bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytokine mRNA expression in intestinal tissue of interleukin-2 deficient mice with bowel inflammation
Authors: Autenrieth I B , Bucheler N , Bohn E , Heinze G , Horak I
Published: June 2010

Background—Mice deficient in interleukin-2 (IL-2) develop inflammatory bowel disease resembling ulcerative colitis in humans. Recent studies provided evidence that αβ T cells, particularly CD4 T cells, rather than B cells, are involved in the pathogenesis of bowel inflammation of IL-2 deficient mice.

Aim—To analyse the pattern of expression of cytokine mRNA in intestinal tissue of normal and IL-2 deficient mice.

Methods—Expression of β-actin, IL-1α, IL-1β, IL-6, IL-10, tumour necrosis factor α (TNF-α), interferon γ (IFN-γ) and transforming growth factor β1 (TGF-β1) mRNA was analysed in colon and small intestinal tissue of both IL-2 deficient (IL-2−/−) mice and normal (wild type) litter mates (IL-2+/+) at different ages by using qualitative, as well as semiquantitative, competitive reverse transcription polymerase chain reaction (RT-PCR). Results were correlated with the phase of progression of the disease, as determined by histology.

Results—IL-2−/− mice had expressed low levels of IL-1α, IL-1β, IL-6, TNF-α, and IFN-γ mRNA in the colon by 1.5 weeks of age. In advance of the development of histologically and clinically detectable bowel inflammation, expression of IL-1α, IL-1β, IL-6, TNF-α, IFN-γ, and IL-10, but not TGF-β1, mRNA increased in the colon of IL-2 deficient mice. In contrast, IL-2+/+ mice expressed TGF-β1 mRNA in colon tissue at 13 and 23 weeks of age, but not IL-1α, IL-1β, IL-6, TNF-α, IL-10, or IFN-γ mRNA. Levels of expression of cytokine mRNA in tissue from the small intestine were comparable in IL-2−/− and IL-2+/+ mice.

Conclusions—Bowel inflammation in IL-2 deficient mice is preceded by an increase in IL-1α, IL-1β, TNF-α, and IFN-γ mRNA expression in colon tissue. Low levels of TGF-β1, but high levels of IL-1α, IL-1β, IL-6, TNF-α, IFN-γ, and IL-10 mRNA expression correlate with the manifestation of severe colitis, and suggest that T cells and macrophages are involved in bowel inflammation of IL-2 deficient mice.
Suppressive effect of oestradiol on chemical hepatocarcinogenesis in rats
Authors: Shimizu I , Yasuda M , Mizobuchi Y , Ma Y-R , Liu F , Shiba M , Horie T , Ito S
Published: June 2010

Aims—To examine the effects of oestradiol and testosterone on the early carcinogenic changes expressed in rat liver from the diethylnitrosamine (DEN), 2-acetylaminofluorene (AAF), partial hepatectomy (PH) model of hepatocarcinogenesis.

Methods—Preneoplastic liver lesions were evaluated using immunohistochemical analysis of glutathione-S-transferase placental form (GST-P) expression; oestrogen and androgen receptor levels were measured by radioimmunoassay.

Results—Oestradiol administration to non-castrated DEN-AAF-PH treated males resulted in a decrease in the area of GST-P positive foci, while testosterone increased the serum oestradiol level and reduced the area. In males, castration alone and castration with oestradiol replacement significantly reduced the GST-P positive area, and increased the hepatic oestrogen receptor level. In DEN-AAF-PH treated females, castration with testosterone replacement was associated with a significant increase in the GST-P positive area and the hepatic androgen receptor level.

Conclusion—These findings suggest that exogenous and endogenous oestradiol can suppress chemical hepatocarcinogenesis. It appears that oestrogen receptors may be involved in the inhibition of malignant transformation of preneoplastic liver cells, while androgens and androgen receptors are involved in hepatocarcinogenesis.
Cost effectiveness of treatment for gastro-oesophageal reflux disease in clinical practice: a clinical database analysis
Authors: Eggleston A , Wigerinck A , Huijghebaert S , Dubois D , Haycox A
Published: June 2010

Background—Previous evaluations of the cost effectiveness of antireflux medication used in gastro-oesophageal reflux disease (GORD) have been based on results obtained in controlled clinical trials. Unfortunately such an approach does not necessarily identify the therapeutic option which provides the greatest benefit from available resources in real life situations. To make an informed choice requires a recognition that the costs and benefits of therapy in practice may differ from those identified in trials.

Aims—To evaluate, based on a retrospective prescription database analysis, the cost effectiveness of alternative treatment options for patients with uncomplicated GORD. The analysis assesses health service resource use during the first six months of treatment in three groups of patients initially prescribed cisapride (CIS), ranitidine (RAN), or omeprazole (OME).

Methods—The MediPlus™ UK database was used to identify all health care resources consumed by patients in the three treatment groups during their first six months of treatment. Patients with more complicated GORD, as indicated by initial referral to a specialist or outpatient hospital visit (<13%), were excluded from the analysis.

Results—The average cost per patient for the initial six months of treatment for CIS, RAN, and OME based therapies was £136, £177, and £189 per patient, respectively. A major element underlying this cost variation was the acquisition cost and quantity of antireflux medication required by patients. The average number of one month equivalent prescriptions consumed during this six month period was 1.85 (CIS), 2.57 (RAN), and 2.96 (OME) with associated costs of £49 (CIS), £67 (RAN), and £105 (OME). Antacid and alginate/antacid use was higher in the CIS and RAN groups (about 1.0 antacid prescription per patient versus 0.4 for OME), but their contribution to the total cost per patient was less than 2%. The number of general practitioner consultations over the six month period for each treatment group was 2.4 (CIS), 2.9 (RAN), and 2.6 (OME) with associated costs of £60.31 (CIS), £73.06 (RAN), and £65.52 (OME). The average number of non-drug interventions (referrals, outpatient visits, endoscopies, barium meals, or x rays) was 0.34 in the RAN group compared with less than 0.2 in the CIS and OME groups. The costs associated with such interventions were £23.80 (RAN), £9.60 (CIS), and £11.10 (OME) per patient.

Conclusion—The data indicate that the “step up” approach, starting with a prokinetic or H2 receptor antagonist, represents the most cost effective initial therapeutic strategy for a primary care physician to adopt when faced with a patient with first diagnosis of uncomplicated GORD.
Human intestinal M cells exhibit enterocyte-like intermediate filaments
Authors: Kucharzik T , Lügering N , Schmid K W , Schmidt M A , Stoll R , Domschke W
Published: June 2010

Background—The derivation and ultrastructural composition of M cells covering the lymphoid follicles of Peyer’s patches is still unknown. Results from different animal models have shown that there are species specific differences in the composition of intermediate filaments between M cells and neighbouring enterocytes. Little is known, however, about intermediate filaments of human M cells.

Aims—To compare components of the cytoskeleton of human M cells with those of adjacent absorptive enterocytes.

Methods—The expression and localisation of different cytokeratins, vimentin, and desmin in M cells was determined on follicle associated epithelia of human appendix using immunohistochemistry and immunogold electron microscopy.

Results—Cytokeratins specific for human intestinal epithelial cells such as cytokeratins 8, 18, 19, and 20 were expressed in both absorptive enterocytes and M cells with no differences in intensity and cellular distribution between both cell types. Vimentin and desmin, tissue specific markers of either mesenchymal or myogenic cells, as well as other cytokeratins were not detectable in enterocytes or M cells.

Conclusion—This is the first study on the structure of intermediate filaments in human intestinal M cells. Our results show that in contrast to several animal models, human M cells apparently do not differ from adjacent enterocytes in the composition of their intermediate filament cytoskeleton. The presence of enterocyte like cytokeratins and the absence of other cytokeratins as well as of vimentin and desmin supports the hypothesis of an epithelial origin of human intestinal M cells and suggests that M cells may derive from differentiated enterocytes.
Predictive factors for survival of patients with inoperable malignant distal biliary strictures: a practical management guideline
Authors: Prat F , Chapat O , Ducot B , Ponchon T , Fritsch J , Choury A D , Pelletier G , Buffet C
Published: June 2010

Background—Stenting is the treatment of choice for inoperable malignant strictures of the common bile duct. Criteria for the choice of stents (plastic versus metallic) remain controversial because predicting survival is difficult.

Aims—To define prognostic factors in order to improve the cost effectiveness of endoscopic palliation.

Patients—One hundred and one patients were included in a prospective trial. Seven prognostic variables for survival were analysed (age, sex, bilirubinaemia, weight loss, presence of liver metastases, and tumour histology and size). All patients were followed until death or at least one year after inclusion. By the end of the study, 81 (80.2%) patients had died.

Results—In univariate analysis, the variables associated with survival were weight loss (p<0.05) and tumour size (p<0.01). By multivariate analysis, tumour size was the only independent prognostic factor (p<0.05). A threshold of 30 mm at diagnosis distinguished two survival profiles: the median survival of patients with a tumour greater than 30 mm was 3.2 months, whereas it was 6.6 months for patients with a tumour less than 30 mm (p<0.001).

Conclusions—A practical strategy could be based on tumour size at diagnosis: a metal stent should be systematically chosen for patients with an inoperable tumour smaller than 30 mm, while larger tumours are efficiently palliated by a plastic stent.
Anticipation in familial Crohn’s disease
Authors: Grandbastien B , Peeters M , Franchimont D , Gower-Rousseau C , Speckel D , Rutgeerts P , Belaïche J , Cortot A , Vlietinck R , Colombel J-F
Published: June 2010

Background—Offspring with a family history of Crohn’s disease have an earlier age of onset than their parents. This might be due to genetic anticipation, characterised by earlier and/or more severe disease in subsequent generations.

Aims—To investigate the possibility of genetic anticipation in affected parent-child pairs with Crohn’s disease from France and Belgium.

Patients and methods—In a cohort of 160 multiply affected families with Crohn’s disease, 57 parent-first affected child pairs were detected. Clinical characteristics (age at diagnosis, disease extent, and type) of both parents and children were registered and compared.

Results—Children were younger than their parents at diagnosis in 48/57 (84%) pairs. The median age at diagnosis was 16 years younger in children than in parents (p<0.0001). However, the difference was related to the age at diagnosis in the parents and was not present in 12 parent-child pairs with an early age at diagnosis for the parents. In most cases, disease extent and type were not considered more severe in children than in parents. Parental sex affected neither age at diagnosis nor extent and type of disease in children.

Conclusion—Patients in the second affected generation acquire their disease at an earlier time in life in some but not all familial cases of Crohn’s disease. Several explanations including genetic anticipation and environmental factors might explain this phenomenon.
Omeprazole induces altered bile acid metabolism
Authors: Shindo K , Machida M , Fukumura M , Koide K , Yamazaki R
Published: June 2010

Background—It has been reported that the acidity of gastric contents could be an important factor in regulating jejunal flora.

Aims—To investigate the effects of omeprazole induced changes in gastric pH on jejunal flora and bile acid metabolism.

Methods—Twenty one patients with gastric ulcer and 19 healthy volunteers were studied. Deconjugation of bile acids was detected using a bile acid breath test. Jejunal fluid was aspirated using a double lumen tube with a rubber cover on the tip and deconjugation was examined using thin layer chromatography. Fat malabsorption was detected by a triolein breath test.

Results—In the bile acid breath test, expired breath samples from all patients and healthy volunteers showed significantly greater 14CO2 specific activity after omeprazole treatment (20 mg/day) than before treatment. Bacterial overgrowth was found in the jejunal fluid and gastric juice of both ulcer patients and healthy volunteers after omeprazole treatment. The following species were identified: Escherichia coli,Candida albicans, enterococcus, Lactobacillus bifidus, Bacteroides vulgatus, B uniformis, Eubacterium lentum, Eu parvum, and Corynebacterium granulosum. All of these species, except E coli and C albicans, deconjugate bile acids. There was a significant correlation between14CO2 activity and gastric pH, both before and after omeprazole treatment in both groups. The triolein breath test revealed impaired fat absorption in both groups after omeprazole treatment.

Conclusions—Both patients with gastric ulcer and healthy volunteers exhibited increased deconjugation of bile acids caused by bacterial overgrowth in the jejunum and fat malabsorption after omeprazole treatment. The bacterial overgrowth consisted of both anaerobes and aerobes with deconjugation ability and was probably associated with an omeprazole induced shift to neutral pH in the gastric juice.
Major virulence factors, VacA and CagA, are commonly positive inHelicobacter pylori isolates in Japan
Authors: Maeda S , Ogura K , Yoshida H , Kanai F , Ikenoue T , Kato N , Shiratori Y , Omata M
Published: June 2010

Background—VacA and CagA proteins have been reported to be major virulence factors of Helicobacter pylori. However, antibodies against these proteins are frequently found in the sera of Japanese patients regardless of their gastroduodenal status.

Aim—To evaluate the expression of VacA and CagA proteins by H pylori strains isolated in Japan.

Methods—By using specific antibodies raised against recombinant VacA and CagA proteins, the expression of VacA and CagA was evaluated in 68 H pylori strains isolated from Japanese patients; a vacuolating assay and genotyping of thevacA gene were also used in the evaluation. The results were analysed in relation to the gastroduodenal diseases of the hosts.

Results—VacA and CagA proteins were expressed in 59/68 (87%) and in 61/68 (90%) isolates respectively. The vacuolating assay was positive in 57/68 (84%) isolates, indicating that most immunologically VacA positive strains produced active cytotoxin. The prevalence of infection with strains expressing CagA and positive for vacuolating activity (Type I) was very high, 54/68 (79%), irrespective of the gastroduodenal status of the host.

Conclusion—Most H pylori isolates in Japan are positive for vacuolating cytotoxin and CagA, and thus these virulence factors cannot be used as markers to discern the risk of developing serious gastroduodenal pathologies in the hosts. However, the high prevalence of infection with strains positive for vacuolating cytotoxin and CagA may contribute to the characteristics of H pylori infection in Japan.
Oxidative DNA damage accumulation in gastric carcinogenesis
Authors: Farinati F , Cardin R , Degan P , Rugge M , Di Mario F , Bonvicini P , Naccarato R
Published: June 2010

Background—Gastric carcinogenesis is a multifactorial, multistep process, in which chronic inflammation plays a major role.

Aims—In order to ascertain whether free radical mediated oxidative DNA damage is involved in such a process, concentrations of 8-hydroxydeoxyguanosine (8OHdG), a mutagenic/carcinogenic adduct, and thiobarbituric acid reactive substances (TBARS), as an indirect measure of free radical mediated damage, were determined in biopsy specimens from patients undergoing endoscopy.

Patients—Eighty eight patients were divided into histological subgroups as follows: 27 with chronic non-atrophic gastritis, 41 with atrophic gastritis, six with gastric cancer, and 14 unaffected controls.

Methods—Intestinal metaplasia,Helicobacter pylori infection, and disease activity were semiquantitatively scored. 8OHdG concentrations were assessed by HPLC with electrochemical detection, and TBARS concentrations were fluorimetrically assayed.

Results—8OHdG concentrations (mean number of adducts/105 dG residues) were significantly higher in chronic atrophic gastritis (p=0.0009). Significantly higher concentrations were also detected in the presence of severe disease activity (p=0.02), intestinal metaplasia (p=0.035), and H pylori infection (p=0.001). TBARS concentrations were also higher in atrophic gastritis, though not significantly so. In a multiple logistic regression analysis, 8OHdG concentrations correlated best with the presence and severity of H pylori infection (r=0.53, p=0.002).

Conclusions—Chronic gastritis is characterised by the accumulation of oxidative DNA damage with mutagenic and carcinogenic potential. H pylori infection is the major determinant for DNA adduct formation.
Expression of arylamine N-acetyltransferase in human intestine
Authors: Hickman D , Pope J , Patil S D , Fakis G , Smelt V , Stanley L A , Payton M , Unadkat J D , Sim E
Published: June 2010

Background—ArylamineN-acetyltransferases in humans (NAT1 and NAT2) catalyse the acetylation of arylamines including food derived heterocyclic arylamine carcinogens. Other substrates include the sulphonamide 5-aminosalicylic acid (5-ASA), which is an NAT1 specific substrate; N-acetylation of 5-ASA is a major route of metabolism. NAT1 and NAT2 are both polymorphic.

Aims—To investigate NAT expression in apparently healthy human intestines in order to understand the possible role of NAT in colorectal cancer and in the therapeutic response to 5-ASA.

Methods—The intestines of four organ donors were divided into eight sections. DNA was prepared for genotypingNAT1 and NAT2 and enzymic activities of NAT1 and NAT2 were determined in cytosols prepared from each section. Tissue was fixed for immunohistochemistry with specific NAT antibodies. Western blotting was carried out on all samples of cytosol and on homogenates of separated muscle and villi after microdissection.

Results—NAT1 activity of all cytosols was greater than NAT2 activity. NAT1 and NAT2 activities correlated with the genotypes of NAT1 and NAT2 and with the levels of NAT1 staining determined by western blotting. The ratio of NAT1:NAT2 activities showed interindividual variations from 2 to 70. NAT1 antigenic activity was greater in villi than in muscle. NAT1 was detected along the length of the villi in the small intestine. In colon samples there was less NAT1 at the base of the crypts with intense staining at the tips.

Conclusions—The interindividual variation in NAT1 and NAT2 in the colon could affect how individuals respond to exposure to specific NAT substrates including carcinogens and 5-ASA.
Tumour necrosis factor-α enhances intraepithelial lymphocyte proliferation and migration
Authors: Ebert E C
Published: June 2010

Background—Tumour necrosis factor α (TNF-α) is a proinflammatory cytokine found in abundance in diseased intestine.

Aims—The T cell production of TNF-α and the impact of this cytokine on intestinal T cell proliferation, migration, and cytotoxicity were studied.

Methods—Intestinal lymphocytes from normal jejunum were used. TNF-α production in culture supernates was measured by enzyme linked immunosorbent assay (ELISA). Lymphocyte proliferation was measured using 3H thymidine uptake; migration, using transwell chambers; and cytotoxicity of HT-29 colon cancer cells, using the chromium-51 release assay.

Results—TNF-α was produced mainly by the CD8+ T cells in the intraepithelial lymphocytes (IEL) and the CD4+ T cells in the lamina propria lymphocytes in response to CD2 stimulation: 478 (94) and 782 (136) pg/ml, respectively. TNF-α (1 ng/ml or greater) augmented proliferation of IEL in response to interleukin 2 (IL-2), IL-7, or antibody to CD3 due to increased activation that did not involve IL-2 production or receptor generation. Conversely, antibody to TNF-α reduced IEL proliferation in response to IL-2 or IL-7. TNF-α also induced calcium mobilisation and chemokinesis (by 2.8 (0.5) fold over spontaneous migration). TNF-α had no effect on lymphokine activated killer cell activity.

Conclusions—TNF-α increases the proliferation and migration of IEL, which may expand their number in the epithelium.
Clonal analysis of isolated intestinal metaplastic glands of stomach using X linked polymorphism
Authors: Nomura S , Kaminishi M , Sugiyama K , Oohara T , Esumi H
Published: June 2010

Background—Monoclonal precancerous cells undergo successive biochemical and genetic changes during the multistep process of carcinogenesis in the gastrointestinal tract. Despite a high association with intestinal-type stomach cancer (differentiated adenocarcinoma of the stomach), the role of intestinal metaplasia is unclear in stomach carcinogenesis.

Aims—To study the clonality of intestinal metaplasia.

Methods—The clonality of 86 single intestinal metaplastic glands isolated by EDTA treatment from gastrectomy specimens from patients with cancer were investigated. The methylation sensitive restriction enzyme HpaII and polymerase chain reaction (PCR) were used to detect a polymorphic human androgen receptor gene locus linked to an inactive X chromosome.

Results—Forty one (48%) intestinal metaplastic glands were heterotypic (mixed cells of different allelic methylation) and 45 (52%) were homotypic (cell population of the same allelic methylation), while almost all the single pyloric glands were homotypic. Eleven of 13 intestinal metaplastic mucosae that were 6 mm in diameter contained glands that had originated from different cells. There were no strong relationships between clonal type and location or histological type of intestinal metaplasia.

Conclusion—Intestinal metaplasia in general is not a lesion that arises or proceeds monoclonally.
cagA positive and negative Helicobacter pyloristrains are simultaneously present in the stomach of most patients with non-ulcer dyspepsia: relevance to histological damage
Authors: Figura N , Vindigni C , Covacci A , Presenti L , Burroni D , Vernillo R , Banducci T , Roviello F , Marrelli D , Biscontri M , Kristodhullu S , Gennari C , Vaira D
Published: June 2010

Background/Aims—Infection with Helicobacter pylori strains harbouring the cagA gene (cagA+) is associated with an increased risk of developing peptic ulcer and gastric cancer. The aim of this study was to assess whether H pylori isolates with different cagA status were present in patients with non-ulcer dyspepsia, and whether a variable cagA status is relevant to histological gastric mucosal damage and glandular cell proliferation.

Methods—Well separated H pyloricolonies (between 2 and 25) from primary plates, per gastric area, for each of 19 patients with non-ulcer dyspepsia were examined forcagA by hybridisation. Western blotting was used to examine both representative colonies for CagA expression and the patients’ sera for antibody response to CagA. Glandular gastric cell proliferation was assessed immunohistochemically.

Results—Of the 747 colonies examined, 45.3% werecagA+. All colonies from four patients werecagA+, and all colonies from two patients werecagA−. In 13 patients (68%) both cagA+ andcagA− colonies were found. CagA expression of isolates corresponded to their cagA status. H pyloristrains with different CagA molecular masses were present in three patients. Results based on all 19 patients studied showed that the prevalence of cagA+ colonies in areas with mucosal atrophy associated or not with intestinal metaplasia (67.9%) was significantly higher than in normal mucosa (44.7%) and mucosa from patients with chronic gastritis (44.0%) (p< 0.001). High levels of cell proliferation were associated with histological atrophy with or without intestinal metaplasia, but not with the possession of cagA by organisms colonising the same mucosal sites.

Conclusions—Most patients with non-ulcer dyspepsia are infected by both cagA+ and cagA−H pylori colonies. The cagA status of infecting organisms may play a role in the development of atrophy and intestinal metaplasia.
Mediation by NF-κB of cytokine induced expression of intercellular adhesion molecule 1 (ICAM-1) in an intestinal epithelial cell line, a process blocked by proteasome inhibitors
Authors: Jobin C , Hellerbrand C , Licato L L , Brenner D A , Sartor R B
Published: June 2010

Background/aims—The gene promoter for the intercellular adhesion molecule ICAM-1 possesses binding sites for several transcriptional factors, including nuclear factor κB (NF-κB). The role of NF-κB in ICAM-1 gene regulation was therefore examined by using different proteasome inhibitors in tumour necrosis factor α (TNF-α) stimulated IEC-6 rat intestinal epithelial cells.

Methods—ICAM-1 expression was analysed by enzyme linked immunosorbent assay (ELISA), reverse transcriptase polymerase chain reaction, and immunohistochemistry. Steady state levels of cytoplasmic IκB protein were evaluated by western blot, and nuclear translocation of NF-κB was determined by electrophoretic mobility shift assay and immunofluorescence staining. Cell adhesion was assayed by measuring the binding of fluorescence labelled MOLT-4 cells.

Results—TNF-α induced ICAM-1 mRNA and protein expression in IEC-6 cells, which was followed by increased adhesion of MOLT-4 lymphocytes. Blocking TNF-α induced IκBα degradation with proteasome inhibitors reduced TNF-α induced NF-κB activation and ICAM-1 gene induction and notably decreased MOLT-4 cell adhesion without affecting Jun N-terminal kinase (JNK/SAPK) activity or de novo protein synthesis.

Conclusion—TNF-α induction of ICAM-1 expression is mediated by the transcription factor NF-κB and can be inhibited by blocking IκBα degradation. Thus the IκB/NF-κB system is a promising target for pharmacological modulation of the expression of adhesion molecules and other inflammatory genes in the intestine.
Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role
Authors: Quinton J-F , Sendid B , Reumaux D , Duthilleul P , Cortot A , Grandbastien B , Charrier G , Targan S R , Colombel J-F , Poulain D
Published: June 2010

Background—Perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) are a well recognised marker for ulcerative colitis. Antibodies to oligomannosidic epitopes of the yeastSaccharomyces cerevisiae (ASCA) are a new marker associated with Crohn’s disease.

Aims—To assess the value of detecting pANCA and/or ASCA for the diagnosis of ulcerative colitis and Crohn’s disease.

Methods—Serum samples were obtained from 100 patients with Crohn’s disease, 101 patients with ulcerative colitis, 27 patients with other miscellaneous diarrhoeal illnesses, and 163 healthy controls. Determination of pANCA and ASCA was performed using the standardised indirect immunofluorescence technique and an ELISA, respectively.

Results—The combination of a positive pANCA test and a negative ASCA test yielded a sensitivity, specificity, and positive predictive value of 57%, 97%, and 92.5% respectively for ulcerative colitis. The combination of a positive ASCA test and a negative pANCA test yielded a sensitivity, specificity, and positive predictive value of 49%, 97%, and 96% respectively for Crohn’s disease. Among patients with miscellaneous non-inflammatory bowel disorders, three were ASCA positive and two were pANCA positive. One control was ASCA positive. The presence of ASCA in patients with Crohn’s disease was associated with small bowel involvement.

Conclusion—ASCA and pANCA are strongly associated with Crohn’s disease and ulcerative colitis, respectively. Combination of both tests could help the diagnosis of inflammatory bowel disease.
Symptoms and visceral perception in severe functional and organic dyspepsia
Authors: Mertz H , Fullerton S , Naliboff B , Mayer E A
Published: June 2010

Background—Hypersensitivity of gastric afferent pathways may play an aetiological role in symptoms of functional dyspepsia.

Aims—To determine whether patients with severe organic dyspepsia (associated with tissue irritation/injury) and those with functional dyspepsia (no detectable tissue irritation) differ in their perception of gastric distension and whether this difference is reflected in differences in their gastrointestinal and psychological symptoms.

Methods—Perceptual thresholds, referral patterns, and gastrointestinal and psychological symptoms were compared in 23 patients with functional dyspepsia, 10 organic dyspeptics, and 15 healthy controls.

Results—Fifteen (65%) functional dyspeptics and no organic dyspeptics had reduced perceptual thresholds for fullness, discomfort, or pain (odds ratio (OR) 19.56, 95% confidence interval (CI) 1.95 to 476.09, p=0.0017). Either reduced perceptual thresholds or altered referral was found in 20 (87%) functional dyspeptics and four (20%) organic dyspeptics (OR 10.0, 95% CI 1.34 to 89.54, p=0.014). During sham distension fullness, discomfort and pain were reported by healthy controls, organic dyspeptics, and functional dyspeptics. A sham response of pain but no other sensation was more frequent among functional dyspeptics (43%) than healthy controls (7%) (OR 10.77, 95% CI 1.10 to 257.35, p=0.026). Gastrointestinal and psychological symptoms and gastric compliance were similar in the functional and organic groups.

Conclusions—Alterations in the perception of gastric distension distinguishes between functional and organic dyspepsia, while symptoms do not. A total of 87% of functional dyspeptics studied had evidence of altered visceral afferent function. In this study population, psychological abnormalities or changes in compliance did not explain the findings.
Intractable vomiting due to a brainstem lesion in the absence of neurological signs or raised intracranial pressure
Authors: Mann S D , Danesh B J , Kamm M A
Published: June 2010

The case of a 30 year old man who was believed to have a gastrointestinal motility disorder causing his chronic vomiting is reported. He had been well until 21 months previously when he had developed recurrent vomiting which would occur up to 10 times in a 24 hour period. Vomiting was not precipitated by eating and was not associated with any other symptoms. He had lost 25 kg in weight. A psychiatric assessment did not reveal a psychogenic cause for his vomiting. A brainstem magnetic resonance imaging scan revealed an area of low signal in the low midbrain just above the pons to the left of the midline. After gadolinium contrast injection the area enhanced. There was little or no mass effect, that is minimal displacement of normal structures, and minimal oedema. The appearance was that of a low grade or early brainstem tumour. There were no features of haemorrhage or infarct. The patient was managed with oral dexamethasone, resulting in prompt resolution of his symptoms. A search for a central neurological cause is recommended in a patient with unexplained persistent vomiting, even in the absence of other features to suggest a neurological problem. Autonomic function testing may provide additional information.
Identification of gases responsible for the odour of human flatus and evaluation of a device purported to reduce this odour
Authors: Suarez F L , Springfield J , Levitt M D
Published: June 2010

Background/Aims—While the social significance of flatus derives mainly from its odour, previous studies have focused on the non-odoriferous components of rectal gas. The aims of the present study were to determine the role of sulphur-containing gases in flatus odour and test the efficacy of a device purported to reduce this odour.

Methods—Flatus was quantitatively collected via rectal tube from 16 healthy subjects who ingested pinto beans and lactulose to enhance flatus output. The concentrations of sulphur-containing gases in each passage were correlated with odour intensity assessed by two judges. Odour intensity was also determined after treatment of flatus samples with zinc acetate, which binds sulphydryl compounds (hydrogen sulphide and methanethiol), or activated charcoal. Utilising gas-tight Mylar pantaloons, the ability of a charcoal lined cushion to adsorb sulphur-containing gases instilled at the anus of eight subjects was assessed.

Results—The main sulphur-containing flatus component was hydrogen sulphide (1.06 (0.2) μmol/l), followed by methanethiol (0.21 (0.04) μmol/l) and dimethyl sulphide (0.08 (0.01) μmol/l) (means (SEM)). Malodour significantly correlated with hydrogen sulphide concentration (p⩽0.001). Zinc acetate reduced sulphur gas content but did not totally eliminate odour, while activated charcoal removed virtually all odour. The cushion adsorbed more than 90% of the sulphur gases.

Conclusion—Sulphur-containing gases are the major, but not the only, malodorous components of human flatus. The charcoal lined cushion effectively limits the escape of these sulphur-containing gases into the environment.
Patterns of alcohol consumption after liver transplantation
Authors: Tang H , Boulton R , Gunson B , Hubscher S , Neuberger J
Published: June 2010

Background—Uncertainty exists about the extent and consequences of a return to alcohol consumption after liver transplantation for alcoholic liver disease (ALD).

Aims—To determine the prevalence and consequences of alcohol consumption in patients transplanted for ALD.

Methods—A retrospective case controlled study of all patients transplanted for ALD at the Queen Elizabeth Hospital, Birmingham, between 1987 and 1996.

Results—Seventy patients with ALD were transplanted, of which 59 survived more than three months; 56 were interviewed. Twenty eight had consumed some alcohol after transplantation; for the nine “heavy drinkers” (HD), the median time to resumption of alcohol intake was six months and for the 19 “moderate drinkers” (MD) it was eight months. There was no significant difference in episodes of acute rejection or compliance with medication between those who were abstinent, MD, or HD. Histological evidence of liver injury was common in ALD patients who had returned to drink. Mild fatty change was found in 1/11 biopsy specimens from abstinent patients but moderate to severe fatty change and ballooned hepatocytes were seen in 3/5 MD and 2/5 HD specimens. Two HD patients had early fibrosis. One HD patient has died of alcohol related complications.

Conclusions—Moderate to heavy alcohol consumption occurs in patients transplanted for ALD. Patient recall of abstinence advice is unreliable, and patients return to alcohol mainly within the first year after liver transplantation. Return to alcohol consumption after liver transplantation is associated with rapid development of histological liver injury including fibrosis.
A simple clinical colitis activity index
Authors: Walmsley R S , Ayres R C S , Pounder R E , Allan R N
Published: June 2010

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.
High Fas ligand expression on lymphocytes in lesions of ulcerative colitis
Authors: Ueyama H , Kiyohara T , Sawada N , Isozaki K , Kitamura S , Kondo S , Miyagawa J , Kanayama S , Shinomura Y , Ishikawa H , Ohtani T , Nezu R , Nagata S , Matsuzawa Y
Published: June 2010

Background—The pathogenesis of ulcerative colitis is unclear, but cytotoxic T lymphocytes infiltrating the mucosa have been implicated in mucosal damage. The Fas ligand (FasL), expressed on cytotoxic T lymphocytes, induces apoptosis in cells expressing Fas.

Aim—To analyse FasL expression in affected colonic mucosa to ascertain Fas-FasL interaction in ulcerative colitis.

Methods—FasL mRNA was quantified in colonic mucosal specimens from healthy subjects and patients with ulcerative colitis or Crohn’s disease, using the competitive reverse transcription polymerase chain reaction. FasL mRNA localisation was determined by in situ hybridisation. Expression of Fas in colonic mucosa was analysed immunohistochemically. Phenotypes of lamina propria lymphocytes that expressed FasL were analysed by flow cytometry.

Results—FasL mRNA was strongly expressed in active ulcerative colitis lesions, but not in those associated with active Crohn’s disease or active proctitis-type ulcerative colitis. In situ hybridisation showed that FasL mRNA expression occurred in mononuclear cells infiltrating lesions. Fas was expressed in epithelial cells in ulcerative colitis and Crohn’s disease, and in normal subjects. Cytometry showed that FasL was expressed in CD3 lymphocytes infiltrating the lamina propria in active lesions.

Conclusions—FasL is expressed in CD3 lymphocytes infiltrating into ulcerative colitis but not Crohn’s disease lesions, suggesting that Fas-FasL induced apoptosis participates in the mucosal damage of ulcerative colitis.
Colonic epithelial cell proliferation in hereditary non-polyposis colorectal cancer
Authors: Green S E , Chapman P , Burn J , Burt A D , Bennett M , Appleton D R , Varma J S , Mathers J C
Published: June 2010

Background—Despite the recent discovery of four genes responsible for up to 90% of all cases of hereditary non-polyposis colorectal cancer (HNPCC), there will still be families in whom predictive testing is not possible. A phenotypic biomarker would therefore be useful. An upwards shift of the proliferative compartment in colonic crypts is reported to be one of the earliest changes in premalignant mucosa.

Aims—To assess the role of crypt cell proliferation as a phenotypic biomarker in HNPCC.

Patients—Thirty five patients at 50% risk of carrying the HNPCC gene (21 of whom subsequently underwent predictive testing and hence gene carrier status was known) and 18 controls.

Methods—Crypt cell proliferation was measured at five sites in the colon using two different techniques. Labelling index was determined using the monoclonal antibody MIB1 and whole crypt mitotic index was measured using the microdissection and crypt squash technique. The distribution of proliferating cells within the crypts was also assessed.

Results—There were no significant differences in the total labelling index or mean number of mitoses per crypt, nor in the distribution of proliferating cells within the crypt, between the study and control groups at any site. When the 21 patients in whom gene carrier status was known were analysed separately there were no significant differences in the measured indices of proliferation between the HNPCC gene carriers and non-gene carriers.

Conclusion—Crypt cell proliferation is not a discriminative marker of gene carriage in HNPCC.
CTLA-4 gene polymorphism is associated with predisposition to coeliac disease
Authors: Djilali-Saiah I , Schmitz J , Harfouch-Hammoud E , Mougenot J-F , Bach J-F , Caillat-Zucman S
Published: June 2010

Background—Susceptibility to coeliac disease is strongly associated with particular HLA class II alleles. However, non-HLA genetic factors are likely to be required for the development of the disease. Among candidate genes is the CTLA-4 (cytotoxic T lymphocyte associated) gene located on chromosome 2q33 in humans, which encodes a cell surface molecule providing a negative signal for T cell activation.

Aims—To investigate CTLA-4 exon 1 polymorphism (position 49 A/G) in patients with coeliac disease.

Patients—101 patients with coeliac disease and 130 healthy controls.

Methods—Allele specific hybridisation and restriction enzyme digestion of polymerase chain reaction amplified genomic DNA.

Results—The A allele of the CTLA-4 position 49 polymorphism was found on 82.2% of chromosomes in patients with coeliac disease compared with 65.8% in controls (p<0.0001), mostly in the homozygous form (68.3% in patients versus 47.7% in controls; odds ratio (OR) 2.36, 95% confidence interval (CI) 1.37 to 4.06, p=0.002). Four patients only had the G/G genotype compared with 21 controls (OR 0.21, CI 10.07 to 0.64, p=0.002). These differences were maintained when subjects were stratified according to the HLA class II phenotype, in particular when patients and controls were matched for the presence of the predisposing HLA DQB1*02 (DQ2) allele or HLA-DQA1*0501/DQB1*02 heterodimer.

Conclusion—The CTLA-4 gene polymorphism is a non-HLA determinant that predisposes to coeliac disease. Whether it directly contributes to disease susceptibility or represents a marker for a locus in linkage disequilibrium with CTLA-4 needs further investigation.
Analysis of MHC class II DP, DQ and DR alleles in Crohn’s disease
Authors: Cariappa A , Sands B , Forcione D , Finkelstein D , Podolsky D K , Pillai S
Published: June 2010

Background—Although inflammation in Crohn’s disease is believed to be mediated by activated T cells, genotyping of all MHC class II alleles in white people with this disease has not been reported.

Aims—To perform a detailed molecular analysis of HLA DPB, DQB, and DRB genes in white patients with Crohn’s disease and controls in order to determine if the inheritance of any class II genes confers susceptibility or resistance to this disease.

Methods—Complete molecular typing of HLA class II DPB, DQB, and DRB alleles was performed in 58 white patients with Crohn’s disease and 93 healthy controls using a polymerase chain reaction-sequence specific oligonucleotide based approach.

Results—No significant association with any DPB or DQB alleles was noted in patients with Crohn’s disease. Since our previous studies had shown a strong association of an HLA DRB3*0301/DRB1*1302 haplotype with Crohn’s disease, we re-examined this association using more stringent genotyping criteria. This haplotype was present in 20.7% of patients and 5.4% of controls (p = 0.0066; relative risk = 4.59).

Conclusions—The DRB3*0301/DRB1* 1302 haplotype is the only significant MHC class II association noted in white people with Crohn’s disease and represents the strongest association of any MHC or non-MHC locus with this disease.
Gastroenterology research in the United Kingdom: funding sources and impact
Authors: Lewison G
Published: June 2010

Aims—To determine the sources of funding for UK gastroenterology research papers and the relative impact of papers funded by different groups and of unfunded ones.

Methods—UK gastroenterology papers from 1988–94 were selectively retrieved from theScience Citation Index by means of a specially constructed filter based on their title keywords and journal names. They were looked up in libraries to determine their funding sources and these, together with their numbers of authors, numbers of addresses, and research category (clinical/basic) were considered as input parameters to the research. Output parameters analysed were mean journal impact category, citation counts by papers, and the frequency of citation by a US patent.

Results—Gastroenterology papers comprise about 7% of all UK biomedical research and 46% of them have no acknowledged funding source. One quarter of the papers acknowledged government support, and a similar fraction a private, non-profit source; 11% were funded by the pharmaceutical industry. The papers acknowledging funding had significantly more impact than the others on all three measures. The citing patents had six times more UK inventors than the average for all US Patent and Trademark Office patents in the relevant classes and were mostly generic in application.

Conclusion—The variation in impact of papers funded by different sources can mostly be explained by a simple model based on the input factors (numbers of funding bodies, numbers of authors, numbers of addresses, and research type). The national science base in gastroenterology is important for the underpinning of UK invented patents citing to it.
Poor diagnostic value of colonic CD44v6 expression and serum concentrations of its soluble form in the differentiation of ulcerative colitis from Crohn’s disease
Authors: Reinisch W , Heider K-H , Oberhuber G , Dejaco C , Müllner M , Adolf G R , Gasché C
Published: June 2010

Background—Increased expression of CD44v6 on colonic crypt epithelial cells in ulcerative colitis has been suggested as a diagnostic tool to distinguish ulcerative colitis from colonic Crohn’s disease.

Aims—To investigate colonic CD44v6 expression and serum concentrations of soluble CD44v6 (sCD44v6) in patients with ulcerative colitis and Crohn’s disease.

Methods—Colonic biopsy samples were obtained from 16 patients with ulcerative colitis, 13 with ileocolonic Crohn’s disease, and 10 undergoing polypectomy. Serum samples were obtained from 15 patients with active ulcerative colitis, 20 with active Crohn’s disease, and 20 healthy donors. Colonic CD44v6 expression was evaluated immunohistochemically by monoclonal antibody 2F10 and the higher affinity monoclonal antibody VFF18. Serum sCD44v6 concentrations were measured by ELISA.

Results—2F10 stained colonic epithelium of inflamed ulcerative colitis and Crohn’s disease samples in 80% and 40% of cases, respectively, and VFF18 in 95% and 87%, respectively. Both monoclonal antibodies displayed a sensitivity and specificity of 60% and 87% to differentiate ulcerative colitis from colonic Crohn’s disease. Serum concentrations of sCD44v6 were lower in patients with ulcerative colitis (median 153 ng/ml; interquartile range (IQR) 122–211) compared with Crohn’s disease (219; IQR 180–243) and healthy donors (221; IQR 197–241 (p=0.002)). Its sensitivity and specificity to discriminate ulcerative colitis from Crohn’s disease was 75% and 71%, respectively.

Conclusion—Colonic CD44v6 and serum sCD44v6 concentrations do not facilitate reliable differential diagnosis between ulcerative colitis and Crohn’s disease.