Michael Wolzt

University of Vienna, Wien, Vienna, Austria

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Publications (366)1449.01 Total impact

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    ABSTRACT: Patients with electrolyte imbalances or disorders have a high risk of mortality. It is unknown if this finding from sodium or potassium disorders extends to alterations of magnesium levels. In this cross-sectional analysis, all emergency room patients between 2010 and 2011 at the Inselspital Bern, Switzerland, were included. A multivariable logistic regression model was performed to assess the association between magnesium levels and in-hospital mortality up to 28days. A total of 22,239 subjects were screened for the study. A total of 5339 patients had plasma magnesium concentrations measured at hospital admission and were included into the analysis. A total of 6.3% of the 352 patients with hypomagnesemia and 36.9% of the 151 patients with hypermagnesemia died. In a multivariate Cox regression model hypermagnesemia (HR 11.6, p<0.001) was a strong independent risk factor for mortality. In these patients diuretic therapy revealed to be protective (HR 0.5, p=0.007). Hypomagnesemia was not associated with mortality (p>0.05). Age was an independent risk factor for mortality (both p<0.001). The study does demonstrate a possible association between hypermagnesemia measured upon admission in the emergency department, and early in-hospital mortality. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
    European Journal of Internal Medicine 06/2015; DOI:10.1016/j.ejim.2015.05.013 · 2.30 Impact Factor
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    ABSTRACT: Guideline-recommended therapy has been proven beneficial in heart failure (HF), but general implementation remains poor. The aim of this study was to evaluate the adherence to drug therapy, quality of primary non-drug medical care (NDMC) and its impact on HF outcome. From 13 Austrian health insurance funds, we identified 36 829 patients (77.1 ± 10.8 years, 44.8% men) hospitalised for HF who survived more than 90 days after discharge in the period between April 2006 and June 2010. Drug adherence was analysed from prescriptions filled and NDMC from numbers of physician consultations and diagnostic tests relevant for HF per quarter of a year (medical care index (MedCI)) claimed from the insurance funds. Kaplan-Meier and multivariate Cox regression analyses were performed to identify the association of outcome (survival and death without further admission for HF, readmission for HF) with drug adherence and NDMC. Readmission due to HF or death without prior readmission for HF occurred in 19.7% and 22.5%, respectively. Adherence to angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers, beta-blockers and aldosterone antagonists was 49.3%, 40.4% and 16.1%, respectively, and was associated with better survival by Kaplan-Meier analysis. NDMC was consumed less frequently by deceased (76.0%; MedCI 2.55 ± 3.04) than surviving (79.3%; 3.60 ± 3.81) or readmitted (78.4%; 3.80 ± 4.13) patients (p < 0.001 for deceased vs both other). Drug adherence and NDMC were independent factors associated with better survival by multivariate regression analysis. Guideline-recommended drug therapy remains underutilised in Austria. Drug adherence and quality of NDMC are associated with better outcome in HF patients. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    Pharmacoepidemiology and Drug Safety 05/2015; DOI:10.1002/pds.3790 · 3.17 Impact Factor
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    ABSTRACT: This study demonstrates the applicability of semi-LASER localized dynamic (31)P MRS to deeper lying areas of the exercising human soleus muscle (SOL). The effect of accurate localization and high temporal resolution on data specificity is investigated. To achieve high signal-to-noise ratio (SNR) at a temporal resolution of 6 s, a custom-built human calf coil array was used at 7T. The kinetics of phosphocreatine (PCr) and intracellular pH were quantified separately in SOL and gastrocnemius medialis (GM) muscle of nine volunteers, during rest, plantar flexion exercise, and recovery. The average SNR of PCr at rest was [Formula: see text] in SOL ([Formula: see text] in GM). End exercise PCr depletion in SOL ([Formula: see text] %) was far lower than in GM ([Formula: see text] %). The pH in SOL increased rapidly and, in contrast to GM, remained elevated until the end of exercise. (31)P MRS in single-shots every 6 s localized in the deeper-lying SOL enabled quantification of PCr recovery times at low depletions and of fast pH changes, like the initial rise. Both high temporal resolution and accurate spatial localization improve specificity of Pi and, thus, pH quantification by avoiding multiple, and potentially indistinguishable sources for changing the Pi peak shape.
    MAGMA Magnetic Resonance Materials in Physics Biology and Medicine 04/2015; DOI:10.1007/s10334-015-0484-5 · 2.87 Impact Factor
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    ABSTRACT: Objective: Hypoglycemia, a major side effect of intensive glucose lowering therapy, was recently linked to increased cardiovascular risk in patients with diabetes. Whether increased circulating free fatty acids (FFA) owing to catecholamine-induced lipolysis affect myocardial energy metabolism and thus link hypoglycemia to cardiac vulnerability is unclear. Therefore, the study investigated the impact of hypoglycemia counter-regulation (+/- inhibition of lipolysis) on myocardial lipid content (MYCL) and left-ventricular function in healthy subjects. Research Design and Methods: Nine healthy men were studied in randomized order: (i) insulin-hypoglycemia-test (IHT;ins+/aci-), (ii) IHT during inhibition of adipose tissue lipolysis by acipimox (ins+/aci+), (iii) normoglycemia with acipimox (ins-/aci+) and (iv) normoglycemia with placebo (ins-/aci-). MYCL and cardiac function were assessed employing magnetic resonance spectroscopy/imaging at baseline and at 2 and 6 hours. Results: In response to acute hypoglycemia (i), plasma free fatty acids (FFA, p<.0001) and ejection fraction (EF, from 63.2±5.5 to 69.6±6.3%,p=.0001) significantly increased and were tightly correlated with each other (R=0.68, p=0.0002); this response was completely blunted by inhibition of adipose tissue lipolysis (ii). In the presence of normoglycemia (iii), inhibition of lipolysis was associated with a drop in EF (from 59.2±5.5 to 53.9±6.9%,p=0.005) and a significant decrease in plasma FFA, triglycerides and MYCL (by 48.5%, p=.0001). Conclusiones: The present data indicate that an intact inter-organ-crosstalk between adipose tissue and the heart is prerequisite for catecholamine-mediated myocardial contractility and preservation of myocardial lipid stores in response to acute hypoglycemia. Copyright © 2015, American Journal of Physiology - Endocrinology and Metabolism.
    AJP Endocrinology and Metabolism 02/2015; 308(8):ajpendo.00371.2014. DOI:10.1152/ajpendo.00371.2014 · 4.09 Impact Factor
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    ABSTRACT: Recombinant human follicle stimulating hormone (r-hFSH) is effective and safe for controlled ovarian stimulation. Bemfola(®) (Finox AG, Burgdorf, Switzerland), a new biosimilar r-hFSH, has proven comparable non-clinical pharmacological profiles to those of the widely used Gonal-f(®) (Serono Pharma S.p.A., Bari, Italy). The objective of this study was to show that Bemfola(®) yields comparable clinical pharmacokinetic (PK) and safety profiles to Gonal-f(®) in healthy female subjects. In this randomized, Phase I trial conducted in healthy female volunteers (N = 32), a 2-period, balanced 2-treatment crossover design was used. A single subcutaneous dose of 225 IU Bemfola(®) or Gonal-f(®) was administered in each treatment period per sequence. Blood was collected for pharmacokinetic analysis until 10 days after each r-hFSH treatment. For down-regulation of endogenous FSH subjects were given a depot injection with leuprolide acetate prior to the study drug in either sequence. Pharmacokinetic data was available for 23 subjects. No appreciable differences in key PK parameters were detected between the r-hFSH products as per non-compartmental PK analysis [i.e. for Bemfola(®) and Gonal-f(®) respectively AUC0-192 424.90 and 432.75 IU h/L, C max 0.98 and 0.95 IU/L, T max 24.0 h (range 6.0-24.0) and 24.0 h (range 9.0-24.0), t 1/2 43.58 h [standard deviation (SD 14.17)] and 42.58 h (SD 16.47), and K e 0.0075 1/h (SD 0.003) and 0.0077 1/h (SD 0.002)]. Subgroup analysis for estradiol (E2) response was similar for Bemfola(®) and Gonal f(®) (AUC(0--120) p = 0.21 and C max p = 0.82). No major safety issues were identified and no immunogenic reaction to r-hFSH was observed. The results of this study indicate that a single dose of Bemfola(®) exhibits pharmacokinetic and safety profiles comparable to Gonal-f(®) in healthy young women.
    European Journal of Drug Metabolism and Pharmacokinetics 01/2015; DOI:10.1007/s13318-015-0257-6 · 1.31 Impact Factor
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    Studies in health technology and informatics 01/2015; 210:946.
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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 &amp Visual Science 12/2014; 56(1). DOI:10.1167/iovs.14-15581 · 3.66 Impact Factor
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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; 53(01). DOI:10.5414/CP202076 · 1.04 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 12/2014; 79(2). DOI:10.1253/circj.CJ-14-1028 · 3.69 Impact Factor
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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; 12(11). DOI:10.1111/jth.12726 · 5.55 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; 68(11). DOI:10.1111/ijcp.12513 · 2.54 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 05/2014; 27(5). DOI:10.1002/nbm.3092 · 3.56 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. DOI:10.1002/mrm.25242 · 3.40 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; 44(6). DOI:10.1111/eci.12274 · 2.83 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; 27(6). DOI:10.1007/s40620-014-0074-z · 2.00 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; 55(4). DOI:10.1167/iovs.13-13784 · 3.66 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; DOI:10.1016/j.vph.2014.01.007 · 4.62 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; 92. DOI:10.1016/j.mvr.2014.01.004 · 2.43 Impact Factor

Publication Stats

7k Citations
1,449.01 Total Impact Points

Institutions

  • 1993–2015
    • University of Vienna
      • • Department of Internal Medicine III
      • • Division of Gastroenterology and Hepatology
      Wien, Vienna, Austria
  • 1991–2015
    • Medical University of Vienna
      • • Department of Clinical Pharmacology
      • • Exzellenzzentrum Hochfeld-MR
      • • 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
  • 1998–2011
    • Vienna General Hospital
      Wien, Vienna, Austria
  • 2008
    • Clinical pharmacology of Miami
      Miami, Florida, United States
  • 2006–2007
    • Wiener Krankenanstaltenverbund
      Wien, Vienna, Austria
    • Hanusch Krankenhaus
      Wien, Vienna, Austria
  • 2005
    • University of Leipzig
      • Institut für Laboratoriumsmedizin, Klinische Chemie und Molekulare Diagnostik
      Leipzig, Saxony, Germany
  • 2004
    • Università Telematica San Raffaele
      Milano, Lombardy, Italy
    • University of Gothenburg
      Goeteborg, Västra Götaland, Sweden
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 1999
    • University College London
      • Centre for Clinical Pharmacology and Theraputics
      Londinium, England, United Kingdom