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Dive into the research topics where Hans-Georg Eichler is active.

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Featured researches published by Hans-Georg Eichler.


American Journal of Cardiology | 1995

Measuring extracellular matrix turnover in the serum of patients with idiopathic or ischemic dilated cardiomyopathy and impact on diagnosis and prognosis

Gu¨nter Klappacher; Patrick Franzen; Doris Haab; Mohammad Reza Mehrabi; Michael Binder; Karina Plesch; Richard Pacher; Michael Grimm; Ingrid Pribill; Hans-Georg Eichler; H. Dietmar Glogar

Circulating levels of extracellular matrix components were measured by radioimmunoassays and tested if they were useful for clinical staging in chronic heart failure. In 41 patients with dilated cardiomyopathy (33 idiopathic and 8 ischemic cases), the serum concentrations of procollagen type III aminoterminal peptide (PIIINP), type I collagen telopeptide (ICTP), and basement membrane laminin were significantly higher than in 30 healthy controls regardless of the underlying etiology. Patients with serum values of PIIINP, ICTP, and laminin > 7 micrograms/L, 7.6 micrograms/L, and 2.3 U/ml, respectively, were at higher relative risk for advanced clinical stage, poor hemodynamic condition, hyponatremia, heart transplantation, and death during follow-up than patients with low levels, with the exception that serum laminin > 2.3 U/ml was not significantly associated with hyponatremia and heart transplantation. Despite their interdependence on liver function, circulating levels of PIIINP and ICTP were independent predictors of mortality. In 17 of the 41 patients with cardiomyopathy whose explanted hearts were available for histologic evaluation, serum PIIINP, ICTP, and laminin significantly correlated with the myocardial area fractions of their tissue analogues (PIIINP vs myocardial collagen type III, r = 0.784, p = 0.0013; serum ICTP vs myocardial collagen type I, r = 0.603, p = 0.0527; and serum laminin vs myocardial laminin, r = 0.605, p = 0.0411). In conclusion, the increase in extracellular matrix turnover, which may partially be derived from fibrosis in the myocardium, can be measured in the serum of patients with dilated cardiomyopathy, and has an impact on risk stratification and prognosis.


Clinical Pharmacology & Therapeutics | 2012

adaptive Licensing: Taking the Next Step in the Evolution of Drug approval

Hans-Georg Eichler; Kenneth A. Oye; Lynn G. Baird; E. Abadie; Jeffrey R. Brown; Chester L. Drum; J Ferguson; Sarah Garner; P. K. Honig; M. Hukkelhoven; J. C W Lim; Robyn Lim; M. M. Lumpkin; G. Neil; B. O'Rourke; E. Pezalla; D. Shoda; V. Seyfert-Margolis; E. V. Sigal; J. Sobotka; D. Tan; Thomas F. Unger; Gigi Hirsch

Traditional drug licensing approaches are based on binary decisions. At the moment of licensing, an experimental therapy is presumptively transformed into a fully vetted, safe, efficacious therapy. By contrast, adaptive licensing (AL) approaches are based on stepwise learning under conditions of acknowledged uncertainty, with iterative phases of data gathering and regulatory evaluation. This approach allows approval to align more closely with patient needs for timely access to new technologies and for data to inform medical decisions. The concept of AL embraces a range of perspectives. Some see AL as an evolutionary step, extending elements that are now in place. Others envision a transformative framework that may require legislative action before implementation. This article summarizes recent AL proposals; discusses how proposals might be translated into practice, with illustrations in different therapeutic areas; and identifies unresolved issues to inform decisions on the design and implementation of AL.


Clinical Pharmacology & Therapeutics | 2000

Paroxetine decreases platelet serotonin storage and platelet function in human beings

Nicole Hergovich; Martin Aigner; Hans-Georg Eichler; Jesusa Entlicher; Christa Drucker; Bernd Jilma

Serotonin is a platelet agonist and potent vasoconstrictor that has recently received attention concerning its potential role in acute coronary artery thrombosis. Selective serotonin‐reuptake inhibitors, such as paroxetine, are widely used antidepressant agents. We sought to characterize the potential inhibitory effect of paroxetine on platelet function.


British Journal of Ophthalmology | 2000

Evaluation of the Zeiss retinal vessel analyser.

Kaija Polak; Guido T. Dorner; Barbara Kiss; Elzbieta Polska; Oliver Findl; Georg Rainer; Hans-Georg Eichler; Leopold Schmetterer

AIM To investigate the reproducibility and sensitivity of the Zeiss retinal vessel analyser, a new method for the online determination of retinal vessel diameters in healthy subjects. METHODS Two model drugs were administered, a peripheral vasoconstrictor (the α receptor agonist phenylephrine) and a peripheral vasodilator (the nitric oxide donor sodium nitroprusside) in stepwise increasing doses. Nine healthy young subjects were studied in a placebo controlled double masked three way crossover design. Subjects received intravenous infusions of either placebo or stepwise increasing doses of phenylephrine (0.5, 1, or 2 μg/kg/min) or sodium nitroprusside (0.5, 1, or 2 μg/kg/min). Retinal vessel diameters were measured with the new Zeiss retinal vessel analyser. Retinal leucocyte velocity, flow, and density were measured with the blue field entoptic technique. The reproducibility of measurements was assessed with coefficients of variation and intraclass correlation coefficients. RESULTS Placebo and phenylephrine did not influence retinal haemodynamics, although the α receptor antagonist significantly increased blood pressure. Sodium nitroprusside induced a significant increase in retinal venous and arterial diameters (p<0.001 each), leucocyte density (p=0.001), and leucocyte flow (p=0.024) despite lowering blood pressure to a significant degree. For venous and arterial vessel size measurements short term coefficients of variation were 1.3% and 2.6% and intraclass correlation coefficients were 0.98 and 0.96, respectively. The sensitivity was between 3% and 5% for retinal veins and 5% and 7% for retinal arteries. CONCLUSIONS These data indicate that the Zeiss retinal vessel analyser is an accurate system for the assessment of retinal diameters in healthy subjects. In addition, nitric oxide appears to have a strong influence on retinal vascular tone.


Nature Reviews Drug Discovery | 2011

Bridging the efficacy–effectiveness gap: a regulator's perspective on addressing variability of drug response

Hans-Georg Eichler; Eric Abadie; Alasdair Breckenridge; Bruno Flamion; Lars L. Gustafsson; Hubert G. M. Leufkens; Malcolm Rowland; Christian K. Schneider; Brigitte Bloechl-Daum

Drug regulatory agencies should ensure that the benefits of drugs outweigh their risks, but licensed medicines sometimes do not perform as expected in everyday clinical practice. Failure may relate to lower than anticipated efficacy or a higher than anticipated incidence or severity of adverse effects. Here we show that the problem of benefit–risk is to a considerable degree a problem of variability in drug response. We describe biological and behavioural sources of variability and how these contribute to the long-known efficacy–effectiveness gap. In this context, efficacy describes how a drug performs under conditions of clinical trials, whereas effectiveness describes how it performs under conditions of everyday clinical practice. We argue that a broad range of pre- and post-licensing technologies will need to be harnessed to bridge the efficacy–effectiveness gap. Successful approaches will not be limited to the current notion of pharmacogenomics-based personalized medicines, but will also entail the wider use of electronic health-care tools to improve drug prescribing and patient adherence.


Nature Reviews Drug Discovery | 2008

Balancing early market access to new drugs with the need for benefit/risk data: a mounting dilemma

Hans-Georg Eichler; Francesco Pignatti; Bruno Flamion; Hubert G. M. Leufkens; Alasdair Breckenridge

Drug regulatory agencies are increasingly pressed by the challenge of finding the appropriate balance between the need for rapid access to new drugs and the need to ensure comprehensive data on their benefits and risks. This dilemma is not new, but has been made more prominent by recent high-profile drug withdrawals and conflicting demands, including the need to improve the efficiency of drug development on one hand, and the need to avoid exposing patients to unnecessary risks or possibly ineffective treatments on the other. Here, we summarize the current demands by stakeholders and the scientific and regulatory issues at stake, describe existing and emerging regulatory approaches, and speculate on future directions, such as evolution of the current regulatory model from a one-off marketing authorization to a life-cycle approach.


Clinical Pharmacology & Therapeutics | 1995

Application of microdialysis to clinical pharmacokinetics in humans

Markus Müller; Rainer Schmid; Apostolos Georgopoulos; Astrid Buxbaum; Carola Wasicek; Hans-Georg Eichler

Measurement of drug concentrations in tissues would be useful for clinical pharmacokinetic studies, but appropriate experimental methods are not available at present. The aim of this study was to assess the scope and limitations of the microdialysis technique for human tissue pharmacokinetic studies.


Circulation | 1999

Heparin Blunts Endotoxin-Induced Coagulation Activation

Thomas Pernerstorfer; Ursula Hollenstein; J.-B. Hansen; Maarten Knechtelsdorfer; Petra Stohlawetz; Wolfgang Graninger; Hans-Georg Eichler; Wolfgang Speiser; Bernd Jilma

BACKGROUND Lipopolysaccharide (LPS) is a major trigger of sepsis-induced disseminated intravascular coagulation (DIC) via the tissue factor (TF)/factor VIIa-dependent pathway of coagulation. Experimental endotoxemia has been used repeatedly to explore this complex pathophysiology, but little is known about the effects of clinically used anticoagulants in this setting. Therefore, we compared with placebo the effects of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) on LPS-induced coagulation. METHODS AND RESULTS In a randomized, double-blind, placebo-controlled trial, 30 healthy male volunteers received LPS 2 ng/kg IV followed by a bolus-primed continuous infusion of UFH, LMWH, or placebo. In the placebo group, activation of coagulation caused marked increases in plasma levels of prothrombin fragment F(1+2) (P<0.01) and polymerized soluble fibrin, termed thrombus precursor protein (TpP; P<0.01); TF-positive monocytes doubled in response to LPS, whereas levels of activated factor VII slightly decreased and levels of TF pathway inhibitor remained unchanged. UFH and LMWH markedly decreased activation of coagulation caused by LPS, as F(1+2) and TpP levels only slightly increased; TF expression on monocytes was also markedly reduced by UFH. TF pathway inhibitor values increased after either heparin infusion (P<0.01). Concomitantly, factor VIIa levels dropped by >50% at 50 minutes after initiation of either heparin infusion (P<0.01). CONCLUSIONS This experimental model proved the anticoagulatory potency of UFH and LMWH in the initial phase of experimental LPS-induced coagulation. Successful inhibition of thrombin generation also translates into blunted activation of coagulation factors upstream and downstream of thrombin.


Nature Reviews Drug Discovery | 2010

Relative efficacy of drugs: an emerging issue between regulatory agencies and third-party payers

Hans-Georg Eichler; Brigitte Bloechl-Daum; Eric Abadie; David Barnett; Franz König; Steven Pearson

Drug regulatory agencies have traditionally assessed the quality, safety and efficacy of drugs, and the current paradigm dictates that a new drug should be licensed when the benefits outweigh the risks. By contrast, third-party payers base their reimbursement decisions predominantly on the health benefits of the drug relative to existing treatment options (termed relative efficacy; RE). Over the past decade, the role of payers has become more prominent, and time-to-market no longer means time-to-licensing but time-to-reimbursement. Companies now have to satisfy the sometimes divergent needs of both regulators and payers, and to address RE during the pre-marketing stages. This article describes the current political background to the RE debate and presents the scientific and methodological challenges as they relate to RE assessment. In addition, we explain the impact of RE on drug development, and speculate on future developments and actions that are likely to be required from key players.


American Journal of Physiology-regulatory Integrative and Comparative Physiology | 1997

Role of NO in the O2 and CO2 responsiveness of cerebral and ocular circulation in humans

Leopold Schmetterer; Oliver Findl; Karin Strenn; Ursula Graselli; Johannes Kastner; Hans-Georg Eichler; Michael Wolzt

It is well known that changes in PCO2 or PO2 strongly influence cerebral and ocular blood flow. However, the mediators of these changes have not yet been completely identified. There is evidence from animal studies that NO may play a role in hypercapnia-induced vasodilation and that NO synthase inhibition modulates the response to hyperoxia in the choroid. Hence we have studied the effect of NO synthase inhibition by NG-monomethyl-L-arginine (L-NMMA, 3 mg/kg over 5 min as a bolus followed by a continuous infusion of 30 micrograms.kg-1.min-1) on the changes of cerebral and ocular hemodynamic parameters elicited by hypercapnia and hyperoxia in healthy young subjects. Mean flow velocities in the middle cerebral artery and the ophthalmic artery were measured with Doppler ultrasound, and ocular fundus pulsation amplitude, which estimates pulsatile choroidal blood flow, was measured with laser interferometry Administration of L-NMMA reduced ocular fundus pulsation. (-19%, P < 0.005) but only slightly reduced mean flow velocities in the larger arteries. Hypercapnia (PCO2 = 48 mmHg) significantly increased mean flow velocities in the middle cerebral artery (+26%, P < 0.01) and fundus pulsation amplitude (+16%, P < 0.005) but did not change mean flow velocity in the ophthalmic artery. The response to hypercapnia in the middle cerebral artery (P < 0.05) and in the choroid (P < 0.05) was significantly blunted by L-NMMA. On the contrary, L-NMMA did not affect hyperoxia-induced (PO2 = 530 mmHg) hemodynamic changes. The hemodynamic effects of L-NMMA (at baseline and during hypercapnia) were reversed by coadministration of L-arginine. The present study supports the concept that NO has a role in hypercapnia induced vasodilation in humans.It is well known that changes in [Formula: see text] or[Formula: see text] strongly influence cerebral and ocular blood flow. However, the mediators of these changes have not yet been completely identified. There is evidence from animal studies that NO may play a role in hypercapnia-induced vasodilation and that NO synthase inhibition modulates the response to hyperoxia in the choroid. Hence we have studied the effect of NO synthase inhibition by N G-monomethyl-l-arginine (l-NMMA, 3 mg/kg over 5 min as a bolus followed by a continuous infusion of 30 μg ⋅ kg-1 ⋅ min-1) on the changes of cerebral and ocular hemodynamic parameters elicited by hypercapnia and hyperoxia in healthy young subjects. Mean flow velocities in the middle cerebral artery and the ophthalmic artery were measured with Doppler ultrasound, and ocular fundus pulsation amplitude, which estimates pulsatile choroidal blood flow, was measured with laser interferometry. Administration ofl-NMMA reduced ocular fundus pulsations (-19%, P < 0.005) but only slightly reduced mean flow velocities in the larger arteries. Hypercapnia ([Formula: see text] = 48 mmHg) significantly increased mean flow velocities in the middle cerebral artery (+26%, P < 0.01) and fundus pulsation amplitude (+16%, P < 0.005) but did not change mean flow velocity in the ophthalmic artery. The response to hypercapnia in the middle cerebral artery ( P < 0.05) and in the choroid ( P < 0.05) was significantly blunted by l-NMMA. On the contrary,l-NMMA did not affect hyperoxia-induced ([Formula: see text] = 530 mmHg) hemodynamic changes. The hemodynamic effects ofl-NMMA (at baseline and during hypercapnia) were reversed by coadministration ofl-arginine. The present study supports the concept that NO has a role in hypercapnia-induced vasodilation in humans.

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Michael Wolzt

Medical University of Vienna

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Leopold Schmetterer

Medical University of Vienna

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Oliver Findl

Moorfields Eye Hospital

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Oswald Wagner

Medical University of Vienna

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Markus Müller

Medical University of Vienna

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Hubert Pehamberger

Medical University of Vienna

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