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Halper B.,University of Vienna | Hofmann M.,University of Vienna | Oesen S.,University of Vienna | Franzke B.,University of Vienna | And 8 more authors.
Exercise Immunology Review | Year: 2015

Rationale: The TGF-β superfamily has been shown to play an important role in a wide range of physiological as well as pathological processes including ageing, immune modulation, atherosclerosis and cancer development. The aim of the current study was to investigate (i) whether TGF-β signalling in peripheral blood mononuclear cells (PBMCs) would differ between young and old females and (ii) whether physical performance parameters of elderly women would be related to the expression of TGF-β or its receptors. Methods: Sixteen healthy young (22-28 years; YF) and 90 healthy older (65-92 years; OF) females participated in the study. In addition to several components of health-related physical fitness, circulating CRP and TGF-β levels were determined together with the mRNA expression of TGF-β, TGF-βRI, TGF-βRII, and miRNA-21 (known to interfere with TGF-β signalling) in PBMCs. Results: Physical fitness as determined by 6-minutes walking test (YF:median 932 (range 573-1254) m; OF:360 (114-558) m), handgrip strength (YF: 32 (24-39) kg; OF:18(10-30) kg), relative isokinetic peak torque of knee extensors (YF:1.9 (1.2-2.3) Nm/kg; OF:1.0 (0.2-1.9) Nm/kg and flexors (YF: 1.1 (0.7-1.5) Nm/kg; OF: 0.5 (0.2-1.0) Nm/kg was substantially lower in older women (p<0.001 for all comparisons). These changes were paralleled by an increase in hs-CRP (YF: 0.9 (0.1-4.3)mg/L; OF: 2.3 (0.3-56.7)mg/L,p<0.001). Serum levels of TGF-β and TGF-β mRNA levels from PBMCs did not differ between young and old women whereas, both TGF-βRI/GAPDH (YF: 4.07 (1.38-14.60); OF: 2.08 (0.14-28.81); p=0.020) and TGF-βRII/GAPDH levels (YF: 3.16 (1.14-10.25); OF: 1.71 (0.51-14.86); p=0.020) were lower with respect to old age. In elderly women, only TGF-βRI expression correlated negatively with miRNA-21 expression in PBMCs (ρ=-0.315; p=0.004). Interestingly, hs-CRP and miRNA correlated positively with handgrip strength (ρ=0.237 and ρ=243, p<0.05), while none of the TGF-β-related parameters were related to physical performance. Conclusion: The results suggest that age affects TGF-β signalling in leukocytes by altering the expression levels of its receptors. These changes seem to occur independently of physical fitness of old women. © 2002 by Hinnak Northoff.


Tinchon A.,Kaiser Franz Joseph Hospital | Oberndorfer S.,State Hospital Of St Polten | Marosi C.,Vienna University Hospital | Ruda R.,University of Turin | And 3 more authors.
Journal of Neuro-Oncology | Year: 2012

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. Compared with other malignancies, remote metastases in GBM are rare. However, multicentric spreading within the central nervous system is common and also metastases to the spinal cord have been reported. Some of these drop metastases may also lead to malignant spinal cord compression (MSCC). We retrospectively identified nine patients from 2001 to 2010 and performed data analysis according to a standardized clinical protocol. We also provide a review of the literature on this rare condition. MSCC from cerebral GBM is rare and is found in approximately 1 % of GBM patients. Median age of 54 years in this case series is comparable with that of GBM patients without MSCC. Treatment regimens for cerebral GBM and overall survival was similar to those for patients without MSCC. Spinal metastasis seems to occur in the advanced state of the disease, and the outcome subsequently is extremely poor. All patients presented with multicentric radiological features of GBM on cerebral MRI when MSCC was diagnosed. Subependymal enhancement is another common radiological finding in GBM patients with spinal drop metastases. Steroids and focal radiotherapy were used to treat all patients, with little clinical benefit. This study is the largest case series of MSCC from cerebral GBM. Multicentric cerebral distribution and subependymal enhancement of GBM are observed on cerebral MRI at the time of MSCC. On the basis of our results, no specific treatment recommendations for MSCC in GBM patients can be given. However, accurate diagnosis of MSCC in GBM patients with spinal signs and symptoms can lead to adequate management of symptoms and improvement of quality of life in terms of best palliative care. © 2012 Springer Science+Business Media, LLC.


Siller-Matula J.M.,Medical University of Vienna | Huber K.,Wilhelminenhospital | Christ G.,Kaiser Franz Joseph Hospital | Schror K.,Heinrich Heine University Düsseldorf | And 3 more authors.
Heart | Year: 2011

Context: Enhanced platelet inhibition by clopidogrel decreases the risk of ischemic events but carries a risk for a concomitant increase in bleeding. Objectives: To compare the efficacy and safety of two clopidogrel loading regimens (300mg vs. 600mg) in patients undergoing percutaneous coronary intervention (PCI) at one month after start of therapy. Data sources: A systematic literature search of MEDLINE, EMBASE, CENTRAL, and Web of Science databases using predefined search terms for relevant articles in any language. Study selection and data extraction: Randomised controlled trials and non-randomised studies reporting adjusted effect estimates were included. Summary estimates of the risks ratios (RRs) with therapy were calculated using a random-effect model. Outcomes evaluated were combined major adverse cardiovascular events (MACE) and major bleedings. Results: Seven studies met the inclusion criteria and included 25,383 patients. A 600mg clopidogrel loading was associated with a 34% relative risk reduction of MACE (RR=0.66; 95% confidence intervals CI=0.52-0.84; p<0.001). Sub-analysis revealed a 47% risk reduction of MACE in randomised trials (RR=0.53; 95% CI=0.32-0.88; p=0.01) and a 31% relative risk reduction in non-randomised trials (RR=0.69; 95%CI=0.54-0.90; p=0.005) in patients receiving 600mg loading with clopidogrel. In patients suffering from acute coronary syndrome, 600mg clopidogrel loading was associated with a 24% relative risk reduction in MACE (RR=0.76; 95%CI=0.60-0.95; p=0.02). Importantly, the 600mg clopidogrel loading dose was not associated with an increased risk of major bleedings (RR=0.91; 95% CI=0.73-1.15; p=0.44). Conclusions: This meta-analysis demonstrates that intensified clopidogrel loading with 600mg reduces the rate of major cardiovascular events without increase in major bleeding compared to 300mg in patients undergoing PCI during one month follow-up.


Siller-Matula J.M.,Medical University of Vienna | Jilma B.,Medical University of Vienna | Schror K.,Heinrich Heine University Düsseldorf | Christ G.,Kaiser Franz Joseph Hospital | Huber K.,Wilhelminenhospital
Journal of Thrombosis and Haemostasis | Year: 2010

To investigate whether proton pump inhibitors (PPIs) negatively affect clinical outcome in patients treated with clopidogrel. Systematic review and meta-analysis. Outcomes evaluated were combined major adverse cardiac events (MACE), myocardial infarction (MI), stent thrombosis, death and gastrointestinal bleeding. Studies included were randomized trials or post-hoc analyzes of randomized trials and observational studies reporting adjusted effect estimates. Twenty five studies met the selection criteria and included 159-138 patients. Administration of PPIs together with clopidogrel corresponded to a 29% increased risk of combined major cardiovascular events [risk ratio (RR)-=-1.29, 95% confidence intervals (CI)-=-1.15-1.45] and a 31% increased risk of MI (RR-=-1.31, 95%CI-=-1.12-1.53). In contrast, PPI use did not negatively influence the mortality (RR-=-1.04, 95%CI-=-0.93-1.16), whereas the risk of developing a gastrointestinal bleed under PPI treatment decreased by 50% (RR-=-0.50, 95% CI-=-0.37-0.69). The presence of significant heterogeneity might indicate that the evidence is biased, confounded or inconsistent. The sensitivity analysis, however, yielded that the direction of the effect remained unchanged irrespective of the publication type, study quality, study size or risk of developing an event. Two studies indicate that PPIs have a negative effect irrespective of clopidogrel exposure. In conclusion, concomitant PPI use might be associated with an increased risk of cardiovascular events but does not influence the risk of death. Prospective randomized trials are required to investigate whether a cause-and-effect relationship truly exists and to explore whether different PPIs worsen clinical outcome in clopidogrel treated patients as the PPI-clopidogrel drug-drug interaction does not seem to be a class effect. © 2010 International Society on Thrombosis and Haemostasis.


Angelini C.,University of Padua | Grisold W.,Kaiser Franz Joseph Hospital | Nigro V.,Telethon Institute of Genetics and Medicine
Acta Myologica | Year: 2011

We investigated the clinical and molecular pattern of two young men affected by dysferlinopathy, that was first diagnosed as polymyositis. We show that their symptoms and clinical course although progressive were peculiar, as well as their biopsy suggesting a subsequent analysis of dysferlin protein by western blotting. Molecular analysis of dysferlin gene revealed pathogenetic mutations in both cases. In such cases a screening with Western blot followed by DNA analysis of dysferlin gene is therefore recommended. We present a diagnostic algorythm for patients with suspected myositis but presenting signs of disease progression and poor response to steroids.


Ageing, inactivity and obesity are associated with chronic low-grade inflammation contributing to a variety of lifestyle-related diseases. Transforming growth factor- (TGF-) is a multimodal protein with various cellular functions ranging from tissue remodelling to the regulation of inflammation and immune functions. While it is generally accepted that aerobic exercise exerts beneficial effects on several aspects of immune functions, even in older adults, the effect of resistance training remains unclear. The aim of this study was to investigate whether progressive resistance training (6months) with or without nutritional supplementation (protein and vitamins) would influence circulating C-reactive protein and TGF- levels as well as TGF- signalling in peripheral mononuclear cells (PBMCs) of institutionalised adults with a median age of 84.5 (65.0-97.4) years.Elastic band resistance training significantly improved performance as shown by the arm-lifting test (p=0.007), chair stand test (p=0.001) and 6-min walking test (p=0.026). These results were paralleled by a reduction in TGF- receptor I (TGF-RI) mRNA expression in PBMCs (p=0.006), while circulating inflammatory markers were unaffected. Protein and vitamin supplementation did not provoke any additional effects. Interestingly, muscular endurance of upper and lower body and aerobic performance at baseline were negatively associated with changes in circulating TGF- at the early phase of the study. Furthermore, drop-outs of the study were characterised not only by lower physical performance but also higher TGF- and TGF-RI mRNA expression, and lower miRNA-21 expression.Progressive resistance training with elastic bands did not influence chronic low-grade inflammation but potentially affected TGF- signalling in PBMCs through altered TGF-RI mRNA expression. There appears to be an association between physical performance and TGF- expression in PBMCs of older adults, in which the exact mechanisms need to be clarified.


Strasser E.M.,Kaiser Franz Joseph Hospital | Draskovits T.,Kaiser Franz Joseph Hospital | Praschak M.,Kaiser Franz Joseph Hospital | Quittan M.,Kaiser Franz Joseph Hospital | Graf A.,Medical University of Vienna
Age | Year: 2013

The increase of elderly in our society requires simple tools for quantification of sarcopenia in inpatient and outpatient settings. The aim of this study was to compare parameters determined with musculoskeletal ultrasound (M-US) with muscle strength in young and elderly patients. In this prospective, randomised and observer blind study, 26 young (24.2±3.7 years) and 26 old (age 67.8±4.8 years) patients were included. Muscle thickness, pennation angle and echogenicity of all muscles of musculus quadriceps were measured by M-US and correlated with isometric maximum voluntary contraction force (MVC) of musculus quadriceps. Reproducibility of MUS measurements as well as simple and multiple regression models were calculated. Of all measured M-US variables the highest reproducibility was found formeasurements of thickness (intraclass correlation coefficients, 85-97 %). Simple regression analysis showed a highly significant correlation of thickness measurements of all muscles of musculus quadriceps with MVC in the elderly and in the young. Multiple regression analysis revealed that thickness of musculus vastus medialis had the best correlation with MVC in the elderly. This study showed that measurement of muscle thickness, especially of musculus vastus medialis, by M-US is a reliable, bedside method for monitoring the extent of sarcopenia. © American Aging Association 2013.


Maier C.,Medical University of Vienna | Riedl M.,Medical University of Vienna | Vila G.,Medical University of Vienna | Wolzt M.,Medical University of Vienna | And 3 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2010

Context: Obestatin is cosecreted with and stemming from the same precursor as ghrelin and is apparently involved in energy metabolism. Relatively little is known about the regulation of obestatin release. Objective: The regulation of obestatin release and obestatin-to-ghrelin ratios by meal intake and the cholinergic system were studied in lean and obese subjects. Design, Participants, and Setting: We conducted a randomized, double-blind, placebo-controlled, crossover study with 4 study days in eight obese (body mass index >30 kg/m2) and eight matched lean (body mass index <25 kg/m2) healthy subjects (two males and six females per group) at a University Clinical Research Unit. Interventions: Atropine (1 mg iv) was administered alone and in combination with breakfast (550 kcal) intake, or placebo (isotonic saline) alone and in combination with breakfast. Main Outcome Measures: We measured plasma obestatin and obestatin/ghrelin ratios. Results: Both obestatin and ghrelin/obestatin ratios decreased significantly from baseline by either atropine or meal intake in lean individuals, with the two effects adding up on the combined atropine/breakfast day. In contrast, there were no statistically significant differences in obese subjects, who also showed significantly greater association between ghrelin and obestatin values than their lean counterparts. Conclusions: Obestatin and ghrelin release is differentially regulated by meal intake and the cholinergic system in lean individuals. This regulation is impaired in obesity. Copyright © 2010 by The Endocrine Society.


Tinchon A.,Kaiser Franz Joseph Hospital | Oberndorfer S.,State Hospital Of St Poelten | Marosi C.,Vienna University Hospital | Gleiss A.,Vienna University Hospital | And 5 more authors.
Journal of Neurology | Year: 2015

Patients with glioblastoma multiforme (GBM) and symptomatic seizures are in need of a sufficient antiepileptic treatment. Haematological toxicity is a limiting side effect of both, first line radio-chemotherapy with temozolomide (TMZ) and co-medication with antiepileptic drugs. Valproic acid (VPA) and levetiracetam (LEV) are considered favourable agents in brain tumor patients with seizures, but are commonly reported to induce haematological side effects on their own. We hypothesized, that antiepileptic treatment with these agents has no increased impact on haematological side effects during radio-chemotherapy in the first line setting. We included 104 patients from two neuro-oncologic centres with GBM and standard radio-chemotherapy in a retrospective cohort study. Patients were divided according to their antiepileptic treatment with either VPA, LEV or without antiepileptic drug therapy (control group). Declines in haemoglobin levels and absolute blood cell counts for neutrophil granulocytes, lymphocytes and thrombocytes were analyzed twice during concomitant and once during adjuvant phase. A comparison between the examined groups was performed, using a linear mixed model. Neutrophil granulocytes, lymphocytes and thrombocytes significantly decreased over time in all three groups (all p < 0.012), but there was no significant difference between the compared groups. A significant decline in haemoglobin was observed in the LEV treated group (p = 0.044), but did not differ between the compared groups. As a novel finding, this study demonstrates that co-medication either with VPA or LEV in GBM patients undergoing first line radio-chemotherapy with TMZ has no additional impact on medium-term haematological toxicity. © 2014, European Union.


The assessment of mobility is important in the acute care setting. Existing tests suffer from limitations. The aim of the study was to examine the inter-rater reliability, the validity, the sensitivity to change, and the internal consistency of an ICF based scale.In a prospective study inpatients in the acute care setting with restricted mobility aged above 50 years assigned to rehabilitative treatment were included. Assessment of subscales of the Functional Independence Measure (FIM) and the ICF based Basic Mobility Scale (BMS) were performed at admission and before discharge. Furthermore pain, length of stay in hospital, and post-discharge residential status were recorded. Inter-rater reliability, criterion-concurrent validity, sensitivity to change, and internal consistency were calculated. Furthermore, floor and ceiling effects were determined.One hundred twenty-five patients (79 women/46 men) were included. The BMS showed an excellent inter-rater reliability for the total BMS (ICC BMS: 0.85 (95 % CI: 0.81-0.88). The criterion-concurrent validity was high to excellent (Spearman correlation coefficient: -0.91 in correlation to FIM) and the internal consistency was good (Cronbachs alpha 0.88). The BMS proved to be sensitive to improvements in mobility (Wilcoxons signed rank test: p<0.0001; The effect size for the BMS was 1.075 and the standardized response mean 1.10. At admission, the BMS was less vulnerable to floor effects.The BMS may be used as a reliable and valid tool for the assessment of mobility in the acute care setting. It is easy to apply, sensitive to change during the hospital stay and not vulnerable to floor and ceiling effects.

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