Search

Bile acid processing in the long-term, bile duct obstructed rat liver was studied ex vivo. Twenty four and 72 h, respectively, after bile duct obstruction the isolated liver was perfused with taurodeoxycholate (16 nmol/min per g liver) the bile duct still being closed. Uptake, metabolism and regurgitation profile were traced by bolus injection of tritium-labeled bile acid; in addition, concurrent histological changes were examined by light- and electron microscopy. Ligation caused dilatation of the intrahepatic ductular branches and increased the serum bile acid concentration to 740 +/- 75 microM (controls: 16 +/- 2.12), reaching its maximum within 24 h. At 16 nmol/min per g liver uptake rate was96% in controls and in bile duct obstructed rats. Maximal uptake rates (assessed separately) differed between controls and bile duct obstructed rats (700 nmol/min per g liver vs. 460). Controls excreted more than 80% of labeled bile acid in bile within 10 min after bolus injection. Biliary recovery of label was virtually completed after 30 min. In bile duct obstructed rats excretion of label back to the perfusate effluent (regurgitation) started quantitatively 5 min after bolus application and peaked between 10 and 40 min; after 80 min, effluent recovery was incomplete (about 60% of bolus injected). Biliary bile acids of controls consisted of about 20% taurodeoxycholate-metabolites; bile acids in the perfusate effluent of bile duct obstructed rats of about 55%. The major metabolite in all animal groups was taurocholate; minor metabolites were tauroursocholate, tauro-3 alpha,7 = 0,12 alpha-cholanoic acid and 3-sulfo-taurodeoxycholate. Histologically, inflammation and periportal edema were present after 1 day of bile duct obstruction. After 3 days, marked proliferation of bile ductules was the dominant histological feature. It is concluded that during initial bile duct obstruction, bile acid processing is not altered, although ultrastructural alterations occur early.

Brainstem auditory (BAEPs) and somatosensory evoked potentials (SEPs) have been shown to be useful in detecting brainstem or cortical dysfunction in neurological diseases and in combination with other methods to diagnose brain death (37,38). These neurophysiological methods are simple and easy to perform. BAEPs and SEPs can even be easily recorded in intensive care units and guarantee a standardized examination. Moreover, these methods require no extensive patient cooperation and are not heavily influenced by learning effects. The role of BAEPs in the evaluation and diagnosis of hepatic encephalopathy is not clear. BAEPs are obviously strongly influenced by the etiology of liver disease and are normal in viral hepatitis, but prolonged in alcoholic liver disease, Wilson's disease or in hepatic coma (8,12). Unfortunately, BAEPs were not compared to psychometric tests. There was no clear-cut differentiation between various hepatic encephalopathy-gradings. At present, the use of BAEPs in the detection of subclinical hepatic encephalopathy cannot be recommended, whereas in comatose patients BAEPs can be useful as a prognostic marker and for follow-up examinations (12). Recently, Pozessere et al. (12) examined 13 comatose patients with advanced coma stages (Glasgow coma scale 5-10) and recorded unspecific changes in their EEG tracings. In all cases of hepatic coma and in one intoxicated patient they found prolongation of interpeak latencies. In addition, in this small study the interpeak latencies correlated well with the clinical outcome of the patients. Only two studies were performed using SEPs to detect neurophysiological alterations in hepatic encephalopathy (32,33). The design as well as the results of these studies are quite different. Despite the small number of patients (n = 10), the prolongation of late components in 50% of patients with hepatic encephalopathy stage 0 could be a promising result (32). The value of SEPs in detecting subclinical hepatic encephalopathy is rather undefined. The fact that the generation of SEPs is due to an activation of complex structures of the central nervous system justifies the need for further investigations with this modality. The recording of visual evoked potentials requires much more methodological and technical effort than the recording of BAEPs or SEPs. The discrimination between pattern reversal (PVEP) and flashlight (FVEP) stimulation is highly important for the proper interpretation of the published data. Most of the studies were done using FVEPs, which are in particular clinically relevant for comatose patients (31). The conclusions of the authors using FVEPs (22-25) are not supported by the American Electroencephalographic Society (31).(ABSTRACT TRUNCATED AT 400 WORDS)

A number of immunosuppressants are used in the treatment of IBD. They have different modes of action but most of them affect different cell types and all are able to increase the number of infections, in particular opportunistic infections. Some may also lead to an increased number of malignomas. This is of particular importance in a disease such as Crohn’s disease, which seems to be at least in part due to an immune deficiency. Data with regard to the differences of the effects of immunosuppressant combinations versus monotherapy are rare. Combinations with steroids, particularly, seem to pose a problem; however, an increased risk most probably also exists for other combinations. Therefore, in order to downregulate inflammation, we should use combined immunosuppression only if really necessary and only for short periods of time. The ultimate goal of the restitution of epithelial integrity and the maintenance of the mucosal barrier will better be achieved by other approaches.

The antiphospholipid syndrome (APS) was described in 1983 as a clinical entity characterized by venous and arterial thrombosis, thrombocytopenia, and recurrent fetal loss. The serological markers of APS are antiphospholipid antibodies (APLA) directed mainly against anionic phospholipids, usually cardiolipin but also phosphatidylserine. Some APLA exhibit lupus anticoagulant activity. Monoclonal gammopathy sometimes occurs with the presence of autoantibodies. In this paper, we describe a patient with the diagnosis of immunocytoma with an IgM, kappa paraprotein with apparent specificity against anionic phospholipids, and lupus anticoagulant activity, but no clinical signs of APS. We describe in this patient the presence of a high titer of monoclonal APLA, which does apparently not induce the clinical symptoms of APS. This might be indicative for the presence of pathogenic and nonpathogenic antiphospholipid antibodies.

Spontaneous bacterial peritonitis (SBP) is considered as result of bacterial translocation from the gastrointestinal lumen to the mesenteric lymph nodes and subsequent circulation. Variants of the NOD2 gene contribute to bacterial translocation and were associated with SBP in a recent study.We determined common NOD2 variants by TaqMan polymerase chain reaction and analysed the ascitic fluid neutrophil count and bacterial culture results in 175 prospectively characterized hospitalized patients with decompensated cirrhosis who underwent diagnostic paracentesis in two German centres.Ten patients presented with culture-positive SBP, 19 with culture-negative SBP and six had bacterascites. Minor allele frequencies for R702W, G908R and 1007fs in subjects with sterile non-neutrocytic ascites were 3.2, 2.5 and 2.5% respectively. Patients with SBP [odds ratio (OR) 2.7; P=0.036], culture-positive SBP (OR 6.0; P=0.012) and bacterascites (OR 6.0; P=0.050) were more often carriers of NOD2 variants than patients with sterile non-neutrocytic ascites. The mutations 1007fs and G908R were associated with culture-positive SBP (P ≤ 0.005) and R702W with bacterascites (P=0.014). There was no significant association of NOD2 variants with culture-negative SBP (OR 1.6; P=0.493). In logistic regression, previous SBP, a higher model for end-stage liver disease (MELD) score and the presence of a NOD2 variant were independent predictors of ascitic fluid infection. The median survival was insignificantly shorter in patients with NOD2 variants (268 vs. 339 days; P=0.386). In patients without hepatocellular carcinoma at study entry (N=148), NOD2 was a predictor of survival after adjustment for the MELD score and age (hazard ratio 1.89; P=0.045).NOD2 variants increase the risk for culture-positive SBP and bacterascites in cirrhosis and may affect survival.

Funktionsstorungen des Magen-Darm-Traktes treten haufig als unerwunschte Begleiterscheinungen bei kritisch kranken Patienten auf. Fehlende Mobilisation, unphysiologische Ernahrung oder der Einfluss diverser Medikamente konnen zu einer verzogerten Magen-Darm-Passage beim Intensivpatienten fuhren. Dabei spielt der gastroosophageale Reflux im Bereich des oberen Gastrointestinaltraktes eine wesentliche Rolle, generell gilt der paralytische Ileus als eine der Hauptkomplikationen bei Intensivpatienten und im Bereich des unteren Gastrointestinaltraktes die intestinale Pseudoobstruktion. Die intraabdominelle Druckerhohung bis hin zum intraabdominellen Kompartment spielt bei einigen Erkrankungen eine wesentliche Rolle und bedarf einer schnellen Therapie.

Background: Recently we found that migration of colonic lamina propria fibroblasts in Crohn's disease patients (CD-CLPF) from inflamed mucosa is significantly reduced as compared to control-CLPF. The behavior of CD-CLPFs isolated from fistulae and strictures was now investigated in detail. Methods: Initially migration assays for all CLPF cultures (CD-CLPF, fibrosis-CLPF, and fistula-CLPF) were performed in the modified 48-well Boyden chamber. Subsequently, for a migration assay more resembling the in vivo situation a 3D matrix model was developed. After seeding of cells into the 3D matrix the CLPF layer was wounded by an ERBIUM:YAG laser leading to circular cell rupture without effect on the extracellular matrix. Results: In the modified Boyden chamber migration of fistula-CLPF was significantly reduced compared to CD-CLPF. This was correlated with a decrease in FAK-protein expression, whereas in migrating fibrosis-CLPF an increase in FAK-protein expression, -autophosphorylation and migratory potential was found. This was confirmed in the 3D matrix wounding assay: Fistula-CLPF migrated less than CD-CLPF, whereas fibrosis-CLPF migrated significantly more in the 3D matrix wounding assay. Between 1 to 36 hours incubation time fibrosis-CLPF always displayed increased migration ability as compared to CD-CLPF. In contrast, fistula-CLPF migratory potential was always below that of CD-CLPF. Conclusions: Myofibroblasts isolated from inflamed, fibrostenotic, or fistulized CD mucosa differ in their migratory potential both in the modified Boyden chamber as well as in a 3D matrix model. These different migratory behaviors could be an explanation for impaired or excess wound healing and subsequently for fistula and fibrosis formation. (Inflamm Bowel Dis 2011;)

Background: A multicenter controlled study was performed to evaluate the effect of high doses of the low molecular weight protease inhibitor gabexate mesilate on mortality and complications associated with moderate and severe acute pancreatitis. Methods: Two hundred twenty-three patients from 29 hospitals were entered in the randomized, double-blind trial. Admission to the study was based on strict criteria excluding mild acute pancreatitis. The patients received placebo or 4 g gabexate mesilate per day intravenously for 7 days. All patients were followed up for 90 days after randomization. The analysis was based on 14 complications, including death. Results: There was no statistical difference in either mortality or complications associated with acute pancreatitis between the placeboand gabexate mesilate groups. Conclusions: The results show that gabexate mesilate was not effective in preventing complications and mortality in acute pancreatitis.

The angiotensin-converting enzyme (ACE)-inhibitor, cilazapril, is converted to its active metabolite, cilazaprilat, by ester hydrolysis in the liver. The pharmacokinetics and pharmacodynamics of a single 1 mg oral dose of cilazapril were investigated in 10 healthy volunteers and in 9 cirrhotic patients with compensated cirrhosis and portal hypertension. A significantly increased mean plasma peak concentration (40.0 ± 13.6 ng/ml vs. 25.5 ± 7.9 ng/ml; p p p p p p 24 h), however, ACE-inhibition was more pronounced in patients (at 72 h: 39.6 ± 6.9% vs. 23.5 ± 8.2%; p 80 vs.

As an experimental model for reduced liver function rats with surgical portacaval shunts (pcs) may be used. Carvedilol, a nonselective β-adrenoceptor antagonist with vasodilating activity, is extensively metabolised by phase I as well as phase II pathways. In order to study the stereoselective pharmacokinetics of carvedilol in liver disease, pcs and control rats were given rac-carvedilol intravenously and p.o. The carvedilol enantiomers and their conjugates were assayed in plasma, urine, and bile. Carvedilol was highly bound to plasma proteins; binding was reduced by pcs. In all groups, the plasma concentrations of (R)-carvedilol exceeded those of (S)-carvedilol significantly. In comparison to the control group the plasma concentrations of both enantiomers increased after pcs, while the difference between the stereoisomers decreased. The total clearance decreased proportionally to the decrease in liver weight (30%). Both the apparent oral clearance, as well as its stereoselectivity were reduced, by up to 90 and 43%, respectively. The biliary clearance of the parent drug after i.v. dosage increased in rats with pcs due to the reduced hepatic metabolism. © 1993 Wiley-Liss, Inc.

Fistulae or leakages of anastomotic junctions of the gastrointestinal tract used to be an indication for surgery. However, patients often are severely ill and endoscopic therapeutic options have been suggested to avoid surgical intervention. This is a retrospective analysis of fibrin glue application in the treatment of gastrointestinal fistulae or anastomotic leakages. The aim of this study was to investigate the value of fibrin glue in the treatment of gastrointestinal fistulae and leakages. From September 1996 to November 2002, 52 patients with gastrointestinal fistulae or insufficiencies have been treated endoscopically including the use of fibrin glue (Tissucol Duo S®, Baxter, Unterschleissheim, Germany). Clinical data comprising concomitant therapies and results were analysed by chart review. Twenty-six lesions were located in the oesophagus or gastroesophageal junction, 4 in the stomach, 7 in the small intestine, 13 colorectal and 2 in the pancreas. The duration of treatment ranged from 12 to 1,765 days. Two to 81 ml fibrin glue (median 8.5) was used in 1–40 sessions (median 4). All patients received antibiotics; additional endoscopic options were frequently applied. Endoscopic therapy cured 55.7% patients (n = 29); 36.5% (n = 19) were cured with fibrin glue as sole endoscopic option. In 23.1% (n = 12), surgical intervention became necessary. Patients without major infectious complications tended to have a higher cure rate without surgery (87.5% vs. 50%). Eleven patients died (21.1%). Endoscopic therapy is a valuable option in the treatment of fistulae and anastomotic insufficiencies of the gastrointestinal tract. It usually is applied repeatedly. Fibrin glue is a mainstay of this procedure. Major infectious complications seem to define a subgroup of patients with poorer outcome.

Many reports, mainly from the US and Canada but also a recent report from a center in Europe, have documented the increasing impact of Clostridium difficile infections in patients with inflammatory bowel disease (IBD) during the last years. To determine the prevalence of C. difficile infections in hospitalized IBD patients in a tertiary referral center in Germany, we conducted this retrospective analysis.Data of all IBD in-patients treated due to an acute flare of their IBD at the Department of Internal Medicine I of the University of Regensburg between January 1, 2001, and June 30, 2008, were analyzed. In patients with a concomitant diagnosis of C. difficile infection, further variables such as IBD-related treatment at the time of infection or outcome were examined.In total, 995 in-patients with IBD were treated in this hospital [638 patients with Crohn's disease (CD), 357 with ulcerative colitis (UC)] during the study period. Of these, 279 patients with CD and 242 patients with UC were admitted with an acute flare and suffering from diarrhea and abdominal pain. Only 10 of those were diagnosed as having a concomitant infection with C. difficile. Six patients were female and the median age was 49 years (range: 15-80). Six patients with C. difficile infections suffered from UC and 4 patients from CD, all with previous colonic involvement. Eight patients used immunosuppressive therapies; only 2 patients were treated with antibiotics before infection.In contrast to recent reports from other countries, only a low percentage of hospitalized patients with acute flares of their IBD were identified as having an underlying C. difficile infection in this German tertiary referral center. However, in IBD patients with an acute flare, a concomitant C. difficile infection should be excluded, especially in patients with immunosuppressive treatment and colonic involvement of their disease. Further research is needed to evaluate if regions with different risks of C. difficile infections exist and to find out more about potential reasons for this observation.

Background: A disturbed regulation of Toll-like receptor (TLR) signal transduction resulting in the exclusive activation of proinflammatory signaling pathways may be critical for the perpetuation of established chronic colitis. Glycogen synthase kinase 3-b (GSK3-b) was recently identified as an important regulator of TLR signaling mediating excessive inflammatory responses. The aim of this study was to assess the role of GSK3-b activity in chronic intestinal inflammation. Methods: Chronic colitis was induced by dextran sodium sulfate (DSS) treatment. Mice were treated intraperitoneally with phosphate-buffered saline (PBS), CpG-ODN, or GSK3-b inhibitors (SB216763, LiCl). Intestinal inflammation was evaluated by histologic analysis and cytokine secretion of mesenteric lymph node cells (MLC). Nuclear extracts of MLC and lamina propria mononuclear cells (LPMC) were analyzed for nuclear factor kappaB (NF-jB) and CREB activity. Murine and human intestinal immune cells were stimulated in vitro with CpG-ODN, lipopolysaccharide (LPS), or anti-CD3 with or without LiCl. Results: GSK3-b blockade significantly reduced chronic intestinal inflammation and even abolished the colitis-intensifying effects of CpG-ODN treatment. In vitro inhibition of GSK3-b reduced the proinflammatory phenotype of both murine and human intestinal immune cells from chronic inflamed tissue. In vivo blockade of GSK3-b resulted in a shift from NF-jB activity toward CREB activity in murine MLC and LPMC. Conclusions: Blockade of GSK3-b attenuates excessive proinflammatory TLR-mediated immune responses. GSK3-b inhibition therefore constitutes a promising therapeutic option for selectively reducing exaggerated intestinal immune reactions toward the luminal flora in inflammatory bowel disease. (Inflamm Bowel Dis 2010;16:1850–1858)

Background: Migration of colonic lamina propria fibroblasts (CLPF) is an important mechanism during wound healing in inflammatory bowel disease (IBD). The concentration of prostaglandin E2 (PGE2) is increased in the intestinal mucosa of IBD patients. We therefore investigated the role of PGE2 in CLPF migration. Methods: Primary cultures of CLPF were isolated from healthy controls and Crohn's disease patients. Migration assays were performed in the Boyden chamber and scratch assays. EP receptors, PGE2, intracellular cyclic adenosine monophosphate (cAMP), expression and distribution of F-actin, α-smooth muscle actin (SMA), and myosin light chain (MLC) were determined by immunoblotting, immunocytochemistry, and enzyme-linked immunosorbent assay (ELISA). Results: All four EP receptor subtypes were present on CLPF. PGE2 and agonists to the EP2 and EP4 receptor reduced the migration of CLPF. Blockade of the EP2 and the EP4 receptor inhibited the effect of PGE2 on CLPF migration. An increase in intracellular cAMP reduced CLPF migration. PGE2 increased the concentrations of cAMP in CLPF, with abrogation after addition of EP2 and EP4 receptor antagonists. PGE2 and forskolin decreased the expression of α-SMA and F-actin and reduced cell polarization and lamellipodium formation in a scratch assay. In addition, forskolin reduced the phosphorylation of MLC (pMLC) and led to lack of accumulation of pMLC in the leading edge of CLPF. Conclusions: PGE2 reduced the migration of CLPF via elevation of intracellular cAMP. Potential mechanisms are changes in expression of cytoskeletal proteins, failure of CLPF to polarize, and a decreased amount of pMLC. This might be a possible reason for the impairment of intestinal wound healing in IBD. Inflamm Bowel Dis 2010

Bolus impaction in the esophagus is a common indication for emergency endoscopy. The aim of this study was to determine the most common causes of esophageal bolus impaction. In this retrospective study, data of 54 patients (41 male, 13 female) with bolus impaction in the esophagus were analyzed. Type and localization of the bolus and the endoscopic extraction tool used were evaluated. In 48 of 54 patients (89%), biopsy samples were taken of the esophagus for histological examination. Mean age of the patients was 53 ± 20 years. Fourteen of 54 patients (26%) had experienced bolus impaction previously. Meat bolus (n = 35, 65%) was the most common cause of esophageal obstruction. In most cases, boluses were found in either the distal (n = 31) or the proximal (n = 18) esophagus. In 22 patients (41%), the bolus was pushed into the stomach by the endoscope. In most other cases the bolus, including foreign bodies, could be removed with the 5-arm polyp grasper or alligator forceps. Main causes of bolus impaction were eosinophilic esophagitis (n = 10) or reflux disease with or without peptic stenosis (n = 10), respectively. Bolus impaction is frequently correlated with eosinophilic esophagitis and reflux esophagitis; therefore, diagnostic workup should include esophageal biopsy sampling.

Background Cryptococcus neoformans is an encapsulated yeast and the most frequent cryptococcal species found in humans. Cryptococcosis is considered an opportunistic infection as it affects mainly immunosuppressed individuals. In humans, C. neoformans causes three types of infections: pulmonary cryptococcosis, cryptococcal meningitis and wound or cutaneous cryptococcosis. Case Presentation An 81-year-old woman developed severe necrotizing cellulitis on her left arm without any preceding injury. The patient had been treated with systemic corticosteroids over twenty years for rheumatoid arthritis (RA). Skin biopsies of the wound area were initially interpreted as cutaneous vasculitis of unknown etiology. However, periodic acid Schiff staining and smear analysis later revealed structures consistent with Cryptococcus neoformans, and the infection was subsequently confirmed by culture. After the initiation of therapy with fluconazole 400 mg per day the general condition and the skin ulcers improved rapidly and the patient was discharged to a rehabilitation facility. Subsequently surgical debridement and skin grafting were performed. Conclusions Opportunistic infections such as cryptococcosis can clinically and histologically mimic cutaneous vasculitis and have to be investigated rigorously as a differential diagnosis in immunosuppressed patients.

Non-alcoholic fatty liver disease (NAFLD) is considered as the most common liver disease in Western countries with still rising prevalence due to a lifestyle favoring the development of the metabolic syndrome. Aim: To investigate the prevalence of ultrasound-diagnosed NAFLD in patients with referral for sonographic examination of the abdomen, and to determine risk factors. Methods: After exclusion of patients with known liver disease or risk factors for secondary NAFLD, a total of 155 arbitrarily selected patients (mean age 53.6±17.4 years; 52.6% male) from the interdisciplinary ultrasound department of a German University Hospital were included in this prospective study. Each patient underwent a standardized ultrasound, anthropometric and biochemical examination. Results: The prevalence of ultrasound-diagnosed NAFLD was 40.0%. NAFLD-patients had significantly higher body mass index (BMI) and waist-to-hip ratio, higher rates of reported hypertension and diabetes mellitus, and lower HDL cholesterol serum levels. Furthermore, NAFLD-patients revealed significantly higher serum ALT levels (23.2±22.1 U/l vs. 15.0±8.2 U/l; p=0.001), lower AST/ALT ratio (1.76±0.79 vs. 2.11±0.94; p=0.019), and notably, decreased flow in the portal vein (22.9±6.3 cm/s vs. 26.7±10.5 cm/s; p=0.011). Multivariate analysis revealed BMI (odds ratio (OR): 14.05; 95% Confidence interval (CI): 3.3-59.8), AST/ALT ratio (OR: 0.39; CI: 0.18-0.82), and HDL-C (OR: 4.33; CI: 1.6-11.9) as independent risk factors. Conclusions: Ultrasound-diagnosed NAFLD is frequent in patients with referral for ultrasound examination of the abdomen, and our findings further support that NAFLD is the hepatic manifestation of the metabolic syndrome with obesity being the most important risk factor.

Inflammatory bowel diseases are chronic inflammatory diseases that comprise of two forms - Crohn's disease (CD) and ulcerative colitis (UC) - characterized by aberrant responses to luminal bacteria in genetically susceptible individuals. Whereas inflammation is limited to the large intestine in patients with UC, CD can affect all parts of the gastrointestinal tract. During disease exacerbations, pharmacological or surgical intervention is usually needed to re-establish remission; however, current therapeutic interventions cannot cure CD. As a subgroup of patients with CD will not be able to remain in remission with available drugs or suffer from side effects, new therapeutic strategies are needed.This review focuses on emerging drugs in the treatment of CD and reviews data on their efficacy and safety. An extensive review of the available literature was undertaken using MEDLINE to identify relevant studies.The reader will learn about current therapeutic strategies in patients with CD and gain insights into emerging new drugs.As modification of the clinical course of CD becomes the therapeutic paradigm, potential future treatments have to induce mucosal healing in order to prevent long-term complications. New biologics show promising results.

AIM: To explore the role of heat shock protein-90 (HSP-90) for nitrergic vasorelaxation in the splanchnic circulation in rats with and without portal hypertension. METHODS: Neuronal nitric oxide synthase (nNOS) and HSP-90 were analyzed by immunofluorescence, western blotting and co-immunoprecipitation in the mesenteric vasculature and isolated nerves of portal-vein-ligated (PVL) rats and sham operated rats. In vitro perfused de-endothelialized mesenteric arterial vasculature was preconstricted with norepinephrine (EC80) and tested for nNOS-mediated vasorelaxation by periarterial nerve stimulation (PNS, 2-12 Hz, 45V) before and after incubation with geldanamycin (specific inhibitor of HSP-90 signalling, 3 μg/mL) or L-NAME (non-specific NOS-blocker, 10-4 mol/L). RESULTS: nNOS and HSP-90 expression was significantly increased in mesenteric nerves from PVL as compared to sham rats. Moreover, nNOS and HSP-90 were visualized in mesenteric nerves by immunofluorescence and immunoprecipitation of nNOS co-immunoprecitated HSP-90 in sham and PVL rats. PNS induced a frequency-dependent vasorelaxation which was more pronounced in PVL as compared to sham rats. L-NAME and geldanamycin markedly reduced nNOS-mediated vasorelaxation abrogating differences between the study groups. The effect of L-NAME and geldanamycin on nNOS-mediated vasorelaxation was significantly greater in PVL than in sham animals. However, no difference in magnitude of effect between L-NAME and geldanamycin was noted. CONCLUSION: HSP-90 acts as a signalling mediator of nNOS-dependent nerve mediated vascular responses in mesenteric arteries, and the increased nitrergic vasorelaxation observed in portal hypertension is mediated largely by HSP-90.

Background Pfeifer-Weber-Christian disease (PWCD) is a rare inflammatory disorder of the subcutaneous fatty tissue. The diagnosis and therapy of this rare type of panniculitis is still controversial and will be discussed in this article. Case presentation We here report the rare case of a 64-year old male patient, with PWCD. The patient suffered from rheumatoid arthritis for several years, but then developed relapsing fever and recently occurring painful subcutaneous nodules predominantly at the inner part of his left upper limb with no signs of synovitis. Finally, a biopsy from one of the nodules revealed lobular panniculitis with mixed cell infiltrate, which was conformable only with PWCD, after excluding several differential diagnoses. In our patient PWCD developed despite immunosuppressive therapy with steroids and different disease modifying drugs, which the patient received to treat his underlying rheumatoid arthritis. However, when DMARD therapy was switched to Ciclosporin A the patient's symptoms resolved. Conclusion Our observation supports the hypothesis that T cells are involved in the pathogenesis of PWCD. Thus, T cell modifying drugs should be primarily used to treat patients with this rare disorder.

Xanthohumol (XN) is a major prenylated chalcone found in hops, which is used to add bitterness and flavor to beer. In this study, we first investigated the effects of XN on hepatocytes and hepatic stellate cells (HSC), the central mediators of liver fibrogenesis. XN inhibited the activation of primary human HSC and induced apoptosis in activated HSC in vitro in a dose dependent manner (0-20 microM). In contrast, XN doses as high as 50 microM did not impair viability of primary human hepatocytes. However, in both cell types XN inhibited activation of the transcription factor NFkappaB and expression of NFkappaB dependent proinflammatory genes. In vivo, feeding of XN reduced hepatic inflammation and expression of profibrogenic genes in a murine model of non-alcoholic steatohepatitis. These data indicate that XN has the potential as functional nutrient for the prevention or treatment of non-alcoholic steatohepatitis or other chronic liver disease.

Peroxisome proliferator-activated receptor-gamma and cyclooxygenase-2 are ­frequently overexpressed on cholangiocarcinoma (CC) cells and adjacent stroma cells, and might be potential therapeutic targets. A pilot phase II trial was started to analyze the activity of angiostatically scheduled chemotherapy, capecitabine 2 × 1 g/m2from day 15 to 28 every 3 weeks combined with an antiinflammatory/angiostatic therapy, daily 45 mg oral pioglitazone and 25 mg oral rofecoxib day 1+ in advanced CC. All 21 consecutively included patients (mean age 64 years) suffered from non-resectable far-advanced CC, 62% were pretreated. The median dose of capecitabine per cycle was 76% of that planned; the median duration of treatment was 6.8 months (range 2 to 30+). Only three patients suffered from grade 3 toxicity (hand-foot syndrome n = 2, edema n = 1). Therapy continuation was refused in one patient with HFS grade 3. Objective response was achieved in 29% of the cases including one cCR, 29% achieved SD >6 months. Median overall survival was 8 months. The median overall survival in this unselected, partially pretreated patient population compares to that observed in selected patient populations receiving second generation combination chemotherapies which were shown to be accompanied with considerable hematotoxicity. The present completely oral therapy approach combines convenience, low toxicity and efficacy, and fits to the general patients characteristics: elderly patients with tumor-associated comorbidity. Randomized trials will definitely clarify the impact of antiinflammatory treatment strategies on survival.

Introduction We report the first case of a patient who underwent simultaneous kidney and pancreas transplantation and who then suffered from repeated episodes of severe gastrointestinal bleeding over a period of seven years. Locating the site of gastrointestinal bleeding is a challenging task. This case illustrates that detection of an arterio-enteric fistula can be very difficult, especially in technically-challenging situations such as cases of severe intra-abdominal adhesions. It is important to consider the possibility of arterio-enteric fistulas in cases of intermittent bleeding episodes, especially in transplant patients. Case presentation A 40-year-old Caucasian man received a combined pancreas-kidney transplantation as a result of complications from diabetes mellitus type I. Thereafter, he suffered from intermittent clinically-relevant episodes of gastrointestinal bleeding. Repeat endoscopic, surgical, scintigraphic, and angiographic investigations during his episodes of acute bleeding could not locate the bleeding site. He finally died in hemorrhagic shock due to arterio-enteric bleeding at the kidney graft site, which was diagnosed post-mortem. Conclusions In accordance with the literature, we suggest considering the removal of any rejected transplant organs in situations where arterio-enteric fistulas seem likely but cannot be excluded by repeat conventional or computed tomography-angiographic methods. Arterio-enteric fistulas may intermittently bleed over many years.

Ascites and plasma concentrations of soluble tumor necrosis factor receptors p55 and p75 were measured in a prospective study in 34 patients (35 occasions of ascites) with hepatic (5 infected and 21 uninfected) and malignancy-related (9) ascites. All patients had high concentrations of both soluble tumor necrosis factor receptors in ascites and plasma; these were about 500 times higher than the corresponding tumor necrosis factor-α concentrations. Ascites levels of soluble tumor necrosis factor receptors p55 and soluble tumor necrosis factor receptors p75 were significantly elevated in patients with malignancy-related (p55: 26.0 ± 8.6 ng/ml; p75: 20.5 ± 17.4 ng/ml; mean S.D.) and infected ascites (p55: 25.1 ± 10.9 ng/ml, p75: 22.6 ± 11.0 ng/ml) compared with patients with uncomplicated hepatic ascites (p55: 10.1 ± 4.4 ng/ml; p75: 6.0 ± 2.6 ng/ml). Patients with infected or malignancy-related ascites also showed higher soluble tumor necrosis factor receptor concentrations in plasma than did patients with plain hepatic ascites. Successful antibiotic treatment of peritonitis reduced soluble tumor necrosis factor receptor p55 and p75 ascites levels in three patients from 24.2 ± 15.2 ng/ml to 10.7 ± 1.9 ng/ml and from 20.2 ± 14.4 ng/ml to 7.5 ± 1.8 ng/ml, respectively. Soluble tumor necrosis factor receptors p55 and p75 at cutoff levels of 16.5 ng/ml and 9.5 ng/ml, respectively, differentiated between infected or malignant and plain hepatic ascites with diagnostic accuracies of 94% and 89%, respectively. They did not differentiate between infected and malignant ascites. The concentrations of soluble tumor necrosis factor receptor p55 were usually higher in ascites than in plasma in all subgroups of patients. Levels of soluble tumor necrosis factor receptor p75 were also higher in ascites than in plasma in patients with malignant and infected ascites, but soluble tumor necrosis factor receptor p75 levels were usually higher in plasma than in ascites in patients with uncomplicated hepatic ascites. The concentrations of both tumor necrosis factor receptors correlated well in ascites (r = 0.83, p < 0.001) and plasma (r = 0.85, p < 0.001) but only weakly with tumor necrosis factor-α levels in ascites (p55: r = 0.32, p = 0.03; p75: r = 0.29, p = 0.047) and not with tumor necrosis factor-α in plasma. The high soluble tumor necrosis factor receptor concentrations found in ascites may influence the local bioavailability of tumor necrosis factor and might have an impact on the treatment of peritoneal carcinomatosis with recombinant tumor necrosis factor. Furthermore, the determination of soluble tumor necrosis factor receptors could be of value for the differential diagnosis of ascites. (HEPATOLOGY 1992;16:749–755.)

The ascites and serum concentrations of interleukin-6 (IL-6) and interleukin-1 (IL-1) were determined in 21 patients with hepatic ascites and in 9 patients with malignancy-associated ascites. There was no evidence for bacterial peritonitis in any patients. All ascites samples contained high amounts of immunoreactive IL-6 [hepatic ascites 1730 +/- 2130 pg/ml (mean +/- SD), 1160 pg/ml (median); malignant ascites 4020 +/- 1510 pg/ml (mean), 3820 pg/ml (median)] but no IL-1. The mean ascites to serum ratios of IL-6 were 96 (median 49) in patients with hepatic ascites and 587 (median 480) in patients with malignant ascites. Ascites IL-6 was biologically active as determined by the B9 cell bioassay. The results indicate that even in the absence of infection IL-6 is produced in high amounts in the peritoneal cavity of patients with hepatic or malignant ascites.

It has been suggested that leucocytes play an important role in the pathogenesis of complicated pancreatitis. Indeed, increased plasma concentrations of neutrophil elastase as a marker of neutrophil activation could be detected in patients with a severe course of the disease. Recently, interleukin-8 (IL-8) has been described as a novel neutrophil activating peptide. To determine the role of IL-8 in acute pancreatitis we measured its serum concentrations by a specific enzyme-linked immunosorbent assay in 10 patients with acute pancreatitis daily during the first week of hospitalization. IL-8 levels were compared with plasma concentrations of neutrophil elastase and the clinical course of the disease. Three of the patients had uncomplicated pancreatitis, while seven showed various extrapancreatic complications. Patients with complicated pancreatitis had statistically significant (P less than 0.05) higher mean values of IL-8 (121 +/- 41 pg/ml-1 vs. 13 +/- 6 pg ml-1, mean +/- SEM) and neutrophil elastase (547 +/- 35 ng ml-1 vs. 250 +/- 20 ng ml-1) than patients with uncomplicated disease. There was a positive correlation (r = 0.52, P less than 0.0001) between IL-8 and neutrophil elastase in the lower concentration range of IL-8 (less than 100 pg ml-1). At IL-8 levels greater than 100 pg ml-1 neutrophil elastase was always greatly elevated; however, under these conditions the relationship between IL-8 and elastase was no longer linear. No measurable IL-8 concentrations were found when plasma elastase was less than 200 ng ml-1. During follow-up, initially elevated IL-8 concentrations decreased in correlation with clinical improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased serum concentrations of acute-phase proteins can be found in active inflammatory bowel disease. Because interleukin 6 (IL-6) is one of the main mediators of acute-phase protein synthesis by the liver, the serum concentrations of IL-6 and the acute-phase proteins C-reactive protein, alpha 1-antitrypsin, and alpha 1-acid glycoprotein were determined in 70 patients with Crohn's disease (CD) and 23 patients with ulcerative colitis (UC). Disease activities were determined by established clinical activity indices. Serum IL-6 concentrations were significantly (P less than 0.005) increased in patients with CD (mean +/- SEM, 6.8 +/- 0.9 U/mL) compared with patients with UC (mean, less than 4 U/mL) and healthy controls (mean, less than 4 U/mL). Of patients with CD, 68.5% had serum IL-6 concentrations of greater than or equal to 4 U/mL, compared with 21.7% of patients with UC and 0% of healthy controls. There was a tendency toward higher serum IL-6 concentrations in patients with active CD than in patients with inactive disease. However, these differences were not statistically significant. There was no correlation between IL-6 serum concentrations and clinical activity indices, possibly because of the short circulatory lifetime and rapid hepatic clearance of IL-6 from the portal venous blood. In contrast to serum IL-6, acute-phase proteins, which have a longer circulatory lifetime, were significantly correlated with clinical activity indices. Only the follow-up of individual patients with initially highly active disease showed a further increase in IL-6 levels during acute exacerbations of the inflammatory process. The results show that most patients with even moderately active CD have significantly increased serum concentrations of IL-6, most probably reflecting a continuous stimulation of IL-6-producing cells.

To validate cardiovascular alarms in critically ill patients in an experimental setting by generating a database of physiologic data and clinical alarm annotations, and report the current rate of alarms and their clinical validity. Currently, monitoring of physiologic parameters in critically ill patients is performed by alarm systems with high sensitivity, but low specificity. As a consequence, a multitude of alarms with potentially negative impact on the quality of care is generated.Prospective, observational, clinical study.Medical intensive care unit of a university hospital.Data from different medical intensive care unit patients were collected between January 2006 and May 2007.Physiologic data at 1-sec intervals, monitor alarms, and alarm settings were extracted from the surveillance network. Video recordings were annotated with respect to alarm relevance and technical validity by an experienced physician. During 982 hrs of observation, 5934 alarms were annotated, corresponding to six alarms per hour. About 40% of all alarms did not correctly describe the patient condition and were classified as technically false; 68% of those were caused by manipulation. Only 885 (15%) of all alarms were considered clinically relevant. Most of the generated alarms were threshold alarms (70%) and were related to arterial blood pressure (45%).This study used a new approach of off-line, video-based physician annotations, showing that even with modern monitoring systems most alarms are not clinically relevant. As the majority of alarms are simple threshold alarms, statistical methods may be suitable to help reduce the number of false-positive alarms. Our study is also intended to develop a reference database of annotated monitoring alarms for further application to alarm algorithm research.

To investigate a genetic polymorphism of the monocyte chemotactic protein-1 (MCP-1) gene in patients with spontaneous bacterial peritonitis (SBP).MCP-1 genotyping was performed in 23 patients with SBP and 83 cirrhotic control patients with non-infected ascites.The frequency of carriers of the G-allele was lower in SBP patients but this difference did not reach statistical significance. However, in the subgroup of patients with alcoholic cirrhosis (n = 80), carriers of the G-allele were significantly less frequent in SBP-patients (38.1%) than in cirrhotic controls (67.8%, P = 0.021).In patients with alcoholic liver cirrhosis, the -2518 MCP-1 genotype AA is a risk factor for the development of SBP.

Objective The purpose of this feasibility study was to prospectively evaluate an optimized multidetector computed tomographic protocol for the diagnosis of active obscure gastrointestinal bleeding (OGIB). Methods Between October 2006 and February 2008, patients admitted for active OGIB were included in this prospective unicenter study. Water was administered orally and rectally as neutral luminal contrast material. A contrast-enhanced 16-row multidetector computed tomography (MDCT) was performed in the arterial and venous phases. Mesenteric digital subtraction angiography was carried out immediately after MDCT as standard of reference. Results Six patients were included in this study. Multidetector computed tomography identified the bleeding site and source in 5 (83%) of the patients. Digital subtraction angiography was performed in 4 patients, and the result was positive in 1 (25%) of the patients. Multidetector computed tomography detected the site and source of bleeding in 2 patients whose digital subtraction angiographic result was negative. Conclusions The results of this feasibility study indicate that optimized MDCT is an excellent diagnostic tool for the diagnosis of active OGIB.

No detailed data are available on hepatic clearance, postprandial release, and distribution profile of metabolically active adipokines in splanchnic blood compartments such as portal and hepatic veins. This would be a prerequisite for understanding the role of visceral adipose tissue-derived adipokines in metabolism. Adiponectin, resistin, leptin, and visfatin concentrations were measured by enzyme-linked immunosorbent assay in peripheral veins, arterial blood, hepatic veins, and portal veins in 50 patients with liver cirrhosis undergoing transjugular intrahepatic portosystemic shunt implantation, in 6 patients with normal liver function, and in fasted and fed rats. Adiponectin, leptin, resistin, and visfatin did not differ among blood compartments in normal-weight probands in the fasted state. Adiponectin and leptin levels were similar in patients with and without liver cirrhosis. Systemic visfatin levels were decreased and resistin levels were increased in liver cirrhosis. Visfatin secretion was higher from visceral than from peripheral subcutaneous adipose tissue in liver cirrhosis. There was no hepatic clearance of visfatin. Leptin secretion was higher from peripheral than from visceral adipose tissue. Leptin did not undergo hepatic clearance. Resistin and adiponectin did not differ between blood compartments in liver cirrhosis. Resistin concentrations increased upon feeding in rats, and there was an increase in the postprandial clearance of adiponectin by the liver. A postprandial increase of leptin concentrations was restricted to peripheral adipose tissue in rats. The results give insight into the dynamics of splanchnic adipokine concentrations and help critically interpret data derived from messenger RNA expression studies.

Adiponectin is believed to exert hepatoprotective effects and induces CXCL8, a chemokine that functions as a survival factor, in vascular cells. In the current study, it is demonstrated that adiponectin also induces CXCL8 expression in primary human hepatocytes but not in hepatocellular carcinoma cell lines. Knock down of the adiponectin receptor (AdipoR) 1 or AdipoR2 by small-interfering RNA indicates that AdipoR1 is involved in adiponectin-stimulated CXCL8 release. Adiponectin activates nuclear factor (NF)-κB in primary hepatocytes and pharmacological inhibition of NF-κB, the p38 mitogen-activated protein kinase, and extracellular signal-regulated kinase (ERK) 1/ERK2 reduces adiponectin-mediated CXCL8 secretion. Furthermore, adiponectin also activates STAT3 involved in interleukin (IL)-6 and leptin-mediated CXCL8 induction in primary hepatocytes. Inhibition of JAK2 by AG-490 does not abolish adiponectin-stimulated CXCL8, indicating that this kinase is not involved. Pretreatment of primary cells with “STAT3 Inhibitor VI,” however, elevates hepatocytic CXCL8 secretion, demonstrating that STAT3 is a negative regulator of CXCL8 in these cells. In accordance with this assumption, IL-6, a well-characterized activator of STAT3, reduces hepatocytic CXCL8. Therefore, adiponectin-stimulated induction of CXCL8 seems to be tightly controlled in primary human hepatocytes, whereas neither NF-κB, STAT3, nor CXCL8 are influenced in hepatocytic cell lines. CXCL8 is a survival factor, and its upregulation by adiponectin may contribute to the hepatoprotective effects of this adipokine.

The presentation of scientific posters gives young scientists the opportunity to present their data in the setting of a medical congress. In preparation of the organization of the 116th Congress of the German Society of Internal Medicine (DGIM) 2010, the authors evaluated the poster rounds at the 115th Congress of the DGIM 2009 by using a questionnaire that was given to poster presenters, poster chairmen, and visitors. The authors sought to receive an instructive criticism for the organization in 2010.Distribution of questionnaires containing ten questions with preformulated response options and an additional field for further comments to all presenters, chairmen, and visitors of the poster rounds during the 115th Congress of the DGIM (April 2009).159 questionnaires were returned and evaluated. Almost all respondents quoted the poster presentation as being important for their scientific work (98%). In general, they were satisfied with the discussion at the poster rounds (83%). The amount of posters within one round was criticized by 41%, as was the inadequate adherence to time constraints and time frame and room conditions themselves.The poster exhibition of the 115th Congress of the DGIM 2009 was evaluated positively by most of the respondents to the survey. Nevertheless, helpful hints were retrieved as how to further improve poster rounds. They should be respected when planning the exhibition at the congress in 2010.

Despite the initial belief that non-alcoholic fatty liver disease is a benign disorder, it is now recognized that fibrosis progression occurs in a significant number of patients. Furthermore, hepatic steatosis has been identified as a risk factor for the progression of hepatic fibrosis in a wide range of other liver diseases. Here, we established an in vitro model to study the effect of hepatic lipid accumulation on hepatic stellate cells (HSCs), the central mediators of liver fibrogenesis. Primary human hepatocytes were incubated with the saturated fatty acid palmitate to induce intracellular lipid accumulation. Subsequently, human HSCs were incubated with conditioned media (CM) from steatotic or control hepatocytes. Lipid accumulation in hepatocytes induced the release of factors that accelerated the activation and proliferation of HSC, and enhanced their resistance to apoptosis, largely mediated via activation of the PI-3-kinase pathway. Furthermore, CM from steatotic hepatocytes induced the expression of the profibrogenic genes TGF-beta, tissue inhibitor of metallo-proteinase-1 (TIMP-1), TIMP-2 and matrix-metallo-proteinase-2, as well as nuclear-factor kappaB-dependent MCP-1 expression in HSC. In summary, our in vitro data indicate a potential mechanism for the pathophysiological link between hepatic steatosis and fibrogenesis in vivo. Herewith, this study provides an attractive in vitro model to study the molecular mechanisms of steatosis-induced fibrogenesis, and to identify and test novel targets for antifibrotic therapies in fatty liver disease.

Due to the novel reimbursement policies, hospitals face substantial conflicts regarding best patient care and optimal utilization of resources. In order to optimize patient treatment, a central patients admission (CPA) unit has been established.All patients electively referred to the hospital were primarily treated by a medical specialist at the CPA unit. According to an appropriateness evaluation protocol established with the medical service of the health insurances of Bavaria ("MDK-Bayern"), patients were treated as inpatients or outpatients. The impact of this novel admission procedure was assessed for a period of 30 months.Within 30 months following establishment of the CPA unit, 10% of the patients were treated as outpatients, whereas 90% of referred patients were admitted as inpatients. Nonetheless, numbers of inpatients increased by 20.7% after 24 months compared to 12 months following establishment of the CPA unit with a substantial increase of patients referred by external medical specialists. In addition, there were no cases of inappropriate admission.The CPA unit is an ideal instrument for treating patients cross-sectorally as well as more effectively and economically advocating reorganization. Establishment of a CPA unit leads to greater satisfaction among patients, referring physicians, and medical staff.

Accelerated glycolysis is one of the biochemical characteristics of cancer cells. The glucose transporter isoform 1 (GLUT1) gene encodes a key rate-limiting factor in glucose transport into cancer cells. However, its expression level and functional significance in hepatocellular cancer (HCC) are still disputed. Therefore, we aimed to analyze the expression and function of the GLUT1 gene in cases of HCC. We found significantly higher GLUT1 mRNA expression levels in HCC tissues and cell lines compared with primary human hepatocytes and matched nontumor tissue. Immunohistochemical analysis of a tissue microarray of 152 HCC cases revealed a significant correlation between Glut1 protein expression levels and a higher Ki-67 labeling index, advanced tumor stages, and poor differentiation. Accordingly, suppression of GLUT1 expression by siRNA significantly impaired both the growth and migratory potential of HCC cells. Furthermore, inhibition of GLUT1 expression reduced both glucose uptake and lactate secretion. Hypoxic conditions further increased GLUT1 expression levels in HCC cells, and this induction was dependent on the activation of the transcription factor hypoxia-inducible factor-1alpha. In summary, our findings suggest that increased GLUT1 expression levels in HCC cells functionally affect tumorigenicity, and thus, we propose GLUT1 as an innovative therapeutic target for this highly aggressive tumor.

It was the aim to investigate the hypothesis that the new C1q/TNF-family member CTRP-3 (C1q/TNF-related protein-3) acts anti-inflammatory in human monocytes from healthy controls and patients with type 2 diabetes mellitus (T2D).Monocytes were isolated from 20 healthy controls and 30 patients with T2D. IL-6 and TNF concentrations were measured by ELISA. CTRP-3 was expressed in insect cells and used for stimulation experiments.Basal IL-6 and TNF were not different in control and in T2D monocytes. LPS-stimulation (1 microg/ml) significantly (p0.001) increased IL-6 and TNF in the supernatants of control and in T2D monocytes to a similar extent. CTRP-3 (1 microg/ml) significantly (p=0.03) inhibited LPS-induced IL-6 in control monocytes but not in T2D monocytes. TNF upon co-stimulation with LPS and CTRP-3 was significantly (p=0.012) lower in control than in T2D monocytes. LPS-induced TNF concentration was significantly and positively correlated with serum total cholesterol and LDL cholesterol in T2D patients.CTRP-3 inhibits LPS-induced IL-6 and TNF release. This anti-inflammatory effect is lost in T2D. Serum cholesterol concentration affects the pro-inflammatory potential of LPS to induce TNF release from T2D monocytes in the presence or absence of CTRP-3. CTRP-3 might partly account for the pro-inflammatory state in T2D.

A 17-year-old patient was transferred to the emergency room with an impacted food bolus by colleagues from the Department of Otorhinolaryngology. The examination of ear, nose and throat revealed significant amounts of saliva in both recessus piriformis, a radiologic examination of the esophagus showed a foreign body with a diameter of 1.6 cm in the region of the transitional zone of esophagus and stomach with a support level of the contrast medium. Clinical examination and laboratory tests showed no abnormalities. An emergency gastroscopy was performed. The foreign body, already evident in the barium swallow, was found in the distal esophagus. The foreign body was identified as a food bolus and gently advanced into the stomach with the aid of the gastroscope. In the stomach further food residues were detected and the examination was aborted because of increased risk of aspiration. On the next day, an elective gastroscopy was performed. Several biopsies were obtained from the esophagus because eosinophilic esophagitis (EE) was suspected due to clinical symptoms. Histological work-up showed a significant amount of eosinophilic granulocytes (15 eosinophils/HPF, 400 x) and reactive changes in the distal esophagus. Therefore, EE was diagnosed. Fluticasone therapy led to amelioration of symptoms and there was no evidence of recurring bolus impaction during follow-up.

Background: A frequent complication of Crohn's disease (CD) is the formation of strictures and stenoses. Strictures are characterized by a fibrosis of the bowel wall, induced by abnormal wound healing. Functional changes of colonic lamina propria fibroblasts (CLPF) reflected by increased proliferation and collagen synthesis, increased contractility or reduced migratory potential, indicate a change of the phenotype. We aimed to investigate differences in gene expression profiles between CLPF isolated from normal, inflamed and strictured areas of CD patients. Methods: We applied two methods of gene expression analysis, subtractive hybridisation and Affimetrix® microarrays to find differences in mRNA expression patterns. Findings were verified by dot blot analysis. Results: Using subtractive screening and dot blot analysis 74 clones could be confirmed to be differentially expressed in CD CLPF from nonstrictured areas compared to control CLPF. Fibronectin (transcript variant 1, NM_002026) could be confirmed as being upregulated in CD with a ratio of 143. Collagen (type I, NM_000089) was upregulated in CD with a ratio of 17. 41 clones could be confirmed as differentially expressed in CD CLPF derived from strictures compared to control CLPF. Five clones were identified as chitinase 3-like 1 (cartilage glycoprotein-39) and confirmed with dot blot with a ratio of 2.1. In an independent approach, microarray analysis showed upregulation of chitinase 3-like 1 (signal log ratio 1.9) in CD CLPF from strictures compared to control CLPF thus confirming subtractive hybridization. Conclusions: In the light of the current literature a number of interesting candidates resulted from the multiplicity of identified genes. In regard to the functional changes of CLPF during stenosis and other dysfunctions some proteins might represent a therapeutic target.

The long-term outcome of patients requiring resuscitation after cardiac arrest, whether in hospital or out of hospital, depends heavily on swift and appropriate care (1, 2). First aid courses, e.g., as part of the training for driving tests, or as further training in certain occupations, offer a wide variety of training in basic life support (BLS) for laypersons. In contrast to this, physicians in Germany are only required to undergo resuscitation training (RT) while they are still studying, as part of the procedure for registration to practice. Neither anesthetists nor doctors of internal medicine are required to refresh their knowledge of BLS and advanced cardiac life support (ACLS) as part of their continuing education. Resuscitation situations are quite rare in clinical practice, too rare to allow clinicians simply to acquire the necessary skills through experience over time (3). Several studies have shown knowledge of BLS and ACLS to be alarmingly low among physicians (4– 8). This study sets out to define what German-speaking hospitals offer in terms of in-hospital RT, what the training includes, and how it is carried out. In addition, it characterizes who usually performs the resuscitation.