bluuebunny/crossref_metadata_2025 huggingface dataset:
Antigastric autoantibodies in Helicobacter pyloriinfection: implications of histological and clinical parameters of gastritis
Authors: Faller G , Steininger H , Kränzlein J , Maul H , Kerkau T , Hensen J , Hahn E G , Kirchner T
Published: June 2010

Background—It has recently been shown that humoral antigastric autoreactivities occur in a substantial number ofHelicobacter pylori infected patients.

Aims—To analyse the relevance of such antigastric autoantibodies for histological and serological parameters of the infection as well as for the clinical course.

Methods—Gastric biopsy samples and sera from 126 patients with upper abdominal complaints were investigated for evidence of H pylori infection using histology and serology. Autoantibodies against epitopes in human gastric mucosa were detected by immunohistochemical techniques. Histological and clinical findings of all patients were then correlated with the detection of antigastric autoantibodies.

Results—H pylori infection was significantly associated with antigastric autoantibodies reactive with the luminal membrane of the foveolar epithelium and with canalicular structures within parietal cells. The presence of the latter autoantibodies was significantly correlated with the severity of body gastritis, gastric mucosa atrophy, elevated fasting gastrin concentrations, and a decreased ratio of serum pepsinogen I:II. Furthermore the presence of anticanalicular autoantibodies was associated with a greater than twofold reduced prevalence for duodenal ulcer.

Conclusion—The data indicate that antigastric autoantibodies play a role in the pathogenesis and outcome of H pylori gastritis, in particular in the development of gastric mucosal atrophy.
Efficacy and safety of the peripheral kappa agonist fedotozine versus placebo in the treatment of functional dyspepsia
Authors: Read N W , Abitbol J L , Bardhan K D , Whorwell P J , Fraitag B
Published: June 2010

Background—Peripheral kappa receptor agonists may provide a new therapeutic approach for the treatment of functional dyspepsia.

Aims—To evaluate, in a large multicentre trial, the use of the kappa receptor agonist fedotozine to improve symptoms associated with functional dyspepsia.

Methods—Two or more of the following persistent symptoms were required for inclusion: epigastric pain, early satiety, epigastric fullness or distension, nausea, vomiting, and a feeling of slow digestion. On completing a two week placebo washout, 271 patients were randomised into two groups to receive 30 mg fedotozine three times daily or placebo for six weeks under double blind conditions.

Results—The improvement in the overall intensity of dyspeptic symptoms (main efficacy criterion) was significantly more pronounced in the fedotozine group (p=0.002) compared with placebo, as was epigastric pain (p=0.004) and nausea (p=0.01); the improvement in postprandial fullness was nearly significant (p=0.052). Inability to finish a meal and slow digestion were unaffected. The patient global score, the average of the five individual symptoms, was notably ameliorated with fedotozine (p=0.021). The safety of fedotozine was excellent.

Conclusions—Fedotozine at 30 mg three times daily is safe and more effective than placebo for the relief of key symptoms associated with functional dyspepsia.
The effect of octreotide on gastric emptying at a dosage used to prevent complications after pancreatic surgery: a randomised, placebo controlled study in volunteers
Authors: van Berge Henegouwen M I , van Gulik Th M , Akkermans L M A , Jansen J B M J , Gouma D J
Published: June 2010

Background—Octreotide is used in many centres to prevent complications after pancreatic surgery. Delayed gastric emptying is a another complication occurring in around 30% of patients after pancreatoduodenectomy (PD) and causes prolonged hospital stay. The influence of octreotide on this complication is doubtful.

Aims—To assess the effect of octreotide, at the clinical dosage used after pancreatic surgery, on gastric emptying in healthy volunteers.

Subjects and methods—Eight healthy male volunteers (mean age 22.5 years) participated in this double blind, placebo controlled study. On day 1 subjects received 100 μg of octreotide or placebo subcutaneously, three times daily and on day 2, one hour after the fourth injection, gastric emptying, postprandial cholecystokinin (CCK) release, and mouth to caecum transit time (MCTT) were measured. This protocol was repeated after one week, in a crossover design. On the test day subjects received a liquid test meal (1.57 MJ/300 ml) and gastric emptying measurements were performed with applied potential tomography, a non-invasive, validated technique which measures gastric emptying through impedance differences. From the gastric emptying curves, lag time, t50, and postlag emptying rate were measured. MCTT was measured using the hydrogen breath test.

Results—Lag time decreased from 29.6 (6.3) (mean (SEM)) to 12.2 (4.6) minutes (p<0.05) during octreotide treatment; t50 decreased from 87.8 (12.0) to 47.5 (8.2) minutes (p<0.02) and there was a trend towards an increased postlag emptying rate (0.8 to 1.6% per minute; p=0.07). MCTT increased from 150 (12.7) to 229 (17.9) minutes during octreotide treatment (p<0.01). Octreotide suppressed postprandial CCK release (p<0.05).

Conclusions—MCTT was delayed by octreotide, suggesting impairment of small bowel transit. Octreotide administered at the clinical dosage for pancreatic surgery accelerates gastric emptying, mainly by shortening the lag time. Suppression of postprandial CCK release may be involved in this process. Octreotide administration is therefore not a contributing factor in the pathogenesis of delayed postoperative gastric emptying after PD and might even play a role in preventing this complication.
Hepatitis G virus infection in chronic liver disease
Authors: Guilera M , Sáiz J C , López-Labrador F X , Olmedo E , Ampurdanés S , Forns X , Bruix J , Parés A , Sánchez-Tapias J M , de Anta M T Jiménez , Rodés J
Published: June 2010

Background—The hepatitis G virus (HGV), a recently identified member of the Flaviviridae family, can cause chronic infection in man but the role of this agent in chronic liver disease is poorly understood.

Aims—To evaluate the prevalence and meaning of HGV infection in a large series of patients with chronic liver disease.

Subjects—Two hundred volunteer blood donors, 179 patients with chronic hepatitis C, 111 with chronic hepatitis B, 104 with alcoholic liver disease, 136 with hepatocellular carcinoma, and 24 with cryptogenic chronic liver disease were studied.

Methods—HGV RNA was investigated in serum samples by reverse transcription and polymerase chain reaction amplification of the 5′ non-coding region of HCV and hybridisation to a specific probe. The main features of HGV RNA seropositive and seronegative patients were compared.

Results—The prevalence of HGV infection was 3% in blood donors, 7% in chronic hepatitis C, 8% in chronic hepatitis B, 2% in alcoholic liver disease, 4% in hepatocellular carcinoma, and 8% in cryptogenic chronic liver disease. HGV infected patients tended to be younger than non-infected patients but no differences concerning sex, possible source of infection, clinical manifestations, biochemical and virological parameters, or severity of liver lesions were found.

Conclusions—The prevalence of HGV infection in chronic liver disease seems to be relatively low in our area. Infection with HGV does not seem to play a significant pathogenic role in patients with chronic liver disease related to chronic HBV or HCV infection or to increased alcohol consumption, or in those with cryptogenic chronic liver disease.
Putrescine as a source of instant energy in the small intestine of the rat
Authors: Bardócz S , Grant G , Brown D S , Pusztai A
Published: June 2010

Background and aims—It has been suggested that putrescine acts as a growth factor in the gut, but its exact function in some aspects of cellular metabolism is still in question. The aim of the present work was to identify some functions of putrescine in small bowel metabolism.

Animals—Rats (about 80 g), in groups of five, were given either phytohaemagglutinin- or lactalbumin-containing diets, fed ad libitum or were fasted for 48 hours and re-fed for six or twelve hours before being killed.

Methods—Uptake of intraperitoneally or intragastrically administered [14C]putrescine and its conversion to succinate by the rat small bowel mucosa was measured. Tissue polyamine and succinate contents were measured by high performance liquid chromatography and amino acid analysis respectively.

Results—Uptake of putrescine by the small bowel mucosa from the systemic circulation and conversion of about 30% of this to succinate occurs in the epithelium of the healthy small bowel. Compared with rats given food ad libitum, putrescine uptake was doubled in fasted animals and more than 70% of it was converted to succinate. All these changes returned to control values on refeeding. Using phyto- haemagglutinin induced gut growth as a model, the uptake of putrescine from the systemic circulation by the serosal side of the small intestinal epithelium was increased immediately after growth was stimulated. During phytohaemagglutinin induced growth of the gut, putrescine was converted to succinate in the same proportion as in the healthy small bowel.

Conclusions—The experiments identified a novel function for putrescine in gut metabolism: it can be used as an instant energy source when required.
13C labelled cholesteryl octanoate breath test for assessing pancreatic exocrine insufficiency
Authors: Ventrucci M , Cipolla A , Ubalducci G M , Roda A , Roda E
Published: June 2010

Background—A non-invasive test for assessment of fat digestion has been developed based on the intraluminal hydrolysis of cholesteryl-[1-13C]octanoate by pancreatic esterase.

Aims—To determine the diagnostic performance of this breath test in the assessment of exocrine pancreatic function.

Methods—The test was performed in 20 healthy controls, 22 patients with chronic pancreatic disease (CPD), four with biliopancreatic diversion (BPD), and 32 with non-pancreatic digestive diseases (NPD); results were compared with those of other tubeless tests (faecal chymotrypsin and fluorescein dilaurate test).

Results—Hourly recoveries of13CO2 were significantly lower in CPD when compared with healthy controls or NPD. In patients with CPD with mild to moderate insufficiency, the curve of 13CO2recovery was similar to that of healthy controls, while in those with severe insufficiency it was flat. In three patients with CPD with severe steatorrhoea, a repeat test after pancreatic enzyme supplementation showed a significant rise in13CO2 recovery. The four BPD patients had low and delayed 13CO2 recovery. Only eight of the 32 patients with NPD had abnormal breath test results. There was a significant correlation between the results of the breath test and those of faecal chymotrypsin, the fluorescein dilaurate test, and faecal fat measurements. For the diagnosis of pancreatic disease using the three hour cumulative 13CO2 recovery test, the sensitivity was 68.2% and specificity 75.0%; values were similar to those of the other two tubeless pancreatic function tests. In seven healthy controls, nine patients with CPD, and nine with NPD a second breath test was performed using Na-[1-13C]octanoate and a pancreatic function index was calculated as the ratio of13C recovery obtained in the two tests: at three hours this index was abnormal in eight patients with CPD and in three with NPD.

Conclusion—The cholesteryl-[1-13C]octanoate breath test can be useful for the diagnosis of fat malabsorption and exocrine pancreatic insufficiency.
Activation peptide of carboxypeptidase B in serum and urine in acute pancreatitis
Authors: Appelros S , Thim L , Borgström A
Published: June 2010

Background—The pathophysiology of acute pancreatitis involves activation of the pancreatic proenzymes. Levels of the trypsinogen activation peptide in urine in acute pancreatitis has been shown to correlate with the severity of disease. However, this peptide is unstable in urine and, because of its low molecular mass, difficult to measure. Procarboxypeptidase B has a larger activation peptide which could be more suitable for analysis in serum and urine.

Aims—To study the presence of the activation peptide from procarboxypeptidase B (CAPAP) in serum and urine in acute pancreatitis.

Patients—Urine and serum samples were obtained within 48 hours of admittance from 40 patients with acute pancreatitis. Severity was classified retrospectively according to levels of C-reactive protein and clinical course. Thirty four patients with abdominal pain from other causes were studied as controls.

Methods—CAPAP was purified from human pancreatic juice. Specific antibodies were obtained and a radioimmunoassay was developed.

Results—Levels of CAPAP in serum and urine in acute pancreatitis correlate with the severity of the attack. CAPAP is very stable, and urine contains only CAPAP whereas, in serum, cross reacting procarboxypeptidase B is found together with CAPAP.

Conclusions—CAPAP could be a valuable tool in the diagnosis and early determination of severity in acute pancreatitis.
Eradicating Helicobacter pylori reduces hypergastrinaemia during long term omeprazole treatment
Authors: El-Nujumi A , Williams C , Ardill J E , Oien K , McColl K E L
Published: June 2010

Background—Both proton pump inhibitor drug treatment and Helicobacter pylori infection cause hypergastrinaemia in man.

Aims—To determine whether eradicating H pylori is a means of reducing hypergastrinaemia during subsequent proton pump inhibitor treatment.

Methods—Patients with H pylori were randomised to treatment with either anti-H pylori or symptomatic treatment. One month later, all received four weeks treatment with omeprazole 40 mg/day for one month followed by 20 mg/day for six months. Serum gastrin concentrations were measured before and following each treatment.

Results—In the patients randomised to anti-H pylori treatment, eradication of the infection lowered median fasting gastrin by 48% and meal stimulated gastrin by 46%. When gastrin concentrations one month following anti-H pylori/symptomatic treatment were used as baseline, omeprazole treatment produced a similar percentage increase in serum gastrin in the H pylori infected and H pylorieradicated patients. Consequently, in the patients in which H pylori was not eradicated, median fasting gastrin concentration was 38 ng/l (range 26–86) at initial presentation and increased to 64 ng/l (range 29–271) after seven months omeprazole, representing a median increase of 68% (p<0.005). In contrast, in the patients randomised to H pylori eradication, median fasting gastrin at initial presentation was 54 ng/l (range 17–226) and was unchanged after seven months omeprazole at 38 ng/l (range 17–95).

Conclusion—Eradicating H pylori is a means of reducing the rise in gastrin during subsequent long term omeprazole treatment. In view of the potential deleterious effects of hypergastrinaemia it may be appropriate to render patients H pylori negative prior to commencing long term proton pump inhibitor treatment.
Conclusive evidence of endotoxaemia in biliary obstruction
Authors: Clements W D B , Erwin P , McCaigue M D , Halliday I , Barclay G R , Rowlands B J
Published: June 2010

Background—Endotoxaemia is implicated in the pathophysiology of obstructive jaundice. The EndoCab enzyme linked immunosorbent assay (ELISA) is a novel assay which measures endogenous antibody (IgG) to the inner core region of circulating endotoxins (ACGA).

Aims—To investigate the significance of endotoxaemia in biliary obstruction using the EndoCab assay and assess the specificity of the humoral response to endotoxin compared with an exogenous antigenic challenge (tetanus toxoid, TT).

Methods—Three groups of adult male Wistar rats were studied: no operation, sham operation, and bile duct ligation for 21 days (BDL). In the second study, rats rats received prior immunisation with TT.

Results—In the preliminary experiment, plasma ACGA was significantly increased in the BDL group (306.6 (18.3)% versus 119.9 (6.7)% and 105.2 (4.6)% in the sham and no operation groups, respectively; p<0.001). Although the mean endotoxin concentration in the BDL group was greater than that in the control groups this was not significant. There was a strong positive correlation between ACGA and endotoxin concentrations (p=0.0021). In the second study mean ACGA after 21 days of BDL was significantly elevated (267.1 (31.2)% versus 101.6 (21.2)% at baseline, p<0.0001). ACGA was unaffected in the other two groups. TT antibody concentrations fell in all three groups; only in the BDL group was the fall significant (97.6 (5.3)% versus 78.8 (4.2)% at baseline, p<0.05).

Conclusions—The specific rise in ACGA supports the hypothesis that endotoxin has an integral role in the pathophysiology of obstructive jaundice. The production of anticore glycolipid antibodies specifically reflects systemic endotoxaemia in this model. The EndoCab assay provides a novel, sensitive, and specific method for endotoxin detection.
Prevalence and clinical features of selective immunoglobulin A deficiency in coeliac disease: an Italian multicentre study
Authors: Cataldo F , Marino V , Ventura A , Bottaro G , Corazza G R ,   the Italian Society of Paediatric Gastroenterology and Hepatology (SIGEP) “Club del Tenue” Working Groups on Coeliac Disease
Published: June 2010

Background—Selective immunoglobulin A (IgA) deficiency (SIgAD) is associated with coeliac disease (CD).

Aim—To make a retrospective study of the association of SIgAD with CD in Italy.

Methods—Hospital medical records of 2098 patients consecutively diagnosed as having CD were reviewed.

Results—Of 2098 patients with CD, 54 (2.6%) had SIgAD, representing a 10–16-fold increase over that in the population in general. This increase was not influenced by age or geographical factors. Patients with SIgAD had a higher incidence of silent forms (7/54, 13%), recurrent infections (16/54, 29.6%), and atopic diseases (7/54, 13%) than those without. The association with autoimmune and malignant diseases and the outcome after eating a gluten free diet were similar in patients with or without SIgAD. In all patients with SIgAD, antibodies for IgA gliadin and endomysium were absent, but serum levels of IgG anti-gliadin antibodies were high in almost all of them (51/54).

Conclusions—Serum IgA should be measured in order to be able to interpret negative results for IgA anti-gliadin antibodies and anti-endomysial antibodies in patients being screened for CD. Since some patients with CD and SIgAD may be negative for IgG anti-gliadin antibodies, an intestinal biopsy should be performed in all suspected cases.
Gut barrier function in malnourished patients
Authors: Welsh F K S , Farmery S M , MacLennan K , Sheridan M B , Barclay G R , Guillou P J , Reynolds J V
Published: June 2010

Background—The integrity of the gastrointestinal mucosa is a key element in preventing systemic absorption of enteric toxins and bacteria. In the critically ill, breakdown of gut barrier function may fuel sepsis. Malnourished patients have an increased risk of postoperative sepsis; however, the effects of malnutrition on intestinal barrier function in man are unknown.

Aims—To quantify intestinal barrier function, endotoxin exposure, and the acute phase cytokine response in malnourished patients.

Patients—Malnourished and well nourished hospitalised patients.

Methods—Gastrointestinal permeability was measured in malnourished patients and well nourished controls using the lactulose:mannitol test. Endoscopic biopsy specimens were stained and morphological and immunohistochemical features graded. The polymerase chain reaction was used to determine mucosal cytokine expression. The immunoglobulin G antibody response to endotoxin and serum interleukin 6 were measured by enzyme linked immunosorbent assay.

Results—There was a significant increase in intestinal permeability in the malnourished patients in association with phenotypic and molecular evidence of activation of lamina propria mononuclear cells and enterocytes, and a heightened acute phase response.

Conclusions—Intestinal barrier function is significantly compromised in malnourished patients, but the clinical significance is unclear.
Diagnostic yield of push-type enteroscopy in relation to indication
Authors: Landi B , Tkoub M , Gaudric M , Guimbaud R , Cervoni J P , Chaussade S , Couturier D , Barbier J P , Cellier C
Published: June 2010

Background—Push-type enteroscopy, a recent method for investigating the small intestine, is currently undergoing assessment. Its diagnostic yield varies in the studies reported to date.

Aim—To assess the diagnostic value of push-type enteroscopy according to indication.

Patients and methods—From January 1994 to September 1995, 152 consecutive patients (mean age 34 years) underwent push-type enteroscopy (jejunoscopy, n=93; retrograde ileoscopy, n=17; and double way enteroscopy, n=42). The indications were: unexplained iron deficiency anaemia or macroscopic gastrointestinal bleeding (n=76), radiological abnormalities of the small intestine (n=23), chronic diarrhoea and/or malabsorption syndrome (n=18), abdominal pain (n=12), and miscellaneous (n=23). All patients had undergone previous negative aetiological investigations.

Results—The jejunum and ileum were explored through 120 cm (30–160 cm) and 60 cm (20–120 cm). Digestive bleeding: lesions of the small bowel were found in 6% of the patients with isolated iron deficiency anaemia and 20% of patients with patent digestive haemorrhage. Radiological abnormalities of the small intestine: push-type enteroscopy provided a diagnosis or modified the interpretation of radiological findings in 18/23 cases (78%). Chronic diarrhoea and/or malabsorption: push-type enteroscopy yielded explanatory findings in four cases (22%). Abdominal pain: push-type enteroscopy provided no diagnosis.

Conclusion—In this series, push-type enteroscopy was of particular value in investigating patients with radiological abnormalities of the small intestine. It was of some value in the exploration of patent digestive haemorrhage or chronic diarrhoea, but not of abdominal pain. Its value was limited in the exploration of iron deficiency anaemia.
Assessment of symptomatic response as predictor ofHelicobacter pylori status following eradication therapy in patients with ulcer
Authors: McColl K E L , El-Nujumi A , Murray L S , El-Omar E M , Dickson A , Kelman A W , Hilditch T E
Published: June 2010

Background—Helicobacter pylorieradication therapy is routinely used for treating patients with peptic ulcer disease.

Aims—To assess the value of symptomatic response to H pylori eradication therapy as a marker of post-treatment H pylori status.

Patients and methods—One hundred and nine dyspeptic patients with active duodenal or gastric ulceration associated with H pylori infection had their symptoms measured by a validated questionnaire before and three months followingH pylori eradication therapy. The symptomatic response was compared with post-treatment H pylori status as determined by the 14C urea breath test.

Results—An eradication rate of 84% was achieved. Of the 92 patients eradicated of H pylori, 47% experienced complete or near complete resolution of dyspepsia. Of the 17 patients in whom the infection was not eradicated, only one (6%) experienced resolution of dyspepsia. Resolution of dyspepsia was therefore a powerful predictor of eradication of H pyloriwith a predictive value of 98%. In contrast, persistence of dyspepsia was a weak predictor of persisting infection with a predictive value of only 25%. Excluding patients with endoscopic evidence of coexisting oesophagitis and/or retrosternal discomfort or reflux at initial presentation did not increase the predictive value of persisting dyspepsia for persisting infection.

Conclusions—Complete resolution of dyspeptic symptoms is a powerful predictor of eradication of H pylori infection in ulcer patients. Persistence of symptoms is a weak predictor of persisting infection and patients with persisting dyspepsia must have their H pylori status rechecked to guide future management.
Nitroxide radical attenuates ischaemia/reperfusion injury to the rat small intestine
Authors: Udassin R , Haskel Y , Samuni A
Published: June 2010

Background—Free radicals are associated with post-ischaemic intestinal injury and contribute to major clinical problems primarily in premature infants. Various antioxidative means and modes of intervention, previously tested, have demonstrated only limited efficacy.

Aims—To study the protective activity of the stable nitroxide radical 4-OH, 2,2,6,6-tetramethylpiperidine-1-oxyl (TPL) and its respective hydroxylamine (TPL-H) against ischaemia/reperfusion (I/R) injury.

Methods—An isolated loop of ileum was created in laboratory male Sabra rats and constantly perfused with warmed normal saline. Intestinal injury was elicited through clamping of the superior mesenteric rat artery followed by reperfusion. Either TPL or TPL-H was given intravenously immediately before ischaemia or reperfusion and continuously afterwards. The rate of mucosal to lumen clearance of para-aminohippurate (PAH) was used to evaluate intestinal mucosal injury. Serum and perfusate levels of both TPL and TPL-H were measured using electron paramagnetic resonance spectrometry.

Results—The increase in intestinal permeability induced by I/R was significantly inhibited by both TPL and TPL-H. The nitroxide was effective also when given immediately before reperfusion.

Conclusion—Through a continuous exchange, TPL and TPL-H act as self-replenishing antioxidants and thus protect from intestinal injury. This demonstrates the potential of the family of nitroxide antioxidants against oxidative stress in general and I/R injury in particular.
Identification of distinct upper and lower gastrointestinal symptom groupings in an urban population
Authors: Talley N J , Boyce P , Jones M
Published: June 2010

Background—The current classification dividing patients with functional gastrointestinal symptoms into subgroups remains controversial.

Aims—To determine whether distinct symptom groupings exist in the community.

Methods—A random sample of Sydney residents in Penrith, Australia was mailed a validated self report questionnaire. Gastrointestinal symptoms including the Rome criteria for irritable bowel syndrome (IBS) and dyspepsia were measured.

Results—Among 730 respondents, the 12 month age and gender adjusted prevalence (adjusted to the Australian population) of IBS, dyspepsia, and gastro-oesophageal reflux were 11.8% (95% confidence interval (CI) 9.3 to 14.3%), 11.5% (95% CI 9.6 to 14.6%), and 17.5% (95% CI 14.2 to 19.9%), respectively. In total, 60% of the population reported four or more gastrointestinal symptoms. There was considerable overlap of IBS with dyspepsia and among the dyspepsia subgroups by application of the Rome criteria. Independently, 10 symptom groupings were identified by factor analysis. The underlying constructs measured by these factors were generally the major abdominal syndromes recognised by the Rome classification: dyspepsia, IBS, reflux, painless constipation, painless diarrhoea, and bloating, in addition to a number of more specific symptom groupings.

Conclusion—Gastrointestinal symptoms are common and overlap in the community, but distinct upper and lower abdominal symptom groupings can be identified.
Management of occluded biliary Wallstents
Authors: Tham T C K , Carr-Locke D L , Vandervoort J , Wong R C K , Lichtenstein D R , Van Dam J , Ruymann F , Chow S , Bosco J J , Qaseem T , Howell D , Pleskow D , Vannerman W , Libby E D
Published: June 2010

Background—Wallstents (Schneider Stent, Inc., USA) used for the palliation of malignant biliary strictures, although associated with prolonged patency, can occlude. There is no consensus regarding the optimal management of Wallstent occlusion.

Aims—To evaluate the efficacy of different endoscopic methods for managing biliary Wallstent occlusion.

Methods—A multicentre retrospective study of patients managed for a biliary Wallstent occlusion.

Results—Data were available for 38 patients with 44 Wallstent occlusions, all of which had initial endoscopic management. Twenty four patients had died and 14 were alive after a median follow up of 231 (30–1095) days following Wallstent occlusion. Occlusions were managed by insertion of another Wallstent in 19, insertion of a plastic stent in 20, and mechanical cleaning in five. Endoscopic management was successful in 43 (98%). Following management of the occlusion, bilirubin decreased from 6.0 (0.5–34.3) to 2.1 (0.2–27.7) mg/100 ml (p<0.05). No complications occurred. The median duration of second stent patency was 75 days (95% confidence interval 43 to 107) after insertion of another Wallstent, 90 days (71 to 109) after insertion of a plastic stent, and 34 days (30 to 38) after mechanical cleaning (NS). The respective median survivals were 70 days (22–118), 98 days (54–142), and 34 days (30–380) (NS). Incremental cost effective analysis showed that plastic stent insertion is the most cost effective option.

Conclusion—Although all three methods are equally effective in managing an occluded Wallstent, the most cost effective method appears to be plastic stent insertion.
Evidence for altered hepatic matrix degradation in genetic haemochromatosis
Authors: George D K , Ramm G A , Powell L W , Fletcher L M , Walker N I , Cowley L L , Crawford D H G
Published: June 2010

Background—Altered matrix degradation contributes to fibrosis in some liver diseases but the role of matrix degradation in fibrogenesis associated with genetic haemochromatosis has not previously been addressed.

Aims—To measure serum concentrations of tissue inhibitor of metalloproteinase 1 (TIMP-1) and matrix metalloproteinases (MMP), MMP-1, MMP-2, and MMP-3 in patients with haemochromatosis and control subjects.

Patients—Forty patients with haemochromatosis and 19 healthy control subjects. Ten of the 40 patients were studied before and after venesection therapy.

Methods—Serum levels of TIMP-1, MMP-1, MMP-2, and MMP-3 were measured by enzyme immunoassay and correlated to hepatic iron concentration and degree of histological fibrosis.

Results—Serum TIMP-1 was increased in patients with haemochromatosis compared with controls (163 (30) versus 123 (28) ng/ml, p<0.0002). Mean serum TIMP-1 concentration of patients with haemochromatosis without fibrosis was significantly higher than in controls (153 (16) versus 123 (28) ng/ml, p=0.03). Serum TIMP-1 concentration correlated with both hepatic iron concentration and hepatic iron index (r=0.42, p<0.01; r=0.42, p<0.01). Serum MMP-2 concentrations correlated with increasing degree of fibrosis in patients with haemochromatosis (r=0.38, p=0.01). The mean MMP-1:TIMP-1, MMP-2:TIMP-1 and age/sex matched MMP-3:TIMP-1 ratios were significantly lower in patients with haemochromatosis than controls (0.11 (0.06) versus 0.2 (0.14), p=0.02; 3.32 (0.9) versus 3.91 (0.81), p=0.05; and 0.26 (0.12) versus 0.47 (0.27), p=0.007, respectively). Following venesection, MMP-2 and MMP-3 concentrations increased by 11% (p=0.03) and 19% (p=0.03), respectively.

Conclusions—This study provides the first evidence of an alteration in matrix degradation in haemochromatosis that may be a contributing factor to hepatic fibrogenesis in this disease.
Dietary fibre and intestinal microflora: effects on intestinal morphometry and crypt branching
Authors: McCullough J S , Ratcliffe B , Mandir N , Carr K E , Goodlad R A
Published: June 2010

Background—Fermentable dietary fibre has many effects on the gastrointestinal tract. One is to alter epithelial crypt cell proliferation, especially in the colon. A discrepancy between epithelial cell production rates and intestinal weights has been noted previously: crypt cell production rates only increase if bacterial fermentation occurs, but intestinal wet weight can increase in the same animals without bacterial fermentation of fibre.

Aims—To quantify intestinal cell populations in order to resolve the above paradox.

Methods—Conventional and germ-free rats were fed fibre-free or fibre supplemented diets and their intestines were quantified by morphometry.

Results—There was evidence of fibre associated muscle hypertrophy in the colon, but the main effect of fibre was an increase in the number of crypts per circumference and also the number of branched crypts in the proximal colon in both groups. There was also a large increase in the number of branched crypts in the mid colon of the germ-free rats (both fibre-free and fibre supplemented). Fibre had a direct (bacteria independent) effect on goblet cells in the small intestine and a direct effect on the goblet cells in the colon, which was attenuated by the presence of bacteria. There was a notable decline in the number of enteroendocrine cells in the small intestine of the germ-free animals.

Conclusions—Fibre has several direct and indirect effects on the gut. In the proximal colon it can directly increase the number of crypts present. This provides a means for increasing intestinal mass in addition to intestinal crypt cell production.
Enteric neuronal plasticity and a reduced number of interstitial cells of Cajal in hypertrophic rat ileum
Authors: Ekblad E , Sjuve R , Arner A , Sundler F
Published: June 2010

Background—Partial obstruction of the ileum causes a notable hypertrophy of smooth muscle cells and enteric neurones in the proximally located intestine.

Aims—To study the expression of neuromessengers in the hypertrophic ileum of rat as little is known about neuromessenger plasticity under these conditions. To investigate the presence of interstitial cells of Cajal (ICC) in hypertrophic ileum.

Methods—Ileal hypertrophy was induced by circumferential application of a strip of plastic film for 18–24 days. Immunocytochemistry, in situ hybridisation, nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry, and ethidium bromide staining were used to investigate the number of enteric neurones expressing neuropeptides and nitric oxide synthase, and the frequency of ICC.

Results—In the hypertrophic ileum several neuronal populations showed changes in their expression of neuromessengers. Myenteric neurones expressing vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide, and galanin were notably increased in number. In submucous ganglia the number of VIP immunoreactive neurones decreased while those expressing VIP mRNA increased. NADPH diaphorase positive submucous neurones increased dramatically while the number of neuronal type nitric oxide synthase expressing ones was unchanged. The number of ICC decreased notably in hypertrophic ileum.

Conclusion—Enteric neurones change their levels of expression of neuromessengers in hypertrophic ileum. ICC are also affected. The changes are presumably part of an adaptive response to the increased work load.
Impact of corticotropin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome
Authors: Fukudo S , Nomura T , Hongo M
Published: June 2010

Background—Corticotropin-releasing hormone (CRH) plays a key role in modulating intestinal motility in stressed animals.

Aims—To evaluate the effect of CRH on intestinal motility in humans and to determine whether patients with irritable bowel syndrome (IBS) have an exaggerated response to CRH.

Subjects—Ten IBS patients diagnosed by Rome criteria and 10 healthy controls.

Methods—CRH (2 μg/kg) was intravenously administered during duodenal and colonic manometry and plasma adrenocorticotropic hormone (ACTH) was measured by radioimmunoassay.

Results—CRH induced motility of the descending colon in both groups (p<0.001) and induced greater motility indexes in IBS patients than in controls (p<0.05). CRH produced duodenal phase III motor activity in 80% of the subjects and duodenal dysmotility in 40% of IBS patients. Abdominal symptoms evoked by CRH in IBS patients lasted significantly longer than those in controls (p<0.05). CRH induced significant increases in plasma ACTH levels in both groups (p<0.001) and produced significantly higher plasma ACTH levels in IBS patients than in controls (p<0.001).

Conclusion—Human intestinal motility is probably modulated by exogenous CRH. The brain-gut in IBS patients may have an exaggerated response to CRH.
Endogenous benzodiazepine-like compounds and diazepam binding inhibitor in serum of patients with liver cirrhosis with and without overt encephalopathy
Authors: Avallone R , Zeneroli M L , Venturini I , Corsi L , Schreier P , Kleinschnitz M , Ferrarese C , Farina F , Baraldi C , Pecora N , Frigo M , Baraldi M
Published: June 2010

Background/Aim—Despite some controversy, it has been suggested that endogenous benzodiazepine plays a role in the pathogenesis of hepatic encephalopathy. The aim of the present study was to evaluate the concentrations of endogenous benzodiazepines and the peptide, diazepam binding inhibitor, in the blood of patients with liver cirrhosis with and without overt encephalopathy, and to compare these levels with those of consumers of commercial benzodiazepines.

Subjects—Normal subjects (90), benzodiazepine consumers (14), and cirrhotic patients (113) were studied.

Methods—Endogenous benzodiazepines were measured by the radioligand binding technique after high performance liquid chromatography (HPLC) purification. The presence of diazepam andN-desmethyldiazepam was assayed by HPLC-electrospray tandem mass spectrometry. Diazepam binding inhibitor was studied in serum by radioimmunoassay.

Results—Endogenous benzodiazepines were below the limit of detection in 7% of patients with encephalopathy. When detectable, their levels were at least comparable with those of benzodiazepine consumers and correlated with the liver dysfunction but not the stage of encephalopathy. Serum levels of diazepam binding inhibitor tended to decrease when endogenous benzodiazepines levels increased.

Conclusions—Endogenous benzodiazepines may accumulate in patients with liver cirrhosis during the course of the disease, and the phenomenon appears to be independent of the presence or absence of encephalopathy.
Effect of atropine on gastro-oesophageal reflux and transient lower oesophageal sphincter relaxations in patients with gastro-oesophageal reflux disease
Authors: Lidums I , Checklin H , Mittal R K , Holloway R H
Published: June 2010

Background—Atropine reduces the rate of reflux episodes in normal subjects by inhibition of transient lower oesophageal sphincter (LOS) relaxations. The aim of this study was to investigate the effect of atropine on the rate and mechanisms of reflux in patients with reflux disease.

Methods—Oesophageal motility and pH were recorded for one hour after a meal in 15 patients with reflux disease. On separate days, atropine (15 μg/kg bolus intravenously, 4 μg/kg/h infusion) or saline were given and maintained for the recording period.

Results—Atropine significantly reduced basal LOS pressure from 7.1 (2.2) to 2.9 (1.3) mm Hg (mean (SEM)). Atropine also reduced the rate of reflux episodes from 5.0 (2.0–8.75) to 1.0 (0–6.25) per hour (median (interquartile range)) largely because of a decrease in the rate of transient LOS relaxations from 2.0 (0–4.75) to 0 (0–0) per hour and abolition of reflux during swallow induced LOS relaxation. There was no change in the rate of reflux episodes because of absent basal LOS pressure.

Conclusions—Atropine inhibits reflux in patients with reflux disease largely by inhibition of transient LOS relaxations and swallow induced LOS relaxation. These findings suggest that pharmacological control of reflux through control of transient LOS relaxations is possible in patients with reflux disease.
Periacinar stellate shaped cells in rat pancreas: identification, isolation, and culture
Authors: Apte M V , Haber P S , Applegate T L , Norton I D , McCaughan G W , Korsten M A , Pirola R C , Wilson J S
Published: June 2010

Background—The pathogenesis of pancreatic fibrosis is unknown. In the liver, stellate cells (vitamin A storing cells) play a significant role in the development of fibrosis.

Aims—To determine whether cells resembling hepatic stellate cells are present in rat pancreas, and if so, to compare their number with the number of stellate cells in the liver, and isolate and culture these cells from rat pancreas.

Methods—Liver and pancreatic sections from chow fed rats were immunostained for desmin, glial fibrillary acidic protein (GFAP), and α smooth muscle actin (α-SMA). Pancreatic stellate shaped cells were isolated using a Nycodenz gradient, cultured on plastic, and examined by phase contrast and fluorescence microscopy, and by immunostaining for desmin, GFAP, and α-SMA.

Results—In both liver and pancreatic sections, stellate shaped cells were observed; these were positive for desmin and GFAP and negative for α-SMA. Pancreatic stellate shaped cells had a periacinar distribution. They comprised 3.99% of all pancreatic cells; hepatic stellate cells comprised 7.94% of all hepatic cells. The stellate shaped cells from rat pancreas grew readily in culture. Cells cultured for 24 hours had an angular appearance, contained lipid droplets manifesting positive vitamin A autofluorescence, and stained positively for desmin but negatively for α-SMA. At 48 hours, cells were positive for α-SMA.

Conclusions—Cells resembling hepatic stellate cells are present in rat pancreas in a number comparable with that of stellate cells in the liver. These stellate shaped pancreatic cells can be isolated and cultured in vitro.
Enhanced fibroblast growth factor 5 expression in stromal and exocrine elements of the pancreas in chronic pancreatitis
Authors: Ishiwata T , Kornmann M , Beger H G , Korc M
Published: June 2010

Background—Fibroblast growth factor 5 (FGF-5) belongs to a group of mitogenic and angiogenic heparin binding growth factors but its potential role in chronic inflammatory conditions is not known.

Aims—To compare FGF-5 expression in the normal pancreas and in the pancreas of patients with chronic pancreatitis (CP) and to characterise FGF-5 expression and secretion in TAKA-1 cells, an immortalised Syrian hamster pancreatic duct cell line.

Methods and results—Northern blotting revealed the presence of a 4.0 kb FGF-5 mRNA transcript in both normal and CP tissue samples. Densitometric analysis indicated that the transcript levels were increased by a factor of 1.44 in CP tissue samples compared with normal tissue samples (p=0.039). By immunohistochemisty and in situ hybridisation, FGF-5 was faintly expressed in ductal and islet cells in the normal pancreas. In contrast, in CP tissue samples, there was abundant expression of FGF-5 in ductal, acinar, and islet cells, as well as in periductal fibroblasts. FGF-5 was also expressed in TAKA-1 cells as determined by Northern blotting. By immunoblotting of heparin-sepharose precipitates, TAKA-1 cells were shown to secrete FGF-5 into the medium.

Conclusion—Exocrine and stromal derived FGF-5 has the potential to participate in autocrine and paracrine pathways that may contribute to the pathobiology of chronic pancreatitis.
Expression of inducible nitric oxide synthase activity in human colon epithelial cells: modulation by T lymphocyte derived cytokines
Authors: Kolios G , Rooney N , Murphy C T , Robertson D A F , Westwick J
Published: June 2010

Background—Nitric oxide (NO) synthesis and inducible nitric oxide synthase (iNOS) expression are increased in colonic biopsy specimens from patients with ulcerative colitis, but the cellular source of NO production is not known.

Aims—To examine the distribution of iNOS in human colonic mucosa and to explore the ability of T lymphocyte derived cytokines to regulate iNOS expression and activity in human colonic epithelial cells.

Methods—iNOS expression was examined using immunohistochemistry in colonic biopsy samples from 12 patients with ulcerative colitis and three with infectious colitis and compared with 10 normal controls. In vitro iNOS expression and activity were determined in HT-29 cell cultures; nitrite levels were measured using a fluorescent substrate, iNOS mRNA expression by northern blot analysis, and iNOS protein expression by western blot analysis.

Results—No iNOS expression was detected (10 of 10) in non-inflamed mucosa derived from normal controls. In 11 of 12 cases of newly diagnosed ulcerative colitis, iNOS protein was expressed in the epithelial cells, while no other positive cells were found in the lamina propria. Similar iNOS labelling was found in colonic biopsy samples from patients with infectious colitis in the acute phase, but when re-examined in samples from patients in total remission, no iNOS staining was observed. Both interleukin (IL)-13 and IL-4, but not IL-10, are potent inhibitors of iNOS expression and activity induced by an optimal combination of cytokines, namely IL-1α, tumour necrosis factor α and interferon γ.

Conclusions—The data suggest that the epithelium is the major source of iNOS activity in ulcerative colitis and that IL-13 and IL-4 may act as intrinsic regulators of NO generation in intestinal inflammation.
Inflammatory bowel disease-like enteritis and caecitis in a senescence accelerated mouse P1/Yit strain
Authors: Matsumoto S , Okabe Y , Setoyama H , Takayama K , Ohtsuka J , Funahashi H , Imaoka A , Okada Y , Umesaki Y
Published: June 2010

Background—A new subline of the senescence accelerated mouse (SAM) P1/Yit strain has been established which shows spontaneous enteric inflammation under specific pathogen free (SPF) conditions.

Aims—To elucidate the pathogenesis of enteric inflammation in this new subline.

Methods—The SPF and germ free (GF) SAMP1/Yit strains were used. Histological, immunological, and microbiological characterisation of the mice with enteric inflammation was performed.

Results—Histologically, enteritic inflammation developed as a discontinuous lesion in the terminal ileum and caecum with the infiltration of many inflammatory cells after 10 weeks of age. The activity of myeloperoxidase, and both immunolocalisation and mRNA expression of inducible nitric oxide synthase increased in the lesion. CD3-ε positive T cells, neutrophils, and macrophages were more numerous in the inflamed mucosa of the SAMP1/Yit strain. The GF SAMP1/Yit strain did not show any inflammation in the intestinal wall, by the age of 30 weeks, and the enteritis and caecitis developed 10 weeks after the conventionalisation of the GF SAMP1/Yit strain.

Conclusion—Enteric inflammation in the ileum and caecum developed in the SAMP1/Yit strain. The pathophysiological characteristics of the disease in this mouse have some similarities to those of human inflammatory bowel disease (IBD). This mouse strain should be a useful model system for elucidating the interaction between the pathogenesis of IBD and the gut microflora.