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Combination of "low-dose" ribavirin and interferon alfa-2a therapy followed by interferon alfa-2a monotherapy in chronic HCV-infected nonresponders and relapsers after interferon alfa-2a monotherapy

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World Journal of Gastroenterology 2001年第2期7卷 222-227页

作者： Perdita Wietzke-Braun Volker Meier Felix Braun Giuliano Ramadori abteilung für gastroenterologie und endokrinologie Georg-August-UniversitatGottingenGermany

AIM To report on the efficacy, safety and tolerability of interferon alfa-2a combined with a "low dose" of ribavirin for relapsers and non responders to alpha interferon *** Thirty-four chronic hepatitis C virus-infected non-responders to interferon alfa2a monotherapy (a course of at least 3 months treatment) and 13 relapsers to interferon alfa 2a monotherapy (a dose of 3 to 6 million units three times per week for at least 20 weeks but not more than 18 months) were treated with the same dose of interferon alfa-2a used before (3 to 6 million units three times per week) and ribavirin (10 mg/ kg daily) for 6 months. In complete responders, interferon alfa-2a was administered for further 6 months at the same dose used before as *** Seven (20.6%) of 34 non-responders stopped the combined therapy due to adverse events, including two patients with histological and clinical Child A cirrhosis. In 17/27 (63%)non-responders, the combined therapy was stopped after three months because of non-response. Ten of the 27 non-responders completed the 1;2-month treatment course. At a mean follow up of 28 months (16- 37 months)after the treatment, 4/10 (15%) previous non-responders still remained complete responders,All 13 previous relapsers completed the 12-month treatment course. At a mean follow up of 22months (9 - 36 months) after treatment, 6/13(46%) the previous relapsers were stillsustained complete *** Our treatment schedule of the combined therapy for 6 months of interferon alfa2a with a low dose of ribavirin (10 mg/kg/day)followed by 6 months of interferon alfa-2amonotherapy is able to induce a sustainedcomplete response rate in 15% of non-responders and 46% of relapsers with chronic hepatitis C virus-related liver diseases comparable to those obtained with the standarddoses of ribavirin 1000 - 1200 mg/*** prospective controlled trials using lower total amounts of ribavirin in combination with interferon should be p

关键词： hepatitis C, chronic/drug therapy interferon alpha-2a/therapeutic use interferon alpha-2a/administration & dosage ribavirin/administration & dosage ribavirin/therapeutic use

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Treatment of genotype 2 and 3 chronic hepatitis C virus-infected patients

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World Journal of Gastroenterology 2005年第39期11卷 6188-6192页

作者： Perdita Wietzke-Braun Volker Meier Katrin Neubauer-Saile Sabine Mihm Giuliano Ramadori abteilung für gastroenterologie und endokrinologie Georg-August-Universitt Gttingen Germany

AIM： Before pegylated interferon alpha （IFN） was introduced for the therapy of chronic hepatitis C virus （HCV）-induced hepatitis, conventional thrice weekly IFN therapy was supplemented by ribavirin. Also, at that time, higher and more frequent doses of IFN were expected to be more effective than the standard regimen of 3 MU thrice weekly. As ribavirin significantly increases side effects and negatively influences the quality of life particularly in young patients, we started a prospective non-randomized study with a daily IFN-2a monotherapy as an initial treatment for chronic hepatitis C. METHODS： Forty-six consecutive chronic HCV-infected patients received 3 MU IFN-2a per day as an initial treatment. Patients with genotype 2 or 3 （n = 12） were treated for 24 wk, and patients with genotypes other than 2 or 3 （n = 34） for 48 wk. Treatment outcome was followed up for 48 wk after the end of treatment （EOT）. Virological response was defined as the absence of detectable serum HCV-RNA. Patients without virological response at 12 wk after the start of treatment received low-dose ribavirin （10 mg（kg·d）） additionally. RESULTS： During treatment, three genotype 3 patients were excluded from the study due to incompliance. The remaining patients （n = 9） infected with genotype 2 or 3 showed an initial virological response rate of 100%. Six patients （66.7%） were still found to be virus-free at the end of follow-up period. In these patients, initial virological response was evident already after 2 wk of treatment. In contrast, initial virological response occurred first after 4 wk of treatment in the three patients who relapsed （33.3%）. In comparison, patients infected with genotypes other than 2 or 3 （n = 34） showed an initial virological response rate of only 23.5% （n = 8）, and even in combination with ribavirin a sustained virological response （SVR） rate of only 11.8% （n = 4） could be achieved. CONCLUSION： In chronic HCV-infected patients with genotype 2 or 3, a SVR can be expe

关键词： Chronic hepatitis C virus infection Genotype 2 and 3 Alpha interferon Daily dose interferon therapy

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HCV-RNA positivity in peripheral blood mononuclear cells of patients with chronic HCV-infection: does it really mean viral replication?

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World Journal of Gastroenterology 2001年第2期7卷 228-234页

作者： Volker Meier Sabine Mihm Perdita Wietzke-Braun Guliano Ramadori Georg-August-Universitat gottingen Zentrum innere medizinAbteilung Für Gastroenterologie Und EndokrinologieRobert-Koch-Straβe 4037075 GottingenGermany

AIM: To analyze the association of HCV-RNA with peripheral blood mononuclear cells (PBMC) and to answer the question whether HCV-RNA positivity in PBMC is due to viral replication. METHODS: HCV-RNA was monitored in serum and PBMC preparations from 15 patients with chronic HCV infection before, during and after an IFN-alpha therapy using a nested RT/PCR technique. In a second approach, PBMC from healthy donors were incubated in HCV positive plasma. RESULTS: In the IFN-alpha responding patients,HCV-RNA disappeared first from total RNA preparations of PBMC and then from serum. In contrast, in relapsing patients, HCV-RNA reappeared first in serum and then in PBMC. A quantitative analysis of the HCV-RNA concentration in serum was performed before and after transition from detectable to non detectable HCV-RNA in PBMC-RNA and vice versa. When HCV-RNA was detectable in PBMC preparations, the HCV concentration in serum was significantly higher than the serum HCV-RNA concentration when HCV-RNA in PBMC was not detectable. Furthermore, at no time during the observation period was HCV specific RNA observed in PBMC, if HCV-RNA in serum was under the detection limit. Incubation of PBMC from healthy donors with several dilutions of HCV positive plasma for two hours showed a concentration dependent PCR positivity for HCV-RNA in reisolated PBMC. CONCLUSION: The detectability of HCV-RNA in total RNA from PBMC seems to depend on the HCV concentration in serum. Contamination or passive adsorption by circulating virus could be the reason for detection of HCV-RNA in PBMC preparations of chronically infected patients.

关键词： Adult Aged Antiviral Agents Female Hepacivirus Hepatitis C, Chronic Humans Interferon-alpha Leukocytes, Mononuclear Male Middle Aged RNA, Viral Research Support, Non-U.S. Gov't Reverse Transcriptase Polymerase Chain Reaction Viral Load Virus Replication

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Malnutrition affects quality of life in gastroenterology patients

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World Journal of Gastroenterology 2006年第21期12卷 3380-3385页

作者： Kristina Norman Henriette Kirchner Herbert Lochs Matthias Pirlich Klinik mil Schwerpunkt gastroenterologie Hepatologie und endokrinologie Charité-Universit(a|¨)tsmedizin Berlin Campus MitteGermany

AIM： To investigate the association between malnutrition and quality of life in patients with benign gastrointestinal ***： Two hundred patients （104 wellnourished and 96 malnourished） were assessed according to the Subjective Global Assessment, anthropometric measurements and bioelectrical impedance analysis. Quality of life was determined with the validated Medical Outcomes Study 36-item Short-Form General Health Survey （SF 36）. Muscle function was assessed by hand grip strength and peak ***： Body mass index, body cell mass, arm muscle area and hand grip strength were significantly lower in the malnourished patients. Quality of life was generally lower when compared to norm values. Seven out of eight quality of life scales （excluding bodily pain） were significantly reduced in the malnourished patients. Comparing patients with liver cirrhosis and inflammatory bowel disease （IBD）, patients with IBD experienced significantly lower values in the perception of bodily pain, social functioning and rnenta/health. Malnourished liver cirrhotics suffered reductions in more scales （six out of eight） than malnourished IBD patients did （four out of eight）.CONCLUSION： Quality of life is generally low in benign gastrointestinal disease and is further reduced in patients who are classified as malnourished. It appears that liver cirrhosis patients experience a higher quality of life than IBD patients do, but the impact of malnutrition seems to be greater in liver cirrhosis than in IBD.

关键词： Quality of life Malnutrition Gastrointestinal disease Liver cirrhosis Inflammatory bowel disease

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Initial steroid-free immunosuppression after liver transplantation in recipients with hepatitis c virus related cirrhosis

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World Journal of Gastroenterology 2004年第15期10卷 2213-2217页

作者： Perdita Wietzke-Braun Felix Braun Burckhart Sattler Giuliano Ramadori Burckhardt Ringe abteilung for gastroenterologie und endokrinologie Georg-August-Universitt37075 GttingenGermany Georg-August-Universitt 37075 GttingenGermany Zentrum Pathologie Georg-August-Universitt37075 GttingenGermany

AIM:Steroids can increase hepatitis C virus(HCV) *** liver transplantation(LTx),steroids are commonly used for immunosuppression and acute rejection is usually treated by high steroid *** can worsen the outcome of recurrent HCV ***, we evaluated the outcome of HCV infected liver recipients receiving initial steroid-free immunosuppression. METHODS:Thirty patients undergoing LTx received initial steroid-free *** for LTx included 7 patients with HCV related *** immunosuppression consisted of tacrolimus 2×0.05mg/kg.d po and mycophenolate mofetil(MMF)2×15mg/kg.d *** tacrolimus dosage was adjusted to trough levels in the target range of 10-15μg/L during the first 3 mo and 5-10μg/L *** of acute rejection were verified histologically. RESULTS:Patient and graft survival of 30 patients receiving initial steroid-free immunosuppression was 86% and 83% at 1 and 2 *** rejection occurred in 8/30 patients, including 1 HCV infected *** HCV-infected patients had HCV genotype Ⅱ(lb).HCV seropositivity occurred within the first 4 mo after *** virus load was not remarkably increased during the first year after ***,grafts had no severe recurrent hepatitis. CONCLUSION:From our experience,initial steroid-free immunosuppression does not increase the risk of acute rejection in HCV infected liver ***,none of the HCV infected patients developed serious chronic liver *** suggests that it may be beneficial to avoid steroids in this particular group of patients after LTx.

关键词： Liver Transplantation Adult Drug Therapy, Combination Female Hepatitis C Humans Immunosuppressive Agents Liver Cirrhosis Male Middle Aged Mycophenolic Acid derivatives Postoperative Care Tacrolimus

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Adult-to-adult right lobe living donor liver transplantation:Comparison of endoscopic retrograde cholangiography with standard T2-weighted magnetic resonance cholangiography for evaluation of donor biliary anatomy

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World Journal of Gastroenterology 2006年第36期12卷 5820-5825页

作者： Perdita Wietzke-Braun Felix Braun Dieter Müller Thomas Lorf Burckhardt Ringe Giuliano Ramadori abteilung für gastroenterologie und endokrinologie Georg-August-Universitt Gttingen Germany Klinik für Allgemeine Chirurgie und Thorax-chirurgie Universitt Schleswig-Holstein Campus Kiel Germany abteilung für Diagnostische Radiologie Georg-August-Universitt Gttingen Germany Klinik für Allgemeine Chirurgie Georg-August-Universitt Gttingen Germany Center for Liver Pancreas and Biliary Disease Drexel University College of Medicine Philadelphia United States

AIM: To compare the value of endoscopic retrograde cholangiography (ERC) and standard T2-weighted magnetic resonance cholangiography (MRC) in the evaluation process as adult-to-adult right lobe living donor liver transplantation (LDLTx) demands a successful outcome, and exact knowledge of the biliary tree is implicated to avoid biliary complications, ***: After starting the LDLTx program, 18 liver transplant candidates were selected for LDLTx by a stepwise evaluation process. ERC and standard T2-weighted MRC were performed to evaluate the biliary system of the donor liver. The anatomical findings of ERC and MRC mapping were compared using the Ohkubo classification. RESULTS: ERC allowed mapping of the whole biliary system in 15/15 (100%) cases, including 14/15 (93.3%) with biliary variants while routine MRC was only accurate in 2/13 (15.4%) cases. MRC was limited in depicting the biliary system proximal of the hepatic bifurcation. Postoperative biliary complications occurred in 2 donors and 8 recipients. Biliary complications were associated with Ohkubo type C, E or G in 6/8 recipients, and 2/3 recipients with biliary leak received a graft with multiple (≥2) bile ducts. CONCLUSION: Pretransplant ERC is safe and superior over standard MRC for detection of biliary variations that occur with a high frequency. However, precise knowledge of biliary variants did not reduce the incidence of postoperative biliary complications.

关键词： Living donor liver transplantation Donors biliary tree Endoscopic retrograde cholangiography Magnetic resonance cholangiography

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Controlled and reversible induction of differentiation and activation of adult human hepatocytes by a biphasic culture technique

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World Journal of Gastroenterology 2005年第14期11卷 2080-2087页

作者： Marcus K.H. Auth Kim A. Boost Kerstin Leckel Wolf-Dietrich Beecken Tobias Engl Dietger Jonas Elsie Oppermann Philip Hilgard Bernd H. Markus Wolf-Otto Bechstein Roman A. Blaheta Universit(a|¨)ts-Kinderklinik Essen abteilung für Allgemeine P(a|¨)diatrie Germany Zentrum der An(a|¨)sthesiologie und Wiederbelebung Johann Wolfgang Goethe-Universit(a|¨)t Frankfurt am MainGermany Klinik für Allgemein-und Gef(a|¨)βchirurgie Germany Klinik für Urologie und Kinderurologie Zentrum der Chirurgie Johann Wolfgang Goethe-Universit(a|¨)tFrankfurt am MainGermany Klinik für Allgemein- und Gef(a|¨)βchirurgie Germany Universit(a|¨)tsklinikum Essen abteilung für gastroenterologie und Hepatologie Germany Klinik für Allgemein- und Viszeralchirurgie St(a|¨)dt. Klinikum Kemperhof KoblenzGermany

AIM:Clinical application of human hepatocytes (HC) is hampered by the progressive loss of growth and differentiation in vitro. The object of the study was to evaluate the effect of a biphasic culture technique on expression and activation of growth factor receptors and differentiation of human adult HC. METHODS: Isolated HC were sequentially cultured in a hormone enriched differentiation medium (DM) containing nicotinamide, insulin, transferrin, selenium, and dexame-thasone or activation medium (AM) containing hepatocyte growth factor (HGF), epidermal growth factor (EGF), and granulocyte-macrophage colony-stimulating factor (GMCSF). Expression, distribution and activation of the HC receptors (MET and EGFR) and the pattern of characteristic cytokeratin (CK) filaments were measured by fluorometry, confocal microscopy and Western blotting. RESULTS: In the biphasic culture system, HC underwent repeated cycles of activation (characterized by expression and activation of growth factor receptors) and re-differentiation (illustrated by distribution of typical filaments CK-18 but low or absent expression of CK-19). In AM increased expression of MET and EGFR was associated with receptor translocation into the cytoplasm and induction of atypical CK-19. In DM low expression of MET and EGFR was localized on the cell membrane and CK-19 was reduced. Receptor phosphorylation required embedding of HC in collagen type I gel. CONCLUSION: Control and reversible modulation of growth factor receptor activation of mature human HC can be accomplished in vitro, when defined signals from the extracellular matrix and sequential growth stimuli are provided. The biphasic technique helps overcome dedifferentiation, which occurs during continuous stimulation by means of growth factors.

关键词： Human hepatocytes Differentiation Hepatocyte growth factor Epidermal growth factor HGF receptor EGF receptor Cytokeratin Collagen gel

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Die　Glykoproteinsynthese　antraler　Magenschleimhaut　beichronischer　Gastritis　Typ　B

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Journal of Huazhong University of Science and Technology(Medical Sciences) 1994年第2期14卷 71-76页

作者：田德安 abteilung für gastroenterologie Tongji Klinik Tongji medizinische Universität China abteilung für gastroenterologie und Stoffwechsel Innere Medizin II Universität Ulm Deutschland

In der vorliegenden Arbeit wurde sowohl der Einflu der entzundlichen Zellen als auch einer H. pylori-Infektion auf den Glykoproteinstoffwechsel antraler Magenschleimhautzellen bei Patienten mit chronischer Gastritis untersucht. Dabei wurde die Methode von der Organkultur und derAutoradiographie verwendet. Der Soffwechselweg der Glykoproteine im Verlauf der Inkubationszeit konnte durch Autoradiographie belegt werden. Die Autoradiographie zeigt, da eine floride Gastritis durch die zunehmende Glykoproteinsynthese der antralen Schleimzellen charakterisiert ist (n = 26, Pund einer gesteigerten Glykoproteinsynthese konnte jedoch nicht beobachtet *** Mechanismus der gesteigerten Biosynthese der Glykoproteine bei chronischen Gastritis wurde in dieser Arbeit diskutiert. Dieentzundliche Zellen und die freigesetzte Mediatoren spielen wahrscheinlich dabei eine wichtige Rolle.

关键词： Glykoprotein gastritis helicobacter pylori

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Synthesis　of　Glycoproteins　by　Mucosa　of　Gastric　Antrum　in　Chronic　GastritisB

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Journal of Huazhong University of Science and Technology(Medical Sciences) 1994年第2期14卷 76-76页

作者： TIAN De-an(Department of Gastroenterolegy, Tongji Hospital, Tongji Medical University, WuhanPeter MalfertheinerDepartment of Gastroenterolegy and Metabolism, Internal Medicine H ,Ulm University, Germany) abteilung für gastroenterologie Tongji Klinik Tongji medizinische Universität.

The tissue culture and autoradiography techniques were used to study the effect of infiltration by inflammatory cells and of HP infection on the synthesis of glycoproteins by the gastric antrum. The results showed that in active phase of gastritis, the synthesis of glycoprotein was increased but no correlation between HP infection and synthesis of glycoprotein was noted. The machanism of increased synthesis in chronic gastritis was discussed. It is suggested that the inflammatory cells and media released by them may play important role.

关键词： gastritis glycoproteinshelicobacter pylori

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从多利到波来:用体细胞核转移克隆

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德国医学 1999年第6期16卷 367-368页

作者： Darius Moradpour Hubert E.Blum 郝连杰 Medizinische Universitsklinik Freiburg Abteilung Irmere Medizin Ⅱ Gastroenterologie Hepatologie trod Endokrinologie D-79106 Freiburg Germany 同济医科大学附属同济医院

绵羊多利(Dolly)是第一只从成年动物成熟体细胞克隆出来的哺乳动物,这一研究一方面向基础生物发生学原则提出了挑战;另一方面为生殖生物学、医学以及制药学等的基础研究和应用开创了全新的前景。因此,用体细胞核转移克隆的技术具有巨大... 详细信息

绵羊多利(Dolly)是第一只从成年动物成熟体细胞克隆出来的哺乳动物,这一研究一方面向基础生物发生学原则提出了挑战;另一方面为生殖生物学、医学以及制药学等的基础研究和应用开创了全新的前景。因此,用体细胞核转移克隆的技术具有巨大潜在意义。同时,它也提出了伦理问题,不仅在专业领域,而且在社会上引起广泛的讨论。

关键词：体细胞核克隆多利波来特点应用

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