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"text": "\n142836\nConsensus on performing skin biopsies, laboratory workup, evaluation of tissue samples and reporting of the results in patients with suspected cutaneous graft-versus-host disease.\n\nHillen, U\n\nHäusermann, P\n\nMassi, D\n\nJanin, A\n\nWolff, D\n\nLawitschka, A\n\nGreinix, H\n\nMeyer, R\n\nZiemer, M\n\nBeiträge in Fachzeitschriften\nISI:000353457100017\n25265987.0\n10.1111/jdv.12737\nNone\nHistopathological diagnosis including selection of lesions, the determination of the best point of time for biopsy and workup is not trivial in cutaneous graft-versus-host disease (GvHD).\n To develop interdisciplinary recommendations on performing, the laboratory work up and reporting of the results of skin biopsies in patients with suspected cutaneous GvHD.\n A working group consisting of dermatopathologists, dermatologists, transplant-physicians and transplant-pathologists prepared recommendations for performing skin biopsies, laboratory workup and evaluation of tissue samples, and reporting of the results in patients with cutaneous GvHD. After achieving a consensus within the working group, a survey that comprised the core issues of the recommendations was electronically sent out to 72 alloHSCT centres within Germany, Austria, and Switzerland and their Departments of Pathology. The answers were discussed in a Consensus Conference and final recommendations were established.\n Twenty-five centres responded to the clinical and 17 centres to the histopathological survey. Questions addressed to the clinicians comprised the indication for skin biopsy in chronic GvHD (cGvHD) and acute GvHD (aGvHD) and the appropriate point of time for skin biopsy. Eighty-eight per cent agreed that the skin biopsy is generally indicated in patients with suspected cGvHD lacking diagnostic features. In contrast, with suspected aGvHD, only 62% of respondents felt that skin biopsy was necessary even if GvHD had not been confirmed in another organ. Although restricted due to the fact that immunosuppression is often applied in an emergency setting most centres supported skin biopsies before initiation of topical or systemic immunosuppression. The majority of pathologists agreed that in non-sclerotic GvHD a punch biopsy is adequate, whereas in sclerotic GvHD a scalpel biopsy is preferred.\n While a consensus on the need for biopsies in cGvHD was reached the value of skin biopsies in aGvHD and subsequent biopsies during therapy requires further evaluation.\n © 2014 European Academy of Dermatology and Venereology.\n\nGreinix, Hildegard\n\n\n"
},
{
"text": "\n142867\nTotal colonic aganglionosis: a systematic review and meta-analysis of long-term clinical outcome.\n\nLaughlin, DM\n\nFriedmacher, F\n\nPuri, P\n\nBeiträge in Fachzeitschriften\nISI:000307521600003\n22842648.0\n10.1007/s00383-012-3117-3\nNone\nTotal colonic aganglionosis (TCA) is a severe form of Hirschsprung's disease (HD), occurring in less than 10 % of the cases. It is a challenging surgical condition and outcomes of pull-through (PT) surgery are reported to be inferior to those in patients with recto-sigmoid HD. As even large centres only see a few patients with TCA, there is little information on the long-term outcome of patients after PT operation for TCA. The aim of this meta-analysis was to investigate the long-term clinical outcome in patients with TCA.\n MEDLINE(®) and EMBASE(®) databases were searched for relevant articles that reported the outcomes of patients with TCA published between 1980 and 2011. The search terms were "Hirschsprung's disease", "Total colonic aganglionosis" AND "Outcome". All published studies containing adequate clinical data for a mean follow-up period of not less than 4 years were included. Reference lists of retrieved articles were reviewed for additional cases. Detailed records of morbidity and mortality were extracted and analysed.\n This search yielded 225 articles reporting on outcomes in TCA. Of these, 189 were excluded for having too short a follow-up period, small or single case series, inadequate clinical data and duplicated patient groups. Ultimately, 36 articles from 37 centres containing useful clinical information on the outcomes of TCA in 969 patients were identified. There were 152 early deaths prior to PT (15.7 %). Of 817 survivors, 739 underwent PT. The mortality rate for TCA post-PT was 5.7 %. The most frequently reported post-operative complication was enterocolitis in 42 % of the cases. 17.5 % of patients underwent subsequent major surgery including redo PT, stoma reformation or other laparotomy. Long-term follow-up data were available in 396 patients. Satisfactory or normal bowel control was reported in 60 % of the patients. Soiling, faecal incontinence or other poor outcome was reported in 33.5 % of the cases and 6.5 % of the patients had undergone conversion to a permanent ileostomy for post-operative complications.\n This meta-analysis reveals that a large number of patients with TCA have long-term problems with bowel control.\n\n\n"
},
{
"text": "\n145847\nMitogen-Inducible Gene-6 Mediates Feedback Inhibition from Mutated BRAF towards the Epidermal Growth Factor Receptor and Thereby Limits Malignant Transformation.\n\nMilewska, M\n\nRomano, D\n\nHerrero, A\n\nGuerriero, ML\n\nBirtwistle, M\n\nQuehenberger, F\n\nHatzl, S\n\nKholodenko, BN\n\nSegatto, O\n\nKolch, W\n\nZebisch, A\n\nBeiträge in Fachzeitschriften\nISI:000356327000116\n26065894.0\n10.1371/journal.pone.0129859\nPMC4466796\nBRAF functions in the RAS-extracellular signal-regulated kinase (ERK) signaling cascade. Activation of this pathway is necessary to mediate the transforming potential of oncogenic BRAF, however, it may also cause a negative feedback that inhibits the epidermal growth factor receptor (EGFR). Mitogen-inducible gene-6 (MIG-6) is a potent inhibitor of the EGFR and has been demonstrated to function as a tumor suppressor. As MIG-6 can be induced via RAS-ERK signaling, we investigated its potential involvement in this negative regulatory loop. Focus formation assays were performed and demonstrated that MIG-6 significantly reduces malignant transformation induced by oncogenic BRAF. Although this genetic interaction was mirrored by a physical interaction between MIG-6 and BRAF, we did not observe a direct regulation of BRAF kinase activity by MIG-6. Interestingly, a selective chemical EGFR inhibitor suppressed transformation to a similar degree as MIG-6, whereas combining these approaches had no synergistic effect. By analyzing a range of BRAF mutated and wildtype cell line models, we could show that BRAF V600E causes a strong upregulation of MIG-6, which was mediated at the transcriptional level via the RAS-ERK pathway and resulted in downregulation of EGFR activation. This feedback loop is operational in tumors, as shown by the analysis of almost 400 patients with papillary thyroid cancer (PTC). Presence of BRAF V600E correlated with increased MIG-6 expression on the one hand, and with inactivation of the EGFR and of PI3K/AKT signaling on the other hand. Importantly, we also observed a more aggressive disease phenotype when BRAF V600E coexisted with low MIG-6 expression. Finally, analysis of methylation data was performed and revealed that higher methylation of MIG-6 correlated to its decreased expression. Taken together, we demonstrate that MIG-6 efficiently reduces cellular transformation driven by oncogenic BRAF by orchestrating a negative feedback circuit directed towards the EGFR.\n\nHatzl, Stefan\n\nQuehenberger, Franz\n\nZebisch, Armin\n\n\n"
},
{
"text": "\n154704\nThe Value of Median Nerve Sonography as a Predictor for Short- and Long-Term Clinical Outcomes in Patients with Carpal Tunnel Syndrome: A Prospective Long-Term Follow-Up Study.\n\nMarschall, A\n\nFicjian, A\n\nStradner, MH\n\nHusic, R\n\nZauner, D\n\nSeel, W\n\nSimmet, NE\n\nKlammer, A\n\nHeizer, P\n\nBrickmann, K\n\nGretler, J\n\nFürst-Moazedi, FC\n\nThonhofer, R\n\nHermann, J\n\nGraninger, WB\n\nQuasthoff, S\n\nDejaco, C\n\nBeiträge in Fachzeitschriften\nISI:000383893500005\n27662617.0\n10.1371/journal.pone.0162288\nPMC5035047\nTo investigate the prognostic value of B-mode and Power Doppler (PD) ultrasound of the median nerve for the short- and long-term clinical outcomes of patients with carpal tunnel syndrome (CTS).\n Prospective study of 135 patients with suspected CTS seen 3 times: at baseline, then at short-term (3 months) and long-term (15-36 months) follow-up. At baseline, the cross-sectional area (CSA) of the median nerve was measured with ultrasound at 4 levels on the forearm and wrist. PD signals were graded semi-quantitatively (0-3). Clinical outcomes were evaluated at each visit with the Boston Questionnaire (BQ) and the DASH Questionnaire, as well as visual analogue scales for the patient's assessment of pain (painVAS) and physician's global assessment (physVAS). The predictive values of baseline CSA and PD for clinical outcomes were determined with multivariate logistic regression models.\n Short-term and long-term follow-up data were available for 111 (82.2%) and 105 (77.8%) patients, respectively. There was a final diagnosis of CTS in 84 patients (125 wrists). Regression analysis revealed that the CSA, measured at the carpal tunnel inlet, predicted short-term clinical improvement according to BQ in CTS patients undergoing carpal tunnel surgery (OR 1.8, p = 0.05), but not in patients treated conservatively. Neither CSA nor PD assessments predicted short-term improvement of painVAS, physVAS or DASH, nor was any of the ultrasound parameters useful for the prediction of long-term clinical outcomes.\n Ultrasound assessment of the median nerve at the carpal tunnel inlet may predict short-term clinical improvement in CTS patients undergoing carpal tunnel release, but long-term outcomes are unrelated to ultrasound findings.\n\nDejaco, Christian\n\nGraninger, Winfried\n\nHermann, Josef\n\nHusic, Rusmir\n\nMoazedi-Fürst, Florentine\n\nQuasthoff, Stefan\n\nStradner, Martin Helmut\n\n\n"
},
{
"text": "\n160909\n[Who Should Provide Persons with Familial Risk of Colorectal Cancer with Information on Early Detection? - The View of those Affected].\n\nPlath, J\n\nSiebenhofer, A\n\nSchulz-Rothe, S\n\nGüthlin, C\n\nBeiträge in Fachzeitschriften\nISI:000446897700010\n28628929.0\n10.1055/s-0042-124671\nNone\nColonoscopy is recommended for persons with a familial risk of colorectal cancer (CRC) before they reach 55 years of age. The aim of this analysis was to ask affected persons aged 40-54 years whether they had found out about early detection of CRC and from which institutions and media they would like to obtain such information.\n Analysis of data from a cross-sectional study: In a general practice setting, those with a positive family history of CRC were asked to provide written information.\n In total, 191 persons with a positive family history of CRC participated in the study: 59.6% had already found out about early detection of CRC. Out of this, 67.0% had received information from their physicians. Most of the participants wanted information on early detection of CRC to be provided by the general practitioner (98.9% completely or mostly agree), and by health insurers (74.5% completely or mostly agree). The participants would rather not prefer to receive information from public institutions such as the public health department (69.5% not or mostly not agree) and private organizations such as self-help groups (80.9% not or mostly not agree). Approximately half would prefer to receive such information via TV. More men than women would prefer to source such information from the internet (completely or mostly agree: 66.7 vs. 43.8%), or newspapers and magazines (completely or mostly agree: 53.6 vs. 41.8%).\n A survey in a general practice setting found that more than half of persons with familial risk of CRC had already obtained information on early detection. The setting of the survey on preferred information sources possibly encouraged participants to put general practitioners in the first place. Furthermore, the results of this nationwide unique cohort of persons aged 40-54 with a familial risk of CRC show that their information-seeking behavior was not more pronounced than average and that men and women can be provided with information in different ways.\n © Georg Thieme Verlag KG Stuttgart · New York.\n\nSiebenhofer-Kroitzsch, Andrea\n\n\n"
},
{
"text": "\n161262\nThe Icatibant Outcome Survey: experience of hereditary angioedema management from six European countries.\n\nCaballero, T\n\nAberer, W\n\nLonghurst, HJ\n\nMaurer, M\n\nZanichelli, A\n\nPerrin, A\n\nBouillet, L\n\nAndresen, I\n\nIOS Study Group\n\nBeiträge in Fachzeitschriften\nISI:000406075900043\n28370444.0\n10.1111/jdv.14251\nPMC5575527\nHereditary angioedema (HAE) due to C1-inhibitor deficiency (C1-INH-HAE) is a rare, potentially fatal, bradykinin-mediated disease. Icatibant is a bradykinin B2 receptor antagonist originally approved in 2008 in the European Union and 2011 in the United States as an acute therapy option for HAE attacks in adults.\n To compare demographics, disease characteristics and treatment outcomes of icatibant-treated HAE attacks in patients with C1-INH-HAE enrolled in the Icatibant Outcome Survey across six European countries: Austria, France, Germany, Italy, Spain and the UK.\n The Icatibant Outcome Survey [IOS; Shire, Zug, Switzerland (NCT01034969)] is an international observational study monitoring the safety and effectiveness of icatibant. Descriptive, retrospective analyses compared IOS country data derived during July 2009-April 2015.\n Overall, 481 patients with C1-INH-HAE provided demographic data. A significant difference across countries in age at onset (P = 0.003) and baseline attack frequency (P < 0.001) was found although no significant differences were found with respect to gender (majority female; P = 0.109), age at diagnosis (P = 0.182) or delay in diagnosis (P = 0.059). Icatibant was used to treat 1893 attacks in 325 patients with majority self-administration in all countries. Overall, significant differences (all P < 0.001) were found across countries in time to treatment [median 1.8 h; median range: 0.0 (Germany-Austria) to 4.4 (France) h], time to resolution [median 6.5 h; median range: 3 (Germany-Austria) to 12 (France) h] and attack duration [median 10.5 h; median range: 3.1 (Germany-Austria) to 18.5 (France) h].\n These data form the first European cross-country comparison of disease characteristics and icatibant use in patients with C1-INH-HAE who are enrolled in IOS. International variation in icatibant practice and treatment outcomes across the six European countries assessed highlight the need to further investigate the range of country-specific parameters driving regional variations in icatibant use.\n © 2017 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.\n\nAberer, Werner\n\n\n"
},
{
"text": "\n166090\nLysine restricted diet for pyridoxine-dependent epilepsy: first evidence and future trials.\n\nvan Karnebeek, CD\n\nHartmann, H\n\nJaggumantri, S\n\nBok, LA\n\nCheng, B\n\nConnolly, M\n\nCoughlin, CR\n\nDas, AM\n\nGospe, SM\n\nJakobs, C\n\nvan der Lee, JH\n\nMercimek-Mahmutoglu, S\n\nMeyer, U\n\nStruys, E\n\nSinclair, G\n\nVan Hove, J\n\nCollet, JP\n\nPlecko, BR\n\nStockler, S\n\nBeiträge in Fachzeitschriften\nISI:000310720200014\n23022070.0\n10.1016/j.ymgme.2012.09.006\nNone\nTo evaluate the efficacy and safety of dietary lysine restriction as an adjunct to pyridoxine therapy on biochemical parameters, seizure control, and developmental/cognitive outcomes in children with pyridoxine-dependent epilepsy (PDE) caused by antiquitin (ATQ) deficiency.\n In this observational study, seven children with confirmed ATQ deficiency were started on dietary lysine restriction with regular nutritional monitoring. Biochemical outcomes were evaluated using pipecolic acid and α-aminoadipic semialdehyde (AASA) levels in body fluids; developmental/cognitive outcomes were evaluated using age-appropriate tests and parental observations.\n Lysine restriction was well tolerated with good compliance; no adverse events were reported. Reduction in biomarker levels (measurement of the last value before and first value after initiation of dietary lysine restriction) ranged from 20 to 67% for plasma pipecolic acid, 13 to 72% for urinary AASA, 45% for plasma AASA and 42% for plasma P6C. For the 1 patient in whom data were available and who showed clinical deterioration upon interruption of diet, cerebrospinal fluid levels decreased by 87.2% for pipecolic acid and 81.7% for AASA. Improvement in age-appropriate skills was observed in 4 out of 5 patients showing pre-diet delays, and seizure control was maintained or improved in 6 out 7 children.\n This observational study provides Level 4 evidence that lysine restriction is well tolerated with significant decrease of potentially neurotoxic biomarkers in different body compartments, and with the potential to improve developmental outcomes in children with PDE caused by ATQ deficiency. To generate a strong level of evidence before this potentially burdensome dietary therapy becomes the mainstay treatment, we have established: an international PDE consortium to conduct future studies with an all-inclusive integrated study design; a website containing up-to-date information on PDE; a methodological toolbox; and an online registry to facilitate the participation of interested physicians, scientists, and families in PDE research.\n Copyright © 2012 Elsevier Inc. All rights reserved.\n\nPlecko, Barbara\n\n\n"
},
{
"text": "\n166319\nInhalation Injury in the Burned Patient.\n\nFoncerrada, G\n\nCulnan, DM\n\nCapek, KD\n\nGonzález-Trejo, S\n\nCambiaso-Daniel, J\n\nWoodson, LC\n\nHerndon, DN\n\nFinnerty, CC\n\nLee, JO\n\nBeiträge in Fachzeitschriften\nISI:000473111300005\n29461292.0\n10.1097/SAP.0000000000001377\nPMC5825291\nInhalation injury causes a heterogeneous cascade of insults that increase morbidity and mortality among the burn population. Despite major advancements in burn care for the past several decades, there remains a significant burden of disease attributable to inhalation injury. For this reason, effort has been devoted to finding new therapeutic approaches to improve outcomes for patients who sustain inhalation injuries.The three major injury classes are the following: supraglottic, subglottic, and systemic. Treatment options for these three subtypes differ based on the pathophysiologic changes that each one elicits.Currently, no consensus exists for diagnosis or grading of the injury, and there are large variations in treatment worldwide, ranging from observation and conservative management to advanced therapies with nebulization of different pharmacologic agents.The main pathophysiologic change after a subglottic inhalation injury is an increase in the bronchial blood flow. An induced mucosal hyperemia leads to edema, increases mucus secretion and plasma transudation into the airways, disables the mucociliary escalator, and inactivates hypoxic vasocontriction. Collectively, these insults potentiate airway obstruction with casts formed from epithelial debris, fibrin clots, and inspissated mucus, resulting in impaired ventilation. Prompt bronchoscopic diagnosis and multimodal treatment improve outcomes. Despite the lack of globally accepted standard treatments, data exist to support the use of bronchoscopy and suctioning to remove debris, nebulized heparin for fibrin casts, nebulized N-acetylcysteine for mucus casts, and bronchodilators.Systemic effects of inhalation injury occur both indirectly from hypoxia or hypercapnia resulting from loss of pulmonary function and systemic effects of proinflammatory cytokines, as well as directly from metabolic poisons such as carbon monoxide and cyanide. Both present with nonspecific clinical symptoms including cardiovascular collapse. Carbon monoxide intoxication should be treated with oxygen and cyanide with hydroxocobalamin.Inhalation injury remains a great challenge for clinicians and an area of opportunity for scientists. Management of this concomitant injury lags behind other aspects of burn care. More clinical research is required to improve the outcome of inhalation injury.The goal of this review is to comprehensively summarize the diagnoses, treatment options, and current research.\n\nCambiaso Daniel, Janos\n\n\n"
},
{
"text": "\n170857\nObesity and overweight as a risk factor for pneumonia in polytrauma patients: a retrospective cohort study.\n\nMica, L\n\nKeller, C\n\nVomela, J\n\nTrentz, O\n\nPlecko, M\n\nKeel, MJ\n\nBeiträge in Fachzeitschriften\nISI:000330457400022\n24064885.0\n10.1097/TA.0b013e31829a0bdd\nNone\nObesity is a growing problem in western societies. The aim of this retrospective cohort study was to determine the association between the overweight and obese polytrauma patients and pneumonia after injury.\n A total of 628 patients with an Injury Severity Score (ISS) of 16 or greater and 16 years or older were included in this retrospective study. The sample was subdivided into three groups as follows: body mass index (BMI) of less than 25 kg/m2; BMI of 25 kg/m2 to 30 kg/m2; and BMI more than 30 kg/m2. The Murray score was assessed at admission and at its maximum during hospitalization to determine pulmonary problems. Pneumonia was defined as bacteriologically positive sputum with appropriate radiologic and laboratory changes (C-reactive protein and interleukin 6). Data are given as mean ± SEM. One-way analysis of variance and the Kruskal-Wallis test were used for the analyses, and the significance level was set at p < 0.05; Bonferroni-Dunn test was performed as post hoc analysis.\n The Abbreviated Injury Scale (AIS) score for the thorax was 3.2 ± 0.1 in the group with a BMI of less than 25 kg/m2, 3.3 ± 0.1 in the group with a BMI of 25 kg/m2 to 30 kg/m2, and 2.8 ± 0.2 in the group with BMI of more than 30 kg/m2 (p = 0.044). The Murray score at admission was elevated with increasing BMI (0.8 ± 0.8 for BMI < 25 kg/m2, 0.9 ± 0.9 for BMI 25–30 kg/m2, and 1.0 ± 0.8 for BMI > 30 kg/m2; p = 0.137); the maximum Murray score during hospitalization revealed significant differences (1.2 ± 0.9 for BMI < 25 kg/m2, 1.6 ± 1.0 for BMI 25–30 kg/m2, and 1.5 ± 0.9 for BMI > 30 kg/m2; p < 0.001). The incidence of pneumonia also increased with increasing BMI (1.6% for BMI < 25 kg/m2, 2.0% for BMI 25–30 kg/m2, and 3.1% for BMI > 30 kg/m2; p = 0.044).\n Obesity leads to an increased incidence of pneumonia in a polytrauma situation.\n Prognostic/epidemiologic study, level IV.\n\nPlecko, Michael\n\n\n"
},
{
"text": "\n178295\nGlobal Burden of Small Vessel Disease-Related Brain Changes on MRI Predicts Cognitive and Functional Decline.\n\nJokinen, H\n\nKoikkalainen, J\n\nLaakso, HM\n\nMelkas, S\n\nNieminen, T\n\nBrander, A\n\nKorvenoja, A\n\nRueckert, D\n\nBarkhof, F\n\nScheltens, P\n\nSchmidt, R\n\nFazekas, F\n\nMadureira, S\n\nVerdelho, A\n\nWallin, A\n\nWahlund, LO\n\nWaldemar, G\n\nChabriat, H\n\nHennerici, M\n\nO'Brien, J\n\nInzitari, D\n\nLötjönen, J\n\nPantoni, L\n\nErkinjuntti, T\n\nBeiträge in Fachzeitschriften\nISI:000504225600039\n31699021.0\n10.1161/STROKEAHA.119.026170\nPMC6924941\nBackground and Purpose- Cerebral small vessel disease is characterized by a wide range of focal and global brain changes. We used a magnetic resonance imaging segmentation tool to quantify multiple types of small vessel disease-related brain changes and examined their individual and combined predictive value on cognitive and functional abilities. Methods- Magnetic resonance imaging scans of 560 older individuals from LADIS (Leukoaraiosis and Disability Study) were analyzed using automated atlas- and convolutional neural network-based segmentation methods yielding volumetric measures of white matter hyperintensities, lacunes, enlarged perivascular spaces, chronic cortical infarcts, and global and regional brain atrophy. The subjects were followed up with annual neuropsychological examinations for 3 years and evaluation of instrumental activities of daily living for 7 years. Results- The strongest predictors of cognitive performance and functional outcome over time were the total volumes of white matter hyperintensities, gray matter, and hippocampi (P<0.001 for global cognitive function, processing speed, executive functions, and memory and P<0.001 for poor functional outcome). Volumes of lacunes, enlarged perivascular spaces, and cortical infarcts were significantly associated with part of the outcome measures, but their contribution was weaker. In a multivariable linear mixed model, volumes of white matter hyperintensities, lacunes, gray matter, and hippocampi remained as independent predictors of cognitive impairment. A combined measure of these markers based on Z scores strongly predicted cognitive and functional outcomes (P<0.001) even above the contribution of the individual brain changes. Conclusions- Global burden of small vessel disease-related brain changes as quantified by an image segmentation tool is a powerful predictor of long-term cognitive decline and functional disability. A combined measure of white matter hyperintensities, lacunar, gray matter, and hippocampal volumes could be used as an imaging marker associated with vascular cognitive impairment.\n\nFazekas, Franz\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n180078\nCorrelation between work impairment, scores of rhinitis severity and asthma using the MASK-air<sup>®</sup> App.\n\nBédard, A\n\nAntó, JM\n\nFonseca, JA\n\nArnavielhe, S\n\nBachert, C\n\nBedbrook, A\n\nBindslev-Jensen, C\n\nBosnic-Anticevich, S\n\nCardona, V\n\nCruz, AA\n\nFokkens, WJ\n\nGarcia-Aymerich, J\n\nHellings, PW\n\nIvancevich, JC\n\nKlimek, L\n\nKuna, P\n\nKvedariene, V\n\nLarenas-Linnemann, D\n\nMelén, E\n\nMonti, R\n\nMösges, R\n\nMullol, J\n\nPapadopoulos, NG\n\nPham-Thi, N\n\nSamolinski, B\n\nV Tomazic, P\n\nToppila-Salmi, S\n\nVentura, MT\n\nYorgancioglu, A\n\nBousquet, J\n\nPfaar, O\n\nBasagaña, X\n\nMASK study group\n\nBeiträge in Fachzeitschriften\nISI:000520882500001\n31995656.0\n10.1111/all.14204\nNone\nIn allergic rhinitis, a relevant outcome providing information on the effectiveness of interventions is needed. In MASK-air (Mobile Airways Sentinel Network), a visual analogue scale (VAS) for work is used as a relevant outcome. This study aimed to assess the performance of the work VAS work by comparing VAS work with other VAS measurements and symptom-medication scores obtained concurrently.\n All consecutive MASK-air users in 23 countries from June 1, 2016 to October 31, 2018 were included (14, 89 users; 205, 04 days). Geolocalized users self-assessed daily symptom control using the touchscreen functionality on their smart phone to click on VAS scores (ranging from 0 to 100) for overall symptoms (global), nose, eyes, asthma and work. Two symptom-medication scores were used: the modified EAACI CSMS score, and the MASK control score for rhinitis. To assess data quality, the intra-individual response variability (IRV) index was calculated.\n A strong correlation was observed between VAS work and other VAS. The highest levels for correlation with VAS work and variance explained in VAS work were found with VAS global, followed by VAS nose, eye and asthma. In comparison to VAS global, the mCSMS and MASK control score showed a lower correlation with VAS work. Results are unlikely to be explained by a low quality of data arising from repeated VAS measures.\n VAS work correlates with other outcomes (VAS global, nose, eye and asthma) but less well with a symptom-medication score. VAS work should be considered as a potentially useful AR outcome in intervention studies.\n © 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.\n\nTomazic, Peter Valentin\n\n\n"
},
{
"text": "\n187283\nLoss of Function of Lysosomal Acid Lipase (LAL) Profoundly Impacts Osteoblastogenesis and Increases Fracture Risk in Humans.\n\nHelderman, RC\n\nWhitney, DG\n\nDuta-Mare, M\n\nAkhmetshina, A\n\nVujic, N\n\nJayapalan, S\n\nNyman, JS\n\nMisra, BB\n\nRosen, CJ\n\nCzech, MP\n\nKratky, D\n\nRendina-Ruedy, E\n\nBeiträge in Fachzeitschriften\nISI:000647556800003\n33838322.0\n10.1016/j.bone.2021.115946\nNone\nLysosomal acid lipase (LAL) is essential for cholesteryl ester (CE) and triacylglycerol (TAG) hydrolysis in lysosomes. Clinically, an autosomal recessive LIPA mutation causes LAL deficiency (LAL-D), either Wolman Disease or Cholesterol Ester Storage Disease (CESD). LAL-D is associated with ectopic neutral lipid accumulation in the liver, small intestine, spleen, adrenal glands, and blood. Considering the importance of unesterified cholesterol and fatty acids in bone metabolism, we hypothesized that LAL is essential to bone formation, and ultimately, skeletal health. To investigate the role of LAL in skeletal homeostasis, we used LAL-deficient (-/-) mice and osteoblast cell cultures. Male LAL-/- mice had lower trabecular BV/TV (12%) compared to WT mice (21%), due to decreased trabecular number and increased trabecular separation; this change was not apparent in the females. While both sexes of LAL-/- mice displayed decreased cortical bone thickness and polar moment of inertia, only the female LAL-/- mice showed increased cortical porosity. Histological analyses revealed that LAL-/- mice tended to have less osteoblasts but no change in osteoclast numbers. In studying the cell-autonomous role of LAL, we observed impaired osteoblastogenesis of LAL-/- calvarial osteoblasts and in bone marrow stromal cells treated with the LAL inhibitor lalistat. Consistent with LAL's role in other tissues, lalistat resulted in profound lipid puncta accumulation and an altered intracellular lipid profile. Finally, we analyzed a large de-identified national insurance database (i.e. 2016/2017 Optum Clinformatics®) which revealed that adults (≥18 years) with CESD (n=3, 76) had a higher odds ratio (OR=1.21; 95% CI=1.03-1.41) of all-cause fracture at any location compared to adults without CESD (n=13.7 M) after adjusting for demographic variables and osteoporosis. These data demonstrate that alterations in LAL have significant clinical implications related to fracture risk and that LAL's modulation of lipid metabolism is a critical for osteoblast function.\n Copyright © 2021. Published by Elsevier Inc.\n\nAkhmetshina, Alena\n\nKratky, Dagmar\n\nVujic, Nemanja\n\n\n"
},
{
"text": "\n1239\nHypervolemic hemodilution in acute ischemic stroke: the Multicenter Austrian Hemodilution Stroke Trial (MAHST).\n\nAichner, FT\n\nFazekas, F\n\nBrainin, M\n\nPölz, W\n\nMamoli, B\n\nZeiler, K\n\nBeiträge in Fachzeitschriften\nISI:000072906600001\n9550505.0\n10.1161/01.STR.29.4.743\nNone\nBACKGROUND AND PURPOSE: Experimental studies suggest a beneficial effect of hemodilution on acute ischemic stroke. This was not proven by previous multicenter trials in the clinical setting. Various reasons have been suggested for the failure of these studies, which we attempted to consider in the Multicenter Austrian Hemodilution Stroke Trial (MAHST). METHODS: MAHST is a randomized, double-blind, placebo-controlled study of hypervolemic hemodilution (HHD) within 6 hours of a clinically first ischemic stroke localized in the middle cerebral artery territory. The treatment consisted of 10% hydroxyethyl starch 200/0.5 (HES) and was tested against pure rehydration with Ringer's lactate over a period of 5 days. Our primary outcome measure was clinical improvement within 7 days as measured by the Graded Neurologic Scale (GNS). We performed an adaptive interim analysis to reevaluate the study goal after entering half of the projected number of patients (n = 200). At least 600 patients per group would have been required for significant results, and therefore we decided to terminate the trial. RESULTS: Ninety-eight patients received HHD and 102 patients placebo. The baseline characteristics were comparable between both groups. In the HHD group the absolute reduction of the hematocrit was 2.5% on day 2 with a maximum of 3.7% on day 5, which compares with a reduction in the placebo group of 1% and 1.9%, respectively. Intention-to-treat analysis showed no significant difference of the change of the GNS scores between HHD-treated (median, -8.5; 95% confidence interval, -14.2 to -4.0) and placebo-treated patients (median, -6.0; 95% confidence interval, -11.0 to 0.0) on day 7, and GNS scores remained similar in both treatment groups throughout the trial. At 3 months, slightly more HHD patients showed complete independence on the Barthel Index (28 versus 24), and fewer HHD than placebo patients had died (13 versus 17), but these differences were not statistically significant. HHD treatment was not associated with any specific adverse event. CONCLUSIONS: Mild HHD is safe but failed to demonstrate a significant beneficial effect over the pure rehydration regimen in patients with acute ischemic stroke.\n\nFazekas, Franz\n\n\n"
},
{
"text": "\n2969\nClear cell carcinoma of the uterine cervix: pathology and prognosis in surgically treated stage IB-IIB disease in women not exposed in utero to diethylstilbestrol.\n\nReich, O\n\nTamussino, K\n\nLahousen, M\n\nPickel, H\n\nHaas, J\n\nWinter, R\n\nBeiträge in Fachzeitschriften\nISI:000085784900010\n10684706.0\n10.1006/gyno.1999.5700\nNone\nOBJECTIVE: The purpose of this research was to compare the clinical behavior, pathology findings, and prognosis of surgically treated FIGO stage IB-IIB clear cell carcinomas of the cervix with those of squamous cell carcinomas and non-clear cell adenocarcinomas. METHODS: Fifteen patients with clear cell adenocarcinomas of the cervix (8 FIGO stage IB, 7 FIGO stage IIB) were reviewed. The control group consisted of 444 squamous cell carcinomas and 59 non-clear cell adenocarcinomas. None of the patients had a history of in utero exposure to diethylstilbestrol. All patients underwent radical abdominal hysterectomy with systematic pelvic lymphadenectomy. All specimens were processed as serial giant frontal sections. The mean follow-up in the clear cell group was 83 (13-182) months. Statistical analysis was done with contingency tables, chi(2) tests, and Fisher's exact test. RESULTS: Twelve of the fifteen clear cell carcinomas (80%) were endophytic and tended toward deep cervical infiltration. Clear cell carcinomas extended to the uterine corpus significantly more often than squamous cell and non-clear cell adenocarcarcinomas (P < 0.001). The rates of parametrial involvement and pelvic lymph node involvement were 40 and 47%, respectively. Four patients (27%), all with positive pelvic nodes, developed recurrences an average of 14 (4-48) months after initial therapy. The extrapelvic sites of relapse were the lung, liver, and bone. Clear cell carcinomas had a worse 5-year survival rate (67%) than squamous cell carcinomas (80%) and non-clear cell adenocarcinomas (77%) but this was not statistically significant (P = 0.6). No significant differences were seen for age, growth pattern, parametrial and vaginal involvement, parametrial and pelvic lymph node metastases, frequency of recurrent disease, and time to first recurrence. CONCLUSION: The clinicopathologic findings and prognosis of surgically treated patients with stage IB-IIB clear cell carcinomas without exposure to diethylstilbestrol in utero are similar to those of patients with squamous cell carcinomas and non-clear cell adenocarcinomas.\n\nHaas, Josef\n\nReich, Olaf\n\nTamussino, Karl\n\n\n"
},
{
"text": "\n13447\nAdrenocortical carcinomas and adrenal pheochromocytomas: mass and enhancement loss evaluation at delayed contrast-enhanced CT.\n\nSzolar, DH\n\nKorobkin, M\n\nReittner, P\n\nBerghold, A\n\nBauernhofer, T\n\nTrummer, H\n\nSchoellnast, H\n\nPreidler, KW\n\nSamonigg, H\n\nBeiträge in Fachzeitschriften\nISI:000226483200023\n15671003.0\n10.1148/radiol.2342031876\nNone\nPURPOSE: To retrospectively measure the adrenal gland attenuation and the percentage loss of adrenal gland enhancement at delayed contrast medium-enhanced computed tomography (CT) in patients with adrenocortical carcinomas and pheochromocytomas and to compare these data with those in patients with adenomas and metastases. MATERIALS AND METHODS: The study protocol was approved by the ethics committee, which waived informed consent. Eleven patients with proved adrenocortical carcinoma, 17 with proved pheochromocytoma, 23 with adrenal adenoma, and 16 with metastasis to the adrenal gland underwent helical CT. Nonenhanced CT was followed by contrast-enhanced CT 1 minute and 10 minutes later. Attenuation and enhancement loss values were calculated. RESULTS: The mean attenuation of adenomas (8 HU +/- 18 [standard deviation]) was significantly lower than those of adrenocortical carcinomas (39 HU +/- 14), pheochromocytomas (44 HU +/- 11), and metastases (34 HU +/- 11) on nonenhanced CT scans (P < .001). Although the mean attenuation values for nonadenomas (ie, adrenocortical carcinomas, pheochromocytomas, and metastases) were significantly higher than the value for adenomas on the 1-minute contrast-enhanced CT scans (P < .001), there was more overlap in attenuation between adenomas and nonadenomas on contrast-enhanced scans than on nonenhanced scans. On the 10-minute delayed contrast-enhanced scans, the mean attenuation of adenomas (32 HU +/- 17) was significantly lower than the mean attenuations of carcinomas (72 HU +/- 15), pheochromocytomas (83 HU +/- 14), and metastases (66 HU +/- 13) (P < .001). At optimal threshold values of 50% for absolute percentage of enhancement loss and 40% for relative percentage of enhancement loss at 10 minutes, both the sensitivity and the specificity for the diagnosis of adenoma were 100% when adenomas were compared with carcinomas, pheochromocytomas, and metastases. CONCLUSION: The enhancement loss in adrenocortical carcinomas and pheochromocytomas is similar to that in adrenal metastases but significantly less than that in adrenal adenomas. The percentage change in contrast material washout is a useful adjunct to absolute CT attenuation values in differentiating adrenal adenomas from adrenocortical carcinomas and pheochromocytomas.\n\nBauernhofer, Thomas\n\nBerghold, Andrea\n\nSamonigg, Hellmut\n\nSchoellnast, Helmut\n\n\n"
},
{
"text": "\n68122\nDistribution of prostate specific antigen (PSA) and percentage free PSA in a contemporary screening cohort with no evidence of prostate cancer.\n\nChun, FK\n\nHutterer, GC\n\nPerrotte, P\n\nGallina, A\n\nValiquette, L\n\nBenard, F\n\nMcCormack, M\n\nBriganti, A\n\nIonescu, C\n\nJeldres, C\n\nGuay, JP\n\nSaad, F\n\nKarakiewicz, PI\n\nBeiträge in Fachzeitschriften\nISI:000247112400012\n17488305.0\n10.1111/j.1464-410X.2007.06923.x\nNone\nOBJECTIVE: To explore the distribution of total prostate specific antigen (PSA) and percentage free/total PSA (%f/tPSA) in healthy volunteers with no clinical evidence of prostate cancer, who participated in prostate cancer screening. SUBJECTS AND METHODS: PSA and %f/tPSA values from 2323 men, who participated in one of three annual prostate cancer screening events between 2004 and 2006, were tabulated according to age strata of 40-49, 50-59, 60-69 and 70-79 years. Local regression smoothing plots provided a graphical display of the relation between age and PSA or %f/tPSA, respectively. All PSA and %f/tPSA analyses were repeated for each age category after excluding, respectively, the top and the bottom 10% of PSA and %f/tPSA values. RESULTS: Within the entire cohort, the median PSA level was 1.0 ng/mL and the median %f/tPSA was 25%. According to the age categories the PSA level and %f/tPSA medians within the entire cohort were, respectively, 0.7, 0.9, 1.3, 1.8 ng/mL and 28.0, 26.0, 24.0 and 25.0%. Of the 2323 men, 438 (18.9%) had a PSA level of >2.5 ng/mL and 1172 (50.5%) had a %f/tPSA of < or = 25%. When either a PSA level of >2.5 ng/mL or a %f/tPSA of < or = 25% were considered, 1235 (53.2%) had one or two abnormal values. Finally, if either a PSA level of >2.5 ng/mL or %f/tPSA of < or = 15% was used, 617 (26.6%) were considered abnormal. CONCLUSION: Half of men with no clinical evidence of prostate cancer should have PSA levels of <1.0 ng/mL and a %f/tPSA of >25%. A PSA level threshold of 2.5 ng/mL would require a biopsy in 20% of men and a %f/tPSA threshold of < or = 25% in half of the men. Alternatively, a %f/tPSA threshold of < or = 15% would decrease the probability to 15%.\n\nHutterer, Georg\n\n\n"
},
{
"text": "\n81996\nAmbrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2.\n\nGalie, N\n\nOlschewski, H\n\nOudiz, RJ\n\nTorres, F\n\nFrost, A\n\nGhofrani, HA\n\nBadesch, DB\n\nMcGoon, MD\n\nMcLaughlin, VV\n\nRoecker, EB\n\nGerber, MJ\n\nDufton, C\n\nWiens, BL\n\nRubin, LJ\n\nBeiträge in Fachzeitschriften\nISI:000256576600008\n18506008.0\n10.1161/CIRCULATIONAHA.107.742510\nNone\nBACKGROUND: Ambrisentan is a propanoic acid-based, A-selective endothelin receptor antagonist for the once-daily treatment of pulmonary arterial hypertension. METHODS AND RESULTS: Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Study 1 and 2 (ARIES-1 and ARIES-2) were concurrent, double-blind, placebo-controlled studies that randomized 202 and 192 patients with pulmonary arterial hypertension, respectively, to placebo or ambrisentan (ARIES-1, 5 or 10 mg; ARIES-2, 2.5 or 5 mg) orally once daily for 12 weeks. The primary end point for each study was change in 6-minute walk distance from baseline to week 12. Clinical worsening, World Health Organization functional class, Short Form-36 Health Survey score, Borg dyspnea score, and B-type natriuretic peptide plasma concentrations also were assessed. In addition, a long-term extension study was performed. The 6-minute walk distance increased in all ambrisentan groups; mean placebo-corrected treatment effects were 31 m (P=0.008) and 51 m (P<0.001) in ARIES-1 for 5 and 10 mg ambrisentan, respectively, and 32 m (P=0.022) and 59 m (P<0.001) in ARIES-2 for 2.5 and 5 mg ambrisentan, respectively. Improvements in time to clinical worsening (ARIES-2), World Health Organization functional class (ARIES-1), Short Form-36 score (ARIES-2), Borg dyspnea score (both studies), and B-type natriuretic peptide (both studies) were observed. No patient treated with ambrisentan developed aminotransferase concentrations >3 times the upper limit of normal. In 280 patients completing 48 weeks of treatment with ambrisentan monotherapy, the improvement from baseline in 6-minute walk at 48 weeks was 39 m. CONCLUSIONS: Ambrisentan improves exercise capacity in patients with pulmonary arterial hypertension. Improvements were observed for several secondary end points in each of the studies, although statistical significance was more variable. Ambrisentan is well tolerated and is associated with a low risk of aminotransferase abnormalities.\n\nOlschewski, Horst\n\n\n"
},
{
"text": "\n90627\nInfluence of blue-light-filtering intraocular lenses on color perception and contrast acuity.\n\nWirtitsch, MG\n\nSchmidinger, G\n\nPrskavec, M\n\nRubey, M\n\nSkorpik, F\n\nHeinze, G\n\nFindl, O\n\nKarnik, N\n\nBeiträge in Fachzeitschriften\nISI:000262276700007\n19118695.0\n10.1016/j.ophtha.2008.08.035\nNone\nPURPOSE: To compare contrast acuity at different illumination levels and color vision and the subjective impression in patients after bilateral cataract surgery with a mixed implantation of a blue-light-filtering and an ultraviolet (UV)-filtering intraocular lens (IOL). DESIGN: Randomized, controlled, double-masked, and bilateral study with intraindividual comparison. PARTICIPANTS: This study included 48 eyes of 24 consecutive patients with age-related cataract. METHODS: Each patient had standardized small incision cataract surgery with IOL implantation into the capsular bag. Patients were randomly assigned to receive a blue-light-filtering Hoya AF-1 (UY) YA-60BB IOL in one eye and a UV-filtering Hoya AF-1 (UV) VA-60BB IOL (Hoya Medical Europe, Frankfurt/Main, Germany) in the contralateral eye. Contrast acuity was measured at illumination levels of 500, 5, and 0.5 lux and contrast levels of 100%, 50%, 25%, 12.5%, and 6.25%. Color vision was assessed using the Lanthony desaturated D-15 test, the Lanthony new color test (Munsell chroma 2 and 4), and an anomaloscope. Blue/yellow foveal threshold was tested applying short-wave automated perimetry. The subjective visual impression of patients was evaluated using a questionnaire. MAIN OUTCOME MEASURES: Contrast acuity, color vision, and foveal threshold. RESULTS: The blue-light-filtering IOLs had worse contrast acuity (P = 0.0004) and foveal threshold (P = 0.008) compared with the UV-filtering IOLs. Color vision tests and high-contrast visual acuity did not show any statistically significant differences between IOLs (P>0.05). On questioning, 3 of 24 patients noticed a difference between the implanted IOLs concerning visual impression. CONCLUSIONS: This study shows that blue-light-filtering IOLs negatively affect contrast acuity and blue/yellow foveal threshold when compared with UV-filtering IOLs. Although the differences were small, the results suggest bilateral implantation of the same IOL type and avoidance of a mixed implantation of a blue-light-filtering IOL in one and a non-blue-light-filtering IOL in the contralateral eye in patients with high demands in color vision. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.\n\n\n"
},
{
"text": "\n93403\nSexual abuse in childhood and youth as psychopathologically relevant life occurrence: cross-sectional survey.\n\nNickel, MK\n\nTritt, K\n\nMitterlehner, FO\n\nLeiberich, P\n\nNickel, C\n\nLahmann, C\n\nForthuber, P\n\nRother, WK\n\nLoew, TH\n\nBeiträge in Fachzeitschriften\nISI:000223463200021\n15311424.0\nNone\nNone\nAIM: To assess the perpetrators of sexual abuse in childhood, forms of simultaneous abuse, and characteristics of the families of origin, and the possible effects of abuse on health in adult life. METHODS: A cross sectional study conducted between 1998 and 2002 included a random group of 936 inpatients (723 women) aged (mean+/-standard deviation) 41.0+/-2.5 years at the psychosomatic clinic in Simbach, Germany. The following questionnaires, previously validated in German, were used to assess the patients: Questionnaire for Life Story and Partnership, Scale for Survey of Quality of Life, Existential Orientation Scale, Leipzig Incidence and Psychological Stress Questionnaire, Questionnaire for Assessment of One's Own Body, Survey of Life Satisfaction, Frankfurt Physical Concept Scale, Giessen Complaint Survey, and the Survey for Collection of Health Behavior Data. We compared the inpatients who had been sexually abused in their childhood (n=250) with other psychiatric inpatients in the control group (n=486). RESULTS: Out of 250 sexually abused patients, 25.7% were victimized by fathers/stepfathers, 4% by mothers/stepmothers, 12.4% by aunts or uncles, 10% by brothers or sisters, 7.6% by grandmothers/grandfathers, 30.1% by family acquaintances, and 29.3% by strangers. Unlike the parents of patients in the control group, the parents of sexually abused patients had more conflicts, especially over alcohol consumption (p<0.001) and extramarital affairs (p<0.001), they divorced more frequently during the first seven years of the patient's life (p<0.001), and had more underlying emotional (p<0.001) and physical illnesses (p=0.006). Significantly more sexually abused patients reported having poor concentration (odds ratio [OR]=5.03; 95% confidence interval [CI]=1.98-9.70; p<0.001) and sexual handicaps (OR=5.16; 95% CI=1.81-11.39; p<0.001), tended to hide their body (OR=3.65; 95% CI=1.69-7.30; p<0.001), abused illicit drugs (OR=2.38; 95% CI=1.08-6.01; p<0.001), had borderline personality disorder (OR=4.21; 95% CI=2.44-8.40; p<0.001), and suicidal ideation (OR=2.87; 95% CI=1.71-5.96; p<0.001). CONCLUSION: The patients who were sexually abused in childhood had significantly less satisfactory lives and more frequent psychiatric illnesses, suicidal ideation, disturbed social functioning and perception of the body, and psychosomatic diseases.\n\nNickel, Marius\n\n\n"
},
{
"text": "\n102358\nRole of aquaporin-4 in the development of brain oedema in liver failure.\n\nWright, G\n\nSoper, R\n\nBrooks, HF\n\nStadlbauer, V\n\nVairappan, B\n\nDavies, NA\n\nAndreola, F\n\nHodges, S\n\nMoss, RF\n\nDavies, DC\n\nJalan, R\n\nBeiträge in Fachzeitschriften\nISI:000279705500012\n20451280.0\n10.1016/j.jhep.2010.02.020\nNone\nBackground 8: Aims: Liver failure is associated with progressive cytotoxic brain oedema (astrocyte swelling), which underlies hepatic encephalopathy (HE). Ammonia and superimposed inflammation are key synergistic factors in HE, but the mechanism(s) involved remain unknown. We aimed to determine whether aquaporin-4 (AQP4), an astrocyte endfeet bi-directional water channel, is associated with the brain oedema of HE. Method: Rats (n = 60) received sham-operation (sham), 5 days hyperammonaemia-inducing diet (HD), galactosamine (GALN) induced acute liver failure (ALF), 4 weeks bile duct-ligation (BDL) induced cirrhosis, or caecal ligation and puncture (CLP), a 24 h model of bacterial peritonitis. Rats from every group (except CLP) were randomised to receive intraperitoneal injections of lipopolysaccharide (LPS; 1 mg/kg) or saline, prior to termination 3 h later. Brain water, AQP4 protein expression (western blot) and AQP4 localisation by immunogold electron microscopy were investigated. Results: Significant hyperammonaemia was observed in saline-injected BDL (p < 0.05), GALN (p < 0.01), and HD (p < 0.01), compared to sham rats. LPS injection did not affect arterial ammonia or plasma biochemistry in any of the treatment groups. Increased brain water was observed in saline-injected GALN (p < 0.05), HD (p < 0.01), and CLP (p < 0.001) compared to sham rats. Brain water was numerically increased in BDL rats, but this failed to reach significance (p = 0.09). U'S treatment further increased oedema significantly in all treatment groups (p < 0.05, respectively). AQP4 expression was significantly increased in saline-injected BDL (p < 0.05), but not other treatment groups, compared to sham rats. Membrane polarisation was maintained in BDL rats. Conclusion: The results suggest that AQP4 is not directly associated with the development of brain oedema in liver failure, hyperammonaemia, or sepsis. In cirrhosis, there is increased AQP4 protein expression, but membrane polarisation, is maintained, possibly in a compensatory attempt to limit severe brain oedema. (C) 2010 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.\n\nStadlbauer-Köllner, Vanessa\n\n\n"
}
]
}