1,638 results on '"Tilman Sauerbruch"'
Search Results
52. Treatment of Oesophageal Varices in Liver Cirrhosis
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Tilman Sauerbruch and Florence Wong
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Liver Cirrhosis ,medicine.medical_specialty ,Resuscitation ,Cirrhosis ,Portal venous pressure ,medicine.medical_treatment ,Adrenergic beta-Antagonists ,Esophageal and Gastric Varices ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Hypertension, Portal ,medicine ,Humans ,Ligation ,business.industry ,medicine.disease ,Portal Pressure ,Rifaximin ,chemistry ,030220 oncology & carcinogenesis ,Disease Progression ,Portal hypertension ,030211 gastroenterology & hepatology ,Portasystemic Shunt, Transjugular Intrahepatic ,business ,Varices ,Gastrointestinal Hemorrhage ,Transjugular intrahepatic portosystemic shunt - Abstract
Background: The development of cirrhosis with resultant portal hypertension can lead to oesophageal varices at a rate of 7% per annum. Bleeding from varices happens when the portal pressure is ≥12 mm Hg and can threaten life. Summary: Eliminating the aetiology of cirrhosis is a pivotal step to prevent the formation of varices. In patients with established varices, primary prophylaxis with non-selective beta blockers (NSBB) may slow down the progression of varices and prevent the first variceal bleed. NSBB, similar to other agents such as renin/angiotensin blockers, statins, and rifaximin, may have the additional advantage of blunting inflammatory stimuli, which can contribute to the progression of varices. Variceal band ligation is an alternative for primary bleeding prophylaxis with excellent results. Any acute variceal bleed should be managed with band ligation after careful resuscitation. Early pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) in decompensated cirrhotic patients is very effective in controlling the bleeding and improves survival. Secondary prophylaxis against further variceal bleeding using NSBB and band ligation is recommended in most other patients. TIPS may be considered in appropriate patients as a secondary prophylaxis against recurrent variceal bleed. Future research should be directed towards the prevention of varices and targeting inflammation to reduce cirrhotic complications. Key Messages: Treatment strategies depend on the stage the patient is at along the natural history of varices: NSBB or band ligation for primary prophylaxis; band ligation or early TIPS for acute bleed; and a combination of NSBB + band ligation or TIPS for secondary prophylaxis (Fig. 1).
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- 2018
53. Anschriften der Herausgeber und Autoren
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Reinhard Brunkhorst, Jürgen Schölmerich, Hans-Dieter Allescher, Thomas Berger, Peter Berlit, Franziska Bertram, Cornelius Bollheimer, Herbert Bruckmayer, Peter Brunotte, Roland Büttner, Klaus-Peter Czudaj, Dominic Dellweg, Matthias Dollinger, Dorothee Dorlars, Matthias Ebert, Matthias Eder, Esther Endlicher, Markus Fahlbusch, Peter Fickert, Gabriele Fluhr, Baptist Gallwitz, Markus Gaubitz, Alexander L. Gerbes, Jens Gerth, Christiane Girlich, Beate Gleissner, Thomas Glück, Stefan K. Gölder, Oliver Gross, Dietrich Gulba, Marianne Haag-Weber, Viola Hach-Wunderle, Michael Hamm, Wolf Harms, Thomas R.W. Herrmann, Walter Hermann, Felix J.F. Herth, Mirja Hickstein, Martin Holtmann, Silke Hörnschemeyer-Decker, Oliver Kastrup, Jutta Keller, Ahmed A. Khattab, Stefan Köppen, Markus A. Kuczyk, Frank Lammert, Ulf Landmesser, Peter Layer, Markus Lerch, Guntram Lock, J.-Matthias Löhr, Hans Peter Lorenzen, Gert Mayer, Stephanie Mayer, Julia Mayerle, Martina Mayr, Axel S. Merseburger, Gerhard A. Müller, Ulf Müller-Ladner, Karsten Müssig, Ralph Naumann, Michael Nebel, Jost Niedermeyer, Florian Obermeier, Peter Otto, Jens Panse, Klaus G. Parhofer, Susanne Petri, Michael Pfeifer, Antje Prasse, Ulrike Raap, Walter Reinisch, Gert Richardt, Felix Rockmann, Bernd Salzberger, Tilman Sauerbruch, Philippe Schafhausen, Carsten Schmidt, Bernd Schönhofer, Friedrich Schorr, Christoph Schrader, Michael Schumann, Andreas Schwartz, Jochen Seufert, Britta Siegmund, Peter Simon, Peter Staib, Andreas Stallmach, Erwin Stark, Bernhard Steinhoff, Johannes Strunk, Ingo H. Tarner, Jürgen Tebbenjohanns, Christian Teschendorf, Theodoros Thomas, Herbert Tilg, Ralph Tölg, Michael Trauner, Peter Wagener, Manuel Wallbach, Thomas Weiss, Fritz von Weizsäcker, Martin Welker, Hans-Jürgen Welkoborsky, Tobias Welte, Burkhard Wiechens, Uwe Wiegand, Reiner Wiest, Jürgen Wilke, Ulrike Woenckhaus, Gunter Wolf, Christian Wrede, Gabriele Birkenfeld, Reinhard Dengler, Robert Dinser, Felix Flohr, Thomas Fühner, Volker Groß, Ingvild Hansen, Johannes Hensen, Marc-Sören Hochtritt, Marius M. Höper, Sarah Kaufmann, Alexandra Keinert, Robert Koch, Manfred Kuhn, Katharina Laubner, Urs Lichtenauer, Helmut Messmann, Jürgen Pausch, Michael Pfreundschuh, Mathias Pletz, Anke Reibetanz, Brigitta Rumberger, Wolff Schmiegel, Michael Seidler, Christoph Tillmanns, Andrea Titz, Sandra Waalkes, Jürgen Weiß, Karin Wollersen, and Stefan Zeuzem
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- 2018
54. Vorwort
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Tilman Sauerbruch
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- 2018
55. Definitionen, Epidemiologie, natürlicher Verlauf und klinisches Erscheinungsbild der Divertikelkrankheit
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J Textor, Astrid Quick, Franz Ludwig Dumoulin, Tilman Sauerbruch, and Ralf Hildenbrand
- Abstract
Die Haufigkeit einer Divertikulose und assoziierter Komplikationen nimmt mit dem Lebensalter zu. Eine Divertikelkrankheit liegt vor, wenn es zu Symptomen oder Komplikationen wie Divertikulitis oder Divertikelblutung gekommen ist. Die Divertikulitis ausert sich mit abdominellen Schmerzen und Entzundungszeichen. Es werden drei Typen mit Unterformen unterschieden: 1. die akute unkomplizierte Divertikulitis ohne Perforation, 2. die akute komplizierte Divertikulitis mit gedeckter Perforation, Mikro- oder Makroabszess oder freier Perforation mit begleitender Peritonitis und 3. die chronisch-rezidivierende Divertikulitis, die zu Komplikationen wie Stenose, Fistelung oder der Ausbildung eines Konglomerattumors fuhren kann. Die Divertikelblutung wird durch eine Ruptur der Vasa recta des Divertikels verursacht und ausert sich klinisch als schmerzlose untere Gastrointestinalblutung, die mit Zeichen des Volumenmangels einhergehen kann. Eine Sonderform stellt die segmentale Kolitis assoziiert mit Divertikulose dar, bei der sich entzundliche Veranderungen finden, die histologisch einer chronisch-entzundlichen Darmerkrankung ahneln.
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- 2018
56. PS-023-Factors predicting survival in patients with high-risk acute variceal bleeding treated with pre-emptive (Early)-TIPS
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Marta Magaz, Christian Jansen, Debora Angrisani, Henning Grønbæk, Irene Conejo Sosa, Javier Martínez, Marie-Angele Robic, Lise Lotte Gluud, Luis Ibañez, Lucio Amitrano, Susana G. Rodrigues, Rafael Bañares, Virginia Hernández-Gea, Manuel J. Rodriguez, Jaime Bosch, Fanny Turon, José Castellote, Carlos Noronha Ferreira, Alberto Monescillo, José María Palazón, Marika Rudler, Jean-Pierre Vinel, Aleksander Krag, Joan Genescà, Maria Anna Guardascione, Manuel Romero Gomez, Agustín Albillos, Jose Luis Mundi, Angelo Luca, Anna Baiges, Alvaro Giraldez-Gallego, Georgina Casanovas, José Luis Calleja Panero, Juan G. Abraldes, Marco Senzolo, José Ferrusquia, Wim Laleman, María-Vega Catalina, Arnulf Ferlitsch, Karel Caca, Frederik Nevens, Joachim Mössner, Dominique Thabut, Elba Llop, Càndid Villanueva, Alessandra Dell'Era, Beate Appenrodt, Helena Masnou, Bogdan Procopet, Marcel Tantau, Edilmar Alvarado, Juan Carlos García-Pagán, Ferran Torres, Tilman Sauerbruch, Nuria Cañete, Massimo Primignani, Alexander Zipprich, Meritxell Casas, Romanno Sassatelli, Manuel Hernández-Guerra, Jonel Trebicka, and Bureau christophe
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Variceal bleeding ,medicine.medical_specialty ,Hepatology ,business.industry ,medicine ,In patient ,business ,Surgery - Published
- 2019
57. Janus-kinase-2 relates directly to portal hypertension and to complications in rodent and human cirrhosis
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Kay Uwe Wagner, Peter P. Sayeski, Jonel Trebicka, Sabine Klein, Frank Erhard Uschner, Christian P. Strassburg, Kanishka Hittatiya, Jennifer Lehmann, Robert Schierwagen, Irela Schierwagen, Steffen Manekeller, Dominik Wolf, Wim Laleman, Johanna Rick, Tilman Sauerbruch, and Len Verbeke
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Liver Cirrhosis ,Male ,0301 basic medicine ,Cirrhosis ,Transcription, Genetic ,Portal venous pressure ,Muscle Proteins ,Severity of Illness Index ,Gastroenterology ,Rats, Sprague-Dawley ,Mice ,Liver disease ,0302 clinical medicine ,Fibrosis ,hemic and lymphatic diseases ,Ascites ,Medicine ,Enzyme Inhibitors ,Myofibroblasts ,Carbon Tetrachloride ,Mice, Knockout ,rho-Associated Kinases ,Microfilament Proteins ,Middle Aged ,Tyrphostins ,Portal Pressure ,Up-Regulation ,Portal hypertension ,Female ,030211 gastroenterology & hepatology ,Collagen ,medicine.symptom ,Signal Transduction ,Adult ,medicine.medical_specialty ,Young Adult ,03 medical and health sciences ,Spontaneous bacterial peritonitis ,Internal medicine ,Hypertension, Portal ,Hepatic Stellate Cells ,Animals ,Humans ,RNA, Messenger ,Ligation ,business.industry ,Janus Kinase 2 ,medicine.disease ,Rats ,Mice, Inbred C57BL ,030104 developmental biology ,Hepatic stellate cell ,Vascular Resistance ,rhoA GTP-Binding Protein ,business ,Rho Guanine Nucleotide Exchange Factors - Abstract
Objective Angiotensin II (AngII) activates via angiotensin-II-type-I receptor (AT1R) Janus-kinase-2 (JAK2)/Arhgef1 pathway and subsequently RHOA/Rho-kinase (ROCK), which induces experimental and probably human liver fibrosis. This study investigated the relationship of JAK2 to experimental and human portal hypertension. Design The mRNA and protein levels of JAK2/ARHGEF1 signalling components were analysed in 49 human liver samples and correlated with clinical parameters of portal hypertension in these patients. Correspondingly, liver fibrosis (bile duct ligation (BDL), carbon tetrachloride (CCl 4 )) was induced in floxed- Jak2 knock-out mice with SM22-promotor (SM22 Cre+ - Jak2 f/f ). Transcription and contraction of primary myofibroblasts from healthy and fibrotic mice and rats were analysed. In two different cirrhosis models (BDL, CCl 4 ) in rats, the acute haemodynamic effect of the JAK2 inhibitor AG490 was assessed using microsphere technique and isolated liver perfusion experiments. Results Hepatic transcription of JAK2/ARHGEF1 pathway components was upregulated in liver cirrhosis dependent on aetiology, severity and complications of human liver cirrhosis (Model for End-stage Liver disease (MELD) score, Child score as well as ascites, high-risk varices, spontaneous bacterial peritonitis). SM22 Cre+ - Jak2 f/f mice lacking Jak2 developed less fibrosis and lower portal pressure (PP) than SM22 Cre− - Jak2 f/f upon fibrosis induction. Myofibroblasts from SM22 Cre+ - Jak2 f/f mice expressed less collagen and profibrotic markers upon activation. AG490 relaxed activated hepatic stellate cells in vitro. In cirrhotic rats, AG490 decreased hepatic vascular resistance and consequently the PP in vivo and in situ. Conclusions Hepatic JAK2/ARHGEF1/ROCK expression is associated with portal hypertension and decompensation in human cirrhosis. The deletion of Jak2 in myofibroblasts attenuated experimental fibrosis and acute inhibition of JAK2 decreased PP. Thus, JAK2 inhibitors, already in clinical use for other indications, might be a new approach to treat cirrhosis with portal hypertension.
- Published
- 2015
58. Chemokine (C-X-C motif) ligand 11 levels predict survival in cirrhotic patients with transjugular intrahepatic portosystemic shunt
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Marie-Luise Berres, Jan Görtzen, Christian Jansen, Hermann E. Wasmuth, Jennifer Lehmann, Tilman Sauerbruch, Christian Trautwein, Daniela C. Kroy, Jonel Trebicka, Henning W. Zimmermann, Christian P. Strassburg, Daniel Thomas, Carsten H. Meyer, and Fabienne Schumacher
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Adult ,Liver Cirrhosis ,Male ,0301 basic medicine ,medicine.medical_specialty ,Alcoholic liver disease ,Time Factors ,Cirrhosis ,Portal venous pressure ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Severity of Illness Index ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Predictive Value of Tests ,Risk Factors ,Fibrosis ,Internal medicine ,Hypertension, Portal ,parasitic diseases ,medicine ,Humans ,Aged ,Proportional Hazards Models ,Creatinine ,Hepatology ,business.industry ,Middle Aged ,medicine.disease ,Chemokine CXCL11 ,Treatment Outcome ,030104 developmental biology ,chemistry ,Case-Control Studies ,Multivariate Analysis ,CXCL9 ,Portal hypertension ,Female ,030211 gastroenterology & hepatology ,Portasystemic Shunt, Transjugular Intrahepatic ,business ,Transjugular intrahepatic portosystemic shunt ,Biomarkers - Abstract
Background & Aims Chemokines, such as CXCR3-ligands, have been identified to play an important role during hepatic injury, inflammation and fibrosis. While CXCL9 is associated with survival in patients receiving transjugular intrahepatic portosystemic shunt (TIPS), the role of CXCL11 in severe portal hypertension remains unknown. Methods CXCL11-levels were measured in 136 patients with liver diseases, and 63 healthy controls. In further 47 cirrhotic patients receiving TIPS, CXCL11 levels were measured in portal and hepatic veins at TIPS insertion by cytometric bead array. CXCL11-levels were measured in 23 patients in cubital vein and right atrium, whereas in 24 patients in portal and hepatic blood at an invasive reevaluation. Results CXCL11-levels were increased with the severity of liver fibrosis. CXCL11-levels from portal, hepatic and cubital veins and right atrium showed a highly significant correlation among each other in these patients. Furthermore, levels of CXCL11 from the right atrium were significantly higher than those from cubital vein. Interestingly, patients with alcoholic cirrhosis had significantly lower CXCL11-levels, than other aetiologies of cirrhosis. After TIPS, CXCL11 levels correlated with the degree of portal pressure and patients with higher CXCL11-levels in portal and hepatic veins showed higher mortality. Multivariate analysis revealed hepatic CXCL11-levels before TIPS, creatinine and age as independent predictors for survival in TIPS patients, whereas MELD score and low portal CXCL11-levels after TIPS predicted long-term survival. Conclusion CXCL11 levels are mainly increased in patients with non-alcoholic cirrhosis and high portal pressure. Moreover, levels of CXCL11 might predict long-time survival of cirrhotic patients bearing TIPS.
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- 2015
59. Esophageal varices: Stage-dependent treatment algorithm
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Jaime Bosch and Tilman Sauerbruch
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0301 basic medicine ,medicine.medical_specialty ,Hepatology ,business.industry ,Esophageal and Gastric Varices ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Esophageal varices ,Text mining ,Acute Disease ,medicine ,Humans ,030211 gastroenterology & hepatology ,Radiology ,Stage (cooking) ,Gastrointestinal Hemorrhage ,business ,Algorithms - Published
- 2016
60. [Statins as a Therapy of Chronic Liver Disease?]
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Tilman, Sauerbruch, Robert, Schierwagen, and Jonel, Trebicka
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Non-alcoholic Fatty Liver Disease ,Chronic Disease ,Humans ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Hepatitis, Chronic - Abstract
Statins have proven effects in the primary and secondary prevention of coronary disease. Besides lowering LDL-cholesterol beneficial pleiotropic consequences of statin therapy are increasingly discussed. Retrospective analyses of large cohort studies have shown favorable effects on the sequels of chronic viral induced liver disease and of non alcoholic fatty liver disease. These findings are substantiated by experimental work showing that statins reduce inflammation, fibrosis and proliferation in the diseased liver. Prospective controlled trials are necessary to elucidate whether, when and where statins have a role in the therapeutic armamentarium for liver disease.
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- 2017
61. [Career, trainee physicians]
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Tilman, Sauerbruch
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Motivation ,Career Choice ,Physicians ,Humans ,Occupations - Abstract
Medicine offers trainee physicians many different possibilities to practice their vocation. Young doctors should try to assess their own motivation and skills as precisely as possible, especially regarding a more theoretical, more practical, more academic or a purely patient-oriented career path. However, different phases of life may bring about changes in priorities. The course for the direction of a career path is often set early on. This is particularly true during the early career phase when institutions, such as medical faculties, have the responsibility to provide authoritative consulting and good mentorship.
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- 2017
62. Expression of vasoactive proteins in gastric antral mucosa reflects vascular dysfunction in patients with cirrhosis and portal hypertension
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Glen Kristiansen, Hans-Peter Fischer, Sören Möller, Jonel Trebicka, Robert Schierwagen, Tilman Sauerbruch, Markus Peck-Radosavljevic, Thomas Reiberger, Kanishka Hittatiya, Cyrus Wix, Flemming Bendtsen, Sabine Klein, Matthias von Heydebrand, and Aleksander Krag
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Liver Cirrhosis ,Male ,Pathology ,RHOA ,Cirrhosis ,Arrestins ,Biopsy ,Denmark ,Portal venous pressure ,Vascular dysfunction ,Polymerase Chain Reaction ,Gastroenterology ,Enos ,Ascites ,Pyloric Antrum ,Splanchnic Circulation ,Portal hypertension ,Antrum ,beta-Arrestins ,rho-Associated Kinases ,biology ,Middle Aged ,Immunohistochemistry ,Portal Pressure ,beta-Arrestin 2 ,medicine.anatomical_structure ,Female ,medicine.symptom ,Adult ,medicine.medical_specialty ,Nitric Oxide Synthase Type III ,Blotting, Western ,Transjugular intrahepatic portosystemic shunt ,Young Adult ,Internal medicine ,Hypertension, Portal ,Gastric mucosa ,medicine ,Humans ,Vasoactive pathways ,RNA, Messenger ,Aged ,Hepatology ,business.industry ,medicine.disease ,biology.organism_classification ,Gastric Mucosa ,Case-Control Studies ,biology.protein ,Portasystemic Shunt, Transjugular Intrahepatic ,rhoA GTP-Binding Protein ,business - Abstract
BACKGROUND & AIMS: Patients with cirrhosis display hypocontractility of splanchnic vessels because of dysregulation of vasoactive proteins, such as decreased effect of RhoA/ROCK and increased activity of β-Arrestin-2 and eNOS. However, it is unknown whether the dysregulation of vasoactive proteins is displayed in other vessels. We investigated whether expression of vasoactive proteins can be evaluated in gastric mucosa vessels.METHODS: Biopsies from the gastric mucosa of 111 patients with cirrhosis were collected at three different centres and from 13 controls. Forty-nine patients had received TIPS. Portal pressure gradient was measured in 49 patients with TIPS and in 16 patients without TIPS. Biopsies from the antrum were conserved in formaldehyde for immunohistochemistry or shock-frozen for PCR and Western blot.RESULTS: The mucosal transcription of vascular markers (αSMA, CD31) was higher in cirrhotic patients than controls, which was confirmed by immunohistochemistry. On average, relative mucosal levels of RhoA and ROCK were lower, while β-Arrestin-2 levels were higher in cirrhotic patients compared to controls. Transcriptional levels of eNOS increased with presence of ascites and grade of oesophageal varices. Patients with TIPS showed less pronounced markers of vascular dysfunction in gastric mucosa.CONCLUSION: This is the first evidence that the expression of vasoactive proteins in mucosa from the gastric antrum of patients with cirrhosis reflects their vascular dysfunction and possibly changes after therapeutic interventions.
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- 2014
63. Cerebral haemodynamics in cirrhotic patients with hepatic encephalopathy
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Manuel Sierra Beltrán, Jonel Trebicka, Misael Uribe-Esquivel, Astrid Ruiz-Margáin, Tilman Sauerbruch, Marina Green-Gómez, Ricardo U Macías-Rodríguez, Andres Duarte-Rojo, Jorge B. Díaz Ramírez, Carlos Cantú-Brito, and Aldo Torre
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Liver Cirrhosis ,medicine.medical_specialty ,Pathology ,Cirrhosis ,Ultrasonography, Doppler, Transcranial ,Statistics, Nonparametric ,Breath Holding ,Liver disease ,Internal medicine ,medicine.artery ,medicine ,Humans ,Autoregulation ,Decompensation ,Hepatic encephalopathy ,Hepatology ,business.industry ,Hemodynamics ,Brain ,medicine.disease ,Pathophysiology ,Cross-Sectional Studies ,Hepatic Encephalopathy ,Middle cerebral artery ,Cardiology ,Regression Analysis ,Portal hypertension ,business ,Biomarkers - Abstract
Background & Aims Factors other than elevated levels of ammonia may be implicated in hepatic encephalopathy (HE) pathophysiology, including abnormal cerebral haemodynamics. Transcranial Doppler ultrasonography (TCD) evaluates cerebrovascular structural integrity and reactivity, through pulsatility index (PI) and breath-holding index (BHI) respectively. The aim of this study was to evaluate cerebral haemodynamics by TCD in patients with compensated and decompensated cirrhosis, and patients with and without HE. Methods We studied 90 subjects by TCD measuring PI and BHI in the middle cerebral artery: 30 with cirrhosis and no HE, 30 with cirrhosis and low-grade HE and 30 healthy subjects. Critical flicker frequency, psychometric hepatic encephalopathy score and West-Haven criteria were performed to assess MHE and HE respectively. Results Pulsatility index increased in decompensated cirrhotics (Child ≥ 7) when compared with compensated cirrhotics and healthy subjects [median (IQR) 1.07 (0.95–1.21) vs 0.90 (0.83–1.05) vs 0.87 (0.78–0.96); P
- Published
- 2014
64. A common polymorphism in the NCAN gene is associated with hepatocellular carcinoma in alcoholic liver disease
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Tobias Müller, Jacob Nattermann, Ulrich Spengler, Benjamin Krämer, Philipp Lutz, Felix Stickel, Janett Fischer, Nasser Semmo, Tilman Sauerbruch, Christian P. Strassburg, Hans Dieter Nischalke, Kanishka Hittatiya, Thomas Berg, Michael Soyka, J Söhne, Jonas Rosendahl, and Hans-Peter Fischer
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Adult ,Male ,medicine.medical_specialty ,Alcoholic liver disease ,Pathology ,Carcinoma, Hepatocellular ,Cirrhosis ,Hepatitis C virus ,Nerve Tissue Proteins ,Single-nucleotide polymorphism ,Biology ,medicine.disease_cause ,Polymorphism, Single Nucleotide ,Gastroenterology ,Cell Line ,Cohort Studies ,Young Adult ,Gene Frequency ,Liver Cirrhosis, Alcoholic ,Risk Factors ,Neurocan ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Lectins, C-Type ,RNA, Messenger ,Liver Diseases, Alcoholic ,Aged ,Aged, 80 and over ,Hepatitis B virus ,Hepatology ,Liver Neoplasms ,Fatty liver ,Hep G2 Cells ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,digestive system diseases ,3. Good health ,Alcoholism ,Chondroitin Sulfate Proteoglycans ,Case-Control Studies ,Hepatocellular carcinoma ,Hepatocytes ,Female - Abstract
Background & Aims The genetic background of alcoholic liver diseases and their complications are increasingly recognized. A common polymorphism in the neurocan ( NCAN ) gene, which is known to be expressed in neuronal tissue, has been identified as a risk factor for non-alcoholic fatty liver disease (NAFLD). We investigated if this polymorphism may also be related to alcoholic liver disease (ALD) and hepatocellular carcinoma (HCC). Methods We analysed the distribution of the NCAN rs2228603 genotypes in 356 patients with alcoholic liver cirrhosis, 126 patients with alcoholic HCC, 382 persons with alcohol abuse without liver damage, 362 healthy controls and in 171 patients with hepatitis C virus (HCV) associated HCC. Furthermore, a validation cohort of 229 patients with alcoholic cirrhosis (83 with HCC) was analysed. The genotypes were determined by LightSNiP assays. The expression of NCAN was studied by RT-PCR and immunofluorescence microscopy. Results The frequency of the NCAN rs2228603 T allele was significantly increased in patients with HCC due to ALD (15.1%) compared to alcoholic cirrhosis without HCC (9.3%), alcoholic controls (7.2%), healthy controls (7.9%), and HCV associated HCC (9.1%). This finding was confirmed in the validation cohort (15.7% vs. 6.8%, OR=2.53; 95%CI: 1.36–4.68; p =0.0025) and by multivariate analysis (OR=1.840; 95%CI: 1.22–2.78; p =0.004 for carriage of the rs2228603 T allele). In addition, we identified and localised NCAN expression in human liver. Conclusions NCAN is not only expressed in neuronal tissue, but also in the liver. Its rs2228603 polymorphism is a risk factor for HCC in ALD, but not in HCV infection.
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- 2014
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65. Effect of hemoperfusion on flecainide serum concentration - a case report
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Tilman Sauerbruch, Martin Steinmetz, Christian Rabe, Georg Nickenig, and Florian Eyer
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Bradycardia ,Adolescent ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,Toxicology ,Ventricular tachycardia ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Humans ,cardiovascular diseases ,Flecainide ,business.industry ,Sodium channel ,030208 emergency & critical care medicine ,General Medicine ,Serum concentration ,medicine.disease ,Hemoperfusion ,Cardiopulmonary Resuscitation ,Anesthesia ,cardiovascular system ,Female ,medicine.symptom ,Drug Overdose ,business ,Anti-Arrhythmia Agents ,medicine.drug - Abstract
Sir,Flecainide inhibits myocardial sodium channels. Consequently, overdose has been associated with bradycardia and polymorphic ventricular tachycardia. [1] To date, there is no established treatme...
- Published
- 2016
66. UEG Week 2013 Oral Presentations
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Arnulf Ferlitsch, Karel Caca, Michaela Neagu, Limas Kupčinskas, Ralf Mohrbacher, Martin Rössle, Wolfgang Kreisel, Jolanta Šumskienė, Tilman Sauerbruch, Beate Appenrodt, Peter Deibert, Roland Greinwald, and Alexander Zipprich
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Udenafil ,medicine.drug_mechanism_of_action ,business.industry ,Gastroenterology ,UEG Week 2013 Oral Presentations ,Pharmacology ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Pharmacotherapy ,Oncology ,030220 oncology & carcinogenesis ,medicine ,Portal hypertension ,030211 gastroenterology & hepatology ,business ,Phosphodiesterase 5 inhibitor ,medicine.drug - Published
- 2013
67. Automated low flow pump system for the treatment of refractory ascites: A multi-center safety and efficacy study
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Germán Soriano, José Such, Pablo Bellot, Reiner Wiest, Stoyan Handshiev, Steven Whittaker, Radin Tzonev, Frederik Nevens, Carlos Guarner, Pedro Zapater, Stefan Zeuzem, C. Moench, K. Katzarov, Beate Appenrodt, Tilman Sauerbruch, Noel Johnson, Chris Verslype, Martin-Walter Welker, Ekart Schott, Assen Petrov, and Markus von Schaewen
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Adult ,Male ,medicine.medical_specialty ,Cirrhosis ,medicine.medical_treatment ,Failure ,Kidney ,Spontaneous bacterial peritonitis ,Model for End-Stage Liver Disease ,Hepatorenal syndrome ,Recurrence ,Ascites ,medicine ,Paracentesis ,Humans ,Hepatic encephalopathy ,Aged ,Aged, 80 and over ,Refractory ,Hepatology ,medicine.diagnostic_test ,business.industry ,Hemodynamics ,Membrane Transport Proteins ,Middle Aged ,medicine.disease ,Surgery ,Treatment Outcome ,Liver ,Female ,medicine.symptom ,business ,Transjugular intrahepatic portosystemic shunt ,Follow-Up Studies - Abstract
Background & Aims: Refractory ascites (RA) affects 10% of patients with advanced cirrhosis and ascites. Usual therapy includes large volume paracentesis, and in selected patients, a transjugular portosystemic shunt (TIPS). These therapies may be associated with increased morbidity: paracentesis may induce circulatory dysfunction and impair quality of life and TIPS may induce encephalopathy and is associated with increased mortality in patients with severe liver dysfunction. We present the results of a multicenter, non-randomized trial to assess the safety and efficacy of a new automated pump system for treatment of RA. Methods: Forty patients at 9 centers (February 2010-June 2011) received an implanted pump for the automated removal of ascites from the peritoneal cavity into the bladder, from where it was eliminated through normal urination. Patients were followed-up for 6 months. The primary study outcome was safety. Secondary outcomes included recurrence of tense ascites and pump performance. Results: Surgical complications occurred early in the study and became less frequent. The pump system removed 90% of the ascites and significantly reduced the median number of large volume paracentesis per month [3.4 (range 1-6) vs. 0.2 (range 0-4); p
- Published
- 2013
68. Hepatic and serum levels of miR-122 after chronic HCV-induced fibrosis
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Jonel Trebicka, Michael Roggendorf, Hans-Peter Dienes, Sergei Viazov, Evrim Anadol, Margarete Odenthal, Inga Wedemeyer, Tilman Sauerbruch, Uta Drebber, N Elfimova, I. Strack, and Jürgen K. Rockstroh
- Subjects
Liver Cirrhosis ,Male ,Pathology ,medicine.medical_specialty ,Genotype ,Biopsy ,Hepatitis C virus ,Medizin ,Hepacivirus ,Biology ,Chronic liver disease ,medicine.disease_cause ,Severity of Illness Index ,Fibrosis ,medicine ,MiR-122 ,Humans ,Liver injury ,Hepatology ,medicine.diagnostic_test ,Hepatitis C ,Hepatitis C, Chronic ,medicine.disease ,MicroRNAs ,Liver ,Liver biopsy ,Disease Progression ,Female ,Hepatic fibrosis ,Biomarkers - Abstract
Background & Aims The progression of liver fibrosis in patients with chronic hepatitis C (CHC) is important to decide on the treatment of the virus. As liver biopsy and liver stiffness measurement for staging of fibrosis present limitations, circulating levels of miR-122 have been suggested as a novel biomarker to predict the extent of liver injury. We evaluated the potential of miR-122 as an indicator of fibrosis progression in CHC infection and performed, for the first time, a comprehensive analysis of hepatic and circulating miR-122 levels in patients with CHC. Methods Patients with well-documented CHC infection were selected from the database of HepNet, the German-Competence-Network on Viral Hepatitis. All patients underwent blood sampling and liver biopsy with grading of inflammation and staging of fibrosis. RNA was extracted from 84 liver biopsies and 164 serum samples of CHC patients. miR-122 levels in liver and serum samples were quantified by real-time PCR normalized to RNU6 or spiked-in RNA, respectively. Results Hepatic levels of miR-122 decreased significantly with the severity of fibrosis ( p =0.001). In addition, circulating miR-122 levels correlated negatively with increasing stages of fibrosis, although the inverse correlation was moderate due to a two-phase miR-122 pattern during fibrosis progression. Thus, circulating miR-122 levels decreased in patients with severe fibrosis (F3, F4), while at early stages with distinct fibrotic structures (F2) and high inflammatory activity, miR-122 serum levels were elevated. Conclusions We conclude that during progression of fibrosis less miR-122 is released into the blood stream due to the loss of liver cells and the decrease of hepatic miR-122 levels. Although the release of circulating miR-122 possibly mirrors acute liver injury, in chronic liver disease and fibrosis, the loss of liver cells and the decreased hepatocellular miR-122 expression render miR-122 an inappropriate marker, when exclusively used for interpretation of fibrosis progression.
- Published
- 2013
69. Inhibition of hepatitis C virus RNA translation by antisense bile acid conjugated phosphorothioate modified oligodeoxynucleotides (ODN)
- Author
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Thomas Lehmann, Annabelle Vogt, Wolfgang H. Caselmann, Gerd A. Kullak-Ublick, Yildiz Yildiz, Tilman Sauerbruch, Joachim W. Engels, Maria A. Gonzalez-Carmona, Per Hoffmann, Ralf Bartenschlager, A. Tamke, Maria Quasdorff, University of Zurich, and Caselmann, Wolfgang H
- Subjects
medicine.drug_class ,viruses ,Gene Expression ,Phosphorothioate Oligonucleotides ,610 Medicine & health ,Hepacivirus ,Virus Replication ,Antiviral Agents ,Bile Acids and Salts ,Genes, Reporter ,In vivo ,Virology ,Gene expression ,medicine ,Humans ,Gene ,Cells, Cultured ,Pharmacology ,Bile acid ,Chemistry ,virus diseases ,Translation (biology) ,Transfection ,Molecular biology ,digestive system diseases ,In vitro ,Internal ribosome entry site ,3004 Pharmacology ,10199 Clinic for Clinical Pharmacology and Toxicology ,Protein Biosynthesis ,Hepatocytes ,2406 Virology - Abstract
Background The 5′-noncoding region (5′NCR) of the HCV-genome comprises an internal ribosome entry site essential for HCV-translation/replication. Phosphorothioate oligodeoxynucleotides (tS-ODN) complementary to this region can inhibit HCV-translation in vitro. In this study, bile acid conjugated tS-ODN were generated to increase cell-selective inhibition of 5′NCR-dependent HCV-translation. Methods Different bile acid conjugated tS-ODN complementary to the HCV5′NCR were selected for their inhibitory potential in an in vitro transcription/translation assay. To analyze OATP (organic anion transporting polypeptides)-selective uptake of bile acid conjugated ODN, different hepatoma cells were stably transfected with the OATP1B1-transporter and primary human hepatocytes were used. An adenovirus encoding the HCV5′NCR fused to the luciferase gene (Ad-GFP-NCRluc) was generated to quantify 5′NCR-dependent HCV gene expression in OATP-overexpressing hepatoma cells and in vivo. Results A 17mer phosphorothioate modified ODN (tS-ODN4_13) complementary to HCV5′NCR was able to inhibit 5′NCR-dependent HCV-translation in an in vitro transcription/translation test system by more than 90% and it was also effective in Huh7-cells containing the HCV subgenomic replicon. Conjugation to taurocholate (tS-ODN4_13T) significantly increased selective ODN uptake by primary human hepatocytes and by OATP1B1-expressing HepG2-cells compared to parental HepG2-cells. Correspondingly, tS-ODN4_13T significantly inhibited HCV gene expression in liver-derived OATP1B1-expressing HepG2- or CCL13-cells up to 70% compared to unconjugated tS-ODN and compared to mismatch taurocholate coupled tS-ODN. In vivo, tS-ODN4_13T showed also a trend to block 5′NCR-dependent HCV gene expression. Conclusions The tested taurocholate conjugated 17mer antisense ODN complementary to HCV5′NCV showed an increased and selective uptake by hepatocytes and liver-derived cells through OATP-mediated transport resulting in enhanced specific inhibition of HCV gene expression in vitro and in vivo. Thus, this novel approach may represent a promising strategy to improve antisense approaches with ODN in the control of hepatitis C infection.
- Published
- 2013
70. Common genetic variation in vitamin D metabolism is associated with liver stiffness
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Michael Trauner, A Höblinger, K Hochrath, Frank Grünhage, Jürgen Geisel, Barbara Obermayer-Pietsch, Marcin Krawczyk, Tilman Sauerbruch, and Frank Lammert
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Adult ,Liver Cirrhosis ,Male ,Heterozygote ,Oxidoreductases Acting on CH-CH Group Donors ,medicine.medical_specialty ,Adolescent ,Vitamin D-binding protein ,Biology ,Polymorphism, Single Nucleotide ,Statistics, Nonparametric ,vitamin D deficiency ,Young Adult ,Liver disease ,Fibrosis ,Internal medicine ,medicine ,Vitamin D and neurology ,Humans ,Genetic Predisposition to Disease ,Vitamin D ,Cytochrome P450 Family 2 ,Alleles ,Aged ,Aged, 80 and over ,Hepatology ,Vitamin D-Binding Protein ,Homozygote ,Middle Aged ,medicine.disease ,Elasticity ,Endocrinology ,Multivariate Analysis ,Linear Models ,Cholestanetriol 26-Monooxygenase ,Elasticity Imaging Techniques ,Female ,Transient elastography ,Hepatic fibrosis - Abstract
Recently, genome-wide studies identified genetic variants that affect serum 25-hydroxyvitamin D levels in healthy populations (rs12785878, near dehydrocholesterol reductase, DHCR7; rs10741657, at CYP2R1; and rs7041, at vitamin D binding protein, GC). Because vitamin D deficiency is associated with advanced liver disease, we hypothesized that these variants are associated with 25(OH)-vitamin D levels and liver fibrosis. Overall, 712 Caucasian patients with chronic liver diseases were included. Liver fibrosis was assessed by transient elastography (TE) and/or histology. Serum levels of 25(OH)-vitamin D were correlated with TE and fibrosis stages. Genotypes were determined using TaqMan assays and tested for association with vitamin D and liver stiffness. Serum 25(OH)-vitamin D levels were inversely correlated with liver stiffness and histology (P < 0.001). Homozygous carriers of the rare DHCR7 allele or the common CYP2R1 allele presented with reduced 25(OH)-vitamin D levels (P < 0.05). The variant rs12785878 in the DHCR7 locus was associated with liver stiffness in both patients with TE
- Published
- 2012
71. NK cells from HCV-infected patients effectively induce apoptosis of activated primary human hepatic stellate cells in a TRAIL-, FasL- and NKG2D-dependent manner
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Christian Körner, Martin Coenen, M Eisenhardt, Benjamin Krämer, Jacob Nattermann, Tilman Sauerbruch, Andreas Glässner, and Ulrich Spengler
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Adult ,Male ,Fas Ligand Protein ,Apoptosis ,In Vitro Techniques ,Biology ,Antiviral Agents ,Polyethylene Glycols ,Pathology and Forensic Medicine ,TNF-Related Apoptosis-Inducing Ligand ,Interferon-gamma ,Interleukin 21 ,Interferon ,Ribavirin ,Hepatic Stellate Cells ,medicine ,Humans ,Molecular Biology ,Aged ,Aged, 80 and over ,Tumor Necrosis Factor-alpha ,Degranulation ,Interferon-alpha ,Cell Biology ,Hepatitis C, Chronic ,Middle Aged ,NKG2D ,Recombinant Proteins ,Killer Cells, Natural ,NK Cell Lectin-Like Receptor Subfamily K ,Case-Control Studies ,Immunology ,Cancer research ,Interleukin 12 ,Hepatic stellate cell ,Female ,Tumor necrosis factor alpha ,medicine.drug - Abstract
In mouse models it has been shown that natural killer (NK) cells can attenuate liver fibrosis via killing of activated hepatic stellate cells (HSCs) in a NKG2D- and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-dependent manner. However, only little data exist regarding interactions of human NK cells with HSCs and their potential role in hepatitis C virus (HCV)-associated fibrogenesis. Therefore, purified NK cells from untreated HCV RNA(+) patients (n=33), interferon-α (IFN-α)-treated patients (n=17) and healthy controls (n=18) were coincubated with activated primary HSCs, and were tested for degranulation (CD107a expression) and secretion of IFN-γ and TNF-α, respectively. Induction of HSC apoptosis was analyzed using an active caspase-3 assay. We found that following coincubation with HSCs a significant increase in CD107a expression could be observed in both NK cells from HCV(+) patients and healthy controls, whereas only negligible secretion of IFN-γ and TNF-α could be detected. More importantly, NK cells from untreated HCV RNA(+) patients were significantly more effective in induction of HSC apoptosis (17.8 ± 9.2%) than NK cells from healthy controls (6.2 ± 2.1%; P
- Published
- 2012
72. Continuation of nonselective beta‐blockers for patients with liver cirrhosis and hemodynamic nonresponse?
- Author
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Tilman Sauerbruch
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0301 basic medicine ,medicine.medical_specialty ,Cirrhosis ,Hepatology ,business.industry ,Hemodynamics ,medicine.disease ,Gastroenterology ,Adrenergic beta-Antagonists ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Text mining ,Internal medicine ,medicine ,030211 gastroenterology & hepatology ,Beta (finance) ,business - Published
- 2017
73. Endotoxin and tumor necrosis factor-receptor levels in portal and hepatic vein of patients with alcoholic liver cirrhosis receiving elective transjugular intrahepatic portosystemic shunt
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Aleksander Krag, Ulrich Spengler, Tilman Sauerbruch, Beate Appenrodt, Peter Schiedermaier, Stefan Gansweid, and Jonel Trebicka
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Adult ,Male ,medicine.medical_specialty ,Cirrhosis ,medicine.medical_treatment ,Portal venous pressure ,Hemodynamics ,Blood Pressure ,Hepatic Veins ,Gastroenterology ,Receptors, Tumor Necrosis Factor ,Liver Cirrhosis, Alcoholic ,Internal medicine ,Hypertension, Portal ,medicine ,Humans ,Receptors, Tumor Necrosis Factor, Type II ,Vein ,Aged ,Aged, 80 and over ,Hepatology ,Portal Vein ,business.industry ,General surgery ,Ultrasonography, Doppler ,Venous blood ,Middle Aged ,medicine.disease ,Endotoxins ,medicine.anatomical_structure ,Blood pressure ,Portal hypertension ,Female ,Portasystemic Shunt, Transjugular Intrahepatic ,business ,Transjugular intrahepatic portosystemic shunt ,Blood Flow Velocity ,Follow-Up Studies - Abstract
Background/aims In cirrhosis portal hypertension can promote bacterial translocation and increase serum endotoxin levels. Vice versa, endotoxin aggravates portal hypertension by induction of systemic and splanchnic vasodilation, and by triggering hepatic inflammatory response via tumor necrosis factor α (TNFα). However, the hepatic elimination of endotoxin in cirrhotic patients with severe portal hypertension, in the absence of acute complications, has not been investigated so far. Methods Twenty patients with alcoholic liver cirrhosis received transjugular intrahepatic portosystemic shunt at an event-free interval for either refractory ascites or recurrent bleeding. During the transjugular intrahepatic portosystemic shunt procedure portal and hepatic venous blood samples were obtained and endotoxin levels were measured by a chromogenic limulus-assay. In 16 of these patients an enzyme-linked immunosorbent assay was used to measure levels of the soluble TNFα-receptors sTNF-R55 and sTNF-R75. Results Portal venous endotoxin levels correlated with portal vein velocity (P=0.03) and arterial systolic blood pressure (P=0.007). Portal endotoxin levels correlated with portal venous sTNF-R75-levels (P=0.039; r=0.521) and hepatic venous sTNF-R55-levels (P=0.009; r=0.669). Hepatic venous levels of both sTNF-R55 and sTNF-R75 correlated directly with the model for end-stage liver disease-score, and inversely with cholinesterase. However, we did not find significant differences in endotoxin levels nor in sTNF-R55-levels and sTNF-R75-levels between portal and hepatic venous blood. Conclusion Endotoxin levels correlated with hemodynamic derangement in cirrhotic severe portal hypertension, and with levels of soluble TNFα-receptors. Soluble TNFα-receptor levels correlated with the severity of liver dysfunction. However, in this study an endotoxin concentration gradient across the liver was absent, suggesting negligible primary hepatic endotoxin elimination in the absence of complications.
- Published
- 2011
74. Darmkrebsfrüherkennung im Nationalen Krebsplan – Aktueller Stand und Empfehlungen für die Weiterentwicklung
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H. Brenner, C. Maar, J. F. Riemann, M. Betzler, and Tilman Sauerbruch
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medicine.medical_specialty ,Cancer prevention ,Gastroenterology ,Offensive ,Cancer ,medicine.disease ,language.human_language ,German ,Documentation ,Political science ,Family medicine ,language ,medicine ,Data Protection Act 1998 ,Working group ,Administration (government) - Abstract
The National Cancer Programme of the German Federal Administration aims to assess the present status of the national fight against cancer in Germany. Experts in their field have analysed the present target-performance comparison in different working groups dealing with topics from cancer prevention to follow-up and have developed recommendations as to how improvements in the various fields of cancer care may be achieved and mainly how these imrpovements may be implemented in day-to-day cancer care. The working group "Advancement of Colon Cancer Screening, Early Detection and Prevention" proposes the establishment of regulatory proposals for a nationwide, population-based, postal invitational process and, according to Pilot-Projects in Bavaria and Baden-Wuerttemberg, to evaluate the essential recommendations in data protection, logistics, documentation and financing. There are already several programmes in preparation--for example, the Saarland Offensive, based on the results of the KolosSal-Study.
- Published
- 2011
75. Progression of liver fibrosis in HIV/HCV genotype 1 co-infected patients is related to the T allele of the rsI2979860 polymorphism of the IL28B gene
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N. Vidovic, U Spcngler, Philipp Lutz, Juergen K. Rockstroh, JC Wasmuth, F Grünhagei, Tilman Sauerbruch, Frank Lammert, H-D Nischalke, and Johannes Oldenburg
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Adult ,Male ,Cirrhosis ,Genotype ,Hepacivirus ,IL28B ,lcsh:Medicine ,Viremia ,HIV Infections ,Polymorphism, Single Nucleotide ,polymorphism ,Liver disease ,Fibrosis ,Antiretroviral Therapy, Highly Active ,Medicine ,Humans ,Allele ,Alleles ,liver fibrosis ,Aged ,biology ,business.industry ,Research ,Interleukins ,Liver Diseases ,lcsh:R ,virus diseases ,HIV ,General Medicine ,Middle Aged ,medicine.disease ,biology.organism_classification ,transient elastography ,Cross-Sectional Studies ,Immunology ,HCV ,Disease Progression ,Elasticity Imaging Techniques ,Female ,Interferons ,business ,Transient elastography - Abstract
Objective HIV/HCV co-infection is characterised by accelerated progression of liver disease. Recently, the rsl2979860 C/T polymorphism in the IL28B gene has been linked to progression towards cirrhosis in HCV mono-infected patients and to treatment response of HCV-infection in HIV/HCV co-infected patients. Our aim was to clarify by non-invasive techniques if this polymorphism affects fibrosis progression in HIV/HCV co-infection. Methods In a cross-sectional design, liver stiffness (transient elastography), surrogate markers of liver fibrosis (APRI and FIB-4 scores) and rsl2979860 genotypes were analysed in 84 HCV/H1V co-infected patients. IL28B genotypes were determined by real-time PCR using a light cycler. In 56 HIV/HCV co-infected patients we also studied progression of fibrosis in relation to rsl2979860 C/T genotypes over two years. Results 82% of the patients were on HAART (74% without detectable HI viremia) and 67% were haemophiliacs, respectively. HCV genotype 1 was present in 62%. Cross-sectional median liver stiffness was 7.4 kPa and correlated with APRI and FIB-4 scores (r = 0.6 each, p < 0.001). Frequencies of IL28B genotypes were: CC 50%, CT 43% and TT 7%. In the cross-sectional analysis liver stiffness values were not different between the various IL28B-genotypes. Upon follow-up under HAART carriers of a C allele did not show further progression, while liver stiffness significantly increased in HIV/HCV co-infected patients with the T allele (p = 0.047). Conclusion Although progression of liver fibrosis was low under HAART in our cohort, progression was more pronounced in HIV/HCV genotype 1 co-infected patients with the T allele.
- Published
- 2011
76. Komplikationen der Leberzirrhose
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Jonel Trebicka, Tilman Sauerbruch, and Beate Appenrodt
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medicine.medical_specialty ,Cirrhosis ,business.industry ,General Medicine ,medicine.disease ,Gastroenterology ,Text mining ,Esophageal varices ,Internal medicine ,Ascites ,Medicine ,medicine.symptom ,business ,Hepatic encephalopathy - Published
- 2011
77. Is beta-trace protein an alternative marker of glomerular filtration rate in liver transplant recipients?
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Thomas Gerhardt, Tilman Sauerbruch, Rainer P. Woitas, Uwe Pöge, Birgit Stoffel-Wagner, and Holger Palmedo
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medicine.medical_specialty ,Creatinine ,Hepatology ,biology ,business.industry ,medicine.medical_treatment ,Area under the curve ,Urology ,Renal function ,Liver transplantation ,urologic and male genital diseases ,Muscle mass ,female genital diseases and pregnancy complications ,Beta-Trace Protein ,chemistry.chemical_compound ,Endocrinology ,Cystatin C ,chemistry ,Internal medicine ,medicine ,biology.protein ,In patient ,business - Abstract
Background: Renal insufficiency is common after liver transplantation (LT). The use of creatinine (Crea) as a marker of the glomerular filtration rate (GFR) is limited in patients after LT. Beta-trace protein (BTP), an alternative marker of GFR, is independent of muscle mass and has not been evaluated in LT recipients. Aim: To evaluate BTP as an alternative tool to monitor renal function in LT recipients. Methods: We determined the diagnostic performance of BTP in comparison to Crea and cystatin C (CysC) in 52 patients, who concomitantly underwent 99mTc-DTPA-clearance measurements. Furthermore, we evaluated bias, precision and accuracy of five recently developed BTP-based equations to estimate GFR. Results: The average measured GFR was 51 (46.1; 56.0) ml/min/1.73 m2. Using a cut-off of 30 ml/min/1.73 m2 the area under the curve (AUC) was nearly identical for all markers. At a decision point of 60 ml/min/1.73 m2 BTP showed only a trend towards a higher AUC compared with Crea and CysC (0.806 vs. 0.754 and 0.760, respectively; P>0.2). In comparison to the modification of diet in renal disease-formula (MDRD) only one of five BTP-based equations displayed a significantly higher accuracy within 30% of the measured GFR (84.6 vs. 59.6%; P=0.006). None of these equations showed a significant improvement compared with MDRD with respect to bias and precision. Conclusions: Beta-trace protein can be used as an alternative diagnostic tool to detect moderate or severe GFR reduction in patients after LT. Furthermore BTP-based equations are able to estimate GFR in LT recipients. However, these equations fail to perform constantly better than the MDRD formula.
- Published
- 2011
78. Role of cannabinoid receptors in alcoholic hepatic injury: steatosis and fibrogenesis are increased in CB2 receptor-deficient mice and decreased in CB1 receptor knockouts
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Jonel Trebicka, Jörg Heller, Erlind Cara, Tilman Sauerbruch, Andreas Zimmer, Ildiko Racz, A. Wojtalla, Sören V. Siegmund, Martin Hennenberg, Sabine Klein, Hans-Peter Fischer, Sebastian Huss, Michaela Granzow, and Robert Schierwagen
- Subjects
Liver injury ,medicine.medical_specialty ,Hepatology ,biology ,Receptor expression ,Fatty liver ,medicine.disease ,Fatty acid synthase ,Endocrinology ,Internal medicine ,medicine ,Hepatic stellate cell ,biology.protein ,Cannabinoid receptor type 2 ,Steatosis ,Receptor - Abstract
Background Alcohol is a common cause of hepatic liver injury with steatosis and fibrosis. Cannabinoid receptors (CB) modulate steatosis, inflammation and fibrogenesis. To investigate the differences between CB(1) and CB(2) in the hepatic response to chronic alcohol intake, we examined CB knockout mice (CB(1)(-/-), CB(2)(-/-)). Methods Eight- to 10-week-old CB(1)(-/-), CB(2)(-/-) and wild-type mice received 16% ethanol for 35 weeks. Animals receiving water served as controls. We analysed triglyceride and hydroxyproline contents in liver homogenates. mRNA levels of CBs, pro-inflammatory cytokines [tumour necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, interleukin (IL)-1β] and profibrotic factors [α-smooth muscle actin (α-SMA), procollagen-Ia, platelet-derived growth factor β receptor (PDGFβ-R)] were analysed by reverse transcription-polymerase chain reaction (RT-PCR). Histology (hemalaun and eosin, oil-red O, CD3, CD45R, CD45, F4/80, Sirius red) characterized hepatic steatosis, inflammation and fibrosis. Activation of lipogenic pathways, activation and proliferation of hepatic stellate cell (HSC) were assessed by western blot [fatty acid synthase (FAS), sterol regulatory element binding protein 1c (SREBP-1c), α-SMA, proliferating cell nuclear antigen (PCNA), cathepsin D]. Results Hepatic mRNA levels of the respective CBs were increased in wild-type animals and in CB(1)(-/-) mice after ethanol intake. Ethanol intake in CB(2)(-/-) mice induced much higher steatosis (SREBP-1c mediated) and inflammation (B-cell predominant infiltrates) compared with wild-type animals and CB(1)(-/-) mice. HSC activation and collagen production were increased in all groups after forced ethanol intake, being most pronounced in CB(2)(-/-) mice and least pronounced in CB(1)(-/-) mice. Discussion The fact that CB(2) receptor knockout mice exhibited the most pronounced liver damage after ethanol challenge indicates a protective role of CB(2) receptor expression in chronic ethanol intake. By contrast, in CB(1) knockouts, the effect of ethanol was attenuated, suggesting aggravation of fibrogenesis and SREBP-1c-mediated steatosis via CB(1) receptor expression after ethanol intake.
- Published
- 2011
79. S3-Leitlinie 'Aszites, spontan bakterielle Peritonitis, hepatorenales Syndrom'
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Matthias M. Dollinger, Beate Appenrodt, Alexander L. Gerbes, Veit Gülberg, M. Schepke, Martin Rössle, Matthias J. Bahr, Reiner Wiest, and Tilman Sauerbruch
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medicine.medical_specialty ,business.industry ,Gastroenterology ,Guideline ,medicine.disease ,language.human_language ,German ,Spontaneous bacterial peritonitis ,Hepatorenal syndrome ,Internal medicine ,Ascites ,language ,medicine ,medicine.symptom ,business - Published
- 2011
80. Validation of the CKD-EPI formula in patients after renal transplantation
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Uwe Pöge, Thomas Gerhardt, Tilman Sauerbruch, Rainer P. Woitas, and Birgit Stoffel-Wagner
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Male ,medicine.medical_specialty ,Validation study ,Urology ,Renal function ,Kidney Function Tests ,urologic and male genital diseases ,Internal medicine ,medicine ,Humans ,In patient ,Prospective Studies ,Prospective cohort study ,reproductive and urinary physiology ,Kidney transplantation ,Transplantation ,business.industry ,Middle Aged ,medicine.disease ,Kidney Transplantation ,female genital diseases and pregnancy complications ,Confidence interval ,Endocrinology ,Nephrology ,Female ,business ,Glomerular Filtration Rate ,Kidney disease - Abstract
Background. Accurate calculation of glomerular filtration rate (GFR) is crucial in the management of patients after kidney transplantation (KTx). Recently, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula was introduced to estimate GFR in chronic kidney disease patients. However, to date the diagnostic value of this equation remains to be determined in patients after KTx. Methods. We analysed the CKD-EPI formula in comparison to the re-expressed Modification of Diet in Renal Disease (MDRD) equation in 170 stable patients after renal transplantation. Correlation, bias, precision and accuracy within 30 and 50% of true GFR were determined. GFR was measured by technetium-diethylenetriamine pentaacetic acid clearance [39.6, 95% confidence interval (CI): 37.3–42.0 mL/min/1.73m 2 ]. Results. The results for the MDRD and CKD-EPI equations correlated well with GFR (0.82; 0.83, respectively). GFR calculated by MDRD (44.1, 95% CI: 41.6–46.8 mL/ min/1.73m 2 ) and CKD-EPI (47.7, 95% CI: 44.7–50.7 mL/ min/1.73m 2 ) overestimated true GFR significantly (P < 0.001). Precision was not significantly different between MDRD and CKD-EPI (10.9 versus 10.0 mL/min/1.73m 2 , respectively). Accuracy within 30% of true GFR was significantly higher for MDRD (71.8%) than for CKD-EPI (64.1%, P ¼ 0.0014). Accuracy within 50% of true GFR did not differ significantly (MDRD: 89.4% versus CKDEPI: 84.7%, P ¼ 0.06). Conclusion. The new CKD-EPI formula did not improve the estimation of GFR in Caucasian patients after renal transplantation in this study.
- Published
- 2011
81. Interferon-lambda serum levels in hepatitis C
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Bernd Kupfer, Tilman Sauerbruch, Jacob Nattermann, Bettina Langhans, Hans Dieter Nischalke, I. Braunschweiger, S. Arndt, Ulrich Spengler, Wibke Schulte, and Johannes Oldenburg
- Subjects
Adult ,Male ,Genotype ,Hepatitis C virus ,Hepacivirus ,Viral Nonstructural Proteins ,Biology ,medicine.disease_cause ,Tetraspanin 28 ,Immune system ,Viral Envelope Proteins ,Antigens, CD ,Interferon ,medicine ,Humans ,Allele ,Aged ,Hepatitis ,NS3 ,Polymorphism, Genetic ,Hepatology ,Interleukins ,Dendritic Cells ,Hepatitis C ,Hepatitis C, Chronic ,Middle Aged ,Viral Load ,Prognosis ,medicine.disease ,Virology ,Toll-Like Receptor 2 ,In vitro ,Cross-Sectional Studies ,Immunology ,Female ,Interferons ,medicine.drug - Abstract
Dendritic cells (DCs) trigger adaptive immune responses and are an important source of antiviral cytokines. In hepatitis C virus (HCV) infection DC function is markedly impaired. Thus far, studies have focused on types I and II interferon (IFN). We studied IFN-lambda1 (IL-29) and IFN-lambda2/3 (IL-28A/B) serum levels in patients with different outcomes of HCV infection.IFN-lambdas were measured by ELISAs detecting IL-29 or IL-28A and IL-28B, respectively. Results were stratified with respect to the recently discovered rs12979860 T/C polymorphism upstream of the IL-28B gene.In general IL-29 serum levels exceeded IL-28A/B at least twofold, with IL-29 and IL-28A/B levels being significantly higher in carriers of the rs12979860 C allele than in TT homozygous individuals (p0.02). IL-29 levels were substantially lower in patients with chronic hepatitis C than in healthy controls (p=0.005) and patients with spontaneously resolved hepatitis (p=0.001). Patients with acute hepatitis C showed IL-29 levels intermediate between chronic hepatitis C and normal controls; and IL-29 serum levels were higher in patients who spontaneously resolved hepatitis C than in those who became chronic. In vitro HCV proteins NS3 and E2 directly inhibited IL-29 production in poly I:C-stimulated purified DCs.Our data suggest that HCV proteins modify IFN-lambda production in DCs. Carriers of the rs12979860 C allele associated with resolution of HCV infection exhibited increased IFN-lambda levels. Moreover, high IFN-lambda levels predisposed to spontaneous resolution of HCV infection. Thus, IFN-lambdas seem to play an important role in the control of hepatitis C.
- Published
- 2011
82. Genetic Variation in IL28B and Treatment-induced Clearance of Hepatitis C Virus in HIV-Positive Patients With Acute and Chronic Hepatitis C
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Bernhard Bienek, Jacob Nattermann, Thomas A. Lutz, Gerd Klausen, Stefan Mauss, Juergen K. Rockstroh, U Naumann, Ulrich Spengler, Michael Rausch, Christoph Mayr, Hans Dieter Nischalke, Knud Schewe, Bonaventura Clotet, Raffaele Bruno, Georg Haerter, Axel Baumgarten, Hans Jörg Stellbrink, Cristina Tural, Mark Danta, Martin Vogel, and Tilman Sauerbruch
- Subjects
Adult ,Male ,Genotype ,Hepatitis C virus ,Hepacivirus ,HIV Infections ,medicine.disease_cause ,Polymorphism, Single Nucleotide ,Virus ,Major Articles and Brief Reports ,Flaviviridae ,medicine ,Humans ,Immunology and Allergy ,Aged ,Aged, 80 and over ,biology ,Interleukins ,Hepatitis C ,Middle Aged ,medicine.disease ,biology.organism_classification ,CD4 Lymphocyte Count ,Treatment Outcome ,Infectious Diseases ,Case-Control Studies ,Immunology ,RNA, Viral ,Regression Analysis ,Female ,Interferons ,Gene polymorphism ,Viral disease - Abstract
Recently, a IL28B (rs 12979860) gene polymorphism was identified as a predictor for response to hepatitis C virus-specific treatment in human immunodeficiency virus (HIV)-uninfected and -infected patients with chronic hepatitis C. In an analysis of HIV-infected patients with acute hepatitis C, we found that the IL28B genotype was associated with serum levels of hepatitis C virus RNA, g-GT, and CD4 cell count. In contrast to HIV-infected patients with chronic hepatitis C, the IL28B genotype was not significantly associated with treatment response rates in patients with acute hepatitis C. Thus, effects of the IL28B single-nucleotide polymorphism may differ in HIV-infected patients with chronic and acute hepatitis C.
- Published
- 2011
83. Heterozygosity for the alpha1-antitrypsin Z allele may confer genetic risk of cholangiocarcinoma
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Frank Lammert, A Höblinger, Tilman Sauerbruch, Frank Grünhage, Vincent Zimmer, F Mihalache, Monica Acalovschi, Marcin Krawczyk, and BC Gärtner
- Subjects
Genetics ,medicine.medical_specialty ,Hepatology ,Haplotype ,Gastroenterology ,Biology ,Loss of heterozygosity ,Minor allele frequency ,Internal medicine ,Genetic variation ,Genotype ,medicine ,Genetic predisposition ,Pharmacology (medical) ,Allele ,Risk factor - Abstract
Aliment Pharmacol Ther 2011; 33: 389–394 Summary Background Alpha1-antitrypsin (α1AT) deficiency caused by Z allele homozygosity represents a well-established risk factor for hepatocellular carcinoma. Previous studies have also implicated α1AT Z heterozygosity in cholangiocarcinogenesis. Aim To assess the ‘common’ Z and S alleles as well as the promoter variant rs8004738 for association with cholangiocarcinoma. Methods We genotyped 182 Caucasian patients and 350 controls for rs28929474 (Z), rs17580 (S) and the variant rs8004738. Exploratory analyses were performed in relation to gender and cholangiocarcinoma localisation. Results rs28929474 was significantly enriched in the cholangiocarcinoma group (4.1 vs. 1.7%; OR 2.46, 95% CI 1.14–5.32; Bonferroni corrected pc = 0.036), reinforced by Armitage trend testing (OR 2.53; pc = 0.032). The rs8004738 (promoter) minor allele tended to be overrepresented in Z heterozygotes (30.0 vs. 16.7%: P = 0.13). Exploratory data analyses suggested a high genetic risk for extrahepatic tumour localisation (OR 3.0; pc = 0.016) and potentially female Z allele carriers (OR 3.37; unadjusted P = 0.022, pc = 0.088). Conclusions These data point to a novel role of α1AT Z heterozygosity as a potential genetic susceptibility factor for cholangiocarcinoma formation and suggest a contribution of aberrant α1AT function in biliary carcinogenesis. However, given the overall low rs28929474 minor allele frequency, larger studies are warranted to confirm and extend our findings.
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- 2010
84. Atorvastatin attenuates hepatic fibrosis in rats after bile duct ligation via decreased turnover of hepatic stellate cells
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Frank Lammert, Hans-Peter Dienes, Sabine Klein, Martin Hennenberg, Tilman Sauerbruch, Annabelle Vogt, Michaela Granzow, Jörg Heller, Margarete Odenthal, Khanwali Shir, Jürg Reichen, and Jonel Trebicka
- Subjects
Liver Cirrhosis ,Male ,medicine.medical_specialty ,Atorvastatin ,medicine.medical_treatment ,Biology ,Rats, Sprague-Dawley ,Fibrosis ,Internal medicine ,Hepatic Stellate Cells ,medicine ,Animals ,Pyrroles ,Ligation ,Cell Proliferation ,Liver injury ,Hepatology ,medicine.disease ,Rats ,CTGF ,Endocrinology ,Cytokine ,Heptanoic Acids ,Biliary tract ,Hepatic stellate cell ,Bile Ducts ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Hepatic fibrosis ,medicine.drug - Abstract
Background & Aims Activation of hepatic stellate cells (HSC) and transdifferentiation to myofibroblasts following liver injury is the main culprit for hepatic fibrosis. Myofibroblasts show increased proliferation, migration, contraction, and production of extracellular matrix (ECM). In vitro , HMG-CoA reductase inhibitors (statins) inhibit proliferation and induce apoptosis of myofibroblastic HSC. To investigate the antifibrotic effects of atorvastatin in vivo we used bile duct ligated rats (BDL). Methods BDL rats were treated with atorvastatin (15mg/kg/d) immediately after ligation (prophylactically) or in on-going fibrosis (therapeutically). Fibrosis was assessed by hydroxyproline content and Sirius-red staining. The activation of HSC was investigated by analysis of αSMA expression. mRNA levels of cytokines and procollagen were analyzed by RT-PCR, and MMP-2 activity by zymography. Proliferation was assessed by expression of cathepsins (B and D), proliferating cell nuclear antigen (PCNA), and Ki67-staining. Apoptosis was characterized by caspase-3 activity, cleavage of PARP-1, and TUNEL assay. Hepatic inflammation was investigated by serum parameters and liver histology. Results Prophylactic and early therapy with atorvastatin significantly attenuated fibrosis and HSC activation. Later therapy lacked significant effects on fibrosis but reduced profibrotic cytokine expression and led to a more quiescent state of HSC with less proliferation and apoptosis, while hepatic inflammation did not change. Conclusions This study shows that very early atorvastatin treatment inhibits HSC activation and fibrosis in the BDL model in vivo , while late treatment reduces HSC turnover and activity. Our findings underline that long-term studies in humans are warranted.
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- 2010
85. Heterozygoter Alpha-1-Antitrypsin-Mangel (PiMZ): Risikofaktor zur Entwicklung eines hepatozellulären Karzinoms in der nicht zirrhotischen Leber?
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A. Hirner, Tilman Sauerbruch, Steffen Manekeller, Hans-Peter Fischer, and P. Propping
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congenital, hereditary, and neonatal diseases and abnormalities ,Cirrhosis ,Alpha 1-antitrypsin deficiency ,Gastroenterology ,Genetic disorder ,Biology ,medicine.disease ,Proinflammatory cytokine ,Loss of heterozygosity ,Hepatocellular carcinoma ,Immunology ,Carcinoma ,medicine ,Allele - Abstract
Here we report on a patient with a primary hepatocellular carcinoma in a non-cirrhotic liver, in whom heterozygosity for an AAT-deficiency allele was found (PiMZ). Based on this observation and the current literature, the possible mechanisms for an eventual contribution of a heterozygosity of a heterozygous AAT-deficiency for a hepatocellular carcinoma are discussed. Alpha-1-antitrypsin (AAT)-deficiency (Laurell-Eriksson syndrome) is a genetic disorder, in which individuals who are homozygous for a deficiency allele are at an increased lifetime risk for pulmonary emphysema, liver cirrhosis, and primary hepatocellular carcinoma. It has been controversially discussed whether the heterozygous form (PiMZ) is also associated with an increased risk for liver diseases. Hepatocarcinogenesis for AAT-deficiency is probably based on a series of toxic events. Precipitation of AAT aggregates in hepatocytes is the initial step. These accumulate in the endoplasmic reticulum and cannot be eliminated from all hepatocytes by proteasomal and non-proteasomal mechanisms. AAT aggregates induce proinflammatory pathways and may be a stimulus for hepatocarcinogenesis. This hypothesis is based mostly on studies of individuals homozygous for a deficiency allele (PiZZ). The mechanism may also play a role in heterozygous patients. Since not all patients with precipitates of AAT-aggregates are develop a hepatocellular carcinoma related comorbidities such as chronic hepatitis B, C, chronic alcohol abuse, or so far unknown genetic and environmental factors may be crucial.
- Published
- 2010
86. Correlation of transient elastography with APRI and FIB-4 in a cohort of patients with congenital bleeding disorders and HCV or HIV/HCV coinfection
- Author
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Tilman Sauerbruch, Ulrich Spengler, R. S. Lochowsky, G. Goldmann, Frank Lammert, Johannes Oldenburg, Juergen K. Rockstroh, N. Vidovic, Frank Grünhage, and JC Wasmuth
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,virus diseases ,Hematology ,General Medicine ,Hepatitis C ,medicine.disease ,Haemophilia ,Gastroenterology ,digestive system diseases ,Virus ,Fibrosis ,Internal medicine ,Cohort ,Immunology ,Coinfection ,Medicine ,business ,Transient elastography ,Liver function tests ,Genetics (clinical) - Abstract
Summary. Patients with inherited bleeding disorders frequently suffer from chronic hepatitis C virus (HCV) mono- or human immunodeficiency virus (HIV)/HCV coinfection. Non-invasive markers for liver fibrosis are warranted for these patients. We tested a large cohort of haemophilic patients with HCV mono- or HIV/HCV coinfection for correlation of transient elastography (TE) with two simple surrogate markers of liver fibrosis and for differences in fibrosis stages according to these markers. We prospectively enrolled HCV-positive patients with congenital bleeding disorders with or without HIV coinfection. Liver function tests and platelet counts were determined and TE was performed. Aspartate aminotransferase-to-platelet ratio index (APRI) and a simple index called FIB-4 were calculated and results were correlated with TE. A total number of 174 patients were included (23% HCV, 36% HIV/HCV coinfected, 33% with cleared HCV and 8% with ongoing HIV but cleared HCV). TE correlated significantly with APRI and FIB-4 (r = 0.60; P 80% with combinations of TE plus APRI and APRI plus FIB-4. HIV/HCV coinfected patients did not present with advanced fibrosis stages when compared with HCV-monoinfected patients. Combinations of two non-invasive markers may significantly reduce the number of liver biopsies in patients with bleeding disorders and advanced liver fibrosis. Furthermore, our data support previous studies that observed a favourable outcome in patients with HIV/HCV and a preserved immune function in times of highly active antiretroviral therapy.
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- 2010
87. Severe respiratory failure due to diffuse alveolar hemorrhage: Clinical characteristics and outcome of intensive care
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Georg Nickenig, Hans Ulrich Klehr, Christian Rabe, Santiago Ewig, Christian Hoff, S. Tasci, Beate Appenrodt, and Tilman Sauerbruch
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Adult ,Lung Diseases ,Male ,medicine.medical_specialty ,ARDS ,Critical Care ,Hemorrhage ,Lung injury ,Critical Care and Intensive Care Medicine ,Severity of Illness Index ,Gastroenterology ,law.invention ,Cohort Studies ,Diagnosis, Differential ,law ,Intensive care ,Internal medicine ,medicine ,Humans ,Hospital Mortality ,Aged ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Diffuse alveolar hemorrhage ,Middle Aged ,Prognosis ,medicine.disease ,Intensive care unit ,Surgery ,Pulmonary Alveoli ,Transplantation ,Treatment Outcome ,Bronchoalveolar lavage ,Respiratory failure ,Female ,Respiratory Insufficiency ,business - Abstract
Background The aim of this study was to characterize patients and report outcome of diffuse alveolar hemorrhage (DAH) requiring intensive care unit support. Patients and Methods Thirty-seven patients were identified. Clinical characteristics and outcome were determined by chart review. Results Eighty-nine percent of patients presented with shortness of breath, 23% with cough, and 3% with hemoptysis. In 9% of patients, a diagnosis of DAH was suspected on admission. Diagnosis was confirmed by finding a progressively hemorrhagic bronchoalveolar lavage fluid in 89% and by a positive iron stain in 11% of patients. Vasculitis was causative in 19%, drug toxicity in 11%, thrombocytopenia in 27%, stem-cell transplantation in 5%, sepsis-associated lung injury in 22%, and unknown mechanisms in 16%. Thirty-two patients were mechanically ventilated, 4 received noninvasive ventilation, and 1 received supplemental oxygen therapy. Overall, 18 (49%) of 37 patients survived the intensive care unit stay. Survival was markedly different between patients with an immunologic/unknown etiology (82%) and patients with thrombocytopenia and/or sepsis (22%). Discussion Diffuse alveolar hemorrhage should be considered in all patients with persistent pulmonary infiltrates. Both bronchoalveolar lavage fluid and iron stain are mandatory diagnostic means. Patients with an immunologic/idiopathic pathogenetic mechanism have a relatively good prognosis, whereas the outcome in individuals with DAH secondary to cancer therapy or sepsis is poor.
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- 2010
88. Eine 25-jährige Patientin mit Pseudoobstruktion des Kolons, Hyponatriämie, hypertensiver Entgleisung und diffusem Schmerzsyndrom
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Henriette J. Tschampa, Philipp Lutz, Daniel Maring, and Tilman Sauerbruch
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Adult ,Gynecology ,Inappropriate ADH syndrome ,medicine.medical_specialty ,Delayed Diagnosis ,business.industry ,Colonic Pseudo-Obstruction ,Pain ,General Medicine ,Delayed diagnosis ,Diagnosis, Differential ,Hydroxymethylbilane Synthase ,Inappropriate ADH Syndrome ,Porphyria, Acute Intermittent ,Hypertension ,medicine ,Humans ,Epilepsy, Generalized ,Female ,business ,Hyponatremia - Abstract
Eine 25-jahrige, hypertone Patientin stellte sich mit seit 10 Tagen bestehenden und zunehmenden diffusen Schmerzen und Obstipation im Notfallzentrum vor. Sie war zuvor mehrfach arztlich gesehen worden, ohne dass verschiedenste Analgetika sowie Metoclopramid zu einer Besserung gefuhrt hatten. Laborchemisch fand sich eine Hyponatriamie. Ein Megakolon und eine Polyneuropathie wurden festgestellt, kurz nach Aufnahme kam es allerdings bei weiter zunehmender Hyponatriamie im Sinne eines SIADH (Syndrom der inadaquaten ADH-Sekretion) zu einem generalisierten Krampfanfall. Passend zur Klinik konnte im Urin eine massiv erhohte Ausscheidung von Porphyrinen gemessen werden und damit, zusammen mit der deutlich erniedrigten Porphobilinogen-Desaminase-Aktivitat, die Diagnose einer akuten intermittierenden Porphyrie gestellt werden. Der Fall illustriert, wie die Diagnose dieses Krankheitsbildes aufgrund seiner Seltenheit und unspezifischen Symptome leicht verschleppt wird, wobei die Gefahr besteht, durch Verordnung von auslosenden Medikamenten die Beschwerden noch zu verschlimmern.
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- 2010
89. S3 Guidelines for Colorectal Carcinoma
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Anke Reinacher-Schick, Werner Hohenberger, Jürgen F. Riemann, P. Frühmorgen, Ulrich R. Fölsch, Volker Heinemann, Gail K. Adler, Claus Rödel, Martin Zeitz, Dirk Arnold, Theodor Junginger, Wolfgang E. Fleig, H.-K. Selbmann, T. Kuhlbacher, P. Propping, Tilman Sauerbruch, I. Kopp, W. Schmitt, Hans-Joachim Schmoll, W. Schmiegel, Axel Holstege, Thomas Seufferlein, Rolf Sauer, Christian Pox, Rainer Porschen, and Ullrich Graeven
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Oncology ,medicine.medical_specialty ,business.industry ,Colorectal cancer ,Internal medicine ,Gastroenterology ,Medicine ,business ,medicine.disease - Published
- 2010
90. p-ANCAs in autoimmune liver disorders recognise human -tubulin isotype 5 and cross-react with microbial protein FtsZ
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Michael Mähler, Ulrich Spengler, Birgit Terjung, Berthold Lechtenberg, Tilman Sauerbruch, Volker Herzog, J Söhne, Judith M. Gottwein, and Marit Muennich
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Adult ,Male ,Cholangitis, Sclerosing ,Autoimmune hepatitis ,Cross Reactions ,Immunofluorescence ,Autoantigens ,Peptide Mapping ,Antibodies, Antineutrophil Cytoplasmic ,Autoimmune Diseases ,Primary sclerosing cholangitis ,Antigen-Antibody Reactions ,Young Adult ,Bacterial Proteins ,Antigen ,Tubulin ,medicine ,Humans ,FtsZ ,Aged ,Anti-neutrophil cytoplasmic antibody ,Aged, 80 and over ,medicine.diagnostic_test ,biology ,Gastroenterology ,Middle Aged ,medicine.disease ,Recombinant Proteins ,Cytoskeletal Proteins ,Hepatitis, Autoimmune ,Microscopy, Fluorescence ,Immunology ,biology.protein ,Electrophoresis, Polyacrylamide Gel ,Female ,Antibody - Abstract
Objective Autoimmune hepatitis and primary sclerosing cholangitis are chronic inflammatory disorders of unknown aetiology, frequently associated with the presence of perinuclear antineutrophil cytoplasmic antibodies (p-ANCAs) directed against an unknown antigen of myeloid cells. Methods and Results Here, it is reported that p-ANCAs in autoimmune liver disorders react with b-tubulin isotype 5 (TBB-5) as autoantigen as well as with its evolutionary bacterial precursor protein FtsZ. Both proteins were confirmed as antigens of p-ANCAs in autoimmune liver disorders by demonstrating reactivity of ANCA-positive sera with recombinant TBB-5 (72e88%) and FtsZ (64e82%) on immunoblots and antigen-specific abrogation of ANCA immunofluorescence when sera had been preabsorbed with tubulin and FtsZ. Using sera from interleukin 10-deficient mice (Il10 e / e ), an animal model of inflammatory bowel disease, it was also demonstrated that antibodies against TBB-5 are generated in response to intestinal microorganisms. However, unlike autoimmune liver disorders, human antibodies to FtsZ in the absence of TBB-5 antibodies were also a frequent finding in non-autoimmune liver diseases (up to 95%). Reactivity to TBB-5 without the presence of FtsZ antibodies was found in very few cases (
- Published
- 2009
91. Gallensteinerkrankungen – Update
- Author
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Michael Neubrand, Tilman Sauerbruch, and Frank Lammert
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- 2009
92. Degree of hepatic dysfunction and improvement of renal function predict survival in patients with HRS type I: a retrospective analysis
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Julia Zielinski, Karl August Brensing, Michael Schepke, Jörg Heller, Beate Appenrodt, and Tilman Sauerbruch
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Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Hepatorenal Syndrome ,Cirrhosis ,medicine.medical_treatment ,Renal function ,Kidney ,Gastroenterology ,Liver disease ,chemistry.chemical_compound ,Hepatorenal syndrome ,Internal medicine ,medicine ,Humans ,Creatinine ,Hepatology ,business.industry ,Middle Aged ,Prognosis ,medicine.disease ,Surgery ,Treatment Outcome ,chemistry ,Female ,Liver function ,Portasystemic Shunt, Transjugular Intrahepatic ,Epidemiologic Methods ,business ,Transjugular intrahepatic portosystemic shunt ,Biomarkers ,Kidney disease - Abstract
Background Hepatorenal syndrome (HRS) is a frequent complication of end-stage liver cirrhosis. HRS type I has a very poor prognosis. From which of the more or less established therapies, such as use of vasoconstrictors together with albumin or placement of a Transjugular Intrahepatic Portosystemic Shunt patients might profit remains elusive. Therefore, it is important to define parameters that predict an improved outcome in respect to kidney function and survival. Methods The clinical charts of 91 patients with cirrhosis and HRS type I were studied. The parameters associated with response to therapy, defined as a decrease in serum creatinine of more than 1.5 mg/dl on day 14 after diagnosis of HRS, and those associated with survival were assessed by multivariate analysis. Results The median survival was 2.7 (1.5-3.8) months. Three independent predictive factors for survival were identified: Child-Pugh score (P = 0.05), Model of End-Stage Liver Disease (MELD) score less than 20 (P = 0.01), and response to therapy (P = 0.02). The Child-Pugh score (P = 0.00) and MELD score less than 20 (P = 0.02) were the parameters independently associated with the response to therapy, which occurred in 26% of the patients. Conclusion Our data of this large monocentric series with HRS type I confirm the poor prognosis in these patients, especially in those with high Child-Pugh and MELD scores, and in those in whom kidney function does not improve within 2 weeks.
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- 2009
93. The HLA‐ER/HLA‐ERGenotype Affects the Natural Course of Hepatitis C Virus (HCV) Infection and Is Associated with HLA‐E–Restricted Recognition of an HCV‐Derived Peptide by Interferon‐γ–Secreting Human CD8+T Cells
- Author
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Thomas Berg, Bettina Langhans, Jürgen K. Rockstroh, D. Schulte, Ulrich Spengler, Tilman Sauerbruch, Verena A. Steinberg, M. Michalk, Martin Vogel, Jacob Nattermann, Benjamin Krämer, Hans Dieter Nischalke, and Christian Körner
- Subjects
Adult ,Male ,Hepatitis C virus ,Hepacivirus ,Human leukocyte antigen ,CD8-Positive T-Lymphocytes ,medicine.disease_cause ,Virus ,Interferon-gamma ,Young Adult ,HLA-E ,HLA Antigens ,medicine ,Humans ,Immunology and Allergy ,Cytotoxic T cell ,Aged ,Aged, 80 and over ,biology ,Histocompatibility Antigens Class I ,Hepatitis C ,Hepatitis C, Chronic ,Middle Aged ,Viral Load ,medicine.disease ,biology.organism_classification ,Virology ,Infectious Diseases ,Case-Control Studies ,Female ,Viral hepatitis - Abstract
Recently, we showed chronic hepatitis C to be associated with increased expression of HLA-E and identified peptide hepatitis C virus (HCV) core amino acids 35-44 as a ligand for HLA-E that stabilizes HLA-E expression, favoring inhibition of natural killer cell cytotoxicity. Here we describe HLA-E-restricted recognition of peptide HCV core amino acids 35-44 by CD8(+) T cells. Frequency of HLA-E-restricted responses was significantly higher in patients homozygous for the HLA-E(R) allele (60% vs 38%; P = .038). Moreover, we found that the HLA-E(R) allelic variant confers protection against chronic infection with HCV genotypes 2 and 3. Taken together, our data indicate an important immunomodulating function of HLA-E in hepatitis C.
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- 2009
94. Regulation of NK cell trafficking by CD81
- Author
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Jacob Nattermann, Claudia Zwank, Benjamin Krämer, Tilman Sauerbruch, Agathe Hartmann, Hans-Dieter Nischalke, D. Schulte, Annabelle Vogt, Christian Körner, J Söhne, Martin Coenen, Martin Hennenberg, Bettina Langhans, M. Michalk, Christoph Möhl, and Ulrich Spengler
- Subjects
Chemokine ,Lymphokine-activated killer cell ,biology ,Tetraspanin ,Moesin ,Janus kinase 3 ,Immunology ,biology.protein ,Interleukin 12 ,Immunology and Allergy ,Cell adhesion ,CD49b ,Cell biology - Abstract
NK cells, a heterogeneous sub-population of lymphocytes, are critically involved in the regulation of both innate and adaptive immune responses in humans. Besides their participation in the control of tumors and viral infections, they also regulate inflammatory processes, mediating both beneficial and detrimental effects. To effectively fulfil their role in immune surveillance, proper trafficking of NK cells is essential. However, the mechanisms and factors governing NK cell recruitment are only poorly dissected. Here, we describe the functional role of tetraspanins, a family of evolutionary conserved cell-surface proteins, in modulating migration and transmigration of human NK cells. We demonstrate expression of various tetraspanins on NK cells. Furthermore, we show that stimulation of the NK cell-expressed tetraspanin CD81 induces phosphorylation of ezrin/radixin/moesin proteins and leads to NK cell polarization thereby facilitating NK cell migration toward various chemokines/cytokines. Finally, we provide evidence for a role of CD81 in promoting adhesion of NK cells to components of the extracellular matrix, a prerequisite for extravasation of lymphocytes in inflamed tissues. Thus, our data suggest that the tetraspanin CD81 is importantly involved in the regulation of NK cell recruitment.
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- 2009
95. Increase of In Vivo Antitumoral Activity by CD40L (CD154) Gene Transfer Into Pancreatic Tumor Cell-Dendritic Cell Hybrids
- Author
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Davorka Messmer, Ingo G.H. Schmidt-Wolf, Peter Brossart, Marcus Gorschlüter, Maria A. Gonzalez-Carmona, John Strehl, Tilman Sauerbruch, Dimitri Flieger, Elisabeth Sievers, Alex-S. Eliu, Carsten Ziske, Volker Schmitz, and Patricia E. Etzrodt
- Subjects
Cytotoxicity, Immunologic ,Male ,Antigenicity ,T-Lymphocytes ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,CD40 Ligand ,Antigen presentation ,Hybrid Cells ,Transfection ,Immunotherapy, Adoptive ,Mice ,Endocrinology ,Cell Line, Tumor ,Internal Medicine ,medicine ,Animals ,Cytotoxic T cell ,CD154 ,Antigen-presenting cell ,Cells, Cultured ,CD40 ,Hepatology ,biology ,Dendritic Cells ,Neoplasms, Experimental ,Immunotherapy ,Dendritic cell ,Flow Cytometry ,Molecular biology ,Mice, Inbred C57BL ,Pancreatic Neoplasms ,Cancer research ,biology.protein ,Female ,T-Lymphocytes, Cytotoxic - Abstract
Fusion of dendritic cells (DC) with tumor cells is an approach in immunotherapy combining antigenicity and capacity of antigen presentation to activate T cells for the induction of tumor-specific cytotoxic immunity. Although there have been reports of clinical benefit, response rates have been limited and further improvements are warranted.We used murine DC and a novel protocol for an effective fusion of those cells with the murine pancreatic cell line Panc02.We observed 2 events: only moderate in vitro and in vivo cytotoxicity of tumor cell/DC hybrids and a down-regulation of costimulatory molecules on fused cells. Therefore, we transfected tumor cell/DC hybrids with an adenovirus expressing CD154 to improve DC activation and generating antitumor immune response without the need of CD4 T cells. High CD154 expression could be obtained by transfection of DC and Panc02 cells prior fusion. Furthermore, vaccination with CD154-transfected tumor cell/DC hybrid led to a significantly increased induction of cytotoxic T cells in vitro and to an improved antitumoral effect in an orthotopic in vivo mouse model.CD154-transfected tumor cell/DC hybrids are a promising approach to increase the efficiency of antitumoral response.
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- 2009
96. Vascular hyporesponsiveness to angiotensin II in rats with CCl4-induced liver cirrhosis
- Author
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Jonel Trebicka, Martin Hennenberg, Jörg Heller, A. Z. Kohistani, and Tilman Sauerbruch
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Liver Cirrhosis ,Male ,Angiotensin receptor ,medicine.medical_specialty ,Blotting, Western ,Clinical Biochemistry ,Vasodilation ,Biochemistry ,Receptor, Angiotensin, Type 1 ,Nitric oxide ,chemistry.chemical_compound ,Internal medicine ,Hypertension, Portal ,Renin–angiotensin system ,medicine ,Animals ,Receptor ,Carbon Tetrachloride ,Rho-associated protein kinase ,Aorta ,Angiotensin II receptor type 1 ,business.industry ,Angiotensin II ,General Medicine ,Rats ,Endocrinology ,chemistry ,business - Abstract
Background Portal hypertension is triggered by vasodilation due to impaired contraction of extrahepatic vessels. Angiotensin II type 1 (AT(1)) receptor-induced vasocontraction is mediated by G proteins and may be desensitized by recruitment of beta-arrestin-2 to the receptor. In this study, we analysed the interaction of AT(1) receptors with beta-arrestin-2 in the context of vascular hypocontractility in rats with CCl(4)-induced cirrhosis. Methods Micronodular liver cirrhosis in rats (n = 15) was induced by regular CCl(4) exposure. Age-matched rats (n = 15) served as controls. Contractility of aortic rings was measured by myography. Protein expressions and phosphorylations were assessed by Western blot analysis, and AT(1) receptor interaction with beta-arrestin-2 by co-immunoprecipitation. Results Aortic rings from CCl(4) rats were hypocontractile to angiotensin II independent of nitric oxide synthases (Nomega-nitro-l-arginine methyl ester 200 microM). Expression of the AT(1) receptor, Galpha(q/11) and the contraction-mediating effector Rho kinase was similar in aortas from both groups. Expression and AT(1) receptor binding of beta-arrestin-2 were up-regulated in aortas from CCl(4) rats. Stimulation of isolated aortas with exogenous angiotensin II caused recruitment of beta-arrestin-2 in aortas from noncirrhotic rats, but no further interaction of AT(1) receptors with beta-arrestin-2 was found in aortas from CCl(4) rats. While angiotensin II stimulation resulted in Rho kinase activation in aortas from noncirrhotic rats but not in aortas from CCl(4) rats, extracellular signal-regulated kinase activation in response to angiotensin II was observed in aortas from both groups. Conclusions Vascular hyporesponsiveness to angiotensin II in CCl(4) rats is due to enhanced interaction of the AT(1) receptor with beta-arrestin-2 and consecutively changed receptor function.
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- 2009
97. Expression of Urotensin II and Its Receptor in Human Liver Cirrhosis and Fulminant Hepatic Failure
- Author
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Ulrich Spengler, Jonel Trebicka, Tilman Sauerbruch, Christoph R. Clemens, Jörg Heller, and Ludger Leifeld
- Subjects
Liver Cirrhosis ,medicine.medical_specialty ,Cirrhosis ,Physiology ,Urotensins ,In Vitro Techniques ,Gastroenterology ,Statistics, Nonparametric ,Receptors, G-Protein-Coupled ,Immunoenzyme Techniques ,Interferon-gamma ,chemistry.chemical_compound ,Fulminant hepatic failure ,Internal medicine ,Humans ,Medicine ,Receptor ,Interleukin-6 ,Portal Vein ,business.industry ,Liver Failure, Acute ,Hepatology ,medicine.disease ,chemistry ,Immunohistochemistry ,Portal hypertension ,business ,Urotensin-II ,Splanchnic - Abstract
Urotensin II [U-II] plasma levels are increased in liver cirrhosis [LC] and are discussed as an important mediator of portal hypertension since the U-II antagonist palosuran has beneficial effects on portal hypertension by increasing splanchnic resistance. Nevertheless, no data are available on the intrahepatic expression of U-II and its receptor [UT] in humans. U-II and UT expression were analyzed in the livers of patients with LC, fulminant hepatic failure [FHF], and normal controls [NC] using immunohistochemistry. Both U-II and UT were expressed in the liver on endothelial cells from arteries, veins, and bile ducts as well as on Kupffer cells. In LC, the total number of U-II-expressing cells was 20% lower compared to NC (P
- Published
- 2009
98. Does therapy of oesophageal varices influences the progression of varices?
- Author
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Leonie Classen, Erwin Biecker, Michael Schepke, and Tilman Sauerbruch
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Liver Cirrhosis ,Male ,medicine.medical_specialty ,Time Factors ,Cirrhosis ,Esophageal and Gastric Varices ,Gastroenterology ,Esophageal varices ,Risk Factors ,Internal medicine ,Confidence Intervals ,medicine ,Humans ,Ligation ,Retrospective Studies ,Hepatology ,medicine.diagnostic_test ,business.industry ,Hazard ratio ,Retrospective cohort study ,Middle Aged ,Prognosis ,medicine.disease ,Confidence interval ,Endoscopy ,Surgery ,Disease Progression ,Female ,Esophagoscopy ,Varices ,business - Abstract
BACKGROUND Aim of this study was to determine the progression time of oesophageal varices in patients with cirrhosis and to study whether therapy of varices has an impact on the progression time. Parameters associated with the progression of oesophageal varices were analyzed as well. METHODS One hundred and eighty-one cirrhotic patients (Child A/B/C: 105/69/15; Child score 7.6+/-2.0, initial variceal grade 1.7+/-0.9) undergoing repeated endoscopy for follow-up and/or treatment of oesophageal varices were retrospectively analyzed. A multivariate logistic regression analysis was applied to identify independent determinants of progression of oesophageal varices. RESULTS Of the 189 patients, 26 patients were on beta-blocker therapy only, 52 patients underwent ligation therapy only, and 37 patients received a combination of ligation and beta-blocker therapy of varices. The mean time of progression of oesophageal varices by one grade was 384+/-364 days. This interval did not vary significantly between patients who underwent no treatment or were on a beta-blocker and/or ligation therapy. The serum bilirubin (hazard ratio 1.030; 95% confidence interval, 1.004, 1.055; P
- Published
- 2009
99. Renal impairment after liver transplantation - a pilot trial of calcineurin inhibitor-free vs. calcineurin inhibitor sparing immunosuppression in patients with mildly impaired renal function after liver transplantation
- Author
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Holger Palmedo, Birgit Terjung, Ulrich Spengler, Jörg C. Kalff, P Knipper, Tilman Sauerbruch, Rainer P. Woitas, and Thomas Gerhardt
- Subjects
Male ,medicine.medical_specialty ,medicine.medical_treatment ,Calcineurin Inhibitors ,Urology ,Renal function ,lcsh:Medicine ,Pilot Projects ,Liver transplantation ,Kidney ,Mycophenolic acid ,GFR ,chemistry.chemical_compound ,Internal medicine ,medicine ,calcineurin inhibitor ,impaired renal function ,Humans ,Enzyme Inhibitors ,Glucocorticoids ,Immunosuppression Therapy ,Creatinine ,liver transplantation ,Dose-Response Relationship, Drug ,business.industry ,Research ,lcsh:R ,mycophenolate mofetil ,Immunosuppression ,Alanine Transaminase ,General Medicine ,Middle Aged ,Mycophenolic Acid ,medicine.disease ,Calcineurin ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Kidney Failure, Chronic ,Prednisone ,Drug Therapy, Combination ,Female ,business ,medicine.drug ,Kidney disease ,Glomerular Filtration Rate - Abstract
Objectives Chronic kidney disease is frequent in patients after orthotopic liver transplantation (OLT) and has impact on survival. Patients receiving calcineurin inhibitors (CNI) are at increased risk to develop impaired renal function. Early CNI reduction and concomitant use of mycophenolat mofetil (MMF) has been shown to improve renal function. Methods The aim of this trial was to compare dose-reduced CNI/MMF versus CNI-free MMF/prednisone-based treatment in stable patients after OLT with respect to glomerular filtration rate (GFR). 21 patients [GFR 44.9 ± 9.9 mL/min/1.73 m2 measured by 99m-Tc-DTPA-clearance, serum creatinine (SCr) 1.5 ± 0.42 mg/dL] were randomized either to exchange CNI for 10 mg prednisone (group 1; n = 8) or to receive CNI at 25% of the initial dose (group 2; n = 13) each in combination with 1000 mg MMF b.i.d. Results At month 12 mean SCr (-0.3 ± 0.4 mg/dL, p = 0.031) and GFR improved (8.6 ± 13.1 mL/min/1.73 m2, p = 0.015) in group 2 but remained unchanged in group 1. Main side effects were gastroinstestinal symptoms (14.3%) and infections (4.8%). Two biopsy proven, steroid-responsive rejections occurred. In group 1 mean diastolic blood pressure (BP) increased by 11 ± 22 mmHg (p = 0.03). Conclusions Reduced dose CNI in combination with MMF but not CNI-free-immunosuppression leads to improvement of GFR in patients with moderately elevated SCr levels after OLT. Addition of steroids resulted in increased diastolic blood pressure presumably counterbalancing the benefits of CNI withdrawal on renal function.
- Published
- 2009
100. Chromocolonoscopy detects more adenomas than white light colonoscopy or narrow band imaging colonoscopy in hereditary nonpolyposis colorectal cancer screening
- Author
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Frank Lammert, P. Kahl, Robert Hüneburg, Reinhard Büttner, P. Propping, Tilman Sauerbruch, Christian Rabe, N. Rahner, and C. Lamberti
- Subjects
Adenoma ,Adult ,medicine.medical_specialty ,Amsterdam criteria ,Base Pair Mismatch ,Colon ,Colorectal cancer ,Colonic Polyps ,Colonoscopy ,Indigo Carmine ,Gastroenterology ,Diagnosis, Differential ,Germline mutation ,Internal medicine ,medicine ,Humans ,Mass Screening ,Coloring Agents ,Early Detection of Cancer ,Germ-Line Mutation ,Hyperplasia ,medicine.diagnostic_test ,business.industry ,Incidence (epidemiology) ,Cancer ,Middle Aged ,medicine.disease ,Colorectal Neoplasms, Hereditary Nonpolyposis ,Endoscopy ,Colonic Neoplasms ,business ,Precancerous Conditions - Abstract
Individuals carrying germline mutations in one of the genes responsible for hereditary nonpolyposis colon cancer (HNPCC) have a lifetime risk of up to 80 % of developing colorectal cancer. As there is evidence for a higher incidence of flat adenomatous precursors and because an accelerated adenoma-carcinoma sequence has been postulated for these patients, early detection of these lesions is essential. It was the aim of the present study to assess the detection rate of polypoid lesions by comparing chromocolonoscopy with standard white light colonoscopy and narrow-band imaging (NBI) colonoscopy.109 patients were included (98 with a functionally relevant mutation in a mismatch repair gene, 11 fulfilling the strict Amsterdam criteria). In 47 patients, standard colonoscopy was followed by chromocolonoscopy with indigo carmine. In 62 patients, NBI was performed first followed by chromocolonoscopy.A total of 128 hyperplastic and 52 adenomatous lesions were detected. In the first series, 0.5 lesions/patient were identified by standard colonoscopy and 1.5 lesions/patient by chromocolonoscopy ( P0.001). In the second series, 0.7 lesions/patient were detected by NBI colonoscopy and 1.8 lesions/patient by chromocolonoscopy ( P = 0.01). At least one adenoma was detected in 15 % of patients by both standard and NBI colonoscopy compared with 28 % of patients by chromocolonoscopy.According to this study, chromocolonoscopy detects significantly more hyperplastic and, in particular, adenomatous lesions than standard white light colonoscopy or NBI.
- Published
- 2009
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