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Results in Journal Gut: 27,082

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, Xingshun Qi, Chuangye He, Zhengyu Wang, Zhanxin Yin, Jing Niu, Wengang Guo, Wei Bai, Hongbo Zhang, Huahong Xie, et al.
Published: 28 September 2017
by BMJ
Gut, Volume 67, pp 2156-2168; https://doi.org/10.1136/gutjnl-2017-314634

Abstract:
ObjectiveLimited data are available on the prevention of variceal rebleeding in cirrhotic patients with portal vein thrombosis (PVT). This study aimed to compare transjugular intrahepatic portosystemic shunt (TIPS) with covered stents versus endoscopic band ligation (EBL) plus propranolol for the prevention of variceal rebleeding among patients with cirrhosis and PVT.DesignConsecutive cirrhotic patients (94% Child-Pugh class A or B) with PVT who had variceal bleeding in the past 6 weeks were randomly assigned to TIPS group (n=24) or EBL plus propranolol group (EBL+drug, n=25), respectively. Primary endpoint was variceal rebleeding. Secondary endpoints included survival, overt hepatic encephalopathy (OHE), portal vein recanalisation and rethrombosis, other complications of portal hypertension and adverse events.ResultsDuring a median follow-up of 30 months in both groups, variceal rebleeding was significantly less frequent in the TIPS group (15% vs 45% at 1 year and 25% vs 50% at 2 years, respectively; HR=0.28, 95% CI 0.10 to 0.76, p=0.008), with a significantly higher portal vein recanalisation rate (95% vs 70%; p=0.03) and a relatively lower rethrombosis rate (5% vs 33%; p=0.06) compared with the EBL+drug group. There were no statistically significant differences in survival (67% vs 84%; p=0.152), OHE (25% vs 16%; p=0.440), other complications of portal hypertension and adverse events between groups.ConclusionCovered TIPS placement in patients with PVT and moderately decompensated cirrhosis was more effective than EBL combined with propranolol for the prevention of rebleeding, with a higher probability of PVT resolution without increasing the risk of OHE and adverse effects, but this benefit did not translate into improved survival.Trial registration numberClinicalTrials.gov: NCT01326949.
Published: 28 September 2017
by BMJ
Gut, Volume 67, pp 1958-1964; https://doi.org/10.1136/gutjnl-2017-313905

Abstract:
ObjectivePain associated with colonoscopy is a major burden for patients. We investigated modifiable factors associated with patient-reported pain during and after colonoscopy.DesignThis cross-sectional analysis included database records from 23 centres participating in a population-based colonoscopy screening programme in Poland. Colonoscopies were performed under three sedation modalities: none, benzodiazepine-opioid sedation or propofol sedation. We used Gastronet (a validated tool) to assess patients’ pain during and after colonoscopy; pain was scored on a four-point scale (no, little, moderate or severe pain), with moderate to severe defined as painful. We used multivariate logistic regression models to estimate ORs for painful colonoscopy and calculated risk-adjusted ratios of painful colonoscopies per endoscopist and compared it to the mean rate.ResultsOf 35 216 screening colonoscopies in 2014 and 2015 included in our study, 22 725 (64.5%) patients returned valid Gastronet questionnaires. The proportion of examinations described as causing pain during (after) the procedure was 22.5% (14.2%) for unsedated, 19.9% (13.5%) for benzodiazepine-opioid sedation and 2.5% (7.5%) for propofol sedation. Propofol sedation, higher case volume of endoscopists, newest endoscope generation and adequate bowel preparation were significantly associated with lower odds of painful colonoscopy. Pain scores after colonoscopy showed similar associations. Adjusted pain rates during and after colonoscopy varied 11 and over 23-fold, respectively, between endoscopists.ConclusionWe identified several independent, modifiable factors associated with pain during and after colonoscopy, of which individual endoscopist was the most important. Dedicated training should be considered to decrease variability among endoscopists.
, Kevin McGrath, Randall E Brand, Asif Khalid, Herbert J Zeh, Jennifer S Chennat, Kenneth E Fasanella, Georgios I Papachristou, Adam Slivka, David L Bartlett, et al.
Published: 28 September 2017
by BMJ
Gut, Volume 67, pp 2131-2141; https://doi.org/10.1136/gutjnl-2016-313586

Abstract:
Objective: DNA-based testing of pancreatic cyst fluid (PCF) is a useful adjunct to the evaluation of pancreatic cysts (PCs). Mutations in KRAS/GNAS are highly specific for intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), while TP53/PIK3CA/PTEN alterations are associated with advanced neoplasia. A prospective study was performed to evaluate preoperative PCF DNA testing.Design: Over 43-months, 626 PCF specimens from 595 patients were obtained by endoscopic ultrasound (EUS)-fine needle aspiration and assessed by targeted next-generation sequencing (NGS). Molecular results were correlated with EUS findings, ancillary studies and follow-up. A separate cohort of 159 PCF specimens was also evaluated for KRAS/GNAS mutations by Sanger sequencing.Results: KRAS/GNAS mutations were identified in 308 (49%) PCs, while alterations in TP53/PIK3CA/PTEN were present in 35 (6%) cases. Based on 102 (17%) patients with surgical follow-up, KRAS/GNAS mutations were detected in 56 (100%) IPMNs and 3 (30%) MCNs, and associated with 89% sensitivity and 100% specificity for a mucinous PC. In comparison, KRAS/GNAS mutations by Sanger sequencing had a 65% sensitivity and 100% specificity. By NGS, the combination of KRAS/GNAS mutations and alterations in TP53/PIK3CA/PTEN had an 89% sensitivity and 100% specificity for advanced neoplasia. Ductal dilatation, a mural nodule and malignant cytopathology had lower sensitivities (42%, 32% and 32%, respectively) and specificities (74%, 94% and 98%, respectively).Conclusions: In contrast to Sanger sequencing, preoperative NGS of PCF for KRAS/GNAS mutations is highly sensitive for IPMNs and specific for mucinous PCs. In addition, the combination of TP53/PIK3CA/PTEN alterations is a useful preoperative marker for advanced neoplasia.
, , Satoshi Asai, Isao Yokota, Eisuke Akamine, Minoru Kato, Takuji Akamatsu, Kazuhiro Tada, Yoriaki Komeda, Mineo Iwatate, et al.
Published: 28 September 2017
by BMJ
Gut, Volume 67, pp 1950-1957; https://doi.org/10.1136/gutjnl-2017-314215

Abstract:
ObjectiveTo investigate the success rate of cold snare polypectomy (CSP) for complete resection of 4–9 mm colorectal adenomatous polyps compared with that of hot snare polypectomy (HSP).DesignA prospective, multicentre, randomised controlled, parallel, non-inferiority trial conducted in 12 Japanese endoscopy units. Endoscopically diagnosed sessile adenomatous polyps, 4–9 mm in size, were randomly assigned to the CSP or HSP group. After complete removal of the polyp using the allocated technique, biopsy specimens from the resection margin after polypectomy were obtained. The primary endpoint was the complete resection rate, defined as no evidence of adenomatous tissue in the biopsied specimens, among all pathologically confirmed adenomatous polyps.ResultsA total of 796 eligible polyps were detected in 538 of 912 patients screened for eligibility between September 2015 and August 2016. The complete resection rate for CSP was 98.2% compared with 97.4% for HSP. The non-inferiority of CSP for complete resection compared with HSP was confirmed by the +0.8% (90% CI −1.0 to 2.7) complete resection rate (non-inferiority pConclusionsThe complete resection rate for CSP is not inferior to that for HSP. CSP can be one of the standard techniques for 4–9 mm colorectal polyps. (Study registration: UMIN000018328)
R Kiss, I Camby, C Duckworth, R De Decker, I Salmon, J L Pasteels, , P Yeaton
Published: 1 February 1997
by BMJ
Gut, Volume 40, pp 253-261; https://doi.org/10.1136/gut.40.2.253

Abstract:
BACKGROUND/AIMS: Compared with normal colonic mucosa, lectin receptor expression is increased in hyperplastic and neoplastic tissues; some lectins have been shown to influence human colonic epithelial cell proliferation. The aim was to assess further the influence of five lectins (Phaseolus vulgaris (PNA), Griffonia simplicifolia (GSA), concanavalin A (Con A), wheat germ (WGA), and peanut (PHA-L) agglutinins) on cellular growth in three human colorectal cancer cell lines (LoVo, HCT-15 and SW837). METHODS: Cells were cultured in four lectin concentrations (0.1, 1.0, 10, and 100 micrograms/ml) and growth assessed at days 2, 3, 5, and 7. The experiments were performed in media supplemented with either 1% or 10% fetal calf serum (FCS). Growth was assessed using the MTT (3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) colorimetric assay. RESULTS: Growth in each cell line was greatly affected by at least two of the lectins tested. There was some variation in the effect of a given lectin on different cell lines. Lectin effects showed a dose-response and the greatest effects generally resulted from the highest concentrations at the longest culture time. WGA and Con A induced large effects in all cell lines; the effects of Con A were partly blocked by the higher concentration of FCS. PNA had modest and uniform stimulatory effects overall. The effects of GSA and PHA-L varied between cell lines. CONCLUSIONS: The lectins studied all have the potential to affect colonic cancer growth in vitro. Many dietary lectins are resistant to digestion and may have important effects in vitro but the definition of their role in human colonic cancer biology must take into account the variability in lectin response.
, , S Jacob, , K D Bardhan
Published: 1 January 1997
by BMJ
Gut, Volume 40, pp 31-35; https://doi.org/10.1136/gut.40.1.31

Abstract:
BACKGROUND/AIMS: The focal nature of gastric ulcers raises the possibility of underlying regional disturbances in gastric mucosal microcirculation. This study employed fluorescent in vivo microscopy with the aim of directly investigating the response of several areas of the gastric mucosa to 60% ethanol. METHODS: Changes in macromolecular leakage of fluorescein labelled albumin, vessel diameter, and acridine red labelled leucocyte adhesion and rolling were assessed over a period of two hours. A total of 0.5 ml 60% ethanol was topically applied for five minutes to the exteriorised gastric mucosa of anaesthetised rats. RATS: Three distinct patterns of response were found. Areas of lesion formation were small and occurred within five minutes. These areas showed persistent blood flow stasis throughout the course of the experiment, increased leakage (p < 0.02), and no leucocyte adhesion. Peripheral to the lesion, sustained leakage (p < 0.02) was found with adherence of leucocytes (p < 0.01) after lesion formation. Sites more remote to any lesion showed transient leakage and significant numbers of 'rolling' leucocytes (p < 0.01) were observed again after the lesion had formed. CONCLUSIONS: Despite widespread exposure of the entire gastric mucosa to 60% ethanol the resultant mucosal injury was limited. Widespread vascular damage was found reflected by macromolecular leakage, the pattern of which showed regional variation.
Steven P O’Hara, , Nicholas F LaRusso
Published: 21 July 2017
by BMJ
Gut, Volume 66, pp 1873-1877; https://doi.org/10.1136/gutjnl-2017-314249

Abstract:
In primary sclerosing cholangitis (PSC), annular fibrosis around intrahepatic and extrahepatic bile ducts leads to progressive liver disease for which there is no effective therapy except liver transplantation.1 The concentric accumulation of connective tissue around bile ducts suggests that the cholangiocyte plays an integral role in PSC pathogenesis. However, what initiates changes in cholangiocyte phenotype and how cholangiocytes interact with cells in the peribiliary extracellular matrix like immune cells and stromal components is largely unknown. Over the last 10 years, genome-wide association studies in PSC have revealed >20 risk genes.2–5 A significant observation that can be derived from these data, which also applies to other non-Mendelian phenotypes, is that the predominant risk contribution is likely to come from one or more environmental sources, rather than the genetic aberrations. Indeed, in PSC, we estimate that <10% of the overall liability is accounted for by the genetic findings; with extrapolations into hypothetical, larger study populations, it is unlikely to exceed 30%–40%.6 7 Research dissecting the remaining environmental contribution to PSC and other complex diseases is methodologically challenging. The exposures of an organism throughout life as a whole have recently been referred to as the exposome8 and include a myriad of components of both the external (eg, xenobiotics) and internal (eg, gut microbes) milieu. There is a long tradition and effective means for detecting infectious exposures in medicine. Robert Koch in the late 19th century proposed criteria to identify a disease as infectious.9 These included (i) the organism is regularly associated with the disease, (ii) the organism can be isolated from the diseased host and grown in culture and (iii) the disease can be reproduced when the organism is introduced into a healthy susceptible host. With the development of nucleic acid sequence-based identification of microbes, as well as the …
Mairi H McLean
Published: 9 October 2017
by BMJ
Gut, Volume 66, pp 2033-2034; https://doi.org/10.1136/gutjnl-2017-315186

Abstract:
### Th17 cells; friend or foe in intestinal homeostasis? Hegazy AN, West NR, Stubbington MJT, et al . Circulating and tissue-resident CD4+ T cells with reactivity to intestinal microbiota are abundant in healthy individuals and function is altered during inflammation. Gastroenterology 2017 Aug. pii: S0016-5085(17)35979-6. doi: 10.1053/j.gastro.2017.07.047. (Epub ahead of print). Intestinal immune responses are tightly regulated to provide the necessary protection against pathogenic organisms while controlling responses to commensal species. Characterising T cell responses to bacteria is an important aspect of the puzzle. In humans, circulating memory T cells recognise peptides derived from gut bacteria and can cross-react to pathogens. While the process may be beneficial during homeostasis, this potentially contributes to inflammatory conditions such as IBD when regulatory aspects are dysfunctional. Currently, there is a lack of knowledge regarding the type, frequency and functional phenotype of T cells that react to intestinal microbes in the gut and how these immune cells change during chronic intestinal inflammation. This study by Hegazy and colleagues used a combination of experimental approaches to address these questions. The data demonstrate that circulating enteric bacteria-reactive CD4+ T cells co-express chemokine receptors including CCR4, CCR6 and CCR7, with a smaller fraction also expressing gut-related homing receptors α4β7 and CCR9 promoting access to secondary lymphoid organs. The microbiota-reactive T cells displayed Th17 and Th1 characteristics and in some cases produced interleukin (IL)-10. A clear Th17 bias was seen in gut-resident cells in IBD although these observations were also evident in healthy individuals. The authors suggest that the continuous luminal sampling of the intestinal microbiota and response to epithelial breaches, such as during an infection, provides a plethora of memory T cells with potential reactivity towards newly encountered pathogens. Therefore, contrary to previous assumptions, these T cells may actually be promoting intestinal homeostasis rather than inflammation. ### Inflammatory responses in NAFLD Hart KM, Fabre T, Sciurba JC, et al . Type two immunity …
, Ryan D. Warren, Maurice P. Barrett, Katryna Cisek, Anubhav Das, , Eimear Hurley, Micheal O‘Riordain, Fergus Shanahan,
Published: 7 October 2017
by BMJ
Gut, Volume 67, pp 1454-1463; https://doi.org/10.1136/gutjnl-2017-314814

Abstract:
Background and aims: Microbiota alterations are linked with colorectal cancer (CRC) and notably higher abundance of putative oral bacteria on colonic tumours. However, it is not known if colonic mucosa-associated taxa are indeed orally derived, if such cases are a distinct subset of patients or if the oral microbiome is generally suitable for screening for CRC.Methods: We profiled the microbiota in oral swabs, colonic mucosae and stool from individuals with CRC (99 subjects), colorectal polyps (32) or controls (103).Results: Several oral taxa were differentially abundant in CRC compared with controls, for example, Streptococcus and Prevotellas pp. A classification model of oral swab microbiota distinguished individuals with CRC or polyps from controls (sensitivity: 53% (CRC)/67% (polyps); specificity: 96%). Combining the data from faecal microbiota and oral swab microbiota increased the sensitivity of this model to 76% (CRC)/88% (polyps). We detected similar bacterial networks in colonic microbiota and oral microbiota datasets comprising putative oral biofilm forming bacteria. While these taxa were more abundant in CRC, core networks between pathogenic, CRC-associated oral bacteria such as Peptostreptococcus, Parvimonas and Fusobacterium were also detected in healthy controls. High abundance of Lachnospiraceae was negatively associated with the colonisation of colonic tissue with oral-like bacterial networks suggesting a protective role for certain microbiota types against CRC, possibly by conferring colonisation resistance to CRC-associated oral taxa and possibly mediated through habitual diet.Conclusion: The heterogeneity of CRC may relate to microbiota types that either predispose or provide resistance to the disease, and profiling the oral microbiome may offer an alternative screen for detecting CRC.
Farzan F Bahin, Steven J Heitman, Khalid N Rasouli, Hema Mahajan, Duncan McLeod, Eric Y T Lee, Stephen J Williams, Michael J Bourke
Published: 7 October 2017
by BMJ
Gut, Volume 67, pp 1965-1973; https://doi.org/10.1136/gutjnl-2017-313823

Abstract:
ObjectiveTo compare the cost-effectiveness of endoscopic submucosal dissection (ESD) and wide-field endoscopic mucosal resection (WF-EMR) for removing large sessile and laterally spreading colorectal lesions (LSLs) >20 mm.DesignAn incremental cost-effectiveness analysis using a decision tree model was performed over an 18-month time horizon. The following strategies were compared: WF-EMR, universal ESD (U-ESD) and selective ESD (S-ESD) for lesions highly suspicious for containing submucosal invasive cancer (SMIC), with WF-EMR used for the remainder. Data from a large Western cohort and the literature were used to inform the model. Effectiveness was defined as the number of surgeries avoided per 1000 cases. Incremental costs per surgery avoided are presented. Sensitivity and scenario analyses were performed.Results1723 lesions among 1765 patients were analysed. The prevalence of SMIC and low-risk-SMIC was 8.2% and 3.1%, respectively. Endoscopic lesion assessment for SMIC had a sensitivity and specificity of 34.9% and 98.4%, respectively. S-ESD was the least expensive strategy and was also more effective than WF-EMR by preventing 19 additional surgeries per 1000 cases. 43 ESD procedures would be required in an S-ESD strategy. U-ESD would prevent another 13 surgeries compared with S-ESD, at an incremental cost per surgery avoided of US$210 112. U-ESD was only cost-effective among higher risk rectal lesions.ConclusionS-ESD is the preferred treatment strategy. However, only 43 ESDs are required per 1000 LSLs. U-ESD cannot be justified beyond high-risk rectal lesions. WF-EMR remains an effective and safe treatment option for most LSLs.Trial registration numberNCT02000141.
, Kazunori Oda, Nobuo Funao, Akira Nishimura, , Takashi Kawai, Kiyoshi Ashida,
Published: 7 October 2017
by BMJ
Gut, Volume 67, pp 1042-1051; https://doi.org/10.1136/gutjnl-2017-314010

Abstract:
ObjectiveTo assess the non-inferiority of vonoprazan to lansoprazole for secondary prevention of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulcer (PU) and the safety of vonoprazan during extended use.DesignA phase 3, 24-week, multicenter, randomised, double-blind (DB), active-controlled study, followed by a phase 3, ≥28 week, multicenter, single-blind, parallel-group extension study (EXT) in outpatients (n=642) receiving long-term NSAID therapy who are at risk of PU recurrence. The patients received vonoprazan (10 mg or 20 mg) or lansoprazole 15 mg once daily. For DB, non-inferiority of the proportion of patients with recurrent PU within 24 weeks was analysed by Farrington and Manning test (significance level 2.5%, non-inferiority margin 8.3%; primary endpoint), recurrent PU within 12 weeks, bleeding and time-to-event of PU (secondary endpoint) and treatment-emergent adverse events (TEAEs). For EXT, TEAEs (primary endpoint), recurrent PU and safety (secondary) were assessed up to 104 weeks for patients in the extension study.ResultsThe non-inferiority of vonoprazan 10 mg and 20 mg to lansoprazole 15 mg was verified (percentage difference –2.2%,95% CI –6.2% to 1.8%, pConclusionThe non-inferiority of vonoprazan (10 and 20 mg) was verified in patients receiving long-term NSAIDs in DB; it was effective and well tolerated in EXT for longer than 1 year, with a safety profile similar to lansoprazole (15 mg).Trial registration numbersNCT01452750, NCT01456260; Results.
Ji Young Bang, Shantel Hebert-Magee, Udayakumar Navaneethan, Muhammad K Hasan, Robert Hawes,
Published: 7 October 2017
by BMJ
Gut, Volume 67, pp 2081-2084; https://doi.org/10.1136/gutjnl-2017-315154

Abstract:
As cytological aspirates from endoscopic-ultrasound-guided fine needle aspiration (EUS-FNA) has limited diagnostic sensitivity and are suboptimal for molecular profiling and morphological characterisation of certain neoplasms, a fine needle biopsy (FNB) with three-pronged (Franseen geometry) cutting edge has been developed to procure histology. In a randomised trial of 46 patients with pancreatic masses, procurement of histological core tissue as evidenced by total tissue and tumour areas was significantly higher for 22G FNB than FNA needle. Also, retention of tissue architecture and presence of desmoplastic fibrosis, which are critical for ancillary testing and molecular profiling, respectively, were significantly higher for FNB.
Mitchell Bijnen, Tatjana Josefs, , Constantijn J Maalsen, José Van De Gaar, Maria Vroomen, Erwin Wijnands, , , , et al.
Published: 26 October 2017
by BMJ
Gut, Volume 67, pp 1317-1327; https://doi.org/10.1136/gutjnl-2016-313654

Abstract:
Objective: Obesity is a risk factor for non-alcoholic steatohepatitis (NASH). This risk has been attributed to visceral adipose tissue (vAT) expansion associated with increased proinflammatory mediators. Accumulation of CD11c+ proinflammatory adipose tissue macrophages (ATM) is an important driver of vAT inflammation. We investigated the role of ATMs in hepatic inflammation during NASH development.Design: vAT isolated from lean, obese or ATM-depleted (using clodronate liposomes) obese mice was transplanted to lean ldlr-/- acceptor mice. Systemic and hepatic inflammation was assessed either after 2 weeks on standard chow or after 8 weeks on high cholesterol diet (HCD) to induce NASH.Results: Transplanting donor vAT from obese mice increased HCD-induced hepatic macrophage content compared with lean-transplanted mice, worsening liver damage. ATM depletion prior to vAT transplantation reduced this increased hepatic macrophage accumulation. On chow, vAT transplantation induced a more pronounced increase in circulating and hepatic neutrophil numbers in obese-transplanted than lean-transplanted mice, while ATM depletion prior to vAT transplantation reversed this effect. Microarray analysis of fluorescence-activated cell sorting of CD11c+ and CD11c macrophages isolated from donor adipose tissue showed that obesity resulted in enhanced expression of neutrophil chemotaxis genes specifically in CD11c+ ATMs. Involvement of the neutrophil chemotaxis proteins, CXCL14 and CXCL16, was confirmed by culturing vAT. In humans, CD11c expression in vAT of obese individuals correlated with vAT expression of neutrophil chemotactic genes and with hepatic expression of neutrophil and macrophage marker genes.Conclusion: ATMs from obese vAT induce hepatic macrophage accumulation during NASH development, possibly by enhancing neutrophil recruitment.
Anthony Lopez, Anne-Marie Bouvier, Valérie Jooste, Vanessa Cottet, Gaëlle Romain, Jean Faivre, Sylvain Manfredi, Come Lepage
Published: 26 October 2017
by BMJ
Gut, Volume 68, pp 111-117; https://doi.org/10.1136/gutjnl-2016-312093

Abstract:
Objective: Population-based studies on colorectal malignant polyps (MPs) are scarce. The aim of this study was to describe time trends in the incidence of colorectal MPs before and after the introduction of a colorectal mass-screening programmein 2003 and to assess outcomes (survival and recurrence) after endoscopic or surgical resection in patients with MPs.Design: We included 411 patients with MPs diagnosed between 1982 and 2011 in a well-defined population. Age-standardised incidence rates were calculated. Univariate and multivariate 5-year recurrence and net survival analyses were performed according to gross morphology.Results: Age-standardised incidence of MPs in patients aged 50–74 years doubled from 5.4 in 1982–2002 to 10.9 per 100 000 in 2003–2011. Pedunculated MPs were more frequently resected endoscopically (38.2%) than were sessile MPs (19.1%; p<0.001). For patients with pedunculated MPs and a pathological margin ≥1 mm, the 5 -year cumulative recurrence rate did not differ significantly between surgical and endoscopic resection (8.2% and 2.4%, respectively). For patients with sessile MPs, it was 3.0% after first-line or second-line surgical resection, 8.6% after endoscopic resection and 17.9% after transanal resection (p=0.016). The recurrence rate decreased dramatically for patients with sessile MPs from 11.3% (1982–2002) to 1.2% (2003–2009) (p=0.010) and remained stable for pedunculated MPs at 4.6% and 6.7%, respectively. Five-year net survival was 81.0% when pathological margins were <1 mm and 95.6% when ≥1 mm (p=0.024).Conclusion: Outcomes following polypectomy in patients with a pathological margin ≥1 mm are similar to those following surgery in the general population. Endoscopic resection needs to be completed by surgery if pathological margins are less than 1 mm.
Joaquim Javary, Nathalie Allain-Courtois, Nicolas Saucisse, Pierre Costet, Capucine Heraud, Fadila Benhamed, Costet Pierre, Corinne Bure, Nestor Pallares-Lupon, Marcio Do Cruzeiro, et al.
Published: 26 October 2017
by BMJ
Gut, Volume 67, pp 2192-2203; https://doi.org/10.1136/gutjnl-2017-314208

Abstract:
Objective: The AAA+ ATPase Reptin is overexpressed in hepatocellular carcinoma and preclinical studies indicate that it could be a relevant therapeutic target. However, its physiological and pathophysiological roles in vivo remain unknown. This study aimed to determine the role of Reptin in mammalian adult liver.Design and results: We generated an inducible liver-specific Reptin knockout (RepinLKO) mouse model. Following Reptin invalidation, mice displayed decreased body and fat mass, hypoglycaemia and hypolipidaemia. This was associated with decreased hepatic mTOR protein abundance. Further experiments in primary hepatocytes demonstrated that Reptin maintains mTOR protein level through its ATPase activity. Unexpectedly, loss or inhibition of Reptin induced an opposite effect on mTORC1 and mTORC2 signalling, with: (1) strong inhibition of hepatic mTORC1 activity, likely responsible for the reduction of hepatocytes cell size, for decreased de novo lipogenesis and cholesterol transcriptional programmes and (2) enhancement of mTORC2 activity associated with inhibition of the gluconeogenesis transcriptional programme and hepatic glucose production. Consequently, the role of hepatic Reptin in the pathogenesis of insulin resistance (IR) and non-alcoholic fatty liver disease consecutive to a high-fat diet was investigated. We found that Reptin deletion completely rescued pathological phenotypes associated with IR, including glucose intolerance, hyperglycaemia, hyperlipidaemia and hepatic steatosis.Conclusion: We show here that the AAA +ATPase Reptin is a regulator of mTOR signalling in the liver and global glucido-lipidic homeostasis. Inhibition of hepatic Reptin expression or activity represents a new therapeutic perspective for metabolic syndrome.
I-Lin Frank Chen, Kai-Wen Liu, Tao-Qian Tang, Wen-Lun Wang
Published: 28 September 2017
by BMJ
Gut, Volume 67, pp 1645-1646; https://doi.org/10.1136/gutjnl-2017-315087

Abstract:
A 62-year-old male without significant medical history presented with intermittent epigastric pain and abdominal fullness for 2 months. He denied having bloody stool or weight loss. He visited the outpatient department, where the CT scan of abdomen was performed (figure 1). He then underwent oesophagogastroduodenoscopy (EGD), which revealed a subepithelial tumour at gastric antrum with obstruction of the pylorus (figure 2 and video in the online supplementary file 1). Endoscopic ultrasound sonography (EUS) was performed …
Kesavan Kandiah, Fergus J Q Chedgy, Sharmila Subramaniam, , , , Prateek Sharma, Oliver Pech, Pradeep Bhandari
Published: 28 September 2017
by BMJ
Gut, Volume 67, pp 2085-2091; https://doi.org/10.1136/gutjnl-2017-314512

Abstract:
BackgroundBarrett’s oesophagus is an established risk factor for developing oesophageal adenocarcinoma. However, Barrett’s neoplasia can be subtle and difficult to identify. Acetic acid chromoendoscopy (AAC) is a simple technique that has been demonstrated to highlight neoplastic areas but lesion recognition with AAC remains a challenge, thereby hampering its widespread use.ObjectiveTo develop and validate a simple classification system to identify Barrett’s neoplasia using AAC.DesignThe study was conducted in four phases: phase 1—development of component descriptive criteria; phase 2—development of a classification system; phase 3—validation of the classification system by endoscopists; and phase 4—validation of the classification system by non-endoscopists.ResultsPhases 1 and 2 led to the development of a simplified AAC classification system based on two criteria: focal loss of acetowhitening and surface patterns of Barrett’s mucosa. In phase 3, the application of PREDICT (Portsmouth acetic acid classification) by endoscopists improved the sensitivity and negative predictive value (NPV) from 79.3% and 80.2% to 98.1% and 97.4%, respectively (pConclusionWe developed and validated a classification system known as PREDICT for the diagnosis of Barrett’s neoplasia using AAC. The improvement seen in the sensitivity and NPV for detection of Barrett’s neoplasia in phase 3 demonstrates the clinical value of PREDICT and the similar improvement seen among non-endoscopists demonstrates the potential for generalisation of PREDICT once proven in real time.
M J Carter, A J Lobo,
Published: 1 September 2004
by BMJ
Abstract:
A comprehensive literature search was performed using electronic databases (Medline, PubMed, and Ovid; keywords: “inflammatory bowel disease”, “ulcerative colitis”, and “Crohn’s disease”) by Dr Carter. A preliminary document was drafted by Dr Carter, Dr Lobo, and contributing authors. This was summarised by Dr Travis and revised after circulation first to the committee and then to members of the IBD section of the BSG, before submission to the Clinical Services’ Committee.
, C. Saro, F González-Huix, F. Suárez, M Forné, J M Viver
Published: 1 September 2004
by BMJ
Gut, Volume 53, pp 1363-1365; https://doi.org/10.1136/gut.2004.040675

Abstract:
Background: There is little information about the effect of infliximab on the clinical course of liver disease in Crohn’s disease patients with concomitant hepatitis B virus (HBV) infection. Theoretically, immunosuppression induced by infliximab will facilitate viral replication which could be followed by a flare or exacerbation of disease when therapy is discontinued. There are no specific recommendations on surveillance and treatment of HBV before infliximab infusion. Two cases of severe hepatic failure related to infliximab infusions have been described in patients with rheumatic diseases. Patients and methods: Hepatitis markers (C and B) and liver function tests were prospectively determined to 80 Crohn’s disease patients requiring infliximab infusion in three hospitals in Spain. Results: Three Crohn’s disease patients with chronic HBV infection were identified. Two of the three patients with chronic HBV infection suffered severe reactivation of chronic hepatitis B after withdrawal of infliximab therapy and one died. A third patient, who was treated with lamivudine at the time of infliximab therapy, had no clinical or biochemical worsening of liver disease during or after therapy. From the remaining 80 patients, six received the hepatitis B vaccine. Three patients had antibodies to both hepatitis B surface antigen (anti-HBs) and hepatitis B core protein (anti-HBc) with normal aminotransferase levels, and one patient had positive anti-hepatitis C virus (HCV) antibodies, negative HCV RNA, and normal aminotransferase levels. Except for the patients with chronic HBV infection, no significant changes in hepatic function were detected. Conclusions: Patients with Crohn’s disease who are candidates for infliximab therapy should be tested for hepatitis B serological markers before treatment and considered for prophylaxis of reactivation using antiviral therapy if positive.
Published: 1 September 2004
by BMJ
Gut, Volume 53, pp 1340-1344; https://doi.org/10.1136/gut.2004.039883

Abstract:
Background: In predicted severe acute pancreatitis, many patients develop organ failure and recover without local complications, and mortality is only 14–30%. It has been suggested that half of patients with progressive early organ failure may die, but there are no data to relate death or local complications to duration of early (week 1) organ failure. Aims: To determine mortality rates in patients with transient (48 hours) early organ failure and to show whether persistent organ failure predicts death or local complications. Patients: A total of 290 patients with predicted severe acute pancreatitis previously studied in a trial of lexipafant, recruited from 78 hospitals through 18 centres in the UK. Method: Manual review of trial database to determine: the presence of organ failure (Marshall score ⩾2) on each of the first seven days in hospital, duration of organ failure, and outcome of pancreatitis (death, complications by Atlanta criteria). Results: Early organ failure was present in 174 (60%) patients. After transient organ failure (n = 71), outcome was good: one death and 29% local complications. Persistent organ failure (n = 103) was followed by 36 deaths and 77% local complications, irrespective of onset of organ failure on admission or later during the first week. Conclusion: Duration of organ failure during the first week of predicted severe acute pancreatitis is strongly associated with the risk of death or local complications. Resolution of organ failure within 48 hours suggests a good prognosis; persistent organ failure is a marker for subsequent death or local complications.
, M Allocca, P Cantù, M Mangano, D Savojardo, S Carmagnola, P A Bianchi
Published: 1 September 2004
by BMJ
Gut, Volume 53, pp 1227-1231; https://doi.org/10.1136/gut.2003.035246

Abstract:
Background: Morphine reduces the rate of transient lower oesophageal sphincter (LOS) relaxations but its site of action is presently unknown. There are no data available concerning its motor effects on the proximal stomach, an important site for triggering transient LOS relaxations. Aim: To evaluate the effect of morphine on the rate of transient LOS relaxations and motor function of the proximal stomach. Subjects and methods: In 19 healthy subjects, concurrent transient LOS relaxations with a sleeve sensor and motor function of the proximal stomach with a bag connected to an electronic barostat were recorded during pressure controlled (n = 9) and volume controlled (n = 10) gastric distensions after intravenous administration of placebo and morphine 100 μg/kg. Results: During pressure controlled distensions, intrabag volume was markedly decreased by morphine (median 189 ml (interquartile range 101–448) v 404 (265–868) after placebo; p<0.01) as was the rate of transient LOS relaxations (0.5/30 minutes (0.4–2) v 2.5 (2–4); p<0.01). When intrabag volume was kept constant (525 ml (490–600)) (that is, in volume controlled distensions), the rate of transient LOS relaxations was not affected by morphine (2/30 minutes (2–3) v 2.5 (2–3)). Gastric contractions decreased after morphine similarly during pressure controlled and volume controlled distensions (8.5/30 minutes (4–10) v 15.5 (9.5–20.5), p<0.02; and 6.5 (0–24) v 19.5 (12–22), p<0.05). Conclusions: The effect of morphine on transient LOS relaxations is dependent on the decrease in volume of the proximal stomach. Our data suggest that pharmacological interventions which decrease fundal volume should result in control of transient LOS relaxation mediated gastro-oesophageal reflux.
Published: 1 September 2004
by BMJ
Gut, Volume 53, pp 1374-1384; https://doi.org/10.1136/gut.2003.022111

Abstract:
Triple therapy, including two antibiotics, amoxicillin and clarithromycin, and a proton pump inhibitor given for a week has been recommended as the treatment of choice at several consensus conferences.1–6 However, this treatment may fail for several reasons, as reported elsewhere.7 In fact, the main reason for failure was found to be H pylori resistance to one of the antibiotics used (that is, clarithromycin). Other treatments have also been proposed, including metronidazole, a drug for which resistance is also a problem although to a lesser extent, as well as tetracycline, fluoroquinolones, and rifamycins for which resistance has become an emerging issue.8,9
, T Masaoka, H Hosoda, T Ota, Y Minegishi, S Nomura, K Kangawa, H Ishii
Published: 1 February 2004
by BMJ
Gut, Volume 53, pp 187-194; https://doi.org/10.1136/gut.2003.021568

Abstract:
Background and aim: Although ghrelin, a novel growth hormone releasing peptide localised mainly in the gastric fundus, is reported not only to accelerate food passage and gastrointestinal motility but also to affect appetite and weight control, regulation of gastric ghrelin secretion under the conditions of gastric Helicobacter pylori infection is unknown. The present study was designed to investigate plasma and gastric ghrelin levels in Mongolian gerbils with H pylori colonisation of the gastric mucosa. Methods: Gerbils orally inoculated with H pylori were examined after inoculation. To examine preproghrelin mRNA expression in the gastric mucosa, cDNA encoding the gerbil preproghrelin and glyceraldehyde-3-phosphate dehydrogenase homologue was isolated and a quantitative reverse transcription-polymerase chain reaction system was established. Results: In gerbils showing H pylori colonisation (H pylori group), expression of preproghrelin mRNA and total ghrelin levels were significantly decreased 17 and 23 weeks later (p<0.01). Although the number of ghrelin immunoreactive cells decreased as the stomach weight increased, the gastric contents of total and active ghrelin in this group were the same as those in controls. Gastric myeloperoxidase activity showed a positive correlation with plasma ghrelin levels. On the other hand, at 17 weeks, plasma ghrelin levels were significantly increased in the H pylori group (p<0.05), suggesting a compensatory increase in secretion of the peptide at this time point. Conclusion: The present experimental study demonstrated that gastric and plasma ghrelin dynamics are altered in response to H pylori infection.
Robert R Cima
Published: 1 February 2004
by BMJ
Gut, Volume 53, pp 306-307; https://doi.org/10.1136/gut.2003.001719

Abstract:
Ulcerative colitis (UC), one of the major categories of inflammatory bowel disease (IBD), is characterised by chronic colonic mucosal inflammation of unknown aetiology. Unlike the other major form of IBD, Crohn’s disease (CD), UC is pathologically limited to the rectum and colon, facilitating definitive surgical therapy. Whereas the role of surgery in CD is primarily to treat complications of the disease process, surgery in UC is curative for the intestinal manifestations of the disease and nearly eliminates the risk of future malignancy. There exist three major indications for surgical intervention in UC. The first indication is for treatment of acute, medically unresponsive flares. The second is for poorly controlled symptomatic disease or to address intolerable treatment side effects. Lastly, surgery is performed for the possibility of malignancy after longstanding symptomatic or asymptomatic disease. Because there are indications for surgery, both early in the course of the disease and during the chronic disease phase, which may be asymptomatic, early curative surgical intervention is a reasonable alternative to prolonged medical management. Currently, surgical intervention is accomplished safely, with good functional results, and with a high degree of patient satisfaction. Historically, definitive surgical treatment of UC required removal of the colon, rectum, and anus and creation of a permanent ileostomy. Since the early 1980s, surgical therapy has evolved to removal of the entire colon and rectum followed by construction of an ileal pouch that is anastomosed to the anal canal. This procedure is known as a proctocolectomy and ileal pouch anal anastomosis (IPAA).1 IPAA avoids the need for a permanent ostomy and maintains the …
E E Wheeler, D N Challacombe
Published: 1 January 1997
by BMJ
Gut, Volume 40, pp 57-60; https://doi.org/10.1136/gut.40.1.57

Abstract:
BACKGROUND: Experimental evidence suggests that hormones may regulate small intestinal adaptation after surgical resection. AIMS: To characterise the effect of recombinant human growth hormone (GH), insulin-like growth factor-I (IGF-I) and insulin on crypt epithelial cell proliferation in the human duodenal mucosa cultured in vitro. PATIENTS: Thirty nine adults had endoscopic duodenal biopsy specimens taken, which were histologically normal and pair matched specimens from each patient acted as their own control. METHODS: Paired biopsy specimens from patients were cultured in vitro, with or without the addition of GH (0.004 IU/ml), IGF-I (400 ng/ml) or insulin (50 micrograms/ml), alone or in combination. After 22 hours, vincristine sulphate was added to the cultures and three hours later specimens were removed and fixed, and DNA stained by the Feulgen method. Intestinal crypts were microdissected and crypt epithelial cell proliferation determined by estimating mean numbers of accumulated metaphase arrests/crypt present in tests and controls between 22-25 hours of culture. RESULTS: The addition of GH, IGF-I, and insulin, alone or in combination, significantly increased crypt epithelial cell proliferation in test explants compared with controls. IGF-I was most potent and its trophic effect was modified by insulin. CONCLUSIONS: GH, IGF-I, and insulin are involved in the regulation of crypt cell proliferation in the human small intestine in vitro and possibly in vivo.
J G Silcock, M G Bramble
Published: 1 February 1997
by BMJ
Gut, Volume 40, pp 192-195; https://doi.org/10.1136/gut.40.2.192

Abstract:
In June 1990 a survey of members of the endoscopy section of the British Society of Gastroenterology showed that 47% of respondents were offering some form of open access gastroscopy (OAG). Only 10% offered true (non-censored) OAG. The survey was repeated in June 1994. The overall provision of OAG had risen to 74%, most of whom were offering true OAG. Censored OAG is still widely practised and characterised by referral letters to a consultant in contrast with the use of referral forms (p < 0.001). Referral forms are being increasingly used and are an effective way of capturing important data such as the patients' symptoms (100%), previous treatment (87%), non-steroidal anti-inflammatory drug or aspirin use (78%), suspected diagnosis (74%), and other medical conditions (72%). Forms were used to establish clinical responsibility with the general practitioner in 64% of units. Standardised referral and reporting forms were used by 27% of respondents. A perceived inability to cope with the expected workload was still the most commonly cited reason for not being able to offer OAG. Although 20% of units with a single handed endoscopist were able to offer OAG, this compared with 68% of units with two or more endoscopists (p < 0.001). Only three units indicated that an OAG service had had to be withdrawn, but a further 12 consultants (nine units) were now offering an age restricted service because of excessive workload. Two thirds of the respondents not offering OAG were hoping to do so in the near future. True OAG has increased from 10% to 41% in four years.
, E T H Fontham, , J C Bravo, M B Piazuelo, M C Camargo,
Published: 1 November 2005
by BMJ
Gut, Volume 54, pp 1536-1540; https://doi.org/10.1136/gut.2005.072009

Abstract:
Background:Helicobacter pylori infection induces progressive inflammatory changes in the gastric mucosa that may lead to gastric cancer. Understanding long term effects resulting from the cure of this infection is needed to design cancer prevention strategies. Methods: A cohort of 795 adults with preneoplastic gastric lesions was randomised to receive anti-H pylori treatment and/or antioxidants. At the end of six years of intervention, those who did not receive anti-H pylori treatment were offered it. Gastric biopsies were obtained at baseline, and at 3, 6, and 12 years. A histopathology score was utilised to document changes in gastric lesions. Non-linear mixed models were used to estimate the cumulative effect of H pylori clearance on histopathology scores adjusted for follow up time, interventions, and confounders. Results: Ninety seven per cent of subjects were H pylori positive at baseline, and 53% were positive at 12 years. Subjects accumulated 1703 person years free of infection. A multivariate model showed a significant regression in histopathology score as a function of the square of H pylori negative time. Subjects who were H pylori negative had 14.8% more regression and 13.7% less progression than patients who were positive at 12 years (p = 0.001). The rate of healing of gastric lesions occurred more rapidly as years free of infection accumulated, and was more pronounced in less advanced lesions. Conclusions: Preneoplastic gastric lesions regress at a rate equal to the square of time in patients rendered free of H pylori infection. Our findings suggest that patients with preneoplastic gastric lesions should be treated and cured of their H pylori infection.
, M Nicolaus, R Roggel, M Katschinski, M Storr, H J Woerle, B Göke
Published: 1 February 2006
by BMJ
Gut, Volume 55, pp 243-251; https://doi.org/10.1136/gut.2004.059741

Abstract:
Background: Exogenous use of the intestinal hormone glucagon-like peptide 1 (GLP-1) lowers glycaemia by stimulation of insulin, inhibition of glucagon, and delay of gastric emptying. Aims: To assess the effects of endogenous GLP-1 on endocrine pancreatic secretion and antro-pyloro-duodenal motility by utilising the GLP-1 receptor antagonist exendin(9-39)amide (ex(9-39)NH2). Methods: Nine healthy volunteers underwent four experiments each. In two experiments with and without intravenous infusion of ex(9-39)NH2 300 pmol/kg/min, a fasting period was followed by intraduodenal glucose perfusion at 1 and 2.5 kcal/min, with the higher dose stimulating GLP-1 release. Antro-pyloro-duodenal motility was measured by perfusion manometry. To calculate the incretin effect (that is, the proportion of plasma insulin stimulated by intestinal hormones) the glycaemia observed during the luminal glucose experiments was mimicked using intravenous glucose in two further experiments. Results: Ex(9-39)NH2 significantly increased glycaemia during fasting and duodenal glucose. It diminished plasma insulin during duodenal glucose and significantly reduced the incretin effect by approximately 50%. Ex(9-39)NH2 raised plasma glucagon during fasting and abolished the decrease in glucagon at the high duodenal glucose load. Ex(9-39)NH2 markedly stimulated antroduodenal contractility. At low duodenal glucose it reduced the stimulation of tonic and phasic pyloric motility. At the high duodenal glucose load it abolished pyloric stimulation. Conclusions: Endogenous GLP-1 stimulates postprandial insulin release. The pancreatic α cell is under the tonic inhibitory control of GLP-1 thereby suppressing postprandial glucagon. GLP-1 tonically inhibits antroduodenal motility and mediates the postprandial inhibition of antral and stimulation of pyloric motility. We therefore suggest GLP-1 as a true incretin hormone and enterogastrone in humans.
, L Wang, Y Wang, , P-Q Yuan, C Maillot, S V Coutinho, J A McRoberts, A Bayati, H Mattsson, et al.
Published: 1 February 2006
by BMJ
Gut, Volume 55, pp 172-181; https://doi.org/10.1136/gut.2004.051391

Abstract:
Background and aims: Activation of corticotropin releasing factor 1 (CRF1) receptors is involved in stress related responses and visceral pain, while activation of CRF2 receptors dampens the endocrine and some behavioural stress responses. We hypothesised that CRF2 receptor activation may influence visceral pain induced by colorectal distension (CRD) in conscious rats, and assessed the possible sites and mechanisms of action. Methods: Male Sprague-Dawley rats were exposed to CRDs (60 mm Hg, 10 minutes twice, with a 10 minute rest interval). Visceromotor responses (VMR) were measured by electromyography or visual observation. Spinal (L6–S1) extracellular signal regulated kinase 1/2 (ERK 1/2) activation following in vivo CRD and CRF2 receptor gene expression in the T13–S1 dorsal root ganglia (DRG) and spinal cord were determined. Inferior splanchnic afferent (ISA) activity to CRD (0.4 ml, 20 seconds) was assessed by electrophysiological recording in an in vitro ISA nerve-inferior mesenteric artery (intra-arterial)-colorectal preparation. Results: In controls, VMR to the second CRD was mean 31 (SEM 4)% higher than that of the first (p<0.05). The selective CRF2 agonist, human urocortin 2 (hUcn 2, at 10 and 20 μg/kg), injected intravenous after the first distension, prevented sensitisation and reduced the second response by 8 (1)% and 30 (5)% (p<0.05) compared with the first response, respectively. RT-PCR detected CRF2 receptor gene expression in the DRG and spinal cord. CRD (60 mm Hg for 10 minutes) induced phosphorylation of ERK 1/2 in neurones of lumbosacral laminae I and IIo and the response was dampened by intravenous hUcn 2. CRD, in vitro, induced robust ISA spike activity that was dose dependently blunted by hUcn 2 (1–3 μg, intra-arterially). The CRF2 receptor antagonist, astressin2-B (200 μg/kg subcutaneously or 20 μg intra-arterially) blocked the hUcn 2 inhibitory effects in vivo and in vitro. Conclusions: Peripheral injection of hUcn 2 blunts CRD induced visceral pain, colonic afferent, and spinal L6-S1 ERK 1/2 activity through CRF2 receptor activation in rats.
G Schimpl, M A Pabst, G Feierl, A Kuesz, , S Takahashi, M E Hollwarth
Published: 1 December 1999
by BMJ
Gut, Volume 45, pp 904-910; https://doi.org/10.1136/gut.45.6.904

Abstract:
BACKGROUND Bacterial translocation (BT) plays a major role in the pathophysiological process of spontaneous infections in portal hypertension (PH) and cholestatic jaundice. The major mechanisms promoting BT in experimental animal models are the disruption of the intestinal ecological equilibrium and disruption of the intestinal mucosal barrier. The enzymes xanthine dehydrogenase (XD) and xanthine oxidase (XO) are often implicated as a significant source of oxidants which have a major impact on the impairment of intestinal barrier function. AIM To investigate the incidence of BT in rats with PH and obstructive jaundice, and to evaluate the impact of XD and XO. METHODS Animals were subjected to sham laparotomy (SL), PH by calibrated stenosis of the portal vein, and common bile duct ligation (CBDL). They were fed either a standard pellet diet or a tungsten supplemented molybdenum-free diet. Four weeks after the operative procedure, intestinal colonisation and BT to portal vein, vena cava, mesenteric lymph nodes, liver, and spleen were determined. Intestinal XD and XO activity were measured enzymatically and histochemically. RESULTS Significant (p<0.01) intestinal bacterial overgrowth was present in all PH and CBDL groups compared with the SL group. In normally fed animals after SL, BT occurred in 12%. In PH and after CBDL, the rate of BT increased significantly (p<0.05) to 28% and 54% respectively. In the jejunum of normally fed animals subjected to PH or CBDL, a significant increase in XO was observed (p<0.01). Animals fed a tungsten supplemented diet showed a significant attenuation of BT to 14% in PH and 22% after CBDL (p<0.05). Tungsten treatment completely suppressed jejunal XD and XO activities. CONCLUSIONS Significant intestinal bacterial overgrowth, BT, and XD to XO conversion occurred in PH and after CBDL. XD and XO inactivation by a tungsten supplemented molybdenum-free diet significantly reduced the incidence of BT without affecting intestinal bacterial overgrowth. These data strongly support the hypothesis that increased XD to XO conversion may contribute to intestinal barrier failure in PH and after CBDL.
M Voutilainen, , M Juhola, , P Sipponen, C The Central Finland Endoscopy Study Group
Published: 1 November 1999
by BMJ
Gut, Volume 45, pp 644-648; https://doi.org/10.1136/gut.45.5.644

Abstract:
BACKGROUND/AIMS Intestinal metaplasia (IM) is a common finding at the oesophagogastric junction, but the aetiopathogenesis of the different IM subtypes—that is, incomplete IM (specialised columnar epithelium, SCE) and complete IM— and their associations with gastro-oesophageal reflux disease and Helicobacter pylori gastritis are unclear. METHODS 1058 consecutive dyspeptic patients undergoing gastroscopy were enrolled. The gastric, oesophagogastric junctional, and oesophageal biopsy specimens obtained were stained with haematoxylin and eosin, alcian blue (pH 2.5)-periodic acid Schiff, and modified Giemsa. RESULTS Complete junctional IM was detected in 196 (19%) of the 1058 subjects, and in 134 (13%) was the sole IM subtype. Incomplete junctional IM (SCE) was detected in 101 (10%) subjects, of whom 62 (61%) also had the complete IM subtype. Of patients with normal gastric histology (n = 426), 6% had complete IM and 7% junctional SCE. The prevalence of both types of IM increased with age in patients with either normal gastric histology or chronic gastritis (n = 611). Epithelial dysplasia was not detected in any patients with junctional IM. In multivariate analysis, independent risk factors for incomplete junctional IM were age (odds ratio (OR) 1.3 per decade, 95% confidence interval (CI) 1.2 to 1.6), endoscopic erosive oesophagitis (OR 1.9, 95% CI 1.1 to 3.2), and chronic cardia inflammation (OR 2.9, 95% CI 1.3 to 6.2), but not gastric H pylori infection (OR 1.0, 95% CI 0.6 to 1.7). In univariate analysis, junctional incomplete IM was not associated with cardia H pylori infection. Independent risk factors for “pure” complete junctional IM (n = 134) were age (OR 1.2 per decade, 95% CI 1.0 to 1.4), antral predominant non-atrophic gastritis (OR 2.6, 95% CI 1.3 to 5.2), antral predominant atrophic gastritis (OR 2.1, 95% CI 1.1 to 5.2), and multifocal atrophic gastritis (OR 7.1, 95% CI 2.5 to 19.8). In univariate analysis, junctional complete IM was strongly associated with chronic cardia inflammation and cardia H pylori infection (p<0.001). CONCLUSIONS Both complete and incomplete junctional IM are independent acquired lesions that increase in prevalence with age. Although IM subtypes often occur simultaneously, they show remarkable differences in their associations with gastritis and erosive oesophagitis: junctional complete IM is a manifestation of multifocal atrophic gastritis, while the incomplete form (SCE) may result from carditis and gastro-oesophageal reflux disease. The frequency of dysplasia in intestinal metaplasia at the oesophagogastric junction appears to be low.
J A Tibble, G Sigthorsson, R Foster, D Scott, M K Fagerhol, A Roseth, I Bjarnason
Published: 1 September 1999
by BMJ
Gut, Volume 45, pp 362-366; https://doi.org/10.1136/gut.45.3.362

Abstract:
The diagnosis of non-steroidal anti-inflammatory drug (NSAID) induced enteropathy is difficult, requiring enteroscopy or the use of four day faecal excretion of 111In labelled white cells. To assess faecal calprotectin (a non-degraded neutrophil cytosolic protein) as a method for diagnosing NSAID enteropathy. Single stool faecal calprotectin concentrations were compared with the four day faecal excretion of 111In labelled white cells in 47 patients taking NSAIDs. The prevalence and severity of NSAID enteropathy was assessed using this method in 312 patients (192 with rheumatoid arthritis, 65 with osteoarthritis, 55 with other conditions) taking 18 different NSAIDs. The four day faecal excretion of 111In white cells correlated significantly with faecal calprotectin concentrations. In the group of 312 patients on NSAIDs faecal calprotectin concentrations were significantly higher than in controls, the prevalence of NSAID enteropathy being 44%. The prevalence and severity of NSAID enteropathy was independent of the particular type or dose of NSAID being taken or other patient variables. Assay of faecal calprotectin provides a simple practical method for diagnosing NSAID enteropathy in man. Forty four per cent of patients receiving these drugs had NSAID induced enteropathy when assessed by this technique; 20% of these had comparable levels of inflammation to that previously reported in patients with inflammatory bowel disease.
A Rasquin-Weber, P E Hyman, , D R Fleisher, J S Hyams, P J Milla,
Published: 1 September 1999
by BMJ
Abstract:
This is the first attempt at defining criteria for functional gastrointestinal disorders (FGIDs) in infancy, childhood, and adolescence. The decision-making process was as for adults and consisted of arriving at consensus, based on clinical experience. This paper is intended to be a quick reference. The classification system selected differs from the one used in the adult population in that it is organized according to main complaints instead of being organ-targeted. Because the child is still developing, some disorders such as toddler’s diarrhea (or functional diarrhea) are linked to certain physiologic stages; others may result from behavioral responses to sphincter function acquisition such as fecal retention; others will only be recognizable after the child is cognitively mature enough to report the symptoms (e.g., dyspepsia). Infant regurgitation, rumination, and cyclic vomiting constitute the vomiting disorders. Abdominal pain disorders are classified as: functional dyspepsia, irritable bowel syndrome (IBS), functional abdominal pain, abdominal migraine, and aerophagia. Disorders of defecation include: infant dyschezia, functional constipation, functional fecal retention, and functional non-retentive fecal soiling. Some disorders, such as IBS and dyspepsia and functional abdominal pain, are exact replications of the adult criteria because there are enough data to confirm that they represent specific and similar disorders in pediatrics. Other disorders not included in the pediatric classification, such as functional biliary disorders, do occur in children; however, existing data are insufficient to warrant including them at the present time. For these disorders, it is suggested that, for the time being, clinicians refer to the criteria established for the adult population.
, M. Delvaux, F Azpiroz, M Camilleri, , D G Thompson
Published: 1 September 1999
by BMJ
Abstract:
Many of the symptoms characteristic of the functional gastrointestinal disorders (FGID) are consistent with dysfunction of the motor and/or sensory apparatus of the digestive tract. Those aspects of sensorimotor dysfunction most relevant to the FGID include alterations in: gut contractile activity; myoelectrical activity; tone and compliance; and transit, as well as an enhanced sensitivity to distension, in each region of the gastrointestinal tract. Assessment of these phenomena involves a number of techniques, some well established and others requiring further validation. Using such techniques, researchers have reported a wide range of alterations in sensory and in motor function in the FGID. Importantly, however, relationships between such dysfunction and symptoms have been relatively weak, and so the clinical relevance of the former remains unclear. Moreover, the proportions of patients in the various symptom subgroups who display dysfunction, and the extent and severity of their symptoms, require better characterization. On a positive note, progress is occurring on several fronts, especially in relation to functional dyspepsia and irritable bowel syndrome, and based on the data gathered to date, a number of areas where further advances are required can be highlighted.
V Savarino, , G Celle
Published: 1 July 1999
by BMJ
Abstract:
The urea breath test (UBT) is one of the most important non-invasive methods for detecting Helicobacter pylori infection. The test exploits the hydrolysis of orally administered urea by the enzyme urease, which H pylori produces in large quantities. Urea is hydrolysed to ammonia and carbon dioxide, which diffuses into the blood and is excreted by the lungs. Isotopically labelled CO2 can be detected in breath using various methods. Labelling urea with 13C is becoming increasingly popular because this non-radioactive isotope is innocuous and can be safely used in children and women of childbearing age. Breath samples can also be sent by post or courier to remote analysis centres. The test is easy to perform and can be repeated as often as required in the same patient. A meal must be given to increase the contact time between the tracer and the H pylori urease inside the stomach. The test has been simplified to the point that two breath samples collected before and 30 minutes after the ingestion of urea in a liquid form suffice to provide reliable diagnostic information. The cost of producing 13C-urea is high, but it may be possible to reduce the dosage further by administering it in capsule form. An isotope ratio mass spectrometer (IRMS) is generally used to measure 13C enrichment in breath samples, but this machine is expensive. In order to reduce this cost, new and cheaper equipment based on non-dispersive, isotope selective, infrared spectroscopy (NDIRS) and laser assisted ratio analysis (LARA) have recently been developed. These are valid alternatives to IRMS although they cannot process the same large number of breath samples simultaneously. These promising advances will certainly promote the wider use of the 13C-UBT, which is especially useful for epidemiological studies in children and adults, for screening patients before endoscopy, and for assessing the efficacy of eradication regimens.
M P A Ebert, , C Haeckel, K Rutkowski, R M Schmid, M Wagner, G Adler, H U Schulz, A Roessner, P Malfertheiner
Published: 1 July 1999
by BMJ
Gut, Volume 45, pp 105-111; https://doi.org/10.1136/gut.45.1.105

Abstract:
BACKGROUND/AIMS Chronic pancreatitis is an inflammatory disease of the exocrine pancreas associated with extensive fibrosis, enlarged pancreatic ducts, acinar cell degeneration, and the formation of tubular complexes. The molecular and biochemical alterations associated with these histological changes are not kown. Generally, the new family of TFF peptides (formerly known as P-domain peptides or trefoil factors) is aberrantly expressed during chronic inflammatory diseases of the gastrointestinal tract. METHODS Using human pancreatic tissues obtained from patients with chronic pancreatitis and murine pancreatic tissues obtained from transgenic mice overexpressing transforming growth factor α (TGF-α), the expression and cellular distribution of TFF1 was analysed using northern blot analysis, polymerase chain reaction (PCR), and immunohistochemistry. RESULTS In the normal human pancreas, TFF1 was scarce, with only a few ducts exhibiting cytoplasmic TFF1 immunoreactivity. In contrast, human chronic pancreatitis tissue specimens exhibited strong TFF1 immunoreactivity in ductal cells, areas of ductal hyperplasia, and tubular complexes. Semiquantitative PCR analysis of TFF1 mRNA levels showed enhanced expression of TFF1 in the pancreas of patients with chronic pancreatitis. Furthermore, TFF1 mRNA levels were detectable in the pancreas in four of five transgenic mice overexpressing TGF-α. In contrast, four of five wild type mice did not exhibit a TFF1 mRNA transcript. In addition, while no specific TFF1 immunoreactivity was present in the pancreas of the wild type mice, ductal epithelial cells and duct-like tubular complexes in the pancreas of the transgenic mice overexpressing TGF-α exhibited pronounced TFF1 immunoreactivity. CONCLUSIONS Ductal cells and tubular complexes in pancreatic fibrosis express TFF1. As the 5′-flanking region of TFF1 contains an epidermal growth factor responsive enhancer region and the expression of epidermal growth factor and TGF-α is enhanced in pancreatic fibrosis, the enhanced expression of TFF1 in pancreatic fibrosis may be mediated by TGF-α.
W M Wong, R Poulsom,
Published: 1 June 1999
by BMJ
Gut, Volume 44, pp 890-895; https://doi.org/10.1136/gut.44.6.890

Abstract:
In humans, three trefoil peptides or trefoil factors (TFF) are known. The first trefoil peptide discovered was pS2/TFF1 or breast cancer oestrogen inducible gene— discovered during a search for oestrogen induced mRNAs from the mammary carcinoma cell line MCF7 in 1982.1 In the same year, TFF2 (formerly spasmolytic polypeptide, SP) was purified and extracted from porcine pancreas during the preparation of porcine insulin.2-4 Several years later, it was noticed that these peptides share a common novel sequence motif,5 , 6 later named the trefoil domain7 or P-domain (fig 1).8 The third mammalian protein in the family, ITF/TFF3 (previously called intestinal trefoil factor, ITF or hP1.B) was later discovered as a rat cDNA sequence in 19919 and the human cDNA sequence was reported in 1993.10-12 These peptides are resistant to thermal and enzymatic digestion, largely because the TFF domain shows a structure tightly held together by three pairs of disulphide bonds, which is encoded by shuffled modules highly conserved during evolution from amphibians to mammals (fig 1). TFF1 and TFF3 contain one trefoil domain, TFF2 has two and in the amphibianXenopus, there are molecules containing multiple trefoil domains.13-16 All three human trefoil genes are clustered on chromosome 21q22.3.17-21 The present nomenclature is based on the work of a group at a Conférence Philippe Laudat in which pS2 was named TFF1, spasmolytic polypeptide TFF2 and intestinal trefoil factor TFF3. It was recommended that different species be indicated by a lower case letter prefixed to the peptide name—for example, hTFF1 for human pS2, rTFF3 for rat ITF, etc.22 This article will mainly focus on recent proposals for the role of these peptides in epithelial inflammation, repair, and neoplasia in the gastrointestinal tract.
E A Carapeti, M A Kamm, P J McDonald, S J D Chadwick, D Melville, R K S Phillips
Published: 1 May 1999
by BMJ
Gut, Volume 44, pp 727-730; https://doi.org/10.1136/gut.44.5.727

Abstract:
BACKGROUNDTopical application of glyceryl trinitrate (GTN) ointment heals chronic anal fissures, providing an alternative to the traditional first line treatment of surgical sphincterotomy.AIMSTo determine the most effective dose of topical GTN for treatment of chronic anal fissures and to assess long term results.METHODSSeventy consecutive patients with chronic anal fissure, were randomly allocated to eight weeks treatment with placebo, 0.2% GTN three times daily, or GTN starting at 0.2% with weekly 0.1% increments to a maximum of 0.6%, in a double blind study.RESULTSAfter eight weeks fissure had healed in 67% of patients treated with GTN compared with 32% with placebo (p=0.008). No significant difference was seen between the two active treatments. Headaches were reported by 72% of patients on GTN compared with 27% on placebo (pCONCLUSIONSGTN is a good first line treatment for two thirds of patients with anal fissure. An escalating dose of GTN does not result in earlier healing. Significant recurrence of symptomatic fissures and a high incidence of headaches are limitations of the treatment.
T Wester, D S O’Briain, P Puri
Published: 1 May 1999
by BMJ
Gut, Volume 44, pp 666-674; https://doi.org/10.1136/gut.44.5.666

Abstract:
BACKGROUND Nitric oxide is the most important transmitter in non-adrenergic non-cholinergic nerves in the human gastrointestinal tract. Impaired nitrergic innervation has been described in Hirschsprung’s disease, hypertrophic pyloric stenosis, and intestinal neuronal dysplasia (IND). Recent findings indicate that hyperganglionosis, one of the major criteria of IND, is age dependent. However, information is scanty regarding the neurone density in normal human bowel in the paediatric age group. AIMS To determine neurone density, morphology, and nitric oxide synthase distribution of the normal myenteric plexus at different ages during infancy and childhood. METHODS Specimens were obtained from small bowel and colon in 20 children, aged one day to 15 years, at postmortem examination. Whole mount preparations were made of the myenteric plexus, which were subsequently stained using NADPH diaphorase histochemistry (identical to nitric oxide synthase) and cuprolinic blue (a general neuronal marker). The morphology of the myenteric plexus was described and the neurone density estimated. RESULTS The myenteric plexus meshwork becomes less dense during the first years of life. The density of ganglion cells in the myenteric plexus decreases significantly with age during the first three to four years of life. The NADPH diaphorase positive (nitrergic) subpopulation represents about 34% of all neurones in the myenteric plexus. CONCLUSIONS The notable decrease in neurone density in the myenteric plexus during the first years of life indicates that development is still an ongoing process in the postnatal enteric nervous system. Applied to the clinical situation, this implies that interpretation of enteric nervous system pathology is dependent on the age of the patient.
C P Tran, G A Cook, , L Thim,
Published: 1 May 1999
by BMJ
Gut, Volume 44, pp 636-642; https://doi.org/10.1136/gut.44.5.636

Abstract:
BACKGROUND The trefoil peptides are major secretory products of mucus cells of the gastrointestinal tract and show increased expression after inflammatory or ulcerative damage. Recombinant human TFF2 (spasmolytic polypeptide) has been shown to be cytoprotective, and enhances repair in models of gastric injury. AIMS To test the healing effects of recombinant human (h)TFF2 in a rat model of chronic colitis. METHODS Colitis was induced by intracolonic administration of dinitrobenzene sulphonic acid in ethanol. Mucosal repair was quantified macroscopically, microscopically by image analysis of tissue histology, and by measuring myeloperoxidase activity. RESULTS Initial validation studies showed that maximal injury and inflammation occurred at the end of the first week after colitis induction (active phase), and that spontaneous healing was complete by eight weeks. Once daily intrarectal application of hTFF2 (2.5 mg/kg; approximately 0.5 mg/rat) for five days after maximal damage had been sustained, reduced both microscopic and macroscopic injury by 80% and inflammatory index by 50% compared with vehicle controls. In addition, endogenous concentrations of rat TFF2 and TFF3 (intestinal trefoil factor) were increased in the active phase of colitis and were reduced to basal levels by hTFF2 treatment. CONCLUSIONS This study has shown that hTFF2 enhances the rate of colonic epithelial repair, and reduces local inflammation in a rat model of colitis, and suggests that luminal application of trefoil peptides may have therapeutic potential in the treatment of inflammatory bowel disease.
M F Neurath, C Becker, K Barbulescu
Published: 1 December 1998
by BMJ
Gut, Volume 43, pp 856-860; https://doi.org/10.1136/gut.43.6.856

Abstract:
NF-κB is a pleiotropic transcription factor with key functions in the intestinal immune system. NF-κB family members control transcriptional activity of various promoters of proinflammatory cytokines, cell surface receptors, transcription factors, and adhesion molecules that are involved in intestinal inflammation. The perpetuated activation of NF-κB in patients with active inflammatory bowel disease suggests that regulation of NF-κB activity is a very attractive target for therapeutic intervention. Such strategies include antioxidants, proteasome inhibitors, inhibition of NF-κB by adenoviral IκBα expression vectors, and antisense DNA targeting of NF-κB. These approaches will hopefully permit the design of new treatment strategies for chronic intestinal inflammation.
R A Al-Mufti, R C N Williamson,
Published: 1 October 1998
by BMJ
Gut, Volume 43, pp 564-570; https://doi.org/10.1136/gut.43.4.564

Abstract:
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.
A Stadnicki, R B Sartor, R Janardham, I Stadnicka, A A Adam, C Blais, R W Colman
Published: 1 September 1998
by BMJ
Gut, Volume 43, pp 365-374; https://doi.org/10.1136/gut.43.3.365

Abstract:
Background—The plasma kallikrein-kinin (K-K) system is activated in acute and chronic relapsing intestinal inflammation induced in Lewis rats by intramural injection of exogenous bacterial components.Aims—To determine whether this effect is model specific, K-K system activation was investigated in a modified indomethacin induced enterocolitis model, as well as bradykinin 2 (B2) receptor distribution in the normal and acutely inflamed intestine.Methods—Lewis rats injected with daily sublethal doses of indomethacin for two days developed acute (two days) and chronic (14 days) intestinal inflammation. Plasma prekallikrein (amidolytic), high molecular weight kininogen (HK, coagulant) and cleavage of HK (western blot) were assayed to detect K-K activation.Results—Liver and spleen weights were significantly higher, and body weights and haematocrit values were significantly lower in the indomethacin group than in the control group. During both acute and chronic phases, rats displayed K-K system activation manifested by a significant decrease in plasma prekallikrein and HK functional levels, and by HK cleavage. Plasma T kininogen (a major acute phase protein) was significantly elevated. B2 receptors were identified in both normal and inflammatory intestine with more prominent specific immunohistochemical staining in the acutely inflamed tissue.Conclusions—K-K system activation occurs in association with both acute and chronic phases of intestinal injury, regardless of the triggering agent, suggesting that activation of this system is integrally involved in intestinal inflammation in genetically susceptible hosts. Localisation of B2 receptors across intestinal layers provides a structural basis for the kinin function in the intestine.
S Matsumoto, Y Okabe, H Setoyama, K Takayama, J Ohtsuka, H Funahashi, A Imaoka, Y Okada, Y Umesaki
Published: 1 July 1998
by BMJ
Gut, Volume 43, pp 71-78; https://doi.org/10.1136/gut.43.1.71

Abstract:
Background—A new subline of the senescence accelerated mouse (SAM) P1/Yit strain has been established which shows spontaneous enteric inflammation under specific pathogen free (SPF) conditions.Aims—To elucidate the pathogenesis of enteric inflammation in this new subline.Methods—The SPF and germ free (GF) SAMP1/Yit strains were used. Histological, immunological, and microbiological characterisation of the mice with enteric inflammation was performed.Results—Histologically, enteritic inflammation developed as a discontinuous lesion in the terminal ileum and caecum with the infiltration of many inflammatory cells after 10 weeks of age. The activity of myeloperoxidase, and both immunolocalisation and mRNA expression of inducible nitric oxide synthase increased in the lesion. CD3-ε positive T cells, neutrophils, and macrophages were more numerous in the inflamed mucosa of the SAMP1/Yit strain. The GF SAMP1/Yit strain did not show any inflammation in the intestinal wall, by the age of 30 weeks, and the enteritis and caecitis developed 10 weeks after the conventionalisation of the GF SAMP1/Yit strain.Conclusion—Enteric inflammation in the ileum and caecum developed in the SAMP1/Yit strain. The pathophysiological characteristics of the disease in this mouse have some similarities to those of human inflammatory bowel disease (IBD). This mouse strain should be a useful model system for elucidating the interaction between the pathogenesis of IBD and the gut microflora.
J E Crabtree
Published: 1 July 1998
by BMJ
Gut, Volume 43, pp 7-8; https://doi.org/10.1136/gut.43.1.7

Abstract:
The development of a vaccine against H pylori which confers long term protective immunity is the best strategy to circumvent the problem of antibiotic resistance and to eradicate H pylori on a global scale. The feasibility of inducing protective immune responses to helicobacter by oral vaccination with bacterial antigens and a mucosal adjuvant was initially demonstrated in the H felis murine model.4-6 Vaccination with both H pylori urease5 and heat shock proteins (HspA and HspB)6 protected against subsequent challenge withH felis. However, H felis lacks many of the virulence factors present inH pylori, such as thecag pathogenicity island7 and the cytotoxin VacA,8 precluding analysis of these antigens as candidate vaccines in the H felis model. The development of mouse adapted H pyloristrains which cause chronic infection in mice was a major advance.9 The H pylori mouse model has permitted the testing of vaccines containing purifiedH pylori antigens against homologous challenge infection.9 To date, a number of protectiveH pylori antigens have been identified which confer immunity against H pylori infection in the mouse, including purified VacA,9urease,9 CagA,10 and catalase.11
R S Walmsley, R C S Ayres, R E Pounder, R N Allan
Published: 1 July 1998
by BMJ
Gut, Volume 43, pp 29-32; https://doi.org/10.1136/gut.43.1.29

Abstract:
Background—The appropriate medical treatment of patients with ulcerative colitis is determined largely by the severity of symptoms. Hospital assessment of the severity of disease activity includes investigation of laboratory indices and sigmoidoscopic assessment of mucosal inflammation.Aims—To develop a simplified clinical colitis activity index to aid in the initial evaluation of exacerbations of colitis.Methods—The information for development of the simple index was initially evaluated in 63 assessments of disease activity in patients with ulcerative colitis where disease activity was evaluated using the Powell-Tuck Index (which includes symptoms, physical signs, and sigmoidoscopic appearance). The new index was then further evaluated in 113 assessments in a different group of patients, by comparison with a complex index utilising clinical and laboratory data, as well as five haematological and biochemical markers of disease severity.Results—The newly devised Simple Clinical Colitis Activity Index, consisting of scores for five clinical criteria, showed a highly significant correlation with the Powell-Tuck Index (r=0.959, p<0.0001) as well as the complex index (r=0.924, p<0.0001) and all laboratory markers (p=0.0003 to p<0.0001).Conclusions—This new Simple Colitis Activity Index shows good correlation with existing more complex scoring systems and therefore could be useful in the initial assessment of patients with ulcerative colitis.
, P S Haber, , I D Norton, , M A Korsten, R C Pirola,
Published: 1 July 1998
by BMJ
Gut, Volume 43, pp 128-133; https://doi.org/10.1136/gut.43.1.128

Abstract:
Background—The pathogenesis of pancreatic fibrosis is unknown. In the liver, stellate cells (vitamin A storing cells) play a significant role in the development of fibrosis.Aims—To determine whether cells resembling hepatic stellate cells are present in rat pancreas, and if so, to compare their number with the number of stellate cells in the liver, and isolate and culture these cells from rat pancreas.Methods—Liver and pancreatic sections from chow fed rats were immunostained for desmin, glial fibrillary acidic protein (GFAP), and α smooth muscle actin (α-SMA). Pancreatic stellate shaped cells were isolated using a Nycodenz gradient, cultured on plastic, and examined by phase contrast and fluorescence microscopy, and by immunostaining for desmin, GFAP, and α-SMA.Results—In both liver and pancreatic sections, stellate shaped cells were observed; these were positive for desmin and GFAP and negative for α-SMA. Pancreatic stellate shaped cells had a periacinar distribution. They comprised 3.99% of all pancreatic cells; hepatic stellate cells comprised 7.94% of all hepatic cells. The stellate shaped cells from rat pancreas grew readily in culture. Cells cultured for 24 hours had an angular appearance, contained lipid droplets manifesting positive vitamin A autofluorescence, and stained positively for desmin but negatively for α-SMA. At 48 hours, cells were positive for α-SMA.Conclusions—Cells resembling hepatic stellate cells are present in rat pancreas in a number comparable with that of stellate cells in the liver. These stellate shaped pancreatic cells can be isolated and cultured in vitro.
, T L Peeters, M F J Stolk, V B Nieuwenhuijs, , , G P Van Berge Henegouwen, L M A Akkermans
Published: 1 June 1998
by BMJ
Gut, Volume 42, pp 830-835; https://doi.org/10.1136/gut.42.6.830

Abstract:
Background—Animal studies have shown that motilin affects gall bladder motility. In humans, no effect has been shown, but erythromycin, a motilin receptor agonist, induces gall bladder emptying.Aims—To explore the effect of increasing doses of exogenous motilin on gall bladder volume and antral contractility in the fasted state in humans.Methods—After an overnight fast, eight healthy men received increasing intravenous doses of Leu13-motilin (KW-5139) or 0.9% NaCl in a double blind, randomised fashion. Gall bladder volume and antral contraction frequency were determined by ultrasonography.Results—Infusion of motilin increased plasma motilin levels. Motilin induced a reduction in gall bladder volume of 8.0 (5.0)%, 17.1 (5.0)%, 18.5 (4.7)%, and 16.1 (4.9)% of baseline volume at the end of infusion of 2, 4, ,8 and 16 pmol/kg/min respectively, compared with mean stable gall bladder volumes during placebo infusion (p<0.05). Antral contraction frequency increased during motilin infusion, but not during placebo infusion (p<0.05).Conclusions—Exogenous motilin reducted fasting gall bladder volume and increased antral contractions. After reaching maximal reduction, the gall bladder volume did not decrease further during continuous motilin infusion at higher doses and stayed at the same reduced volume. The degree of gall bladder volume reduction during motilin infusion mimicked gall bladder emptying preceding antral phase III activity of the migrating motor complex in humans. This study indicates that motilin may play a physiological role in the regulation of gall bladder emptying in the fasted state.
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