bluuebunny/crossref_metadata_2025 huggingface dataset:
Drinking habits as cofactors of risk for alcohol induced liver damage
Authors: Bellentani S , Saccoccio G , Costa G , Tiribelli C , Manenti F , Sodde M , Croce’ L Saveria , Sasso F , Pozzato G , Cristianini G , Brandi and the Dionysos Study Group G
Published: June 2010

Background—The Dionysos Study is a cohort study of the prevalence of chronic liver disease in the general population of two northern Italian communities. It included 6917 subjects, aged 12–65 (69% of the total population).

Aims—The aim of this part of the study was to examine the relationship of daily alcohol intake, type of alcoholic beverage consumed, and drinking patterns to the presence of alcohol induced liver damage in an open population.

Patients and methods—6534 subjects, free of virus related chronic liver disease and participating in the first cross-sectional part of the study, were fully examined. Each subject underwent: (a) medical history and physical examination, (b) evaluation of alcohol intake using an illustrated dietary questionnaire, and (c) routine blood tests. More invasive diagnostic procedures were performed when indicated.

Results—Multivariate analysis showed that the risk threshold for developing either cirrhosis or non-cirrhotic liver damage (NCLD) was ingestion of more than 30 g alcohol per day in both sexes. Using this definition, 1349 individuals (21% of the population studied) were at risk. Of these, only 74 (5.5% of the individuals at risk) showed signs of liver damage. The prevalence of “pure” alcoholic cirrhosis was 0.43% (30 of 6917), representing 2.2% of the individuals at risk, with a ratio of men to women of 9:1, while 44 (3.3% of the individuals at risk) showed persistent signs of NCLD. After 50 years of age, the cumulative risk of developing both NCLD and cirrhosis was significantly higher (p<0.0001) for those individuals who regularly drank alcohol both with and without food than for those who drank only at mealtimes.

Conclusions—Our data show that in an open population the risk threshold for developing cirrhosis and NCLD is 30 g ethanol/day, and this risk increases with increasing daily intake. Drinking alcohol outside mealtimes and drinking multiple different alcoholic beverages both increase the risk of developing alcohol induced liver damage.
Hepatic histology in hepatitis C virus carriers coinfected with hepatitis G virus
Authors: Petrik J , Guella L , Wight D G D , Pearson G M , Hinton J , Parker H , Allain J-P , Alexander G J M
Published: June 2010

Background—A novel flavivirus has been described recently and designated hepatitis G virus (HGV). The virus is transmitted by the parenteral route but it is uncertain whether it is associated with chronic liver disease because liver biopsy is difficult to justify in this group.

Aims—To examine histological features of liver biopsy in patients infected with hepatitis C virus (HCV) according to the presence or absence of HCV and HGV RNA.

Methods—One hundred and thirty one consecutive HCV carriers undergoing staging liver biopsy were studied retrospectively. In each, HCV RNA and HGV RNA were detected by reverse transcription polymerase chain reaction on serum samples collected at the time of biopsy. The presence of each RNA was correlated with histological features blind to the RNA results; individual histological features of inflammation or fibrosis were scored separately.

Results—Nineteen patients were positive for both HGV and HCV RNA in serum, 91 were positive for HCV RNA alone, two were positive for HGV RNA alone, and 19 were negative for both RNA species. Neither age nor sex differed between the groups; a greater proportion of intravenous drug users were HGV RNA positive, but this was not statistically significant. There was no effect of HGV coinfection on the stage of fibrosis or any other histological parameter except steatosis; patients with HCV and HGV RNA had a higher mean score for fat than those patients with HCV RNA alone (p<0.05).

Conclusions—HGV coinfection has no important effects on histological features in chronic HCV carriers. It is unlikely that HGV infection causes chronic liver disease.
The association between primary biliary cirrhosis and coeliac disease: a study of relative prevalences
Authors: Kingham J G C , Parker D R
Published: June 2010

Background—Coexistent primary biliary cirrhosis (PBC) and coeliac disease has been recorded but the association has not been systematically studied.

Aims—To determine relative prevalences of PBC and coeliac disease in a defined population over a 12 year period.

Patients and methods—All patients with PBC or coeliac disease in a stable population of 250 000 in South Wales were identified from a clinical register and laboratory records.

Results—Sixty seven patients with PBC and 143 patients with coeliac disease have been diagnosed and followed over a median of 86 (4–135) months; point prevalences in 1996 were 20 per 100 000 for PBC and 54 per 100 000 for coeliac disease. PBC in patients with coeliac disease was sought by investigating abnormal liver function tests. Ten (7%) had persistent abnormalities and three had PBC. Coeliac disease in patients with PBC was sought by investigating malabsorption, haematinic deficiency, positive antigliadin antibody, or coeliac disease family history. Eleven patients underwent duodenal biopsy revealing one further coeliac disease case. Four patients (three women) have both conditions giving a point prevalence for patients with both conditions of 1.6 per 100 000 (95% confidence limits 0.44 to 4.1 per 100 000). Prevalence of PBC in patients with coeliac disease was 3% and of coeliac disease in patients with PBC was 6%.

Conclusion—A 12 year study of a stable 250 000 population revealed a relative prevalence of PBC in 3% of 143 patients with coeliac disease and of coeliac disease in 6% of 67 patients with PBC. PBC and coeliac disease are therefore associated. Screening for PBC in patients with coeliac disease using antimitochondrial antibody testing and screening for coeliac disease in patients with PBC with antigliadin antibody testing or duodenal biopsy are recommended.
Is the association between irritable bowel syndrome and abuse explained by neuroticism? A population based study
Authors: Talley N J , Boyce P M , Jones M
Published: June 2010

Background—In outpatients and the community, an association between abuse (particularly sexual abuse) and irritable bowel syndrome (IBS) has been observed, but whether there is a causal link continues to be disputed.

Aims—To test the hypothesis that psychological factors explain the apparent association between abuse and IBS.

Methods—A sample of residents of Penrith (a Sydney suburb sociodemographically similar to the Australian population) selected randomly from the electoral rolls (that by law include the entire population of age 18 years and above) was mailed a validated self report questionnaire. Measured were gastrointestinal (GI) symptoms including the Rome criteria for IBS, abuse (including the standardised Drossman questions), neuroticism (Eysenck Personality Questionnaire), and psychological morbidity (General Health Questionnaire).

Results—The response rate was 64% (n=730); 12% fulfilled the Rome criteria for IBS. Overall abuse in childhood (odds ratio (OR)=2.02, 95% confidence interval (CI) 1.29 to 3.15) but not adulthood (OR=1.39, 95% CI 0.88 to 2.19) was associazted with IBS univariately. Neuroticism and psychological morbidity were also univariately associated with abuse in childhood, abuse in adulthood, and IBS, respectively. However, by logistic regression, abuse in childhood was not associated with IBS after controlling for age, gender, and psychological factors (OR=1.34, 95% CI 0.83 to 2.17). The results were not altered by restricting the analyses to more severe forms of abuse, and were not explained by interactions between abuse and psychological variables.

Conclusion—There is an association between abuse and IBS in the community, but this may be explained in part by other psychological factors. Based on a path analysis, we postulate that abuse may induce the expression of neuroticism that in turn leads to IBS.
Developmental expression of mucin genes in the human gastrointestinal system
Authors: Reid C J , Harris A
Published: June 2010

Background and aims—Mucin glycoproteins play a key role in the normal function of the epithelium lining the gastrointestinal tract. The expression of mucin genes, MUC 3, 4, 5AC, 5B, 6, 7, and 8 in human fetal tissues was examined to establish the localisation and age of onset of expression of each mucin gene during human development.

Methods—Mucin gene expression was assayed by mRNA in situ hybridisation.

Results—Expression of MUC3 was detected in the small intestine and colon from 13 weeks gestation onwards and at low levels in the main pancreatic duct at 13 weeks only. MUC4 expression was seen at a low level in the colonic epithelium from 13 weeks of gestation but not elsewhere in the gastrointestinal tract. MUC5AC mRNA was detected in the colon at 17 weeks and at high levels in the stomach at 23 weeks. MUC6transcripts were evident in the pancreatic ducts from 13 weeks of gestation and at high levels in the stomach at 23 weeks.MUC5B, MUC7, and MUC8transcripts were not detected.

Conclusions—Mucin genes are expressed from the early mid-trimester of gestation in the developing human fetal gastrointestinal tract.
Inhibition of phenolsulphotransferase by salicylic acid: a possible mechanism by which aspirin may reduce carcinogenesis
Authors: Harris R M , Hawker R J , Langman M J S , Singh S , Waring R H
Published: June 2010

Background—Recent epidemiological evidence has shown that chronic use of aspirin decreases susceptibility to bowel cancer. Animal studies have shown that sulphotransferase inhibitors coadministered with sulphation activated carcinogens dramatically reduce the incidence of cancer.

Aims—To investigate the effect of the main aspirin breakdown product, salicylic acid, on the P and M isoforms of phenolsulphotransferase from human platelets and colonic mucosa.

Methods—Platelets were obtained from healthy blood donors and isolated within 24 hours after donation. Samples of colonic mucosa were obtained at resection for non-malignant disease. Phenolsulphotransferase activity was measured in cellular homogenates using a standard radiolabelling assay.

Results—Salicylic acid consistently and selectively inhibited the P form of phenolsulphotransferase at subtherapeutic concentrations in both tissue samples. A 50% inhibition of sulphation by the P phenolsulphotransferase occurred at salicylic acid concentrations of about 40 and 130 μM in platelets and bowel mucosa respectively. M phenolsulphotransferase was virtually unaffected by salicylic acid up to a concentration of 1.5 mM (the therapeutic plasma concentration for salicylates when treating rheumatoid arthritis is about 1–2 mM).

Conclusion—The action of salicylic acid on P phenolsulphotransferase, by preventing the excessive activation of carcinogens, is a possible additional pathway by which aspirin can reduce cancer risk.
Focal reduction of villous blood flow in early indomethacin enteropathy: a dynamic vascular study in the rat
Authors: Kelly D A , Piasecki C , Anthony A , Dhillon A P , Pounder R E , Wakefield A J
Published: June 2010

Background—Oral indomethacin causes villous shortening, microvascular damage, and distortion, which might induce mucosal ischaemia and necrosis.

Aims—In order to determine the early events in indomethacin induced jejunal injury we examined the temporal relations between morphological damage and changes in villous blood flow following indomethacin.

Methods—In anaesthetised rats, mid jejunal villi were exteriorised in a chamber and observed by fluorescence microscopy. Blood flow in surface capillaries was calculated from velocities and diameters. Indomethacin was applied by both luminal and intravenous routes for 90 minutes, after which the animal was perfusion fixed and the villi were processed for histological examination. Control animals received intravenous or luminal bicarbonate (1.25%).

Results—Blood flow slowed in individual villi at 20 minutes, and progressed to complete stasis (in another group) by 45 minutes. Histological examination at 20 minutes revealed microvascular distortion, but no villous shortening: crypt depth:villous height ratios were 0.356 (0.02) in test and 0.386 (0.01) in surrounding villi (p>0.5). At stasis, the villi under study showed epithelial clumping and were shortened: crypt depth:villous height ratios were 0.92 (0.2) in test and 0.42 (0.06) in surrounding villi (p<0.02). Vehicle alone had no effect on either blood flow or histology.

Conclusions—Focal slowing of villous blood flow and microvascular distortion precede villus shortening and epithelial disruption, and indicate that damage to surface microvasculature is an early event in indomethacin induced mucosal injury in this model.
Functional gastrointestinal disorders: psychological, social, and somatic features
Authors: Bennett E J , Piesse C , Palmer K , Badcock C-A , Tennant C C , Kellow J E
Published: June 2010

Background—Psychological, social, and extraintestinal (somatic) disturbances are prominent features of functional gastrointestinal disorders (FGID); little attention, however, has been given to differences in the nature of these disturbances in the various FGID subgroups.

Aims—(1) To determine whether psychological, social, and extraintestinal factors are associated with specific FGID, and/or with the overall severity and extent of FGID disturbance (the number of coexistent FGID subgroups present in any individual); and (2) to determine whether chronic social stressors link gastrointestinal, extraintestinal, and emotional symptomatologies in FGID.

Patients—One hundred and eighty eight outpatients, fulfilling standard criteria for one or more functional gastroduodenal or functional bowel disorders.

Methods—Utilising detailed and objective interview and questionnaire methods, detailed gastrointestinal, extraintestinal, psychological, and social data were collected.

Results—Chronic stressors and extraintestinal and emotional symptomatologies were prominent features of functional dyspepsia (FD) and irritable bowel syndrome (IBS) alone. These particular features were, however, highly specific for particular FD and/or IBS subgroups. The chronic threat component of social stressors predicted the nature and extent of multisystem (gastrointestinal, extraintestinal, and emotional) symptomatology.

Conclusions—Notable differences between the various FGID subgroups support the symptom based classification of FGID. Chronic stressor provoked psychological and extraintestinal disturbance is most specific for the FD-IBS group of syndromes.
Compared with parenteral nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis
Authors: Windsor A C J , Kanwar S , Li A G K , Barnes E , Guthrie J A , Spark J I , Welsh F , Guillou P J , Reynolds J V
Published: June 2010

Background—In patients with major trauma and burns, total enteral nutrition (TEN) significantly decreases the acute phase response and incidence of septic complications when compared with total parenteral nutrition (TPN). Poor outcome in acute pancreatitis is associated with a high incidence of systemic inflammatory response syndrome (SIRS) and sepsis.

Aims—To determine whether TEN can attenuate the acute phase response and improve clinical disease severity in patients with acute pancreatitis.

Methods—Glasgow score, Apache II, computed tomography (CT) scan score, C reactive protein (CRP), serum IgM antiendotoxin antibodies (EndoCAb), and total antioxidant capacity (TAC) were determined on admission in 34 patients with acute pancreatitis. Patients were stratified according to disease severity and randomised to receive either TPN or TEN for seven days and then re-evaluated.

Results—SIRS, sepsis, organ failure, and ITU stay, were globally improved in the enterally fed patients. The acute phase response and disease severity scores were significantly improved following enteral nutrition (CRP: 156 (117–222) to 84 (50–141), p<0.005; APACHE II scores 8 (6–10) to 6 (4–8), p<0.0001) without change in the CT scan scores. In parenterally fed patients these parameters did not change but there was an increase in EndoCAb antibody levels and a fall in TAC. Enterally fed patients showed no change in the level of EndoCAb antibodies and an increase in TAC.

Conclusion—TEN moderates the acute phase response, and improves disease severity and clinical outcome despite unchanged pancreatic injury on CT scan. Reduced systemic exposure to endotoxin and reduced oxidant stress also occurred in the TEN group. Enteral feeding modulates the inflammatory and sepsis response in acute pancreatitis and is clinically beneficial.
Cytokine profiles of cultured microvascular endothelial cells from the human intestine
Authors: Nilsen E M , Johansen F-E , Jahnsen F L , Lundin K E A , Scholz T , Brandtzaeg P , Haraldsen G
Published: June 2010

Background and aims—Cytokine production by endothelial cells has, for practical reasons, been chiefly studied in human umbilical vein endothelial cells (HUVEC) but, because tissue-specific differences apparently exist, the role of human intestinal microvascular endothelial cells (HIMEC) as a source of mucosal cytokines was also assessed.

Methods—The expression of cytokine transcripts in HIMEC was screened by means of reverse transcription polymerase chain reaction (RT-PCR) and compared with cytokine profiles of HUVEC. Production of cytokines was investigated by bioassay and enzyme linked immunosorbent assay (ELISA).

Results—In the basal unstimulated state, HIMEC and HUVEC cultures contained detectable mRNA for interleukin (IL)-3, IL-7, IL-8, IL-11, IL-14, IL-15, tumour necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and granulocyte-macrophage colony stimulating factor (GM-CSF). However, message was undetectable for IL-2, IL-4, IL-5, IL-9, IL-10, IL-12p40, IL-13, and interferon (IFN)-γ in the resting as well as the stimulated state. Stimulation of HIMEC and HUVEC with recombinant human (rh) IL-1β or rhTNF-α induced cell associated bioactive IL-1α but not IL-1β, as well as enhanced secretion of both IL-6 and IL-8. Furthermore, transcript levels for GM-CSF and TNF-α were enhanced by rhIL-1β or rhTNF-α in both cell types. Supernatants from Th1-like or Th0-like gluten reactive intestinal T cell clones derived from patients with coeliac disease elicited cytokine profiles in both HIMEC and HUVEC similar to those revealed after rhIL-1β or rhTNF-α stimulation.

Conclusions—These data demonstrate that the intestinal microvascular endothelium may contribute to the cytokine network of the intestinal mucosa with the ability to respond to locally generated cytokines and to produce potent inflammatory mediators.
Small bowel transit of a bran meal residue in humans: sieving of solids from liquids and response to feeding
Authors: Hebden J M , Blackshaw P E , Perkins A C , D’Amato M , Spiller R C
Published: June 2010

Background—Ileal motor patterns are adapted to the propulsion of viscous meal residue, such as bran, which accumulates in the distal ileum postprandially.

Aims—To examine the effects of a second liquid/solid meal on ileal emptying.

Subjects and methods—Eleven healthy fasting subjects consumed a 1.47 MJ pancake containing 15 g bran and 5 MBq Technetium-99m labelled amberlite resin (meal A). Gastric emptying and transit through the left upper quadrant (proximal) and right lower quadrant (distal) small bowel regions and colon were assessed scintigraphically. Transit was compared with and without a second Indium-111 liquid/solid DTPA labelled 2.28 MJ meal (B) given three hours after the first meal.

Results—Gastric emptying of meal A was slower than meal B (the time for 50% of the activity to leave the stomach (T50) being 113 (11) minutes versus 48 (3) minutes respectively, p<0.01, n=11). Both meals passed rapidly through the proximal small bowel (T50 meal A = 57 (14) minutes versus T50 meal B = 42 (11) minutes). Transit of meal A through the distal small bowel was much slower (T50 more than 390 minutes versus 176 (29) minutes for meal B, p<0.01), resulting in meal B overtaking meal A and entering the colon earlier. Ingestion of the second meal (B) resulted in significantly less meal A marker entering the colon (5 (3)%) at 11 hours than when meal A was taken alone (18 (4)%) (p<0.05, n=8).

Conclusions—The distal small bowel selectively retains bran, allowing liquid phase markers through to the colon. Consuming a second liquid/solid meal does not stimulate ileal transit of bran which seems to be propelled quicker by fasting motor patterns.
Reactive oxygen species activity and lipid peroxidation inHelicobacter pylori associated gastritis: relation to gastric mucosal ascorbic acid concentrations and effect of H pylori eradication
Authors: Drake I M , Mapstone N P , Schorah C J , White K L M , Chalmers D M , Dixon M F , Axon A T R
Published: June 2010

Background—Helicobacter pylori is an independent risk factor for gastric cancer, and this association may be due to the bacterium causing reactive oxygen species mediated damage to DNA in the gastric epithelium. High dietary ascorbic acid intake may protect against gastric cancer by scavenging reactive oxygen species.

Aims—To assess reactive oxygen species activity and damage in gastric mucosa in relation to gastric pathology and mucosal ascorbic acid level, and to determine the effect of H pylori eradication on these parameters.

Patients—Gastric biopsy specimens were obtained for analysis from 161 patients undergoing endoscopy for dyspepsia.

Methods—Reactive oxygen species activity and damage was assessed by luminol enhanced chemiluminescence and malondialdehyde equivalent estimation respectively. Ascorbic acid concentrations were measured using HPLC.

Results—Chemiluminescence and malondialdehyde levels in gastric mucosa were higher in patients with H pylori gastritis than in those with normal histology. Successful eradication of the bacterium led to decreases in both parameters four weeks after treatment was completed. Gastric mucosal ascorbic acid and total vitamin C concentrations were not related to mucosal histology, but correlated weakly with reactive oxygen species activity (chemiluminescence and malodialdehyde levels).

Conclusions—Data suggest that reactive oxygen species play a pathological role in H pylori gastritis, but mucosal ascorbic acid is not depleted in this condition.
Serum and liver HCV RNA levels in patients with chronic hepatitis C: correlation with clinical and histological features
Authors: De Moliner L , Pontisso P , De Salvo G L , Cavalletto L , Chemello L , Alberti A
Published: June 2010

Background—Liver disease in chronic hepatitis C virus (HCV) infection ranges from minimal lesions to liver cirrhosis, eventually evolving to hepatocellular carcinoma. Whether and how HCV determines the different clinical and histological manifestations of the disease is not fully understood.

Aims—To verify whether the amount of virus in individual patients could be related to the severity of liver injury.

Patients and methods—Levels of HCV RNA were measured in serum in 96 consecutive patients with chronic hepatitis type C using a signal amplification assay. The relation between viraemic values and the corresponding viral load in the liver was assessed in a subgroup of 21 patients in whom HCV RNA was measured in serum samples and liver specimens obtained at the same time.

Results—A positive correlation was observed between the amount of viral nucleic acid in the two compartments, indicating that levels of viraemia reflect the amount of virus present in the liver. Viral load did not correlate with aminotransferase activities nor with histological diagnosis, and serum and liver levels of HCV RNA were not significantly different in patients infected by the various HCV genotypes.

Conclusions—Measurement of HCV replication in serum is a mirror of viral replication in the liver. The extent of replicative activity of HCV does not seem to play a role in the modulation of the associated hepatic disease.
Effect of sodium ion coupled nutrient transport on intestinal permeability in chronically catheterised rats
Authors: Uhing M R
Published: June 2010

Background—The significance of Na-nutrient cotransport induced alterations in paracellular permeability is controversial. Most previous studies have measured intestinal permeability using in vitro methods or in vivo methods immediately after surgical bowel manipulation, and therefore may not be applicable to normal physiological conditions.

Aims—To determine whether activation of Na coupled nutrient transport increases intestinal permeability under normal physiological conditions.

Methods—The effect of Na-nutrient cotransport on intestinal permeability was measured in unrestrained, unanaesthetised, chronically catheterised male Sprague-Dawley rats using two different methods: measurement of the rate of absorption of passively absorbed hexoses, mannitol and l-glucose; and measurement of the mannitol:urea diffusion ratio.

Results—l-Glucose and mannitol absorption were not increased in the presence ofd-glucose, alanine, maltose, or peptides. The mannitol:urea diffusion ratio was not increased by the presence ofd-glucose. The presence of d-glucose in the intestinal lumen for 20 minutes did not alter intestinal permeability.

Conclusions—Under normal physiological conditions, Na coupled nutrient transport does not increase intestinal permeability.
The histamine H3 receptor agonistNα-methylhistamine produced byHelicobacter pylori does not alter somatostatin release from cultured rabbit fundic D-cells
Authors: Beales I L P , Calam J
Published: June 2010

Background—The mechanisms underlying the suppression of somatostatin dependent reflexes in Helicobacter pylori infection are not fully determined. The H pyloriproduct Nα-methylhistamine and inflammatory mediators such as tumour necrosis factor-α (TNF-α) may be responsible for the alterations in somatostatin release.

Aims—To examine the effect of Nα-methylhistamine on somatostatin release from cultured somatostatin-secreting D-cells.

Methods—Rabbit fundic D-cells were obtained by collagenase-EDTA digestion and enriched by centrifugal elutriation and cultured for 40 hours. The effects ofNα-methylhistamine on somatostatin release soon after stimulation (two hours) and after more prolonged exposure (24 hours) were assessed.

Results—Nα-Methylhistamine (1 nM–1 μM) had no effect on basal or carbachol or adrenaline stimulated release over two hours. Similarly with prolonged exposure no effect on somatostatin cell content or release was identified. In contrast, TNF-α (24 hours) led to a dose dependent fall in both somatostatin content and release.

Conclusions—Nα-Methylhistamine had no direct inhibitory effects on D-cells, but TNF-α both significantly reduced the cellular content and inhibited release. Inflammatory cytokines, rather thanNα-methylhistamine, are therefore likely to be responsible for directly inhibiting D-cell function in H pylori infection.
Measurement of gluten using a monoclonal antibody to a coeliac toxic peptide of A gliadin
Authors: Ellis H J , Rosen-Bronson S , O’Reilly N , Ciclitira P J
Published: June 2010

Background—Future European Community regulations will require a sensitive and specific assay for measurement of coeliac toxic gluten proteins in foods marketed as gluten-free. To avoid spurious cross reactions with non-toxic proteins, specific antibodies and target antigens are required. A synthetic 19 amino acid peptide of A gliadin has been shown to cause deterioration in the morphology of small intestinal biopsy specimens of coeliac patients in remission.

Aims—To develop an assay for detection of gluten in foods, based on measurement of a known toxic peptide.

Methods—A monoclonal antibody raised against the toxic A gliadin peptide, with a polyclonal anti-unfractionated gliadin capture antibody, was used to develop a double sandwich enzyme linked immunosorbent assay (ELISA) for the measurement of gluten in foods.

Results—Standard curves for gliadin and for rye, barley, and oat prolamins were produced. The sensitivity of the assay was 4 ng/ml of gliadin, 500 ng/ml for rye prolamins, and 1000 ng/ml for oat and barley prolamins. The assay could detect gluten in cooked foods, although at reduced sensitivity. Prolamins from coeliac non-toxic rice, maize, millet, and sorghum did not cross react in the assay. A variety of commercially available gluten- free foods were analysed; small quantities of gluten were detected in some products.

Conclusion—The assay may form the basis of a sensitive method for measurement of gluten in foods for consumption by patients with coeliac disease.
Helicobacter pylori specific nested PCR assay for the detection of 23S rRNA mutation associated with clarithromycin resistance
Authors: Maeda S , Yoshida H , Ogura K , Kanai F , Shiratori Y , Omata M
Published: June 2010

Background—Clarithromycin is one of the most important antibiotics for Helicobacter pylori eradication. However, 5–10% of strains are reported to be resistant. It has been shown that one point mutation in the 23S rRNA gene is associated with resistance to clarithromycin.

Aims—To establish a polymerase chain reaction (PCR) system which amplifies a segment of the 23S rRNA gene containing the mutation points with primers specific forH pylori, so that H pylori infection and the mutation associated with clarithromycin resistance can be examined simultaneously.

Methods—To detectH pylori infection and the mutation simultaneously, primers specific for the H pylori 23S rRNA gene were designed based on sequence conservation among H pylori strains and sequence specificity as compared with other bacteria. DNA from 57 cultured strains and from 39 gastric juice samples was amplified in the seminested 23S rRNA PCR. Clinical applicability was evaluated in 85 patients.

Results—DNA samples from 57 cultured strains were all amplified. The novel assay and the urease A PCR agreed in 37/39 gastric juice samples with no false positives. The assay did not amplify the DNA of bacteria other thanH pylori. Eight of 85 samples had the mutation before treatment. In clarithromycin based treatment, eradication was achieved in 2/5 (40%) with the mutation and 29/34 (85%) without the mutation.

Conclusion—The assay using gastric juice is quick (within 12 hours) and non-invasive (endoscopy not required), enabling rapid initiation of appropriate antibiotic treatment.
Early gastric stump cancer following distal gastrectomy
Authors: Kaneko K , Kondo H , Saito D , Shirao K , Yamaguchi H , Yokota T , Yamao G , Sano T , Sasako M , Yoshida S
Published: June 2010

Background—Gastric stump cancer (GSC) is usually diagnosed at an advanced stage, and consequently the prognosis is poor.

Aims—To investigate the clinicopathological characteristics of GSC at an early stage to assist in its identification, and thereby improve its prognosis.

Methods—Forty three patients with resected early GSC were compared with 156 patients with resected primary early cancer in the upper third of the stomach.

Results—Sixty five per cent (28/43) of the early GSC patients showed the elevated type endoscopically, although the frequency of the depressed type in GSC has tended to increase in the past five years. This occurred in less than 26% (40/156) of the primary early cancers. Half of the early GSCs were located on the lesser curvature (47%), and revealed differentiated adenocarcinoma (81%) histologically. The male:female ratio of early GSC cases was about 6:1, which was much higher than that in patients with primary early cancer. The five year survival rates of patients with early GSCs and early primary cancers were 84% and 95%, respectively. GSC had a favourable prognosis, if it was detected at an early stage.

Conclusion—To detect early GSC, our results suggest that special attention should be given to elevated as well as depressed lesions on the lesser curvature of the stomach, particularly in men, during endoscopic examinations.
Enhanced expression of monocyte tissue factor in patients with liver cirrhosis
Authors: Saliola M , Lorenzet R , Ferro D , Basili S , Caroselli C , Di Santo A , Sallese M , Violi F
Published: June 2010

Background—Previous studies have shown that cirrhotic patients produce increased amounts of thrombin but the underlying mechanism is still unknown.

Aims—To analyse the relation between the rate of thrombin generation and monocyte expression of tissue factor (TF) in cirrhosis.

Patients—Thirty three cirrhotic patients classified as having low (n=7), moderate (n=17), or severe (n=9) liver failure according to Child-Pugh criteria.

Methods—Prothrombin fragment F1+2, monocyte TF activity and antigen, and endotoxaemia were measured in all patients. Polymerase chain reaction (PCR) analysis of TF mRNA was performed in monocytes of five cirrhotic patients.

Results—Prothrombin fragment F1+2 was higher in cirrhotic patients than in controls (p<0.0001). Monocytes from cirrhotic patients had higher TF activity and antigen than those from controls (p<0.001) with a progressive increase from low to severe liver failure. Monocyte expression of TF was significantly correlated with plasma levels of F1+2 (TF activity:r=0.98, p<0.0001; TF antigen:r=0.95, p<0.0001) and with endotoxaemia (TF activity: r=0.94, p<0.0001; TF antigen:r=0.91, p<0.0001). PCR analysis of TF mRNA showed TF expression only in three patients with endotoxaemia (more than 15 pg/ml).

Conclusions—Cirrhotic patients have enhanced expression of TF which could be responsible for clotting activation, suggesting that endotoxaemia might play a pivotal role.
The influence of a preserved colon on the absorption of medium chain fat in patients with small bowel resection
Authors: Jeppesen P B , Mortensen P B
Published: June 2010

Background—Medium chain C8–C10 triglycerides (MCTs) improve fat absorption in short bowel patients. Effects on overall energy absorption remain unknown.

Aims—To determine whether MCTs and medium chain fatty acids (MCFAs) are absorbed in the colon like the short chain fatty acids (SCFAs) or are lost in faeces similarly to long chain fatty acids (LCFAs).

Methods—Nine small bowel resected patients without and 10 with a colon in continuity excreted 2–6 MJ/day and were randomised and crossed over between two high fat diets (10 MJ/day, 50% as fat), based on either long chain triglycerides (LCT) alone or equal quantities of LCT and MCT.

Results—Patients with a colon absorbed C8–C10 fatty acids considerably better than patients without a colon at similar and extreme levels of LCFA malabsorption; the colonic impact on absorption of C14–18 fatty acids was negligible. MCT redoubled fat (MCT+LCT) absorption from 23% to 58% in patients with a colon, and increased overall bomb calorimetric energy absorption from 46% to 58%. The increase in fat absorption from 37% to 46% in patients without a colon did not improve overall energy absorption because malabsorption of carbohydrate and protein increased.

Conclusion—In small bowel resected patients, the colon seems to serve as a digestive organ for medium chain fat, probably absorbed as MCFAs, perhaps because like the SCFAs, they are water soluble. Only patients with a colon gained from MCT treatment.
Appendicectomy, childhood hygiene, Helicobacter pylori status, and risk of inflammatory bowel disease: a case control study
Authors: Duggan A E , Usmani I , Neal K R , Logan R F A
Published: June 2010

Aims—To examine the relation between inflammatory bowel disease and appendicectomy, childhood domestic hygiene, andHelicobacter pylori infection.

Methods—Case control study involving 213 patients with ulcerative colitis, 110 with Crohn’s disease, and 337 controls having elective surgery.

Results—Nine patients with ulcerative colitis (4.5%) reported a previous appendicectomy compared with 57 controls (19%) (odds ratio (OR) 0.20, 95% confidence interval (CI) 0.1–0.4, p<0.0001). The inverse association was unaffected by excluding operations performed after the age of onset of ulcerative colitis and was stronger for appendicectomy performed before age 20 (OR 0.14). No association with appendicectomy was found for Crohn’s disease and no associations with tonsillectomy for either disease. The availability of a fixed hot water supply in early childhood (before age 11) was associated with Crohn’s disease (OR for hot water not always versus always available 0.56, 95% CI 0.3–0.9, p=0.02) but not with ulcerative colitis. No other aspect of domestic hygiene before or after age 11 was associated with either Crohn’s disease or ulcerative colitis. Although H pylori seroprevalence was positively associated with overcrowding (p<0.001) and the absence of running hot water in childhood it was not associated with the presence of either Crohn’s disease or ulcerative colitis. H pyloriseroprevalence was no lower in patients who had been exposed to sulphasalazine than in controls or those not exposed.

Conclusions—Our findings confirm the strong inverse association between previous appendicectomy and the development of ulcerative colitis and suggest that the protective effect is greater for appendicectomy performed in childhood.
A requiem for the cholecystokinin provocation test?
Authors: Smythe A , Majeed A W , Fitzhenry M , Johnson A G
Published: June 2010

Background—The cholecystokinin provocation test (CCKPT) has been claimed to predict a better symptomatic result after cholecystectomy in patients with acalculous biliary pain.

Aims—To examine the predictive value of the CCKPT for symptom relief after cholecystectomy in both CCKPT positive and negative patients.

Patients and methods—Fifty eight patients with acalculous biliary pain underwent CCKPT with serial ultrasound gall bladder volumetry. CCKPT positive patients were offered cholecystectomy; negative patients were reassessed and were offered a cholecystectomy if symptoms persisted. Six months after cholecystectomy, the CCKPT was repeated.

Results—Of 32 CCKPT positive patients, 27 underwent cholecystectomy and of these, 18 (67%) became symptom-free. Postoperatively, 20 of 25 patients converted to CCKPT negative but five remained CCKPT positive and were symptomatic. Of the 26 CCKPT negative patients, nine became symptom-free without cholecystectomy; six of 14 (42.8%) patients undergoing cholecystectomy became asymptomatic and remained CCKPT negative. Cholecystectomy seemed to reduce symptoms in both groups, but there was no significant difference in the symptomatic outcome between preoperative CCKPT positive and negative patients.

Conclusions—In this study, cholecystokinin provocation testing did not predict symptomatic benefit from cholecystectomy and we suggest it should no longer be used in the evaluation of patients with acalculous biliary pain.
Decreased expression of the interleukin 2 receptor on CD8 recipient lymphocytes in intestinal grafts rendered tolerant by liver transplantation in rats
Authors: Sarnacki S , Nakai H , Calise D , Azuma T , Brousse N , Révillon Y , Cerf-Bensussan N
Published: June 2010

Background—In a previous study, it was shown that a spontaneously tolerated DA (RT1a) liver allograft in a PVG (RT1c) recipient was able to induce tolerance of a DA small bowel graft performed 17 days later in spite of infiltration of the intestinal grafts by mononuclear cells.

Aims—To compare the phenotype of graft infiltrating cells in rejecting and tolerated small bowel grafts in order to elucidate the mechanism(s) which block the graft infiltrating cells from mediating rejection.

Methods—Multiparameter immunofluorescence was used to compare the phenotype and state of activation of donor and recipient cells isolated from intestinal grafts rejected or tolerated after liver transplantation.

Results—Three differences were found. Firstly, there was a more rapid replacement of lamina propria (LP) cells by recipient lymphocytes in tolerated than in rejected grafts. Secondly, the proportion of LP recipient CD8αβ+ lymphocytes bearing the high affinity receptor for interleukin 2 was significantly less in tolerated grafts (1.1%, range 0–2%) than in rejected grafts (21.3%, range 9–26%). Finally, tolerated grafts contained significantly less NK lymphocytes (NKR-P1+) and macrophages than rejected intestinal allografts.

Conclusions—These observations make it possible to delineate clear cut differences in the phenotype of cells infiltrating rejecting versus tolerated grafts. Furthermore, the data suggest that liver transplantation induces tolerance of intestinal grafts by hampering the activation of recipient TcRαβ+ CD8αβ+ T cells and subsequently the recruitment of non-specific effector cells.
Proabsorptive and prosecretory roles for nitric oxide in cholera toxin induced secretion
Authors: Turvill J L , Mourad F H , Farthing M J G
Published: June 2010

Background

Cholera toxin causes small intestinal hypersecretion by inducing a coordinated response from enterocytes, enterochromaffin cells, enteric neurones, and the vascular supply. Nitric oxide has been implicated in the function of these separate components.

Aims

To explore the role of nitric oxide in the totality of cholera toxin induced secretion in vivo.

Methods

One group of adult male Wistar rats was treated with the nitric oxide synthase inhibitors NG-nitro-l-arginine methyl ester (l-NAME; subcutaneously or intraluminally), NG-methyl-l-arginine (l-NMA), or 7-nitroindazole. A second group of rats was treated withl-arginine (intraperitoneally or intraluminally) ord-arginine. The small intestine was isolated between two cannulae and instilled with 75 μg cholera toxin or saline for two hours. Small intestinal perfusion of a plasma electrolyte solution containing [14C]-PEG was undertaken to determine net water and electrolyte movement. After the experiment macroscopic and microscopic intestinal appearances were noted and jejunal 5-hydroxytryptamine concentrations were determined.

Results

Both l-arginine and l-NAME induced secretion in the basal state, but only when administered intraluminally. Systemically appliedl-NAME caused a dose dependent reduction in cholera toxin induced secretion. This was paralleled by l-NMA but not by 7-nitroindazole or by intraluminally applied l-NAME. Systemically applied l-NAME caused notable cyanosis of the intestine, consistent with mesenteric ischaemia, but no microscopic abnormalities. Systemically applied l-arginine but notd-arginine also reduced cholera toxin induced secretion and inhibited 5-hydroxytryptamine release.

Conclusion

Nitric oxide has a duality of roles in cholera toxin induced secretion, acting both as an absorbagogue and a secretagogue. Its mechanisms of action include the maintenance of mucosal perfusion and enterochromaffin cell stabilisation.
Comparison of a low dose polyethylene glycol electrolyte solution with lactulose for treatment of chronic constipation
Authors: Attar A , Lémann M , Ferguson A , Halphen M , Boutron M-C , Flourié B , Alix E , Salmeron M , Guillemot F , Chaussade S , Ménard A-M , Moreau J , Naudin G , Barthet M
Published: June 2010

Background

Polyethylene glycol (PEG) 3350 is a non-absorbable, non-metabolised osmotic agent used in lavage solutions for gut cleansing.

Aims

To compare the efficacy of PEG and lactulose in chronic constipation.

Methods

A total of 115 patients with chronic constipation entered a multicentre, randomised, comparative trial. They initially received two sachets containing either PEG (13 g/sachet) or lactulose (10 g/sachet) and were given an option to change the dose to one or three sachets/day, depending on response.

Results

Ninety nine patients completed the trial. After four weeks, patients in the PEG group (n=50) had a higher number of stools and a lower median daily score for straining at stool than patients in the lactulose group (n=49). Overall improvement was greater in the PEG group. Clinical tolerance was similar in the two groups, but flatus was less frequently reported in the PEG group. The mean number of liquid stools was higher in the PEG group but the difference was significant only for the first two weeks. There were no serious adverse events and no significant change in laboratory tests in either group. At the end of the study, the number of sachets used by the patients was 1.6 (0.7)/day in the PEG group and 2.1 (0.7)/day in the lactulose group. Sixty one patients completed a further two months open study of one to three sachets PEG daily; there was no loss of efficacy and no serious toxicity.

Conclusion

Low dose PEG 3350 was more effective than lactulose and better tolerated.
Gallstones: an intestinal disease?
Authors: VAN ERPECUM K J , VAN BERGE-HENEGOUWEN G P
Published: June 2010

Current evidence suggests that impaired intestinal motility may facilitate gallstone formation by influencing biliary deoxycholate levels or by modulating interdigestive gall bladder motility (fig 2), although a primary intestinal defect in gallstone pathogenesis has not yet been demonstrated. In the cold war period, most interesting events, from a political point of view, occurred at the border between capitalist and communist systems, near the iron curtain. Similarly, the gall bladder and biliary tract can be viewed as the border between liver and intestinal tract, where many interesting things occur with profound impact on both systems. Combined efforts by researchers in the field of hepatology and gastrointestinal motility should brake down the Berlin wall of ignorance of one of the most common diseases in the Western world.
Hepatic and splanchnic nitric oxide activity in patients with cirrhosis
Authors: Sarela A I , Mihaimeed F M A , Batten J J , Davidson B R , Mathie R T
Published: June 2010

BACKGROUND

In animal models of cirrhosis, altered activity of nitric oxide (NO) has been implicated in the pathogenesis of increased intrahepatic portal vascular resistance and abnormal mesenteric vasodilatation.

AIMS

To investigate NO activity in the liver and splanchnic vascular bed of patients with cirrhosis.

METHODS

Activity of the calcium dependent constitutive and calcium independent inducible isoforms of NO synthase (cNOS and iNOS, respectively) was assayed biochemically in biopsy specimens of liver and a vascular portion of the greater omentum (representative of mesenteric vasculature) obtained from patients with cirrhosis undergoing liver transplantation (n=14) and non-cirrhotic control patients undergoing liver resection for metastases (n=9). The concentration of NO metabolites (NO2 + NO3) in portal and peripheral venous plasma was measured.

RESULTS

The activity of cNOS was lower in cirrhotic compared with non-cirrhotic subjects for both liver and omentum. Hepatic and omental iNOS activities did not differ significantly between the two groups. Portal (NO2 + NO3) was threefold higher in cirrhotic than non-cirrhotic patients, but no differences were observed in systemic venous samples from the two groups.

CONCLUSIONS

The activity of cNOS is diminished in the cirrhotic human liver. The resultant decrease in constitutive NO release may promote an increase in the intrahepatic portal vascular resistance. Elevated portal venous (NO2 + NO3) indicates enhanced splanchnic vascular release of NO in cirrhotic patients, but the absence of increased NOS activity in the mesenteric vasculature suggests differential regulation of NO synthesis within the splanchnic vascular bed.