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"text": "\n108242\nComputer assisted localization in endoscopic sinus surgery--state of the art? The Insta Trak system].\n\nLuxenberger, W\n\nKöle, W\n\nStammberger, H\n\nReittner, P\n\nBeiträge in Fachzeitschriften\nISI:000081315500005\n10439350.0\n10.1055/s-2007-996879\nNone\nImage-guided surgery is increasingly acknowledged as useful technology also for endoscopic sinus surgery. For many years our department has been involved in the development and testing of devices for image-guided endoscopic sinus surgery. Since January 1997 we have been testing the "Insta Trak" System, which is based on electromagnetic tracking and was especially designed for use in endoscopic sinus surgery.\n We tested practicability and accuracy of the system in a wide range of cases from standard sphenoethmoidectomies to tricky frontal sinus surgery, from endoscopic tumour surgery to endoscopic repair of CSF fistulas. System accuracy was assessed by means of visual landmarks which could be clearly identified endoscopically as well as via computer screen. Additionally we measured the time for setting up the system, total operating time and rating of the subjective surgeon's assessment of the system's usefulness in each particular case.\n We present the results according accuracy and practicability in 45 patients, who were operated on under computer-aided guidance. Our overall experience with the "Insta Trak" system was very positive. It was no longer the indeed promising, but still rather circumstantial and not always reliable technique we were used to. Operating the system was relatively easy and did not require excessive computer skills. We measured an average accuracy of 0.69 mm with a maximum deviation of 2 mm in a single test measurement. Incorrect use of the device, however, may significantly increase the possible weight of system errors.\n The system accuracy was high and "Insta Trak" proved to be practicable and efficient in daily clinical routine. Especially in complicated cases like revision surgery "Insta Trak" proved to be extremely helpful. Whether a system like "Insta Trak" will be definitely able to lower complication rates in FESS is still an open question. Certainly in the near future no such navigational device will become a substitute for the surgeon's understanding of anatomy. In our opinion and experience "Insta Trak" is a significant development in sinus surgery. However, one must be aware of the fact that it cannot be more than yet another and indeed helpful tool.\n\nLuxenberger, Wolfgang\n\n\n"
},
{
"text": "\n123994\nVisual field constriction in children with shunt-treated hydrocephalus.\n\nRudolph, D\n\nSterker, I\n\nGraefe, G\n\nTill, H\n\nUlrich, A\n\nGeyer, C\n\n\n\nBeiträge in Fachzeitschriften\nISI:000283473700015\n21039173.0\n10.3171/2010.8.PEDS1042\nNone\nObject. Many ophthalmological abnormalities are described in conjunction with hydrocephalus. The results of visual field diagnosis remain a matter of further discussion. The aim of this study was to investigate visual field deficits in children with shunt-treated hydrocephalus. Methods. All children over 6 years of age treated for hydrocephalus at the authors' institute between December 2007 and December 2008 were included in the study. The children underwent an ophthalmological investigation for strabismus and binocular function, ophthalmoscopy, visual acuity, and refraction. The special focus was the visual field diagnosis, which the authors established in all children with cognitive conditions. The investigation was made by using the Goldmann visual field examination (kinetic perimetry). Children with and without visual field defects were compared concerning age at the time of ophthalmological examination, genesis of hydrocephalus, and frontooccipital horn ratio measured on current CT or MR images. Results. Complete investigations were undertaken in 56 children (24 girls and 32 boys, mean age 15.1 years). The following orthoptic pathological entities were diagnosed: 29 children have a strabismus in 29 cases, 17 of these have an exotropia, 12 an esotropia, 4 children a hypotropia, 2 a hypertropia and 3 children a heterophoria. A nystagmus was found in 10 children. The ocular fundus investigation showed 13 children with an optic nerve atrophy. A visual field diagnosis was possible in 44 of the 56 patients and was incomplete in 12 patients with cognitive deficits or inadequate compliance. In 24 of 42 children there was a concentric visual field constriction between 10 degrees and 50 degrees out of the center. Children with visual field deficits were older than those with a normal visual field (p = 0.051). Nine of 10 children with postmenigitic hydrocephalus had a visual field defect (p = 0.025). In children with visual field defects the frontooccipital horn ratio was significantly higher (p = 0.013). Conclusions. The results suggest that children with shunt-treated hydrocephalus have a higher risk of having ophthalmological abnormalities. Visual field deficits are often a problem in these patients. A diagnostic visual field examination can complete the ophthalmological monitoring in patients with hydrocephalus, especially in patients with large ventricles. Children with postmeningitic hydrocephalus should be ophthalmologically monitored more frequently and intensively. (DOI: 10.3171/2010.8.PEDS1042)\n\nTill, Holger\n\n\n"
},
{
"text": "\n139955\nPathogenic ischemic stroke phenotypes in the NINDS-stroke genetics network.\n\nAy, H\n\nArsava, EM\n\nAndsberg, G\n\nBenner, T\n\nBrown, RD\n\nChapman, SN\n\nCole, JW\n\nDelavaran, H\n\nDichgans, M\n\nEngström, G\n\nGiralt-Steinhauer, E\n\nGrewal, RP\n\nGwinn, K\n\nJern, C\n\nJimenez-Conde, J\n\nJood, K\n\nKatsnelson, M\n\nKissela, B\n\nKittner, SJ\n\nKleindorfer, DO\n\nLabovitz, DL\n\nLanfranconi, S\n\nLee, JM\n\nLehm, M\n\nLemmens, R\n\nLevi, C\n\nLi, L\n\nLindgren, A\n\nMarkus, HS\n\nMcArdle, PF\n\nMelander, O\n\nNorrving, B\n\nPeddareddygari, LR\n\nPedersén, A\n\nPera, J\n\nRannikmäe, K\n\nRexrode, KM\n\nRhodes, D\n\nRich, SS\n\nRoquer, J\n\nRosand, J\n\nRothwell, PM\n\nRundek, T\n\nSacco, RL\n\nSchmidt, R\n\nSchürks, M\n\nSeiler, S\n\nSharma, P\n\nSlowik, A\n\nSudlow, C\n\nThijs, V\n\nWoodfield, R\n\nWorrall, BB\n\nMeschia, JF\n\nBeiträge in Fachzeitschriften\nISI:000345516600249\n25378430.0\n10.1161/STROKEAHA.114.007362\nPMC4286169\nNINDS (National Institute of Neurological Disorders and Stroke)-SiGN (Stroke Genetics Network) is an international consortium of ischemic stroke studies that aims to generate high-quality phenotype data to identify the genetic basis of pathogenic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium.\n Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major pathogenic groups without weighting toward the most likely cause) and causative ischemic stroke subtypes in 16 954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded readjudication of 1509 randomly selected cases.\n The distribution of pathogenic categories varied by study, age, sex, and race (P<0.001 for each). Overall, only 40% to 54% of cases with a given major ischemic stroke pathogenesis (phenotypic subtype) were classified into the same final causative category with high confidence. There was good agreement for both causative (κ 0.72; 95% confidence interval, 0.69-0.75) and phenotypic classifications (κ 0.73; 95% confidence interval, 0.70-0.75).\n This study demonstrates that pathogenic subtypes can be determined with good reliability in studies that include investigators with different expertise and background, institutions with different stroke evaluation protocols and geographic location, and patient populations with different epidemiological characteristics. The discordance between phenotypic and causative stroke subtypes highlights the fact that the presence of an abnormality in a patient with stroke does not necessarily mean that it is the cause of stroke.\n © 2014 American Heart Association, Inc.\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n143477\nThe significance of pretreatment anemia in the era of R-IPI and NCCN-IPI prognostic risk assessment tools: a dual-center study in diffuse large B-cell lymphoma patients.\n\nTroppan, KT\n\nMelchardt, T\n\nDeutsch, A\n\nSchlick, K\n\nStojakovic, T\n\nBullock, MD\n\nReitz, D\n\nBeham-Schmid, C\n\nWeiss, L\n\nNeureiter, D\n\nWenzl, K\n\nGreil, R\n\nNeumeister, P\n\nEgle, A\n\nPichler, M\n\nBeiträge in Fachzeitschriften\nISI:000367920300008\n25677782.0\n10.1111/ejh.12529\nNone\nAnemia is frequently identified at the time of diagnosis in patients with diffuse large B-cell lymphoma (DLBCL); however, studies addressing the prognostic significance of this important clinical parameter are lacking.\n In this dual-center study of patients with DLBCL (n = 556) treated with rituximab-containing regimens, we evaluated the prognostic relevance of anemia at diagnosis in a training set (n = 211) and validated our findings in a second independent patient cohort (n = 345). Using Kaplan-Meier curves as well as univariate and multivariate Cox regression models, we analyzed the impact of anemia on 5-year overall survival (OS) and 5-year disease-free survival (DFS) alongside established prognostic indicators including age, tumor stage, the revised International Prognostic Index (R-IPI), and the recently published NCCN-IPI. The influence of anemia on the predictive accuracy of IPI, R-IPI, and NCCN-IPI prognosis scores was subsequently determined using the Harrell's concordance index.\n Anemia was an independent predictor of impaired OS and DFS at 5 years in both DLBCL patient cohorts (P < 0.001, log-rank test). In multivariate analysis, hemoglobin level was also a strong and independent prognostic indicator in patients stratified according to R-IPI or NCCN-IPI score. In survival analysis, the estimated concordance index, using IPI, R-IPI, and NCCN-IPI stratification measures (0.69, 0.64, and 0.70, respectively), improved to 0.70, 0.68, and 0.73, respectively, when anemia was also considered.\n In this study, we have demonstrated that anemia at the time of diagnosis is an independent predictor of impaired clinical outcome in DLBCL. Furthermore, consideration of hemoglobin levels may improve the accuracy of recently established prognostic tools in lymphoma. Our data encourage further evaluation of the prognostic utility of this readily accessible biological parameter in prospective clinical trials.\n © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.\n\nBeham-Schmid, Christine\n\nDeutsch, Alexander\n\nNeumeister, Peter\n\nPichler, Martin\n\n\n"
},
{
"text": "\n144780\nStudy protocol of REGOSARC trial: activity and safety of regorafenib in advanced soft tissue sarcoma: a multinational, randomized, placebo-controlled, phase II trial.\n\nBrodowicz, T\n\nLiegl-Atzwager, B\n\nTresch, E\n\nTaieb, S\n\nKramar, A\n\nGruenwald, V\n\nVanseymortier, M\n\nClisant, S\n\nBlay, JY\n\nLe Cesne, A\n\nPenel, N\n\nBeiträge in Fachzeitschriften\nISI:000351337800001\n25884155.0\n10.1186/s12885-015-1143-y\nPMC4369830\nAngiogenesis, among other signaling pathways, plays a key-role in sarcoma biology. Regorafenib (RE) has recently been shown to be effective in imatinib and sunitinib-refractory GIST in a phase III trial.\n We are conducting an international trial (France, Austria and Germany) consisting in 4 parallel double-blind placebo-controlled randomized (1/1) phase II trials to assess the activity and safety of RE in doxorubicin-refractory STS (ClinicalTrials.gov: NCT01900743). Each phase II trial is dedicated to one of the 4 following histological subgroups: liposarcoma, leiomyosarcoma, synovial sarcoma and other sarcoma. Within each randomized trial the following stratification factors will be applied: countries and prior exposure to pazopanib. Key-eligibility criteria are: measurable disease, age ≥18, not > 3 previous systemic treatment lines for metastatic disease, metastatic disease not amenable to surgical resection. The primary endpoint is progression-free survival (PFS) according to central radiological review. Secondary endpoints are: Toxicity (NCI-CTC AE V4.0); time to progression; Growth modulation index in pts receiving RE after randomization; 3 and 6 months PFS-Rates, best response rate and overall survival. Each phase II trial will be separately analyzed. In 3 trials, statistical assumptions are: PFS0 = 1.6 & PFS1 = 4.6 months; 1-sided α = 0.1; β = 0.05 with a total sample size of 192 pts. To take into account the rarity of synovial sarcoma, the statistical assumptions are: PFS0 = 1.6 & PFS1 = 4.6 months; 1-sided α = 0.1; β = 0.2 Tumor assessment is done monthly during the 4 first months, and every 3 months thereafter. After central radiological confirmation of tumor progression, an optional open-label option is offered to eligible patients.\n The design of this trial allows an assessment of regorafenib activity over placebo in four sarcoma strata and might provide evidence for launching a phase III trial. This study includes both integrative and exploratory translational research program. The study is enrolling since June 2013 (TRIAL REGISTRATION NUMBER: EudraCT N°: 2012-005743-24, on the 15(th) February 2012).\n\nLiegl-Atzwanger, Bernadette\n\n\n"
},
{
"text": "\n151440\nDaclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection.\n\nFontana, RJ\n\nBrown, RS\n\nMoreno-Zamora, A\n\nPrieto, M\n\nJoshi, S\n\nLondoño, MC\n\nHerzer, K\n\nChacko, KR\n\nStauber, RE\n\nKnop, V\n\nJafri, SM\n\nCastells, L\n\nFerenci, P\n\nTorti, C\n\nDurand, CM\n\nLoiacono, L\n\nLionetti, R\n\nBahirwani, R\n\nWeiland, O\n\nMubarak, A\n\nElSharkawy, AM\n\nStadler, B\n\nMontalbano, M\n\nBerg, C\n\nPellicelli, AM\n\nStenmark, S\n\nVekeman, F\n\nIonescu-Ittu, R\n\nEmond, B\n\nReddy, KR\n\nBeiträge in Fachzeitschriften\nISI:000373566800008\n26890629.0\n10.1002/lt.24416\nNone\nDaclatasvir (DCV) is a potent, pangenotypic nonstructural protein 5A inhibitor with demonstrated antiviral efficacy when combined with sofosbuvir (SOF) or simeprevir (SMV) with or without ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection. Herein, we report efficacy and safety data for DCV-based all-oral antiviral therapy in liver transplantation (LT) recipients with severe recurrent HCV. DCV at 60 mg/day was administered for up to 24 weeks as part of a compassionate use protocol. The study included 97 LT recipients with a mean age of 59.3 ± 8.2 years; 93% had genotype 1 HCV and 31% had biopsy-proven cirrhosis between the time of LT and the initiation of DCV. The mean Model for End-Stage Liver Disease (MELD) score was 13.0 ± 6.0, and the proportion with Child-Turcotte-Pugh (CTP) A/B/C was 51%/31%/12%, respectively. Mean HCV RNA at DCV initiation was 14.3 × 6 log10 IU/mL, and 37% had severe cholestatic HCV infection. Antiviral regimens were selected by the local investigator and included DCV+SOF (n = 77), DCV+SMV (n = 18), and DCV+SMV+SOF (n = 2); 35% overall received RBV. At the end of treatment (EOT) and 12 weeks after EOT, 88 (91%) and 84 (87%) patients, respectively, were HCV RNA negative or had levels <43 IU/mL. CTP and MELD scores significantly improved between DCV-based treatment initiation and last contact. Three virological breakthroughs and 2 relapses occurred in patients treated with DCV+SMV with or without RBV. None of the 8 patient deaths (6 during and 2 after therapy) were attributed to therapy. In conclusion, DCV-based all-oral antiviral therapy was well tolerated and resulted in a high sustained virological response in LT recipients with severe recurrent HCV infection. Most treated patients experienced stabilization or improvement in their clinical status.\n © 2016 American Association for the Study of Liver Diseases.\n\nStauber, Rudolf\n\n\n"
},
{
"text": "\n174591\nIncreasing access to integrated ESKD care as part of universal health coverage.\n\nHarris, DCH\n\nDavies, SJ\n\nFinkelstein, FO\n\nJha, V\n\nDonner, JA\n\nAbraham, G\n\nBello, AK\n\nCaskey, FJ\n\nGarcia, GG\n\nHarden, P\n\nHemmelgarn, B\n\nJohnson, DW\n\nLevin, NW\n\nLuyckx, VA\n\nMartin, DE\n\nMcCulloch, MI\n\nMoosa, MR\n\nO'Connell, PJ\n\nOkpechi, IG\n\nPecoits Filho, R\n\nShah, KD\n\nSola, L\n\nSwanepoel, C\n\nTonelli, M\n\nTwahir, A\n\nvan Biesen, W\n\nVarghese, C\n\nYang, CW\n\nZuniga, C\n\nWorking Groups of the International Society of Nephrology’s 2nd Global Kidney Health Summit\n\nBeiträge in Fachzeitschriften\nISI:000461917600001\n30904051.0\n10.1016/j.kint.2018.12.005\nNone\nThe global nephrology community recognizes the need for a cohesive strategy to address the growing problem of end-stage kidney disease (ESKD). In March 2018, the International Society of Nephrology hosted a summit on integrated ESKD care, including 92 individuals from around the globe with diverse expertise and professional backgrounds. The attendees were from 41 countries, including 16 participants from 11 low- and lower-middle-income countries. The purpose was to develop a strategic plan to improve worldwide access to integrated ESKD care, by identifying and prioritizing key activities across 8 themes: (i) estimates of ESKD burden and treatment coverage, (ii) advocacy, (iii) education and training/workforce, (iv) financing/funding models, (v) ethics, (vi) dialysis, (vii) transplantation, and (viii) conservative care. Action plans with prioritized lists of goals, activities, and key deliverables, and an overarching performance framework were developed for each theme. Examples of these key deliverables include improved data availability, integration of core registry measures and analysis to inform development of health care policy; a framework for advocacy; improved and continued stakeholder engagement; improved workforce training; equitable, efficient, and cost-effective funding models; greater understanding and greater application of ethical principles in practice and policy; definition and application of standards for safe and sustainable dialysis treatment and a set of measurable quality parameters; and integration of dialysis, transplantation, and comprehensive conservative care as ESKD treatment options within the context of overall health priorities. Intended users of the action plans include clinicians, patients and their families, scientists, industry partners, government decision makers, and advocacy organizations. Implementation of this integrated and comprehensive plan is intended to improve quality and access to care and thereby reduce serious health-related suffering of adults and children affected by ESKD worldwide.\n Copyright © 2019 International Society of Nephrology. All rights reserved.\n\nSchneditz, Daniel\n\n\n"
},
{
"text": "\n176363\nUsing body mass index ignores the intensive training of elite special force personnel.\n\nTafeit, E\n\nCvirn, G\n\nLamprecht, M\n\nHohensinn, M\n\nMoeller, R\n\nHamlin, M\n\nHorejsi, R\n\nBeiträge in Fachzeitschriften\nISI:000480264200003\n31084214.0\n10.1177/1535370219848986\nPMC6690141\nBody mass index is a common and well-known measure in daily life. A body mass index higher than 25 is assumed to be an indicator for overweight and obesity and a high amount of total body fat. But body mass index overestimates body fat in subjects with high muscle mass and underestimates it in persons with a low lean body mass, especially in elderly and diseased persons. In the present study, we investigate the performance of the body mass index as a measure of body fatness and its ability to distinguish between well-trained and untrained subjects. Twenty-one well-trained male members of a police task force named "Cobra" and 38 non-active controls, matched by age, weight and height were participants of the study. The age range of these subjects was between 30 and 45 years. Subcutaneous adipose tissue thicknesses and body fat distributions were measured non-invasively by an optical device named the "Lipometer." Statistics were performed with SPSS. We found that the body mass index did not show a difference between the two groups, whereas all Lipometer results were able to discriminate significantly between the trained and untrained subjects. Furthermore, the receiver operating characteristic curve analysis was calculated and all Lipometer measurements provided significant results up to a correct classification of all subjects of 86.4%, which was for the lateral thigh body site. In conclusion, the body mass index was not able to recognize the difference between trained and untrained participants, while body fat distribution measured with the Lipometer was able to distinguish more clearly the large body fat differences between these two groups. Impact statement Body mass index (BMI) is a common measure of body fatness but overestimates body fat in subjects with high muscle mass. We have developed previously a device named "Lipometer, an alternative way to measure body fatness. We show herein that the Lipometer is able to distinguish more clearly (than the BMI) the large body fat differences between well-trained and untrained subjects. Thus, the Lipometer is superior to BMI with respect to body fat measurements.\n\nCvirn, Gerhard\n\nHorejsi, Renate\n\nTafeit, Erwin\n\n\n"
},
{
"text": "\n181637\nMulticentre, non-interventional study of the efficacy and tolerability of linaclotide in the treatment of irritable bowel syndrome with constipation in primary, secondary and tertiary centres: the Alpine study.\n\nPohl, D\n\nFried, M\n\nLawrance, D\n\nBeck, E\n\nHammer, HF\n\nBeiträge in Fachzeitschriften\nISI:000512773400004\n31892640.0\n10.1136/bmjopen-2018-025627\nPMC6955540\nWe evaluated the effectiveness and tolerability of linaclotide, a minimally absorbed guanylate cyclase-C agonist, in patients with irritable bowel syndrome with constipation (IBS-C) in routine clinical practice.\n A multicentre, non-interventional study conducted between December 2013 and November 2015 across 31 primary, secondary and tertiary centres in Austria and Switzerland.\n The study enrolled 138 patients aged ≥18 years with moderate-to-severe IBS-C. Treatment decision was at the physician's discretion. Patients with known hypersensitivity to the study drug or suspected mechanical obstruction were excluded. The mean age of participants was 50 years, and >75% of the patients were women. 128 patients completed the study.\n Data were collected at weeks 0 and 4 in Austria and weeks 0, 4 and 16 in Switzerland. The primary effectiveness endpoints included severity of abdominal pain and bloating (11-point numerical rating scale [0=no pain/bloating to 10=worst possible pain/bloating]), frequency of bowel movements and physicians' global effectiveness of linaclotide. Treatment-related adverse events (AEs) were recorded.\n Following a 4-week treatment period, the mean intensity score of abdominal pain was reduced from 5.8 at baseline to 2.7, while the bloating intensity score was reduced from 5.8 at baseline to 3.1e (both indices p<0.001). The frequency of mean weekly bowel movements increased from 2.1 at baseline to 4.5 at week 4 (p<0.001). Global effectiveness and tolerability of linaclotide were assessed by the treating physicians as 'good' or 'excellent' in >70% of patients. In total, 31 AEs were reported in 22 patients, the most common being diarrhoea, reported by 6 (7%) and 8 (15.4%) patients in Austria and Switzerland, respectively.\n Patients with IBS-C receiving linaclotide experienced effective treatment of moderate-to-severe symptoms in routine clinical practice. Linaclotide was safe and well tolerated and no new safety concerns were raised, supporting results from previous clinical trials.\n © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.\n\nHammer, Heinz\n\n\n"
},
{
"text": "\n183400\nExercise Pulmonary Resistances Predict Long-Term Survival in Systemic Sclerosis.\n\nZeder, K\n\nAvian, A\n\nBachmaier, G\n\nDouschan, P\n\nForis, V\n\nSassmann, T\n\nMoazedi-Fuerst, FC\n\nGraninger, WB\n\nHafner, F\n\nBrodmann, M\n\nSalmhofer, W\n\nOlschewski, H\n\nKovacs, G\n\nBeiträge in Fachzeitschriften\nISI:000632441600055\n32931822.0\n10.1016/j.chest.2020.08.2110\nNone\nPulmonary hemodynamics during exercise may reveal early pulmonary vascular disease and may be of clinical and prognostic relevance in systemic sclerosis (SSc). We aimed to assess the prognostic relevance of exercise pulmonary resistances in patients with SSc with no or mildly increased mean pulmonary arterial pressure (mPAP).\n Are pulmonary resistances at peak exercise independent predictors of mortality in systemic sclerosis?\n All SSc patients with resting mPAP < 25 mm Hg and at least one year of follow-up data who underwent symptom-limited exercise right heart catheterization between April 2005 and December 2018 were analyzed retrospectively. Age-adjusted Cox regression analysis was used to evaluate the association between pulmonary resistances and all-cause mortality.\n The cohort consisted of 80 patients: 73 women and 7 men with a mean age of 57 years (interquartile range [IQR], 47-67 years) and a mean follow-up time of 10.4 years (IQR, 8.5-11.8 years). At baseline, resting mPAP of ≤ 20 mm Hg and 21 to 24 mm Hg was found in 68 and 12 patients, respectively. Pulmonary vascular resistance (PVR) and total pulmonary resistance (TPR) at peak exercise were associated significantly with mortality (P = .006 [hazard ratio (HR), 2.20; 95% CI, 1.26-3.87] and P = .026 [HR, 1.56; 95% CI, 1.06-2.29]), whereas resting PVR and TPR were not (P = .087 [HR, 2.27; 95% CI, 0.89-5.83] and P = .079 [HR, 1.88; 95% CI, 0.93-3.80]). The mPAP per cardiac output (CO) and transpulmonary gradient (TPG) per CO slopes were associated significantly with mortality (P = .047 [HR, 1.14; 95% CI, 1.002-1.286] and P = .034 [HR, 1.34; 95% CI, 1.02-1.76]) as well. The area under the receiver operating characteristic curve for exercise PVR to predict 10-year mortality was 0.917 (95% CI, 0.797-1.000).\n PVR and TPR at peak exercise, mPAP/CO slope, and TPG/CO slope are predictors of age-adjusted long-term mortality in SSc patients with no or mildly increased pulmonary arterial pressure.\n Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.\n\nAvian, Alexander\n\nBachmaier, Gerhard\n\nBrodmann, Marianne\n\nDouschan, Philipp\n\nForis, Vasile\n\nGraninger, Winfried\n\nHafner, Franz\n\nKovacs, Gabor\n\nMoazedi-Fürst, Florentine\n\nOlschewski, Horst\n\nSalmhofer, Wolfgang\n\nSassmann, Teresa\n\nZeder, Katarina Eleonora\n\n\n"
},
{
"text": "\n183619\nThe Elevated Pre-Treatment C-Reactive Protein Predicts Poor Prognosis in Patients with Locally Advanced Rectal Cancer Treated with Neo-Adjuvant Radiochemotherapy.\n\nPartl, R\n\nLukasiak, K\n\nThurner, EM\n\nRenner, W\n\nStranzl-Lawatsch, H\n\nLangsenlehner, T\n\nBeiträge in Fachzeitschriften\nISI:000586829800001\n33023215.0\n10.3390/diagnostics10100780\nPMC7601888\nThe aim of the present study was to investigate the association of the pre-treatment C-reactive protein (CRP) plasma level with survival outcomes in a cohort of 423 consecutive patients with locally advanced rectal cancer treated with neo-adjuvant radiochemotherapy followed by surgical resection. To evaluate the prognostic value of the CRP level for clinical endpoints recurrence-free survival (RFS), local-regional control (LC), metastases-free survival (MFS), and overall survival (OS), uni- and multivariate Cox regression analyses were applied, and survival rates were calculated using Kaplan-Meier analysis. The median follow-up time was 73 months. In univariate analyses, the pre-treatment CRP level was a significant predictor of RFS (hazard ratio (HR) 1.015, 95% CI 1.006-1.023; p < 0.001), LC (HR 1.015, 95% CI 1.004-1.027; p = 0.009), MFS (HR 1.014, 95% CI 1.004-1.023; p = 0.004), and OS (HR 1.016, 95% CI 1.007-1.024; p < 0.001). Additionally, univariate analysis identified the MRI circumferential resection margin (mrCRM) and pre-treatment carcinoembryonic antigen (CEA) as significant predictor of RFS (HR 2.082, 95% CI 1.106-3.919; p = 0.023 and HR 1.005, 95% CI 1.002-1.008; p < 0.001). Univariate analysis also revealed a significant association of the mrCRM (HR 2.089, 95% CI 1.052-4.147; p = 0.035) and CEA (HR 1.006, 95% CI 1.003-1.008; p < 0.001) with MFS. Age and CEA were prognostic factors for OS (HR 1.039, 95% CI 1.013-1.066; p = 0.003 and HR 1.005, 95% CI 1.002-1.008; p < 0.001). In multivariate analysis that included parameters with a p-level < 0.20 in univariate analysis, the pre-treatment CRP remained a significant prognostic factor for RFS (HR 1.013, 95%CI 1.001-1.025; p = 0.036), LC (HR 1.014, 95% CI 1.001-1.027; p = 0.031), and MFS (HR 1.013, 95% CI 1.000-1.027; p = 0.046). The results support the hypothesis that an elevated pre-treatment CRP level is a predictor of poor outcome. If confirmed by additional studies, this easily measurable biomarker could contribute to the identification of patients who might be candidates for more aggressive local or systemic treatment approaches or the administration of anti-inflammatory drugs.\n\nLangsenlehner, Tanja\n\nLukasiak, Katarzyna\n\nPartl, Richard\n\nRenner, Wilfried\n\nStranzl-Lawatsch, Heidi\n\n\n"
},
{
"text": "\n184807\nModelling the effect of a dedicated hip fracture unit on patient outcomes using segmented robust linear regression techniques.\n\nValsamis, EM\n\nHusband, H\n\nBurchette, D\n\nMilošević, M\n\nBakota, B\n\nBeiträge in Fachzeitschriften\nNone\n32423783.0\n10.1016/j.injury.2020.03.056\nNone\nTypically, a healthcare intervention is evaluated by comparing data before and after its implementation using statistical tests. Comparing group means can miss underlying trends and lead to erroneous conclusions. Segmented linear regression can be used to reveal secular trends but is susceptible to outliers. We described a novel method using segmented robust regression techniques to evaluate the effect of introducing a dedicated hip fracture unit (HFU).\n We retrospectively analysed patient outcomes from a total of 2777 patients sustaining proximal femoral fragility fractures over a 6-year period at a Level 1 Major Trauma Centre. We compared time to surgical intervention and length of hospital stay before and after the implementation of the HFU using group comparison tests, segmented ordinary regression and robust regression techniques to evaluate the effect of the intervention.\n Group comparison tests did not identify a significant difference in time to surgery pre and post- HFU. Segmented regression revealed that there was a significant reduction in time to surgery but that this predated the introduction of the HFU. Group comparison tests did not identify a significant difference in length of stay pre and post-HFU. Ordinary segmented regression demonstrated that there was a constant reduction in length of stay, which accelerated after the introduction of the HFU. Robust regression identified that this change occurred prior to the HFU.\n There was a significant decrease in time to surgical intervention during the study period that occurred long before the introduction of the HFU, and that cannot be attributed to the HFU itself. Length of stay started dropping early in the study period and was unrelated to the HFU. However, with robust regression we concluded that the HFU was effective in reducing relatively long hospital stays (outliers). Several explanatory factors that may have affected the observed trends in time to surgery and length of stay were identified.\n Robust regression is a useful adjunct to ordinary segmented linear regression techniques in modelling retrospective time-series and dealing with outliers. The changes observed in hip fracture patient outcomes over a 6-year period was likely multifactorial.\n Copyright © 2020 Elsevier Ltd. All rights reserved.\n\n\n"
},
{
"text": "\n2333\nSerum antibodies against the heat shock protein 60 are elevated in patients with osteosarcoma.\n\nTrieb, K\n\nGerth, R\n\nWindhager, R\n\nGrohs, JG\n\nHolzer, G\n\nBerger, P\n\nKotz, R\n\nBeiträge in Fachzeitschriften\nISI:000085325400008\n10776793.0\n10.1016/S0171-2985(00)80091-1\nNone\nOsteosarcoma is the most frequent malignant bone tumor, mainly occurring in the second and third decade of life. Diagnosis is limited to clinical symptoms, radiology and histology, but so far no diagnostic laboratory tests are available. Heat shock proteins (hsp), highly conserved proteins performing vital intracellular chaperoning functions and preventing cells from death, have been shown to be involved in tumor immunity. We analyzed 75 sera from 23 patients with high-grade osteosarcoma, 8 patients with chondrosarcoma, 10 patients with Ewing's sarcoma, 5 patients with soft tissue sarcoma, 11 patients with benign bone tumors at the time of diagnosis and from 18 healthy controls with an indirect one-site enzyme linked immunosorbent assay (ELISA) for the presence of anti-hsp60 and 70 antibodies. In these assays 10/23 osteosarcoma patients (43%) had anti-hsp60 antibodies with a mean +/- S.D. titer of 0.382 +/- 0.243 U/ml. Only one of the 18 healthy controls (1/18, 5.6%; titer 0.22 U/ml), two of the Ewing's sarcoma patients (2/10, 20%; titer 0.2 +/- 0.09 U/ml), two of the patients with a benign bone tumor (2/11, 18%; titer 0.22 +/- 0.16 U/ml) and one of the chondrosarcoma patients (1/8, 12.5%; titer 0.14 U/ml) were positive, whereas all others, including all soft tissue sarcomas were negative throughout. Anti-hsp60 antibodies in patients with osteosarcoma are therefore significantly increased (p < 0.05). 19/23 (83%) of osteosarcoma biopsy specimens expressed hsp60 immunohistochemically and all specimens from patients with a positive anti-hsp60 serum titer expressed hsp60. The level of the anti-hsp60 antibodies did not correlate with clinical parameters such as response to preoperative chemotherapy, duration of symptoms, age, gender, tumor size, serum alkaline-phosphatase levels and metastases. Although no difference in anti-hsp70 antibodies could be observed between sera from patients and healthy controls, a positive correlation was found for the presence of anti-hsp70 serum antibodies and lung metastases at the time of diagnosis in osteosarcoma patients. These data suggest an increase of anti-hsp60 antibodies at the time of first diagnosis of osteosarcoma. These findings should therefore give rise to further investigations on a group of new markers for the diagnosis of osteosarcoma.\n\n\n"
},
{
"text": "\n3282\nHigh mutation frequency at Ha-ras exons 1-4 in squamous cell carcinomas from PUVA-treated psoriasis patients.\n\nKreimer-Erlacher, H\n\nSeidl, H\n\nBäck, B\n\nKerl, H\n\nWolf, P\n\nBeiträge in Fachzeitschriften\nISI:000170619600030\n11547572.0\n10.1562%2F0031-8655%282001%29074%3C0323%3AHMFAHR%3E2.0.CO%3B2\nNone\nClinical follow-up studies have revealed that PUVA-treated patients are at increased risk of skin cancer, particularly squamous cell carcinoma (SCC). However, since psoralen and UVA (PUVA) is not only a potent mutagen and carcinogen but also an immunosuppressor, and since other (co)carcinogenic factors often exist in psoriasis patients, the exact causes and mechanisms of PUVA-associated SCC are still not completely understood. In order to fill this gap the tools of molecular epidemiology are being used to study the SCC mutational spectra of p53 and Ha-ras, two of the most commonly mutated genes in human cancers. A previous mutation analysis revealed that SCC in PUVA-treated patients often carried mutated p53 genes and that many of the mutations had the UV fingerprint (i.e. C-->T or CC-->TT transitions at dipyrimidine sites). In the present study DNA-sequencing analysis revealed a total of 18 Ha-ras missense or nonsense mutations at exons 1-4 in 13 of 17 SCC (76%) from 8 of 11 (73%) PUVA-treated psoriasis patients. Six of the 18 mutations (33%) were of UV-fingerprint type (C-->T transitions), five (28%) were at 5'-TpG sites (i.e. potential psoralen-binding sites and thus potentially caused by PUVA) and seven were of other type (39%), including six G:C-->T:A transversions at hotspot codon 12. In addition, in the case of 6 of the 11 subjects (55%) both tumor and normal skin samples contained a T:A-->C:G base change at codon 27 (a 5'-ATT site), a change previously hypothesized to be a possible silent Ha-ras polymorphism at one allele. When we compared the present Ha-ras mutation spectrum with the p53 mutation spectrum from a previous study of the samples, we found that approximately half of the tumors harbored mutations in both Ha-ras and p53. Together, our results indicate that Ha-ras mutations are present in a large proportion of PUVA-associated SCC and that UVB, PUVA and other agents may induce Ha-ras mutations and act together with p53 in the formation of SCC in psoriasis patients.\n\nKerl, Helmut\n\nWolf, Peter\n\n\n"
},
{
"text": "\n43824\nStress fractures in the juvenile skeletal system.\n\nNiemeyer, P\n\nWeinberg, A\n\nSchmitt, H\n\nKreuz, PC\n\nEvverbeck, V\n\nKasten, P\n\nBeiträge in Fachzeitschriften\nISI:000235902600013\n16541382.0\n10.1055/s-2005-865649\nNone\nStress fractures affecting the juvenile skeletal system are rare and are described as having a good prognosis. Precisely because these fractures are so rare, studies allowing clear and generally applicable conclusions are lacking. The object of the present study was a systematic analysis of patients with stress fractures in an immature skeletal system, with special reference to the frequently difficult and delayed diagnosis and to the forms of therapy considered appropriate. Twenty-five patients with a total of 27 stress fractures affecting bones with the growth plates still open were examined according to a standardized procedure. The average duration of follow-up was 4.8 years (SD +/- 2.3) and the average age at occurrence 12.9 years (SD +/- 4.31). The risk factors were largely the same as those in adults. The most frequent site was the tibia (48% of cases; n = 13), followed by the metatarsal bones. Most (26/27) fractures were treated conservatively, with an average duration of therapy of 8.9 weeks (SD 8.2 weeks). Ultimately, 17 (63%) of the fractures healed in such a way as to allow the patients to return to full athletic activity with no restrictions within 3 months after diagnosis. In 9 cases (33%) it was not possible to achieve complete absence of symptoms within 12 months after diagnosis was made. No pseudarthroses were observed. There was a significant correlation between clinical outcome recorded as "free of symptoms" and an early diagnosis (less than 2 weeks after first symptoms (p = 0.033) and a fracture line seen on MR tomography in contrast to a stress reaction with merely increased signal intensity (p = 0.037). Overall, a strikingly high proportion of these patients had a prolonged course. This is attributable partly to the delay in diagnosis and to inappropriate initial treatment. When stress fractures were recognizable by a demonstrable fracture line--in contrast to just an edema--on MR tomography and their diagnosis was followed by an adequate form of therapy the chances of complete healing seemed to be better. It is essential to carry out targeted imaging investigations, e.g., by means of MR tomography, when there is a reason to consider a stress reaction. Furthermore, stress fractures should be adequately treated until all symptoms have disappeared.\n\nWeinberg, Annelie-Martina\n\n\n"
},
{
"text": "\n72092\nEffects of physicochemical agents on murine epidermal Langerhans cells and Thy-1-positive dendritic epidermal cells.\n\nAberer, W\n\nRomani, N\n\nElbe, A\n\nStingl, G\n\nBeiträge in Fachzeitschriften\nISI:A1986AZD4900011\n2868057.0\nNone\nNone\nThe possibility that Thy-1-positive dendritic epidermal cells (Thy-1+DEC) may contribute to the immunologic functions of murine epidermal cells (EC) prompted us to simultaneously assess the effects of certain immunomodulating physicochemical agents on both Thy-1+DEC and Ia-bearing Langerhans cells (LC). C3H/He mice received one of the following treatment modalities: UV-B irradiation (four consecutive days); psoralen plus UV-A (PUVA; three times a week for three consecutive weeks); topically and systemically applied glucocorticosteroids (GCS). Beginning 2 days after the last treatment, animals were sacrificed and the structure and surface marker expression of Ia+EC and Thy-1+DEC were assessed by immunohistologic means on epidermal sheet preparations from ear skin by using appropriate monoclonal antibodies. Whereas low-dose UV-B irradiation (4 X 100 or 200 J/m2) had little, if any, effect on either Ia+EC or Thy-1+DEC, high-dose UV-B (4 X 700 or 1000 J/m2) or PUVA treatment led to an almost complete disappearance of both surface characteristics. Immunoelectron microscopic studies revealed that in the case of LC, high-dose UV-B or PUVA treatment results in the disappearance of their anti-Ia reactivity but leaves their ultrastructural morphology intact. In sharp contrast, Thy-1+DEC escape ultrastructural detection after PUVA treatment and are greatly reduced in number after high-dose UV-B. Ia+EC continuously reappeared with both treatment modalities over a course of 4 to 6 wk, whereas even after 14 to 22 wk Thy-1+DEC were present only in negligible numbers. Similar to high-dose UV-B or PUVA therapy, administration of GCS resulted in the disappearance of both anti-Thy-1- and anti-Ia-reactive cells. Ultrastructural studies disclosed, however, that these steroid-induced alterations in the surface characteristics were accompanied by a dramatic reduction of the LC population but were not paralleled by morphologic changes of Thy-1+DEC. In the course of 7 wk after cessation of steroid treatment, the number of both Ia+EC and Thy-1+DEC had returned to normal values. The selective removal of either of these two dendritic epidermal cell populations by physicochemical agents may provide an excellent strategy to further clarify the functional properties of both LC and Thy-1+DEC.\n\nAberer, Werner\n\n\n"
},
{
"text": "\n111349\nRole of inflammation-related gene polymorphisms in patients with central retinal vein occlusion.\n\nMaier, R\n\nSteinbrugger, I\n\nHaas, A\n\nSelimovic, M\n\nRenner, W\n\nEl-Shabrawi, Y\n\nWerner, C\n\nWedrich, A\n\nSchmut, O\n\nWeger, M\n\nBeiträge in Fachzeitschriften\nISI:000291152700018\n21269700.0\n10.1016/j.ophtha.2010.10.014\nNone\nObjective: Central retinal vein occlusion (CRVO) is a vision-threatening disease, primarily occurring among patients aged more than 60 years. Several risk factors, including arterial hypertension and diabetes mellitus, have been identified. Compression of the central retinal vein by an atherosclerotic retinal artery at the lamina cribrosa also has been implicated in the pathogenesis of the disease. Functional gene polymorphisms of cytokines or chemokines previously shown to affect atherogenesis or hemostasis are potential risk factors for CRVO. The present study investigates a hypothesized association between inflammation-related gene polymorphisms and the presence of CRVO in a relatively large cohort of patients. Design: Case-control study. Participants: The study group consisted of 315 patients with CRVO and 335 control subjects. Methods: Determination of genotypes was done by 5' exonuclease assay (TaqMan). Main Outcome Measures: Genotypes of interleukin (IL)1 beta -511C>T, IL1 receptor antagonist (IL1RN) 1018T>C, IL4 -584C>T, IL6 -174G>C, IL10 -592C>A, IL18 183A>G, tumor necrosis factor (TNF)-alpha -308G>A, monocyte chemoattractant protein (MCP)-1/CCL2 -2518A>G, IL8 -251A>T, and RANTES (CCL5) -403G>A polymorphisms. Results: Genotype distributions and allele frequencies of the investigated gene polymorphisms did not significantly differ between both groups (P>0.05). Arterial hypertension, diabetes mellitus, and cigarette smoking were significantly more frequent in patients with CRVO than among control subjects (arterial hypertension: 67.0% vs. 52.2%, P<0.001; diabetes mellitus: 16.8% vs. 6.3%, P<0.001, cigarette smoking: 32.1% vs. 23.6%, P = 0.02). In a logistic regression analysis, the presence of arterial hypertension was associated with an odds ratio (OR) of 1.75 (95% confidence interval [CI], 1.26-2.44) in those with CRVO, whereas an OR of 2.52 (95% CI, 1.46-4.35) was found in those with diabetes mellitus. A history of cigarette smoking was associated with an OR of 1.57 (95% CI, 1.09 - 2.25) for CRVO. Conclusions: Our data suggest that the investigated inflammation-related gene polymorphisms are unlikely major risk factors for CRVO. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2011; 118: 1125-1129 (C) 2011 by the American Academy of Ophthalmology.\n\nEl-Shabrawi, Yosuf\n\nHaas, Anton\n\nRenner, Wilfried\n\nWedrich, Andreas\n\nWeger, Martin\n\n\n"
},
{
"text": "\n116705\nEuropean guidelines for the diagnosis and management of upper urinary tract urothelial cell carcinomas: 2011 update. European Association of Urology Guideline Group for urothelial cell carcinoma of the upper urinary tract.\n\nRoupret, M\n\nZigeuner, R\n\nPalou, J\n\nBoehle, A\n\nKaasinen, E\n\nSylvester, R\n\nBabjuk, M\n\nOosterlinck, W\n\nEuropean Association of Urology Guideline Group for urothelial cell carcinoma of the upper urinary tract\n\nBeiträge in Fachzeitschriften\nISI:000299355900002\n22036956.0\n10.1016/j.acuro.2011.09.001\nNone\nCONTEXT: The European Association of Urology (EAU) Guideline Group for urothelial cell carcinoma of the upper urinary tract (UUT-UCC) has prepared new guidelines to aid clinicians in assessing the current evidence-based management of UUT-UCC and to incorporate present recommendations into daily clinical practice. OBJECTIVE: This paper provides a brief overview of the EAU guidelines on UUT-UCC as an aid to clinicians in their daily practice. EVIDENCE ACQUISITION: The recommendations provided in the current guidelines are based on a thorough review of available UUT-UCC guidelines and papers identified using a systematic search of Medline. Data on urothelial malignancies and UUT-UCCs in the literature were searched using Medline with the following keywords: urinary tract cancer, urothelial carcinomas, upper urinary tract, carcinoma, transitional cell, renal pelvis, ureter, bladder cancer, chemotherapy, nephroureterectomy, adjuvant treatment, neoadjuvant treatment, recurrence, risk factors, and survival. A panel of experts weighted the references. EVIDENCE SYNTHESIS: There is a lack of data in the current literature to provide strong recommendations due to the rarity of the disease. A number of recent multicentre studies are now available, whereas earlier publications were based only on limited populations. However, most of these studies have been retrospective analyses. The TNM classification 2009 is recommended. Recommendations are given for diagnosis as well as for radical and conservative treatment; prognostic factors are also discussed. Recommendations are provided for patient follow-up after different therapeutic options. CONCLUSIONS: These guidelines contain information for the diagnosis and treatment of individual patients according to a current standardised approach. When determining the optimal treatment regimen, physicians must take into account each individual patient's specific clinical characteristics with regard to renal function including medical comorbidities; tumour location, grade and stage; and molecular marker status. Copyright © 2011 AEU. Published by Elsevier Espana. All rights reserved.\n\nZigeuner, Richard\n\n\n"
},
{
"text": "\n117775\nCharacteristics of relaxation induced by calcitonin gene-related peptide in contracted rabbit basilar artery.\n\nSutter, B\n\nSuzuki, S\n\nKassell, NF\n\nLee, KS\n\nBeiträge in Fachzeitschriften\nISI:A1995PZ08000015\n7815140.0\n10.3171/jns.1995.82.1.0091\nNone\nIncreasing evidence suggests that disturbances in the modulatory influence of the vasoactive peptide, calcitonin gene-related peptide (CGRP), contribute to the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). However, only limited success has been achieved in trials attempting to ameliorate vasospasm by modifying CGRP function. To better understand the potential utility of targeting CGRP-mediated relaxation, it is important both to identify the interactions CGRP may have with other elements of the vasospastic response and to characterize the mechanisms through which CGRP elicits vasodilative effects. The present studies examined the effects of CGRP on vascular responsiveness using tension measurements of ring strips of rabbit basilar artery maintained in vitro. Pretreatment of vessels with CGRP (100 nM) inhibited vasoconstrictor responses to the potent protein kinase C (PKC) activator, phorbol 12, 3-dibutyrate (PDB). This particular contractile response was selected because PKC-mediated vasoconstriction is a critical component of the vasospastic response after SAH. In a posttreatment paradigm, CGRP was also found to reverse established constriction responses to PDB (2 nM) and histamine (3 microM) in a dose-dependent manner. When tested against the maximum effective dose of PDB (30 nM) in the posttreatment paradigm, CGRP (100 nM) did not elicit significant relaxation. However, after washing both of these drugs out of the test chamber, a persistent effect of CGRP was revealed: the decay of PDB-induced contraction was accelerated in vessels that had previously been treated with CGRP. These findings indicate that CGRP elicits both immediate and sustained influences on contractile responses mediated by PKC. Finally, two potential mechanisms for the vascular response to CGRP were examined. Adenosine triphosphate (ATP)-sensitive K+ channels do not appear to participate in CGRP-mediated dilation; inhibitors of these channels, glibenclamide and tolbutamide, did not block CGRP-induced relaxation. In contrast, a possible role for the nucleotide cyclic adenosine monophosphate (cAMP) in the vascular response to CGRP was indicated by the dose-dependent elevation of cAMP levels by CGRP. Together these studies indicate that CGRP can modulate the contractile response to PKC activation. These effects are associated with increases in the levels of cAMP, but occur independently of fluxes through ATP-sensitive K+ channels.\n\nSutter, Bernhard\n\n\n"
},
{
"text": "\n117777\nEffects of subarachnoid hemorrhage on vascular responses to calcitonin gene-related peptide and its related second messengers.\n\nSutter, B\n\nSuzuki, S\n\nArthur, AS\n\nKassell, NF\n\nLee, KS\n\nBeiträge in Fachzeitschriften\nISI:A1995RR00100021\n7666231.0\n10.3171/jns.1995.83.3.0516\nNone\nCalcitonin gene-related peptide (CGRP) is a potent vasodilator and a primary signaling molecule in neurovascular communication. In the present study, the authors examined cerebrovascular responses to CGRP and its related second messenger systems during cerebral vasospasm induced by subarachnoid hemorrhage (SAH). Tension measurements were performed in vitro on ring strips of basilar arteries obtained from rabbits subjected to artificial SAH and from control (non-SAH) animals. In vessels from SAH animals, which were preconstricted with serotonin, the vasorelaxant response to CGRP was attenuated. Because it has been suggested that vasodilation elicited by CGRP is mediated by cyclic 3', '-adenosine monophosphate (cAMP) and/or cyclic 3', '-guanosine monophosphate (cGMP), the vascular effects of directly activating these second messenger systems were also examined. The relaxant effect of forskolin, which activates adenylate cyclase directly, was slightly enhanced after SAH. In contrast, the relaxant effect of nitroglycerin (GTN), which activates soluble guanylate cyclase directly, was unchanged after SAH. The attenuation of CGRP-induced vasorelaxation could be the result of a modification in its ability to stimulate the production of second messengers. Experiments testing the capacity of CGRP to elevate cAMP levels showed no significant differences between vessels from non-SAH and SAH animals. Similarly, the resting levels of cAMP and the forskolin-induced elevations of cAMP did not differ between non-SAH and SAH animals. In contrast, cGMP levels were lower in resting and CGRP-treated vessels from SAH animals than in those from non-SAH animals. No significant differences in the levels of cGMP were observed between non-SAH and SAH vessels treated with GTN. This study indicates that CGRP-induced vasodilation is attenuated during vasospasm in a rabbit model of SAH. The findings also demonstrate that vasodilatory responses mediated by cAMP and cGMP are intact, although the levels of cGMP in SAH vessels are reduced. Together, these observations suggest that an attenuation in the capacity of vessels to dilate in response to CGRP occurs during cerebral vasospasm, and this change in CGRP vasoactivity is a result of modifications prior to, or independent of, the elevation of cyclic nucleotide second messengers.\n\nSutter, Bernhard\n\n\n"
}
]
}