bluuebunny/crossref_metadata_2025_split huggingface dataset:
A monoclonal anti-interleukin 8 antibody (WS-4) inhibits cytokine response and acute lung injury in experimental severe acute necrotising pancreatitis in rabbits
Authors: Osman M O , Kristensen J U , Jacobsen N O , Lausten S B , Deleuran B , Deleuran M , Gesser B , Matsushima K , Larsen C G , Jensen S L 
Published: June 2010

Background—Interleukin 8 (IL-8) has recently been proposed to have an important role in mediating the development of the systemic sequelae associated with severe acute pancreatitis.Aims—To define the role of IL-8 in acute pancreatitis by neutralising its effects with a monoclonal anti-IL-8 antibody (WS-4), in a rabbit model of severe acute pancreatitis.Methods—Acute pancreatitis was induced by retrograde injection of 5% chenodeoxycholic acid into the pancreatic duct and duct ligation. Twenty rabbits were divided equally into two groups: acute pancreatitis controls received physiological saline and the treated group received WS-4, 30 minutes before induction of acute pancreatitis.Results—Pretreatment of animals with WS-4 resulted in significant down regulation of serum IL-8 and tumour necrosis factor α (TNF-α) from three to six hours after induction of acute pancreatitis (p=0.011 and 0.047 for IL-8 and 0.033 and 0.022 for TNF-α, respectively). In addition, a significant reduction in the CD11b and CD18 positive cells and the amount of interstitial neutrophil infiltration in the lungs from WS-4 treated animals was seen. In contrast, WS-4 did not alter the amount of pancreatic necrosis and the serum concentrations of amylase, lipase, calcium, and glucose.Conclusion—WS-4 cannot change the amount of pancreatic necrosis induced by injection of 5% bile acid, but does reduce the acute lung injury, presumably through inhibition of circulating IL-8 and TNF-α, and CD11b/CD18 in lung tissue. Therefore, a role of IL-8 in the progression of acute pancreatitis and the development of its systemic complications is suggested.
Distribution and metabolism of intravenously administered trefoil factor 2/porcine spasmolytic polypeptide in the rat
Authors: Poulsen S S , Thulesen J , Nexø E , Thim L 
Published: June 2010

Background—Trefoil peptides are secreted by mucus producing cells in the gastrointestinal tract and are supposed to be involved in oligomerisation processes of the mucin glycoproteins in the lumen. Endocrine functions have also been suggested.Aims—To target possible binding sites for iodine-125 labelled porcine spasmolytic polypeptide (pSP) in an in vivo rat model.Methods—125I-pSP was given by intravenous injection to female Spraque-Dawley rats. The distribution of 125I-pSP was assessed by gamma counting of samples of organs and by autoradiography of paraffin wax embedded sections. The degradation of 125I-pSP was studied by trichloroacetic acid precipitation, and the saturability of binding by administration of excess unlabelled peptide.Results—125I-pSP was taken up in the kidneys and the gastrointestinal tract and was excreted almost unmetabolised in the urine. In the stomach, it could be displaced by unlabelled pSP in a dose dependent manner. Autoradiography showed grains in mucous neck cells, parietal cells, the mucus layer, and the pyloric glands of the stomach; in Brunner’s glands and the Paneth cells in the small intestine; and in cells in the lower part of the crypts in the colon.Conclusions—125I-pSP from the circulatory system is taken up by mucus producing cells in the gastrointestinal tract. The binding can be displaced by non-radioactive pSP, suggesting the presence of a receptor.
Evidence for a lipid specific effect in nutrient induced human proximal gastric relaxation
Authors: McLaughlin J T , Troncon L E A , Barlow J , Heggie L J , Thompson D G 
Published: June 2010

Background/Aim—The presence of lipid in the upper gut is able to modify gastrointestinal motor performance, but its influence on the relaxation of the human stomach, which is known to modify gastric emptying, remains incompletely understood. The relaxation of the proximal stomach in response to various lipid concentrations was therefore studied in healthy volunteers. Since the observed effects could be mediated through osmolality or energy sensitive pathways, the effects of equicaloric and equiosmolar non-lipid solutions were also determined.Methods—The tone of the proximal stomach was measured during stepwise inflation of a non-compliant bag sited in the proximal stomach, both before and after a test meal was delivered intragastrically. Iso-osmolar lipid emulsions were diluted in iso-osmolar saline at concentrations of 1.25, 2.5, 5, 10, and 20%. NaCl solutions at osmolalities of 300, 600, 1200 and 2400 mmol/kg and glucose solutions of 836 and 3344 kJ/l were also given.Results—All lipid meals of 2.5% or greater concentration induced a reduction in gastric tone in a non-dose-dependent manner, responses to 5% lipid (median (range) 74 (62–92)%) being similar to those to 20% lipid (80 (55–83)%; p>0.05). No relaxation was elicited by isocaloric glucose. NaCl only consistently caused relaxation at 2400 mmol/kg.Conclusion—Lipid meals reduce human proximal gastric tone by a lipid specific mechanism, independently of their energy content or osmolality.
Heterozygotes for HFE mutations have no increased risk of advanced alcoholic liver disease
Authors: Grove J , Daly A K , Burt A D , Guzail M , James O F W , Bassendine M F , Day C P 
Published: June 2010

Background—Iron overload is common in the livers of alcoholics and may play a role in disease pathogenesis. An MHC like gene, HFE,has recently been identified that is mutated in most patients with hereditary haemochromatosis (C282Y in 90% and H63D in 45% of the remainder).Aim—To examine the hypothesis that these mutations determine hepatic iron status in alcoholics and play a role in predisposition to advanced alcoholic liver disease.Methods—TheHFE gene was genotyped in 257 patients with alcoholic liver disease and 117 locally matched healthy volunteers. In addition, iron staining was scored (0–4) on biopsy specimens from fibrotic/cirrhotic patients with and withoutHFE mutations matched for age and sex.Results—Some 15.7% of fibrotic/cirrhotic patients were C282Y heterozygotes compared with 13.7% of controls (p = 0.77). One control and three patients were C282Y homozygotes. Of chromosomes without the C282Y mutation, 68/442 (15.4%) of patients’ chromosomes carried the H63D mutation compared with 36/216 (16.6%) of control chromosomes (p = 0.91). Significant (>grade 1) hepatocyte iron staining was seen in 6/23 C282Y heterozygotes and 4/26 H63D heterozygotes compared with 4/23 controls.Conclusions—Possession of a single copy of either of the two HFEmutations influences neither liver iron content nor the risk of fibrotic disease in alcoholics.
Two way push videoenteroscopy in investigation of small bowel disease
Authors: Bouhnik Y , Bitoun A , Coffin B , Moussaoui R , Oudghiri A , Rambaud J C 
Published: June 2010

Aims—To evaluate the diagnostic yield and safety of a new push type videoenteroscope (PVE) for diagnosis of small bowel disease.Methods—Three hundred and thirteen patients were referred for one or two way PVE from December 1993 to June 1996. Indications for PVE were: an unexplained iron deficiency anaemia with or without clinically evident gastrointestinal bleeding; or a complementary investigation for suspected small bowel disease, after a small bowel barium follow through (SBBFT) considered as normal or abnormal, but without a definite diagnosis.Results—A jejunoscopy and a retrograde ileoscopy were carried out in 306 and 234 patients, respectively. In patients with isolated anaemia (n=131) and those with clinically evident gastrointestinal bleeding associated anaemia (n=72), PVE provided a diagnosis in 26 (19.8%) and 22 (30.5%) cases, respectively. Lesions found were located in the jejunoileum in 30 (14.7%) patients and in the gastroduodenum or the colon in 18 (8.8%) patients—that is, within the reach of the conventional gastroscope/colonoscope. In patients with normal (n=54) or abnormal (n=56) SBBFT, PVE provided a diagnosis in 17 (31%) and 27 (48%) cases, respectively. In 25% of cases, the abnormal appearance of SBBFT was not confirmed. The site of the radiological abnormality was not reached in 27% of cases. Lesions were located at the jejunum and the ileum in 59 (64%) and 33 (36%) cases, respectively.Conclusions—PVE is useful in around 30% of cases of unexplained anaemia or after an SBBFT which failed to provide an accurate aetiological diagnosis. Use of retrograde videoenteroscopy increases diagnostic yield by one third.
The relation between gastric vitamin C concentrations, mucosal histology, and CagA seropositivity in the human stomach
Authors: Zhang Z W , Patchett S E , Perrett D , Katelaris P H , Domizio P , Farthing M J G 
Published: June 2010

Background—Vitamin C may be protective against gastric cancer though infection withHelicobacter pylori is associated with a reduction in intragastric concentrations of vitamin C.Aims—To examine the effects ofH pylori infection, gastric juice pH, the severity and extent of gastric inflammation, and CagA antibody status of the individual on gastric juice and mucosal vitamin C concentrations.Patients—One hundred and fifteen patients undergoing routine gastroscopy for investigation of dyspepsia.Methods—High performance liquid chromatography was used to determine vitamin C concentrations. CagA antibody was detected by western blot analysis.Results—Gastric juice ascorbic acid concentration was significantly lower in patients infected withH pylori compared with those uninfected (19.3 μmol/l (interquartile range (IQR) 10.7–44.5) versus 66.9 μmol/l (IQR 24.4–94.2), p=0.003). The reduction in gastric juice ascorbic acid concentration was inversely related to the severity of gastritis (p=0.01). CagA positive patients had significantly lower gastric juice ascorbic acid concentrations than CagA negative ones (14.8 μmol/l (IQR 7.9–52.2) versus 39 μmol/l (IQR 19.9–142.2), p=0.05). Decreased gastric juice dehydroascorbic acid concentrations were observed in patients with gastric atrophy and intestinal metaplasia. Mucosal ascorbic acid concentrations were also significantly lower in infected patients than uninfected patients (p=0.04).Conclusions—The reduction in gastric vitamin C concentrations is related to gastric juice pH, the severity and extent of gastritis, the presence of H pylori, and the CagA antibody status of the individual. These findings may have implications in H pyloriassociated carcinogenesis.
On the protective mechanisms of nitric oxide in acute pancreatitis
Authors: Werner J , Castillo C Fernández-del , Rivera J A , Kollias N , Lewandrowski K B , Rattner D W , Warshaw A L 
Published: June 2010

Background—Ectopic protease activation, microcirculatory changes, and leucocyte activation are the main events in the pathogenesis of acute pancreatitis. Nitric oxide (NO) is known to be a key mediator in the normal and inflamed pancreas.Aims—To investigate the targets on which NO exerts its effect in caerulein induced pancreatitis.Methods—Acute pancreatitis was induced in rats which additionally received either the NO synthase substrate, l-arginine; the NO donor, sodium nitroprusside; or the NO synthase inhibitor, N-nitro-l-arginine methyl ester (l-NAME). At six hours, pancreatic injury (oedema, leucocyte content, ectopic trypsinogen activation) was analysed and pancreatic oxygenation and perfusion were determined. A direct influence of NO on amylase secretion and trypsinogen activation was evaluated separately in vitro.Results—Both NO donors reduced the grade of inflammation. l-NAME increased the severity of inflammation, while decreasing pancreatic tissue oxygenation. Although neither amylase secretion nor intracellular trypsinogen activation in caerulein stimulated pancreatic acini was influenced by either NO donors or inhibitors, both NO donors decreased intrapancreatic trypsinogen activation peptide (TAP) and pancreatic oedema in vivo, andl-NAME increased TAP.Conclusions—NO protects against injury caused by pancreatitis in the intact animal but has no discernible effect on isolated acini. It is likely that in pancreatitis NO acts indirectly via microcirculatory changes, including inhibition of leucocyte activation and preservation of capillary perfusion.
Increased state of activation of CD4 positive T cells and elevated interferon γ production in pouchitis
Authors: Stallmach A , Schäfer F , Hoffmann S , Weber S , Müller-Molaian I , Schneider T , Köhne G , Ecker K-W , Feifel G , Zeitz M 
Published: June 2010

Background—Immunoregulatory abnormalities of T cells might be of importance in the pathogenesis of pouchitis after ileoanal pouch anastomosis (IAP).Aims—To characterise T cell subsets, their state of activation, and production of cytokines in inflamed and non-inflamed pouches in patients with ulcerative colitis (UC) and familial adenomatous polyposis (FAP). The influence of T cell activation on mucosal transformation was also studied.Patients—Mucosal biopsy specimens were taken from 42 patients with IAP (33 with UC and nine with FAP).Methods—Mononuclear cells were isolated by standard techniques and characterised by three colour flow cytometry. Interferon γ (IFN-γ) production was studied using the ELISPOT technique.Results—In patients with UC with pouchitis there was a significant increase in the CD4:CD8 ratio, expression of activation markers on CD3+ cells, and number of IFNγ producing mononuclear cells compared with patients with UC without pouchitis (CD4:CD8 ratio 1.3 (range 0.7–2.7) versus 0.6 (0.1–1.0), p=0.012). In addition, a positive correlation between increased crypt depth and the number of CD4+ cells (r=0.57) was shown.Conclusion—The observed increase in activated mucosal CD4+ T cells and IFN-γ production might lead to mucosal destruction and crypt hyperplasia as seen in pouchitis.
Hyperbaric oxygen: a novel modality to ameliorate experimental colitis
Authors: Rachmilewitz D , Karmeli F , Okon E , Rubenstein I , Better O S 
Published: June 2010

Background—Hyperbaric oxygen (HBO) has been suggested to be beneficial in inflammatory bowel disease but the mechanisms responsible for its therapeutic effects have not been elucidated.Aim—To assess the effect of HBO treatment on colonic damage in two models of experimental colitis, and to examine whether this effect is mediated by modulation of NO synthesis.Methods—Colitis was induced by either flushing the colon with 2 ml 5% acetic acid or intracolonic administration of 30 mg trinitrobenzenesulphonic acid (TNB) dissolved in 0.25 ml 50% ethanol. Rats were exposed to HBO (100% oxygen at 2.4 atmosphere absolute) for one hour twice on the day of colitis induction and once daily thereafter. Control rats were treated only with acetic acid or TNB. Rats were killed 24 hours after acetic acid administration or one and seven days after TNB treatment. The colon was isolated, washed, and weighed, the lesion area was measured, and mucosal scrapings were processed for determination of myeloperoxidase (MPO) and NO synthase (NOS) activities, prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) generation.Results—In control rats exposed for seven days to HBO, colonic NOS activity was significantly decreased by 61%, compared with its activity in untreated rats (2.93 (0.17) nmol/g/min). HBO significantly reduced by 51 and 62% the extent of injury induced by acetic acid and TNB respectively. The protection provided by HBO was accompanied by a significant decrease in colonic weight, PGE2 generation, MPO, and NOS activities. In acetic acid colitis, LTB4 generation was also significantly decreased.Conclusions—(1) HBO effectively decreases colitis induced by acetic acid and TNB. (2) The decreased NOS activity induced by HBO suggests that reduction in NO generation may be among the mechanisms responsible for the anti-inflammatory effect of HBO. (3) HBO may be considered in the treatment of patients with refractory inflammatory bowel disease.
Effect of chronic and acute cigarette smoking on the pharyngo-upper oesophageal sphincter contractile reflex and reflexive pharyngeal swallow
Authors: Dua K , Bardan E , Ren J , Sui Z , Shaker R 
Published: June 2010

Background—Cigarette smoking is known to affect adversely the defence mechanisms against gastro-oesophageal reflux. The effect of smoking on the supraoesophageal reflexes that prevent aspiration of gastric contents has not been previously studied.Aims—To elucidate the effect of cigarette smoking on two of the supraoesophageal reflexes: the pharyngo-upper oesophageal sphincter (UOS) contractile reflex; and the reflexive pharyngeal swallow.Methods—Ten chronic smokers and 10 non-smokers were studied, before and 10 minutes after real or simulated smoking, respectively. UOS pressure and threshold volume for the reflexes were determined using a UOS sleeve assembly. Two modes of fluid delivery into the pharynx were tested: rapid injection and slow injection.Results—For both rapid and slow injections, the threshold volume for triggering the pharyngo-UOS contractile reflex was significantly higher in smokers than in non-smokers (rapid: smokers 0.42 (SE 0.07) ml, non-smokers 0.16 (0.04) ml; slow: smokers 0.86 (0.06) ml, non-smokers 0.38 (0.1) ml; p<0.05). During rapid injection, the threshold volume for reflexive pharyngeal swallow was higher in smokers (smokers 0.94 (0.09) ml, non-smokers 0.46 (0.05) ml; p<0.05). Acute smoking further increased the threshold volume for the pharyngo-UOS contractile reflex and reflexive pharyngeal swallow during rapid injection.Conclusions—Smoking adversely affects stimulation of the pharyngo-UOS contractile reflex and pharyngeal reflexive swallow. These findings may have implications in the development of reflux related respiratory complications among smokers.
Urokinase and the intestinal mucosa: evidence for a role in epithelial cell turnover
Authors: Gibson P R , Birchall I , Rosella O , Albert V , Finch C F , Barkla D H , Young G P 
Published: June 2010

Background—The functions of urokinase in intestinal epithelia are unknown.Aims—To determine the relation of urokinase expressed by intestinal epithelial cells to their position in the crypt-villus/surface axis and of mucosal urokinase activity to epithelial proliferative kinetics in the distal colon.Methods—Urokinase expression was examined immunohistochemically in human intestinal mucosa. Urokinase activity was measured colorimetrically in epithelial cells isolated sequentially from the crypt-villus axis of the rat small intestine. In separate experiments, urokinase activity and epithelial kinetics (measured stathmokinetically) were measured in homogenates of distal colonic mucosa of 14 groups of eight rats fed diets known to alter epithelial turnover.Results—From the crypt base, an ascending gradient of expression and activity of urokinase was associated with the epithelial cells. Median mucosal urokinase activities in each of the dietary groups of rats correlated positively with autologous median number of metaphase arrests per crypt (r=0.68; p<0.005) and per 100 crypt cells (r=0.75; p<0.001), but not with crypt column height.Conclusions—Localisation of an enzyme capable of leading to digestion of cell substratum in the region where cells are loosely attached to their basement membrane, and the association of its activity with indexes of cell turnover, suggest a role for urokinase in facilitating epithelial cell loss in the intestine.
A prospective evaluation of magnetic resonance cholangiopancreatography in patients with suspected bile duct obstruction
Authors: Adamek H E , Albert J , Weitz M , Breer H , Schilling D , Riemann J F 
Published: June 2010

Background—The value of magnetic resonance cholangiopancreatography (MRCP) is under debate.Aims—To assess the diagnostic accuracy of MRCP and endoscopic retrograde cholangiopancreatography (ERCP) and to determine whether MRCP may help to prevent unnecessary interventional procedures.Methods—Eighty six patients with suspected common bile duct obstruction who presented between January and December 1996 were enrolled. Twenty six were excluded due to anatomical reasons or because MRCP or ERCP could not be performed successfully. Results of MRCP were interpreted by two radiologists and a gastroenterologist unaware of clinical diagnosis. Final diagnosis was determined by ERCP and histopathological findings or a follow up of at least 12 months.Results—MRCP images of diagnostic quality were obtained in all 60 patients. Thirteen patients had a clear bile duct. Sensitivity and specificity for the detection of any abnormality (n=47) were 89% and 92%, and for the detection of malignancy (n=27) 81% and 100%, respectively. These results were equivalent to the respective figures of ERCP (91% and 92% for any abnormality, and 93% and 94% for malignant diseases).Conclusions—MRCP is as sensitive as ERCP in the evaluation of bilary tract diseases. As the specificity of this non-invasive technique is close to 100%, MRCP may prevent inappropriate invasive explorations of the common bile duct and pancreatic duct.
Fatigue in primary biliary cirrhosis
Authors: Cauch-Dudek K , Abbey S , Stewart D E , Heathcote E J 
Published: June 2010

Background—Fatigue is a frequent and debilitating symptom in patients with primary biliary cirrhosis (PBC).Aims—To study fatigue in relation to sleep, depression, and liver disease severity.Methods—Patients with PBC completed validated self report questionnaires measuring fatigue, sleep quality, depression, and functional capacity. Verbally reported fatigue and observer rated measure of depression and ursodeoxycholic acid (UDCA) use were recorded. Liver biochemistry and tests to rule out metabolic causes of fatigue were performed.Results—Mean age of the 88 patients enrolled was 57 years; 86% were female and mean duration of disease was 6.6 years. Median bilirubin was 13 μmol/l (mean 18.6). Verbally reported fatigue (for more than six months) was present in 60 patients (68%). The self rated Fatigue Severity Score (FSS) correlated well with verbally reported fatigue (p=0.0001). The FSS did not correlate with age, duration of disease, serum bilirubin, Mayo Risk Score, or UDCA use, but correlation was seen with sleep quality. Fatigued patients had more sleep problems and higher depression scores than non-fatigued patients. Self rated depression was present in 28% (17/60) of fatigued compared with 4% (1/28) of non-fatigued patients.Conclusions—Long term fatigue affected 68% of the patients with PBC but it was not related to the severity of their liver disease. Poor sleep quality and depression were commonly associated with fatigue.