bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of long term simvastatin administration as an adjunct to ursodeoxycholic acid: evidence for a synergistic effect on biliary bile acid composition but not on serum lipids in humans
Authors: Lanzarotto F , Panarotto B , Sorbara R , Panteghini M , Pagani F , Sosta S , Lanzini A 
Published: January 2010

BACKGROUNDStimulated bile acid synthesis preferentially utilises newly synthesised cholesterol, raising the posssiblity that combination of simvastatin (an inhibitor of cholesterol synthesis) with ursodeoxycholic acid (UDCA; a stimulator of bile acid synthesis) may result in reduced bile acid synthesis and greater enrichment of the pool with UDCA than that achieved with UDCA treatment alone.AIMSTo investigate the effect of simvastatin and UDCA given alone and in combination on serum and biliary lipid and biliary bile acid composition.METHODSEighteen patients with primary non-familial hypercholesterolaemia were studied during treatment with simvastatin 20 mg/day, UDCA 10 mg/kg/day, and a combination of the two drugs. Each regimen was given in random order for three months following a three month lead in period.RESULTSSimvastatin significantly reduced serum low density lipoprotein (LDL) cholesterol but biliary cholesterol concentration remained unchanged. Combination of the two drugs had no synergistic effect on serum cholesterol concentration, but significantly increased the proportion of UDCA in the bile acid pool from 35% during UDCA to 48% during combination treatment (p<0.04).CONCLUSIONSResults showed that: (1) simvastatin reduces serum LDL cholesterol but has no effect on biliary cholesterol concentration, supporting the concept that newly synthesised cholesterol is not the preferential source for biliary cholesterol; and (2) combination of simvastatin with UDCA has the predicted effect of enhancing the proportion of UDCA in the pool. This effect may be of benefit in the treatment of cholestatic liver diseases.
The role of apolipoprotein E and glucose intolerance in gallstone disease in middle aged subjects
Authors: Niemi M , Kervinen K , Rantala A , Kauma H , Päivänsalo M , Savolainen M J , Lilja M , Kesäniemi Y A 
Published: January 2010

BACKGROUNDThe polymorphism of apolipoprotein E has been suggested to be associated with the cholesterol content of gallstones, the crystallisation rate of gall bladder bile, and the prevalence of gallstone disease (GSD).AIMSTo investigate whether apolipoprotein E polymorphism modulates the susceptibility to GSD at the population level and to study the possible associations between impaired glucose tolerance, diabetes, and GSD.METHODSApolipoprotein E phenotypes were determined in a middle aged cohort of 261 randomly selected hypertensive men, 259 control men, 257 hypertensive women, and 267 control women. All subjects without a documented history of diabetes were submitted to a two hour oral glucose tolerance test (OGTT). GSD was verified by ultrasonography.RESULTSIn women with apolipoprotein E2 (phenotypes E2/2, 2/3, and 2/4) compared with women without E2 (E3/3, 4/3, and 4/4), the odds ratio for GSD was 0.28 (95% confidence interval 0.08–0.92). There was no protective effect in men. The relative risk for GSD was 1.2 (0.8–1.7) for hypertensive women and 1.8 (1.0–2.7) for hypertensive men. In a stepwise multiple logistic regression model, E2 protected against GSD in women, whereas two hour blood glucose in the OGTT, serum insulin, and plasma triglycerides were risk factors. Elevated blood glucose during the OGTT was also a significant risk factor for GSD in men.CONCLUSIONSThe data suggest that apolipoprotein E2 is a genetic factor providing protection against GSD in women. In contrast, impaired glucose tolerance and frank diabetes are associated with the risk of GSD.
The natural course of hepatitis C virus infection 18 years after an epidemic outbreak of non-A, non-B hepatitis in a plasmapheresis centre
Authors: Datz C , Cramp M , Haas T , Dietze O , Nitschko H , Froesner G , Muss N , Sandhofer F , Vogel W 
Published: January 2010

BACKGROUNDThe natural history of hepatitis C virus (HCV) infection is variable and factors determining the course of the illness are unclear. AIMSTo determine the natural course of HCV infection in a well characterised group of patients 18 years after an epidemic outbreak of non-A, non-B hepatitis at a plasmapheresis centre.METHODSBetween 1994 and 1996, 20 of 30 affected individuals were studied. HCV infection was confirmed using second and third generation ELISA test kits. HCV RNA was detected by a polymerase chain reaction (PCR) method and HCV genotyping was performed by analysing amplicons from the conserved 5′-non-translated region generated by nested PCR. Thirty two liver biopsies were carried out in 14 patients.RESULTSHCV antibodies were detected in all subjects. Eighteen patients had abnormal liver enzymes and 17 were HCV RNA positive, all of whom were infected with genotype 1a. Ninety per cent of this cohort showed evidence of chronic HCV infection with 50% having progressive liver disease and 20% cirrhosis 18 years after acute onset of non-A, non-B hepatitis. Considerable variation in disease outcome occurred between individuals and no correlation with clinical features of the acute illness was found.CONCLUSIONSVariability in the consequences of HCV infection in cases infected with the same virus suggests that host factors are important in determining disease outcome. The factors which determine differences in the natural history of the disease still remain to be elucidated.
Managing Budd-Chiari syndrome: a retrospective review of percutaneous hepatic vein angioplasty and surgical shunting
Authors: Fisher N C , McCafferty I , Dolapci M , Wali M , Buckels J A C , Olliff S P , Elias E 
Published: January 2010

BACKGROUNDThe role of percutaneous hepatic vein angioplasty in the management of Budd-Chiari syndrome has not been well defined. Over a 10 year period at our unit, we have often used this technique in cases of short length hepatic vein stenosis or occlusion, reserving surgical mesocaval shunting for cases of diffuse hepatic vein occlusion or failed angioplasty.AIMSTo review the outcome of angioplasty and surgical shunting to define their respective roles.PATIENTSAll patients treated by angioplasty or surgical shunting for non-malignant hepatic vein obstruction over a ten year period from 1987 to 1996.METHODSA case note review of pretreatment features and clinical outcome.RESULTSAngioplasty was attempted in 21 patients with patent hepatic vein branches and was succesful in 18; in three patients treatment was unsuccessful and these patients had surgical shunts. Fifteen patients were treated by surgical shunting only. Mortality according to definitive treatment was 3/18 following angioplasty and 8/18 following surgery; in most cases this reflected high risk status prior to treatment. Venous or shunt reocclusion rates were similar for both groups and were associated with subtherapeutic warfarin in half of these cases. Most surviving patients in both groups are asymptomatic although one surgical patient has chronic hepatic encephalopathy.CONCLUSIONWith appropriate case selection, many patients with Budd-Chiari syndrome caused by short length hepatic vein stenosis or occlusion may be managed successfully by angioplasty alone. Medium term outcome is good following this procedure provided that anticoagulation is maintained. Further follow up is required to assess for definitive benefits but we suggest that this should be included as a valid initial approach in the algorithm for management of Budd-Chiari syndrome.
Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification
Authors: Lundell L R , Dent J , Bennett J R , Blum A L , Armstrong D , Galmiche J P , Johnson F , Hongo M , Richter J E , Spechler S J , Tytgat G N J , Wallin L 
Published: January 2010

BACKGROUNDEndoscopic oesophageal changes are diagnostically helpful and identify patients exposed to the risk of disease chronicity. However, there is a serious lack of agreement about how to describe and classify the appearance of reflux oesophagitisAIMSTo examine the reliability of criteria that describe the circumferential extent of mucosal breaks and to evaluate the functional and clinical correlates of patients with reflux disease whose oesophagitis was graded according to the Los Angeles system.METHODSForty six endoscopists from different countries used a detailed worksheet to evaluate endoscopic video recordings from 22 patients with the full range of severity of reflux oesophagitis. In separate studies, Los Angeles system gradings were correlated with 24 hour oesophageal pH monitoring (178 patients), and with clinical trials of omeprazole treatment (277 patients).RESULTSEvaluation of circumferential extent of oesophagitis by the criterion of whether mucosal breaks extended between the tops of mucosal folds, gave acceptable agreement (mean κ value 0.4) among observers. This approach is used in the Los Angeles system. An alternative approach of grouping the circumferential extent of mucosal breaks as occupying 0–25%, 26–50%, 51–75%, 76–99%, or 100% of the oesophageal circumference, gave unacceptably high interobserver variation (mean κ values 0–0.15) for all but the lowest category of extent (mean κ value 0.4). Severity of oesophageal acid exposure was significantly (p<0.001) related to the severity grade of oesophagitis. Preteatment oesophagitis grades A–C were related to heartburn severity (p<0.01), outcomes of omeprazole (10 mg daily) treatment (p<0.01), and the risk for symptom relapse off therapy over six months (p<0.05).CONCLUSIONSResults add further support to previous studies for the clinical utility of the Los Angeles system for endoscopic grading of oesophagitis.
Corpus gastritis is protective against reflux oesophagitis
Authors: El-Serag H B , Sonnenberg A , Jamal M M , Inadomi J M , Crooks L A , Feddersen R M 
Published: January 2010

BACKGROUNDGastric acid is important in the pathogenesis of reflux oesophagitis. Acid production by the gastric corpus is reduced in corpus gastritis.AIMSTo determine whether corpus gastritis protects against reflux oesophagitis.METHODSPatients presenting for elective oesophagogastroduodenoscopy were studied. Two biopsy specimens were taken from the antrum, corpus, and cardia and stained with haematoxylin/eosin and Diff-Quick II stains. The presence and severity of gastritis were graded according to a modified updated Sydney classification.RESULTSOf 302 patients, 154 had endoscopic signs of reflux oesophagitis. There was no difference between patients with and controls without oesophagitis in the overall infection rates with Helicobacter pylori. Acute or chronic corpus gastritis occurred less often in patients with than those without reflux oesophagitis. Compared with controls, corpus gastritis was less severe in patients with reflux oesophagitis. The presence of acute or chronic gastritis in the corpus was significantly correlated with either type of gastritis in other areas of the stomach. In a multivariate logistic regression, age, sex, smoking status, and the presence of chronic corpus gastritis all exerted a significant influence on the presence of reflux oesophagitis. Chronic corpus gastritis was associated with a 54% reduced risk for reflux oesophagitis.CONCLUSIONSWhile infection withH pylori alone may not affect the occurrence of reflux oesophagitis, the development of chronic corpus gastritis seems to be protective.
A prospective randomised trial of a “test and treat” policy versus endoscopy based management in youngHelicobacter pylori positive patients with ulcer-like dyspepsia, referred to a hospital clinic
Authors: Heaney A , Collins J S A , Watson R G P , McFarland R J , Bamford K B , Tham T C K 
Published: January 2010

BACKGROUNDManagement of dyspepsia remains a controversial area. Although the EuropeanHelicobacter pylori study group has advised empirical eradication therapy without oesophagogastroduodenoscopy (OGD) in young H pylori positive dyspeptic patients who do not exhibit alarm symptoms, this strategy has not been subjected to clinical trial.AIMSTo compare a “test and treat” eradication policy against management by OGD.PATIENTSConsecutive subjects were prospectively recruited from open access OGD and outpatient referrals.METHODSH pylori status was assessed using the carbon-13 urea breath test.H pylori positive patients were randomised to either empirical eradication or OGD. Symptoms and quality of life scores were assessed at baseline and subsequent reviews over a 12 month period.RESULTSA total of 104H pylori positive patients aged under 45 years were recruited. Fifty two were randomised to receive empirical eradication therapy and 52 to OGD. Results were analysed using an intention to treat policy. Dyspepsia scores significantly improved in both groups over 12 months compared with baseline; however, dyspepsia scores were significantly better in the empirical eradication group. Quality of life showed significant improvements in both groups at 12 months; however, physical role functioning was significantly improved in the empirical eradication group. Fourteen (27%) in the empirical eradication group subsequently proceeded to OGD because of no improvement in dyspepsia.CONCLUSIONSThis randomised study strongly supports the use of empirical H pylori eradication in patients referred to secondary practice; it is estimated that 73% of OGDs in this group would have been avoided with no detriment to clinical outcome.
Synergistic effects of interferon γ and tumour necrosis factor α on T84 cell function
Authors: Fish S M , Proujansky R , Reenstra W W 
Published: January 2010

BACKGROUNDInflammatory bowel disease (IBD) is characterised by chronic intestinal inflammation and increased epithelial permeability. Both tumour necrosis factor α (TNF-α) and interferon γ (IFN-γ) have been implicated in IBD.AIMSTo understand better the effects of these cytokines on epithelial cell function.METHODST84 cells were cultured with IFN-γ and TNF-α and changes in transepithelial resistance (TER), fluorescein isothiocyanate (FITC) dextran flux, short circuit current (Isc), cystic fibrosis transmembrane conductance regulator (CFTR) protein levels, cell morphology, TNF receptor gene expression, and apoptosis were assayed.RESULTSRelative to controls, significant changes (p<0.05) occurred in cells incubated with IFN-γ for two days: TER was decreased to 20 (6.2)%, FITC–dextran flux was increased by 109 (19)-fold, cAMP and Ca dependentIsc were decreased to 51 (6.4)% and 24 (2.2)%, respectively, and CFTR levels were decreased to 47 (11)%. Cell morphology was altered but cell death was not induced. TNF receptor mRNA levels were increased. When added with IFN-γ, TNF-α accelerated IFN-γ dependent changes. Relative to controls, significant changes occurred after one day of culture with IFN-γ plus TNF-α: TER was decreased to 27 (3.5)%, FITC–dextran flux was increased by 185 (45)-fold, and cAMP and Ca dependentIsc were decreased to 66 (12)% and 35 (6.8)%, respectively. TNF-α also enhanced IFN-γ dependent changes in cell morphology but did not induce cell death.CONCLUSIONIFN-γ alters T84 cell epithelial properties and TNF-α can enhance these effects, perhaps due to IFN-γ dependent increases in TNF receptor gene expression. Overall, these studies suggest that in IBD, TNF-α may have synergistic effects on IFN-γ mediated alterations of epithelial cell function.
Reduced oxidative and nitrosative damage in murine experimental colitis in the absence of inducible nitric oxide synthase
Authors: Zingarelli B , Szabó C , Salzman A L 
Published: January 2010

BACKGROUNDOxidative and nitrosative stress have been implicated in the pathogenesis of inflammatory bowel diseases.AIMSTo study the role of nitric oxide (NO) derived from inducible NO synthase (iNOS) in an experimental model of murine enterocolitis.METHODSTrinitrobenzene sulphonic acid (TNBS) was instilled per rectum to induce a lethal colitis in iNOS deficient mice and in wild type controls. The distal colon was evaluated for histological evidence of inflammation, iNOS expression and activity, tyrosine nitration and malondialdehyde formation (as indexes of nitrosative and oxidative stress), myeloperoxidase activity (as index of neutrophil infiltration), and tissue localisation of intercellular adhesion molecule 1 (ICAM-1).RESULTSTNBS administration induced a high mortality and weight loss associated with a severe colonic mucosal erosion and ulceration, increased myeloperoxidase activity, increased concentrations of malondialdehyde, and an intense staining for nitrotyrosine and ICAM-1 in wild type mice. Genetic ablation of iNOS gene conferred to mice a significant resistance to TNBS induced lethality and colonic damage, and notably reduced nitrotyrosine formation and concentrations of malondialdehyde; it did not, however, affect neutrophil infiltration and intestinal ICAM-1 expression in the injured tissue.CONCLUSIONData show that activation of iNOS is required for nitrosative and oxidative damage in experimental colitis.
Strictures in Crohn’s disease are characterised by an accumulation of mast cells colocalised with laminin but not with fibronectin or vitronectin
Authors: Gelbmann C M , Mestermann S , Gross V , Köllinger M , Schölmerich J , Falk W 
Published: January 2010

BACKGROUND/AIMSIntestinal fibrosis and stricture formation is an unresolved problem in Crohn’s disease. The aim of this study was to investigate whether mast cells accumulate in these tissues and whether their localisation is associated with extracellular matrix components.METHODSMast cells were visualised by immunohistochemical staining of the mast cell specific proteases chymase and tryptase. Their localisation in relation to extracellular matrix components was shown by immunohistochemical double labelling.RESULTSIn strictures in Crohn’s disease, a striking accumulation of mast cells was seen particularly in the hypertrophied and fibrotic muscularis propria, with a mean (SEM) mast cell number of 81.3 (14.9)v 1.5 (0.9)/mm2 in normal bowel (p<0.0005). All mast cells in the muscularis propria were colocalised with patches of laminin. In contrast, in the submucosa, laminin was exclusively found in the basal lamina of blood vessels where many adherent mast cells were seen. No colocalisation of mast cells was found with fibronectin or vitronectin.CONCLUSIONSThe large accumulation of mast cells in the muscle layer of strictured bowel suggests a functional role for these cells in the hypertrophic and fibrotic response of the smooth muscle cells. The colocalisation with laminin indicates a mechanism of interaction between smooth muscle cells and mast cells that may be important in the role of mast cells in the process of fibrosis.
Oral contraceptive use and the clinical course of Crohn’s disease: a prospective cohort study
Authors: Cosnes J , Carbonnel F , Carrat F , Beaugerie L , Gendre J-P 
Published: January 2010

BACKGROUNDWomen with Crohn’s disease are usually advised not to take oral contraceptives, but, unlike smoking, there is no clear association between current oral contraceptive use and more severe disease.AIMTo assess the effect of oral contraceptive use on the clinical course of Crohn’s disease.PATIENTS331 women, aged 16–50 years, with Crohn’s disease and Crohn’s disease activity index <200, were enrolled consecutively during a one year period. Patients were classified at inclusion as oral contraceptive users or non-users and smokers or non-smokers.METHODSA prospective 12–18 month cohort study was used. The main outcome measures were flare up rate and time to flare up.RESULTSIn total, 134 women used oral contraceptives, in most cases low oestrogen formulations. During the study period, 61 oral contraceptive users (46%) developed a flare up, compared with 85 non-users (43%). The hazard ratio for oral contraceptive use was 1.11 (95% confidence interval 0.80 to 1.55). Variables associated with flare up were smoking status, recently active disease, baseline Crohn’s disease activity index, and presence of anoperineal lesions. The same results were obtained when the analysis was restricted to patients eligible for a relapse prevention trial.CONCLUSIONUnlike smoking, oral contraceptives have no effect on Crohn’s disease activity.
Gut origin of sepsis: a prospective study investigating associations between bacterial translocation, gastric microflora, and septic morbidity
Authors: MacFie J , O’Boyle C , Mitchell C J , Buckley P M , Johnstone D , Sudworth P 
Published: January 2010

AIMSTo investigate the “gut origin of sepsis” hypothesis.METHODSProspective controlled study of 279 surgical patients in which cultures of nasogastric aspirates were compared with those obtained from mesenteric lymph nodes taken at laparotomy and the organisms cultured from subsequent septic complications. Bacterial translocation was confirmed if positive cultures were obtained from mesenteric lymph nodes. Postoperative sepsis was defined as any positive culture in the postoperative period. Bacterial species obtained in gastric microflora, mesenteric lymph nodes, and postoperative septic complications were compared.RESULTSOnly 85/279 patients (31%) had a sterile nasogastric aspirate; the most frequently identified organism was Candida spp. (54%) and the most common enteric organism cultured was E coli (20%). Multiple organisms were isolated in 39% and occurred more frequently in patients aged over 70 years, those undergoing non-elective surgery, and in those requiring proximal gastrointestinal surgery. Postoperative sepsis was more common in these patients. Bacterial translocation occurred in 21% and was significantly more frequent in those with multiple organisms in their nasogastric aspirates. E coli was the commonest organism isolated from the lymph node specimens (48%) and septic foci (53%). Fungal translocation did not occur. An identical genus was identified in the nasogastric aspirate and the septic focus in 30% of patients, in the nasogastric aspirate and the lymph node in 31%, and in the lymph node and a postoperative septic focus in 45%.CONCLUSIONSProximal gut colonisation is associated with both increased bacterial translocation and septic morbidity. The commonality of organisms identified supports the gut origin of sepsis hypothesis.
Intestinal crypt cell apoptosis in murine acute graft versus host disease is mediated by tumour necrosis factor α and not by the FasL-Fas interaction: effect of pentoxifylline on the development of mucosal atrophy
Authors: Stüber E , Büschenfeld A , von Freier A , Arendt T , Fölsch U R 
Published: January 2010

BACKGROUNDMurine T cell mediated acute semiallogeneic graft versus host disease (GVHD) is characterised by lymphocytic infiltrates, crypt hyperplasia, and villous atrophy. It has been shown that programmed cell death (apoptosis) of the crypt epithelium takes place during the intestinal manifestation of acute GVHD.AIMSTo investigate which of the two most investigated inductors of apoptosis (Fas ligand (FasL) and tumour necrosis factor α (TNF-α)) is responsible for the induction of apoptosis in this animal model.METHODSAnimals undergoing acute semiallogeneic GvH reaction were treated with neutralising anti-TNF-α, two different anti-FasL antibodies, or pentoxifylline.RESULTSAnti-TNF-α application inhibited the appearance of apoptotic cells in the intestinal mucosa, whereas anti-FasL antibodies had no influence on mucosal apoptosis. In addition, the transfer of FasL deficient (gld) donor lymphocytes still induced crypt cell apoptosis, villous atrophy, and crypt hyperplasia. Furthermore, when the animals were treated with pentoxifylline, a known inhibitor of TNF-α secretion in vitro and in vivo, there was significant normalisation of the intestinal morphology accompanied by inhibition of epithelial apoptosis.CONCLUSIONSThe FasL-Fas interaction is not involved in the induction of apoptosis during acute GVHD. However, neutralisation of TNF-α by an antibody or by pentoxifylline inhibits the occurrence of apoptosis and of mucosal atrophy in this animal model. These results have implications for the treatment of immunologically mediated human atrophic gut diseases—for example, diet refractory cases of coeliac disease.