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"text": "\n182361\nEffect of Intrauterine Growth Restriction on Cerebral Regional Oxygen Saturation in Preterm and Term Neonates during Immediate Postnatal Transition.\n\nBaik-Schneditz, N\n\nPichler, G\n\nSchwaberger, B\n\nBinder-Heschl, C\n\nMileder, L\n\nReiss, IKH\n\nAvian, A\n\nGreimel, P\n\nKlaritsch, P\n\nUrlesberger, B\n\nBeiträge in Fachzeitschriften\nISI:000591174700009\n32516786.0\n10.1159/000507583\nNone\nIntrauterine growth restriction (IUGR) is associated with adverse perinatal outcome. Affected fetuses commonly display typical blood flow redistribution towards the brain ("brain sparing"). Accordingly, increased cerebral oxygen saturation has been observed in IUGR neonates within the first days of life.\n The aim of our study was to assess cerebral oxygenation behavior during immediate neonatal transition in IUGR infants.\n This is a retrospective single-center observational cohort study. Cerebral regional oxygen saturation (crSO2) was measured with near-infrared spectroscopy in neonates during the first 15 min after birth. Neonates with IUGR (IUGR group) were matched for gestational age (±1 week) and gender with neonates that were appropriate for gestational age (AGA). The AGA:IUGR matching ratio was 3:1. Arterial oxygen saturation (SpO2), heart rate (HR), crSO2, and cerebral fractional tissue oxygen extraction (cFTOE) were compared between the groups.\n Between August 2010 and October 2017, 45 neonates with IUGR were identified and matched to 135 AGA neonates. Mean gestational age was 33.1 ± 3.0 weeks in the IUGR group and 33.5 ± 2.7 weeks in the AGA group. Mean birth weight was 1, 59 ± 582 g in the IUGR group and 2, 51 ± 679 g in the AGA group. There was a significant group difference in crSO2 beginning at 5 min and continuing for the rest of the observation time with higher crSO2 values in the IUGR group (main effect group: p = 0.011; interaction time × group: p = 0.039). In cFTOE, a significant difference could be observed at 5-9 and 11-13 min with lower rates of oxygen extraction in the IUGR group (main effect group: p = 0.025; interaction time × group: p = 0.463). Concerning SpO2 and HR, there was no significant difference between the IUGR and the AGA neonates.\n Neonates of the IUGR group did show significantly higher crSO2 values and significantly lower cFTOE values already during immediate neonatal transition compared to the AGA group.\n © 2020 S. Karger AG, Basel.\n\nAvian, Alexander\n\nBaik-Schneditz, Nariae\n\nBinder-Heschl, Corinna\n\nGreimel, Patrick\n\nKlaritsch, Philipp\n\nMileder, Lukas Peter\n\nPichler, Gerhard\n\nSchwaberger, Bernhard Christian\n\nUrlesberger, Berndt\n\n\n"
},
{
"text": "\n182798\nProspective Randomized Observational Pilot Trial Evaluating the Effect of Different Durations of Interdisciplinary Early Intervention and Family Support in Parents of Very Low Birth Weight Infants (Early Bird Study).\n\nResch, B\n\nHofbauer-Krug, C\n\nPansy, J\n\nPrechtl, K\n\nAvian, A\n\nKurz, R\n\nBeiträge in Fachzeitschriften\nISI:000553836500001\n32719760.0\n10.3389/fpubh.2020.00242\nPMC7349967\nBackground: Early childhood intervention (ECI) is a holistic approach for infants with or at risk for psychomotor and/or cognitive and/or behavioral impairment. It aims to optimally support them and positively influence their neurodevelopmental outcome. The right dosage of intervention and when the intervention should start are still to be determined. Hypothesis: Parents are more satisfied when the duration of ECI is longer (120 min once a week) than the usual 90-min session. Methods: We developed a parental questionnaire (both mother and father) that evaluated the level of satisfaction of parents with the intervention. We compared 120 with 90 min of ECI per week during the school year 2017/18. Included were parents of very low birth weight infants (<1, 00 g) following informed consent. ECI was initiated at the NICU at an infant age of ≥ 2 weeks. Parents were randomized (https://www.randomizer.at/) to a 120- or 90-min duration and had to answer the questionnaire to the approximate time-point of 1, 3, and 6 months. Answers were classified as strongly agree, agree, neither agree nor disagree, disagree, and strongly disagree except for the last question, which directly rated the ECI professional. Results: Eleven fathers (55%) and 19 mothers (95%) of the 10 parents of each group participated in the study. Demographic data did not differ between groups, and the median time-points of questionnaire answers were 77, 137, and 220 days, respectively. Overall, 120-min ECI sessions were not superior to 90-min sessions for both parents regarding parental satisfaction during the study time. We found no differences between fathers and mothers and minimal changes over time. All parents were satisfied with the ECI professionals, irrespective of ECI duration. Conclusion: An ECI duration of 120 min once per week was not superior to a 9- min duration regarding parental satisfaction with ECI professionals and their work.\n Copyright © 2020 Resch, Hofbauer-Krug, Pansy, Prechtl, Avian and Kurz.\n\nAvian, Alexander\n\nPansy, Jasmin\n\nResch, Bernhard\n\n\n"
},
{
"text": "\n1303\nIncreased content and transport of substance P and calcitonin gene-related peptide in sensory nerves innervating inflamed tissue: evidence for a regulatory function of nerve growth factor in vivo.\n\nDonnerer, J\n\nSchuligoi, R\n\nStein, C\n\nBeiträge in Fachzeitschriften\nISI:A1992JE54600016\n1380138.0\n10.1016%2F0306-4522%2892%2990237-V\nNone\nThe responses of sensory neuropeptides during unilateral, Freund's adjuvant-induced, paw inflammation in the rat were examined. After five days of inflammation, the substance P and calcitonin gene-related peptide content in the sciatic nerve supplying the inflamed paw were increased by 60-75% when compared with the contralateral side. At this time-point, there was also a 30-40% increase in the substance P and calcitonin gene-related peptide content of the dorsal root ganglia (L4-L6), and a 40% increase in the calcitonin gene-related peptide content of the L4-L6 segments of the dorsal spinal cord on the inflammation side. In the dorsal root ganglia, calcitonin gene-related peptide content was also increased as early as 12 h and 48 h after induction of paw inflammation. On day 5 of inflammation, the axonal transport of both sensory neuropeptides towards the inflamed paw, as determined after sciatic nerve ligation, was also markedly increased as compared with the control side. Despite this increased transport, the amount of substance P and calcitonin gene-related peptide present in the inflamed paw itself was either reduced or remained unchanged from day 1 through to day 5 of inflammation pointing towards reduced storage and increased release of the peptides in the inflamed tissue. Nerve growth factor content was markedly increased in the sciatic nerve of the inflamed paw with a peak of +136% at time-point 24 h after induction of inflammation. When rats were systemically treated with anti-nerve growth factor serum, the increase in neuropeptide content in the sciatic nerve of the inflamed paw (day 5) was prevented. On the other hand, local injections of nerve growth factor for 5 days into a noninflamed paw were able to induce an increase in substance P and calcitonin gene-related peptide content in the supplying sciatic nerve. These findings point towards a regulatory function for nerve growth factor in vivo in the stimulation of sensory neuropeptide synthesis during prolonged inflammatory processes.\n\nDonnerer, Josef\n\nSchuligoi, Rufina\n\n\n"
},
{
"text": "\n2210\nReaction of term newborns with prolonged postnatal dyspnoea to early oxygen, mask continuous positive airway pressure, and volume expansion: a prospective, randomised, clinical trial.\n\nHauer, AC\n\nRosegger, H\n\nHaas, J\n\nHaxhija, EQ\n\nBeiträge in Fachzeitschriften\nISI:A1996VC94200014\n8874117.0\n10.1007/BF02002912\nNone\nIn a prospective, randomised, open trial 103 term newborns with persisting dyspnoea, tachypnoea and/or cyanosis were treated with oxygen for 5-10 min and then with oxygen plus mask continuous positive airway pressure (CPAP) for another 5-15 min. Cases with overt prenatal or intrapartum obstetric pathology had been excluded from the study. Forty-one infants (40%) responded to this procedure within 10-25 min. The remaining 62 infants (60%) were randomly allocated to one of three forms of further treatment: continuation of mask CPAP for 20 min (group A, n = 24), volume expansion with 9 ml of 3 ml albumin, 3 ml glucose, and 3 mEq of sodium bicarbonate (group B, n = 24), or volume expansion with 4.5 ml albumin and 4.5 ml glucose (group C, n = 14). There was no statistical difference in birth weight, gestational age or Apgar scores at 1 and 5 min between the infants of the groups. Time to normalisation of symptoms was significantly shorter in the volume expansion groups (B: 45 +/- 41 min, range 20-180, and C: 80 +/- 72 min, range 20-210) than in the mask CPAP group (A; 224 +/- 256 min, range 30-1200, P = 0.02). There were statistical differences in umbilical cord and capillary pH values among the infants of the three groups, but the response to therapy was not related to the degree of acidaemia. Thirty-four infants (33%) who did not respond were admitted to a special care unit for further examination (group A: 21/24, group B: 7/24; group C: 6/14). Of these, 23 had no abnormal findings, 8 infants had radiological signs of transitory respiratory distress, and 1 had a non-tension pneumothorax. Septicaemia was found in two infants. No infant was intubated. At discharge all 103 infants did well. Conclusion: Incremental application of simple primary care procedures including volume expansion (with or without alkali) in term newborns with persisting postnatal tachypnoea and dyspnoea helps avoid overtreatment and unnecessary separation from the mothers in most cases and reliably selects infants who need close monitoring or special treatment.\n\nHaas, Josef\n\nHauer, Almuthe\n\nHaxhija, Emir\n\n\n"
},
{
"text": "\n65112\nAlterations in gap junction protein expression in human benign prostatic hyperplasia and prostate cancer\n\nHabermann, H\n\nRay, V\n\nHabermann, W\n\nPrins, GS\n\nBeiträge in Fachzeitschriften\nISI:000172133900068\nNone\n10.1016/S0022-5347(05)65548-6\nNone\nPurpose: Gap junctions composed of connexin proteins have an essential role in intercellular communication and differentiation. Dysregulation of connexin expression is believed to have a role in carcinogenesis. The human prostate has been reported to express connexin 32 and 43. However, the expression pattern in prostate cancer is controversial, while to our knowledge connexin expression has not been reported in benign prostatic hyperplasia (BPH). To understand the potential involvement in prostate disease connexin 32 and 43 expression was evaluated in a series of normal prostate, BPH and prostate cancer specimens that were surgically removed due to bladder outlet obstruction. Materials and Methods: Frozen sections of 23 normal, 43 BPH and 40 cancer involved prostates were evaluated for the presence, staining intensity and pattern of connexin 32 and 43 by immunocytochemical testing. Results: In all specimens examined connexin 43 stain was punctate along the borders of the basal epithelial cells, whereas connexin 32 immunolocalized to luminal epithelial cells: In normal prostate connexin 43 and 32 were present in 87% and 65% of specimens, respectively, at low to moderate stain intensity. Importantly none of the normal samples were negative for each connexin. In BPH specimens there was a marked increase in the incidence and intensity of connexin 43 and 32 immunostaining within epithelial cells. In addition, 23% of BPH samples showed strong connexin 43 expression in stromal cells. In contrast, connexin was decreased in prostate cancer specimens, of which 65% and 38% were negative for connexin 43 and 32, respectively, and 28% were negative for each type. In poorly differentiated tumors connexin 43 and 32 were present in only 10% and 40% of tumors, respectively, at low immunostaining intensity. Conclusions: In normal human prostate basal cells communicate via connexin 43 gap junctions, whereas luminal cells communicate via connexin 32 gap junctions. In BPH gap junctional intercellular communication is increased in epithelial and stromal cells, which may have a role in BPH pathogenesis. In prostate cancer gap junctional intercellular communication is decreased, is as indicated by decreased expression of connexin 43 and 32 with severe loss in poorly differentiated prostate cancer. These alterations in connexin expression may have a role in dedifferentiation and tumor progression.\n\nHabermann, Walter\n\n\n"
},
{
"text": "\n106208\nFunctional variant in complement C3 gene promoter and genetic susceptibility to temporal lobe epilepsy and febrile seizures.\n\nJamali, S\n\nSalzmann, A\n\nPerroud, N\n\nPonsole-Lenfant, M\n\nCillario, J\n\nRoll, P\n\nRoeckel-Trevisiol, N\n\nCrespel, A\n\nBalzar, J\n\nSchlachter, K\n\nGruber-Sedlmayr, U\n\nPataraia, E\n\nBaumgartner, C\n\nZimprich, A\n\nZimprich, F\n\nMalafosse, A\n\nSzepetowski, P\n\nBeiträge in Fachzeitschriften\nISI:000281864100008\n20862287.0\n10.1371/journal.pone.0012740\nPMC2940893\nHuman mesial temporal lobe epilepsies (MTLE) represent the most frequent form of partial epilepsies and are frequently preceded by febrile seizures (FS) in infancy and early childhood. Genetic associations of several complement genes including its central component C3 with disorders of the central nervous system, and the existence of C3 dysregulation in the epilepsies and in the MTLE particularly, make it the C3 gene a good candidate for human MTLE.\n A case-control association study of the C3 gene was performed in a first series of 122 patients with MTLE and 196 controls. Four haplotypes (HAP1 to 4) comprising GF100472, a newly discovered dinucleotide repeat polymorphism [(CA)8 to (CA)15] in the C3 promoter region showed significant association after Bonferroni correction, in the subgroup of MTLE patients having a personal history of FS (MTLE-FS+). Replication analysis in independent patients and controls confirmed that the rare HAP4 haplotype comprising the minimal length allele of GF100472 [(CA)8], protected against MTLE-FS+. A fifth haplotype (HAP5) with medium-size (CA)11 allele of GF100472 displayed four times higher frequency in controls than in the first cohort of MTLE-FS+ and showed a protective effect against FS through a high statistical significance in an independent population of 97 pure FS. Consistently, (CA)11 allele by its own protected against pure FS in a second group of 148 FS patients. Reporter gene assays showed that GF100472 significantly influenced C3 promoter activity (the higher the number of repeats, the lower the transcriptional activity). Taken together, the consistent genetic data and the functional analysis presented here indicate that a newly-identified and functional polymorphism in the promoter of the complement C3 gene might participate in the genetic susceptibility to human MTLE with a history of FS, and to pure FS.\n The present study provides important data suggesting for the first time the involvement of the complement system in the genetic susceptibility to epileptic seizures and to epilepsy.\n\n\n"
},
{
"text": "\n128593\nOral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: a randomized dose-guiding, safety, and tolerability study of four doses of AZD0837 vs. vitamin K antagonists.\n\nLip, GY\n\nRasmussen, LH\n\nOlsson, SB\n\nJensen, EC\n\nPersson, AL\n\nEriksson, U\n\nWåhlander, KF\n\nSteering Committee\n\nBeiträge in Fachzeitschriften\nISI:000272454800025\n19690349.0\n10.1093/eurheartj/ehp318\nPMC2785945\nAims Oral anticoagulation with vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) is effective but has significant limitations. AZD0837, a new oral anticoagulant, is a prodrug converted to a selective and reversible direct thrombin inhibitor (AR-H067637). We report from a Phase II randomized, dose-guiding study (NCT00684307) to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of extended-release AZD0837 in patients with AF. Methods and results Atrial fibrillation patients (n = 955) with >= 1 additional risk factor for stroke were randomized to receive AZD0837 (150, 300, or 450 mg once daily or 200 mg twice daily) or VKA (international normalized ratio 2-3, target 2.5) for 3-9 months. Approximately 30% of patients were naive to VKA treatment. Total bleeding events were similar or lower in all AZD0837 groups (5.3-14.7%, mean exposure 138-145 days) vs. VKA (14.5%, mean exposure 161 days), with fewer clinically relevant bleeding events on AZD0837 150 and 300 mg once daily. Adverse events were similar between treatment groups; with AZD0837, the most common were gastrointestinal disorders (e.g. diarrhoea, flatulence, or nausea). D-Dimer, used as a biomarker of thrombogenesis, decreased in all groups in VKA-naive subjects with treatment, whereas in VKA pre-treated patients, D-dinner levels started tow and remained low in all groups. As expected, only a few strokes or systemic embolic events occurred. In the AZD0837 groups, mean S-creatinine increased by similar to 10% from baseline and returned to baseline following treatment cessation. The frequency of serum alanine aminotransferase >= 3 x upper limit of normal was similar for AZD0837 and VKA. Conclusion AZD0837 was generally well tolerated at all doses tested. AZD0837 treatment at an exposure corresponding to the 300 mg od dose in this study provides similar suppression of thrombogenesis at a potentially lower bleeding risk compared with dose-adjusted VKA.\n\nPilger, Ernst\n\n\n"
},
{
"text": "\n140042\nAnticoagulant treatment in German family practices - screening results from a cluster randomized controlled trial.\n\nUlrich, LR\n\nMergenthal, K\n\nPetersen, JJ\n\nRoehl, I\n\nRauck, S\n\nKemperdick, B\n\nSchulz-Rothe, S\n\nBerghold, A\n\nSiebenhofer, A\n\nBeiträge in Fachzeitschriften\nISI:000344573400001\n25344288.0\n10.1186/s12875-014-0170-0\nPMC4213473\nOral anticoagulation (OAC) with coumarins and new anticoagulants are highly effective in preventing thromboembolic complications. However, some studies indicate that over- and under-treatment with anticoagulants are fairly common. The aim of this paper is to assess the appropriateness of treatment in patients with a long-term indication for OAC, and to describe the corresponding characteristics of such patients on the basis of screening results from the cluster randomized PICANT trial.\n Randomly selected family practices in the federal state of Hesse, Germany, were visited by study team members. Eligible patients were screened using an anonymous patient list that was generated by the general practitioners' software according to predefined instructions. A documentation sheet was filled in for all screened patients. Eligible patients were classified into 3 categories (1: patients with a long-term indication for OAC and taking anticoagulants, 2: patients with a long-term indication for OAC but not taking anticoagulants, 3: patients without a long-term indication for OAC but taking an anticoagulant on a permanent basis). IBM SPSS Statistics 20 was used for descriptive statistical analysis.\n We screened 2, 36 randomly selected, potentially eligible patients from 52 family practices. 275 patients could not be assigned to one of the 3 categories and were therefore not considered for analysis. The final study sample comprised 1, 61 screened patients, 1, 41 of whom belonged to category 1, 78 to category 2, and 42 to category 3. INR values were available for 1, 04 patients of whom 1, 13 presented INR values within their therapeutic ranges. The majority of screened patients had very good compliance, as assessed by the general practitioner. New antithrombotic drugs were prescribed in 6.1% of cases.\n The screening results showed that a high proportion of patients were receiving appropriate anticoagulation therapy. The numbers of patients with a long-term indication for OAC therapy that were not receiving oral anticoagulants, and without a long-term indication that were receiving OAC, were considerably lower than expected. Most patients take coumarins, and the quality of OAC control is reasonably high.\n Current Controlled Trials ISRCTN41847489.\n\nBerghold, Andrea\n\nSiebenhofer-Kroitzsch, Andrea\n\n\n"
},
{
"text": "\n140745\nCa(2+) /calmodulin-dependent protein kinase II equally induces sarcoplasmic reticulum Ca(2+) leak in human ischaemic and dilated cardiomyopathy.\n\nFischer, TH\n\nEiringhaus, J\n\nDybkova, N\n\nFörster, A\n\nHerting, J\n\nKleinwächter, A\n\nLjubojevic, S\n\nSchmitto, JD\n\nStreckfuß-Bömeke, K\n\nRenner, A\n\nGummert, J\n\nHasenfuss, G\n\nMaier, LS\n\nSossalla, S\n\nBeiträge in Fachzeitschriften\nISI:000345755200007\n25201344.0\n10.1002/ejhf.163\nNone\nThe sarcoplasmic reticulum (SR) Ca(2+) leak is an important pathomechanism in heart failure (HF). It has been suggested that Ca(2+) /calmodulin-dependent protein kinase II (CaMKII) is only relevant for the induction of the SR Ca(2+) leak in non-ischaemic but not in ischaemic HF. Therefore, we investigated CaMKII and its targets as well as the functional effects of CaMKII inhibition in human ischaemic cardiomyopathy (ICM, n = 37) and dilated cardiomyopathy (DCM, n = 40).\n Western blots showed a significantly increased expression (by 54 ± 9%) and autophosphorylation at Thr286 (by 129 ± 29%, P < 0.05 each) of CaMKII in HF compared with healthy myocardium. However, no significant difference could be detected in ICM compared with DCM as to the expression and autophosphorylation of CaMKII nor the phosphorylation of the target sites ryanodine receptor 2 (RyR2)-S2809, RyR2-S2815, and phospholamban-Thr17. Isolated human cardiomyocytes (CMs) of patients with DCM and ICM showed a similar frequency of diastolic Ca(2+) sparks (confocal microscopy) as well as of major arrhythmic events (Ca(2+) waves, spontaneous Ca(2+) transients). Despite a slightly smaller size of Ca(2+) sparks in DCM (P < 0.01), the calculated SR Ca(2+) leak [Ca(2+) spark frequecy (CaSpF) × amplitude × width × duration] did not differ between CMs of ICM vs. DCM. Importantly, CaMKII inhibition by autocamide-2-related inhibitory peptide (AIP, 1 µmol/L) reduced the SR Ca(2+) leak by ∼80% in both aetiologies (P < 0.05 each) and effectively decreased the ratio of arrhythmic cells (P < 0.05).\n Functional and molecular measures of the SR Ca(2+) leak are comparable in human ICM and DCM. CaMKII is equally responsible for the induction of the 'RyR2 leakiness' in both pathologies. Thus, CaMKII inhibition as a therapeutic measure may not be restricted to patients suffering from DCM but rather may be beneficial for the majority of HF patients.\n © 2014 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.\n\nHolzer, Senka\n\n\n"
},
{
"text": "\n146317\nThe role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation: Endorsed by the Association for Research into Arterial Structure and Physiology (ARTERY) Society.\n\nVlachopoulos, C\n\nXaplanteris, P\n\nAboyans, V\n\nBrodmann, M\n\nCífková, R\n\nCosentino, F\n\nDe Carlo, M\n\nGallino, A\n\nLandmesser, U\n\nLaurent, S\n\nLekakis, J\n\nMikhailidis, DP\n\nNaka, KK\n\nProtogerou, AD\n\nRizzoni, D\n\nSchmidt-Trucksäss, A\n\nVan Bortel, L\n\nWeber, T\n\nYamashina, A\n\nZimlichman, R\n\nBoutouyrie, P\n\nCockcroft, J\n\nO'Rourke, M\n\nPark, JB\n\nSchillaci, G\n\nSillesen, H\n\nTownsend, RR\n\nBeiträge in Fachzeitschriften\nISI:000360100700030\n26117398.0\n10.1016/j.atherosclerosis.2015.05.007\nNone\nWhile risk scores are invaluable tools for adapted preventive strategies, a significant gap exists between predicted and actual event rates. Additional tools to further stratify the risk of patients at an individual level are biomarkers. A surrogate endpoint is a biomarker that is intended as a substitute for a clinical endpoint. In order to be considered as a surrogate endpoint of cardiovascular events, a biomarker should satisfy several criteria, such as proof of concept, prospective validation, incremental value, clinical utility, clinical outcomes, cost-effectiveness, ease of use, methodological consensus, and reference values. We scrutinized the role of peripheral (i.e. not related to coronary circulation) noninvasive vascular biomarkers for primary and secondary cardiovascular disease prevention. Most of the biomarkers examined fit within the concept of early vascular aging. Biomarkers that fulfill most of the criteria and, therefore, are close to being considered a clinical surrogate endpoint are carotid ultrasonography, ankle-brachial index and carotid-femoral pulse wave velocity; biomarkers that fulfill some, but not all of the criteria are brachial ankle pulse wave velocity, central haemodynamics/wave reflections and C-reactive protein; biomarkers that do no not at present fulfill essential criteria are flow-mediated dilation, endothelial peripheral arterial tonometry, oxidized LDL and dysfunctional HDL. Nevertheless, it is still unclear whether a specific vascular biomarker is overly superior. A prospective study in which all vascular biomarkers are measured is still lacking. In selected cases, the combined assessment of more than one biomarker may be required. \n Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.\n\nBrodmann, Marianne\n\n\n"
},
{
"text": "\n148665\nClinical and morphometric parameters of frailty for prediction of mortality following hepatopancreaticobiliary surgery in the elderly.\n\nWagner, D\n\nBüttner, S\n\nKim, Y\n\nGani, F\n\nXu, L\n\nMargonis, GA\n\nAmini, N\n\nKamel, IR\n\nPawlik, TM\n\nBeiträge in Fachzeitschriften\nISI:000368805900012\n26604018.0\n10.1002/bjs.10037\nNone\nAlthough frailty is a known determinant of poor postoperative outcomes, it can be difficult to identify in patients before surgery. The authors sought to develop a preoperative frailty risk model to predict mortality among patients aged 65 years or more.\n Clinical and morphometric data including total psoas area (TPA), total psoas volume (TPV) and psoas density (Hounsfield unit average calculation, HUAC) were collected for patients undergoing hepatopancreaticobiliary (HPB) surgery between 2012 and 2014. Multivariable Cox proportional hazards regression was used to identify preoperative risk factors associated with 1-year mortality.\n The median age of the 518 patients included in the study was 72 (i.q.r. 68-76) years; 55·6 per cent of patients were men, and half of the cohort had multiple co-morbidities (Charlson co-morbidity index (CCI) of 4 or more, 55·6 per cent). TPA cut-offs to define sarcopenia were 552·7 mm(2) /m(2) in women and 702·9 mm(2) /m(2) in men; cut-offs for TPV were 18·2 cm(3) /m(2) in women and 26·2 cm(3) /m(2) in men, whereas HUAC cut-offs were 31·1 HU in women and 33·3 HU in men. The overall 1-year mortality rate was 14·1 per cent. In multivariable analysis, risk factors associated with 1-year mortality included CCI of 4 or above (hazard ratio (HR) 2·91, 95 per cent c.i. 1·47 to 5·77; P = 0·002), malignant disease (HR 3·94, 1·17 to 13·30; P = 0·027) and sarcopenia by HUAC (HR 1·85, 1·10 to 3·10; P = 0·021). A weighted 25-point composite score was developed to stratify patients at risk of 1-year postoperative mortality. The 1-year mortality rate was noted to be 2·5 per cent among patients scoring 0-10 (low risk), 17·3 per cent among patients scoring 11-20 (intermediate risk) and 29·2 per cent among those scoring between 21 and 25 (high risk) (P < 0·001).\n Clinical and morphometric measures of frailty accurately predict the risk of 1-year mortality following HPB surgery in elderly patients, and can be used to risk-stratify patients appropriately.\n © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.\n\nWagner, Doris\n\n\n"
},
{
"text": "\n164520\nCitrullinated histone H3, a biomarker of neutrophil extracellular trap formation, predicts the risk of venous thromboembolism in cancer patients.\n\nMauracher, LM\n\nPosch, F\n\nMartinod, K\n\nGrilz, E\n\nDäullary, T\n\nHell, L\n\nBrostjan, C\n\nZielinski, C\n\nAy, C\n\nWagner, DD\n\nPabinger, I\n\nThaler, J\n\nBeiträge in Fachzeitschriften\nISI:000426167400015\n29325226.0\n10.1111/jth.13951\nPMC6294121\nEssentials Neutrophil extracellular traps (NETs) might play a role in cancer-related coagulopathy. We determined NET biomarkers and followed cancer patients for venous thromboembolism (VTE). We found a constant association with VTE for citrullinated histone H3. Biomarkers of NET formation could reflect a novel pathomechanism of cancer-related VTE.\n Background Neutrophil extracellular traps (NETs) are decondensed chromatin fibers that might play a role in the prothrombotic state of cancer patients. Objectives To investigate whether the levels of citrullinated histone H3 (H3Cit), a biomarker for NET formation, cell-free DNA (cfDNA) and nucleosomes predict venous thromboembolism (VTE) in cancer patients. Patients/Methods Nine-hundred and forty-six patients with newly diagnosed cancer or progression after remission were enrolled in this prospective observational cohort study. H3Cit, cfDNA and nucleosome levels were determined at study inclusion, and patients were followed for 2 years. VTE occurred in 89 patients; the cumulative 3-month, 6-month, 12-month and 24-month incidence rates of VTE were 3.7%, 6.0%, 8.1%, and 10.0%, respectively. Results Patients with elevated H3Cit levels (> 75th percentile of its distribution, n = 236) experienced a higher cumulative incidence of VTE (2-year risk of 14.5%) than patients with levels below this cut-off (2-year risk of 8.5%, n = 710). In a competing-risk regression analysis, a 100 ng mL-1increase in H3Cit level was associated with a 13% relative increase in VTE risk (subdistribution hazard ratio [SHR] 1.13, 95% confidence interval [CI] 1.04-1.22). This association remained after adjustment for high VTE risk and very high VTE risk tumor sites, D-dimer level, and soluble P-selectin level (SHR 1.13, 95% CI 1.04-1.22). The association of elevated nucleosome and cfDNA levels with VTE risk was time-dependent, with associations with a higher risk of VTE only during the first 3-6 months. Conclusion These data suggest that biomarkers of NET formation are associated with the occurrence of VTE in cancer patients, indicating a role of NETs in the pathogenesis of cancer-associated thrombosis.\n © 2018 International Society on Thrombosis and Haemostasis.\n\nPosch, Florian\n\n\n"
},
{
"text": "\n175144\nPrevalence, geographic risk factor, and development of a standardized protocol for fungal isolation in cystic fibrosis: Results from the international prospective study "MFIP".\n\nDelhaes, L\n\nTouati, K\n\nFaure-Cognet, O\n\nCornet, M\n\nBotterel, F\n\nDannaoui, E\n\nMorio, F\n\nLe Pape, P\n\nGrenouillet, F\n\nFavennec, L\n\nLe Gal, S\n\nNevez, G\n\nDuhamel, A\n\nBorman, A\n\nSaegeman, V\n\nLagrou, K\n\nGomez, E\n\nCarro, ML\n\nCanton, R\n\nCampana, S\n\nBuzina, W\n\nChen, S\n\nMeyer, W\n\nRoilides, E\n\nSimitsopoulou, M\n\nManso, E\n\nCariani, L\n\nBiffi, A\n\nFiscarelli, E\n\nRicciotti, G\n\nPihet, M\n\nBouchara, JP\n\nBeiträge in Fachzeitschriften\nISI:000466454900011\n30348610.0\n10.1016/j.jcf.2018.10.001\nNone\nBackground: Fungi are increasingly recognized for their potential role in contributing to pulmonary damage in Cystic Fibrosis (CF). We therefore designed a prospective international study aimed at (i) determining the prevalence of fungi isolated from sputum samples collected from a large CF population, (ii) comparing the performance of different media used for fungal culture, and (iii) proposing a standardized protocol suitable for CF routine microbiology. Methods: An international, consensually designed prospective study was set up (https://www.ecfs.eu/special-projects/mucofong-international-project). All centers worked according to the same protocol approved by Lille Ethical Committee. CF sputa were inoculated onto eight semi-selective media incubated at 37 degrees C T or 25 degrees C-30 degrees C for 15 days, and inspected twice weekly for fungal growth. Results: A total of 469 sputa were collected from patients at 18 European and one Australian CF centers. Positive cultures for fungal growth were significantly associated with patient ages. Aspergillus fumigatus was the most frequently isolated mold. We identified a growing European North-to-South gradient of Scedosporium prevalence, while yeasts, Aspergillus section Fumigati, Cladosporium and Penicillium were significantly more prevalent in the Northern regions. Conclusions: According to the CHi-squared Automatic Interaction Detector method, we propose a consensual protocol based on two media (YPDA or Sabouraud medium, and B(+) medium) to detect the main opportunistic molds in CF context; the use of an additional medium being recommended according to the patient's clinical status. This standardized protocol allows us to have an accurate overview of the respiratory mycobiome on the culturomic side in CF. (C) 2018 Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.\n\nBuzina, Walter\n\n\n"
},
{
"text": "\n176453\nEfficacy of Albumin Treatment for Patients with Cirrhosis and Infections Unrelated to Spontaneous Bacterial Peritonitis.\n\nFernández, J\n\nAngeli, P\n\nTrebicka, J\n\nMerli, M\n\nGustot, T\n\nAlessandria, C\n\nAagaard, NK\n\nde Gottardi, A\n\nWelzel, TM\n\nGerbes, A\n\nSoriano, G\n\nVargas, V\n\nAlbillos, A\n\nSalerno, F\n\nDurand, F\n\nBañares, R\n\nStauber, R\n\nPrado, V\n\nArteaga, M\n\nHernández-Tejero, M\n\nAziz, F\n\nMorando, F\n\nJansen, C\n\nLattanzi, B\n\nMoreno, C\n\nCampion, D\n\nGronbaek, H\n\nGarcia, R\n\nSánchez, C\n\nGarcía, E\n\nAmorós, A\n\nPavesi, M\n\nClària, J\n\nMoreau, R\n\nArroyo, V\n\nBeiträge in Fachzeitschriften\nNone\n31394283.0\n10.1016/j.cgh.2019.07.055\nNone\nWe performed a randomized trial to determine whether albumin should be administered to patients with infections unrelated to spontaneous bacterial peritonitis (SBP).\n We performed a multicenter, open-label trial in which 118 patients with cirrhosis, non-SBP infections, and additional risk factors for poor outcome were randomly assigned to receive antibiotics plus albumin (study group; n = 61) or antibiotics alone (control group; n = 57). The primary outcome was in-hospital mortality; secondary outcomes were effect of albumin on disease course.\n There were no significant differences at baseline between groups in results from standard laboratory tests, serum markers of inflammation, circulatory dysfunction, or liver severity scores. However, the combined prevalence of acute on chronic liver failure (ACLF) and kidney dysfunction was significantly higher in the study group (44.3% vs 24.6% in the control group; P = .02), indicating greater baseline overall severity. There was no significant difference in the primary outcome between groups (13.1% in the study group vs 10.5% in the control group; P = .66). Circulatory and renal functions improved in only the study group. A significantly higher proportion of patients in the study group had resolution of ACLF (82.3% vs 33.3% in the control group; P = .03). A significantly lower proportion of patients in the study group developed nosocomial infections (6.6% vs 24.6% in the control group; P = .007).\n In a randomized trial of patients with advanced cirrhosis and non-SBP infections, in-hospital mortality was similar between those who received albumin plus antibiotics vs those who received only antibiotics (controls). However, patients given albumin were sicker at baseline and, during the follow-up period, a higher proportion had ACLF resolution and a lower proportion had nosocomial infections. ClinicalTrials.gov no: NCT02034279.\n Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.\n\nStauber, Rudolf\n\n\n"
},
{
"text": "\n185925\nComparative transcriptomics reveals candidate carotenoid color genes in an East African cichlid fish.\n\nAhi, EP\n\nLecaudey, LA\n\nZiegelbecker, A\n\nSteiner, O\n\nGlabonjat, R\n\nGoessler, W\n\nHois, V\n\nWagner, C\n\nLass, A\n\nSefc, KM\n\nBeiträge in Fachzeitschriften\nISI:000521340900004\n31948394.0\n10.1186/s12864-020-6473-8\nPMC6966818\nCarotenoids contribute significantly to animal body coloration, including the spectacular color pattern diversity among fishes. Fish, as other animals, derive carotenoids from their diet. Following uptake, transport and metabolic conversion, carotenoids allocated to body coloration are deposited in the chromatophore cells of the integument. The genes involved in these processes are largely unknown. Using RNA-Sequencing, we tested for differential gene expression between carotenoid-colored and white skin regions of a cichlid fish, Tropheus duboisi "Maswa", to identify genes associated with carotenoid-based integumentary coloration. To control for positional gene expression differences that were independent of the presence/absence of carotenoid coloration, we conducted the same analyses in a closely related population, in which both body regions are white.\n A larger number of genes (n = 50) showed higher expression in the yellow compared to the white skin tissue than vice versa (n = 9). Of particular interest was the elevated expression level of bco2a in the white skin samples, as the enzyme encoded by this gene catalyzes the cleavage of carotenoids into colorless derivatives. The set of genes with higher expression levels in the yellow region included genes involved in xanthophore formation (e.g., pax7 and sox10), intracellular pigment mobilization (e.g., tubb, vim, kif5b), as well as uptake (e.g., scarb1) and storage (e.g., plin6) of carotenoids, and metabolic conversion of lipids and retinoids (e.g., dgat2, pnpla2, akr1b1, dhrs). Triglyceride concentrations were similar in the yellow and white skin regions. Extracts of integumentary carotenoids contained zeaxanthin, lutein and beta-cryptoxanthin as well as unidentified carotenoid structures.\n Our results suggest a role of carotenoid cleavage by Bco2 in fish integumentary coloration, analogous to previous findings in birds. The elevated expression of genes in carotenoid-rich skin regions with functions in retinol and lipid metabolism supports hypotheses concerning analogies and shared mechanisms between these metabolic pathways. Overlaps in the sets of differentially expressed genes (including dgat2, bscl2, faxdc2 and retsatl) between the present study and previous, comparable studies in other fish species provide useful hints to potential carotenoid color candidate genes.\n\nHois, Victoria\n\n\n"
},
{
"text": "\n1620\nMechanisms of Ca2+ store depletion in single endothelial cells in a Ca(2+)-free environment.\n\nPaltauf-Doburzynska, J\n\nFrieden, M\n\nGraier, WF\n\nBeiträge in Fachzeitschriften\nISI:000081705600002\n10463098.0\n10.1054/ceca.1999.0038\nNone\nDepletion of agonist-sensitive Ca2+ stores results in activation of capacitative Ca2+ entry (CCE) in endothelial cells. The proportion of Ca2+ stores contributing to the regulation of CCE is unknown. In fura-2/am loaded single endothelial cells freshly isolated from bovine left circumflex coronary arteries, we investigated whether a resting period in a Ca(2+)-free environment results in emptying of bradykinin-sensitive Ca2+ stores (BsS) and activation of CCE. In a Ca(2+)-free environment, depletion of BsS occurred in a time-dependent manner (59% after 10 min in Ca(2+)-free solution). This effect was prevented by inhibition of the Na(+)-Ca2+ exchange but not by a blockade of ryanodine-sensitive Ca2+ release (RsCR). In contrast to BsS, mitochondrial Ca2+ content remained unchanged in the Ca(2+)-free environment. Remarkably, activity of CCE (monitored as Mn2+ influx) did not increase after depletion of BsS in the Ca(2+)-free environment. In contrast to Mn2+ influx, the effect of re-addition of Ca2+ to elevate bulk Ca2+ concentration ([Ca2+]b) decreased with the time the cells rested in Ca(2+)-free buffer. This decrease was prevented by an inhibition of RsCR. In low Na+ conditions the effect of Ca2+ on [Ca2+]b was reduced while it did not change the time the cells rested in Ca(2+)-free solution. After a 2 min period in low Na+ conditions, ryanodine-induced Ca2+ extrusion was markedly diminished. Inhibition of RsCR re-established the effect of Ca2+ on [Ca2+]b in low Na+ conditions. Collapsing subplasmalemmal Ca2+ stores with nocodazole, increased the effect of Ca2+ on [Ca2+]b. In nocodazole-treated cells, the effect of Ca2+ on [Ca2+]b was not reduced in Ca(2+)-free environment. These data indicate that activation of CCE is not associated with the agonist-sensitive Ca2+ pools that deplete rapidly in a Ca(2+)-free environment. Subplasmalemmal ryanodine-sensitive Ca2+ stores (RsS) are emptied in Ca(2+)-free/low Na+ solution and re-sequester Ca2+ which enters the cells prior an increase in [Ca2+]b occurs. Thus, in endothelial cells there are differences in the functions of various subplasmalemmal Ca2+ stores (i.e. BsS and RsS), which include either activation of CCE or regulation of subplasmalemmal Ca2+.\n\nGraier, Wolfgang\n\n\n"
},
{
"text": "\n9086\nPolycystic ovarian disease: endocrinological parameters with specific reference to growth hormone and somatomedin-C.\n\nUrdl, W\n\nBeiträge in Fachzeitschriften\nISI:A1988N507200003\n3408273.0\n10.1007/BF00931548\nNone\nThirty-three women (22-38 years old) with polycystic ovarian disease (PCOD) were included in this study. The criteria for diagnosis were: an LH/FSH ratio greater than 2.0; polycystic ovaries, diagnosed by means of palpation and ultrasound; androgenism and menstrual cycle abnormalities. Using endocrine parameters, we attempted to define distinct forms of PCOD. The patients were placed in three groups according to serum levels of testosterone (T) and 17 alpha-hydroxyprogesterone (17 alpha OHP) and the estrone/androstendione (E1/delta 4A) ratio. Patients in group I (n = 18) had an elevated T level (greater than 1.0 ng/ml) and a 17 alpha OHP level under 4.0 ng/ml. This type of POCD was called the "androgen" type. Patients in group II (n = 7) had normal T- and 17 alpha OHP levels under 4.0 ng/ml and an elevated (E1/delta 4A) ratio. This type of PCOD was called the "estrogen" type. Group III (n = 8) comprised patients with 17 alpha OHP levels over 4.0 ng/ml. This type of PCOD was called the "adrenocortical" type. In two patients of this group, a modified ACTH test revealed late-onset congenital hyperplasia. The endocrine parameters of the patients with PCOD were compared with those of 17 adult without signs of PCOD. Statistical evaluation was done by variance analysis. Women with acromegaly often show signs of androgenism as well as menstrual cycle abnormalities. This may indicate an association between the growth factors human growth hormone (HGH) and somatomedin-C (Sm-C) and the biosynthese and metabolism of steroid hormone. Recent experiments have demonstrated such associations. Our study showed an association between the HGH and Sm-C levels and abnormal steroid hormone concentrations in women with androgen type PCOD (group I). These patients had a significantly decreased HGH level, a significantly decreased HGH/Sm-C ratio, and an increased average Sm-C level. These data suggest that elevated Sm-C levels can, by a negative-feedback mechanism, inhibit pituitary HGH production. We discuss the possible mechanisms causing elevation of plasma Sm-C, HGH, steroid hormones, excessive food intake, and possibly prolactin seem responsible for the clinical manifestation of increased Sm-C production in adolescence and for its level in the fertile years of patients.\n\n\n"
},
{
"text": "\n12592\nBlunt liver trauma in children.\n\nSchmidt, B\n\nSchimpl, G\n\nHöllwarth, ME\n\nBeiträge in Fachzeitschriften\nISI:000226285200007\n15459780.0\n10.1007/s00383-004-1276-6\nNone\nDiagnostic evaluation and treatment of blunt liver trauma in children have changed essentially over the last decades. In the period between January 1975 and December 2002, a total of 45 children, 18 girls and 27 boys, between the ages of 1 and 16 years (mean 8.19) were treated for liver rupture following blunt abdominal trauma. The most common causes of injury were traffic accidents (49%), followed by falls (22%), direct trauma due to impact (20%) and being run over by a vehicle (9%). A total of 26 patients had one or more concomitant injuries; the injury severity score was between 16 and 57 (mean 22.9), and 16 patients had additional injuries to other solid abdominal organs. Since we last used laparotomies to explore the abdomen and manage liver ruptures in 1984, we divided our patients into two groups with respect to the choice of diagnostic and treatment modalities: group I, consisting of children treated before 1984, and group II, consisting of children treated after 1985. In group I (n=12), a diagnosis was made in eight cases based on exploratory laparotomy, in two cases based on sonography and laparoscopy, in one case based on laparoscopy only, and in another case based on sonography only. In eight cases the rupture was treated operatively; there was one postsurgical sepsis and one ileus due to adhesions. One child hemorrhaged to death when the vena cava ruptured during surgery. In group II (n=33), sonography was sufficient for a diagnosis in 18 cases. In 12 cases an additional computed tomographic scan was performed following initial sonography, and in three cases a diagnostic laparotomy was done elsewhere. In five cases the rupture was treated operatively in other hospitals. Twenty-eight patients could be treated conservatively and without any complications. One child died 3 days after the accident as a result of a severe brain injury. Over the past 15 years we have seen a clear tendency toward conservative treatment of our patients, which is also in agreement with current literature. Initial sonography, supplemented by computed tomography when necessary, allows not only noninvasive initial diagnostic evaluation but is also helpful in the further course in hemodynamic stable patients. All patients who had been treated conservatively (n=30) had no complications related to the liver rupture.\n\nHöllwarth, Michael\n\nSchmidt, Barbara\n\n\n"
},
{
"text": "\n61223\nFemoral neck fractures in childhood\n\nMayr, J\n\nHirner, V\n\nStyhler, W\n\nPosch, E\n\nJelen, M\n\nLinhart, WE\n\nKohlmaier, W\n\nNeubauer, T\n\nSchwarz, N\n\nBeiträge in Fachzeitschriften\nISI:000074736300003\n9677840.0\n10.1007/s001130050291\nNone\nIn a retrospective multicenter study we followed-up 30 fractures of the neck of the femur in children aged 11 years (1.5-15 years) for 4.8 years (0.5-20.0 years). It is the aim of this study to analyse factors possibly related to outcome, like age at injury, type of fracture, interval between injury and treatment, method of stabilization and postoperative interval until full weight bearing. At follow-up subjective parameters (pain, weather sensitiveness), clinical parameters (range of motion, claudication, leg length discrepancies) and radiological parameters (hip series) were investigated and medical charts and roentgenograms were reviewed using a standardized protocol. 29 of 30 children (96.7%) have sustained displaced fractures. Non-operative treatment has been applied in 4 children. 26 femoral neck fractures (type I: 1, type II: 8, type III: 17) were stabilized by internal fixation using screws and/or pins. Following non-operative treatment one child suffered a coxa vara and another child suffered a avascular femoral head necrosis in combination with coxa vara and leg length shortening of 4 cm. Following operative treatment 9 of 26 children (34.6%) suffered a avascular femoral head necrosis and 3 children (11.5%) suffered a coxa vara. In 6 of 26 children (23%) we observed leg length discrepancies > 2 cm. We were not able to demonstrate any significant follow-up result differencies between the groups of children who have sustained type II or type III fractures, or between the groups of children aged < 10 years when compared to children aged > 10 years, or between the group of children who were operated on within 6 hours after the accident when compared to the group of children operated > 6 hours after the accident. We observed no significant follow-up result differences between the groups of children who had different intervals between operation and full weight bearing. Operative fracture management remains the treatment of choice in the majority of displaced femoral neck fractures in children. However, in our limited study we were not able to demonstrate any significant follow-up result differences between the group of children treated by immediate open reduction and internal fixation (interval injury - operation < 6 hours) when compared to children who had been operated > 6 hours after the injury.\n\nLinhart, Wolfgang\n\n\n"
},
{
"text": "\n70914\nCa2+ sensitization in idiopathic dilated human myocardium. Differential in vitro effects of (+)-(5-methyl-6-phenyl)-1,3,5,6-tetrahydro-3,6-methano-1,5-benzodiazoci ne-2,4-dione, a novel purely Ca2+sensitizing agent, and (+)-5-(1-(3,4-dimethoxybenzoyl)-1,2,3,4-tetrahydroquinolin-6-yl)-6-meth yl-3, 6-dihydro-2H-1,3,4-thiadiazin-2-one on skinned fibres and isolated ventricular strips.\n\nHerzig, JW\n\nChiesi, M\n\nDepersin, H\n\nGrüninger, S\n\nHasenfuss, G\n\nKubalek, R\n\nLeutert, T\n\nPieske, B\n\nPioch, K\n\nWenk, P\n\nHolubarsch, C\n\nBeiträge in Fachzeitschriften\nISI:A1996UW12900007\n8767348.0\nNone\nNone\n(+)-(5-Methyl-6-phenyl)-1, , , -tetrahydro-3, -methano-1, 5-benzodiazocine-2, -dione (CAS 165755-40-8, CGP 48506) is a novel Ca2+ sensitizing agent devoid of any other positive inotropic mechanism, particularly phosphodiesterase (PDE) III inhibition. 5-(1-(3, -Dimethoxybenzoyl)-1, , , -tetrahydroquinolin-6-yl)-6-met hyl-3, 6-dihydro-2H-1, , -thiadiazin-2-one (CAS 120223-04-3, EMD 53998) is a PDE III inhibitor with a Ca2+ sensitizing activity residing in its (+)-enantiomer, EMD 57033 (CAS 147527-31-9). In skinned fibres and electrically stimulated left ventricular strips from idiopathic dilated human hearts, New York Heart Association (NYHA) class IV, the Ca2+ sensitizing and inotropic effects of the benzodiazocine CGP 48506 and the thiadiazinones EMD 53998 or EMD 57033 were compared. Both CGP 48506 and EMD 53998 induce a left shift of the Ca2+ activation curve of force towards lower Ca2+ concentrations in skinned fibres, which indicates Ca2+ sensitization. Only EMD 53998, but not CGP 48506, increases skinned fibre force at both minimum (resting) and maximally activating Ca2+ concentrations. This is taken as an argument for a principal difference in the mechanisms of the Ca2+ sensitizing actions of the two compounds. CGP 48506 is shown not to influence the amplitude of the Ca2+ transient in rat cardiomyocytes. On the other hand, both CGP 48506 and EMD 57033 show comparable, though quantitatively different, positive inotropic effects in electrically stimulated left ventricular strip preparations. It is unclear whether the PDE III inhibitory component of the profile of actions of EMD 57033 may play a role in preventing the increase in diastolic tension as expected from the skinned fibre experiments. It is noteworthy that both Ca2+ sensitizing agents act as positive inotropic compounds in the end-stage failing human heart where other inotropic agents like beta 1-adrenergic agonists or PDE inhibitors have been described to fail.\n\n\n"
}
]
}