bluuebunny/crossref_metadata_2025_split huggingface dataset:
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/AimsConclusive 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.MethodsBacteria 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.ResultsOropharyngeal 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.ConclusionsSmall 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

BackgroundThe pathophysiological mechanisms in non-ulcer dyspepsia are incompletely understood.AimsTo compare gastric motor and sensory functions in Helicobacter pyloripositive or negative patients with non-ulcer dyspepsia.PatientsSeventeen patients with non-ulcer dyspepsia and 16 asymptomatic controls.MethodsThe 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).ResultsGastric 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.ConclusionImpaired 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

BackgroundInterstitial 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.AimTo investigate ICCs in the human fetal small bowel using c-kit immunohistochemistry.SubjectsSmall 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.MethodsImmunohistochemical 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.Resultsc-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.ConclusionsICCs 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.