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| 1 | Diagnostic criteria for acute liver failure due to Wilson disease显示文摘AIM: To describe the diagnostic criteria for acute liver failure due to Wilson disease (WD), which is an uncommon cause of acute liver failure (ALF). METHODS: We compared findings of patients presenting with ALF due to WD to those with ALF of other etiologies. RESULTS: Previously described criteria, such as low alkaline phosphatase activity, ratio of low alkaline phosphatase to total bilirubin or ratio of high aspartate aminotransferase (AST) to alanine aminotransferase (ALT), failed to identify patients with ALF due to WD. There were significant differences in low ALT and AST activities (53 ± 43 vs 1982 ± 938, P < 0.0001 and 87 ± 44 vs 2756 ± 2941, P = 0.037, respectively), low choline esterase activity (1.79 ± 1.2 vs 4.30 ± 1.2, P = 0.009), high urine copper concentrations (93.4 ± 144.0 vs 3.5 ± 1.8, P = 0.001) and low hemoglobin (7.0 ± 2.2 vs 12.6 ± 1.8, P < 0.0001) in patients with ALF caused by WD as compared with other etiologies. Interestingly, 4 of 7 patients with ALF due to WD survived without liver transplantation. CONCLUSION: In ALF, these criteria can help establish a diagnosis of WD. Where applicable, slit- lamp examination for presence of Kayser-Fleischer rings and liver biopsy for determination of hepatic copper concentration still remain important for the diagnosis of ALF due to WD. The need for liver transplantation should be evaluated carefully as the prognosis is not necessarily fatal. | Christoph Eisenbach Olivia Sieg Wolfgang Stremmel Jens Encke Uta Merle | 2007 | World Journal of Gastroenterology2007，13，11： | 14 |
| 2 | Aquaporin-8 expression is reduced in ileum and induced in colon of patients with ulcerative colitis显示文摘AIM: To study susceptibility genes which may play a potential role in the pathogenesis and etiology of inflammatory bowel disease (IBD). METHODS: To identify potential susceptibility genes we performed global gene expression profiling in patients with IBD and control specimens. For determination of an intrinsic gene expression profile in ulcerative colitis (UC) and Crohn’s disease (CD) compared to normal subjects, mucosal biopsies of non-inflamed regions of the colon and the terminal ileum were subjected to DNA microarray analysis. Real-time RT-PCR and immunohistochemistry were used for verification of selected regulated candidate genes and a genetic analysis was performed. RESULTS: We could show that aquaporin-8 (AQP8) mRNA and protein levels were significantly increased in the colon of UC patients compared to controls. Genetic analysis of the six exons and the promoter region of AQP8, however, revealed no mutations or polymorphisms in IBD patients. CONCLUSION: Our results suggest that upregulation of AQP8 in the colon of UC patients represents a secondary phenomenon which may, due to altered water exchange of the distal intestinal mucosa, disturb the physiologic colonic mucus barrier and thus lead to chronic infla- mmation and ulceration. | Alexandra Zahn Christoph Moehle Thomas Langmann Robert Ehehalt Frank Autschbach Wolfgang Stremmel Gerd Schmitz | 2007 | World Journal of Gastroenterology2007，13，11： | 13 |
| 3 | Serum levels of soluble Fas, nitric oxide and cytokines in acute decompensated cirrhotic patients显示文摘AIM: To evaluate plasma levels of nitrite/nitrate (NOx), soluble Fas (sFas) antigen, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in patients with com- pensated and acute decompensated cirrhosis and to evaluate mediators causing acute decompensation in liver cirrhosis. METHODS: This prospective study was conducted in the medical intensive care unit of an academic tertiary center. Fifty-five patients with acute decompensation (gastrointestinal hemorrhage, encephalopathy, hydropic decompensation) and twenty-five patients with compen- sated liver cirrhosis were included. Blood samples were taken for analyses of sFas, Nox, IL-6, TNF-α. Liver en- zymes and kidney functions were also tested. RESULTS: In patients with acute decompensation, plas- ma sFas levels were higher than in non-decompensated patients (15 305 ±4646 vs 12 458 ±4322 pg/mL,, P < 0.05). This was also true for the subgroup of patients with alcoholic liver cirrhosis (P < 0.05). The other media- tors were not different and none of the parameters pre- dicted survival, except for ALT (alanine-aminotransfer- ase). In patients with portal-hypertension-induced acute hemorrhage, NOx levels were significantly lower than in patients with other forms of decompensation (70.8 ± 48.3 vs 112.9 ± 74.9 pg/mL, P < 0.05). When NOx lev- els were normalized to creatinine levels, the difference disappeared. IL-6, TNF-α and sFas were not different between bleeders and non-bleeders. In decompensated patients sFas, IL-6 and NOx levels correlated positively with creatinine levels, while IL-6 levels were dependent on Child class. CONCLUSION: In acute decompensated cirrhotic pa- tients sFas is increased, suggesting a role of apoptosis in this process and patients with acute bleeding have lower NOx levels. However, in this acute complex clinical situa-tion, kidney function seems to have a predominant influ- ence on mediator levels. | Christoph Elsing Sabine Harenberg Wolfgang Stremmel Thomas Herrmann | 2007 | World Journal of Gastroenterology2007，13，3： | 10 |
| 4 | Are heat stroke and physical exhaustion underestimated causes of acute hepatic failure?显示文摘While cardiopulmonary symptoms are common in patients undergoing classical or, due to physical exercise, exertional heat stroke, the failure of other organs is a rarely described phenomenon. Here we present two cases of acute hepatic failure, one due to classic heat shock, while the other occurred while the patient was doing a marathon-type running. Both cases presented with very high transaminases and significantly elevated international normalized ratio (INR). No other causes for liver failure could be identified but physical exhaustion and hyperthermia. | Kilian Weigand Carina Riediger Wolfgang Stremmel Christa Flechtenmacher Jens Encke | 2007 | World Journal of Gastroenterology2007，13，2： | 8 |
| 5 | Entecavir as treatment for reactivation of hepatitis B in immunosuppressed patients显示文摘AIM: To study the efficacy and safety of entecavir (ETV) as first-line therapy for hepatitis B virus (HBV) reactivation due to immunosuppression. METHODS: Four patients that were treated with different immunosuppressive regimens for hematological malignancies, who presented with HBV reactivation were treated with ETV. Clinical outcome, biochemical and virological factors, including quantitative hepatitis B surface antigen (HBsAg) were studied. RESULTS: In all patients, ETV induced suppression of HBV, and rapid clinical improvement without side effects. In one patient with an alanine aminotransferase (ALT) flare, tenofovir was added after 3 mo of treatment. Until death from disease progression at 6 mo after treatment initiation, this patient did not clear HBV infection. Retrospectively, it is highly probable that thepatient had been non-adherent. In the other three patients, the virological responses were associated with an expeditious decrease in quantitative HBsAg titers with negativity after 2 mo, and all three had HBsAg seroconversion. In one patient, HBV DNA reached a plateau after 3 mo, before becoming undetectable after 1 year, despite early ALT normalization and undetectable quantitative HBsAg. CONCLUSION: ETV seems to be effective and safe treatment for HBV reactivation. Monitoring of quantitative HBsAg might be an additional useful tool to monitor treatment response. | Sylvia Brost Paul Schnitzler Wolfgang Stremmel Christoph Eisenbach | 2010 | World Journal of Gastroenterology2010，16，43： | 7 |
| 6 | Noninvasive indocyanine green plasma disappearance rate predicts early complications,graft failure or death after liver transplantation显示文摘BACKGROUND:Early detection of graft malfunction or postoperative complications is essential to save patients and organs after orthotopic liver transplantation (OLT).Predictive tests for graft dysfunction are needed to enable earlier implementation of organ-saving interventions following transplantation.This study was undertaken to assess the value of indocyanine green plasma disappearance rates (ICG-PDRs) for predicting postoperative complications,graft dysfunction and patient survival following OLT.METHODS:Eighty-six patients undergoing OLT were included in this single-centre trial.ICG-PDR was assessed daily for the first 7 days following OLT.Endpoints were graft loss or death within 30 days and postoperative complications,graft loss,or death within 30 days.RESULTS:Postoperative complications of 31 patients included deaths (12 patients) or graft losses.ICG-PDR was significantly different in patients whose endpoints were graft loss or death beginning from day 3 and in those whose endpoints were graft loss,death,or postoperative complications beginning from day 4 after OLT.For day 7 measurements,receiver operating characteristic curve analysis revealed an ICG-PDR cut-off for predicting death or graft loss of 9.6% per min (a sensitivity of 75.0%,a specificity of 72.6%,positive predictive value 0.35 negative predictive value 0.94).For prediction of graft loss,death or postoperative complications,the ICG-PDR cut-off was 12.3%per min (a sensitivity of 68.9%,a specificity of 66.7%,positive predictive value 0.57,negative predictive value 0.77).CONCLUSIONS:ICG-PDR measurements on postoperative day 7 are predictive of early patient outcomes following OLT.The added value over that of routinely determined laboratory parameters is low. | Lutz Schneider Martin Spiegel Sebastian Latanowicz Markus A Weigand Jan Schmidt Jens Werner Wolfgang Stremmel Christoph Eisenbach | 2011 | Hepatobiliary & Pancreatic Diseases International2011，10，4： | 6 |
| 7 | First clinical trial of a newly developed capsule endoscope with panoramic side view for small bowel: A pilot study显示文摘 | Kilian Friedrich Sven Gehrke Wolfgang Stremmel Andreas Sieg | 2013 | J Gastroenterol Hepatol2013，，9： | 4 |
| 8 | Intestinal-borne dermatoses significantly improved by oral application of Escherichia coli Nissle 1917显示文摘AIM: To evaluate the effect of oral Escherichia coli(E. coli) Nissle application on the outcome of intestinalborne dermatoses.METHODS: In a randomized, controlled, non-blinded prospective clinical trial 82 patients with intestinal-borne facial dermatoses characterized by an erythematous papular-pustular rash were screened. At the initiation visit 37 patients entered the experimental arm and 20 patients constituted the control arm. All 57 patients were treated with a vegetarian diet and conventional topical therapy of the dermatoses with ointments containing tetracycline, steroids and retinoids. In the experimental arm patients received a one month therapy with oral E. coli Nissle at a maintenance dose of 2 capsules daily. The experimental group was compared to a non-treatment group only receiving the diet and topical therapy. The primary outcome parameter was improvement of the dermatoses, secondary parameters included life quality and adverse events. In addition the immunological reaction profile(Ig A, interleucin-8 and interferon-a) was determined. Furthermore the changes of stool consistency and the microbiota composition over the time of intervention were recorded.RESULTS: Eighty-nine percent of the patients with acne, papular-pustular rosacea and seborrhoic dermatitis responded to E. coli Nissle therapy with significant amelioration or complete recovery in contrastto 56% in the control arm(P < 0.01). Accordingly, in the E. coli Nissle treated patients life quality improved significantly(P < 0.01), and adverse events were not recorded. The clinical improvement was associated with a significant increase of Ig A levels to normal values in serum as well as suppression of the proinflammatory cytokine IL-8(P < 0.01 for both parameters). In the E. coli Nissle treated group a shift towards a protective microbiota with predominance of bifidobacteria and lactobacteria(> 107 CFU/g stool) was observed in 79% and 63% of the patients, respectively(P < 0.01), compared to no change in the control group without E. coli Nissle. Moreover, the detection rate of a pathogenic flora dropped from 73% to 14 % of the patients in the experimental arm(P < 0.01) with no significant change in the control arm(accounting 80% before and 70% after the observation period, P > 0.05). Accordingly, stool consistency, color and smell normalized in the E. coli Nissle treated patients. CONCLUSION: E. coli Nissle protects the mucus barrier by overgrowth of a favorable gut microbiota with less immunoreactive potential which finally leads to clinical improvement of intestinal borne dermatoses. | Elina Manzhalii Daniel Hornuss Wolfgang Stremmel | 2016 | World Journal of Gastroenterology2016，22，23： | 4 |
| 9 | Serum bile acid profiling reflects enterohepatic detoxification state and intestinal barrier function in inlammatory bowel disease显示文摘AIM:To determine free and conjugated serum bile acid (BA) levels in in? ammatory bowel disease (IBD) subgroups with defi ned clinical manifestations.METHODS: Comprehensive serum BA profiling was performed in 358 IBD patients and 310 healthy controls by liquid chromatography coupled to electrospray ionization tandem mass spectrometry.RESULTS: Serum levels of hyodeoxycholic acid, the CYP3A4-mediated detoxification product of the secondary BA lithocholic acid (LCA), was increased significantly in Crohn's disease (CD) and ulcerative colitis (UC), while most other serum BA species were decreased significantly. Total BA, total BA conjugate, and total BA glycoconjugate levels were decreased only in CD, whereas total unconjugated BA levels were decreased only in UC. In UC patients with hepatobiliary manifestations, the conjugated primary BAs glycocholic acid, taurocholic acid, and glycochenodeoxycholic acid were as significantly increased as the secondary BAs LCA, ursodeoxycholic acid, and tauroursodeoxycholic acid compared to UC patients without hepatobiliary manifestations. Finally, we found that in ileocecal resected CD patients, the unconjugated primary BAs, cholic acid and chenode-oxycholic acid, were increased significantly compared to controls and patients without surgical interventions.CONCLUSION: Serum BA profiling in IBD patients that indicates impaired intestinal barrier function and increased detoxification is suitable for advanced diagnostic characterization and differentiation of IBD subgroups with defined clinical manifestations. | Carsten Gnewuch Gerhard Liebisch Thomas Langmann Benjamin Dieplinger Thomas Mueller Meinhard Haltmayer Hans Dieplinger Alexandra Zahn Wolfgang Stremmel Gerhard Rogler Gerd Schmitz | 2009 | World Journal of Gastroenterology2009，15，25： | 4 |
| 10 | Copper toxicosis gene MURRl is not changed in Wilson disease patients with normal blood ceruloplasmin levels显示文摘瞄准:在为 MURR1 编码的基因为改变分析我们的威尔森疾病病人队(n=106 ) 。方法:有威尔森疾病的确定的诊断的病人但是正常血浆铜蓝蛋白血层次为我们的学习被选择(n = 14 ) 。有在 ATP7B 基因的二个已知的引起疾病的变化的病人没被包括。人的 MURR1 基因的三前 ons 被聚合酶链反应在 genomic DNA 的扩大以后定序。结果:我们的学习没揭示在威尔森疾病病人的 MURR1 顺序导致一个氨基酸变化的任何变化。在编码顺序的 472 bp 的多型性能被证实。结论:MURR1 基因不与正常浆液血浆铜蓝蛋白层次在威尔森疾病病人的致病起作用。 | Karl Heinz Weiss Uta Merle Mark Schaefer Peter Ferenci Joachim Fullekrug Wolfgang Stremmel | 2006 | World Journal of Gastroenterology2006，12，14： | 4 |
| 11 | Treatment of hepatitis C virus infection显示文摘Acute and chronic hepatitis C virus (HCV) infection remains a serious health problem worldwide, however, there has been advancement in the treatment of HCV infection due to standard treatment using pegylated interferon and ribavirin. The literature indicates that therapy for HCV is becoming more individualized. In addition to considering genotype and viral RNA levels before treatment, achievement of an early virologic response (EVR) and a rapid virologic response (RVR) is now possible during therapy. Moreover, problem patients, such as non-responders, relapsers, HIV or HBV co- infected patients, patients with liver cirrhosis, and pre- or post-liver transplantation patients are an increasing fraction of the patients requiring treatment. This article reviews the literature regarding standard treatments and problem patients with acute and chronic HCV infection. It also includes discussion on contraindications and side effects of treatment with interferon and ribavirin, as well as new drug development. | Kilian Weigand Wolfgang Stremmel Jens Encke | 2007 | World Journal of Gastroenterology2007，13，13： | 4 |
| 12 | Analysis of the human Atox 1 homologue in Wilson patients显示文摘AIM: To analyze the metallochaperone antioxidant-1 (Atox1) gene sequence in Wilson disease patients. METHODS: Mutation analysis of the four exons of the Atox1 gene including the intron- exon boundaries was performed in 63 Wilson disease patients by direct sequencing. RESULTS: From 63 selected patients no mutations were identified after the entire coding region including the intron- exon boundaries of Atox1 were sequenced. One known polymorphism within the Atox1 gene (5’UTR -99 T>C) in 31 (49%) of the Wilson patients as well as one previously undescribed variation (5’UTR -68 C>T) in 2 of the Wilson patients could be detected. Statistical analyses revealed that the existence of a variation within the Atox1- gene showed a tendency towards an earlier onset of the disease. CONCLUSION: Based on the data of this study, no major role can be attributed to Atox1 in the pathophysiology or clinical variation of Wilson disease. | Isabel Simon Mark Schaefer Jürgen Reichert Wolfgang Stremmel | 2008 | World Journal of Gastroenterology2008，14，15： | 4 |
| 13 | Biliary phosphatidylcholine and lysophosphatidylcholine profiles in sclerosing cholangitis显示文摘AIM:To analyze phospholipid profiles in intrahepatic bile from patients with primary sclerosing cholangitis(PSC)and secondary sclerosing cholangitis(SSC).METHODS:Intrahepatic bile specimens collected via endoscopic retrograde cholangiography from 41 patients were analyzed.Fourteen of these patients were diagnosed with PSC,10 with SSC,11 with choledocholithiasis or no identifiable biliary disease,and 6 with cholangiocellular carcinoma(CCC).Bile acid,cholesterol,protein,and bilirubin contents as well as pancreas lipase activity in bile were determined by biochemical methods.Phosphatidylcholine(PC)and lysophosphatidylcholine(LPC)species were quantified using nanoelectrospray ionization tandem mass spectrometry.RESULTS:Bile from all the examined patient groups showed a remarkably similar PC and LPC species composition,with only minor statistical differences.Total biliary PC concentrations were highest in controls(8030±1843 mol/L)and lowest in patients with CCC(1969±981 mol/L)(P=0.005,controls vs SSC and CCC,respectively,P<0.05).LPC contents in bile were overall low(4.2%±1.8%).Biliary LPC/PC ratios and ratios of biliary PC to bilirubin,PC to cholesterol,PC to protein,and PC to bile acids showed no intergroup differences.CONCLUSION:PC and LPC profiles being similar in patients with or without sclerosing cholangitis,these phospholipids are likely not of major pathogenetic importance in this disease group. | Annika Gauss Robert Ehehalt Wolf-Dieter Lehmann Gerhard Erben Karl-Heinz Weiss Yvonne Schaefer Petra Kloeters-Plachky Adolf Stiehl Wolfgang Stremmel Peter Sauer Daniel Nils Gotthardt | 2013 | World Journal of Gastroenterology2013，19，33： | 3 |
| 14 | Is stenting necessary after balloon dilation of post-transplantation biliary strictures? Results of a prospective comparative study显示文摘 | H. Kulaksiz K. Weiss D. Gotthardt G. Adler W. Stremmel A. Schaible A. Dogan A. Stiehl P. Sauer | 2008 | Endoscopy2008，，09： | 2 |
| 15 | 磷脂酰胆碱缓释剂有益于慢性活动性溃疡性结肠炎患者 | Stremmel W. Merle U. Zahn A. 赵菊辉 | 2005 | 世界核心医学期刊文摘(胃肠病学分册)2005，0，10： | 2 |
| 16 | Genetic vaccination with Flt3-L and GM-CSF as adjuvants: Enhancement of cellular and humoral mmune responses that results in protective immunity in a murine model of hepatitis C virus infection显示文摘AIM: To investigate whether transfection of plasmid DNA encoding these cytokines enhances both humoral and cellular immune responses to hepatitis C virus (HCV) in a murine model. METHODS: We established a tumor model of HCV infection using syngenic mouse myeloma cells stably transfected with NS5. Co-vaccination of DNA encoding granulocyte macrophage colony-stimulating factor (GM- CSF) and Flt-3 ligand together with a plasmid encoding for the HCV NS5 protein was carried out. Mice were sacrificed 14 d after the last immunization event with collection of spleen cells and serum to determine humoral and cellular immune responses. RESULTS: Co-vaccination of DNA encoding GM-CSF and Flt-3 ligand together with a plasmid encoding for the HCV NS5 protein induced increased antibody responses and CD4+ T cell proliferation to this protein. Vaccination with DNA encoding GM-CSF and Flt-3L promoted protection against tumor formation and/or reduction in mice co- immunized with cytokine-encoding DNA constructs. This suggests this strategy is capable of generating cytotoxic T lymphocyte activity in vivo. Following inoculation withplasmid DNA encoding Flt-3L, no increase in spleen size or in dendritic cell (DC) and natural killer cell numbers was observed. This was in contrast to a dramatic increase of both cell types after administration of recombinant Flt3-L in vivo. This suggests that vaccination with plasmid DNA encoding cytokines that regulate DC generation and mobilization may not promote unwanted side effects, such as autoimmunity, splenic fibrosis or hematopoietic malignancies that may occur with administration of recombinant forms of these proteins. CONCLUSION: Our data support the view that plasmid DNA vaccination is a promising approach for HCV immunization, and may provide a general adjuvant vaccination strategy against malignancies and other pathogens. | Jens Encke Jomo Bernardin Jasmin Geib Gocha Barbakadze Raymond Bujdoso Wolfgang Stremmel | 2006 | World Journal of Gastroenterology2006，12，44： | 2 |
| 17 | Perspectives for gene therapy of Wilson disease 显示文摘 | Merle U Stremmel W Encke J | 2007 | Curr Gene Ther2007，7，3： | 1 |
| 18 | Procalcitonin is avalid marker of infection in decompensated cirrhosis 显示文摘 | CONNERT S STREMMEL W ELSING C | 2003 | ZGastroenterol2003，41，2： | 1 |
| 19 | Perspectives for gene therapy of Wilson disease显示文摘 | Merle U Stremmel W Encke J | 2007 | Curr Gene Ther2007，7，3： | 1 |
| 20 | Kinetics of thrombornodulin re- lease and endothelial cell injury by neutrophil-derived proteases and oxygen radical显示文摘 | Boehrne MW Galle P Stremmel W | 2002 | Immunology2002，107，3： | 1 |
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