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Publications (28)
Clinical studies support a role for anidulafungin as first-line treatment of invasive candidiasis in critically ill patients and postulate no need for dose adjustments in mild to severe renal failure. Although intensive care patients requiring renal replacement therapy are at particular risk of invasive fungal infection, no pharmacokinetic data on...
Granulocyte colony-stimulating factor (G-CSF) has been associated with the induction of a hypercoagulable state in patients as well as peripheral blood stem donors. Interestingly, sparse data exist on the kinetics of platelet and coagulation activation in response to G-CSF and it is unknown if G-CSF augments shear-dependent platelet function. These...
See also Levi M. Disseminated intravascular coagulation or extended intravascular coagulation in massive pulmonary embolism. This issue, pp 1475–6; Leitner JM, Jilma B, Spiel AO, Sterz F, Laggner AN, Janata KM. Massive pulmonary embolism leading to cardiac arrest is associated with consumptive coagulopathy presenting as disseminated intravascular c...
A consumptive coagulopathy resembling disseminated intravascular coagulation (DIC) has been seen in patients with massive pulmonary embolism (PE). We hypothesized that a DIC-like condition is relevant in patients whose pulmonary embolism leads to cardiopulmonary arrest and cardiopulmonary resuscitation (CPR).
This hypothesis was tested by the use o...
Drug-induced hepatotoxicity is a frequent cause of liver disease and acute liver failure, particularly in patients treated with multiple drugs. Several antibacterial drugs have the potential to cause severe liver injury and failure. This article aims to increase the awareness and understanding of drug induced liver injury (DILI) due to antibacteria...
We aimed to determine the prognostic value of troponin T (TNT) for in-hospital and 1-yr mortality in a large sample of patients with pulmonary embolism (PE). Patients presenting at the emergency department of a tertiary care centre from January 1998 to December 2006 with PE were included. A blood sample was taken at the time of presentation. To det...
Racial differences in coagulation are poorly understood. While some studies suggest a 'prothrombotic' coagulation profile in blacks compared with whites, others report an increased bleeding risk for blacks in various clinical settings. Moreover, preclinical data suggest a link between the Duffy antigen (=DARC, Duffy antigen receptor of chemokines)...
Monocyte chemoattractant protein-1 (MCP-1, CCL-2) binds to the Duffy antigen (DARC) on red blood cells, which act as a sink for several chemokines including MCP-1. In this study it is hypothesized that DARC may alter the pharmacokinetics of infused recombinant human MCP-1 (rhMCP-1). The primary aim of this first in man trial is to compare the pharm...
The aim of this study was to compare the efficacy of Lutrate 3.75 and 7.5 mg depot to marketed references Lucrin 3.75 mg and Procrin 7.5 mg depot.
20 healthy male volunteers were randomly assigned to receive 1 of 4 active single dose treatments in this double-blind, parallel-group pilot study. Leuprolide acetate and testosterone levels were quantif...
Selectins mediate the adhesion of leukocytes to activated endothelial cells and activated platelets. In addition to these cell-to-cell interactions, they influence the fibrin content and size of venous thrombi in different animal models. However, the exact role of selectins in human endotoxemia still remains unclear. We aimed to investigate the eff...
Venous thrombosis (VT) is a highly prevalent disease. Risk factors can be genetic or acquired. The well-established genetic polymorphisms predisposing to thrombophilic disorders can be divided into rare 'loss-of-function mutations' in anticoagulant proteins and common 'gain-of-function mutations' in procoagulant proteins, which are weaker risk fact...
Endothelial Progenitor Cells (EPCs) are a specific subtype of haematopoietic stem cells that contribute to the repair of injured endothelium. Treatment with atorvastatin has been shown to increase EPC counts in patients with stable coronary artery disease. Numbers of circulating EPCs decrease in various inflammatory diseases. Thus, we hypothesized...
The Duffy receptor is a promiscuous receptor for chemokines and selectively binds CXC and CC chemokines with high affinity. Preclinical data show that presence of the Duffy receptor on red blood cells may influence plasma levels of proinflammatory cytokines and chemokines and be protective during inflammation. This trial was designed to investigate...
Endothelial progenitor cells (EPCs) are a specific subtype of hematopoietic stem cells that migrate from the bone marrow to the peripheral circulation where they contribute to the repair of injured endothelium and to the formation of new blood vessels. Levels of circulating EPCs have been investigated in different inflammatory disease states. Howev...
BIBT986 is a dual inhibitor of factors Xa and IIa. The aim of this study was to compare with placebo the effect of three doses of BIBT986 on coagulation, platelet activation, and inflammation. This was a prospective, randomized, double-blind, placebo-controlled, parallel-group dose escalation trial in 48 healthy male volunteers. Participants receiv...
Ethnic neutropenia is common in people of African descent. As interleukin-8 (IL-8) and granulocyte colony stimulating factor (G-CSF) bind to receptors on neutrophils, ethnic differences in neutrophil counts are hypothesized to result in different plasma levels of these cytokines. A prospective study was conducted in 72 healthy young volunteers. Neu...
Reparixin antagonizes interleukin-8 (IL-8) on the level of signal transduction in vitro. We hypothesized that IL-8 mediates some of the reactions occurring during acute inflammation and specifically that IL-8 may be a mediator of endotoxin induced neutrophilia. We therefore tested the effects of reparixin on humoral and cellular parameters in LPS-i...
Background: BIBT 986 is a novel potent anticoagulant that dually inhibits Factors Xa and IIa. We hypothesized that BIBT 986 would dose-dependently decrease endotoxin-induced, tissue factor triggered coagulation activation. Hence it was the aim of the study to compare with placebo the anticoagulant activity of three dosages of BIBT 986 on parameters...
Primary aim: To evaluate the modulating effects of age and sex on changes in plasma lipid levels in the response to highly active antiretroviral therapy (HAART). Secondary aim: To study insulin, leptin, adiponectin, E-selectin and P-selectin levels and their relation to demographics.
Comparative, longitudinal, open cohort-study.
Tertiary care cente...
Current anticoagulant development focuses on agents with predictable pharmacokinetic and pharmacodynamic (PD) properties. BIBT 986 is a novel potent anticoagulant with a dual mechanism of action: it competitively inhibits factor (F) Xa and FIIa.
To determine the safety, tolerability, pharmacokinetics (PK) and PD of BIBT 986 following intravenous in...
We hypothesized that infusion of recombinant human antithrombin without concomitant heparin would have dose-dependent anticoagulant properties and potentially decrease endotoxin (lipopolysaccharide [LPS])-induced cytokine production. This was a randomized, double-blind, placebo-controlled study in parallel groups enrolling 30 healthy male volunteer...
The protein C pathway serves as a modulating system with both anti-inflammatory and anticoagulant properties and is intimately involved in the pathophysiology of inflammation and sepsis. Treatment with recombinant human activated protein C (rhAPC) can reduce the mortality of severe sepsis. We investigated whether an elevation of plasma protein C le...
Background: Antithrombin (AT) had beneficial effects on mortality of septic patients in an a priori defined subpopulation of the Kypersept trial, which received no concomitant administration of heparin.
Objectives: We hypothesized that recombinant human (rh)AT (without concomitant heparin) has anticoagulant properties and may decrease cytokine prod...
Platelet activation is a hallmark of acute coronary syndromes. Numerous lines of evidence suggest a mechanistic link between von Willebrand factor or platelet hyperfunction and myocardial damage in patients with acute coronary syndromes. Thus, we assessed whether platelet function under high shear rates (collagen adenosine diphosphate closure times...
