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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

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

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

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

Management of occluded self-expanding biliary metal stents in malignant biliary disease

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Hepatobiliary & Pancreatic Diseases International 2018年第1期17卷 49-54页

作者： Simon Nennstiel Isolde Tschurtschenthaler Bruno Neu Hana Algül Monther Bajbouj Roland M. Schmid Stefan von Delius Andreas Weber klinik und poliklinik fur Innere Medizin Ⅱ Klinikum rechts der Isar der Technischen Universitar Manchen Ismaninger Straβe 22 Munich 81675 Germany medizinische klinik II Krankenhaus Landshut-Achdorf Academic Teaching Hospital Technische Universitar Munchen Achdorferweg 3 Landshut 84036Germany

Background: Occlusion of self-expanding metal stents(SEMS) in malignant biliary obstruction occurs in up to 40% of patients. This study aimed to compare the different techniques to resolve stent occlusion in our collective of ***: Patients with malignant biliary obstruction and occlusion of biliary metal stent at a tertiary referral endoscopic center were retrospectively identified between April 1, 1994 and May 31, 2014. The clinical records were further analyzed regarding the characteristics of patients, malignant strictures, SEMS,management strategies, stent patency, subsequent interventions, survival time and case ***: A total of 108 patients with biliary metal stent occlusion were identified. Seventy-nine of these patients were eligible for further analysis. Favored management was plastic stent insertion in 73.4% patients. Second SEMS were inserted in 12.7% patients. Percutaneous transhepatic biliary drainage and mechanical cleansing were conducted in a minority of patients. Further analysis showed no statistically significant difference in median overall secondary stent patency(88 vs. 143 days, P = 0.069), median survival time(95 vs. 192 days, P = 0.116), median subsequent intervention rate(53.4% vs. 40.0%, P = 0.501)and median case charge(€5145 vs. €3473, P = 0.803) for the treatment with a second metal stent insertion compared to plastic stent insertion. In patients with survival time of more than three months,significantly more patients treated with plastic stents needed re-interventions than patients treated with second SEMS(93.3% vs. 57.1%, P = 0.037).Conclusions: In malignant biliary strictures, both plastic and metal stent insertions are feasible strategies for the treatment of occluded SEMS. Our data suggest that in palliative biliary stenting, patients especially those with longer expected survival might benefit from second SEMS insertion. Careful patient selection is important to ensure a proper decision for either management

关键词： Self-expanding metal stents Biliary tract neoplasms Endoscopic retrograde cholangiopancreatography Biliary tract diseases Complications

Targeting metabolic rewiring might decrease spread of tumor cells: Mitochondrial tRNA modifications promote cancer metastasis

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Signal Transduction and Targeted Therapy 2022年第11期7卷 3987-3988页

作者： Maik Luu Alexander Visekruna Lehrstuhl für Zelluläre Immuntherapie Medizinische Klinik und Poliklinik IIUniversitätsklinikum WürzburgWürzburgGermany Institute for Medical Microbiology and Hygiene Philipps-UniversityMarburgGermany

In a recent study published in Nature,Delaunay and colleagues demonstrate that tRNA modifications in mitochondria have the potential to affect the synthesis of mitochondrial proteins involved in oxidative phosphorylation(OXPHOS),which drives the invasive spread of cancer *** inhibition of one particular RNA-modifying enzyme was sufficient to prevent the cancer cell invasion and dissemination.

关键词： invasion metastasis cancer

Diagnostische Bedeutung von pentavalenter ^(99m)Tc-Dimercaptobern-steinsure ([V]-DMSA) bei Kopf-Hals-Tumoren

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2000年第4期20卷 303-307页

作者：安锐 Abteilung für Nuklearmedizin Xiehe Hospital Tongji Medizinische Universität Wuhan klinik und poliklinik für Nuklearmedizin Universität Bonn Bonn Deutschland

The purpose of this investigation was to assess the biodistribution of 99mTc-[V]-DMSA in human being, and its di- agnostic value in patients with head and neck tumours. 20 patients with histologically confirmed head and neck tumours were ex- amined with planar as well as SPECT scintigraphy. Whole body scintigraphy in different time after injection of 99mTc-[V]-DM- SA was performed to assess the major sequential organ biodistribution. Our results showed that the blood clearance of 99mTc- [V]-DMSA was bi-exponential. All organs except kidneys showed a relatively rapid elimination of 99mTc-[V]-DMSA. The kid- neys showed a increasing accumulation in the first 2 h, which is probably due to the tubular reabsorption of 99mTc-[V]-DMSA. In 15 of 20 patients, 19 lesions could be proven by means of planar scintigraphy (corresponding sensitivity of 75%). 29 lesions in 18 patients could however be detected by the application of SPECT (corresponding sensitivity of 90%). Except primary tumours and local lymphadenmetastases in 5 patients distant metastases (3 thorax wall, 1 liver and 1 inguinal/paravesicle) were found. Altogether a sensitivity of 76. 9% and a specificity of 71. 4% were calculated for the detection of primary tumour. The sensitivi- ty and specificity for the exploration of lymphadenmetastases were 75% and 100%. In conclusion, this study shows that 99m Tc-[V]-DMSA, particularly with SPECT imaging, is useful in localising the primary tumours and lymphadenmetastases as well as distant metastases of head and neck tumours. The possible therapeutic application of 188/186Re-[V]-DMSA is also evaluated.

关键词： mTc-[V]-DMSA head and neck tumour: diagnosis

Patient age and duration of colonoscopy are predictors for adenoma detection in both proximal and distal colon

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World Journal of Gastroenterology 2015年第2期21卷 525-532页

作者： Peter Klare Stefan Ascher Alexander Hapfelmeier Petra Wolf Analena Beitz Roland M Schmid Stefan von Delius Ⅱ.medizinische klinik Klinikum rechts der IsarTechnischen Universit?t München81675 MunichGermany Institut für medizinische Statistik und Epidemiologie Klinikum rechts der IsarTechnische Universit?t München81675 MunichGermany

AIM: To investigate the relation of patient characteristics and procedural parameters to the endoscopic detection rate of colonic adenomas. Further to study,which factors may be capable to predict the localization of adenomatous ***: We used the data base of a prospective randomized colonoscopy study(The Colo Cap trial) to identify patients being diagnosed with colon adenoma. Logistic regression analysis was conducted to reveal predictors for adenoma detection in the entire colon and also with respect to the proximal and distal part. Covariates including age, gender, duration of colonoscopy and comorbidities were defined to determine association between predictors and adenoma ***: Equal numbers of adenomas were detected in the proximal and distal side of the splenic flexure [126(57%) vs 94(43%), P = 0.104]. Simultaneous occurrence of adenomas in both sides of the colon was rare. The appearance of both proximal and distal adenoma was associated with increasing age(P = 0.008 and P = 0.024) and increasing duration of colonoscopy(P und to be a predictor for the detection of distal adenoma(P = 0.041). CONCLUSION: Increasing age and longer duration of colonoscopy are factors with a strong impact on adenoma detection both in the proximal and distal colon. Since proximal adenomas occurred in absence of distal adenomas, complete colonoscopy should be performed for screening.

关键词： Adenoma Colorectal carcinoma Distal Colonoscopy Pr

Multiple Imputation of Missing Data:A Simulation Study on a Binary Response

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Open Journal of Statistics 2013年第5期3卷 370-378页

作者： Jochen Hardt Max Herke Tamara Brian Wilfried Laubach medizinische Psychologie und medizinische Soziologie Klinik fur Psychosomatische Medizin und PsychotherapieUniversitatsmedizin MainzMainzGermany

Currently, a growing number of programs become available in statistical software for multiple imputation of missing values. Among others, two algorithms are mainly implemented: Expectation Maximization (EM) and Multiple Imputation by Chained Equations (MICE). They have been shown to work well in large samples or when only small proportions of missing data are to be imputed. However, some researchers have begun to impute large proportions of missing data or to apply the method to small samples. A simulation was performed using MICE on datasets with 50, 100 or 200 cases and four or eleven variables. A varying proportion of data (3% - 63%) was set as missing completely at random and subsequently substituted using multiple imputation by chained equations. In a logistic regression model, four coefficients, i.e. non-zero and zero main effects as well as non-zero and zero interaction effects were examined. Estimations of all main and interaction effects were unbiased. There was a considerable variance in the estimates, increasing with the proportion of missing data and decreasing with sample size. The imputation of missing data by chained equations is a useful tool for imputing small to moderate proportions of missing data. The method has its limits, however. In small samples, there are considerable random errors for all effects.

关键词： Multiple Imputation Chained Equation Large Proportion Missing Main Effect Interaction Effect