Michael Wolzt

Medical University of Vienna, Wien, Vienna, Austria

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Publications (349)1341.07 Total impact

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    ABSTRACT: Purpose: Beneficial effects of dietary supplements in AMD are related to anti-oxidative properties. In the AREDS 1 study, a reduced progression to late stage AMD was found using vitamin C, E, zinc and ß-carotene. We previously showed that the AREDS 1 formulation restores the O2-induced retinal vasoconstrictor response of retinal vessels in a human endotoxin (LPS) model. Methods: We hypothesized that the abnormal O2-induced retinal red blood cell (RBC) flow response can be modulated by a different formulation (Vitamin C, E and zinc, lutein/zeaxanthin, selen, taurine, Aronia extract and omega-3 free fatty acids). 43 healthy subjects were included in this randomized, double masked, placebo-controlled parallel group study. The reactivity of retinal arterial and venous diameter, RBC velocity and flow to 100% O2 breathing was investigated in the absence and presence of 2 ng/kg LPS. Between the two study days was a 14 days period of daily dietary supplement intake. Results: The decrease in retinal art. diameter, RBC velocity and flow during 100% O2 breathing was significantly diminished after LPS infusion. Dietary supplement intake for 14 days almost restored the response of retinal hemodynamic parameters to 100% O2 after LPS administration. This effect was significant for retinal art. diameter (p = 0.03 between groups), RBC velocity and flow (each p < 0.01 between groups). Conclusions: The present data indicate restoring of the RBC flow response to 100% O2 after LPS administration. This is likely due to an amelioration of endothelial dysfunction resulting from oxidative stress, a factor involved in AMD pathophysiology. Copyright © 2014 by Association for Research in Vision and Ophthalmology.
    Investigative ophthalmology & visual science. 12/2014;
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    ABSTRACT: Introduction: Experimental studies have shown that liposomal curcumin can exert a reduction in tumor growth in pancreatic and colorectal cancer. In this phase I clinical trial we investigated the pharmacokinetics, safety, and tolerability of intravenously administered liposomal curcumin in healthy subjects. Material and methods: 50 male and female participants were included in this randomized, placebo-controlled double-blind phase I dose escalation study. Subjects received a single dose of liposomal curcumin (10 - 400 mg/m2; n = 2 - 6 per group) or placebo over 2 hours intravenously. Results: Dose-dependent increases in the plasma concentrations of curcumin and its metabolite tetrahydrocurcumin (THC) were detected. After the end of drug infusion, curcumin and THC plasma concentrations decreased within 6 - 60 minutes below the limit of quantification. Mean urinary excretion was ~ 0.1% of total systemic clearance. Liposomal curcumin was tolerated well, but a transient red blood cell echinocyte formation with concomitant increase in mean cellular volume was observed at dosages ≥ 120 mg/m2. Conclusion: Short-term intravenous dosing of liposomal curcumin appears to be safe up to a dose of 120 mg/m2. Changes in red blood cell morphology may represent a dose limiting sign of toxicity.
    International journal of clinical pharmacology and therapeutics 12/2014; · 1.20 Impact Factor
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    ABSTRACT: Background:The clinical value of T-wave variability (T-var) for ventricular arrhythmia (VA) risk prediction was evaluated.Methods and Results:Three 20-min Holter-ECG-based T-var measurements (I1 at baseline, I2 after 6.5±1.6 months and I3 after 13.1±2.0 months) were done in 121 patients. T-var was defined as the amplitude variability of the T-wave with the maximum of T-wave oscillation. The endpoint was a fast, potentially fatal VA (>240 beats/min). During follow-up (20±4 months) 20/121 patients (55% ischemic heart disease, 15% preserved left ventricular ejection fraction [LVEF]) had fast VA terminated by ICD or external shock. Although T-var did not differ between patients with vs. without fast VA at baseline (I1: 10.7±7.3 µV vs. 7.8±4.1 µV, P=0.170), patients with fast VA had higher T-var compared to those without fast VA at 2 subsequent measurements (I2: 14.0±6.5 µV vs. 8.2±3.6 µV, P=0.030; I3: 17.0±5.4 µV vs. 8.8±4.6 µV, P=0.004). The increase in T-var between I1 and I2 was higher in patients with fast VA (∆T-var=7.0±9.3 µV), as compared to patients without (∆T-var=0.4±4.3 µV). After adjustment for LVEF in a multiple logistic regression model, the odds ratio for developing fast VA was 1.1 (P=0.056) for each 1-µV increment in T-var at I1.Conclusions:T-var is elevated in patients with fast VA, and both elevation of T-var and increase in T-var may complement LVEF in VA risk stratification.
    Circulation journal : official journal of the Japanese Circulation Society. 12/2014;
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    ABSTRACT: Background Patients with acute coronary syndrome and concomitant atrial fibrillation may require antithrombotic triple therapy but clinical evidence of safety and efficacy is poor. We have therefore studied the combination of different antithrombotic medicines on coagulation activation in an in vivo model in the skin microvasculature.Methods and ResultsPlatelet activation (β-thromboglobulin [β-TG]) and thrombin generation (prothrombin fragment 1+2 [F1+2], thrombin-antithrombin complex [TAT]) were studied in an open-label, randomized, parallel group trial in 60 healthy male subjects (n=20 per group) who received ticagrelor and acetylsalicylic acid (ASA) in combination with dabigatran (150 mg bid) or rivaroxaban (20 mg od) or phenprocoumon (INR 2.0-3.0). Coagulation biomarkers in shed blood were assessed at 3 h after monotherapy of the medicines under study, at 3 h post triple therapy dosing and at steady state trough conditions.Ticagrelor, dabigatran or rivaroxaban single doses caused comparable decreases in shed blood β-TG and were more pronounced than phenprocoumon at an INR of 2.0-3.0. In contrast, thrombin generation was more affected by rivaroxaban and phenprocoumon than with dabigatran. During triple therapy a similarly sustained inhibition of platelet activation and thrombin generation with a maximum decrease of β-TG, F1+2 and TAT at 3 h post dosing was noted which remained below pre-dose levels at trough steady state.ConclusionA triple therapy at steady state with ticagrelor plus ASA in combination with dabigatran or rivaroxaban is as effective as a combination with phenprocoumon on platelet activation and thrombin generation in vivo.This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 09/2014; · 6.08 Impact Factor
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    ABSTRACT: AimsWe aimed to evaluate the association of the nutritional status by using the nutritional risk index (NRI) with metabolic and inflammatory biomarkers, and appetite-regulatory hormones in a cohort of stable patients with heart failure (HF), and to analyse its prognostic value.Methods and resultsIn this prospective observational cohort study, we included 137 stable chronic HF patients (median age, 60 years; median body mass index, 27 kg/m2) with optimised medical treatment. Baseline NRI of < 113 (n = 45) was associated with a significant increase in the levels of ghrelin (p < 0.001), peptide YY (p = 0.007), pentraxin-3 (p = 0.001), tumour necrosis factor-alpha (p = 0.018), adiponectin (p < 0.0001) and the N-terminal prohormone of brain natriuretic peptide (NT-proBNP; p < 0.0001) compared with those in patients with NRI of ≥ 113. The NRI was found to be correlated with the homoeostasis model assessment of insulin resistance index (r = 0.444; p < 0.0001) and inversely correlated with the NT-proBNP level (r = −0.410; p < 0.0001). The overall mortality rate was 20%. A baseline NRI of < 113 was associated with a higher risk of all-cause mortality (log rank = 0.031).Conclusion We propose that the NRI is a useful and easily applicable tool for the early identification of nutritional depletion in patients with chronic HF as it discriminates metabolic changes prior to the clinical manifestation of body wasting. Furthermore, poor nutritional status, represented as a low NRI, is associated with an increased incidence of death in such cases.
    International Journal of Clinical Practice 08/2014; · 2.43 Impact Factor
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    Proceedings of the ISMRM, Milano, Italy; 05/2014
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    Proceedings of the ISMRM, Milano, Italy; 05/2014
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    ABSTRACT: PurposeThe aim of this study was to develop a measurement protocol for noninvasive simultaneous perfusion quantification and T2*-weighted MRI acquisition in the exercising calf muscle at 7 Tesla.Methods Using a nonmagnetic ergometer and a dedicated in-house built calf coil array, dynamic pulsed arterial spin labeling (PASL) measurements with a temporal resolution of 12 s were performed before, during, and after plantar flexion exercise in 16 healthy volunteers.ResultsPostexercise peak perfusion in gastrocnemius muscle (GAS) was 27 ± 16 ml/100g/min, whereas in soleus (SOL) and tibialis anterior (TA) muscles it remained at baseline levels. T2*-weighted and ASL time courses in GAS showed comparable times to peak of 161 ± 72 s and 167 ± 115 s, respectively. The T2*-weighted signal in the GAS showed a minimum during exercise (88 ± 6 % of the baseline signal) and a peak during the recovery (122 ± 9%), whereas in all other muscles only a signal decrease was observed (minimum 91 ± 6% in SOL; 87 ± 8% in TA).Conclusion We demonstrate the feasibility of dynamic perfusion quantification in skeletal muscle at 7 Tesla using PASL. This may help to better investigate the physiological processes in the skeletal muscle and also in diseases such as diabetes mellitus and peripheral arterial disease. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 04/2014; early view. · 3.27 Impact Factor
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    ABSTRACT: Background Physicians refer proteinuric patients to kidney biopsy in order to clarify the issue of underlying renal disease. We compared kidney biopsy results with classical outcome parameters in a large cohort of patients with biopsy proven glomerulonephritis (GN).Methods In a retrospective analysis, 2,687 patients with different forms of GN from 123 Austrian centres were investigated. Patient characteristics, the diagnosis of GN and its respective subtype and clinical symptoms such as arterial hypertension, hematuria, amount of proteinuria and estimated glomerular filtration rate (eGFR) were tested for their association with all-cause mortality and progression to end stage renal disease (ESRD).ResultsDuring a median follow-up of 129.9 months (IQR 89.6;177.7) 688 patients (25.6%) died and 718 patients required dialysis (29.4%). In multivariate Cox regression analysis age (HR 1.06), female sex (HR 0.71), eGFR (HR 0.74), the diagnosis of GN and its subtypes predicted patient survival (all p<0.01) whereas the amount of proteinuria was not associated with patient survival. The incidence of progression to ESRD was associated with female sex (HR 0.71), eGFR (HR 0.65), amount of proteinuria (HR 1.15) and the diagnosis of GN and its subtypes (all p<0.01). Nephrotic or nephritic syndromes were not associated with patient survival or progression to ESRD and did not add further predictive value to outcome of GN.Conclusion Our study demonstrates histological diagnosis of GN and its specific subtype predict patient survival and dialysis incidence. Therefore, kidney biopsy should be an integral part of routine diagnostic assessment in patients with any forms of suspected GN.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 04/2014; · 3.37 Impact Factor
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    ABSTRACT: Skeletal muscle metabolism is impaired in disorders like diabetes mellitus or peripheral vascular disease. The skeletal muscle echo planar imaging (EPI) signal (SEPI ) and its relation to energy metabolism are still debated. Localised 31P MRS and SEPI data from gastrocnemius medialis of 19 healthy subjects were combined in one scanning session to study direct relationships between phosphocreatine (PCr), pH kinetics and parameters of T2∗ time courses. Dynamic spectroscopy (semi-LASER) and EPI were performed immediately before, during and after 5 min of plantar flexions. Data were acquired in a 7 T MR scanner equipped with a custom-built ergometer and a dedicated (31) P/(1) H radio frequency (RF) coil array. Using a form-fitted multi-channel (31) P/(1) H coil array resulted in high signal-to-noise ratio (SNR). PCr and pH in the gastrocnemius medialis muscle were quantified from each (31) P spectrum, acquired every 6 s. During exercise, SEPI (t) was found to be a linear function of tissue pH(t) (cross-correlation r = -0.85 ± 0.07). Strong Pearson's correlations were observed between post exercise time-to-peak (TTP) of SEPI and (a) the time constant of PCr recovery τPCr recovery (r = 0.89, p < 10(- 6) ), (b) maximum oxidative phosphorylation using the linear model, Qmax, lin (r = 0.65, p = 0.002), the adenosine-diphosphate-driven model, Qmax,ADP (r = 0.73, p = 0.0002) and (c) end exercise pH (r = 0.60, p = 0.005). Based on combined accurately localised 31P MRS and T2∗ weighted MRI, both with high temporal resolution, strong correlations of the skeletal muscle SEPI during exercise and tissue pH time courses and of post exercise SEPI and parameters of energy metabolism were observed. In conclusion, a tight coupling between skeletal muscle metabolic activity and tissue T2∗ signal weighting, probably induced by osmotically driven water shift, exists and can be measured non-invasively, using NMR at 7 T. © 2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.
    NMR in Biomedicine 03/2014; · 3.45 Impact Factor
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    ABSTRACT: Glomerular filtration rate (GFR) in patients with chronic kidney disease (CKD) identifies patients at risk for death or end-stage renal disease (ESRD). CKD staging by GFR should incorporate proteinuria to augment risk stratification. We therefore tested the predictive power of the combination of GFR with proteinuria in patients with different histologically-diagnosed types of glomerulonephritis (GN). In a retrospective analysis, 2,687 patients with different forms of GN from 123 Austrian centres were investigated. Full data sets were available from 1,892 subjects. Classes of CKD on the basis of estimated GFR (eGFR) and of proteinuria grouped as <1, 1-3.5, and >3.5 g/24 h were tested for their association with all-cause mortality and ESRD. During a median follow-up of 130 months [interquartile range (IQR) 90; 178] 478 patients (25.3 %) died. Median eGFR was 49 ml/min/1.73 m(2) (IQR 24; 81) and proteinuria 3.8 g/24 h (IQR 1.7; 8.0). Adjusted multivariate Cox regression indicated that renal survival but not overall survival is related to proteinuria >3.5 g/24 h [as opposed to <1 g/24 h; hazard ratio (HR) 1.91] and shows progression to ESRD. However, subgroup analyses revealed that this risk with proteinuria >3.5 g/24 h exists only in patients with immunoglobulin (Ig)A GN (HR 4.93), miscellaneous GN (HR 1.74), and CKD stage 5 (HR 2.50). Additionally, proteinuria is a risk factor for renal survival in males more than in females with GN and proteinuria >3.5 g/24 h (HR 1.91). Proteinuria is a strong risk factor for renal survival particularly in patients with proteinuria >3.5 g/24 h but not for all types of GN, nor for all CKD stages. Proteinuria is not a risk factor for overall survival in patients with GN.
    Journal of nephrology 03/2014; · 2.02 Impact Factor
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    ABSTRACT: Purpose: The Age-Related Eye Disease Study 1 (AREDS1) showed that nutritional supplementation with anti-oxidants and zinc modifies the natural course of AMD. LPS induced oxidative stress diminishes the vasoconstrictor response of retinal vessels to oxygen breathing and was previously shown to be normalized by the AREDS 1 supplements. In the present study we hypothesized that the retinal vascular response can be restored by a different formulation. Methods: In this randomized, double masked, placebo-controlled parallel group study retinal red blood cell (RBC) flow and the reactivity of retinal RBC flow to 100% oxygen breathing were investigated in the absence and presence of 2ng/kg LPS in 40 healthy volunteers. They either received the supplements or placebo for 14 days. Results: Before supplementation LPS reduced retinal arterial vasoconstriction (p<0.001) and reactivity of retinal RBC flow (p=0.03) in response to hyperoxia. Supplementation did not affect baseline retinal RBC flow but normalized the LPS-induced change in the response to hyperoxia. During LPS and hyperoxia the arterial vasoconstrictor response was 4.1±1.0% after administration of placebo and 10.6±0.9% after supplementation (p = 0.005). The response of RBC flow to 100% oxygen breathing during LPS was 52.2±2.1% after administration of placebo and 59.5±2.0% after supplementation (p = 0.033). Conclusions: Our data show that the supplement used in the present study can normalize the response of retinal RBC flow to hyperoxia under LPS administration. This indicates that supplementation can prevent endothelial dysfunction induced by oxidative stress, which is assumed to play a role in the pathophysiology of AMD.
    Investigative ophthalmology & visual science 02/2014; · 3.43 Impact Factor
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    ABSTRACT: Acute inflammation induced by administration of Escherichia coli lipopolysaccharide endotoxin (LPS) reduces plasma concentrations of vitamin C and impairs vascular endothelium-derived nitric oxide (NO) bioactivity. We tested the hypothesis that systemically administered high dose vitamin C restores the endogenous anti-oxidant potential and improves NO-dependent vasodilatation in the forearm vasculature. 36 male subjects were enrolled in this balanced, placebo controlled cross-over study. Forearm blood flow (FBF) reactivity to acetylcholine (ACh) and glyceryl- trinitrate (GTN), a sensitive test for endothelial function, was assessed at baseline and 4hours after LPS-administration (20IU/kg i.v). The effect of two different doses of intravenous vitamin C (Vitamin C-Injektopas®), 320mg/kg and 480mg/kg over 2hours, or placebo on forearm vascular function was studied after LPS. LPS caused transient flu-like symptoms, decreased plasma vitamin C concentrations and reduced the ACh-dependent increase in FBF by up to 76%. Vitamin C at a mean plasma concentration of 3.2 or 4.9mmol/l restored the response to ACh compared to baseline. High dose systemic vitamin C recovers LPS-induced endothelium-dependent vasodilation in the forearm resistance vasculature. This provides a rationale for a further clinical study of the systemic vitamin C effect under inflammatory conditions.
    Vascular Pharmacology 02/2014; · 3.21 Impact Factor
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    ABSTRACT: Pentoxifylline, a nonselective phosphodiesterase inhibitor, shows vasodilator effects in certain vascular beds and reduces blood viscosity. We have previously shown that under states of vasoconstriction an interaction between circulating erythrocytes and leukocytes may play a role in the control of blood flow. The reason for this observation is not entirely clear but may be related to a mechanical interaction between red and white blood cells. In the present study we hypothesized that pentoxifylline may alter this interaction during oxygen-induced vasoconstriction. 24 healthy male subjects participated in this double masked, randomized, placebo-controlled 2 way cross over trail. In order to increase white blood cell count (WBC) count, 300μg of G-CSF were administered intravenously. Vasoconstriction of retinal vessels was induced by oxygen inhalation. 400mg of pentoxifylline or placebo were infused at two different study days. White blood cell flux was assessed with the blue-field entoptic technique. Vessel calibers were measured with a Dynamic Vessel Analyzer (DVA) and red blood cell velocity (RBCV) was determined with Laser Doppler Velocimetry (LDV). Retinal blood flow was calculated based on retinal vessel diameters and RBCV. Administration of G-CSF induced a significant increase in WBC, both in the placebo and the pentoxifylline group (p<0.01 for both groups). Retinal vessel diameter, RBCV, calculated retinal blood flow and white blood cell flow were not altered by administration of pentoxifylline. Hyperoxia induced a pronounced decrease in retinal blood flow parameters. No difference was observed between groups during oxygen breathing in vessel diameters (p=0.54), RBCV (p=0.34), calculated retinal blood flow (p=0.3) and white blood cell flow (p=0.26). Our data indicate that short time administration of pentoxifylline does not alter the oxygen-induced effect on ocular blood flow parameters during leukocytosis. Whether long-term treatment could improve retinal blood flow under states of vasoconstriction remains to be investigated.
    Microvascular Research 01/2014; · 2.93 Impact Factor
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    ABSTRACT: The objective of our project was to create a tool for physicians to explore health claims data with regard to adverse drug reactions. The Java Adverse Drug Event (JADE) tool should enable the analysis of prescribed drugs in connection with diagnoses from hospital stays. We calculated the number of days drugs were taken by using the defined daily doses and estimated possible interactions between dispensed drugs using the Austria Codex, a database including drug-drug interactions. The JADE tool was implemented using Java, R and a PostgreSQL database. Beside an overview of the study cohort which includes selection of gender and age groups, selected statistical methods like association rule learning, logistic regres-sion model and the number needed to harm have been implemented. The JADE tool can support physicians during their planning of clinical trials by showing the occurrences of adverse drug events with population based information.
    Studies in health technology and informatics 01/2014; 198:249.
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    ABSTRACT: BACKGROUND: Resveratrol is a key component of red wine that has been reported to have anti-carcinogenic and anti-aging properties. Additional studies conducted in vitro and in animal models suggested anti-inflammatory properties. However, data from primary human immune cells and in vivo studies are limited. METHODS: A pilot study was performed including 10 healthy volunteers. Plasma cytokine levels were measured over 48h after oral application of 5g resveratrol. To verify the in vivo findings, cytokine release and gene expression in human peripheral blood mononuclear cells (PBMC) and/or monocytes was assessed after treatment with resveratrol or its metabolites and stimulation with several toll-like receptor (TLR)-agonists. Additionally, the impact on intracellular signaling pathways was analyzed using a reporter cell line and Western blotting. RESULTS: Resveratrol treated individuals showed a significant increase in tumor necrosis factor-α (TNF-α) levels 24h after treatment compared to baseline. Studies using human PBMC or isolated monocytes confirmed potentiation of TNF-α production with different TLR agonists, while interleukin (IL)-10 was inhibited. Moreover, we observed significantly enhanced nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NF-κB) activation using a reporter cell line and found increased phosphorylation of p105, which is indicative of alternative NF-κB pathway activation. GENERAL SIGNIFICANCE: By administering resveratrol to healthy humans and utilizing primary immune cells we were able to detect TNF-α enhancing properties of the agent. In parallel, we found enhanced alternative NF-κB activation. We report on a novel pro-inflammatory property of resveratrol which has to be considered in concepts of its biologic activity.
    Biochimica et Biophysica Acta (BBA) - General Subjects 01/2014; 1840(1):95-105. · 3.85 Impact Factor
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    ABSTRACT: Purpose. Heme oxygenase-1 (HO-1) has been proposed to exert pharmacological benefits by its antioxidative and anti-inflammatory effects. HO-1 expression may be affected by the GT length polymorphism in the promoter region of the HO-1 gene. We investigated the inducibility of HO-1 by orally administered curcumin in healthy male subjects and its correlation with the GT length polymorphism. Methods. In an open label uncontrolled phase-1 pilot study, ten male subjects received 12 g of oral curcumin. To investigate the effects of the GT length polymorphism on the inducibility of HO-1, five subjects with homozygous short and five with homozygous long GT genotypes were studied. Plasma concentrations of curcumin, bilirubin, HO-1 mRNA, and protein expression in peripheral blood mononuclear cells (PBMCs) were analyzed over 48 hours. Results. At a detection limit of 1 µg/mL curcumin could not be detected in plasma of any subject. Compared to baseline, HO-1 mRNA and protein levels were not induced in PBMCs at any time point up to 48 hours. There was no correlation between any of the parameters and GT length polymorphism. Conclusions. Oral curcumin administration has low bioavailability and does not induce HO-1 on mRNA or protein level in PBMCs.
    BioMed research international. 01/2014; 2014:458592.
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    ABSTRACT: The objective of this study is to estimate the amount of severe drug-drug interaction warnings per medical specialist group triggered by prescribed drugs of a patient before and after the introduction of a nationwide eMedication system in Austria planned for 2015. The estimations of interaction warnings are based on patients' prescriptions of a single health care professional per patient, as well as all patients' prescriptions from all visited health care professionals. We used a research database of the Main Association of Austrian Social Security Institutions that contains health claims data of the years 2006 and 2007. The study cohort consists of about 1 million patients, with 26.4 million prescribed drugs from about 3,300 different health care professionals. The estimation of interaction warnings show a heterogeneous pattern of severe drug-drug-interaction warnings across medical specialist groups. During an eMedication implementation it has to be considered that different medical specialist groups need customized support.
    Studies in health technology and informatics 01/2014; 198:246.
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    ABSTRACT: The efficacy and safety of different antiplatelet regimes for prevention of stroke in patients at high risk were investigated in a systematic review and meta-analysis. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Web of Science. Twenty-two studies comprising 173 371 patients were included. In the overall population, dual antiplatelet therapy (DAPT) with aspirin and clopidogrel in comparison to aspirin monotherapy reduced the relative risk of total stroke by 20% (risk ratio [RR], 0.80; 95% confidence interval [CI], 0.73-0.88; P<0.0001; I(2)=28%) and of ischemic stroke or transient ischemic attack by 23% (RR, 0.77; 95% CI, 0.69-0.85; P<0.0001; I(2)=18%) without increasing the risk of intracranial hemorrhage. In the secondary prevention cohort, DAPT with aspirin and clopidogrel also reduced the relative risk of total stroke by 24% as compared with aspirin alone (RR, 0.76; 95% CI, 0.68-0.86; P<0.0001; I(2)=0%). DAPT with prasugrel or ticagrelor and aspirin versus DAPT with clopidogrel and aspirin was not associated with a risk reduction of stroke. DAPT with clopidogrel and aspirin compared with aspirin effectively reduces the risk of total and ischemic stroke in the overall cohort consisting of patients with cardiovascular disease without increase in intracranial hemorrhage, as well as decreases the risk of a recurrent total stroke in patients with a previous stroke/transient ischemic attack. Our meta-analysis suggests that DAPT including low-dose aspirin (75-100 mg) and clopidogrel (75 mg) should be further investigated as a strategy to reduce recurrent strokes. http://www.crd.york.ac.uk/prospero. Unique identifier: CRD42011001596.
    Stroke 12/2013; · 6.16 Impact Factor
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    ABSTRACT: Patients with chronic obstructive pulmonary disease (COPD) are at an increased cardiovascular risk; however, the underlying mechanisms for this relationship are ill defined. Altered glucose metabolism may increase cardiovascular risk via impaired endothelial function. We conducted a longitudinal pilot study to assess the interrelationship between systemic vascular function, glucose metabolism, and lung function in patients with COPD. Eighteen non-smoking patients with stable moderate-to-severe COPD [67 % male; median (first to third quartiles) Forced Expiratory Volume in 1 second (FEV1) % predicted: 38 % (28-55 %); body mass index: 26 kg/m(2) (24-28 kg/m(2))] free from cardiovascular risk factors were evaluated. Systemic vascular function was assessed by means of flow-mediated dilation technique of the brachial artery. Laboratory measurements included fasting blood glucose levels, circulating concentrations of insulin, C-reactive protein, and fibrinogen. Homeostatic model assessment of insulin resistance (HOMA-IR) was determined. Measurements were performed at baseline and were repeated after 12 months. Flow-mediated dilation significantly decreased from 13.5 % (11-15 %) at baseline to 9.8 % (6-12 %; p = 0.002) at the follow-up visit, whereas both fasting blood glucose concentrations and HOMA-IR increased from 94 mg/dl (86-103 mg/dl) to 102 mg/dl (94-111 mg/dl; p = 0.027) and from 1.2 (0.8-2.1) to 1.7 (1.2-3.0; p = 0.023), respectively. There was a significant relationship between changes in endothelial function and changes in fasting serum glucose (r = - 0.483, p = 0.009), HOMA-IR (r = - 0.441, p = 0.019), and FEV1 (r = 0.336, p = 0.05). Altered glucose metabolism may be associated with progression of endothelial dysfunction in patients with COPD.
    Wiener klinische Wochenschrift 12/2013; · 0.81 Impact Factor

Publication Stats

5k Citations
1,341.07 Total Impact Points

Institutions

  • 1991–2014
    • Medical University of Vienna
      • • Department of Clinical Pharmacology
      • • Universitätsklinik für Innere Medizin I
      Wien, Vienna, Austria
    • IST Austria
      Klosterneuberg, Lower Austria, Austria
  • 2012
    • Arbor Research Collaborative for Health
      Ann Arbor, Michigan, United States
  • 2011
    • Karl Landsteiner Institut
      Wien, Vienna, Austria
    • Heinrich-Heine-Universität Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2009–2011
    • Hanusch Krankenhaus
      Wien, Vienna, Austria
  • 2008
    • Clinical pharmacology of Miami
      Miami, Florida, United States
  • 2006–2007
    • Wiener Krankenanstaltenverbund
      Wien, Vienna, Austria
  • 1993–2007
    • University of Vienna
      • • Department of Internal Medicine III
      • • Division of Gastroenterology and Hepatology
      Vienna, Vienna, Austria
  • 2003–2006
    • Vienna General Hospital
      Wien, Vienna, Austria
  • 2004
    • AstraZeneca
      Tukholma, Stockholm, Sweden
    • Ospedale di San Raffaele Istituto di Ricovero e Cura a Carattere Scientifico
      Milano, Lombardy, Italy
  • 1999
    • University College London
      • Centre for Clinical Pharmacology and Theraputics
      London, ENG, United Kingdom