bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gastric ulcer healing in the rat: kinetics and localisation of de novo procollagen synthesis
Authors: Shahin M , Gillessen A , Pohle T , Weber C , Schuppan D , Herbst H , Domschke W 
Published: June 2010

Background and aims—To gain further insight into the role of the extracellular matrix during healing of peptic ulcers, sequential changes of procollagen expression were studied over 30 days of ulcer healing.Materials and methods—Procollagens α1(I), α1(III), and α1(IV) RNA and their polypeptides were assessed in acetic acid induced rat gastric ulcers by in situ hybridisation and immunohistochemistry.Results—Three days after ulcer induction, intense hybridisation signals were obtained with all probes, with procollagen α1(I) showing the highest transcript levels. Procollagen gene expression remained elevated up to day 15, but was reduced to initial low levels on day 30. Immunohistochemical staining documented increased deposition of the three procollagen types parallel to their respective transcript levels, again with type I showing the earliest and the most prominent deposits. The highest procollagen transcript levels were found in the intact submucosa surrounding the ulcer margins, followed by the muscularis propria and the serosa, with the lamina propria exhibiting the lowest transcript levels.Conclusion—The procollagens studied are regulated differentially at the transcriptional and post-transcriptional levels. The early onset and long duration of procollagen expression as well as the involvement of all layers of the gastric wall points to their central structural and functional role in gastric ulcer healing.
K-ras mutations in patients with early colorectal cancers
Authors: Andreyev H J N , Tilsed J V T , Cunningham D , Sampson S A , Norman A R , Schneider H J , Clarke P A 
Published: June 2010

Background—Published data are contradictory about the importance of K-ras mutations in advanced tumours and are not available for early cancers.Aims—To establish whether specific K-ras mutations are prognostic markers in early stage colorectal adenocarcinoma.Methods—The presence of K-ras exon 1 mutations were correlated with tumour recurrence in two groups of patients: group 1 was a consecutive series of patients with resected colorectal adenocarcinoma at low risk of recurrence; group 2 were patients referred for chemotherapy after relapse of previously resected early stage tumours. K-ras mutations were detected by direct sequencing of whole tissue samples in all patients and in some, the leading edge and centre of the tumour were also microdissected out individually and sequenced.Results—Mutations were present in 26 (26.5%) of 98 patients in group 1; 14 patients developed a recurrence, four (28.5%) of whom had a K-ras mutation. Seventy nine patients have not developed tumour recurrence, 22 (28%) of whom had a mutation (p=0.84). K-ras mutations were present in five of 14 patients in group 2. Microdissection did not increase the number of mutations detected.Conclusions—Individual K-ras genotypes are distributed homogeneously throughout early stage colorectal adenocarcinomas, but detection of a mutation has no apparent prognostic value.
Elevated calcium and activation of trypsinogen in rat pancreatic acini
Authors: Frick T W , Fernández-del-Castillo C , Bimmler D , Warshaw A L 
Published: June 2010

Background—Acute pancreatitis associated with hypercalcaemia has been described in humans and experimental animals. It has been demonstrated that calcium dose dependently accelerates trypsinogen activation, and it is generally believed that ectopic activation of digestive enzymes is an early event in the pathophysiology of acute pancreatitis.Aims and methods—Trypsinogen activation peptide (TAP) was measured in isolated rat pancreatic acini exposed to elevated extracellular calcium in order to investigate the association between calcium and trypsinogen activation in living cells. TAP was determined in the culture medium either before (extracellular compartment) or after (intracellular compartment) cell homogenisation.Results—Neither secretory stimulation nor elevated calcium alone caused an increase in TAP levels. Maximal cerulein or carbachol stimulation superimposed on high medium calcium, however, significantly increased intracellular trypsinogen activation twofold. This increase was inhibited by eitherNG-monomethyl-l-arginine (l-NMMA) or verapamil. Acinar cell morphology and function remained intact as demonstrated by electron microscopy and secretagogue dose-response studies.Conclusions—These results support the hypothesis that increased intracellular trypsinogen activation is an early step in the pathogenesis of hypercalcaemia induced pancreatitis. The model may have a bearing on other types of pancreatitis as elevated cytosolic calcium is thought to be an early event in the pathogenesis of acute pancreatitis in general.
Hirschsprung’s disease: genetic mutations in mice and men
Authors: ROBERTSON K , MASON I , HALL S 
Published: June 2010

Hirschsprung’s disease is a neuronal dysplasia of the hindgut, characterised by a loss of neurones, which affects about 1 in 5000 live births.1 Genetic factors have been implicated in the aetiology of this disease in about 20% of cases and a dominant pattern of inheritance has been revealed in several families.2
3The pathogenesis of the aganglionosis is often attributed to a failure of migration of neural crest cells, although this has not been proven.Recently, mutations in a developmentally regulated receptor tyrosine kinase gene, ret, and mutations in the endothelin receptor-B gene (ENDR-B) have both been linked to familial Hirschsprung’s disease in humans.4-6 Moreover, certain mutant mouse strains—namely piebald lethal and lethal spotted—exhibit striking similarities to the human condition. The mutation which gives rise to piebald lethal has now been found to be in the ENDR-B gene,7 and the mutation associated with lethal spotted occurs in the gene for endothelin-3 (ET-3), a ligand for ENDR-B.8
Two transgenic mouse lines have been developed which also reflect the human disease: ret-k−, which has aloss of function mutation of the retgene,9 and ENDR-B null.10 In addition, the introduction of a Lac-Z reporter gene into neural crest cells of aganglionic mice has made it possible to study directly the fate of enteric neuroblasts which are affected by “Hirschsprung’s-like” mutations.11 Here, we review the possible roles of RET and endothelin in the normal development of the enteric nervous system, and the significance of their mutated forms in the pathogenesis of familial aganglionosis.This review focuses on recent advances in our understanding of the genetic basis of the lesions which have been implicated in congenital forms of Hirschsprung’s disease. Disruption of these genes in the mouse, either by transgenic “knockout” approaches or in mutant mouse lines, offers the prospect of greater understanding of both the cellular and developmental bases of the human disease.
Endoscopic papillary balloon dilatation may preserve sphincter of Oddi function after common bile duct stone management: evaluation from the viewpoint of endoscopic manometry
Authors: Sato H , Kodama T , Takaaki J , Tatsumi Y , Maeda T , Fujita S , Fukui Y , Ogasawara H , Mitsufuji S 
Published: June 2010

Background—Endoscopic papillary balloon dilatation (EPBD) has been reported as a safe and effective alternative to endoscopic sphincterotomy in the management of common bile duct (CBD) stones; its effect on papillary function has yet to be elucidated.Aim—To investigate sphincter of Oddi (SO) motility before and after EPBD to determine its effect on SO function.Patients and methods—The papillary function of 10 patients with CBD stones was studied using endoscopic manometry before and one week after EPBD. The manometric studies were repeated one month after EPBD in seven patients.Results—One week after EPBD, CBD pressure, SO peak pressure, SO basal pressure, and SO frequency decreased significantly. One month after EPBD, however, all parameters increased although the increases in SO basal pressure and CBD pressure were not significant. There was no significant difference in values of any parameter before and one month after EPBD. No serious complications occurred.Conclusion—These data suggest at least partial recovery of papillary function one month after the procedure. EPBD seems to preserve papillary function in treatment of CBD stones; a longer term follow up study with SO manometry should be performed to clarify the effect of EPBD on SO function.
Influencing the practice and outcome in acute upper gastrointestinal haemorrhage
Authors: Rockall T A , Logan R F A , Devlin H B , Northfield T C 
Published: June 2010

Aims—To assess changes in practice and outcome in acute upper gastrointestinal haemorrhage following the feedback of data, the reemphasis of national guidelines, and specific recommendations following an initial survey.Design—A prospective, multicentre, audit cycle. Forty five hospitals from three health regions participed in two phases of the audit cycle.Patients—Phase I: 2332 patients with acute upper gastrointestinal haemorrhage; phase II: 1625 patients with upper gastrointestinal haemorrhage.Methods—Patients were evaluated with respect to management (with reference to the recommendations in the national guidelines), mortality, and length of hospital stay.Results—Following the distribution of data from the first phase of the National Audit and the formulation of specific recommendations for improving practice, the proportion of hospitals with local guidelines or protocols for the management of upper gastrointestinal haemorrhage rose from 71% (32/45) to 91% (41/45); 12 of the 32 hospitals with guidelines during the first phase revised their guidelines following the initial survey. There was a small but significant increase in the proportion of all patients who underwent endoscopy (from 81% to 86%), the proportion who underwent endoscopy within 24 hours of admission (from 50% to 56%), and the use of central venous pressure monitoring in patients with organ failure requiring blood transfusion or those with profound shock (from 30% to 43%). There was, however, no change in the use of high dependency beds or joint medical/surgical management in high risk cases. There was no significant change in crude or risk standardised mortality (13.4% in the first phase and 14.4% in the second phase).Conclusions—Although many of the participating hospitals have made efforts to improve practice by producing or updating guidelines or protocols, there has been only a small demonstrable change in some areas of practice during the National Audit. The failure to detect any improvement in mortality may reflect this lack of change of practice, but may also reflect the fact that a large proportion of the deaths in this unselected study are not preventable; only a very large study could hope to demonstrate a significant change out of the context of a clinical trial.
Antisecretory factor suppresses intestinal inflammation and hypersecretion
Authors: Johansson E , Jennische E , Lange S , Lönnroth I 
Published: June 2010

Background—Antisecretory factor (AF) is a recently identified regulatory protein which inhibits the intestinal fluid secretion induced by cholera toxin.Aims—To test the effect of AF on: (a) inflammation and hypersecretion induced by toxin A fromClostridium difficile; and (b) morphological changes and hypersecretion induced by okadaic acid (the blue mussel toxin) in rat intestinal mucosa.Methods—Morphological changes and fluid accumulation were observed in intestinal loops challenged with 1 μg of toxin A or 3  μg of okadaic acid administered before or after injection of 0.1  μg of recombinant AF (rAF).Results—The cytotoxic and inflammatory reaction caused by toxin A was abolished after treatment with rAF given either intraveneously or intraluminally prior to the toxin or one hour after the toxin. The intestinal fluid response induced by toxin A and okadaic acid was reduced 55–80% by rAF. However, the characteristic increase in goblet cells at the tips of villi in the okadaic acid treated mucosa was not inhibited by rAF.Conclusion—Results suggest that AF might be involved in protection against inflammation and in counteracting dehydration caused by enterotoxins. Both effects are probably mediated via the enteric nervous system.
Search for Mycobacterium paratuberculosis DNA in orofacial granulomatosis and oral Crohn’s disease tissue by polymerase chain reaction
Authors: Riggio M P , Gibson J , Lennon A , Wray D , MacDonald D G 
Published: June 2010

Background—Although intestinal Crohn’s disease has long been suspected to have a mycobacterial cause, possible mycobacterial involvement in orofacial granulomatosis (OFG) and oral lesions of Crohn’s disease has not yet been investigated.Aims—As the slow growingMycobacterium paratuberculosis has been implicated in the aetiology of intestinal Crohn’s disease, the potential involvement of this mycobacterial species in OFG and oral lesions of Crohn’s disease was investigated.Patients—To attempt detection of the organism in OFG and oral Crohn’s disease tissue samples, a polymerase chain reaction (PCR) assay was used on archival formalin fixed, paraffin wax embedded oral tissue sections from 30 patients with OFG, seven with Crohn’s disease, and 12 normal controls.Methods—The PCR assay used was based on primers targeting the 5′ region of the multicopy IS900 DNA insertion element of the M paratuberculosis genome. In order to achieve maximum sensitivity, two rounds of PCR were carried out and amplicons confirmed by Southern blot hybridisation to a digoxigenin labelled IS900 DNA probe.Results—None of the OFG and oral lesions of Crohn’s disease samples were positive forMparatuberculosis and all normal controls were also negative.Conclusions—These results suggest that M paratuberculosis may not be a major aetiological agent in OFG or oral Crohn’s disease lesions, although the use of paraffin wax embedded tissue as opposed to fresh tissue as a sample source could underestimate the true prevalence of the organism.
One week triple therapy for Helicobacter pylori: a multicentre comparative study
Authors: Misiewicz J J , Harris A W , Bardhan K D , Levi S , O’Morain C , Cooper B T , Kerr G D , Dixon M F , Langworthy H , Piper D ,   Lansoprazole Helicobacter Study Group
Published: June 2010

Background—Eradication ofHelicobacter pylori cures and prevents the relapse of duodenal ulceration and also results in histological resolution of chronic active gastritis. Aim—To compare four treatment regimens lasting seven days of a proton pump inhibitor and two antibiotics in the eradication of H pylori.Patients—Men or women with H pylori positive duodenal ulceration or gastritis, or both.Methods—A single blind, prospectively randomised, parallel group, comparative, multicentre study. After a positive CLO test, patients underwent histology, H pylori culture, and a 13C urea breath test to confirm H pyloristatus. Treatment with one of four regimens: LAC, LAM, LCM, or OAM, where L is 30 mg of lansoprazole twice daily, A is 1 g of amoxycillin twice daily, M is 400 mg of metronidazole twice daily, C is 250 mg of clarithromycin twice daily, and O is 20 mg of omeprazole twice daily, was assigned randomly. A follow up breath test was done at least 28 days after completing treatment.Results—H pylori eradication (intention to treat) was 104/121 (86.0%) with LAC, 87/131 (66.4%) with LAM, 103/118 (87.3%) with LCM, and 94/126 (74.6%) with OAM. There was a significant difference (p < 0.001) in the proportion of patients in whom eradication was successful between LAC and LCM when compared with LAM, but no significant difference (p = 0.15) between LAM and OAM. Metronidazole resistance before treatment was identified as a significant prognostic factor with regard to eradication of H pylori. The regimens which contained metronidazole were significantly less effective than those without metronidazole in the presence of pretreatment resistant H pylori. There was no difference among the treatment groups with regard to the incidence and severity of adverse events reported. Conclusions—All four treatment regimens were safe and effective in eradicating H pylori in the patient population studied. LAC was the most efficacious treatment in patients with pretreatment metronidazole resistant H pylori, and was significantly better than LAM and OAM in this group of patients.
Alkyl halides, super hydrogen production and the pathogenesis of pneumatosis cystoides coli
Authors: Florin T H J 
Published: June 2010

Background and aims—The colons of patients with pneumatosis cystoides coli produce excessive H2. Exposure to alkyl halides could explain this. Six consecutive patients who had pneumatosis cystoides coli while taking chloral hydrate (1–5+ g/day) are reported. Patients 2 and 3 were investigated after they had ceased chloral hydrate treatment. One produced methane, the other did not. (Pneumatosis cystoides coli patients are non-methanogenic according to the literature.) Both had overnight fasting breath H2 of less than 10 ppm. A literature review disclosed just one patient who was using chloral at the time of diagnosed pneumatosis cystoides coli, but an epidemic of the disease in workers exposed to trichloroethylene.Methods—(i) In vitro experiments with human faeces: chloral or closely related alkyl halides were added to anaerobic faecal cultures derived from four methane-producing and three non-methanogenic human subjects. H2 and CH4gases were measured. (ii) In vivo animal experiment: chloral hydrate was added to drinking water of four Wistar rats, and faecal H2 compared with control rats.Results—Alkyl halides increased H2 up to 900 times in methanogenic and 10 times in non-methanogenic faecal cultures. The Ki of chloral was 0.2 mM. Methanogenesis was inhibited in concert with the increase in net H2. In the rat experiment, chloral hydrate increased H2 10 times, but did not cause pneumatosis.Conclusions—Chloral and trichloroethylene are alkyl halides chemically similar to chloroform, a potent inhibitor of H2 consumption by methanogens and acetogens. These bacteria are the most important H2-consuming species in the colon. It is postulated that exposure to these alkyl halides increases net H2 production, which sets the scene for “counterperfusion supersaturation” and the formation of gas cysts. In recent times, very low prescribing rates for chloral have caused primary pneumatosis cystoides to become extremely rare. As with primary pneumatosis, secondary pneumatosis cystoides, which occurs if there is small bowel bacterial overgrowth distal to a proximally located gut obstruction, is predicted by counterperfusion supersaturation. “Inherent unsaturation” due to metabolism of O2 is a safety factor, which could explain why gas bubbles do not form more often in tissue with high H2 tension.
Enteropathy in Zambians with HIV related diarrhoea: regression modelling of potential determinants of mucosal damage
Authors: Kelly P , Davies S E , Mandanda B , Veitch A , McPhail G , Zulu I , Drobniewski F , Fuchs D , Summerbell C , Luo N P , Pobee J O M , Farthing M J G 
Published: June 2010

Background—AIDS is characterised by small intestinal mucosal damage, but its aetiopathogenesis is poorly understood. Enteric infections in Africa differ from those in northern countries, where protozoan infections have been associated with severe enteropathy in AIDS patients.Aims—To characterise enteropathy in Zambian AIDS patients compared with local controls, and to assess relative contributions of enteric infection, nutritional impairment, and immune dysfunction.Methods—Computer aided mucosal morphometry of small intestinal biopsy specimens from 56 HIV infected Zambians with persistent diarrhoea and 26 diarrhoea free controls, followed by regression modelling.Results—Patients with HIV related diarrhoea had reduced villous height and increased crypt depth compared with controls. There was no difference between HIV positive and negative controls. In regression models applied to AIDS mucosal measurements, villous height and crypt depth were related to nutritional parameters and to serum soluble tumour necrosis factor receptor p55 concentration. Crypt depth was also related to lamina propria plasma cell count. Intestinal infection was found in 79%, which consisted predominantly of microsporidia in 34%, Isospora belli in 24%, andCryptosporidium parvum in 21%, but detection of these enteropathogens was not related to severity of enteropathy.Conclusions—Nutritional and immune disturbances were associated with enteropathy, accounting for over one third of the variation in mucosal morphometric parameters.
Beta human chorionic gonadotropin concentrations in serum of patients with pancreatic adenocarcinoma
Authors: Syrigos K N , Fyssas I , Konstandoulakis M M , Harrington K J , Papadopoulos S , Milingos N , Peveretos P , Golematis B C 
Published: June 2010

Background—Human chorionic gonadotropin (hCG) is normally produced and secreted by trophoblastic cells during pregnancy and from gestational trophoblastic neoplasms. It is also detected in ovarian, stomach, and colon adenocarcinomas, as well as in squamous cell carcinoma of the oesophagus. Recently, interest in its role in the pathogenesis of tumours has been enlivened after the presence of βhCG in the cell membrane of several malignant cells was shown in vitro.Aims—To investigate the circulating concentrations of βhCG in patients with exocrine pancreatic adenocarcinoma and to examine its potential prognostic value.Patients—Thirty six patients with exocrine pancreatic adenocarcinoma, 12 patients with chronic pancreatitis, and 21 healthy volunteers were studied.Methods—βhCG serum concentrations were detected by the application of a radioimmunoassay technique.Results—Fifteen of 36 patients with pancreatic adenocarcinoma and only one patient with chronic pancreatitis had detectable plasma concentrations of βhCG (p<0.01). The patients with circulating serum titres of βhCG had a worse outcome compared with the group of βhCG negative patients: the difference was statistically significant (p=0.01).Conclusion—More than 40% of pancreatic exocrine tumours produce βhCG and its production is correlated with an adverse effect on outcome.
Mucosal subepithelial binding sites for the bacterial chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (FMLP)
Authors: Anton P , O’Connell J , O’Connell D , Whitaker L , O’Sullivan G C , Collins J K , Shanahan F 
Published: June 2010

Background—The bacterial chemotactic peptideN-formyl-methionine-leucine-phenylalanine (FMLP) is produced by enteric flora and is one of the factors implicated in contributing to inflammatory bowel disease. Expression of receptors for FMLP on human phagocytes (polymorphs and monocytes) is well established, but there is conflicting evidence regarding the potential expression of FMLP receptors on other cells within the mucosa, particularly the epithelial cells.Aims—To map FMLP receptors within intestinal mucosa using several different experimental approaches.Methods and results—Radioligand binding assays with 3H-FMLP revealed no specific binding to primary cultured colonic enterocytes or to the cell line HT29, whereas neutrophils, as expected, exhibited specific binding with a Kd of 19 nM and approximately 2 × 104 receptors per cell. FITC labelled FMLP exhibited specific, displaceable binding on flow cytometry to neutrophils and monocytes but not to 10 gastrointestinal epithelial cell lines. Isolated lamina propria lymphocytes and peripheral blood lymphocytes exhibited no binding. To confirm the absence of receptors on epithelia, reverse transcription polymerase chain reaction for mRNA for the classic FMLP receptor was performed. While the presence of message was detected in activated peripheral blood phagocytes, it was not detected in epithelial cell lines. To exclude the possibility of FMLP binding to other receptors such as tachykinin receptors on epithelia, FITC labelled FMLP binding in tissue sections confirmed that the binding is subepithelial—that is, in the lamina propria.Conclusion—Receptors for FMLP are subepithelial and map to the lamina propria of the gastrointestinal mucosa.