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Open label trial of granulocyte apheresis suggests therapeutic efficacy in chronically active steroid refractory ulcerative colitis

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World Journal of Gastroenterology 2005年第44期11卷 7001-7006页

作者： Wolfgang Kruis Axel Dignass Elisabeth Steinhagen-Thiessen Julia Morgenstern Joachim M(o|¨)ssner Stephan Schreiber Maurizio Vecchi Alberto Malesci Max Reinshagen Robert L(o|¨)fberg Evangelisches Krankenhaus Kalk Medizinische klinik für Hepatologie und Gastroenterologie Medizinische klinik und poliklinik Ⅱ Medizinische klinik Dep of Int Medicine IRCCS Ospedale Policlinico Istituto Clinico Humanitas Innere Medizin Karolinska Institute at the IBD unit

AIM： To study the efficacy, safety, and feasibility of a granulocyte adsorptive type apheresis system for the treatment of patients with chronically active ulcerative colitis despite standard therapy. METHODS： An open label multicenter study was carried out in 39 patients with active ulcerative colitis （CAI 6-8） despite continuous use of steroids （a minimum total dose of 400 mg prednisone within the last 4 wk）. Patients received a total of five aphereses using a granulocyte adsorptive technique （Adacolumn, Otsuka Pharmaceutical Europe, UK）. Assessments at wk 6 and during follow-up until 4 mo comprised clinical （CAI） and endoscopic （EI） activity index, histology, quality of life （IBDQ）, and laboratory tests. RESULTS： Thirty-five out of thirty-nine patients were qualified for intent-to-treat analysis. After the apheresis treatment at wk 6, 13/35 （37.1%） patients achieved clinical remission and 10/35 （28.6%） patients had endoscopic remission （CAI〈4, EI〈4）. Quality of life （IBDQ） increased significantly （24 points, P〈0.01） at wk 6. Apheresis could be performed in all but one patient. Aphereses were well tolerated, only one patient experienced anemia. CONCLUSION： In patients with steroid refractory ulcerative colitis, five aphereses with a granulocyte/ monocyte depleting filter show potential short-term efficacy. Tolerability and technical feasibility of the procedure are excellent.

关键词： Steroid Refractory colitis Ulcerative colitis Granulocyte Apheresis

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Positive predictors for gastroesophageal reflux disease and the therapeutic response to proton-pump inhibitors

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World Journal of Gastroenterology 2014年第14期20卷 4017-4024页

作者： Valentin Becker Stefan Grotz Christoph Schlag Simon Nennstiel Analena Beitz Bernhard Haller Roland M Schmid Alexander Meining Monther Bajbouj Ⅱ. Medizinische klinik und poliklinik Technische Universit?t München Institut für Medizinische Statistik und Epidemiologie Technische Universit?t München

AIM: To identify objective and subjective predictors for the reliable diagnosis of gastroesophageal reflux disease (GERD) and the response to proton pump inhibitor (PPI) therapy.

关键词： Gastroesophageal reflux Gastroesophageal reflux disease Non-erosive reflux disease Impedance pH measurement Follow-up Therapy Proton pump inhibitor

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Dietary copper triggers onset of fulminant hepatitis in the Long-Evans cinnamon rat model

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World Journal of Gastroenterology 2012年第39期18卷 5542-5550页

作者： Ramsi Siaj Vanessa Sauer Sandra Stppeler Hans-Ullrich Spiegel Gabriele Khler Andree Zibert Hartmut HJ Schmidt klinik und poliklinik für Transplantationsmedizin Universittsklinikum MünsterD-48149 MünsterGermany Abteilung Chirurgische Forschung Klinik und Poliklinik für Allgemein-und ViszeralchirurgieUniversittsklinikum MünsterD-48149 MünsterGermany Gerhard-Domagk-Institut für Pathologie Universittsklinikum MünsterD-48149 MünsterGermany

AIM： To investigate the impact of dietary copper given at different time points on the onset of fulminant hepatitis. METHODS： The Long-Evans cinnamon （LEC） rat mod- el of Wilson＇s disease （WD） was used to study the im- pact of high dietary copper （hCu） on the induction of fulminant hepatitis at early or late time points of life. High Cu diet was started in rat pups or in adults （month 5） for three months. Animals that received reduced di- etary copper （rCu） throughout their lifetime served as a control. Hepatitis-associated serum markers （alanine aminotransferase, aspartate transaminase, bilirubin） were analyzed in animal groups receiving hCu or rCu. Liver copper content and liver histology were revealed at sacrifice. A set of 5 marker genes previously found to be affected in injured liver and which are related to angiogenesis （Vegfa）, fat metabolism （Srebf1）, ex- tracellular matrix （Timp1）, oxidative stress （Hmox1）, and the cell cycle （Cdknla） were analyzed by real-time polymerase chain reaction. RESULTS： Regardless of the time point when hCu was started, LEC rats （35/36） developed fulminant hepati- tis and died. Animals receiving rCu （36/36） remained healthy, did not develop hepatitis, and survived long term without symptoms of overt disease, although liver copper accumulated in adult animals （477 ± 75 μg/g）. With regard to start of hCu, onset of fulminant hepatitis was significantly （P 〈 0.001） earlier in adults （35±9 d） that showed pre-accumulation of liver copper as com- pared to the pup group （77±15 d）. Hepatitis-associ- ated serum markers, liver copper and liver histology, as well as gene expression, were affected in LEC rats re- ceiving hCu. However, except for early and rapid onset of hepatitis, biochemical and molecular markers were similar at the early and late time points of disease. CONCLUSION： Rapid onset of fulminant hepatitis in asymptomatic LEC rats with elevated liver copper sug- gests that there is a critical threshold of liver copper which is imp

关键词： Wilson's disease Fulminant hepatitis Acuteliver failure Dietary copper Long-Evans cinnamon rat A TP7B

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Gastrointestinal side effects in children with Wilson's disease treated with zinc sulphate

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World Journal of Gastroenterology 2013年第27期19卷 4356-4362页

作者： Anna Wiernicka Wojciech Jańczyk Maciej Dαdalski Yesim Avsar Hartmut Schmidt Piotr Socha Department of Gastroenterology Hepatology and Malnutritionthe Children's Memorial Health Institute klinik und poliklinik für Transplantationsmedizin University Hospital of Muenster

AIM:To investigate the side effects of a zinc sulphate therapy in a cohort of Polish pediatric patients with Wilson's disease. METHODS:We retrospectively analyzed a cohort of 53 pediatric patients with Wilson's disease treated at the Children's Memorial Health Institute in Warsaw, Poland between the years 1996 and 2011 with zinc sulphate. Patients were diagnosed with Wilson's disease according to the scoring system of Ferenci, with 49 cases confirmed by mutation analysis. Data about the dosage scheme of zinc sulphate, side effects and efficacy and toxicity of the treatment were collected and recorded in the patient's medical chart at each visit to the hospital. RESULTS:Mean age of diagnosis for the entire cohort was 10 years (range, 2.5-17 years). Duration of treatment with zinc sulfate was 83.3 wk (range, 8-344 wk). Side effects, all of gastrointestinal origin, were observed in 21 patients (40% 9 males and 12 females), irrespective of the duration of therapy. Thirteen out of 21 patients were over the age of 10 years. The most common ATP7B mutation was p.H1069Q. Esophagogastroduodenoscopy, performed in 7 patients (33.3%) suffering from persistent and severe abdominal pain, revealed gastrointestinal ulcerations or erosions with negative Helicobacter pylori tests in all subjects investigated. The above mentioned 7 patients were treated with proton pump inhibitors. Three of those experienced resolution of symptoms, whereas proton-pump inhibitors failed to alleviate symptoms of the remaining four children and conversion of therapy to D-penicillamine was needed. CONCLUSION:Zinc sulphate appears to cause significant gastrointestinal side effects, which children on therapy for Wilson's disease should be closely monitored for.

关键词： Wilson’s disease Zinc Abdominal pain Gastrointestinal ulcer Therapy

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Epigastric hernias in children and the use of ultrasound in its diagnosis

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World Journal of Pediatric Surgery 2023年第2期6卷 92-96页

作者： Tatjana T König Laura S Oerters Ljuba Spiller Martin Schwind Mark Born Christina Oetzmann von Sochaczewski Andreas C Heydweiller klinik und poliklinik für Kinderchirurgie Universitätsmedizin der Johannes Gutenberg-Universität MainzMainzGermany Sektion Kinderchirurgie der klinik und poliklinik für Allgemein- Viszeral-Thorax-und GefächirurgieUniversität sklinikum BonnBonnGermany Sektion Kinderradiologie der klinik für Diagnostische und Interventionelle Radiologie Universitätsklinikum BonnBonnGermany

Introduction There is a paucity of clinical data on pediatric epigastric hernias despite them accounting for up to 6%of all hernia repairs in *** aimed to provide additional data to supplement those 117 cases of a recent systematic review and to further clarify the role of ultrasound in diagnosing pediatric epigastric *** We retrospectively included all 60 patients treated for epigastric hernias in children in two tertiary pediatric surgical departments within 12 *** were tested via point-biserial correlation *** Epigastric hernias primarily affected preschool children with a median age of 39 *** vast majority of patients(88%)presented with swelling that was occasionally(30%)accompanied by *** defects could be found during clinical examination in 45%of patients with a median size of 5 mm(95%CI 3 to 10).Smaller defects were less likely to be palpable(r=-0.44,95%CI-0.08 to-0.7,p=0.021).Likewise,ultrasound was used more frequently with smaller fascial defect sizes(r=-0.51,95%Cl-0.16 to-0.74,p=0.007).Laparoscopic repair was used in 11 patients(19%)and more often(4/11)in combination with another simultaneous procedure than open repair(11/48).Conclusions Epigastric hernias are primarily a condition of the preschool *** can be beneficial if the diagnosis cannot be made clinically;otherwise,it is abdicable if it does not change the management of the patient's epigastric *** repairs might be beneficial for children with multiple defects or simultaneous procedures.

关键词： diagnosis primarily otherwise

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Endoscopic stent therapy in patients with chronic pancreatitis:A 5-year follow-up study

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World Journal of Gastroenterology 2013年第5期19卷 715-720页

作者： Andreas Weber Jochen Schneider Bruno Neu Alexander Meining Peter Born Stefan von Delius Monther Bajbouj Roland M Schmid Hana Algül Christian Prinz II Medizinische klinik und poliklinik Klinikum Rechts der IsarTechnische Universitt München81675 MünchenGermany II Medizinische klinik Gastroenterologie und HepatologieHelios Klinikum WuppertalUniversitt Witten/Herdecke42283 WuppertalGermany

AIM:This study analyzed clinical long-term outcomes after endoscopic therapy,including the incidence and treatment of relapse. METHODS:This study included 19 consecutive patients(12 male,7 female,median age 54 years)with obstructive chronic pancreatitis who were admitted to the 2nd Medical Department of the Technical University of *** patients presented severe chronic pancreatitis(stageⅢ°)according to the Cambridge *** majority of the patients suffered intermittent pain attacks.6 of 19 patients had strictures of the pancreatic duct;13 of 19 patients had strictures and *** first endoscopic retrograde pancreatography(ERP)included an endoscopic sphincterotomy, dilatation of the pancreatic duct,and stent *** first control ERP was performed 4 wk after the initial intervention,and the subsequent control ERP was performed after 3 mo to re-evaluate the clinical and morphological *** follow-up was performed annually to document the course of pain and the management of *** course of pain was assessed by a pain scale from 0 to *** date and choice of the therapeutic procedure were documented in case of relapse. RESULTS:Initial endoscopic intervention was successfully completed in 17 of 19 *** 17 patients reported partial or complete pain relief after endoscopic *** therapy failed in 2 patients. Both patients were excluded from further *** failed patient underwent surgery,and the other patient was treated conservatively with pain *** of 19 patients were followed after the successful completion of endoscopic stent *** of 17 patients were lost to *** patient was not avail-able for interviews after the 1st year of *** patients died during the 3rd year of *** both patients chronic pancreatitis was excluded as the cause of *** patient died of myocardial infarction, and one patient succumbed to *** three patient

关键词： Chronic pancreatitis Pain Stent therapy Endoscopic retrograde cholangiopancreatography Pancreaticolithiasis

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Treatment of eosinophlic esophagitis with swallowed topical corticosteroids

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World Journal of Gastroenterology 2020年第36期26卷 5395-5407页

作者： Simon Nennstiel Christoph Schlag klinikum rechts der Isar der Technischen Universität München Klinik und Poliklinik für Innere Medizin IIMunich 81675Germany

Eosinophilic esophagitis(EoE)is an emerging chronic local immune-mediated disease of the *** proton pump inhibitors and food-restrictiondiets swallowed topical corticosteroids(STC)can be offered as a first line therapy according to current *** review describes the background and practical management of STCs in *** far,mainly asthma inhalers containing either budesonide or fluticasone have been administered to the esophagus by swallowing these medications“off label”.Recently esophagus-targeted formulations of topical steroids have been developed showing clinicopathological response rates up to 85%-an orodispersible tablet of budesonide has been approved as the first“in label”medication for EoE in Europe in June *** it was shown that disease remission induction of EoE by STCs is highly effective,there is still a lack of data regarding long-term and maintenance ***,current studies on STC maintenance therapy add some movement into the game.

关键词： Eosinophilic esophagitis Swallowed topical corticosteroids Esophagustargeted formulations of topical steroids Fluticasone Budesonide Budesonide orodispersible tablet Budesonide oral suspension

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速激肽对大鼠小肠上行及下行反射通路的作用(英文)

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Acta Pharmacologica Sinica 2002年第4期23卷 3-9页

作者： Andreas HAHN, Martin STORR, Hans-Dieter ALLESCHER(// Medizinische klinik und poliklinik der Technischen Universitat Munchen, 81675 Munchen, Germany) ll Medizinische klinik und poliklinik der Technischen Universitat München 81675 Mtnchen 德国 ll Medizinische klinik und poliklinik der Technischen Universitat München 81675 Mtnchen1 德国

AIM: To examine the effect of tachykinins on the ascending reflex pathway in rat small intestine, we used different selective neurokinin (NK) receptor antagonists (RA); a) NK1-RA; GR-82334 and CP-96.345, b) NK2-RA: MEN-10.376 and L-659.877. The aim was further to investigate the effect of substance P (SP) on the ascending excitatory and descending inhibitory reflex pathway. METHODS: The whole segments of rat ileum (10 cm in length) were studied in an organ bath. Ascending contraction of circle muscle was elicited by anal electrical stimulation (3 Hz, 1ms, 20 V) and measured as change of intraluminal pressure by a perfused manometric system 2 cm and 4 cm orad of the stimulation site. RESULTS: GR-82334 and CP-96.345 (NK1-RA) caused a significant dose-related inhibition of the oral contraction at a distance of 4 cm: GR-82334 [area: -10 % ± 8 % (10 nmol/L); - 29 %±10 % (1000 nmol/L). P < 0.05, n = 10 ], CP-96.345 [area: -2 %±6 %(0.1 nmol/L);-14 %±10 %(10nmol/ L). P < 0.01, n = 8], whereas the contractil

关键词：速激肽类神经激肽-1受体神经激肽-2受体 P物质

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Arterial thrombosis in the context of HCV-associated vascular disease can be prevented by protein C

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Cellular & Molecular Immunology 2017年第12期14卷 986-996页

作者： Philipp Blüm Joachim Pircher Monika Merkle Thomas Czermak Andrea Ribeiro Hanna Mannell Florian Krötz Alexander Hennrich Michael Spannagl Simone Köppel Erik Gaitzsch Markus Wörnle Medizinische klinik und poliklinik IV InnenstadtKlinikum der Universität München80336 MünchenGermany Walter Brendel Centre of Experimental Medicine and Munich Heart Alliance Ludwig Maximilians University München80336 MünchenGermany Medizinische klinik und poliklinik I Klinikum der Universität München80336 MünchenGermany Abteilung für Transfusionsmedizin Zelltherapeutika und HämostaseologieKlinikum der Universität München80336 MünchenGermany

Hepatitis C virus(HCV)infection is a major problem *** is not limited to liver disease but is frequently complicated by immune-mediated extrahepatic manifestations such as glomerulonephritis or vasculitis.A fatal complication of HCV-associated vascular disease is ***:polyribocytidylic acid(poly(I:C)),a synthetic analog of viral RNA,induces a Toll-like receptor 3(TLR3)-dependent arteriolar thrombosis without significant thrombus formation in venules in *** procoagulant effects are caused by increased endothelial synthesis of tissue factor and PAI-1 without platelet *** addition to human umbilical endothelial cells(HUVEC),human mesangial cells(HMC)produce procoagulatory factors,cytokines and adhesion molecules after stimulation with poly(I:C)or HCV-containing cryoprecipitates from a patient with a HCV infection as *** protein C(APC)is able to prevent the induction of procoagulatory factors in HUVEC and HMC in vitro and blocks the effects of poly(I:C)and HCV-RNA on the expression of cytokines and adhesion molecules in HMC but not in *** vivo,protein C inhibits poly(I:C)-induced arteriolar ***,endothelial cells are de facto able to actively participate in immune-mediated vascular thrombosis caused by viral ***,we provide evidence for the ability of protein C to inhibit TLR3-mediated arteriolar thrombosis caused by HCV infection.

关键词： hepatitis C thrombosis toll-like receptor 3

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Treatment of metastatic colorectal carcinomas by systemic inhibition of vascular endothelial growth factor signaling in mice

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World Journal of Gastroenterology 2005年第28期11卷 4332-4336页

作者： Volker Schmitz Miroslaw Kornek Tobias Hilbert Christian Dzienisowicz Esbher Raskopf Christian Rabe Tilman Sauerbruch Cheng Qian Wolfgang H Caselmann Medizinische klinik und poliklinik I Universitatsklinikum BonnGermany Universidad de Navarra Clinica Universitaria Pamplona Spain Bavarian State Ministry of the Environment Public Health and Consumer Protection Munich 81901 Germany

AIM： Tumor angiogenesis has been shown to be promoted by vascular endothelial growth factor （VEGF） via stimulating endothelial cell proliferation, migration, and survival. Blockade of VEGF signaling by different means has been demonstrated to result in reduced tumor growth and suppression of tumor angiogenesis in distinct tumor entities. Here, we tested a recombinant adenovirus, AdsFItl-3, that encodes an antagonistically acting fragment of the VEGF receptor 1 （Fit-l）, for systemic antitumor effects in pre-established subcutaneous CRC tumors in mice.METHODS： Murine colorectal carcinoma cells （CT26） were inoculated subcutaneously into Balb/c mice for in vivo studies. Tumor size and survival were determined. 293 cell line was used for propagation of the adenoviral vectors. Human lung cancer line A549 and human umbilical vein endothelial cells were transfected for in vitro experiments.RESULTS： Infection of tumor cells with AdsFlt1-3 resulted in protein secretion into cell supernatant, demonstrating correct vector function. As expected, the secreted sFlt1-3 protein had no direct effect on CT26 tumor cell proliferation in vitro, but endothelial cell function was inhibited by about 46% as compared to the AdLacZ control in a tube formation assay. When AdsFlt1-3 （5×10^9 PFU/animal） was applied to tumor bearing mice, we found a tumor inhibition by 72% at d 12 after treatment initiation, in spite of these antitumoral effects, the survival time was not improved. According to reduced intratumoral microvessel density in AdsFlt1-3-treated mice, the antitumor mechanism can be attributed to angiostatic vector effects. We did not detect increased systemic VEGF levels after AdsFlt1-3 treatment and liver toxicity was low as judged by serum alanine aminotransferase determination.CONCLUSION： In this study we confirmed the value of a systemic administration of AdsFItl-3 to block VEGF signaling as antitumor therapy in an experimental metastatic colorectal carcinoma model in mice.

关键词： Colorectal carcinomas Vascular endothelial growth factor Systemic inhibition

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