bluuebunny/crossref_metadata_2025 huggingface dataset:
bax, but notbcl-2, influences the prognosis of human pancreatic cancer
Authors: Friess H , Lu Z , Graber H U , Zimmermann A , Adler G , Korc M , Schmid R M , Büchler M W
Published: June 2010

Background—bcl-2and bax belong to thebcl-2-related gene family, which marks a new class of genes that influence apoptosis. Thebcl-2 oncogene acts as a broad antiapoptotic factor and extends both normal and tumour cell survival. In contrast, the bax gene is a promoter of apoptosis.

Aims—To analyse the expression of bcl-2 andbax in pancreatic cancer and correlate the results with clinical parameters.

Patients—Pancreatic cancer tissue samples were obtained from 28 female and 32 male patients (median age 63, range 43–79 years) having surgery for pancreatic cancer. Normal pancreatic tissues obtained from 18 previously healthy organ donors served as controls.

Methods—The levels ofbcl-2 and baxmRNA expression were analysed by northern blot and the exact site of mRNA transcription was determined by in situ hybridisation. The presence of the corresponding proteins was determined by immunohistochemistry.

Results—Northern blot analysis indicated that, in comparison with the normal pancreas,bcl-2 mRNA was overexpressed in 30% andbax mRNA in 61% of the pancreatic cancer samples. Concomitant overexpression ofbcl-2 and bax was present in 26% of the cancer samples. Pancreatic adenocarcinomas exhibited 3.7-fold and 5.4-fold increases (p<0.001) inbcl-2 and baxmRNA levels respectively. In situ hybridisation showed that bothbcl-2 and baxmRNA were expressed in the cancer cells. Immunohistochemical analysis showed positive Bcl-2 and Bax immunostaining in 28 and 83% of the cancer samples respectively. In multivariate analysis (Cox regression model), bax expression was found to be a strong indicator of survival (p<0.001). Patients whose tumours exhibited Bax immunostaining lived significantly longer (12 months) than those whose tumours were Bax negative (five months) (p<0.039). In contrast, no relation was found between Bcl-2 and survival time.

Conclusions—The data indicate that genes that are involved in the regulation of apoptosis are upregulated in human pancreatic cancer cells. Prolonged survival times in patients in whom apoptosis promoting factors are upregulated indicate that apoptotic pathways are of biological significance in pancreatic cancer.
Age and Helicobacter pylori decrease gastric mucosal surface hydrophobicity independently
Authors: Hackelsberger A , Platzer U , Nilius M , Schultze V , Günther T , Dominguez-Muñoz J E , Malfertheiner P
Published: June 2010

Background—Gastric mucosal surface hydrophobicity (GMSH) is an essential component of the mucosal defence system that is decreased by Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs). Gastric ulcers occur predominantly in elderly subjects, and may thus reflect diminished mucosal resistance.

Aims—To investigate whether aging decreases GMSH.

Patients—One hundred and twenty patients without peptic ulcer disease were divided into three age groups: I (41 years or below); II (41–64 years); and III (65 years or above).

Methods—Biopsy specimens were taken from the antrum, corpus, and cardia for histology (Sydney system), urease testing for H pylori, and for contact angle measurement of GMSH with a goniometer. The presence of specific H pyloriantibodies was checked by immunoblotting.

Results—Fifty two patients (43%) were infected, and 68 were uninfected with H pylori. GMSH at all biopsy sites was lower in H pylori infected subjects (p=0.0001), but also decreased with age independently of infection status (p=0.0001). The most notable decrease in GMSH occurred between age groups I and II in those with, and between age groups II and III in those without, H pylori infection. GMSH was greater in antral than in corpus mucosa in both infected (p=0.0001) and uninfected patients (p=0.0003).

Conclusions—A physiological decrease in GMSH with aging may contribute to the risk of ulcer development in the elderly, and may act synergistically with H pylori and/or NSAIDs on gastric mucosal defence.
Helicobacter pylori in vivo causes structural changes in the adherent gastric mucus layer but barrier thickness is not compromised
Authors: Newton J L , Jordan N , Oliver L , Strugala V , Pearson J , James O F W , Allen A
Published: June 2010

Background—It has been proposed that a pathogenic effect of Helicobacter pylori is a weakening of the protective mucus barrier; however, this remains controversial.

Aims—To clarify the effects of H pylori infection on the mucus gel barrier in vivo.

Methods—Mucus gel polymeric structure and the thickness of the adherent mucus barrier were measured in endoscopic biopsy samples in subjects with and without H pyloriinfection.

Results—There was a significant 18% reduction in the proportion of polymeric gel forming mucin in the adherent mucus layer in H pylori positive compared with negative subjects. There was no change in the adherent mucus thickness betweenH pylori positive and negative subjects without gastric atrophy (mean (SD): 104 (26) μm, 106 (30) μm respectively). There was however a significant reduction in mucus thickness in those H pylori positive subjects with underlying gastric atrophy (84 (13) μm, p=0.03) compared with those without atrophy.

Conclusions—A partial breakdown in gel forming structure of the gastric mucus barrier does occur in H pylori infection per se but this is insufficient to cause a collapse of the mucus barrier.
Mucin gene expression in human embryonic and fetal intestine
Authors: Buisine M P , Devisme L , Savidge T C , Gespach C , Gosselin B , Porchet N , Aubert J P
Published: June 2010

Background—The intestinal epithelium is covered by a continuous layer of mucus which is secreted by well differentiated epithelial cells. Disregulation of the expression of mucins has been reported to have possible implications in the neoplastic process which affects intestinal mucosae. It is well known that preneoplastic and neoplastic tissues can express fetal phenotypic characteristics.

Aims—To assess whether the expression of mucin genes in the intestinal tract is linked to the stage of cellular differentiation and tissue development, by studying the expression of six mucin genes in human fetal small intestine and colon, and also adult tissues.

Methods—In situ hybridisation was used to study mRNA expression of MUC2, MUC3, MUC4, MUC5B, MUC5AC, and MUC6 in 32 human embryos and fetuses (6.5–27 weeks gestation). Normal adult mucosae were used as controls.

Results—Three mucin genes, MUC2, MUC4, and MUC5AC, were differently expressed in fetal intestine compared with expression in normal adults.

Conclusion—These differences in mucin gene expression suggest a possible regulatory role for these products in intestinal epithelial cell differentiation.
Expression of basic fibroblast growth factor in intact and ulcerated human gastric mucosa
Authors: Hull M A , Brough J L , Powe D G , Carter G I , Jenkins D , Hawkey C J
Published: June 2010

Background—Basic fibroblast growth factor (bFGF) promotes angiogenesis and healing of gastric ulcers in rats, and bFGF expression is up regulated in such ulcers. However, little is known about expression of bFGF in human gastric mucosa.

Aims—To investigate bFGF expression in intact human gastric mucosa and gastric ulcers and to determine whether low bFGF content or altered binding by mucosa is associated with ulceration.

Subjects—Endoscopy outpatients, gastrectomy patients, and organ donors.

Methods—bFGF was isolated by heparin affinity chromatography and characterised by western blotting and endothelial cell bioassay. bFGF was measured by immunoassay and its distribution defined by immunohistochemistry and in situ hybridisation. Binding of bFGF by heparan sulphate proteoglycans was investigated by sodium chloride and heparin extraction.

Results—Bioactive bFGF (19 kDa) was detected in normal mucosa but bFGF mRNA was not found. bFGF expression was up regulated in granulation tissue endothelial cells, mononuclear cells, and epithelial cells at the ulcer rim. Gastric ulcer patients had constitutively low bFGF concentrations in intact antral mucosa which were not explained by changes in binding to heparan sulphate proteoglycans.

Conclusions—bFGF expression is up regulated in human gastric ulcers. Low intact mucosal bFGF content is associated with gastric ulceration.
Oncological implications of RET gene mutations in Hirschsprung’s disease
Authors: Sijmons R H , Hofstra R M W , Wijburg F A , Links T P , Zwierstra R P , Vermey A , Aronson D C , Tan-Sindhunata G , Brouwers-Smalbraak G J , Maas S M , Buys C H C M
Published: June 2010

Background—Germline mutations of the RET proto-oncogene identical to those found in the tumour predisposition syndrome multiple endocrine neoplasia type 2A (MEN2A), were detected in 2.5–5% of sporadic and familial cases of Hirschsprung’s disease. Some patients with Hirschsprung’s disease may therefore be exposed to a highly increased risk of tumours.

Aims—To define clinical use of RET gene testing in Hirschsprung’s disease and related patient management from an oncological point of view.

Methods—Sixty patients with Hirschsprung’s disease were screened for RET mutations. In three, MEN2A type RET mutations were detected. Case reports for these three patients are presented.

Results and conclusions—Only 22 families or sporadic patients with Hirschsprung’s disease and MEN2A type RET mutations have been reported. Therefore, it is difficult to predict tumour risk for patients with familial or sporadic Hirschsprung’s disease, and their relatives, who carry these mutations. For these mutation carriers, periodic screening for tumours as in MEN2A is advised, but prophylactic thyroidectomy is offered hesitantly. RET gene testing in familial or sporadic Hirschsprung’s disease is not recommended at present outside a complete clinical research setting. In combined MEN2A/Hirschsprung’s disease families RET gene testing, tumour screening, and prophylactic thyroidectomy are indicated as in MEN2A.
Variable phenotype of familial adenomatous polyposis in pedigrees with 3′ mutation in the APC gene
Authors: Brensinger J D , Laken S J , Luce M C , Powell S M , Vance G H , Ahnen D J , Petersen G M , Hamilton S R , Giardiello F M
Published: June 2010

Background—Germline mutation in the adenomatous polyposis coli (APC) gene on chromosome 5 causes familial adenomatous polyposis. “Attenuated” phenotype has been reported with mutation in the 5′ end of the gene (5′ to codon 158), but genotype-phenotype relations at the 3′ end (3′ to codon 1596) have not been described fully.

Aims—To describe and compare colorectal and extracolonic phenotypes in a case series of families with mutation in the 3′ end of the APC gene.

Methods—Thirty one at risk or affected members from four families with a mutation in the APC gene located at codon 1979 or 2644 were evaluated.

Results—Variable intrapedigree colorectal phenotype was observed: some members at older age had oligopolyposis (fewer than one hundred colorectal adenomas) whereas other members had classic polyposis at young age. Colorectal cancer was diagnosed at older mean age (50 (7) years) in the four families than in classic FAP pedigrees (39 (14) years). Extracolonic lesions characteristic of FAP occurred with 3′ APC mutations, but variability in intrapedigree and interpedigree extracolonic phenotype and dissociation of severity of extracolonic manifestations from number of colorectal polyps was noted.

Conclusions—Families with 3′ mutations of the APC gene exhibit variable intrapedigree phenotype similar to the heterogeneity noted in families with proximal 5′ mutations. Genotyping of FAP and oligopolyposis pedigrees can guide appropriate surveillance of the upper and lower gastrointestinal tract in affected members.
Increased nitric oxide activity in a rat model of acute pancreatitis
Authors: Al-Mufti R A , Williamson R C N , Mathie R T
Published: June 2010

Background—Overproduction of nitric oxide (NO) via induction of the inducible NO synthase (iNOS) is an important factor in the haemodynamic disturbances of several inflammatory states.

Aims—To identify the role of NO in a caerulein induced model of acute pancreatitis in the rat.

Methods—Arterial blood pressure and plasma NO metabolites were measured at zero and seven hours in adult male Wistar rats administered caerulein (n=10) or saline (n=10). Pancreatic activity of NOS (inducible and constitutive) was assayed biochemically. The pancreatic expression and cellular localisation of NOS and nitrotyrosine (a marker of peroxynitrite induced oxidative tissue damage) were characterised immunohistochemically.

Results—Compared with controls at seven hours, the pancreatitis group displayed raised plasma NO metabolites (mean (SEM) 70.2 (5.9) versus 22.7 (2.2) μmol/l, p<0.0001) and reduced mean arterial blood pressure (88.7 (4.6) versus 112.8 (4.1) mm Hg, p=0.008). There was notable iNOS activity in the pancreatitis group (3.1 (0.34) versus 0.1 (0.01) pmol/mg protein/min, p<0.0001) with reduced constitutive NOS activity (0.62 (0.12) versus 0.96 (0.08) pmol/mg protein/min, p=0.031). The increased expression of iNOS was mainly localised within vascular smooth muscle cells (p=0.003 versus controls), with positive perivascular staining for nitrotyrosine (p=0.0012 versus controls).

Conclusions—In this experimental model of acute pancreatitis, iNOS induction and oxidative tissue damage in the pancreas is associated with raised systemic NO and arterial hypotension. Excess production of NO arising from the inducible NO synthase may be an important factor in the systemic and local haemodynamic disturbances associated with acute pancreatitis.
Effect of omeprazole 20 mg twice daily on duodenogastric and gastro-oesophageal bile reflux in Barrett’s oesophagus
Authors: Marshall R E K , Anggiansah A , Manifold D K , Owen W A , Owen W J
Published: June 2010

Background—Both acid and duodenal contents are thought to be responsible for the mucosal damage in Barrett’s oesophagus, a condition often treated medically. However, little is known about the effect of omeprazole on duodenogastric reflux (DGR) and duodenogastro-oesophageal reflux (DGOR).

Aims—To study the effect of omeprazole 20 mg twice daily on DGR and DGOR, using the technique of ambulatory bilirubin monitoring.

Methods—Twenty three patients with Barrett’s oesophagus underwent manometry followed by 24 hour oesophageal and gastric pH monitoring. In conjunction with pH monitoring, 11 patients (group 1) underwent oesophageal bilirubin monitoring and 12 patients (group 2) underwent gastric bilirubin monitoring, both before and during treatment with omeprazole 20 mg twice daily.

Results—In both groups there was a significant reduction in oesophageal acid (pH<4) reflux (p<0.005) and a significant increase in the time gastric pH was above 4 (p<0.005). In group 1, median total oesophageal bilirubin exposure was significantly reduced from 28.9% to 2.4% (p<0.005). In group 2, median total gastric bilirubin exposure was significantly reduced from 24.9% to 7.2% (p<0.005).

Conclusions—Treatment of Barrett’s oesophagus with omeprazole 20 mg twice daily results in a notable reduction in the exposure of the oesophagus to both acid and duodenal contents. In addition, delivery of duodenal contents to the upper gastric body is reduced.
First pass metabolism of ethanol is strikingly influenced by the speed of gastric emptying
Authors: Oneta C M , Simanowski U A , Martinez M , Allali-Hassani A , Parés X , Homann N , Conradt C , Waldherr R , Fiehn W , Coutelle C , Seitz H K
Published: June 2010

Background—Ethanol undergoes a first pass metabolism (FPM) in the stomach and liver. Gastric FPM of ethanol primarily depends on the activity of gastric alcohol dehydrogenase (ADH). In addition, the speed of gastric emptying (GE) may modulate both gastric and hepatic FPM of ethanol.

Aims—To study the effect of modulation of GE on FPM of ethanol in the stomach and liver.

Methods—Sixteen volunteers (eight men and eight women) received ethanol (0.225 g/kg body weight) orally and intravenously, and the areas under the ethanol concentration time curves were determined to calculate FPM of ethanol. In seven of these subjects, FPM of ethanol was measured after the intravenous administration of 10 mg metoclopramide (MCP) and 20 mgN-butylscopolamine (NBS) in separate experiments to either accelerate or delay GE. GE was monitored sonographically by integration of the antral area of the stomach every five minutes for 90 minutes after oral ethanol intake. In addition, gastric biopsy specimens were taken to determine ADH activity and phenotype, as well as to evaluate gastric histology. Blood was also drawn for ADH genotyping.

Results—GE time was significantly delayed by the administration of NBS as compared with controls (p<0.0001) and as compared with the administration of MCP (p<0.0001). This was associated with a significantly enhanced FPM of ethanol with NBS compared with MCP (p = 0.0004). A significant correlation was noted between GE time and FPM of ethanol (r = 0.43, p = 0.0407). Gastric ADH activity did not significantly correlate with FPM of ethanol.

Conclusion—FPM of ethanol is strikingly modulated by the speed of GE. Delayed GE increases the time of exposure of ethanol to gastric ADH and may therefore increase gastric FPM of ethanol. In addition, hepatic FPM of ethanol may also be enhanced as the result of slower absorption of ethanol from the small intestine. Thus a knowledge of GE time is a major prerequisite for studying FPM of ethanol in humans.
Postoperative outcome of Crohn’s disease in 30 children
Authors: Besnard M , Jaby O , Mougenot J F , Ferkdadji L , Debrun A , Faure C , Delagausie P , Peuchmaur M , Aigrain Y , Navarro J , Cézard J P
Published: June 2010

Background—Thirty children operated on for Crohn’s disease (CD) were reviewed (1975–1994). The aim of the study was to assess their postoperative outcome.

Patients—19 boys and 11 girls, aged 15.3 (2) years (range 11.3–20) at surgery were studied.

Results—Surgical indications were acute complications of CD and chronic intestinal illness. Six months after surgery, 11 of 12 patients had been weaned off steroids, and 22 of 23 patients were weaned off nutritional support; 17 patients without recurrrence had a mean (SD) weight gain of 2.1 (8) kg and a height gain of 3.36 (3) cm. During 3.1 (2.7) years follow up, 12 patients (40%) had a recurrence of the disease after 19.4 (14) months (means (SD)): supra-anastomotic recurrence (six), severe perianal disease (two), and chronic illness (four). Six of 14 patients who were treated with mesalazine (13) or azathioprine (one) had recurrences. The postoperative recurrence rate was 50% at two years.

Conclusion—Surgical treatment modifies the immediate outcome of severe or complicated CD, but does not prevent recurrence, despite localised resection or prophylactic postoperative treatment. Extension of the disease before surgery seems to be a major risk factor for postoperative recurrence in children.
Ulcerative colitis has an aggressive course after orthotopic liver transplantation for primary sclerosing cholangitis
Authors: Papatheodoridis G V , Hamilton M , Mistry P K , Davidson B , Rolles K , Burroughs A K
Published: June 2010

Background—The course of inflammatory bowel disease after liver transplantation has been reported as variable with usually no change or improvement, but there may be an increased risk of early colorectal neoplasms. In many centres steroids are often withdrawn early after transplantation and this may affect inflammatory bowel disease activity.

Aims—To evaluate the course of inflammatory bowel disease in primary sclerosing cholangitis transplant patients who were treated without long term steroids.

Methods—Between 1989 and 1996, there were 30 patients transplanted for primary sclerosing cholangitis who survived more than 12 months. Ulcerative colitis was diagnosed in 18 (60%) patients before transplantation; two had previous colectomy. All patients underwent colonoscopy before and after transplantation and were followed for 38 (12–92) months. All received cyclosporin or tacrolimus with or without azathioprine as maintenance immunosuppression.

Results—Ulcerative colitis course after transplantation compared with that up to five years before transplantation was the same in eight (50%) and worse in eight (50%) patients. It remained quiescent in eight and worsened in four of the 12 patients with pretransplant quiescent course, whereas it worsened in all four patients with pretransplant active course (p=0.08). New onset ulcerative colitis developed in three (25%) of the 12 patients without inflammatory bowel disease before transplantation. No colorectal cancer has been diagnosed to date.

Conclusions—Preexisting ulcerative colitis often has an aggressive course, while de novo ulcerative colitis may develop in patients transplanted for primary sclerosing cholangitis and treated without long term steroids.
Eradication of Barrett’s mucosa with argon plasma coagulation and acid suppression: immediate and mid term results
Authors: Van Laethem J-L , Cremer M , Peny M O , Delhaye M , Devière J
Published: June 2010

Background—Intestinal metaplastic mucosa in Barrett’s oesophagus can be replaced by squamous epithelium after mucosal thermal ablation associated with acid suppression therapy.

Aims—To assess whether restoration of squamous epithelium can be obtained after ablation of Barrett’s oesophagus using argon plasma coagulation (APC) associated with proton pump inhibitor (PPI) therapy.

Methods—Thirty one patients with Barrett’s oesophagus received APC. Omeprazole (40 mg/day) was given from the first APC application to one month after completion of the treatment, then given symptomatically. Twenty four hour pH-metry was performed during endotherapy.

Results—Complete re-epithelialisation was visualised at endoscopy in 25/31 patients (81%) after a mean number of 2.4 APC sessions (range 1–4). Only partial squamous re-epithelialisation was observed in three patients and three others had no eradication. At histological assessment, eradication of Barrett’s oesophagus was only confirmed in 19/31 patients (61%) due to the presence of a few residual Barrett’s glands under the new squamous epithelium. Complete eradication was related to a Barrett’s oesophagus segment length of less than 4 cm and the absence of circumferential extension but not to the normalisation of oesophageal acid exposure under PPI therapy. Seventeen patients with apparently complete endoscopic and histological eradication of Barrett’s oesophagus were re-evaluated at one year; eight (47%) disclosed relapsing islands of Barrett metaplasia despite continuous omeprazole therapy (10–40 mg/day).

Conclusions—APC combined with 40 mg omeprazole daily can eradicate Barrett’s mucosa with apparent squamous re-epithelialisation in the majority of patients even in the absence of normalisation of oesophageal acid exposure. However, one year after endotherapy for Barrett’s oesophagus, relapse is frequent but limited in extent.
Irritable bowel syndrome, gastro-oesophageal reflux, and bronchial hyper-responsiveness in the general population
Authors: Kennedy T M , Jones R H , Hungin A P S , O’Flanagan H , Kelly P
Published: June 2010

Background—Associations have been shown between irritable bowel syndrome (IBS) and gastro-oesophageal reflux, between gastro-oesophageal reflux and asthma, and more recently between IBS and bronchial hyper-responsiveness (BHR).

Aims—To explore the inter-relations between these conditions.

Subjects—A randomly selected community sample of 4432 adults.

Methods—A validated postal symptom questionnaire investigating the associations between IBS, gastro-oesophageal reflux symptoms, and symptomatic BHR.

Results—3169 questionnaires (71.7% response) returned by 1451 men and 1718 women were analysed. One year prevalences, in men and women respectively, of IBS were 10.5% and 22.9%, of dyspepsia 26.3% and 25.25%, of gastro-oesophageal reflux symptoms 29.4% and 28.2%, of BHR 13.2% and 14.6%, and of chronic bronchitis 8.3% and 4.9%. Logistic regression showed independent associations between IBS and BHR, gastro-oesophageal reflux symptoms, and dyspepsia. There was no significant independent association between IBS and chronic bronchitis. In men and women the odds ratio with 95% confidence interval (CI) for IBS and gastro-oesophageal reflux symptoms was 2.6 (2.1–3.1; p<0.001) and for IBS and BHR 2.1 (1.7–2.7; p<0.001). These associations held on stratifying for sex and consultation behaviour. IBS, gastro-oesophageal reflux symptoms, and bronchial hyper-responsiveness occurred more frequently together than expected, 2.5% (95% CI 2.41–2.57) of the sample having all three conditions compared with an expected prevalence of 0.7% (95% CI 0.66–0.71). The conditions were independently associated with each other.

Conclusions—These observations may indicate the presence of an underlying disorder producing symptoms in gastrointestinal and respiratory systems.
Urokinase type plasminogen activator receptor expression in colorectal neoplasms
Authors: Suzuki S , Hayashi Y , Wang Y , Nakamura T , Morita Y , Kawasaki K , Ohta K , Aoyama N , Kim S R , Itoh H , Kuroda Y , Doe W F
Published: June 2010

Background—The urokinase type plasminogen activator receptor (uPAR) may play a critical role in cancer invasion and metastasis.

Aims—To study the involvement of uPAR in colorectal carcinogenesis.

Methods—The cellular expression and localisation of uPAR were investigated in colorectal adenomas and invasive carcinomas by in situ hybridisation, immunohistochemistry, and northern and western blot analyses.

Results—uPAR mRNA expression was found mainly in the cytoplasm of dysplastic epithelial cells of 30% of adenomas with mild (19%), moderate (21%), and severe (47%) dysplasia, and in that of carcinomatous cells of 85% of invasive carcinomas: Dukes’ stages A (72%), B (93%), and C (91%). Some stromal cells in the adjacent neoplastic epithelium were faintly positive. Immunoreactivity for uPAR was detected in dysplastic epithelial cells of 14% of adenomas and in carcinomatous cells of 49% of invasive carcinomas. uPAR mRNA and protein concentrations were significantly higher in severe than in mild or moderate dysplasia (p<0.05); they were notably higher in Dukes’ stage A than in severe dysplasia (p<0.05), and significantly higher in Dukes’ stage B than in stage A (p<0.05), but those in stage B were not different from those in stage C or in metastatic colorectal carcinomas of the liver.

Conclusions—Colorectal adenoma uPAR, expressed essentially in dysplastic epithelial cells, was upregulated with increasing severity of atypia, and increased notably during the critical transition from severe dysplasic adenoma to invasive carcinoma. These findings implicate uPAR expression in the invasive and metastatic processes of colorectal cancer.
No relationship between gastric pH, small bowel bacterial colonisation, and diarrhoea in HIV-1 infected patients
Authors: Wilcox C M , Waites K B , Smith P D
Published: June 2010

Background/Aims

Conclusive studies of small bowel bacterial overgrowth in patients with HIV-1 infection are limited. The relation was therefore determined between the quantity and species of bacteria in the proximal small intestine of HIV-1 infected patients and the presence of diarrhoea, gastric acidity, severity of immune deficiency, and clinical outcome.

Methods

Bacteria in the duodenal fluids obtained endoscopically from 32 HIV-1 infected patients, 21 of whom had diarrhoea, and seven control subjects without HIV-1 risk factors were quantified and speciated. Gastric pH was determined at the time of endoscopy. Clinical follow up was performed to assess outcome.

Results

Oropharyngeal Gram positive cocci were present in fluids from 28 patients (88%). Gram negative aerobic or facultatively anaerobic bacteria were present in fluids from 12 patients (38%), and strict anaerobes were detected in six patients (19%), but for both groups colony counts infrequently exceeded 104 colony forming units/ml. The number and species of bacteria did not correlate with the presence of diarrhoea, gastric pH, or CD4 lymphocyte count.

Conclusions

Small bowel bacterial overgrowth is not common in HIV-1 infected patients, regardless of the presence of diarrhoea, and is not associated with hypochlorhydria.
Gastric accommodation in non-ulcer dyspepsia and the roles ofHelicobacter pylori infection and vagal function
Authors: Thumshirn M , Camilleri M , Saslow S B , Williams D E , Burton D D , Hanson R B
Published: June 2010

Background

The pathophysiological mechanisms in non-ulcer dyspepsia are incompletely understood.

Aims

To compare gastric motor and sensory functions in Helicobacter pyloripositive or negative patients with non-ulcer dyspepsia.

Patients

Seventeen patients with non-ulcer dyspepsia and 16 asymptomatic controls.

Methods

The following were evaluated: gastrointestinal symptoms; gastric emptying and orocaecal transit of solids; abdominal vagal function; gastric compliance; fasting and postprandial gastric tone and phasic contractions; symptoms during ingestion of cold water and during the distension of an intragastric bag; and somatic sensitivity and personality profile (Minnesota Multiphasic Personality Inventory, MMPI).

Results

Gastric accommodation was reduced in H pylori negative dyspeptics relative to controls; the degree of accommodation was unrelated toH pylori status in dyspeptics. Increased postprandial gastric sensation was more frequent amongH pylori positive patients (4/5H pylori positive versus 4/12H pylori negative patients). Intragastric meal distribution and orocaecal transit were normal; gastric emptying at four hours was abnormal in 4/17 patients. Vagal dysfunction was rare. Eight of 17 patients had somatisation or depression on MMPI.

Conclusion

Impaired gastric accommodation is frequent in non-ulcer dyspepsia and seems to be unrelated to vagal efferent dysfunction. H pylori infection does not seem to influence gastric accommodation, but is associated with heightened sensitivity in dyspeptics. Therapeutic approaches that restore normal postprandial accommodation and gastric sensitivity should be tested in non-ulcer dyspepsia.
Interstitial cells of Cajal in the human fetal small bowel as shown by c-kit immunohistochemistry
Authors: Wester T , Eriksson L , Olsson Y , Olsen L
Published: June 2010

Background

Interstitial cells of Cajal (ICCs) express the tyrosine kinase receptor c-kit, which is required for their development and spontaneous pacemaker activity in the bowel. From murine models it has been proposed that ICCs do not develop until after birth, but more recent findings indicate that c-kit is expressed early in the embryonic period. The temporal development of ICCs in the human gut remains unknown.

Aim

To investigate ICCs in the human fetal small bowel using c-kit immunohistochemistry.

Subjects

Small bowel specimens were obtained at post mortem examination of 16 fetuses and nine neonates, eight of whom were premature, born at gestational ages of 13 to 41 weeks, without gastrointestinal disorders.

Methods

Immunohistochemical analysis was performed on material fixed in formalin and embedded in paraffin. The specimens were exposed to antibodies raised against c-kit (an ICC marker) and neurone specific enolase (a general neuronal marker). The ABC complex method was used to visualise binding of antibodies to the corresponding antigens.

Results

c-kit immunoreactive cells were visualised from 13 weeks of gestation. The immunoreactivity was mainly localised in association with the myenteric plexus. From about 17–18 weeks of gestation, the ICCs formed a layer along the myenteric plexus, whereas this layer appeared to be disrupted at 13–16 weeks of gestation.

Conclusions

ICCs are c-kit immunoreactive at least from a gestational age of 13 weeks in the human fetal small intestine. From 17–18 weeks of gestation until birth, they form a continuous layer around the myenteric ganglia.
Prospective comparison of faecal incontinence grading systems
Authors: Vaizey C J , Carapeti E , Cahill J A , Kamm M A
Published: June 2010

Background

Existing scales for assessing faecal incontinence have not been validated against clinical assessment, or with regard to reproducibility. They also fail to take into account faecal urgency, and the use of antidiarrhoeal medications.

Aims

To establish the validity, and sensitivity to change, of existing scales and a newly designed incontinence scale.

Methods

(1) Twenty three patients (21 females, median age 57 years) were prospectively evaluated by two independent clinical observers, using three established scales (Pescatori, Wexner, American Medical Systems), a newly devised scale which also includes details about urgency and antidiarrhoeal drugs, and by a 28 day diary. (2) A further 10 female patients were assessed by the same scales before and after surgery for faecal incontinence.

Results

(1) Assessments by two independent clinicians correlated well. All four scales and a diary card correlated highly and significantly with the clinical impression, with the new scale reaching the highest correlation (r=0.79, p<0.001). (2) All except one score changed significantly in response to surgical treatment; the new scale showed the greatest change, at the highest level of significance (p=0.004), and correlated best with the clinicians’ assessment of change (r=0.94, p<0.001).

Conclusions

Existing scales for the assessment of faecal incontinence correlate well with careful clinical impression of severity, and serve as useful and reproducible measures for comparison of patients and treatments. A newly devised scale has shown high clinical validity and utility.
Percutaneous endoscopic gastrostomy feeding in patients with cystic fibrosis
Authors: Williams S G J , Ashworth F , McAlweenie A , Poole S , Hodson M E , Westaby D
Published: June 2010

Background

Malnutrition is a common management problem in patients with cystic fibrosis (CF). Various approaches to supplemental nutrition by both parenteral and enteral routes have been used.

Aim

To analyse the efficacy and acceptability of supplemental overnight feeding using a percutaneous endoscopic gastrostomy (PEG) in patients with CF.

Patients

53 patients with CF (43 adults; age >17 years) with severe pulmonary disease.

Methods

The technical success and complications of PEG insertion were documented together with changes in nutritional and pulmonary status of the cohort.

Results

PEG tubes were successfully inserted in all patients, with immediate complications (respiratory depression) in two (4%) and late complications in 13 (25%). Feeding was well tolerated by 50/51 (98%) of the cohort during a mean (SEM) follow up of 14.5 (2.1) months. The adult cohort had a significant increase in weight and body mass index at six months which was maintained at 12 months. Serum albumin concentration remained stable at six months but had fallen by 12 months, although the differences were not statistically significant. These results were reflected in the paediatric cohort. Pulmonary function in those followed up for one year had apparently stabilised, but the number of admissions to hospital over the year before and the year after PEG did not change. Half of the cohort were accepted for heart-lung/lung transplantation, the improvement in nutritional status being a prerequisite for this.

Conclusion

Supplemental PEG tube feeding is well tolerated and results in a significant improvement in nutritional status and an apparent stabilisation of pulmonary function in severely malnourished CF patients with advanced pulmonary disease.
Botulinum toxin versus pneumatic dilatation in the treatment of achalasia: a randomised trial
Authors: Vaezi M F , Richter J E , Wilcox C M , Schroeder P L , Birgisson S , Slaughter R L , Koehler R E , Baker M E
Published: June 2010

Background

Intrasphincteric injection of botulinum toxin is a new treatment option for achalasia.

Aims

To compare the immediate and long term efficacy of botulinum toxin with that of pneumatic dilatation.

Methods

Symptomatic patients with achalasia were randomised to botulinum toxin (22 patients, median age 57 years) or pneumatic dilatation (20 patients, median age 56 years). Symptom scores were assessed initially, and at one, three, six, nine, and 12 months after treatment. Objective assessment included oesophageal manometry initially and at one month, and barium oesophagram initially and at one, six, and 12 months post-treatment.

Results

Pneumatic dilatation resulted in a significantly (p=0.02) higher cumulative remission rate. At 12 months, 14/20 (70%) pneumatic dilatation and 7/22 (32%) botulinum toxin treated patients were in symptomatic remission (p=0.017). Failure rates were similar initially, but failure over time was significantly (p=0.01) higher after botulinum toxin (50%) than pneumatic dilatation (7%). Pneumatic dilatation resulted in significant (p<0.001) reduction in symptom scores, and lower oesophageal sphincter pressure, oesophageal barium column height, and oesophageal diameter. Botulinum toxin produced significant reduction in symptom scores (p<0.001), but no reduction in objective parameters.

Conclusions

At one year pneumatic dilatation is more effective than botulinum toxin. Symptom improvement parallels objective oesophageal measurements after pneumatic dilatation but not after botulinum toxin treatment for achalasia.
Inhibition of nuclear factor-κB activation improves the survival of rats with taurocholate pancreatitis
Authors: Satoh A , Shimosegawa T , Fujita M , Kimura K , Masamune A , Koizumi M , Toyota T
Published: June 2010

Background

Death in the early stages of severe acute pancreatitis is frequently the result of multiple organ dysfunction, but its mechanism is not clear.

Aims

To investigate the state of nuclear factor-κB (NF-κB) in macrophages of rats with lethal pancreatitis, and to assess the effectiveness of pyrrolidine dithiocarbamate, an inhibitor of NF-κB, on the pathology and mortality.

Methods

Taurocholate pancreatitis was produced in rats, and the severity of the disease, the mortality, and activation of NF-κB in peritoneal and alveolar macrophages were compared in rats receiving pyrrolidine dithiocarbamate (PDTC) treatment and those that were not.

Results

Taurocholate pancreatitis produced massive necrosis, haemorrhage, and severe leucocyte infiltration in the pancreas as well as alveolar septal thickening in the lung. NF-κB was activated in peritoneal and alveolar macrophages six hours after pancreatitis induction. Pretreatment with PDTC dose-dependently attenuated the NF-κB activation and improved the survival of the rats, although it did not affect the early increase in serum amylase and histological findings.

Conclusions

Early blockage of NF-κB activation may be effective in reducing fatal outcome in severe acute pancreatitis.
Anti-inflammatory drugs and variceal bleeding: a case-control study
Authors: De Lédinghen V , Heresbach D , Fourdan O , Bernard P , Liebaert-Bories M P , Nousbaum J B , Gourlaouen A , Becker M C , Ribard D , Ingrand P , Silvain C , Beauchant M
Published: June 2010

Background

Non-steroidal anti-inflammatory drugs (NSAIDs) can have severe gastrointestinal effects and cause peptic ulcers to bleed. Acute bleeding from oesophageal varices is a major complication of cirrhosis of the liver.

Aims

To investigate the role, using a case-control study, of NSAIDs in first bleeding episodes associated with oesophageal or cardial varices in cirrhotic patients.

Patients/Methods

A structured interview was conducted of 125 cirrhotic patients with bleeding mainly related to oesophageal varices and 75 cirrhotic controls with oesophageal varices who had never bled.

Results

Cirrhotic patients who were admitted for bleeding related to portal hypertension were more likely to have used NSAIDs during the week before the index day (31 of 125 (25%)) than the cirrhotic controls (eight of 75 (11%); odds ratio = 2.8, p = 0.016). Use of aspirin alone or combined with other NSAIDs was also more prevalent in the cases (21 of 125 (17%)) than in the controls (three of 75 (4%); odds ratio = 4.9, p = 0.007). Logistic regression analysis showed that NSAID use (p = 0.022, odds ratio = 2.9, 95% confidence interval = 1.8 to 4.7) and variceal size (p<0.001, odds ratio = 4.0, 95% confidence interval = 1.4 to 11.5) were the only variables independently associated with the risk of bleeding.

Conclusions

Aspirin, used alone or combined with other NSAIDs, was associated with a first variceal bleeding episode in patients with cirrhosis. Given the life threatening nature of this complication, the possible benefit of this treatment should be weighed against the risk shown here. No firm conclusions could be drawn on non-aspirin NSAIDs used alone.
Validation of the Rockall risk scoring system in upper gastrointestinal bleeding
Authors: Vreeburg E M , Terwee C B , Snel P , Rauws E A J , Bartelsman J F W M , Meulen J H P vd , Tytgat G N J
Published: June 2010

BACKGROUND

Several scoring systems have been developed to predict the risk of rebleeding or death in patients with upper gastrointestinal bleeding (UGIB). These risk scoring systems have not been validated in a new patient population outside the clinical context of the original study.

AIMS

To assess internal and external validity of a simple risk scoring system recently developed by Rockall and coworkers.

METHODS

Calibration and discrimination were assessed as measures of validity of the scoring system. Internal validity was assessed using an independent, but similar patient sample studied by Rockall and coworkers, after developing the scoring system (Rockall’s validation sample). External validity was assessed using patients admitted to several hospitals in Amsterdam (Vreeburg’s validation sample). Calibration was evaluated by a χ2 goodness of fit test, and discrimination was evaluated by calculating the area under the receiver operating characteristic (ROC) curve.

RESULTS

Calibration indicated a poor fit in both validation samples for the prediction of rebleeding (p<0.0001, Vreeburg; p=0.007, Rockall), but a better fit for the prediction of mortality in both validation samples (p=0.2, Vreeburg; p=0.3, Rockall). The areas under the ROC curves were rather low in both validation samples for the prediction of rebleeding (0.61, Vreeburg; 0.70, Rockall), but higher for the prediction of mortality (0.73, Vreeburg; 0.81, Rockall).

CONCLUSIONS

The risk scoring system developed by Rockall and coworkers is a clinically useful scoring system for stratifying patients with acute UGIB into high and low risk categories for mortality. For the prediction of rebleeding, however, the performance of this scoring system was unsatisfactory.
Giardia induces proliferation and interferon γ production by intestinal lymphocytes
Authors: Ebert E C
Published: June 2010

BACKGROUND

Murine intraepithelial lymphocytes kill Giardia lambia; responses of human intestinal lymphocytes to this parasite are unknown.

AIMS

To examine giardia induced proliferation, interferon γ production, migration, and cytotoxicity by lymphocytes from the human intestine and peripheral blood.

METHODS

Giardia were added to intraepithelial lymphocytes, lamina propria lymphocytes, and peripheral blood lymphocytes, obtained from jejunal mucosa and blood of otherwise healthy patients undergoing gastric bypass surgery for morbid obesity. Proliferation was measured by 3H-thymidine incorporation; frequency of proliferation precursors, by limiting dilution analysis; interferon γ production, by ELISA; cytotoxicity, by 51Cr release of radiolabelled giardia and by release of serine esterases by effector lymphocytes that mediate cytotoxicity.

RESULTS

The CD4+ T lymphocytes from intestine and blood proliferated in response to giardia. The stimulus by the parasite was mitogenic rather than antigenic due to the fact that the peak response was on day 3 rather than day 6, and the large number of precursors was in the range of that for mitogens. CD4+ T lymphocytes from both sites produced interferon γ in response to giardia. Lymphocytes did not migrate towards or kill the parasite.

CONCLUSIONS

Giardia induced the same degree of proliferation and interferon γ production by CD4+ T lymphocytes in intestine and blood, but did not trigger cytotoxicity or migration.
Adenovirus mediated p53 tumour suppressor gene therapy for human gastric cancer cells in vitro and in vivo
Authors: Ohashi M , Kanai F , Ueno H , Tanaka T , Tateishi K , Kawakami T , Koike Y , Ikenoue T , Shiratori Y , Hamada H , Omata M
Published: June 2010

BACKGROUND/AIMS

Gastric cancer is one of the most prevalent forms of cancer in East Asia. Point mutation of the p53 gene has been reported in more than 60% of cases of gastric cancer and can lead to genetic instability and uncontrolled cell proliferation. The purpose of this investigation was to evaluate the potential of p53 gene therapy for gastric cancer.

METHODS

The responses of human gastric cancer cell lines, MKN1, MKN7, MKN28, MKN45, and TMK-1, to recombinant adenoviruses encoding wild type p53 (AdCAp53) were analysed in vitro. The efficacy of the AdCAp53 treatment for MKN1 and MKN45 subcutaneous tumours in nude mice was assessed in vivo.

RESULTS

p53-specific growth inhibition was observed in vitro in two of four gastric cancer cell lines with mutated p53, but not in the wild type p53 cell line. The mechanism of the killing of gastric cancer cells by AdCAp53 was found, by flow cytometric analysis and detection of DNA fragmentation, to be apoptosis. In vivo studies showed that the growth of subcutaneous tumours of p53 mutant MKN1 cells was significantly inhibited by direct injection of AdCAp53, but no significant growth inhibition was detected in the growth of p53 wild type MKN45 tumours.

CONCLUSIONS

Adenovirus mediated reintroduction of wild type p53 is a potential clinical utility in gene therapy for gastric cancers.
Effects of short term sacral nerve stimulation on anal and rectal function in patients with anal incontinence
Authors: Vaizey C J , Kamm M A , Turner I C , Nicholls R J , Woloszko J
Published: June 2010

BACKGROUND

Some patients with faecal incontinence are not amenable to simple surgical sphincter repair, due to sphincter weakness in the absence of a structural defect.

AIMS

To evaluate the efficacy and possible mode of action of short term stimulation of sacral nerves in patients with faecal incontinence and a structurally intact external anal sphincter.

PATIENTS

Twelve patients with faecal incontinence for solid or liquid stool at least once per week.

METHODS

A stimulating electrode was placed (percutaneously in 10 patients, operatively in two) into the S3 or S4 foramen. The electrode was left in situ for a minimum of one week with chronic stimulation.

RESULTS

Evaluable results were obtained in nine patients, with early electrode displacement in the other three. Incontinence ceased in seven of nine patients and improved notably in one; one patient with previous imperforate anus and sacral agenesis had no symptomatic response. Stimulation seemed to enhance maximum squeeze pressure but did not alter resting pressure. The rectum became less sensitive to distension with no change in rectal compliance. Ambulatory studies showed a possible reduction in rectal contractile activity and diminished episodes of spontaneous anal relaxation.

CONCLUSIONS

Short term sacral nerve stimulation notably decreases episodes of faecal incontinence. The effect may be mediated via facilitation of striated sphincter muscle function, and via neuromodulation of sacral reflexes which regulate rectal sensitivity and contractility, and anal motility.