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Search Results: 1 - 10 of 194115 matches for " Klaus G?rlinger "
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Whole blood impedance aggregometry as a biomarker for the diagnosis and prognosis of severe sepsis
Michael Adamzik, Klaus Grlinger, Jürgen Peters, Matthias Hartmann
Critical Care , 2012, DOI: 10.1186/cc11816
Abstract: Eighty patients with severe sepsis and 50 postoperative patients were included in the prospective observational study. Platelet function was determined at the first day of severe sepsis and surgery, respectively, using impedance aggregometry (Multiplate?). Moreover, platelet count, procalcitonin, interleukin 6, C-reactive protein and 30-day mortality were determined.Compared to postoperative patients, platelet aggregation was significantly reduced in patients with severe sepsis (collagen-test: 70.8 (44.4, 83.2) arbitrary units (A.U.) vs. 26.8 (12.7, 45.8) A.U.; P <0.001; median and quartiles). Furthermore, marked differences in platelet function were observed in survivors and non-survivors of severe sepsis (collagen-test: 33.4 (10.9, 48.8) A.U. vs. 12.4 (6.5, 25.0) A.U.; P = 0.001). Kaplan-Meier analysis demonstrated that higher platelet function was associated with a mortality of 10%, while mortality was 40% when platelet function was low (collagen-test; P = 0.002). The odds ratio was 6.0. In both univariate and multivariate analyses (including procalcitonin, IL6, C-reactive protein and platelet count) impedance aggregometry using collagen as the activator proved to be the best and an independent predictor for the diagnosis and prognosis of severe sepsis in critical illness.In severe sepsis, impedance aggregometry allows better prediction of diagnosis and survival than conventional biomarkers and platelet count.Sepsis is the third most common cause of death in western countries. Despite the advances in intensive care medicine the prognosis of the disease has improved only gradually [1]. Concerning the pathophysiology, sepsis has been shown to be caused by a generalized and inappropriate activation of the immune system and hemostasis; both plasma components and platelets are affected by the disease [2].In recent years, evidence has accumulated that platelets and inflammation are tightly coupled. An active function of platelets in inflammation has recently been demon
Early and individualized goal-directed therapy for trauma-induced coagulopathy
Herbert Sch?chl, Marc Maegele, Cristina Solomon, Klaus Grlinger, Wolfgang Voelckel
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine , 2012, DOI: 10.1186/1757-7241-20-15
Abstract: Major brain injury and uncontrolled blood loss remain the primary causes of early trauma-related mortality [1-3]. One-quarter to one-third of trauma patients exhibit trauma-induced coagulopathy (TIC) [4,5], which is associated with increased rates of massive transfusion (MT) and multiple organ failure (MOF), prolonged intensive care unit and hospital stays, and a four-fold increase in mortality [4]. Most patients with coagulopathy also have uncontrolled bleeding, and early diagnosis of the underlying coagulation disorder is paramount for effective treatment.One major challenge in treating severely bleeding trauma patients is to determine whether the blood loss is attributable to surgical causes or coagulopathy. If the patient is coagulopathic, it is paramount to characterize the cause of the coagulopathy and whether thrombin generation is impaired or clot quality or stability is diminished. Recent data suggest that whole-blood viscoelastic tests, such as thromboelastometry (ROTEM?, Tem International GmbH, Munich, Germany) or thrombelastography (TEG?, Haemonetics Corp., Braintree, MA, USA) portray trauma induced coagulopathy (TIC) more accurately and substantially faster than standard coagulation tests [6-8]. There is increasing evidence that these coagulation monitoring devices are helpful in guiding coagulation therapy for heavily bleeding trauma patients according to their actual needs [9].The intention of this review is to examine the concept of individualized, early, goal-directed therapy for TIC, using viscoelastic tests and targeted coagulation therapy. In addition, the AUVA Trauma Hospital algorithm for managing TIC is presented.Fast, reliable diagnosis and characterization of TIC is important. Standard coagulation tests (e.g. prothrombin time [PT], international normalized ratio [INR], prothrombin time index [PTI] and activated partial thromboplastin time [aPTT]) fail to accurately describe the complex nature of TIC for several reasons [4,5]. In vivo coagula
In Vitro impairment of whole blood coagulation and platelet function by hypertonic saline hydroxyethyl starch
Alexander A Hanke, Stephanie Maschler, Herbert Sch?chl, Felix Fl?ricke, Klaus Grlinger, Klaus Zanger, Peter Kienbaum
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine , 2011, DOI: 10.1186/1757-7241-19-12
Abstract: The study was designed as experimental non-randomized comparative in vitro study. Following institutional review board approval and informed consent blood samples were taken from 10 healthy volunteers and diluted in vitro with either HH (HyperHaes?, Fresenius Kabi, Germany), hypertonic saline (HT, 7.2% NaCl), hydroxyethylstarch (HS, HAES6%, Fresenius Kabi, Germany) or NaCl 0.9% (ISO) in a proportion of 5%, 10%, 20% and 40%. Coagulation was studied in whole blood by rotation thrombelastometry (ROTEM) after thromboplastin activation without (ExTEM) and with inhibition of thrombocyte function by cytochalasin D (FibTEM), the latter was performed to determine fibrin polymerisation alone. Values are expressed as maximal clot firmness (MCF, [mm]) and clotting time (CT, [s]). Platelet aggregation was determined by impedance aggregrometry (Multiplate) after activation with thrombin receptor-activating peptide 6 (TRAP) and quantified by the area under the aggregation curve (AUC [aggregation units (AU)/min]). Scanning electron microscopy was performed to evaluate HyperHaes induced cell shape changes of thrombocytes.Statistics: 2-way ANOVA for repeated measurements, Bonferroni post hoc test, p < 0.01.Dilution impaired whole blood coagulation and thrombocyte aggregation in all dilutions in a dose dependent fashion. In contrast to dilution with ISO and HS, respectively, dilution with HH as well as HT almost abolished coagulation (MCFExTEM from 57.3 ± 4.9 mm (native) to 1.7 ± 2.2 mm (HH 40% dilution; p < 0.0001) and to 6.6 ± 3.4 mm (HT 40% dilution; p < 0.0001) and thrombocyte aggregation (AUC from 1067 ± 234 AU/mm (native) to 14.5 ± 12.5 AU/mm (HH 40% dilution; p < 0.0001) and to 20.4 ± 10.4 AU/min (HT 40% dilution; p < 0.0001) without differences between HH and HT (MCF: p = 0.452; AUC: p = 0.449).HH impairs platelet function during in vitro dilution already at 5% dilution. Impairment of whole blood coagulation is significant after 10% dilution or more. This effect can be pinpoin
Comparison of thromboelastometry with procalcitonin, interleukin 6, and C-reactive protein as diagnostic tests for severe sepsis in critically ill adults
Michael Adamzik, Martin Eggmann, Ulrich H Frey, Klaus Grlinger, Martina Br?cker-Preu?, Günter Marggraf, Fuat Saner, Holger Eggebrecht, Jürgen Peters, Matthias Hartmann
Critical Care , 2010, DOI: 10.1186/cc9284
Abstract: In the observational cohort study, blood samples were obtained from patients on the day of diagnosis of severe sepsis (n = 56) and from postoperative patients (n = 52), and clotting time, clot formation time, maximum clot firmness, alpha angle, and lysis index were measured with thromboelastometry. In addition, procalcitonin, interleukin 6, and C-reactive protein levels were determined. For comparison of biomarkers, receiver operating characteristic (ROC) curves were used, and the optimal cut-offs and odds ratios were calculated.In comparison with postoperative controls, patients with sepsis showed an increase in lysis index (97% ± 0.3 versus 92 ± 0.5; P < 0.001; mean and SEM) and procalcitonin (2.5 ng/ml ± 0.5 versus 30.6 ± 8.7; P < 0.001). Clot-formation time, alpha angle, maximum clot firmness, as well as interleukin 6 and C-reactive protein concentrations were not different between groups; clotting time was slightly prolonged. ROC analysis demonstrated an area under the curve (AUC) of 0.901 (CI 0.838 - 0.964) for the lysis index, and 0.756 (CI 0.666 - 0.846) for procalcitonin. The calculated cut-off for the lysis index was > 96.5%, resulting in a sensitivity of 84.2%, and a specificity of 94.2%, with an odds ratio of 85.3 (CI 21.7 - 334.5).The thromboelastometry lysis index proved to be a more reliable biomarker of severe sepsis in critically ill adults than were procalcitonin, interleukin 6, and C-reactive protein. The results also demonstrate that early involvement of the hemostatic system is a common event in severe sepsis.Sepsis is a common cause of death in critically ill patients, and early diagnosis is mandatory to improve the prognosis. Commonly used biomarkers like procalcitonin, C-reactive protein, and interleukin 6 are produced by the host in response to infections. However, the concentrations of these biomarkers can increase in patients with trauma or surgery, even without infection, and, therefore, their diagnostic value in critically ill patients i
Whole blood coagulation and platelet activation in the athlete: A comparison of marathon, triathlon and long distance cycling
AA Hanke, A Staib, K Grlinger, M Perrey, D Dirkmann, P Kienbaum
European Journal of Medical Research , 2010, DOI: 10.1186/2047-783x-15-2-59
Abstract: 68 healthy athletes participating in marathon (MAR, running 42 km, n = 24), triathlon (TRI, swimming 2.5 km + cycling 90 km + running 21 km, n = 22), and long distance cycling (CYC, 151 km, n = 22) were included in the study. Blood samples were taken before and immediately after completion of competition to perform rotational thrombelastometry. We assessed coagulation time (CT), maximum clot firmness (MCF) after intrinsically activation and fibrin polymerization (FIBTEM). Furthermore, platelet aggregation was tested after activation with ADP and thrombin activating peptide 6 (TRAP) by using multiple platelet function analyzer.Complete data sets were obtained in 58 athletes (MAR: n = 20, TRI: n = 19, CYC: n = 19). CT significantly decreased in all groups (MAR -9.9%, TRI -8.3%, CYC -7.4%) without differences between groups. In parallel, MCF (MAR +7.4%, TRI +6.1%, CYC +8.3%) and fibrin polymerization (MAR +14.7%, TRI +6.1%, CYC +8.3%) were significantly increased in all groups. However, platelets were only activated during MAR and TRI as indicated by increased AUC during TRAP-activation (MAR +15.8%) and increased AUC during ADP-activation in MAR (+50.3%) and TRI (+57.5%).While coagulation is activated during physical activity irrespective of type we observed significant platelet activation only during marathon and to a lesser extent during triathlon. We speculate that prolonged running may increase platelet activity, possibly, due to mechanical alteration. Thus, particularly prolonged running may increase the risk of thrombembolic incidents in running athletes.Popularity of marathon running has increased during the last decade. Today, out of 17 million non professional runners in Germany, 100.000 runners participate in marathon competitions. Thrombembolic events have been reported in marathon athletes during competition accounting for considerable morbidity and mortality in otherwise healthy subjects even in the most experienced runners [1-7]. In previous studies, acti
Impact of platelet count on results obtained from multiple electrode platelet aggregometry (Multiplate?)
AA Hanke, K Roberg, E Monaca, T Sellmann, CF Weber, N Rahe-Meyer, K Grlinger
European Journal of Medical Research , 2010, DOI: 10.1186/2047-783x-15-5-214
Abstract: Whole blood samples from 20 healthy volunteers were prepared containing platelet concentrations of 50,000, 100,000, 150,000, 200,000, and 250,000 μl-1 while maintaining hematocrit. Platelet aggregation was induced by collagen, thrombin receptor activating peptide 6 (TRAP-6), adenosine-diphoshate (ADP), and arachidonic acid, respectively, and aggregation was measured by multiple electrode platelet aggregometry (Multiplate?).Results of multiple electrode platelet aggregometry significantly decreased in blood samples with platelet count below normal range. Compared to results measured in blood samples with platelet count within normal range, aggregometry results decreased by 18.4% (p < 0.001) and 37.2% (p < 0.001) in blood samples with a platelet count of 100.000 and 50.000 μl-1, respectively. On the other hand, large interindividual variation has been observed and some blood samples showed normal results even with platelet counts of 50.000 μl-1.The results obtained with Multiplate? Analyzer are influenced by platelet function as well as platelet count thus displaying the overall platelet aggregability within the blood sample rather than platelet function alone.Intensified and combined antiplatelet therapy in cardiology and cardiovascular surgery as well as peri-operative disturbances of haemostasis implicate the need for rapid peri-operative monitoring of platelet function [1-3]. Classical methods for assessment of platelet function, such as Born aggregometry or flow cytometry are time consuming and require preanalytical processing of the blood sample. Therefore, they are harbored in central laboratory environments and are of little use during anaesthesia and surgery. Recently, multiple electrode platelet aggregometry has been introduced and recommended for point-of-care (POC) testing of platelet function [4].Based on impedance aggregometry, first described by Cardinal and Flower [5], the multiple electrode platelet aggregometry (Multiplate? Analyzer, Dynabyte medical
Os cidad?os mundiais entre a liberdade e a seguran?a
Günther, Klaus;
Novos Estudos - CEBRAP , 2009, DOI: 10.1590/S0101-33002009000100002
Abstract: the 9/11 attacks triggered the development of a transnational security architecture that interferes profoundly in individual civil liberties, in the basic rights of state citizens as much as in human rights of the world citizens. the article draws this architecture, shows how it dissolves traditional juridical categories that preserve freedom and discusses why today it's accepted the priority of security over freedom.
Review of extended-release niacin/laropiprant fixed combination in the treatment of mixed dyslipidemia and primary hypercholesterolemia
Klaus G Parhofer
Vascular Health and Risk Management , 2009, DOI: http://dx.doi.org/10.2147/VHRM.S4502
Abstract: f extended-release niacin/laropiprant fixed combination in the treatment of mixed dyslipidemia and primary hypercholesterolemia Review (6209) Total Article Views Authors: Klaus G Parhofer Published Date November 2009 Volume 2009:5 Pages 901 - 908 DOI: http://dx.doi.org/10.2147/VHRM.S4502 Klaus G Parhofer Medical Department II Grosshadern, University of Munich, Germany Abstract: Although statins reduce cardiovascular morbidity and mortality further risk reduction is needed. In this respect low HDL-cholesterol concentrations and/or elevated triglyceride concentrations may be potential treatment targets. Niacin (nicotinic acid) is an effective drug which increases the plasma concentration of high-density lipoprotein (HDL)-cholesterol and decreases the concentration of low-density lipoprotein (LDL)-cholesterol, triglycerides and lipoprotein(a). Clinical studies indicate that niacin can significantly reduce the risk for cardiovascular events. However, niacin is not very commonly used because of significant side effects (especially flushing). Laropiprant is a potent selective antagonist of PGD2-receptor subtype-1 and can thus reduce niacin-induced flushing. Although the addition of laropiprant will reduce the frequency of flushing, it will not completely eliminate this side effect. Laropiprant does not change the effect of niacin on lipids or other side effects of niacin (ie, gastro-intestinal problems, glucose elevation). The combination of niacin with laropiprant may therefore enable use of niacin at higher doses and therefore exploit the full potential of the drug. Endpoint studies that will be published over the next few years will show whether this treatment modality also translates into clinical effect in patients treated with statins. Until publication of these studies niacin/laropiprant should be used only in high-risk patients not achieving lipid goals on statins.
Dialogischer Wandel im therapeutischen Kontext. Von Metaphern, Geschichten und Gleichnissen – Umgangsformen und Sprechweisen Dialogic Transformation in Therapeutic Contexts. Metaphors, Stories and Parables—Manners of Conduct and Speaking Transformación dialógica en contextos terapéuticos. Metáforas, historias y parábolas – maneras de hablar y de conducta
Klaus G. Deissler
Forum : Qualitative Social Research , 2008,
Abstract: Der folgende Aufsatz stellt einen Beitrag zur Diskussion der Annahmen und praktischen Konsequenzen des sozialen Konstruktionismus im therapeutischen Kontext dar. Ausgangspunkt ist die Implikation, dass sprachlich formulierte Metaphern im therapeutischen Prozess wichtig für die therapeutische Interaktion sind, und dass sie nicht nur in therapeutischen Dialogen zum Wandel beitragen. Daher werden ein paar kleine Metaphern dargestellt, die soziale Konstruktionsprozesse zum Inhalt haben und diese zum Teil durch Verfremdungen veranschaulichen. Diese Prozesse werden weiter im psychotherapeutischen Kontext verdeutlicht, indem Diagnosen als aktuelle relationale Konstruktionen verstanden werden. Der Aufsatz wird abgeschlossen mit einem therapeutischen Fallbeispiel, das das dargestellte sozialkonstruktionistische Verst ndnis therapeutischer Dialoge pr gnant herausstellt. URN: urn:nbn:de:0114-fqs0801455 The article contributes to the discussion of the premises and practical consequences of social constructionism in of the context of psychotherapeutic practice. The article is based on the presupposition that the use of metaphors is an important aspect of therapeutic interaction and that they contribute to transformation not only within the therapeutic dialogue. For these ends a few metaphors implying processes of social construction are presented—some gaining their effect of clarification through intended alienation. These processes are exemplified further in the psychotherapeutic context by presenting diagnoses as relational constructions. We end with a brief case study that highlights the social constructionist understanding of therapeutic dialogues. URN: urn:nbn:de:0114-fqs0801455 El artículo contribuye a la discución sobre las premisas y consecuencias prácticas del construccionismo social en el contexto de la práctica psicoterapeuta. El artículo está basado en la presupocición que el uso de metáforas es un aspecto importante de la interacción terapéutica y que ellas contribuyen a la transformación no solo en el diálogo terapéutico. Con ese fin se presentan algunas metáforas que implican procesos de construcción social – algunas tienen efectos de clarificación por medio de la alienación intencional. Además se ejemplifican estos procesos en el contexto psicoterapéutico al presentar a los diagnósticos como construcciones relacionales. Concluimos con un breve estudio de caso individual que subraya el entendimiento socioconstruccionista de los diálogos terapéuticos. URN: urn:nbn:de:0114-fqs0801455
Review of extended-release niacin/laropiprant fixed combination in the treatment of mixed dyslipidemia and primary hypercholesterolemia
Klaus G Parhofer
Vascular Health and Risk Management , 2009,
Abstract: Klaus G ParhoferMedical Department II Grosshadern, University of Munich, GermanyAbstract: Although statins reduce cardiovascular morbidity and mortality further risk reduction is needed. In this respect low HDL-cholesterol concentrations and/or elevated triglyceride concentrations may be potential treatment targets. Niacin (nicotinic acid) is an effective drug which increases the plasma concentration of high-density lipoprotein (HDL)-cholesterol and decreases the concentration of low-density lipoprotein (LDL)-cholesterol, triglycerides and lipoprotein(a). Clinical studies indicate that niacin can significantly reduce the risk for cardiovascular events. However, niacin is not very commonly used because of significant side effects (especially flushing). Laropiprant is a potent selective antagonist of PGD2-receptor subtype-1 and can thus reduce niacin-induced flushing. Although the addition of laropiprant will reduce the frequency of flushing, it will not completely eliminate this side effect. Laropiprant does not change the effect of niacin on lipids or other side effects of niacin (ie, gastro-intestinal problems, glucose elevation). The combination of niacin with laropiprant may therefore enable use of niacin at higher doses and therefore exploit the full potential of the drug. Endpoint studies that will be published over the next few years will show whether this treatment modality also translates into clinical effect in patients treated with statins. Until publication of these studies niacin/laropiprant should be used only in high-risk patients not achieving lipid goals on statins.Keywords: nicotinic acid, flushing, hyperlipidemia, dyslipoproteinemia
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