortened the wavelength of propagation, facilitating the sustenance of re-entries. These findings provide important insights for models of patient-specific risk stratification and therapy planning.\n Copyright © 2019 Biophysical Society. Published by Elsevier Inc. All rights reserved.\n\nPlank, Gernot\n\n\n"
},
{
"text": "\n184481\nNO Synthesis Markers are Not Significantly Associated with Blood Pressure and Endothelial Dysfunction in Patients with Arterial Hypertension: A Cross-Sectional Study.\n\nMalle, O\n\nTrummer, C\n\nTheiler-Schwetz, V\n\nMeinitzer, A\n\nKeppel, MH\n\nGrübler, MR\n\nTomaschitz, A\n\nVoelkl, J\n\nMärz, W\n\nPilz, S\n\nBeiträge in Fachzeitschriften\nISI:000601975300001\n33266290.0\n10.3390/jcm9123895\nPMC7760204\nNitric oxide (NO) synthesis markers, comprising L-homoarginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), are significantly associated with cardiovascular events and mortality. Being involved in NO pathways, they may be of high importance regulating vascular tone and arterial hypertension, but data on this topic are sparse and controversial. In this study, we evaluated whether these NO synthesis markers are associated with blood pressure values and pulse wave velocity (PWV). This analysis was based on the data of the Styrian Vitamin D Hypertension Trial, which included adults with arterial hypertension. We analyzed correlations of NO synthesis markers with 24 h ambulatory blood pressure values and PWV (primary outcomes), as well as with anthropometric and laboratory data. A total of 509 patients were included in the present analysis. The mean age was 61.2 ± 10.5 years, mean PWV was 8.6 ± 2.4 m/s, mean 24 h systolic blood pressure was 127.5 ± 13.8 mmHg and mean 24 h diastolic blood pressure was 76.4 ± 9.5 mmHg. In bivariate analyses, there was a significant positive correlation between homoarginine and 24 h diastolic blood pressure (r = 0.1; p = 0.02), which was revealed to be no longer significant after adjustment for age, gender and glomerular filtration rate (GFR) in multivariate regression analysis. No other significant correlations of any NO synthesis markers with blood pressure or PWV were observed. In line with previous studies, there were inverse associations between homoarginine and age and between ADMA or SDMA and GFR (p < 0.05 for all). This study did not reveal a significant association between homoarginine, ADMA or SDMA and blood pressure or PWV in hypertensive adults. These results suggested that the associations of these parameters with adverse outcome may not be mediated by hypertension and/or endothelial dysfunction.\n\nMalle, Oliver\n\nMärz, Winfried\n\nMeinitzer, Andreas\n\nPilz, Stefan\n\nTheiler-Schwetz, Verena\n\nTrummer, Christian\n\n\n"
},
{
"text": "\n187707\nThe Diagnostic Arthroscopy Skill Score (DASS): a reliable and suitable assessment tool for arthroscopic skill training\n\nAnetzberger, H\n\nBecker, R\n\nEickhoff, H\n\nSeibert, FJ\n\nDoring, B\n\nHaasters, F\n\nMohr, M\n\nReppenhagen, S\n\nBeiträge in Fachzeitschriften\nISI:000645482500001\n33914120.0\n10.1007/s00167-021-06554-3\nNone\nPurpose To develop and validate a novel score to more objectively assess the performance of diagnostic knee arthroscopy using a simulator. Methods A Diagnostic Arthroscopy Skill Score (DASS) was developed by ten AGA (AGA-Society for Arthroscopy and Joint-Surgery) instructors for the assessment of arthroscopic skills. DASS consists of two parts: the evaluation of standardized diagnostic knee arthroscopy (DASS(part1)) and the evaluation of manual dexterity, including ambidexterity and triangulation, using objective measurement parameters (DASS(part2)). Content validity was determined by the Delphi method. One hundred and eleven videos of diagnostic knee arthroscopies were recorded during simulator training courses and evaluated by six specially trained instructors using DASS. Construct validity, measurement error calculated by the minimum detectable change (MDC), internal consistency using Cronbach's alpha and interrater and intrarater reliability were assessed. The Bland-Altman method was used to calculate the intrarater agreement. Results Six skill domains were identified and evaluated for each knee compartment. DASS, DASS(part1, and DASS(part2) showed construct validity, with experts achieving significantly higher scores than competents and novices. MDC was 4.5 +/- 1.7 points for DASS(part1). There was high internal consistency for all domains in each compartment from 0.78 to 0.86. The interrater reliability showed high agreement between the six raters (ICC = 0.94). The evaluation of intrarater reliability demonstrated good and excellent agreement for five raters (ICC > 0.80) and moderate agreement for one rater (ICC = 0.68). The Bland-Altman comparison showed no difference between the first and second evaluations in five out of six raters. Precision, estimated by the regression analysis and comparison with the method of Bland and Altman, was excellent for four raters and moderate for two raters. Conclusions The results of this study indicate good validity and reliability of DASS for the assessment of the surgical performance of diagnostic knee arthroscopy during simulator training. Standardized training is recommended before arthroscopy surgery is considered in patients.\n\nSeibert, Franz\n\n\n"
},
{
"text": "\n127117\nPelvic ring injuries in children. Part I: Epidemiology and primary evaluation. A review of the literature.\n\nGänsslen, A\n\nHildebrand, F\n\nHeidari, N\n\nWeinberg, AM\n\nBeiträge in Fachzeitschriften\nISI:000313143300003\n23286680.0\nNone\nNone\nPediatric pelvic injury is of major significance despite these injuries in children are rare with a suspected yearly rate of 3% of all pelvic injuries. The special pediatric bone anatomy of the pelvis is responsible for different fracture patterns, and overall, a bony or joint injury of the pelvis is an indicator of a severe trauma. The vast majority of pediatric pelvic fractures is the result of a high-energy trauma, especially after strucking by a car or injured as motor vehicle passengers. Additional injuries are common, but additional head injury is only present in 1/3 of patients. An adequate structured primary diagnosis must therefore be mandatory. The a.p. X-ray of the pelvis is still the gold standard to evaluate these injuries. The majority of injuries is mechanically stable with 85-90% expected type A- and B-injuries. Primary management of these injuries is orientated to that of adults. The standard emergency fixation procedure is the external fixator. Definitive treatment depends on the displacement of fractures and the instability of the pelvic ring. In displaced and unstable fractures, today, anatomic reconstruction of the pelvic ring by osteosynthesis is favoured. Due to the potential negative long term consequences of mal-healing child-adapted stabilization techniques should be used. Moratlity is related to concomitant injuries, e.g. severe head injury. Risk factors of mortality are the overall injury severity, additional complex pelvic trauma and the type of pelvic fracture. Nevertheless, growth disturbances occur in rare cases. Therefore, frequent clinical and radiological controls are proposed until the completion of growth. Overall, good and excellent long-term results can be expected in most patients, especially after type A-injuries. But several long-term sequelae can occur in unstable pelvic injuries depending on the instability of the child's pelvis at the time of injury. Overall, there is a good correlation between the clinical and radiological result. Risk factors for a worse result can be additional significant peripelvic injuries (complex pelvic trauma).\n\nWeinberg, Annelie-Martina\n\n\n"
},
{
"text": "\n146421\nPentadecapeptide BPC 157, in clinical trials as a therapy for inflammatory bowel disease (PL14736), is effective in the healing of colocutaneous fistulas in rats: role of the nitric oxide-system.\n\nKlicek, R\n\nSever, M\n\nRadic, B\n\nDrmic, D\n\nKocman, I\n\nZoricic, I\n\nVuksic, T\n\nIvica, M\n\nBarisic, I\n\nIlic, S\n\nBerkopic, L\n\nVrcic, H\n\nBrcic, L\n\nBlagaic, AB\n\nCoric, M\n\nBrcic, I\n\nRokotov, DS\n\nAnic, T\n\nSeiwerth, S\n\nSikiric, P\n\nBeiträge in Fachzeitschriften\nISI:000259683400002\n18818478.0\n10.1254/jphs.FP0072161\nNone\nWe focused on the therapeutic effect of the stable gastric pentadecapeptide BPC 157 and how its action is related to nitric oxide (NO) in persistent colocutaneous fistula in rats (at 5 cm from anus, colon defect of 5 mm, skin defect of 5 mm); this peptide has been shown to be safe in clinical trials for inflammatory bowel disease (PL14736) and safe for intestinal anstomosis therapy. BPC 157 (10 microg/kg, 10 ng/kg) was applied i) in drinking water until the animals were sacrificed at post-operative day 1, 3, 5, 7, 14, 21, and 28; or ii) once daily intraperitoneally (first application 30 min following surgery, last 24 h before sacrifice) alone or with N(G)-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg), L-arginine (200 mg/kg), and their combinations. Sulphasalazine (50 mg/kg) and 6-alpha-methylprednisolone (1 mg/kg) were given once daily intraperitoneally. BPC 157 accelerated parenterally or perorally the healing of colonic and skin defect, leading to the suitable closure of the fistula, macro/microscopically, biomechanically, and functionally (larger water volume sustained without fistula leaking). L-NAME aggravated the healing failure of colocutaneous fistulas, skin, and colon wounds (L-NAME groups). L-Arginine was effective only with blunted NO generation (L-NAME + L-arginine groups) but not without (L-arginine groups). All of the BPC 157 beneficial effects remained unchanged with blunted NO-generation (L-NAME + BPC 157 groups) and with NO substrate (L-arginine + BPC 157 groups) as well as L-NAME and L-arginine co-administration (L-NAME + L-arginine + BPC 157 groups). Sulphasalazine was only moderately effective, and corticosteroid even had an aggravating effect.\n\nBrcic, Iva\n\nBrcic, Luka\n\n\n"
}
]
}