scispace - formally typeset
Search or ask a question

Showing papers in "Zeitschrift Fur Gastroenterologie in 2006"


Journal Article
TL;DR: These guidelines are intended to give evidence-based recommendations for the use of EN in patients who have a complicated course during their ICU stay, focusing particularly on those who develop a severe inflammatory response, i.e. patients who has failure of at least one organ during theirICU stay.
Abstract: Enteral nutrition (EN) via tube feeding is, today, the preferred way of feeding the critically ill patient and an important means of counteracting for the catabolic state induced by severe diseases. These guidelines are intended to give evidence-based recommendations for the use of EN in patients who have a complicated course during their ICU stay, focusing particularly on those who develop a severe inflammatory response, i.e. patients who have failure of at least one organ during their ICU stay. These guidelines were developed by an interdisciplinary expert group in accordance with officially accepted standards and are based on all relevant publications since 1985. They were discussed and accepted in a consensus conference. EN should be given to all ICU patients who are not expected to be taking a full oral diet within three days. It should have begun during the first 24h using a standard high-protein formula. During the acute and initial phases of critical illness an exogenous energy supply in excess of 20-25 kcal/kg BW/day should be avoided, whereas, during recovery, the aim should be to provide values of 25-30 total kcal/kg BW/day. Supplementary parenteral nutrition remains a reserve tool and should be given only to those patients who do not reach their target nutrient intake on EN alone. There is no general indication for immune-modulating formulae in patients with severe illness or sepsis and an APACHE II Score >15. Glutamine should be supplemented in patients suffering from burns or trauma.

905 citations



Journal ArticleDOI
TL;DR: This review summarizes the knowledge about TGF-beta signal transduction in HSCs with special impact on Smad pathways and introduces hepatocyte plasticity and epithelial-to-mesenchymal transition in the liver as a potential feature of fibrogenesis and highlights possible action points of T GF-beta in these contexts.
Abstract: TGF-beta, acting both directly and indirectly, represents a central mediator of fibrogenic remodeling processes in the liver. Besides hepatic stellate cells (HSCs), which are induced by TGF-beta to transdifferentiate to myofibroblasts and to produce extracellular matrix, hepatocytes are also strongly responsive for this cytokine, which induces apoptosis during fibrogenesis and provides growth control in regeneration processes. Based on this, TGF-beta-mediated hepatic responses to injury are the result of a complex interplay between the different liver cell types. In this review we summarize the knowledge about TGF-beta signal transduction in HSCs with special impact on Smad pathways. We further describe a molecular cross-talk between profibrogenic TGF-beta and antifibrogenic IFN-gamma signaling in liver cells. Finally, we introduce hepatocyte plasticity and epithelial-to-mesenchymal transition in the liver, which is well established in tumorigenesis, as a potential feature of fibrogenesis and highlight possible action points of TGF-beta in these contexts.

150 citations


Journal ArticleDOI
TL;DR: It is described in this study that newly created LacZ knockin mice deficient for IL-23 p19 were highly susceptible for the development of experimental T cell-mediated TNBS colitis and showed even more severe colitis than wild-type mice by endoscopic and histologic criteria.
Abstract: Although IL-12 and IL-23 share the common p40 subunit, IL-23, rather than IL-12, seems to drive the pathogenesis of experimental autoimmune encephalomyelitis and arthritis, because IL-23/p19 knockout mice are protected from disease. In contrast, we describe in this study that newly created LacZ knockin mice deficient for IL-23 p19 were highly susceptible for the development of experimental T cell-mediated TNBS colitis and showed even more severe colitis than wild-type mice by endoscopic and histologic criteria. Subsequent studies revealed that dendritic cells from p19-deficient mice produce elevated levels of IL-12, and that IL-23 down-regulates IL-12 expression upon TLR ligation. Finally, in vivo blockade of IL-12 p40 in IL-23-deficient mice rescued mice from lethal colitis. Taken together, our data identify cross-regulation of IL-12 expression by IL-23 as novel key regulatory pathway during initiation of T cell dependent colitis.

120 citations


Journal ArticleDOI
TL;DR: This review will first provide a brief outline on the currently most accepted view of tumor progression and then discuss whether and how the rather new family of tetraspanin molecules might contribute to cancer progression.
Abstract: Tumors of the gastrointestinal tract -- gastric, colorectal, pancreatic and liver tumors -- account for over 50 % of cancer worldwide. The 5-year survival rate varies from > 50 % in colorectal to < 1 % in pancreatic cancer. The high cancer death rate strikingly correlates with the high metastasizing capacity of most gastrointestinal tumors. Therefore and because during the last decade several important hypotheses on metastasis formation could be settled on solid experimental ground, this review will first provide a brief outline on the currently most accepted view of tumor progression and then discuss whether and how the rather new family of tetraspanin molecules might contribute to cancer progression. Notably, some members of this family, in particular, CD82/KAI1 are known as metastasis suppressor genes, while others like CD151 and CO-029 are supposed to promote metastasis formation. The underlying mechanisms are beginning to become unraveled. Tetraspanins assemble complexes of different tetraspanins, integrins and additional transmembrane molecules in microdomains that serve as signaling platform. By creating proximity, tetraspanins modulate functional activity of the associating molecules. In addition, tetraspanins actively contribute to the intracellular traffic of the associating molecules that includes vesicular budding and formation of exosomes that are particularly rich in tetraspanins. Accordingly, the association of certain tetraspanins with the metastatic phenotype as well as the definition of other tetraspanins as metastasis suppressor genes has to be viewed from the perspective of molecular complexes rather than the individual tetraspanin.

49 citations


Journal ArticleDOI
TL;DR: The analyses identified significant genetic and epigenetic alterations in well-differentiated fore- and mid-gut NET and CIMP, similar to Ki-67, might turn out to be of prognostic relevance.
Abstract: Little is known about the molecular pathogenesis of neuroendocrine tumors (NET) of the gastro-entero-pancreatic (GEP) system. We analyzed genetic and epigenetic alterations as well as the CpG island methylator phenotype (CIMP). The study comprised 118 well-differentiated fore- and mid-gut GEP-NET from 71 patients. In addition to loss of heterozygosity (LOH), microsatellite instability (MSI) and the methylation status of various tumor associated genes were examined. The expression profile of p16, APC and MENIN was investigated by immunohistochemistry. None of the tumors was highly microsatellite unstable, LOH was found in 22.2%. Significant differences in promoter hypermethylation were identified in the RUNX3 and the O(6)-MGMT genes. We found a significant loss of p16 expression in insulinomas (p = 0.05) and functional NET (p = 0.01), respectively. APC was expressed less in gastrinomas (p = 0.01) and functional GEP-NET (p = 0.05) vs. nonfunctional tumors. MENIN expression was reduced in pancreatic vs. extrapancreatic NET (p = 0.008) and in insulinomas vs. nonfunctional GEP-NET (p = 0.019) and NET associated with the carcinoid syndrome (p = 0.029). Further CIMP and a Ki-67 index >10% showed a close correlation. Outcome analysis of 19 patients showed a better survival for CIMP-negative patients. The analyses identified significant genetic and epigenetic alterations in well-differentiated fore- and mid-gut NET. CIMP, similar to Ki-67, might turn out to be of prognostic relevance.

46 citations


Journal ArticleDOI
TL;DR: IL-22 promotes liver cell regeneration by increasing hepatic cell proliferation and hepatocyte migration through the activation of Akt and STAT signaling, which is abrogated by SOCS-1/3 overexpression.
Abstract: The IL-10-like cytokine IL-22 is produced by activated T cells. In this study, we analyzed the role of this cytokine system in hepatic cells. Expression studies were performed by RT-PCR and quantitative PCR. Signal transduction was analyzed by Western blot experiments and ELISA. Cell proliferation was measured by MTS and [(3)H]thymidine incorporation assays. Hepatocyte regeneration was studied in in vitro restitution assays. Binding of IL-22 to its receptor complex expressed on human hepatic cells and primary human hepatocytes resulted in the activation of MAPKs, Akt, and STAT proteins. IL-22 stimulated cell proliferation and migration, which were both significantly inhibited by the phosphatidylinositol 3-kinase inhibitor wortmannin. IL-22 increased the mRNA expression of suppressor of cytokine signaling (SOCS)-3 and the proinflammatory cytokines IL-6, IL-8, and TNF-alpha. SOCS-1/3 overexpression abrogated IL-22-induced STAT activation and decreased IL-22-mediated liver cell regeneration. Hepatic IL-22 mRNA expression was detectable in different forms of human hepatitis, and hepatic IL-22 mRNA levels were increased in murine T cell-mediated hepatitis in vivo following cytomegalovirus infection, whereas no significant differences were seen in an in vivo model of ischemia-reperfusion injury. In conclusion, IL-22 promotes liver cell regeneration by increasing hepatic cell proliferation and hepatocyte migration through the activation of Akt and STAT signaling, which is abrogated by SOCS-1/3 overexpression.

45 citations


Journal ArticleDOI
TL;DR: Under pathological situations, hypoxia appears to be a major determinant for liver diseases and cancer, and transcription factors of the HIF family are activated whereas USF proteins have the potential to counteract HIFs.
Abstract: Oxygen has important functions as substrate for biochemical reactions and as modulator of gene expression. In the liver, the physiologically occurring oxygen gradient is a major effector of metabolic zonation. In addition, cross-talks between the O2 signaling and nutrient signaling chains initiate a dynamic zonation pattern. Under pathological situations, hypoxia appears to be a major determinant for liver diseases and cancer. Thereby transcription factors of the HIF family are activated whereas USF proteins have the potential to counteract HIFs. In addition, feedback mechanisms between hypoxia, HIF and the IGF axes appear to exist. Thus, the knowledge of these mechanisms may help to initiate new therapies in diseases with disturbed O2 availability.

41 citations



Journal ArticleDOI
TL;DR: The data confirm that CC is a chronic disorder with a variable course of symptoms during a long-term follow-up and that it is benign with a resolution of diarrhea in up to 50 % of patients receiving anti-inflammatory treatment.
Abstract: Aim The aim of this study was to evaluate the long-term outcome of patients with collagenous colitis 10 years after the diagnosis. Patients and methods In 1989/1990, 65 patients were diagnosed to have collagenous colitis. Initially and after an interval of ten years these patients were asked to complete a questionnaire including onset and duration of diarrhea, stool frequency and consistency, other gastrointestinal symptoms including weight loss, drug history, treatment response and concomitant diseases. Results Questionnaires from 47 patients (72.3 %) (female 40; mean age 68 years, range 41 - 95 years) were available for analysis. After a follow-up of ten years, 11 patients (23.4 %) had persistent diarrhea with no change of frequency and consistency compared to baseline. Four patients (8.5 %) showed a reduction of diarrhea frequency of at least 50 %. Diarrhea was resolved in 23 patients (48.9 %) during the follow-up period. Of those, 20 patients received anti-inflammatory treatment. After a complete resolution of diarrhea during the long-term follow-up, 9 patients (19.2 %) showed recurrence of diarrheal symptoms. None of the patients developed any malignancies of the GI-tract. Conclusion The long-term outcome of CC is benign with a resolution of diarrhea in up to 50 % of patients receiving anti-inflammatory treatment. About 30 % of patients may experience persistent diarrhea even 10 years after diagnosis. Our data confirm that CC is a chronic disorder with a variable course of symptoms during a long-term follow-up.

32 citations



Journal ArticleDOI
TL;DR: In a post-marketing-surveillance study with the probiotic Escherichia coli strain Nissle 1917, EcN is frequently used in practice for the treatment of various, mostly gastrointestinal, complaints and is well tolerated.
Abstract: Introduction: Living microorganisms that enter the gut in an active state and exert a positive influence on the host are called probiotics. Numerous experimental and clinical studies were performed recently and confirm both the efficacy and modes of action of probiotic drugs. Patients and Methods: In a post-marketing-surveillance study with the probiotic Escherichia coli strain Nissle 1917 (EcN) data on the range of indications as well as on efficacy and tolerance were gathered prospectively in 446 centres. The intended treatment duration was limited to a maximum of 12 weeks. Results: EcN was used in 3807 patients with more than 20 different indications, n = 3511 of whom had gastrointestinal complaints: Among others, 1067 patients presented with chronically recurring (n = 728) or protracted diarrhoea (n = 339), 415 with inflammatory bowel disease, 679 with irritable bowel syndrome, and 253 with chronic constipation. The overall efficacy was assessed as good to very good by an average of 81.4 % of the therapists. The stool frequency and consistency as well as the symptoms of meteorism and abdominal pain were improved in very many patients. Suspected cases of side effects were documented in only 2.8 % of the patients. Conclusion: EcN is frequently used in practice for the treatment of various, mostly gastrointestinal, complaints and is well tolerated. Originalarbeit

Journal ArticleDOI
TL;DR: In the emergency-setting SEPS placement without fluoroscopy is feasible and the stent can be easily removed, and in contained perforations without severe mediastinitis of the mid esophagus the SEPS should be discussed as a gentle first-line therapy.
Abstract: Einleitung: Wir beschreiben unsere Erfahrung mit dem passageren Einsatz eines selbstexpandierenden Plastikstents (SEPS) bei Patienten mit nichtmaligner Osophagusleckage. Material und Methoden: Zwischen November 2001 und Mai 2005 wurden 10 Patienten mit einer iatrogenen Perforation (n = 4), einer Leckage nach einem osophagochirurgischen Eingriff (n = 5) und mehreren osophagomediastinalen Fisteln nach Laugenveratzung (n = 1) durch den passageren Einsatz eines SEPS behandelt. Bei 8/10 Patienten erfolgte die Stentplatzierung aufgrund der Notfallsituation ohne Durchleuchtungskontrolle. Die Stententfernung erfolgte mittels einer Stentfasszange. Ergebnisse: Die Leckagenlokalisation befand sich im proximalen (n = 1), mittleren (n = 6) und distalen (n = 3) Osophagus. Die mittlere Leckagengrose betrug 2 cm. Eine Stentplatzierung ohne Durchleuchtungskontrolle war in allen Fallen erfolgreich. Die mittlere Dauer der Stenttherapie betrug 55,5 Tage (Spanne 15 - 438 Tage). Ein Verschluss der Leckage zeigte sich nach komplikationsloser Stententfernung bei 7/10 Patienten. Insgesamt verstarben 4 Patienten wahrend der Nachbeobachtungszeit. Keiner dieser Todesfalle war stentassoziiert. Diskussion: Der passagere Einsatz eines SEPS ist eine sichere und erfolgreiche Methode zur Abdichtung nichtmaligner Osophagusleckagen. Eine Platzierung des Stents ohne Durchleuchtungskontrolle ist moglich. Bei Perforationen von begrenztem Ausmas und ohne ausgepragte Mediastinitis stellt der Einsatz eines SEPS eine schonende Primartherapie dar. Introduction: We report on our experience with the temporary use of a self-expanding plastic stent (SEPS) in the treatment of non-malignant esophageal leaks. Material and Methods: Between November 2001 and May 2005 ten patients with iatrogenic esophageal perforations (n = 4), post-surgical leaks (n = 5) and esophago-mediastinal fistulas after caustic injury (n = 1) were treated by temporary SEPS placement. In eight out of ten patients SEPS placement was done without fluoroscopy due to the emergency setting. Stent removal was performed with a rat-toothed forceps. Results: Leaks were located in the proximal (n = 1), middle (n = 6) and distal (n = 3) parts of the esophagus. The mean leakage size was 2 cm. Stent placement without fluoroscopy was always successful. The median duration of stent therapy was 55.5 days (range 15 438). In 7/10 cases the SEPS was readily removed, showing complete healing of the former leak. Four patients died during the follow-up. However, their deaths were not related to the stent therapy. Discussion: The temporary use of the SEPS represents a safe method for sealing benign esophageal leaks. In the emergency-setting SEPS placement without fluoroscopy is feasible and the stent can be easily removed. In contained perforations without severe mediastinitis of the mid esophagus the SEPS should be discussed as a gentle first-line therapy.

Journal ArticleDOI
TL;DR: The data show that the public opinion is wrong when pretending that hepatitis C today is just a disease of drug addicts, and demonstrates for the first time that many HCV-infected subjects in Germany have problems with their insurance and jobs.
Abstract: BACKGROUND Little is known as yet about the socio-economic consequences for patients with hepatitis C in Germany AIMS AND METHODS The study of the Deutsche Leberhilfe e V, supported by the federal hepatitis competence net, prospectively analyzed questionnaires about quality-of-life, education and work situation, insurance, and various other socio-economical aspects of patients with chronic hepatitis C The questionnaire included questions about the information status of patients concerning hepatitis C in general and their individual disease Overall, 1500 questionnaires were distributed by clinics, general practitioners, patient-support groups and via the internet; 714 were sent back and analyzed RESULTS Most of the 714 patients were born in Germany; 56 % were women and 44 % men, with a mean age of 52 years and a hepatitis duration of 18 years More than 60 % of subjects younger than 65 years of age did not have a regular job, and 27 % were already retired Only 47 % had a sufficient retirement insurance, whereas almost all had a health insurance Only 12 % had an insurance covering work invalidity, and of those who had applied for the latter insurance, it was denied in 29 % About 80 % of subjects reported that the hepatitis disturbed various aspects of their life Only 4 % considered the public knowledge about hepatitis C as good or very good, but 80 % as bad or very bad Of the subjects 40 % did not know how they had been infected; 37 % considered blood products as their infection mode, but only 10 % drug abuse Almost all subjects knew that HCV cannot be transmitted via shaking hands, use of bathrooms, kisses or food (< 1 %, respectively) Surgery (17 %) and the dentist (15 %), however, were mentioned relatively often as a major risk for infection About 80 % of subjects knew recent quantitative data on ALT and HCV-RNA, their genotype and the results of liver biopsy Both mental and physical scores in the SF12 questionnaire were markedly reduced by about one standard deviation in subjects with HCV infection when compared with the general German population Mental and physical scores deteriorated with increases in inflammatory and fibrosis scores Subjects with negative HCV-RNA and normal ALT had the best quality of life, whereas subjects with high levels of HCV-RNA and ALT had the worst CONCLUSIONS The data show that the public opinion is wrong when pretending that hepatitis C today is just a disease of drug addicts Our analysis demonstrates for the first time that many HCV-infected subjects in Germany have problems with their insurance and jobs German subjects are well informed about their infection including genotype, liver histology, ALT and HCV-RNA; on the other hand, there are information deficits and fears concerning the mode of infection The recent analysis clearly shows that HCV-infected subjects consider the public information about the HCV infection as catastrophically bad The recent data in addition show that elimination of HCV decisively ameliorates quality of life, whereas mental and physical health get increasingly worse with progressive liver disease and unsuccessful antiviral therapies

Journal ArticleDOI
TL;DR: Patients should be informed about the possible adverse event of a Listeria infection during anti-TNF- alpha therapy before receiving immunosuppressive treatment, and therapy with TNF-alpha inhibitors should only be executed within a close doctor-patient relationship and in cooperation with specialised centres.
Abstract: A 42-year-old man with steroid-dependent Crohn's disease developed fever, vomiting and headache after the second administration of infliximab. Extensive microbiological and biochemical work-up revealed an atypical meningitis caused by Listeria monocytogenes. After antibiotic therapy of 21 days duration, the patient could be discharged from hospital totally recovered without any further complications. As previously demonstrated, TNF-alpha plays an important role in resistance to Listeria monocytogenes. Listeria infections have been reported in 26 patients receiving TNF-alpha inhibitors. An additional therapy with other immunosuppressants increases the risk for Listeria infections. Listeria meningitis is a seldom adverse event of therapy with TNF-alpha inhibitors but is associated with a high lethality. Therefore patients should be informed about the possible adverse event of a Listeria infection during anti-TNF-alpha therapy before receiving immunosuppressive treatment. Furthermore, therapy with TNF-alpha inhibitors should only be executed within a close doctor-patient relationship and in cooperation with specialised centres.

Journal ArticleDOI
TL;DR: An algorithm is proposed for a modified screening in patients with type 2 diabetes for colorectal carcinoma, an entity that is well amenable to and can potentially be avoided by screening colonoscopy.
Abstract: Colorectal carcinoma is one of the most common tumour entities in Western countries. Colorectal carcinoma and type 2 diabetes mellitus share common risk factors. Recent epidemiological studies show an increased risk for colorectal carcinomas in patients with type 2 diabetes mellitus, even more pronounced at therapy with sulfonylureas or insulin. Moreover, a 3-fold risk increase for patients with insulin-dependent type 2 diabetes mellitus in comparison to the general population has been observed. The hyperinsulinaemia hypothesis is based on the premise that elevated plasma levels of insulin and free IGF-1 promote the proliferation of colon cells and lead to a survival benefit of transformed colon carcinoma cells. This is reflected by an altered tumour biology; in patients with type 2 diabetes, tumour progression is more rapid and tumour-associated mortality is increased. Colorectal carcinoma represents an entity that is well amenable to and can potentially be avoided by screening colonoscopy. Recommendations for colorectal carcinoma screening should employ the recent epidemiologic evidence. All patients with type 2 diabetes should be recommended to undergo colonoscopy before starting insulin therapy, and screening intervals should not exceed 5 years. This work provides a review of the evidence, and an algorithm is proposed for a modified screening in patients with type 2 diabetes.

Journal ArticleDOI
TL;DR: Prometheus therapy significantly improved refractory pruritus in all patients with elevated bile acid levels, but in some patients the clinical benefit was of short duration.
Abstract: OBJECTIVE Severe pruritus is a serious complication of cholestatic liver disease. Prometheus is a recently introduced extracorporeal liver support system with direct toxin adsorption of the patient's albumin fraction (FPSA; fractionated plasma separation and adsorption). Here we report on the effect of Prometheus therapy in patients with intractable cholestatic pruritus. MATERIAL AND METHODS Seven patients with different liver diseases and severe pruritus refractory to all medical treatment efforts for more than 4 weeks were treated with Prometheus (3-5 times, 18+/-3 h total). Pruritus intensity was assessed using the visual analogue scale (VAS; from 0 = no pruritus to 10 = unbearable pruritus), and VAS, serum bile acids and total bilirubin were evaluated directly before and after Prometheus treatment, as well as 4 weeks later. RESULTS After Prometheus therapy, VAS values had dropped significantly from 9+/-1 to 3+/-3 (p<0.001). Likewise, serum bile acids decreased (from 248+/-192 to 101+/-85 micromol/l; p<0.03). All patients, with the exception of one with no initial bile acid elevation, reported a pronounced improvement in pruritus with Prometheus therapy, although in two anicteric patients the amelioration lasted only a few days. In the other four patients a distinct benefit was still observed 4 weeks after the treatment. CONCLUSIONS Prometheus therapy significantly improved refractory pruritus in all patients with elevated bile acid levels, but in some patients the clinical benefit was of short duration. The clinical findings suggest that we have to better characterize those patients who might derive a long-lasting benefit from this invasive and expensive treatment.

Journal ArticleDOI
TL;DR: Experimental evidence strengthens the notion that the liver participates in the induction of oral tolerance, as liver sinusoidal endothelial cells are active in the uptake and cross-presentation of oral antigens from portal venous blood and engage inthe induction of CD8 T cell tolerance towards these antIGens.
Abstract: The liver is an organ with unique immune regulatory potential. This review highlights the experimental evidence for the involvement of hepatic cell populations in the induction of oral tolerance. Although immune tolerance towards oral antigens is mainly induced in the gastrointestinal tract within gut associated lymphatic tissue via generation of regulatory CD4 T cells, there is a further need for tolerance induction outside the gastrointestinal tract, because oral antigens rapidly distribute within minutes systemically through the blood stream. Besides hepatic dendritic cells, liver sinusoidal endothelial cells are active in the uptake and cross-presentation of oral antigens from portal venous blood and engage in the induction of CD8 T cell tolerance towards these antigens. These reports strengthen the notion that the liver participates in the induction of oral tolerance.

Journal ArticleDOI
TL;DR: It is concluded that torsion of the accessory lobes of the liver is a rare finding; radiological imaging does not reveal the diagnosis and most are found at laparotomy.
Abstract: Accessory lobes of the liver (ALL) may be congenital or acquired and are usually of no clinical significance. Torsions of the ALL are exceedingly rare and most are incidental findings at laparotomy, autopsy and in the course of investigation radiological investigations. A total of 17 infant and adult cases have been described previously in the medical literature. Most cases described since 1925 have been diagnosed at laparotomy, we report the 18 th case of torsion of the accessory lobe of the liver in an elderly female which, despite all radiological interventions, required laparoscopy for diagnosis. We conclude that torsion of the accessory lobes of the liver is a rare finding; radiological imaging does not reveal the diagnosis and most are found at laparotomy. Laparoscopy may aid in the diagnosis of torsion of accessory liver lobes. If pain persists, we advocate the use surgical intervention with or without cholecystectomy.

Journal ArticleDOI
TL;DR: The prevalence of chronic hepatitis C is low in the investigated cohorts of orthopaedic patients in Thuringia and Saxonia, however, elevation of aminotransferases occurs surprisingly often.
Abstract: INTRODUCTION: The prevalence of chronic hepatitis C in Germany is about 0.2 - 0.4 %. However, there seems to be regional differences between western and eastern states of the country. Thus, the present study analysed the prevalence of chronic hepatitis C in a cohort of orthopaedic patients in Thuringia. METHODS: Tests for antibodies against hepatitis C virus (anti-HCV) were performed on serum samples of 2026 patients (1183 females, 843 males) admitted for orthopaedic surgery to a university hospital in Thuringia. If anti-HCV was positive, serum was tested for HCV-RNA by polymerase chain reaction (PCR). For the sake of anonymity only age and gender were reported in all patients. In 1465 cases, values of alanine (ALT) and aspartate (AST) aminotransferases were additionally available. The low HCV prevalence was confirmed in a second cohort of orthopaedic patients (n = 929, 599 females, 330 males) investigated at a university hospital in Saxonia. RESULTS: In the Thuringian cohort, anti-HCV was detectable in 12/2026 (0.6 %) individuals (10 females (0.85 %) and 2 males (0.24 %: p = 0.14 %). HCV-RNA was positive in 3/10 of anti-HCV positive females (0.15 % of the study cohort). HCV infection was already known in two cases. Anti-HCV positive patients seemed to be older than anti-HCV negative individuals (64.25 vs. 59.48 years; p = 0.17), as well as HCV-RNA positive cases compared to non-viraemic patients (66.3 vs. 63.6 years; p = 0.32). All HCV-RNA positive females had elevated ALT values. However, ALT and AST were also elevated in 18.2 % and 11.7 % of anti-HCV negative individuals. There was no significant difference between males and females (p = 0.32). In the Saxonian cohort none of 929 individuals were HCV positive. CONCLUSION: The prevalence of chronic hepatitis C is low in the investigated cohorts of orthopaedic patients in Thuringia and Saxonia. However, elevation of aminotransferases occurs surprisingly often. The reasons for elevated aminotransferases and a reliable analysis of the HCV prevalence in different subgroups of the Eastern German population require further evaluation.


Journal ArticleDOI
TL;DR: It is suggested that Crohn's disease-related NAFLD may increase the vulnerability of the liver, which indicates that patients with a known history of CIBD merit special attention.
Abstract: Non-alcoholic fatty liver disease (NAFLD) commonly is associated with chronic inflammatory bowel disease (CIBD) and usually is considered to be stable and benign. However, NAFLD -- and in particular its subset, non-alcoholic steatohepatitis (NASH) -- may lead to progressive liver disease. Moreover, NAFLD sensitizes the liver to injury and increases the risk of developing acute-on-chronic liver failure following a "third hit". We here present one patient with NASH, as probably induced by long-standing Crohn's disease in the absence of ethanol consumption or abuse. The patient acquired an acute HBV infection and died from complications. As based on the clinical and histological findings, Crohn's disease appears to be a risk factor for developing NAFLD and thus to contribute to the progression into NASH. In conclusion, we suggest that Crohn's disease-related NAFLD may increase the vulnerability of the liver, which indicates that patients with a known history of CIBD merit special attention.

Journal ArticleDOI
TL;DR: Diagnosing Clostridium difficile-associated diarrhea should be based both on fecal-cytotoxin detection and culture and treatment with oral vancomycin should be reserved for patients who have contraindications or intolerance to or who have failed to respond to metronidazole.
Abstract: The incidence of antibiotic-associated diarrhea (AAD) differs with the antibiotic and varies from 15 - 25 %. Most cases of AAD are directly or indirectly caused by alterations of gut microflora by the antibiotics resulting in clinically mild AAD cases due to functional disturbances of intestinal carbohydrate or bile acid metabolism. Alternatively, changes in the gut flora allow pathogens to proliferate. Clostridium difficile is responsible for 10 - 15 % of all cases of AAD and almost of all cases of antibiotic-associated pseudomembraneous colitis. There is also a growing body of evidence which supports the responsibility of Klebsiella oxytoca for the development of antibiotic-associated hemorrhagic colitis. Diagnosing Clostridium difficile-associated diarrhea should be based both on fecal-cytotoxin detection and culture. With respect to specific therapy, metronidazol has become the first choice whereas treatment with oral vancomycin should be reserved for patients who have contraindications or intolerance to or who have failed to respond to metronidazole. Probiotics such as Sacharomyces boulardii can reduce the risk of development. Restrictive antibiotic policies (e. g. restricting clindamycin and cephalosporins) and the implementation of a comprehensive hospital infection control have also been shown to be effective in reducing the incidence of AAD.

Journal ArticleDOI
TL;DR: A 64-year-old man who presented to the outpatient clinic with HCC received palliative chemotherapy and finally died 15 months after initial diagnosis of HCC, with homozygosity for the Cys282Tyr mutation.
Abstract: The occurrence of primary hepatocellular carcinoma (HCC) in patients with hereditary hemochromatosis (HH) is well known. Thereby, the development of liver cirrhosis seems to be a prerequisite. Whether or not a hepatic iron overload in the context of hereditary hemochromatosis is an independent risk factor for HCC remains unclear. To date there are only a few reports about HCC arising in non-cirrhotic livers in the presence of HH. We report the case of a 64-year-old man who presented to our outpatient clinic with HCC. Liver cirrhosis could be excluded. Detailed exploration of the patient's history revealed that he had been treated by venesection for about 10 years up to 15 years ago. Subsequent investigations showed an elevated serum ferritin and transferrin saturation. The diagnosis of HH was confirmed by genetic testing, with homozygosity for the Cys282Tyr mutation. The patient received palliative chemotherapy and finally died 15 months after initial diagnosis of HCC.

Journal ArticleDOI
TL;DR: A case of severe Crohn's disease with an esophagobronchial fistula and the successful closure of the fistula tract with the novel liquid polymer sealant "Onyx" is presented and offers a new option for the treatment of this rare complication of Crohn’s disease.
Abstract: Esophageal involvement in Crohn's disease is very rare. In only a small subgroup of these patients -- up to date fourteen cases have been described in the literature -- the course of the illness may be complicated by esophageal fistula formation. The therapy for fistulizing esophageal Crohn's disease so far has been disappointing, recurrence and progression are likely, and surgery still is the primary treatment modality for refractory patients. We here present a case of severe Crohn's disease with an esophagobronchial fistula and the successful closure of the fistula tract with the novel liquid polymer sealant "Onyx". This approach offers a new option for the treatment of this rare complication of Crohn's disease and should be considered if surgery is not possible.

Journal ArticleDOI
TL;DR: The purpose of this representative community study was to survey attitudes toward transplantation in the German population and to identify underlying determinants and existing fears and concerns.
Abstract: The increasing deficit of organs causes a drastic decline in the quality of life and survival of numerous patients in need of a transplantation. The purpose of this representative community study was to survey attitudes toward transplantation in the German population and to identify underlying determinants. Unlike previous surveys, fears and concerns were elicited based on a concrete case vignette. Among the 1,002 participants, 90 % were in favour of organ donation in general; 21 % reported having signed an organ donor card. Consent to organ donation was associated with younger age and higher social class; the same was true for the possession of an organ donor card. In the virtual decision situation, the majority (77 %) voted in favour of an organ donation based on saving lives, consolation for bereaved and the absence of disadvantages for the donor. Common (up to 50 %), however, were also fears and concerns regarding determination of the time of death, displacement of medical concern from the donor to the recipient of the organ, utilisation of organs for other purposes, or explantation before death. The knowledge of the determinants identified, of existing fears and concerns are helpful not only for informing the public, but also for the dialogue with the next of kin of potential donors. Here, it may be helpful not only to address arguments pro organ donation, but also to address potential fears and concerns.

Journal ArticleDOI
TL;DR: New aspects of intestinal glial functions implicate new therapeutic strategies for diseases like Crohn's disease and irritable bowel syndrome.
Abstract: Enteric glia cells (EGCs) play an important role in the maintenance of tissue integrity in the gastrointestinal tract. Thus, genetic ablation of glial fibrillary acidic protein (GFAP)-positive EGCs in mice induced fatal haemorrhagic jejuno-ileitis and led to death within a few days. The exact mechanisms of EGC to contribute to gut homeostasis remain enigmatic. Several lines of evidence implicate that the secretion of neurotrophic factors by EGC may be a part of the glial regulation of gut homoeostasis. The secretion of glia cell-derived neurotrophic factor (GDNF), nerve growth factor (NGF) and transforming growth factor-beta (TGF-beta) contributes to the maintenance of epithelial integrity and the secretion of endothelins might be involved in vasoregulation. These new aspects of intestinal glial functions implicate new therapeutic strategies for diseases like Crohn's disease and irritable bowel syndrome.

Journal ArticleDOI
TL;DR: The present data strongly contrast previous data from Germany, and suggest that DLG5 113A is not associated with disease susceptibility, but there was a tendency for this allele to confer resistance to steroids.
Abstract: BACKGROUND Recent data suggest that haplotypic variants of the DLG5 gene on 10q23 are associated with susceptibility to inflammatory bowel disease (IBD) in Germany. In view of the geographical differences in frequency of genetic markers and the absence of data in Central European patients, our aim was to determine the DLG5 R30Q variant in Hungarian IBD patients. MATERIALS AND METHODS We investigated 773 unrelated IBD patients (age 38.1 +/- 10.3 years; duration, 8.8 +/- 7.5 years; Crohn's disease [CD]: 639; male/female, 309/330; duration, 8.4 +/- 7.1 years; ulcerative colitis [UC]: 134; male/female, 63/71; duration, 10.6 +/- 8.9 years) and 150 healthy subjects. DLG5 R30Q and TLR4 D299G variants were tested by polymerase chain reaction/restriction fragment length polymorphism. DNA was screened for NOD2/CARD15 mutations by denaturing high-performance liquid chromatography. Detailed clinical phenotype was determined by reviewing the medical charts. RESULTS The frequency of the R30Q variant allele was not significantly different in IBD (22.0%), CD (20.8%), and UC (27.6%) patients compared with healthy control subjects (28.0%). In CD, the 113A variant allele was associated with steroid resistance (16.3% vs noncarriers, 7.6%; odds ratio [OR], 2.4; 95% CI 1.3-4.5; P = 0.013). In a logistic regression model carriage of DLG5 R30Q, perianal involvement and frequent relapses were independently associated with steroid resistance. No phenotype-genotype associations were found in UC patients, although a trend toward more extensive disease was observed in carriers of the variant allele (OR = 2.1; 95% CI 0.95-4.4; P = 0.07). CONCLUSIONS The present data strongly contrast previous data from Germany. DLG5 113A is not associated with disease susceptibility, but there was a tendency for this allele to confer resistance to steroids. Further studies are required to evaluate the significance of DLG5 in other populations from geographically diverse regions.

Journal ArticleDOI
TL;DR: The importance of ultrasound to distinguish different aetiologies of diffuse liver diseases is relatively low, but it is a very sensitive means to detect complications of liver cirrhosis and can avoid the uncritical and sequential application of radiological imaging.
Abstract: Conventional B-mode and colour duplex imaging is the first choice imaging technique after history taking and physical examination and for the interpretation of laboratory parameters. In the hands of a gastroenterologist ultrasound has become an equally important diagnostic tool as endoscopy. The constantly evolving technique with its possibility of higher resolution by use of "harmonic imaging" and signal enhancement with contrast medium is the reason for a practically relevant review of the situation. Practical references will be given for diagnostics of the liver and portal system including the spleen. The significance of the sonographic diagnosis of "fatty liver" is critically discussed. The overall importance of ultrasound to distinguish different aetiologies of diffuse liver diseases is relatively low. Nevertheless, it is a very sensitive means to detect complications of liver cirrhosis. Portosystemic shunts and typical changes in blood vessel morphology can be diagnosed by colour duplex sonography and used as indirect signs of advanced damage to liver parenchyma. In addition, ultrasound has its value in the confirmation or exclusion of dilated bile ducts as well as in the detection and differentiation of circumscribed liver lesions. The characterisation of focal liver lesions by ultrasound is sufficient in typical cases. The use of ultrasound contrast media (signal enhancers) raises the rate of differentiation and can avoid the uncritical and sequential application of radiological imaging (computed tomography [CT] or magnetic resonance imaging [MRI]). If in doubt about the nature of a lesion, a histological diagnosis remains indispensable. The examination of the spleen and its feeding vessels is regularly done in cases of diffuse parenchymal liver disease when searching for its complications, e. g., portal hypertension. Focal spleen lesions can be observed especially in the context of lymphoma (infiltration) and other bone marrow diseases. Through the application of contrast media, changes of vascularisation (e. g., infarcts) can be visualised and traumatic lesions can be diagnosed more precisely.

Journal ArticleDOI
TL;DR: In the investigated German sample, no evidence of association of ABCB11 and LXRA to gallstone susceptibility was detected, and the gallstone trait is not allelic to progressive familial cholestasis at the ABCB 11 locus.
Abstract: Genetic susceptibility in the causation of gallbladder diseases was recognized as early as 1937. A major gallstone susceptibility locus (Lith1) was identified in 1995 by quantitative trait locus mapping in mice. Two attractive positional and functional candidate genes in LXRA and ABCB11 are located in this interval. ABCB11 is associated with progressive familial cholestasis. This study was undertaken to investigate LXRA and ABCB11 as candidate genes for gallstone disease in humans. Eight hundred and ten patients who underwent cholecystectomy for symptomatic gallstone disease (median age of onset, 50 years) were compared with 718 sex-matched control individuals. Control individuals were sonographically free of gallstones. Haplotype tagging and all known coding single nucleotide polymorphisms (SNPs) were genotyped for ABCB11 (n=29) and LXRA (n=10). The investigated high-risk patient sample provides a power of greater than 80% for the detection of odds ratios down to 1.55. No evidence of association of the two genes in the single point tagging markers, coding variants or in the sliding window haplotype analysis was detected (all nominal single-point P values>or=.08). In conclusion, in the investigated German sample, no evidence of association of ABCB11 and LXRA to gallstone susceptibility was detected. The gallstone trait is not allelic to progressive familial cholestasis at the ABCB11 locus. Systematic fine mapping of the Lith1 region is required to identify the causative genetic variants for gallstone in mice and humans.