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=125720",
"previous": "https://api-test.medunigraz.at/v1/research/search/publication/?format=api&limit=20&offset=125680",
"results": [
{
"text": "\n187082\nLoss of autophagy protein ATG5 impairs cardiac capacity in mice and humans through diminishing mitochondrial abundance and disrupting Ca2+ cycling.\n\nLjubojević-Holzer, S\n\nKraler, S\n\nDjalinac, N\n\nAbdellatif, M\n\nVoglhuber, J\n\nSchipke, J\n\nSchmidt, M\n\nKling, KM\n\nFranke, GT\n\nHerbst, V\n\nZirlik, A\n\nvon Lewinski, D\n\nScherr, D\n\nRainer, PP\n\nKohlhaas, M\n\nNickel, A\n\nMühlfeld, C\n\nMaack, C\n\nSedej, S\n\nBeiträge in Fachzeitschriften\nNone\n33752242.0\n10.1093/cvr/cvab112\nNone\nAutophagy protects against the development of cardiac hypertrophy and failure. While aberrant Ca2+ handling promotes myocardial remodelling and contributes to contractile dysfunction, the role of autophagy in maintaining Ca2+ homeostasis remains elusive. Here, we examined whether Atg5 deficiency-mediated autophagy promotes early changes in subcellular Ca2+ handling in ventricular cardiomyocytes, and whether those alterations associate with compromised cardiac reserve capacity, which commonly precedes the onset of heart failure.\n RT-qPCR and immunoblotting demonstrated reduced Atg5 gene and protein expression and decreased abundancy of autophagy markers in hypertrophied and failing human hearts. The function of ATG5 was examined using cardiomyocyte-specific Atg5-knockout mice (Atg5-/-). Before manifesting cardiac dysfunction, Atg5-/- mice showed compromised cardiac reserve in response to β-adrenergic stimulation. Consequently, effort intolerance and maximal oxygen consumption were reduced during treadmill-based exercise tolerance testing. Mechanistically, cellular imaging revealed that Atg5 deprivation did not alter spatial and functional organization of intracellular Ca2+ stores or affect Ca2+ cycling in response to slow pacing or upon acute isoprenaline administration. However, high frequency stimulation exposed stunted amplitude of Ca2+ transients, augmented nucleoplasmic Ca2+ load and increased CaMKII activity, especially in the nuclear region of hypertrophied Atg5-/- cardiomyocytes. These changes in Ca2+ cycling were recapitulated in hypertrophied human cardiomyocytes. Finally, ultrastructural analysis revealed accumulation of mitochondria with reduced volume and size distribution, meanwhile functional measurements showed impaired redox balance in Atg5-/- cardiomyocytes, implying energetic unsustainability due to overcompensation of single mitochondria, particularly under increased workload.\n Loss of cardiac Atg5-dependent autophagy reduces mitochondrial abundance and causes subtle alterations in subcellular Ca2+ cycling upon increased workload in mice. Autophagy-related impairment of Ca2+ handling is progressively worsened by β-adrenergic signalling in ventricular cardiomyocytes, thereby leading to energetic exhaustion and compromised cardiac reserve.\n © The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.\n\nAbdellatif, Mahmoud\n\nDalinac, Natasa\n\nHolzer, Senka\n\nRainer, Peter\n\nScherr, Daniel\n\nSedej, Simon\n\nTrummer-Herbst, Viktoria\n\nVoglhuber, Julia\n\nvon Lewinski, Dirk\n\nZirlik, Andreas\n\n\n"
},
{
"text": "\n1025\nExpression of HOXC4, HOXC5, and HOXC6 in human lymphoid cell lines, leukemias, and benign and malignant lymphoid tissue.\n\nBijl, J\n\nvan Oostveen, JW\n\nKreike, M\n\nRieger, E\n\nvan der Raaij-Helmer, LM\n\nWalboomers, JM\n\nCorte, G\n\nBoncinelli, E\n\nvan den Brule, AJ\n\nMeijer, CJ\n\nBeiträge in Fachzeitschriften\nISI:A1996TY33900010\n8634419.0\n10.1182/blood.V87.5.1737.bloodjournal8751737\nNone\nBesides their regulatory role in embryogenesis, homeobox (HOX) genes are expressed in a specific manner in hematopoietic cell lineages, implying a role in the molecular regulation of hematopoiesis. Some HOX C cluster genes are found to be expressed in lymphoid cells of mice and humans. Their function and expression in normal hematopoiesis are still largely unknown. We have studied the mRNA expression of HOXC4, HOXC5, and HOXC6 in several stages of lymphocyte maturation by reverse transcriptase-polymerase chain reaction (RT-PCR) and RNA in situ hybridization (RISH). We examined CD34+/CD38low and CD34+/CD38high cells obtained from normal donor bone marrow (BM), a panel of 19 lymphoid cell lines, several types of leukemias and non-Hodgkin's lymphomas (NHL), and lymphocytes isolated from tonsillar tissue and peripheral blood (PB). HOXC4 and HOXC6 were found to be expressed during maturation in B- and T-lymphoid cells. The expression of each gene was found to be initiated at different cell maturation stages. HOXC4 transcripts were present in CD34+/CD38low cells, which are thought to comprise stem cells and noncommitted progenitor cells, and in subsequent stages to terminally maturated lymphoid cells. HOXC6 expression is initiated in equivalents of prothymocyte and pre-pre-B cell stage and remains present in mature cells. However, HOXC5 is only expressed in neoplastic cell lines and in neoplastic cells of NHL, but not in CD34+ BM cells, nor in resting or activated lymphoid cells isolated from tonsil, PB, or in leukemia cells. In cell lines, weak expression of HOXC5 is initiated in equivalents of pre-B cell and common thymocyte stage and is continuously expressed in mature cell lines. Semi-quantitative RT-PCR showed that expression levels of HOXC5 were much lower than those of HOXC4 and HOXC6; furthermore an increase of expression of HOXC4, HOXC5, and HOXC6 during lymphoid cell differentiation was demonstrated. Thus, mainly mature lymphoid cell lines and neoplastic cells of NHL do express HOXC5, in contrast to the lack of expression in normal lymphoid cells and leukemias. These findings suggest involvement of HOXC5 in lymphomagenesis.\n\n\n"
},
{
"text": "\n38093\nMutations of the TGF-beta type II receptor BMPR2 in pulmonary arterial hypertension.\n\nMachado, RD\n\nAldred, MA\n\nJames, V\n\nHarrison, RE\n\nPatel, B\n\nSchwalbe, EC\n\nGruenig, E\n\nJanssen, B\n\nKoehler, R\n\nSeeger, W\n\nEickelberg, O\n\nOlschewski, H\n\nElliott, CG\n\nGlissmeyer, E\n\nCarlquist, J\n\nKim, M\n\nTorbicki, A\n\nFijalkowska, A\n\nSzewczyk, G\n\nParma, J\n\nAbramowicz, MJ\n\nGalie, N\n\nMorisaki, H\n\nKyotani, S\n\nNakanishi, N\n\nMorisaki, T\n\nHumbert, M\n\nSimonneau, G\n\nSitbon, O\n\nSoubrier, F\n\nCoulet, F\n\nMorrell, NW\n\nTrembath, RC\n\nBeiträge in Fachzeitschriften\nISI:000235172400001\n16429395.0\n10.1002/humu.20285\nNone\nPulmonary arterial hypertension (PAH) is clinically characterized by a sustained elevation in mean pulmonary artery pressure leading to significant morbidity and mortality. The disorder is typically sporadic, and in such cases the term idiopathic PAH (IPAH) is used. However, cases that occur within families (familial PAH (FPAH)) display similar clinical and histopathological features, suggesting a common etiology. Heterozygous mutations of a type II member of the TGF-beta cell signaling superfamily known as BMPR2 on chromosome 2q33 have been identified in many kindreds with FPAH, yet display both reduced penetrance and sex bias. This report presents the compilation of data for 144 distinct mutations that alter the coding sequence of the BMPR2 gene identified in 210 independent PAH subjects. This large data set characterizes the extent of sequence variation and reveals that the majority (71%) of mutations in FPAH and IPAH comprise nonsense, frameshift, and splice-site defects, and gene rearrangements. These predict premature termination of the transcript with likely loss through the process of nonsense-mediated decay (NMD). A total of 44 missense mutations were identified that substitute amino acid residues at highly conserved sites within recognized functional domains of the mature receptor. We assess this category of mutations in the context of their heterogeneous effects on cell signaling when assayed by in vitro cell-based systems. Disease-causing mutation hot-spots within BMPR2 are summarized. Taken together, these observations are likely to aid in the development of targeted mutation detection strategies relevant for patient management. Finally, we examine the age- and sex-dependent reduced penetrance of BMPR2 mutations by reviewing bmpr2 animal models and the requirement for additional genetic and/or environmental modifiers of disease. In conclusion, these data provide compelling genetic evidence that haploinsufficiency is the predominant molecular mechanism underlying disease predisposition, and support the concept of a critical threshold of signaling activity below which disease may be precipitated.\n\nOlschewski, Horst\n\n\n"
},
{
"text": "\n70974\nThe role of SR Ca(2+)-content in blunted inotropic responsiveness of failing human myocardium.\n\nMaier, LS\n\nBraunhälter, J\n\nHorn, W\n\nWeichert, S\n\nPieske, B\n\nBeiträge in Fachzeitschriften\nISI:000176166400009\n11991734.0\n10.1006/jmcc.2002.1527\nNone\nThe effects of inotropic agents are blunted in end-stage failing human myocardium. This has been related to a number of subcellular alterations including desensitization of the beta -adrenergic system. However, it is unknown whether alterations in SR Ca(2+)-handling contribute to blunted inotropic responsiveness of failing myocardium. We tested the hypothesis that the reduced effectiveness of Ca(2+)-dependent inotropic interventions results from the inability of the SR to sufficiently increase its Ca(2+)-content in failing human myocardium. Experiments were performed in ventricular muscle preparations from a total of four non-failing and 18 end-stage failing hearts. Isometric twitch force and SR Ca(2+)-content (using rapid cooling contractures; RCCs) were assessed under basal experimental conditions (1 Hz, 37 degrees C, [Ca(2+)](o) 2.5 mmol/l), and at increasing [Ca(2+)](o) (1.25-15 mmol/l), increasing concentrations of the beta -adrenergic agonist isoproterenol (ISO; 0.01-10 micromol/l), or the glycolytic substrate pyruvate (5-15 mmol/l). In addition, paired RCCs were evoked in a subset of experiments to investigate the relative contribution of SR Ca(2+)-uptake v Na(+)/Ca(2+)-exchange to cytosolic Ca(2+)-elimination. In non-failing human myocardium, Ca(2+), ISO, and pyruvate exerted significant positive inotropic effects (increase in twitch force by maximally 396%, 437%, and 82%, respectively). The inotropic effects were associated with increasing RCCs (by 147%, 193%, and 51%, respectively). In failing myocardium, the inotropic effects of Ca(2+) and ISO were significantly less pronounced (with maximal increases in twitch force by 226% and 138%, respectively), associated with blunted effects on RCCs (increase by 33% and 79%, respectively). In contrast, the inotropic effect of pyruvate was unchanged in failing myocardium (increase by 66%), while the corresponding RCCs increased only by 30%. We conclude that the inotropic effects of Ca(2+), ISO, and pyruvate are associated with a significant increase in SR Ca(2+)-content in non-failing human myocardium. In end-stage failing myocardium, the reduced inotropic response to Ca(2+) and ISO is associated with the inability of the SR to appropriately increase its Ca(2+)-content, possibly related to decreased SR Ca(2+)-ATPase and increased Na(+)/Ca(2+)-exchanger expression. In contrast, the maintained inotropic response to pyruvate despite reduced SR Ca(2+)-loading points to additional subcellular effects such as enhanced myofilament Ca(2+)-responsiveness.\n\n\n"
},
{
"text": "\n75011\nPreoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy.\n\nRosen, G\n\nCaparros, B\n\nHuvos, AG\n\nKosloff, C\n\nNirenberg, A\n\nCacavio, A\n\nMarcove, RC\n\nLane, JM\n\nMehta, B\n\nUrban, C\n\nBeiträge in Fachzeitschriften\nISI:A1982ND87400024\n6174200.0\n10.1002/1097-0142(19820315)49:6<1221::AID-CNCR2820490625>3.0.CO;2-E\nNone\nSince June 1978, 57 patients with primary osteogenic sarcoma of an extremity were treated with high-dose methotrexate (HDMTX) and citrovorum factor rescue (CFR), Adriamycin, and the combination of bleomycin, cyclophosphamide and dactinomycin (BCD) given for 4-16 weeks prior to definitive surgery. Histologic examination of the resected primary tumor determined the effect of preoperative chemotherapy with many primary tumors showing greater than 90% tumor necrosis attributable to preoperative chemotherapy. All patients having this favorable effect of chemotherapy on the primary tumor were continued on the same chemotherapy regimen postoperatively (regimen B). However, in those patients not having a good effect of preoperative chemotherapy on the primary tumor, HDMTX with CFR was subsequently deleted from their postoperative chemotherapy and they were placed on a regimen containing cisplatinum at the dose of 120mg/M2 with mannitol diuresis combined with Adriamycin in addition to BCD (regimen A). In the current study, 35 of the 57 patients did not demonstrate a good effect of chemotherapy on the primary tumor and were assigned to regimen A postoperatively. Of these 35 patients, 32 (91%) have remained continuously free of recurrent or metastatic disease from 6-34 months following the start of therapy. Among the 22 remaining patients having a good histologic response and treated with regimen B postoperatively, there has been only one relapse in a patient who had a local recurrence in the area of an inadequately resected primary tumor three months after the cessation of chemotherapy. Thus, 53 of 57 patients (93%) are continuously with no evidence of recurrent or metastatic disease from 6-35 months (median, 20 months) from the start of treatment. This study demonstrates the value of thorough histologic examination in predicting survival in responding patients and in helping identify patients whose disease-free survival rate can be substantially increased if they are given alternative postoperative adjuvant chemotherapy after failing to have a good response to preoperative chemotherapy. This individualized chemotherapeutic strategy has yielded the highest disease-free survival rate reported to date for osteogenic sarcoma.\n\nUrban, Ernst-Christian\n\n\n"
},
{
"text": "\n121334\nWhole-body MR imaging in children with suspected osteonecrosis after intensive chemotherapy: Preliminary results\n\nBeer, M\n\nStenzel, M\n\nGirschick, H\n\nSchlegel, PG\n\nDargel, K\n\nBeiträge in Fachzeitschriften\nISI:000254189500007\n18278731.0\n10.1055/s-2008-1027185\nNone\nPurpose: Use of multidrug chemotherapy poses the risk of avascular osseous necroses in children. Depiction of the whole body, including clinically non-apparent sites is mandatory for starting early and proper treatment, including surgical approaches in lesions near the joints. We analyzed the value of whole-body MRI in the detection of osteonecrosis, (1) in relation to conventional Xray imaging and clinical symptoms, (2) using different MRI sequences, (3) with follow-up examinations. Materials and Methods: 5 patients suffering from an oncological disease, 13 to 16 years old (3 x ALL, 1 x medulloblastoma, 1 x CML), and recently developing bone pain were examined with X-ray imaging of the particular region and a whole-body MRI (T2w TIRM, T1w TSE sequences, pre- and post-contrast GD-DTPA, including fat suppression techniques). Neck/thorax/abdomen/pelvis, and upper and lower extremities were acquired in the coronal plane, and the feet in sagittal orientation. 4 of 5 patients had at least one follow-up examination (in the mean after 10 +/- 4 months). Results: None of the initial X-ray images revealed an abnormal finding. The whole-body MRI showed in 4 of 5 children bone marrow lesions compatible with osteonecrosis. The locations were around the knee joints (n = 3) and the tibiae/ankle joints (n=4). In addition to the symptomatic sites, MRI revealed additional lesions at the following sites: humerus (n = 5), hip joints (n=4), knee joints (n=6), ankle joints (n = 4). The size varied from small focal lesions to lesions measuring 90% of the whole transverse diameter of the bone. The lesions were able to be detected most easily with heavily T2-weighted (TIRM) sequences, and the diagnosis was most easily established using the non-enhanced TSE T1-weighted sequences. As a consequence of the results of the whole-body MRI, all patients with lesions compatible with osteonecrosis received symptomatic (n=2) or specific (n = 2) therapy. In the follow-up examinations, a higher number of patients showed no changes in the lesions as to size and distribution. 2 patients showed partial resolution of the osteonecroses. Conclusion: Whole-body MR imaging allows early diagnosis of symptomatic as well as clinically non-apparent osteonecroses. It can be used in planning and monitoring surgical and pharmacological therapies.\n\n\n"
},
{
"text": "\n149466\nImmunomodulation by lipid emulsions in pulmonary inflammation: a randomized controlled trial.\n\nHecker, M\n\nLinder, T\n\nOtt, J\n\nWalmrath, HD\n\nLohmeyer, J\n\nVadász, I\n\nMarsh, LM\n\nHerold, S\n\nReichert, M\n\nBuchbinder, A\n\nMorty, RE\n\nBausch, B\n\nFischer, T\n\nSchulz, R\n\nGrimminger, F\n\nWitzenrath, M\n\nBarnes, M\n\nSeeger, W\n\nMayer, K\n\nBeiträge in Fachzeitschriften\nISI:000354855700001\n25962383.0\n10.1186/s13054-015-0933-6\nPMC4438480\nAcute respiratory distress syndrome (ARDS) is a major cause of mortality in intensive care units. As there is rising evidence about immuno-modulatory effects of lipid emulsions required for parenteral nutrition of ARDS patients, we sought to investigate whether infusion of conventional soybean oil (SO)-based or fish oil (FO)-based lipid emulsions rich in either n-6 or n-3 fatty acids, respectively, may influence subsequent pulmonary inflammation.\n In a randomized controlled, single-blinded pilot study, forty-two volunteers received SO, FO, or normal saline for two days. Thereafter, volunteers inhaled pre-defined doses of lipopolysaccharide (LPS) followed by bronchoalveolar lavage (BAL) 8 or 24 h later. In the murine model of LPS-induced lung injury a possible involvement of resolvin E1 (RvE1) receptor ChemR23 was investigated. Wild-type and ChemR23 knockout mice were infused with both lipid emulsions and challenged with LPS intratracheally.\n In volunteers receiving lipid emulsions, the fatty acid profile in the plasma and in isolated neutrophils and monocytes was significantly changed. Adhesion of isolated monocytes to endothelial cells was enhanced after infusion of SO and reduced by FO, however, no difference of infusion on an array of surface adhesion molecules was detected. In neutrophils and monocytes, LPS-elicited generation of pro-inflammatory cytokines increased in the SO and decreased in the FO group. LPS inhalation in volunteers evoked an increase in neutrophils in BAL fluids, which decreased faster in the FO group. While TNF-α in the BAL was increased in the SO group, IL-8 decreased faster in the FO group. In the murine model of lung injury, effects of FO similar to the volunteer group observed in wild-type mice were abrogated in ChemR23 knockout mice.\n After infusion of conventional lipid emulsions, leukocytes exhibited increased adhesive and pro-inflammatory features. In contrast, FO-based lipid emulsions reduced monocyte adhesion, decreased pro-inflammatory cytokines, and neutrophil recruitment into the alveolar space possibly mediated by ChemR23-signaling. Lipid emulsions thus exert differential effects in human volunteers and mice in vivo.\n DRKS00006131 at the German Clinical Trial Registry, 2014/05/14.\n\nMarsh, Leigh\n\n\n"
},
{
"text": "\n160232\nTryptophan breakdown and cognition in bipolar disorder.\n\nPlatzer, M\n\nDalkner, N\n\nFellendorf, FT\n\nBirner, A\n\nBengesser, SA\n\nQueissner, R\n\nKainzbauer, N\n\nPilz, R\n\nHerzog-Eberhard, S\n\nHamm, C\n\nHörmanseder, C\n\nMaget, A\n\nRauch, P\n\nMangge, H\n\nFuchs, D\n\nZelzer, S\n\nSchütze, G\n\nMoll, N\n\nSchwarz, MJ\n\nMansur, RB\n\nMcIntyre, RS\n\nReininghaus, EZ\n\nBeiträge in Fachzeitschriften\nISI:000404815200019\n28482311.0\n10.1016/j.psyneuen.2017.04.015\nNone\nIt has been demonstrated that bipolar disorder (BD) is often accompanied by cognitive deficits across all subdomains including verbal memory, attention and executive functioning. Cognitive deficits are observed both during episodes of mania or depression, as well as during the euthymic phase. It has been proposed that chronic immune-mediated inflammation in the central nervous system results in alterations in neural structures that subserve cognitive function. Kynurenine is an intermediate in the inflammatory cascade and can be peripherally measured to proxy inflammatory activity. Herein, we sought to determine whether serum levels of kynurenine and/or its metabolites were associated with cognitive function in BD.\n In this investigation 68 euthymic individuals with BD according to DSM-IV completed a cognitive test battery to asses premorbid intelligence (Multiple Choice Word Test; MWT-B), verbal memory (California Verbal Learning Test; CVLT), attention (d2 Test of Attention; d2 test, Trail Making Test-A; TMT-A, Stroop word reading/Stroop color naming) and executive functioning (TMT-B, Stroop interference). In addition, fasting blood samples were taken and serum levels of kynurenine and its metabolites 3-hydroxykynurenine and kynurenic acid were analyzed. Subsequently ratios were formed from individual parameters. Patient data were compared with those of a mentally healthy control group (n=93).\n In male participants with BD only we found a significant negative correlation between the 3-hydroxykynurenine to kynurenic acid ratio and performance on the CVLT. Additionally, the kynurenine to 3-hydroxykynurenine ratio was associated with performance on a sub-score of the CVLT. Those associations were neither present in female individuals with BD nor in the control group.\n Our findings suggest that a shift towards the hydroxykynurenine arm of the kynurenine pathway may be associated with poorer memory performance due to its effects on neuronal functioning and neurogenesis in the hippocampus. Our results implicate a mechanistic role of central inflammatory processes in cognitive functions in adults with bipolar disorder.\n Copyright © 2017 Elsevier Ltd. All rights reserved.\n\nBengesser, Susanne\n\nBirner, Armin\n\nDalkner, Nina\n\nFellendorf, Frederike\n\nHamm, Carlo\n\nMaget, Alexander\n\nMangge, Harald\n\nPilz, Rene\n\nPlatzer, Martina\n\nQueissner, Robert\n\nReininghaus, Eva\n\nZelzer, Sieglinde\n\n\n"
},
{
"text": "\n184192\nStudy protocol for assessing the user acceptance, safety and efficacy of a tablet-based workflow and decision support system with incorporated basal insulin algorithm for glycaemic management in participants with type 2 diabetes receiving home health care: A single-centre, open-label, uncontrolled proof-of-concept study.\n\nLibiseller, A\n\nKopanz, J\n\nLichtenegger, KM\n\nMader, JK\n\nTruskaller, T\n\nLackner, B\n\nAberer, F\n\nPandis, M\n\nReinisch-Gratzer, J\n\nAmbrosch, GC\n\nSinner, F\n\nPieber, TR\n\nDonsa, K\n\nBeiträge in Fachzeitschriften\nISI:000594377800003\n32775762.0\n10.1016/j.conctc.2020.100620\nPMC7399114\nDiabetes management can be especially complex for older adults who receive health care at home. Thus, international guidelines recommend basal-insulin regimens due to simpler handling and low hypoglycaemia risk. A basal-insulin algorithm (including basal-plus) was developed to also include participant's health status and subsequently implemented into a tablet-based workflow and decision support system, GlucoTab@MobileCare. This study protocol describes a proof-of-concept study to investigate user acceptance, safety and efficacy of the GlucoTab@MobileCare system in participants receiving home health care.\n The open-label, single-centre, uncontrolled study will recruit a maximum of ten participants with insulin treated type-2-diabetes (age ≥18 years) who receive home health care. During a three month study period participants will receive basal- or basal-plus-insulin therapy once daily as suggested by the GlucoTab@MobileCare system. Statistical analysis will be conducted on an intention-to-treat basis. The primary endpoint is the percentage of tasks (BG measurements, insulin dose calculations, insulin injections) that were performed according to GlucoTab@MobileCare suggestions relative to the total of suggested tasks. Secondary endpoints include user acceptance, safety and efficacy parameters. The study was approved by the ethics committee and regulatory authorities. Before obtaining written informed consent, all participants will receive oral and written information about all aspects of the study. Results will be published in a peer-reviewed journal and at diabetes and geriatric conferences.\n Potential implications may be improved quality and safety of basal-insulin therapy in older adults as well as support for health-care-providers in daily routine including evidence-based knowledge.\n German Clinical Trials Register (DRKS00015059).\n © 2020 The Authors.\n\nAberer, Felix\n\nKopanz, Julia\n\nLibiseller, Angela\n\nLichtenegger, Katharina\n\nMader, Julia\n\nPandis, Marlene\n\nPieber, Thomas\n\nSinner, Frank Michael\n\n\n"
},
{
"text": "\n1522\nLocal nitroglycerin for treatment of anal fissures: an alternative to lateral sphincterotomy?\n\nBacher, H\n\nMischinger, HJ\n\nWerkgartner, G\n\nCerwenka, H\n\nEl-Shabrawi, A\n\nPfeifer, J\n\nSchweiger, W\n\nBeiträge in Fachzeitschriften\nISI:A1997XK09600020\n9221864.0\n10.1007/BF02055444\nNone\nPURPOSE: Nitric oxide is an important neurotransmitter mediating internal anal sphincter relaxation. Patients suffering from fissure-ln-ano were treated with topical nitroglycerine. The clinical evidence for therapeutic adequacy was examined in a prospective, randomized study. METHODS: The study included 35 patients with acute and chronic anal fissures. In Group A, including 20 patients with the clinical diagnosis of acute (12 patients) and chronic (8 patients) anal fissures, treatment consisted of topical nitroglycerine. Group B, consisting of 15 patients (10 acute and 5 chronic fissures), received topical anesthetic gel during therapy. Manometry was performed before and on days 14 and 28 in the course of topical application of either 0.2 percent glyceryl trinitrate ointment or anesthetic gel (lignocaine). Anal pressures were documented by recording the maximum resting and squeeze pressures. RESULTS: In 60 percent of cases treated with topical nitroglycerine (Group A, 11 acute (91.6 percent) and 1 chronic (12.5 percent)), anal fissure healed within 14 days, in contrast to Group B in which no healing was observed. The healing rate after one month was 80 percent (11 acute (91.6 percent) 5 chronic (62.5 percent)) in Group A and was significantly superior to Group B (healing rate, 40 percent: 5 acute (50 percent); 1 chronic (20 percent)). DISCUSSION: Previously increased maximum resting pressures decreased from a mean value of 110 to 87 cm H2O. This represents a mean reduction of 20 percent (P = 0.0022). We also noted a significant decrease in squeeze pressures (from 177.8 to 157.9 cm H2O (11 percent)). However, anal pressures did not decrease significantly in the four chronic fissure patients from Group A, whose fissures only healed after 28 days. Similarly to these Group A chronic fissure patients: no significant anal pressure reduction was observed in any Group B patients, Except for mild headache (20 percent), no side effects of treatment were reported. CONCLUSIONS: Topical application of nitroglycerine represents a new, easily handled, and effective alternative in the treatment of anal fissures. Ail of our patients reported a dramatic reduction in acute anal pain. However, it should be noted that a lack of sphincter tone reduction is a likely reason for the great tendency of chronic anal fissures to recur.\n\nBacher, Heinz\n\nCerwenka, Herwig\n\nMischinger, Hans-Joerg\n\nPfeifer, Johann\n\nWerkgartner, Georg\n\n\n"
},
{
"text": "\n2928\nDoes hyperbaric oxygen enhance the effect of photodynamic therapy in patients with advanced esophageal carcinoma? A clinical pilot study.\n\nMaier, A\n\nAnegg, U\n\nTomaselli, F\n\nRehak, P\n\nSankin, O\n\nFell, B\n\nRenner, H\n\nPinter, H\n\nSmolle-Jüttner, FM\n\nFriehs, GB\n\nBeiträge in Fachzeitschriften\nISI:000085113100009\n10691271.0\n10.1055/s-2000-132\nNone\nBACKGROUND AND STUDY AIMS: Experimental studies have shown that the cytotoxicity of porphyrins and related substances is mediated mainly by singlet oxygen and that hypoxic cells are less affected by porphyrins and light. In a clinical pilot study we assessed the use of photodynamic therapy (PDT) under hyperbaric oxygen (HBO), compared with PDT under normobaric conditions, in patients with advanced esophageal carcinoma. PATIENTS AND METHODS: After diagnostic work-up and staging, photosensitization in all patients was carried out using hematoporphyrine derivate (HpD) (2 mg/kg bodyweight 48 hours prior to PDT). We then applied light at 630 nm (KTP-Nd: YAG laser with DYE box) at dose of 300 J/cm, delivered by a fiber with a radial light-diffusing cylinder (length 1 cm), inserted through the biopsy channel of the endoscope. Of the patients, 14 (12 with stage III cancers, and two with stage IV cancers) were treated by PDT alone, and 17 patients (15 with stage III cancers, and two with stage IV cancers) received PDT under HBO at a level of 2 absolute atmospheric pressures (ATA). Transcutaneous PO2 levels of 500-750 mm Hg under HBO, compared with transcutaneous PO2 levels of 60-75 mm Hg under normobaric conditions, were measured. RESULTS: Improvements regarding dysphagia and stenosis diameter were obtained in both treatment arms with no significant differences (P = 0.36 and 0.14, respectively). The tumor length also decreased in both groups and showed a significant difference in favour of the PDT/ HBO group (P = 0.002). Kaplan-Meier statistics showed median overall survival for the PDT group and the PDT/HBO group as 7.0 and 12 months respectively. The 12-month survival rate was 28.6% for the PDT group and 41.2% for the PDT/HBO group. Logrank test showed a difference in survival in favor of the PDT/HBO group (P = 0.059). No major treatment-related complication occurred, and the 30-day mortality rate was 0%. CONCLUSIONS: Combined PDT/HBO represents a new approach in the treatment of esophageal cancer which, in this pilot study, appears to have enhanced the efficiency of PDT.\n\nAnegg, Udo\n\nMaier, Alfred\n\nSankin, Oliver\n\nSmolle-Juettner, Freyja-Maria\n\n\n"
},
{
"text": "\n22006\nPremarin-induced increases in coronary and uterine blood flow in nonpregnant sheep.\n\nClark, KE\n\nBaker, RS\n\nLang, U\n\nBeiträge in Fachzeitschriften\nISI:000088565500003\n10920301.0\n10.1067/mob.2000.105200\nNone\nOBJECTIVE: Menopause is associated with an increased incidence of cardiovascular disease among women, and estrogen replacement therapy is thought to reduce the risk of coronary artery disease. The mechanism by which this occurs is unclear, but coronary arterial endothelial and vascular smooth muscle cells have been shown to contain estrogen receptors, and their stimulation appears to increase nitric oxide synthesis. One conjugated estrogen preparation (Premarin) is widely used in postmenopausal hormone replacement therapy, but little is known about its effects on cardiovascular hemodynamics. STUDY DESIGN: This study was designed to determine whether Premarin, like 17beta-estradiol, has significant effects on cardiac output and coronary and uterine blood flows at doses used clinically (0.625, 1.25, and 2.5 mg). Nonpregnant oophorectomized sheep were implanted with instruments to measure cardiac output, left coronary (circumflex) artery blood flow, uterine blood flow, heart rate, and systemic arterial blood pressure. After recovery from surgery, the animals received intravenous bolus injections of either 17beta-estradiol (1.0 microg/kg), Premarin (0.625, 1.25, or 2. 5 mg), or vehicle on different days. RESULTS: The 1.0-microg/kg dose of 17beta-estradiol significantly increased coronary blood flow by 15% +/- 2% from baseline (mean +/- SEM). Premarin also increased coronary blood flow significantly at the 1.25- and 2.5-mg dose levels by 12% +/- 3% and 14% +/- 4%, respectively. As expected 17beta-estradiol increased uterine blood flow from a baseline of 15 +/- 3 mL/min to 169 +/- 19 mL/min. Premarin treatment was associated with a significant increase in uterine blood flow, which increased from an average baseline of 14 +/- 4 mL/min to 46 +/- 10 mL/min, 95 +/- 18 mL/min, and 135 +/- 20 mL/min at the three doses tested (0. 625, 1.25, and 2.5 mg, respectively). 17beta-Estradiol also increased cardiac output by 12% +/- 3%. Premarin increased cardiac output 2% +/- 3%, 9% +/- 4%, and 11% +/- 3%, with only the highest dose producing a significant change. 17beta-Estradiol also increased heart rate by 12% +/- 1%, whereas Premarin at doses of 0.625, 1.25, and 2.5 mg increased it by 4% +/- 3%, 7% +/- 4%, and 10% +/- 2%, respectively (increase significant only at the highest dose). Neither 17beta-estradiol nor Premarin altered either stroke volume or systemic arterial pressure. CONCLUSION: Premarin, like 17beta-estradiol, has significant systemic, coronary, and uterine vascular effects. These vascular effects may help to explain in part why these compounds are cardioprotective.\n\n\n"
},
{
"text": "\n120895\nExtranodal extension is a powerful prognostic factor in bladder cancer patients with lymph node metastasis.\n\nFajkovic, H\n\nCha, EK\n\nJeldres, C\n\nRobinson, BD\n\nRink, M\n\nXylinas, E\n\nChromecki, TF\n\nBreinl, E\n\nSvatek, RS\n\nDonner, G\n\nTagawa, ST\n\nTilki, D\n\nBastian, PJ\n\nKarakiewicz, PI\n\nVolkmer, BG\n\nNovara, G\n\nJoual, A\n\nFaison, T\n\nSonpavde, G\n\nDaneshmand, S\n\nLotan, Y\n\nScherr, DS\n\nShariat, SF\n\nBeiträge in Fachzeitschriften\nISI:000325478100033\n22877503.0\n10.1016/j.eururo.2012.07.026\nNone\nLymph node metastasis (LNM) is the most powerful pathologic predictor of disease recurrence after radical cystectomy (RC). However, the outcomes of patients with LNM are highly variable.\n To assess the prognostic value of extranodal extension (ENE) and other lymph node (LN) parameters.\n A retrospective analysis of 748 patients with urothelial carcinoma of the bladder and LNM treated with RC and lymphadenectomy without neoadjuvant therapy at 10 European and North American centers (median follow-up: 27 mo).\n All subjects underwent RC and bilateral pelvic lymphadenectomy.\n Each LNM was microscopically evaluated for the presence of ENE. The number of LNs removed, number of positive LNs, and LN density were recorded and calculated. Univariable and multivariable analyses addressed time to disease recurrence and cancer-specific mortality after RC.\n A total of 375 patients (50.1%) had ENE. The median number of LNs removed, number of positive LNs, and LN density were 15, 2, and 15, respectively. The rate of ENE increased with advancing pT stage (p<0.001). In multivariable Cox regression analyses that adjusted for the effects of established clinicopathologic features and LN parameters, ENE was associated with disease recurrence (hazard ratio [HR]: 1.89; 95% confidence interval [CI], 1.55-2.31; p<0.001) and cancer-specific mortality (HR: 1.90; 95% CI, 1.52-2.37; p<0.001). The addition of ENE to a multivariable model that included pT stage, tumor grade, age, gender, lymphovascular invasion, surgical margin status, LN density, number of LNs removed, number of positive LNs, and adjuvant chemotherapy improved predictive accuracy for disease recurrence and cancer-specific mortality from 70.3% to 77.8% (p<0.001) and from 71.8% to 77.8% (p=0.007), respectively. The main limitation of the study is its retrospective nature.\n ENE is an independent predictor of both cancer recurrence and cancer-specific mortality in RC patients with LNM. Knowledge of ENE status could help with patient counseling, clinical decision making regarding inclusion in clinical trials of adjuvant therapy, and tailored follow-up scheduling after RC.\n Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.\n\n\n"
},
{
"text": "\n125934\nScientific and logistical challenges in designing the CONTROL trial: recombinant factor VIIa in severe trauma patients with refractory bleeding.\n\nDutton, R\n\nHauser, C\n\nBoffard, K\n\nDimsitts, J\n\nBernard, G\n\nHolcomb, J\n\nLeppäniemi, A\n\nTortella, B\n\nBouillon, B\n\nCONTROL Steering Committee\n\nBeiträge in Fachzeitschriften\nISI:000271086500012\n19737846.0\n10.1177/1740774509344102\nNone\nBackground Clinical research in trauma patients poses multiple challenges in study design. These reflect the heterogeneity of injury and treatment, the paucity of acceptable study endpoints aside from mortality, and the difficulties inherent in obtaining informed consent in acutely ill populations. A current example of this problem is the study of recombinant factor VIIa (rFVIIa), which has attracted considerable interest as a systemic procoagulant agent for use in trauma patients with exsanguinating hemorrhage. Purpose To report on the implementation of an international trial - CONTROL intended to assess the efficacy and safety of rFVIIa in trauma, and discuss trauma research study design in light of this experience. Methods The CONTROL trial international steering committee confronted a number of barriers in the design of the CONTROL trial. They addressed methodologies for (1) standardizing entry criteria for trauma patients suffering inherently heterogeneous injuries, (2) obtaining informed consent in an acutely injured population with altered levels of consciousness, (3) avoiding futile care, while recruiting subjects with incompletely diagnosed injuries, (4) standardizing trauma intensive care across different investigating sites and countries, and (5) establishing study endpoints that were both clinically relevant and convincing to regulatory authorities. The resulting study methodology is reported. Results The CONTROL trial began active recruitment in October 2005, and was halted on June 11, 2008 because the observed mortality in the 576 enrolled patients was so far below expectations that the study would lack sufficient statistical power at the planned number of subjects to demonstrate a benefit. The utility of the endpoints selected for study will not be known until completion of data analysis. Limitations Any clinical trial in trauma patients must cope with the urgency of care required, issues of patient heterogeneity, standardization of care across multiple centers, and the difficulties of obtaining informed consent. Conclusion Research in acutely hemorrhaging trauma patients presents numerous scientific and ethical challenges. The methodology of the CONTROL study is presented as an example of how some of these challenges can be approached and managed, and of the pitfalls that may arise. Clinical Trials 2009; 6: 467-479. http://ctj.sagepub.com\n\nUranüs, Selman\n\n\n"
},
{
"text": "\n159927\nThe occurrence of single and multiple organ dysfunction in pediatric electrical versus other thermal burns.\n\nHundeshagen, G\n\nWurzer, P\n\nForbes, AA\n\nVoigt, CD\n\nCollins, VN\n\nCambiaso-Daniel, J\n\nFinnerty, CC\n\nHerndon, DN\n\nBranski, LK\n\nBeiträge in Fachzeitschriften\nISI:000400687400017\n28431417.0\n10.1097/TA.0000000000001356\nPMC5407303\nMultiple organ failure (MOF) is a major contributor to morbidity and mortality in burned children. While various complications induced by electrical injuries have been described, the incidence and severity of single organ failure (SOF) and MOF associated with this type of injury are unknown. The study was undertaken to compare the incidence and severity of SOF and MOF as well as other complications between electrically and thermally burned children.\n Between 2001 and 2016, 288 pediatric patients with electrical burns (EB; n = 96) or thermal burns (CTR; n = 192) were analyzed in this study. Demographic data; length of hospitalization; and number and type of operations, amputations, and complications were statistically analyzed. Incidence of SOF and MOF was assessed using the DENVER2 classification in an additive mixed model over time. Compound scores and organ-specific scores for lung, heart, kidney, and liver were analyzed. Serum cytokine expression profiles of both groups were also compared over time. Significance was accepted at p < 0.05.\n Both groups were comparable in age (CTR, 11 ± 5 years, vs EB, 11 ± 5 years), percent total body surface area burned (CTR, 33% ± 25%, vs EB, 32 ± 25%), and length of hospitalization (CTR, 18 ± 26 days, vs EB, 18 ± 21 days). The percentage of high-voltage injury in the EB group was 64%. The incidence of MOF was lower in the EB group (2 of 96 [2.1%]) than the CTR group (20 of 192 [10.4%]; p < 0.05). The incidence of single organ failure was comparable between groups. Incidence of pulmonary failure was comparable in both groups, but incidence of inhalation injury was significantly higher in the CTR group (p < 0.0001). Patients in the EB group had more amputations (p < 0.001), major amputations (p = 0.001), and combined major amputations (p < 0.01). Mortality was comparable between the groups. Serum cytokine expression profiles were also comparable between the groups.\n In pediatric patients, electrical injury is associated with a lower incidence of MOF than other thermal burns. Early and radical debridement of nonviable tissue is crucial to improve outcomes in the electrical burn patient population.\n Retrospective chart review, level III.\n\nBranski, Ludwik\n\nCambiaso Daniel, Janos\n\nWurzer, Paul\n\n\n"
},
{
"text": "\n168814\nEvaluation of the online-presence (homepages) of plastic-surgical departments in Germany, Austria and Switzerland].\n\nSmolle, C\n\nEylert, G\n\nKronberger, P\n\nMischitz, M\n\nKamolz, LP\n\nBeiträge in Fachzeitschriften\nISI:000442302300011\n30130833.0\n10.1055/a-0609-6527\nNone\nDuring the past decade, the share of households in the EU with internet access has increased from 55 % in 2007 to 85 % in 2016. During that time the internet has become the most commonly used tool for communication and information acquisition. In health-care the website of a department may be advantageous to inform patients adequately and stay in contact with them. The aim of this study was to evaluate the online-presence of plastic surgery departments in the DACH-area (Germany [Deutschland], Austria and Switzerland [Confoederatio Helvetica]).\n Homepages of plastic surgery departments in the DACH-area were identified and evaluated according to 40 different criteria from the five categories "general information", "information brokerage", "science and teaching", "information for patients and relatives" and "information on treatment". Additionally, all departments were searched for using the Google search engine and the rank in the list of search results was documented. The results from departments affiliated with a university and such without affiliation were compared using the t-test as well as the chi2-test.\n Of the 172 departments found, most were from Germany (77 %), followed by Switzerland (15 %) and Austria (8 %). As contact reference, a telephone number was given on all of the homepages and on 95 % of the websites the range of available treatments was elucidated. 95 % of the homepages were available in German, with only 22 % being available in English. At least seven and at max 34 of the 40 criteria were fulfilled. The three least commonly fulfilled criteria were information on first-aid measures in case of injury, information on possible waiting times and information on the number of intensive-care beds available to plastic surgery patients (all 4 %). The median Google-rank of the homepages was first. Departments affiliated to a university met 14 of the examination-criteria significantly more often than those without affiliation.\n The online-presence of plastic surgery department in the DACH-area can be summed up as sufficient. On average homepages of departments affiliated with a university conveyed more information. Nevertheless, information on first-aid measures in case of injuries and multilingual presentation need to be improved.\n © Georg Thieme Verlag KG Stuttgart · New York.\n\nKamolz, Lars-Peter\n\nSmolle, Christian\n\n\n"
},
{
"text": "\n186961\nHealth-related quality of life and stress-related post-transplant trajectories of lung transplant recipients: a three-year follow-up of the Swiss Transplant Cohort Study\n\nBleisch, B\n\nSchuurmans, MM\n\nKlaghofer, R\n\nBenden, C\n\nSeiler, A\n\nJenewein, J\n\nBeiträge in Fachzeitschriften\nISI:000462157300004\n30961347.0\n10.4414/smw.2019.20019\nNone\nLung transplantation (LTx) provides a viable option for the survival of end-stage lung diseases. Besides survival as a clinical outcome measure, health-related quality of life (HRQoL) and psychological distress have become important outcomes in studies investigating the effectiveness of LTx in the short- and long-term.\n To assess and compare HRQoL trajectories of patients after LTx prior to and over a follow-up period of three years post-transplant, and to identify differences regarding distress, HRQoL and patient-related outcomes.\n In this longitudinal study, 27 lung transplant recipients were prospectively examined for psychological distress (Symptom Checklist short version-9; SCL-K-9), health-related quality of life (EuroQOL five dimensions questionnaire; EQ-5D), depression (HADS-Depression scale), and socio-demographic and medical outcomes at two weeks, three months, six months and three years following LTx. Additionally, potential outcome-related predictors for LTx-outcomes at three years post-transplant were assessed. Data were collected in accordance with guidelines set by the STROBE (strengthening the reporting of observational studies in epidemiology) statement.\n Lung transplant recipients showed the most pronounced improvements in HRQoL and reduction in psychological distress between two weeks and three months post-transplant, with relative stable HRQoL and distress trajectories thereafter. The most important predictors of poor somatic health trajectories over time were the pre-transplant disease severity score and the pre-transplant HADS-Depression score. In addition, idiopathic pulmonary fibrosis (IPF) and pre-transplant extracorporeal membrane oxygenation (ECMO)-use predicted poorer survival, while cystic fibrosis was associated with better survival three years post-transplant.\n Lung transplantation yields significant survival and HRQoL benefits, with its peak improvement at three months post-transplant. The majority of patients can preserve these health changes in the long-term. Patients with a worse HRQoL and higher psychological distress at six months post-transplant tended to have a poorer survival post-transplant. Other risk factors for poorer survival included IPF, pre-transplant ECMO-use, pre-transplant symptoms of depression, high pre-transplant disease severity and worse somatic disease severity trajectories. The majority of LTx-recipients were unable to work due to illness-related reasons.\n\nJenewein, Josef\n\n\n"
},
{
"text": "\n187926\nProvision of critical care for the elderly in Europe: a retrospective comparison of national healthcare frameworks in intensive care units.\n\nWernly, B\n\nBeil, M\n\nBruno, RR\n\nBinnebössel, S\n\nKelm, M\n\nSigal, S\n\nvan Heerden, PV\n\nBoumendil, A\n\nArtigas, A\n\nCecconi, M\n\nMarsh, B\n\nMoreno, R\n\nOeyen, S\n\nBollen Pinto, B\n\nSzczeklik, W\n\nLeaver, S\n\nWalther, SM\n\nSchefold, JC\n\nJoannidis, M\n\nFjølner, J\n\nZafeiridis, T\n\nde Lange, D\n\nGuidet, B\n\nFlaatten, H\n\nJung, C\n\nVIP2 study group\n\nBeiträge in Fachzeitschriften\nNone\n34083342.0\n10.1136/bmjopen-2020-046909\nNone\nIn Europe, there is a distinction between two different healthcare organisation systems, the tax-based healthcare system (THS) and the social health insurance system (SHI). Our aim was to investigate whether the characteristics, treatment and mortality of older, critically ill patients in the intensive care unit (ICU) differed between THS and SHI.\n ICUs in 16 European countries.\n In total, 7817 critically ill older (≥80 years) patients were included in this study, 4941 in THS and 2876 in the SHI systems.\n We chose generalised estimation equations with robust standard errors to produce population average adjusted OR (aOR). We adjusted for patient-specific variables, health economic data, including gross domestic product (GDP) and human development index (HDI), and treatment strategies.\n In SHI systems, there were higher rates of frail patients (Clinical Frailty Scale>4; 46% vs 41%; p<0.001), longer length of ICU stays (90±162 vs 72±134 hours; p<0.001) and increased levels of organ support. The ICU mortality (aOR 1.50, 95% CI 1.09 to 2.06; p=0.01) was consistently higher in the SHI; however, the 30-day mortality (aOR 0.89, 95% CI 0.66 to 1.21; p=0.47) was similar between THS and SHI. In a sensitivity analysis stratifying for the health economic data, the 30-day mortality was higher in SHI, in low GDP per capita (aOR 2.17, 95% CI 1.42 to 3.58) and low HDI (aOR 1.22, 95% CI 1.64 to 2.20) settings.\n The 30-day mortality was similar in both systems. Patients in SHI were older, sicker and frailer at baseline, which could be interpreted as a sign for a more liberal admission policy in SHI. We believe that the observed trend towards ICU excess mortality in SHI results mainly from a more liberal admission policy and an increase in treatment limitations.\n NCT03134807 and NCT03370692.\n © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.\n\nEller, Philipp\n\n\n"
},
{
"text": "\n1824\nNitric oxide-dependent and -independent vascular hyporeactivity in mesenteric arteries of portal hypertensive rats.\n\nHeinemann, A\n\nWachter, CH\n\nHolzer, P\n\nFickert, P\n\nStauber, RE\n\nBeiträge in Fachzeitschriften\nISI:A1997XH10700027\n9222564.0\n10.1038/sj.bjp.0701220\nPMC1564775\n1. Increased production of nitric oxide (NO) has been suggested to underlie both the vascular hyporeactivity to vasoconstrictors and the splanchnic vasodilatation seen in portal hypertension. This study assessed the role of NO in the vasoconstrictor hyporeactivity of portal vein-ligated (PVL) rats in isolated and in situ perfused mesenteric arterial beds. 2. Isolated perfused mesenteric arteries of PVL rats were significantly less reactive to noradrenaline (NA), methoxamine (METH), arginine vasopressin (AVP) and endothelin-1 (ET-1) than those from sham-operated (Sham) rats. 3. Blockade of NO synthesis with NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) in isolated perfused mesenteric arteries from PVL rats restored the reactivity to bolus injections of AVP and ET-1, but had little effect on the hyporeactivity to NA or METH. Cyclo-oxygenase inhibition with indomethacin (5 microM) likewise did not restore reactivity to METH of isolated perfused mesenteric arteries of PVL rats. 4. The hyporeactivity to METH seen in isolated perfused mesenteric arteries from PVL rats was reduced by low concentrations of AVP (20 nM) or ET-1 (1 nM) which per se caused only a slight increase in perfusion pressure. When L-NAME (100 microM) was combined with AVP (20 nM) or ET-1 (1 nM), respectively, reactivity to METH of isolated perfused mesenteric arteries of PVL rats was restored to the level seen in Sham rats. These effects of AVP and ET-1 were not mimicked by precontracting the vessels with 5-hydroxytryptamine (5 microM). 5. The differential effects of L-NAME and AVP on the hyporesponsiveness to methoxamine and AVP were corroborated by experiments performed with the in situ perfused mesenteric vascular bed preparation. 6. These data indicate that both NO-dependent and NO-dependent mechanisms are involved in the vasoconstrictor hyporesponsiveness of mesenteric arteries from portal hypertensive rats. The hyporeactivity to AVP and ET-1 is mediated by NO whereas the reduced responsiveness to adrenoceptor agonists appears to be predominantly NO-independent AVP and ET-1, in addition, seem to inhibit the NO-independent mechanism of vascular hyporeactivity, since the hyporesponsiveness to METH was reduced in the presence of AVP or ET-1 and abolished by the combination of these peptides with L-NAME.\n\nFickert, Peter\n\nHeinemann, Akos\n\nHolzer, Peter\n\nStauber, Rudolf\n\n\n"
},
{
"text": "\n83881\nImmunoMax. A maximized immunohistochemical method for the retrieval and enhancement of hidden antigens.\n\nMerz, H\n\nMalisius, R\n\nMannweiler, S\n\nZhou, R\n\nHartmann, W\n\nOrscheschek, K\n\nMoubayed, P\n\nFeller, AC\n\nBeiträge in Fachzeitschriften\nISI:A1995RJ73000018\n7541493.0\nNone\nNone\nBACKGROUND: Since the introduction of mAb, immunohistochemistry has become an important tool in research and in surgical pathology. The most widely used fixative in routine histopathology is formaldehyde, and it has become the gold standard for morphologic tissue preservation. Although the molecular mechanism underlying the tissue fixation is not well understood, it has become clear that available immunoreactive Ag are progressively lost during the fixation process. For a long time, it was thought that formalin-sensitive Ag might be irreversibly destroyed during the fixation process. Although monoclonal anti-Ig Ab frequently worked inadequately, polyclonal anti-Ig Ab were shown to produce reproducible staining results. It thus appeared possible that most cellular Ag might not be irreversibly destroyed but only masked. EXPERIMENTAL DESIGN: Although some Ag may be retrieved under appropriate conditions, there might still be many for which available antigenic epitopes are still too sparse to be visualized, as observed for a large number of leukocyte differentiation Ag. One reliable approach to resolve this dilemma is the use of a combination of an optimized Ag retrieval system and a powerful immunohistochemical staining protocol introducing a biotin amplification step, in which signal amplification is accomplished by covalent deposition of biotin molecules. RESULTS: Cryostat and paraffin sections were stained with the avidin-biotin complex technique and, for comparison, with the new maximized immunohistochemical staining protocol, termed the ImmunoMax method. Each step was monitored to establish how effectively it enhanced the overall sensitivity. Although pretreatment with detergent, protease, a chaotropic substance, or microwave heating resulted in only moderately improved immunostaining, the biotinylated tyramine enhancement step proved to be the most efficient one, although the latter is not sufficient for many Ag when used without pretreatment steps. The combination of an Ag retrieval step with the biotinylated tyramine enhancement step resulted in a 100 to 10, 00-fold boost in sensitivity without loss of specificity. CONCLUSIONS: With the ImmunoMax method, defined Ag can be reproducibly detected in formalin-fixed, paraffin-embedded tissues, and the sensitivity of the method is tremendously enhanced. Moreover, it also allows many previously unreactive or unsatisfactorily reactive Ag to be detected, as shown here for IgD, IgM, and CD7 with the use of mAb.\n\nMannweiler, Sebastian\n\n\n"
}
]
}