bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastric mucosal adaptation to etodolac and naproxen
Authors: LIPSCOMB G. R. , WALLISt N. , ARMSTRONG† G. , GOODMAN M. J. , REES W. D. W.
Published: July 2010

Background: Nonsteroidal anti‐inflammatory drugs (NSAIDs) frequently cause damage to the gastroduodenal mucosa, principally by suppressing mucosal prostaglandin synthesis. However, such acute mucosal injury usually resolves, despite continued NSAID administration, by a process known as adaptation. Newer NSAIDs, such as etodolac, have been developed to minimize effects on prostaglandin synthesis.

Aim: To determine whether etodolac causes less acute damage than naproxen, and whether the damage produced resolves with continued NSAID administration.

Methods: Twenty‐four healthy volunteers were given a 28‐day course of either etodolac 300 mg b.d. or naproxen 500 mg b.d. Gastroduodenal damage was assessed using a modified Lanza scoring system and mucosal blood flow with laser doppler flowmetry at endoscopy before NSAID administration and during days 1, 7 and 28 of continued intake.

Results: Maximum gastric damage (median grade and interquartile range, IOR) occurred during the first 24 h of administration, being greater with naproxen (2.0, IOR 1.0–3.0) than etodolac (1.0, IOR 1.0–1.5; P= 0.03). Such damage was associated with a fall in antral blood flow in the naproxen group (mean ± S.E.M.) from 54.5±3.4 to 43.8±3.4 arbitrary units (P= 0.07) and a slight increase in mucosal blood flow in the etodolac group from 43.5 ± 2.24 to 49.5 + 3.6 arbitrary units. With continued intake this damage resolved in all subjects taking etodolac and in eight of 14 subjects on naproxen. Resolution in the naproxen group was associated with a return to normal of antral blood flow.

Conclusions: These observations suggest that etodolac causes less mucosal damage than naproxen and that adaptation occurs to both.
Eradication of Helicobacter pylori and prevention of recurrence of duodenal ulcer: a randomized, double‐blind, multi‐centre trial of omeprazole with or without clarithromycin
Authors: LOGAN R. P. H. , BARDHAN K. D. , CELESTIN L. R. , THEODOSSI A. , PALMER K. R. , REED P. I. , BARON J. H. , MISIEWICZ J. J.
Published: July 2010

Background: Antimicrobial treatment for Helicobacter pylori eradication is currently recommended for all patients with duodenal ulcer disease, but consensus on the best treatment is lacking.

Methods: Patients with active duodenal ulcer and H. pylori were enrolled in a double‐blind, randomized, placebo‐controlled multi‐centre study. Patients received omeprazole 40 mg daily for 28 days and either clarithromycin 500 mg t.d.s. or placebo t.d.s. for the first 14 days. Patients underwent endoscopy before starting treatment, at 2 weeks, immediately after stopping treatment if unhealed at 2 weeks, and at 1, 6 and 12 months after the end of treatment, or at the recurrence of symptoms. Eradication of H. pylori, duodenal ulcer healing and ulcer recurrence were measured.

Results: One‐hundred and fifty‐four patients were recruited and randomized to omeprazole plus clarithromycin (n= 74) or to omeprazole plus placebo (n= 80). One month after treatment, H. pylori was eradicated in 57 of 69 (83%; 95% CI: 72–91%) patients receiving omeprazole plus clarithromycin, compared with 1 of 75 (1%; 95% CI: 0–7%) receiving omeprazole alone (P < 0.001). In patients receiving omeprazole plus clarithromycin the ulcer healed at 2 weeks in 83% (95% CI: 71–91%) and at 4 weeks in 100% (95% CI: 95–100%), compared with 77% (95% CI: 66–86%) and 97% (95% CI: 91–100%) in those given omeprazole plus placebo (N.S.). Ulcers recurred at 12 months in 6% (95% CI: 1–16%) of patients given omeprazole plus clarithromycin, compared with 76% (95% CI: 63–86%) of patients given omeprazole plus placebo (P < 0.001). The incidence of side‐effects was similar in both treatment groups (38% with clarithromycin dual therapy and 29% with omeprazole plus placebo; P= 0.304). Ninety per cent of patients took at least 90% of their prescribed medication.

Conclusions: Omeprazole plus clarithromycin dual therapy eradicated H. pylori in 83% of patients with duodenal ulcer and significantly decreased 12‐month recurrence from 76% to 6%.
Gastric persorption of bismuth from ranitidine bismuth citrate
Authors: ERASER A. G. , LEWIN J. F. , POUNDER R. E.
Published: July 2010

Aim: To determine whether bismuth penetrates the gastric mucosa after dosing with ranitidine bismuth citrate.

Methods: Twelve patients presenting with dyspepsia were randomized to receive either ranitidine bismuth citrate or placebo, 20–40 min prior to endoscopy. Biopsies were taken from four sites during endoscopy: the first and second parts of the duodenum, the antrum, and the body of the stomach. Biopsies were analysed by electron microscopy and X‐ray microanalysis.

Results: Bismuth particles were found to be interposed between epithelial cells in the antral mucosa of three of eight patients who were dosed with ranitidine bismuth citrate. Columns of bismuth particles could be tracked down the lamina propria and were seen to be surrounding blood vessels. Bismuth particles were observed in the inter‐ and intra‐cellular channels of the endothelial cells of the blood vessels in the lamina propria and also close to the luminal surface of the endothelial cell. This process of persorption was similar to that described in a previous report of electron microscopy appearances of the gastric antrum after dosing with tripotassium dicitrato bismuthate, but was quantifiably smaller and not observed in all the patients dosed with ranitidine bismuth citrate. No penetration of the mucosa by bismuth particles was seen in the body of the stomach or the duodenum.

Conclusion: Penetration of bismuth particles into the gastric mucosa may occur after oral dosing with ranitidine bismuth citrate.
Long term continuous omeprazole treatment of patients with Barrett's oesophagus
Authors: NEUMANN C. S. , IQBAL T. H. , COOPER B. T.
Published: July 2010

Background: The metaplastic columnar epithelium in Barrett's oesophagus has malignant potential.

Aim: To determine whether decreasing acid reflux leads to regression of Barrett's epithelium.

Method: Twenty‐four patients with Barrett's oesophagus were treated with omeprazole 20 mg o.m. in an open, prospective study; 11 were treated for 12 months, and 13 for 24 months. Another group of 17 patients with Barrett's oesophagus was treated with an H2‐receptor antagonist in standard dosage for 12‐36 (mean 23) months. Patients were assessed endoscopically.

Results: No evidence of significant shortening of the length of Barrett's oesophagus was seen in any patient treated for 12 or 24 months with omeprazole. Similarly, no shortening of the length of Barrett's oesophagus was seen in any patient treated with an H2‐receptor antagonist. However, 6 of 11 patients treated with omeprazole for 12 months, and 7 of 13 treated for 24 months, developed macroscopic squamous islands visible below the squamo‐columnar junction. This was not seen in any patient treated with an H2‐receptor antagonist.

Conclusion: Although there can be reappearance of squamous epithelium in Barrett's oesophagus of some patients during treatment with omeprazole 20 mg o.m. over 12–24 months, a significant shortening of the columnar lined segment is not seen.
Treatment of hepatitis B surface antigen carriers in the early stage of the infection using recombinant alpha‐interferon with steroid priming
Authors: GUAN R. , HO K. Y. , YAP I. , KANG J. Y. , TAN C. C. , NG C. , SMITH R. , WEE A.
Published: July 2010

Background: Alpha‐interferon has been found to inhibit hepatitis B virus (HBV) replication in Chinese patients with chronic HBV infection although a sustained effect was rarely achieved in those with normal pre‐treatment serum alanine amino transferase (ALT) levels. Prednisolone priming has been found to be beneficial over treatment with interferon alone in these subjects. We studied the effect of steroid pre‐treatment followed by recombinant interferon alpha‐2a in the treatment of asymptomatic HBV carriers with positive hepatitis Be antigen (HBeAg), hepatitis B viral DNA (HBV‐DNA) and minimal changes in liver histology.

Methods: The treatment regimen included a 6‐week prednisolone priming, a 2 week rest followed by 14 weeks of three times weekly 9 mega units of interferon alpha‐2a injection and 52 weeks of follow‐up. There were seven patients in the treatment group and seven controls.

Results: The mean age, pre‐treatment ALT (normal in all except for one in each of the treatment and control groups), HBV‐DNA levels and histological scores were similar in the two groups. Serum HBV‐DNA levels fell in six patients during treatment and became undetectable in two of them by the end. During follow‐up, serum HBV‐DNA returned to pre‐treatment levels in all patients. None of the treated patients had HBeAg sero‐conversion and none of the controls had spontaneous clearance of HBV‐DNA or sero‐conversion of HBeAg. No improvement of liver histology was observed in any of the treated patients. There were only mild flu‐like side‐effects noted and interferon alpha‐2a was well tolerated at the doses given among treated patients.

Conclusion: Prednisolone priming followed by interferon alpha‐2a treatment has no beneficial effect on HBV carriers in the early stages of chronic hepatitis B infection.
Lipocortin‐1 autoantibody concentration in children with inflammatory bowel disease
Authors: BEATTIE R. M. , GOULDING N. J. , WALKER‐SMITH J. A. , MACDONALD T. T.
Published: July 2010

Background: Corticosteroids are widely used to treat children with inflammatory bowel disease although the response is variable, side‐effects are common, and many patients develop a partial or complete steroid resistance. The mechanism underlying these phenomena are unclear. Corticosteroids mediate some of their actions through lipocortin‐l, and the inductic of autoantibodies to lipocortin has been proposed as a possible mechanism by which steroid efficacy is suboptimal in vivo.

Patients and methods: We have measured serum lipocortin‐1 antibody concentration by ELISA in 38 children with Crohn's disease, 12 with ulcerative colitis and in 15 controls.

Results: IgG and IgA anti‐lipocortin‐1 antibody levels were higher in the Crohn's group than in the ulcerative colitis or control groups. Elevated concentrations did not relate to disease activity, history of steroid therapy or steroid‐responsiveness. Lipocortin IgM antibody status was similar in all three groups.

Conclusion: It is therefore unlikely that serum antibodies to lipocortin‐1 have a role in the development of steroid‐resistance in children with inflammatory bowel disease.
The effect of treatment on lymphokine‐secreting cells in the intestinal mucosa of children with Crohn's disease
Authors: BREESE E. J. , MICHIE C. A. , NICHOLLS S. W. , WILLIAMS C. B. , DOMIZIO† P. , WALKER‐SMITH J. A. , MACDONALD T. T.
Published: July 2010

Background: Recent studies have shown both interleukin 2 (IL‐2) and interferon gamma (IFN) to be elevated in patients with active Crohn's disease compared to ulcerative colitis or non‐inflammatory bowel disease controls. However the effect of treatment on these lymphokines has not been studied.

Patients and methods: Using a reverse haemolytic plaque assay the percentage of lymphokine‐secreting cells was determined in the intestinal mucosa of children with Crohn's disease before and after 8 weeks of treatment with either enteral nutrition, cyclosporin or steroids.

Results: Before treatment, a high percentage of cells isolated from mucosal biopsies secreted IL‐2 or interferon‐gamma. Eight weeks’treatment with the immunosuppressive agents cyclosporin, or with corticosteroids, produced a significant reduction in the percentage of IL‐2 secreting cells, although only for the former was there also a reduction in interferon‐gamma secreting cells. Enteral nutrition however, produced a reduction in lymphokine‐secreting cells equivalent to cyclosporin and produced the best histological and clinical improvement.

Conclusion: Enteral nutrition and cyclosporin can down‐regulate lymphokine secretion in the gut in Crohn's disease.
Patterns of 24‐hour oesophageal acid exposure after acute withdrawal of acid suppression
Authors: ORR W. C. , MELLOW M. H. , GROSSMAN M. R.
Published: July 2010

Aim: To measure 24‐h ambulatory oesophageal pH data in patients with gastro‐oesophageal reflux disease prior to, during and after acute treatment with comparable doses of omeprazole and ranitidine.

Methods: The subjects were 20 adults with at least 8% acid contact time. Ten subjects were treated for 1 week with omeprazole 20 mg q.d.s. and 10 subjects with ranitidine 300 mg t.d.s. All subjects were examined at the end of 1 week of therapy and subsequent to cessation of treatment (1 day for ranitidine and 3 days for omeprazole).

Results: Both drugs produced a statistically significant (P < 0.05) decrease in acid contact time with acute treatment. Omeprazole produced a significantly greater decrease in acid contact time when compared to ranitidine. Subsequent to treatment cessation, the total acid contact time for omeprazole remained significantly less than the baseline level, while ranitidine returned to levels which were not significantly different from the baseline.

Conclusion: These data provide no evidence for a ‘reflux rebound’ subsequent to the cessation of acute acid secretory suppression.
Do non‐steroidal anti‐inflammatory drugs have an effect on gastric cell turnover?
Authors: SANT S. M. , CAHILL R. J. , GILVARRY J. , O'MORAIN C. A.
Published: July 2010

Aim: To study the effect of non‐steroidal anti‐inflammatory drugs (NSAIDs) on gastric cell turnover using an in vitro immunohistochemical method of bromodeoxyuridine (BrDU) uptake.

Methods: Thirty patients undergoing routine upper gastrointestinal endoscopy were studied. Sixteen had taken NSAIDs daily for more than 3 months and there were 14 age‐matched controls. Endoscopic gastric antral biopsies were obtained and stained immediately using the BrDU technique. Cell proliferation was expressed as a labelling index percentage (LI%) defined as the number of BrDU‐labelled nuclei in 10 gastric glands, expressed as a percentage of the total cells in the gastric gland.

Results: Gastric infection with Helicobacter pylori was excluded in all patients. Of the 16 patients on NSAIDs, four had gastritis, four had erosions or ulceration and eight had a normal examination. Endoscopy was normal in all patients in the control group. The LI% (mean ± S.E.M.) in the entire NSAID group was 4.09 ± 0.29 and in the control group 3.57 ± 0.29. No significant difference was observed. In the NSAID patients with gastritis and erosions or ulceration, the LI% was 4.99 ± 0.61 and 3.07 ± 0.32, respectively. There was no significant difference in LI % between the endoscopic subgroups of patients on NSAIDs or between patients on NSAIDs who had normal endoscopy and the control patients.

Conclusion: These results provide evidence that refutes the hypothesis that the prevalence of NSAID gastropathy is due to an effect on gastric cell turnover.
Review article Is Helicobacter pylori transmitted by the gastro‐oral route?
Authors: AXON A. T. R.
Published: July 2010

The manner in which Helicobacter pylori is transmitted is of fundamental importance when considering strategies for its control, yet to date no satisfactory explanation has been advanced to account for its spread from person to person. This is surprising for a disease that affects 50% of the world's population. Attempts to culture H. pylori from faecal material and saliva have met with difficulty, casting some doubt on the likelihood of a faeco‐oral or oro‐oral route of transfer. The infection is easily passed from person to person by gastric intubation.

The hypothesis advanced in this paper is that the natural route of transmission is by gastric juice, specifically as a result of epidemic vomiting in childhood. This theory is supported by literature indicating that acute infection with H. is characterized by vomiting of achlorhydric mucus that may serve as a vehicle for transmission. The hypothesis is consistent with most of the epidemiological data that have been published on H. pylori infection, including its association with childhood overcrowding, the lack of a fixed hot water supply and disadvantaged social conditions.
The effect of polyunsaturated phosphatidyl choline in the treatment of acute viral hepatitis
Authors: GUAN R. , HO K. Y. , KANG J. Y. , YAP I. , GWEE K. A. , TAN C. C.
Published: July 2010

Background: Polyunsaturated phosphatidyl choline is a preparation often advocated for diseases of the liver. Methods: In a randomized open controlled trial, a preparation of polyunsaturated phosphatidyl choline, at a dose of 900 mg orally daily, was given to 22 patients with acute viral hepatitis. A control group of 25 patients was not treated.

Results: Serial serum bilirubin and alanine amino transferase levels were measured up to 12 weeks. The falls in their levels after 2 and 5 weeks, and the lengths of time to their normalization, were not significantly different in the treated group compared to the control group.

Conclusion: The results indicated that polyunsaturated phosphatidyl choline had no beneficial effect on the course of acute viral hepatitis.
Drugs for pH control in upper gastrointestinal bleeding
Authors: BRIJNNER G. , LUNA P. , THIESEMANN C.
Published: July 2010

A few years ago, patients with bleeding peptic ulcers were referred to the surgeon if the bleeding did not stop. Today we have two promising new approaches to prevent emergency surgery. One is endoscopic intervention, the other is the pharmacological approach of blocking the proton pump.

The endoscopical techniques of adrenaline injection, fibrin‐‘glue’ injection, polidocanol injection and heat coagulation can stop active bleeding in over 90% of cases. Pharmacologically, proton pump inhibitors can quickly achieve the optimal pH condition for support of the physiological cascade of haemostasis.

The aim is to keep the intragastric pH above 6.0 for a few days. For the first time this aim can be achieved quickly and reliably by infusion of proton pump inhibitors. The optimal form of application is continuous infusion. Repeated bolus injections do not give optimal results. The optimal dosing was found to be the continuous infusion of 8 mg/h omeprazole or pantoprazole after an initial loading dose of 40–80 mg.
A prospective study of the effectiveness of low dose omeprazole as initial therapy in Zollinger–Ellison syndrome
Authors: TERMANINI B. , GIBRIL F. , STEWART C. A. , WEBER H. C. , JENSEN R. T.
Published: July 2010

Background: The proton pump inhibitors (omeprazole and lansoprazole) are the drugs of choice for the medical management of gastric acid hypersecretion in Zollinger–Ellison syndrome (ZES). These drugs are safe for long‐term therapy but are acid‐labile and high doses are expensive. The recommended starting dose of omeprazole is 60 mg/day. However, it has been shown in recent studies that the maintenance dose of omeprazole could be safely reduced to 20 mg once or twice a day in more than two‐thirds of patients with ZES. The purpose of this study is to determine if an initial starting dose of omeprazole 20 mg/day is safe and effective in patients with ZES.

Methods: Forty‐nine consecutive patients with ZES being treated with ranitidine for at least 2 weeks were admitted to the NIH. Omeprazole 20 mg was started on day 1 of the admission and ranitidine discontinued 4 h after the first dose. Gastric acid output was measured for 1 h prior to the next omeprazole dose on day 2, then on day 3 if the value was > 10 mmol/h on the previous day. If acid‐peptic symptoms developed or the gastric acid output remained > 10 mmol/h on day 3, the patient was considered to have failed omeprazole 20 mg/day initial therapy and the dose titrated daily to achieve adequate control of acid‐peptic symptoms and gastric secretion.

Results: In 33 of the 49 patients (68%) omeprazole 20 mg/day was successful as initial therapy. Sixteen patients (32%) failed this initial omeprazole dose (eight patients owing to persistent peptic symptoms and eight patients owing to inadequate acid control). The final daily omeprazole dose required in these patients was 40 mg in eight patients (16%), 60 mg in one patient (2%) and 80 mg in seven patients (14%). Basal acid output (BAO) was the only clinical or laboratory feature that was significantly different between the two groups in which low dose initial omeprazole therapy was or was not successful: all patients with basal acid output < 20 mmol/h had a successful outcome.

Conclusions: Because of the need to rapidly control gastric acid hypersecretion owing to the high risk of complications from peptic ulcer disease, patients with ZES should continue to be started on omeprazole 60 mg/day and the dose adjusted by acute titration methods as is currently recommended. After a maintenance dose is established, attempts should be undertaken to reduce the dose to 20 mg/day once or twice a day. Only the minority of patients with ZES in whom basal acid output is known to be < 20 mmol/h (20% of patients) should be started on a low initial omeprazole dose.
A survey of dyspepsia in Great Britain
Authors: PENSTON J. G. , POUNDER R. E.
Published: July 2010

Objectives: To determine the prevalence of dyspepsia in the adult population of Great Britain and to describe the clinical features, treatment, effect of dyspepsia on daily lives and perceptions of peptic ulcer disease. Design: Cross‐sectional survey of the adult population using structured questionnaires.

Setting: Subjects interviewed at more than 150 sampling points in England, Scotland and Wales in November 1994.

Subjects: A representative sample of the adult population comprising 2112 subjects, aged 16 years or more.

Main outcome measures: The prevalence of dyspepsia in the adult population and the frequency of various characteristics in dyspeptic subjects.

Results: The prevalence of dyspepsia was 40%. Upper abdominal pain and heartburn were the most frequently reported symptoms. Solitary symptoms were uncommon and there was frequent overlap between‘ulcer‐like’and‘reflux‐like’dyspepsia. Forty‐six per cent of dyspeptic subjects reported moderate or severe symptoms. More than half of symptomatic subjects took medication and 22% had visited their GP during the previous year. Overall, 2% of the survey sample had been absent from work due to dyspepsia. Awareness of the factors precipitating or aggravating peptic ulcer disease was poor, particularly in relation to anti‐inflammatory drugs.

Conclusions: The present study emphasizes the magnitude of the problem of dyspepsia in the adult population of Great Britain. The survey also shows that the public in general, and patients in particular, require more information if they are to avoid factors known to damage the upper alimentary tract.
Correlation of serum pepsinogen with histological atrophy following successful Helicobacter pylori eradication
Authors: KAWAI T. , KAWAKAMI K. , KATAOKA M. , TAKEI K. , TAIRA S. , ITOI T. , MORIYASU F. , TAKAGI Y. , AOKI T. , SERIZAWA H. , RIMBARA E. , NOGUCHI N. , SASATSU M.
Published: July 2010

Background

Levels of pepsinogen have been reported to correlate with the degree of gastric atrophy in Helicobacter pylori‐infected gastric mucosa.

Aim

To investigate the relationship between PG levels and histological atrophy before and after H. pylori eradication.

Methods

Eradication therapy was conducted on 180 H. pylori‐positive patients with upper gastrointestinal conditions. Endoscopy was performed prior to and at 2, 12 and 24 months after successful eradication therapy. Histological findings were scored using the updated Sydney System in the antrum and the corpus of the stomach. Pepsinogen was measured.

Results

Pepsinogen I levels dropped significantly at 2 months after the eradication. By 12 months and 24 months post‐eradication they had risen again. Histological improvement was seen in atrophy at all sites at 24 months after the eradication. A significant correlation between atrophy and pepsinogen I was seen from prior to eradication. The correlation coefficient was greater at 2 months post‐eradication, decreased again at 12 months and was no longer significant at 24 months.

Conclusions

Our results suggest that pepsinogen levels correlate with the degree of gastric mucosal atrophy prior to and soon after successful eradication therapy, but that the degree of correlation subsequently declines over time.
Review article: is there a common principle in the development of gastrointestinal cancers? Stem cells in the origin of cancer
Authors: WRIGHT N. A.
Published: July 2010

Background

Accumulating evidence, outlined in this review, at last provides some elucidation of the orgin of gastrointestinal epithelial tumours.

Methods

New techniques, such as following the process of crypt or gastric gland purification following mutation in genes encoded by the mitochondrial genome, have shown that mutations spead within the proliferative unit, either gastric gland or intestinal crypt, by clonal purification or monoclonal conversion. Spreading otside the crypt or gland then takes place by fission.

Results

Future research should focus on the mecanisim by which mutated stem cells colonize crypts, and on the mechanisms of crypt fission itself.
Interactions between the grading of gastric atrophy associated with Helicobacter pylori infection and the severity of clinical symptoms and delay in gastric emptying in patients with functional dyspepsia
Authors: KADOUCHI K. , TOMINAGA K. , OCHI M. , KAWAMURA E. , SASAKI E. , SHIBA M. , WATANABE T. , FUJIWARA Y. , OSHITANI N. , HIGUCHI K. , SHIOMI S. , ARAKAWA T.
Published: July 2010

Background

Atrophic and inflammatory changes in the gastric mucosa are commonly observed in Japanese patients with functional dyspepsia. However, detailed data regarding the correlation between the severity of these changes and the symptoms of functional dyspepsia are not available.

Aim

To evaluate grading scales of gastric atrophy and inflammation, severity of clinical symptoms, and gastric emptying in patients with functional dyspepsia.

Methods

Ninety‐three patients with dyspepsia were enrolled. The severity of gastric atrophy was graded through serological and histological examination, and gastric inflammation was evaluated histologically. Clinical symptoms were evaluated on the Gastrointestinal Symptoms Rating Scale, including subscales for abdominal pain, acid reflux, diarrhoea, indigestion and constipation. Gastric emptying half‐time was measured using a radioisotope technique.

Results

Helicobacter pylori infection and gastric inflammation influenced neither clinical symptoms nor gastric emptying time. However, a correlation was observed between gastric atrophy as graded by serological examination and indigestion (R = 0.31, P = 0.01). Histological examination also showed a correlation between gastric atrophy and abdominal pain and indigestion (R = 0.31, P = 0.04 and R = 0.35, P = 0.02 respectively).

Conclusion

Gastric atrophy associated with H. pylori infection may be partly responsible for the clinical symptoms experienced by patients with functional dyspepsia.
Colonic mucosal lesions associated with long‐term administration of non‐steroidal anti‐inflammatory drugs
Authors: OHKUSA T. , TERAI T. , ABE S. , KOBAYASHI O. , BEPPU K. , SAKAMOTO N. , KUROSAWA A. , OSADA T. , HOJO M. , NAGAHARA A. , OGIHARA T. , SATO N.
Published: July 2010

Background

Effects of long‐term administration of non‐steroidal anti‐inflammatory drugs (NSAIDs) on the colon have not been well characterized.

Aim

To investigate colonoscopic findings and prevalence of adverse events following long‐term use of NSAIDs.

Methods

The study included 425 patients (mean 66.4 years) treated for over one year with NSAIDs, and 2125 age‐ and sex‐matched patients without NSAIDs as controls. Eligible candidates were selected by medical record review for underlying diseases, pre‐endoscopic symptoms, category of NSAIDs used, and duration of use. We used endoscopy to study lesion characteristics.

Results

The occurrence rate of colonic lesions or bleeding in the NSAIDs user (13/425, 3.1%) was higher than that in controls (28/2125, 1.3%) (p = 0.017). Colitis was found in 10 of the 13 patients. The sigmoid colon, descending colon or both (70.0%) was commonly involved, and showed segmental ischemic colitis features in 8 of the 13 patients (61.5%). Among these, duration of use ranged from 1‐30 years (mean 7.8). Nine of 13 patients (69.2%) took low‐dose aspirin.

Conclusion

The prevalence of colonic lesions in long‐term NSAIDs users is much lower than that of upper gastrointestinal side effects, but higher than that of colonic lesions in non‐NSAIDs users. The most common features of NSAIDs‐associated colitis were segmental ischeznia.
Gastric motility and autonomic activity during obstructive sleep apnea
Authors: URATA M. , FUKUNO H. , NOMURA M. , OGATA T. , ITO S. , NAKAYASU K. , NAKAYA Y.
Published: July 2010

Background

Patients with Obstructive Sleep Apnea Syndrome (OSAS) often experience gastroesophageal reflux disease (GERD).

Aim

To investigate gastric motility and autonomic nervous activity during sleep apnea.

Methods

The subjects of this study were 20 individuals with OSAS who experienced 10 or more sleep apnoea events per hour, as measured with a portable sleep polygraph. A percutaneous electrogastrography (EGG) and fast Fourier transformation analysis was carried out on the results. The mean amplitude was compared for bradygastria, normogastria and tachygastria. Spectral analysis of heart rate variability was performed, and low‐frequency (LF) power, high‐frequency (HF) power and the LF/HF ratio were measured. Oesophagogastroduodenal endoscopy was performed on each subject, and the presence of reflux oesophagitis (RE) was diagnosed according to the Los Angeles (LA) grade classification. Moreover, questionnaire for the diagnosis of reflux disease (QUEST) was carried out.

Results

Normogastria was significantly decreased, and brady‐, tachygastria, or both were increased during sleep apnea (P < 0.01). There was no significant relation between LA grade classification of RE and severity of OSAS. The LF/HF ratio was significantly higher during sleep apnea for patients with RE and OSAS, but the opposite for those with RE without OSAS. Decreased percutaneous arterial oxygen saturation and normogastria were independent risk factors for the severity of RE.

Conclusions

The present study suggested that, in addition to decreased pressure on the pleural cavity, factors affecting the development of RE might include abnormal gastric motility, low oxygen, and increased sympathetic nervous activity during sleep apnea.
Evaluation of gastro‐oesophageal flap valve is useful for diagnosing gastro‐oesophageal reflux disease
Authors: IWAMOTO M. , KATO K. , MIZUNO S. , MIYAMOTO S. , TAKEUCHI R. , IWASAKI A. , ARAKAWA Y.
Published: July 2010

Background

Gastro‐oesophageal flap valve (GEFV) grade correlated with endoscopic reflux oesophagitis (RE) prevalence.

Aim

To investigate relationships among gastro‐oesophageal reflux disease (GERD) symptoms, RE and/or non‐erosive reflux disease (NERD) and GEFV grades in subjects undergoing endoscopy.

Methods

We enrolled 1305 subjects from whom endoscopic results and the results of a self‐administered questionnaire (QUEST) were available. Subjects were evaluated for GERD symptoms (QUEST score), GEFV grade, RE and gastric mucosal atrophy.

Results

Total GERD prevalence, including symptomatic GERD (QUEST score ≥ 4) and/or RE, was 27%. RE grade and prevalence increased with GEFV grade. QUEST scores and GEFV grades showed a positive correlation. NERD prevalence was 14% and increased with GEFV grade, but the relationship was weaker than that between RE and GEFV. Comparing RE‐negative subjects by GEFV grade, GERD symptoms were noted in 10%, 19%, 36% and 52% with GEFV grades I, II, III and IV, respectively. Neither type of gastric mucosal atrophy correlated with GEFV grade.

Conclusions

Total GERD, NERD and RE prevalences increased with GEFV grade. Subjects with high GEFV grades often complain of GERD symptoms, even without RE. Our findings suggest that endoscopic GEFV evaluation provides a useful clinical index for diagnosing GERD.
Differential expression of cyclo‐oxygenase‐2 and nuclear β‐catenin in colorectal cancer tissue
Authors: TATSUGUCHI A. , KISHIDA T. , FUJIMORI S. , TANAKA S. , GUDIS K. , SHINJI S. , FURUKAWA K. , TAJIRI T. , SUGISAKI Y. , FUKUDA Y. , SAKAMOTO C.
Published: July 2010

Background

Both adenomatous polyposis coli (APC) gene mutation and cyclo‐oxygenase (COX)‐2 are thought to play key roles in colorectal carcinogenesis. Nuclear accumulation of β‐catenin results from APC gene mutation, which leads to enhanced transcription and activation of target genes, including cyclin D1. In vitro studies suggest that Cox‐2 transcription is directly regulated by β‐catenin/TCF complexes.

Aim

To investigate the relationship between cellular localization of β‐catenin and COX‐2 in colorectal cancer.

Methods

We performed immunohistochemical analysis of β‐catenin, cyclin D1 and COX‐2 expression in 50 resected colorectal cancer cases.

Results

The proportion of cases positive for cyclin D1 was higher in nuclear β‐catenin‐positive cases than in negative cases (P < 0.001). Serial sections revealed that the co‐localization of cyclin D1 and nuclear β‐catenin was most frequently evident in the tumour cells at the advancing margin of invasive carcinoma. Conversely, there was no association between COX‐2 and nuclear β‐catenin expression, either topographically or statistically. The staining patterns for COX‐2 and nuclear β‐catenin differed; COX‐2 was diffuse and homogeneous, whereas nuclear β‐catenin was focal and preferentially distributed at the invasive margin of cancer cells.

Conclusions

These two important modulators of colorectal tumourigenesis are differentially expressed. Cox‐2 and β‐catenin transcription may be activated by different pathways.
Hypoxia‐inducible factor‐1 alpha and vascular endothelial growth factor expression in ischaemic colitis and ulcerative colitis
Authors: OKUDA T. , AZUMA T. , OHTANI M. , MATSUNAGA S. , MASAKI R. , SATOMI S. , INAGAKI T. , MURAMATSU A. , LEE S. , SUTO H. , ITO Y. , YAMAZAKI Y. , ITO S. , KURIYAMA M.
Published: July 2010

Background

Hypoxia‐inducible factor‐1 alpha (HIF‐1 alpha) is a transcriptional factor induced by ischaemic crisis in many tissues. Vascular endothelial growth factor (VEGF) is an important growth factor that plays a major role in angiogenesis.

Aim

We examined the aetiology and pathophysiology of human ischaemic colitis and ulcerative colitis from the viewpoint of the expression of these two ischaemic factors.

Methods

Thirty‐two patients with ischaemic colitis, 16 with ulcerative colitis and 25 normal controls underwent colonoscopy. Biopsy samples were taken from a colitis lesion and a normal region in the same patient. In the normal controls, four biopsy samples were obtained from each subject. Biopsy samples were subjected to real‐time polymerase chain reaction.

Results

Hypoxia‐inducible factor and VEGF were overexpressed in ischaemic colitis lesions and quickly decreased to normal levels in the healing phase. In contrast, HIF but not VEGF was overexpressed in active ulcerative colitis lesions. In the remission phase of ulcerative colitis, VEGF decreased to low levels, although HIF was continuously overexpressed.

Conclusions

Overexpression of HIF and VEGF contribute to the tolerance of ischaemia in patients with active ischaemic colitis. The inconsistency in their expression might be associated with the chronic intestinal damage characteristic of ulcerative colitis.
Effect of eradication of Helicobacter pylori on genetic instabilities in gastric intestinal metaplasia
Authors: TANAKA A. , WATARI J. , TANABE H. , MAEMOTO A. , FUJIYA M. , ASHIDA T. , DAS K. M. , KOHGO Y.
Published: July 2010

Background

There is little evidence of changes in genetic variations in gastric intestinal metaplasia (GIM) after the eradication of Helicobacter pylori (H. pylori).

Aim

To investigate the effects of H. pylori eradication on genetic GIM variability in patients with and without gastric cancer in a one‐year prospective study.

Methods

We analysed microsatellite instability (MSI) and loss of heterozygosity (LOH) in GIM. Subjects included Gr. A (n = 39): chronic gastritis, and Gr. B (n = 53): intestinal‐type early gastric cancer patients who underwent endoscopic mucosal resection (n = 25) and surgical resection (n = 28).

Results

The frequency of incidence of MSI in GIM was 10.3% and 28.3% for Gr. A and Gr. B, respectively. Gr. B showed a significantly (p = 0.03) higher incidence rate than Gr. A for MSI, but not for LOH. The frequency of MSI declined in both groups post‐eradication, and patients that were positive for MSI before treatment were negative after H. pylori eradication. Unfortunately, however, GIM scores did not decline significantly post‐treatment for either group.

Conclusions

MSI in GIM may be associated with gastric carcinogenesis. H. pylori eradication reduced MSI during the one‐year post‐treatment period, although no histological improvement in GIM was observed. These changes in MSI may explain the decrease in gastric cancer incidence after the eradication of H. pylori.
Molecular mechanisms involved in interleukin‐8 production by normal human oesophageal epithelial cells
Authors: YOSHIDA N. , IMAMOTO E. , UCHIYAMA K. , KURODA M. , NAITO Y. , MUKAIDA N. , KAWABE A. , SHIMADA Y. , YOSHIKAWA T. , OKANOUE T.
Published: July 2010

Background

Increase in interleukin‐8 in the oesophageal mucosa has been associated with the pathogenesis of reflux oesophagitis.

Aim

To assess the effect of bile acids on the interleukin‐8 expression in normal human oesophageal epithelial cells and to determine its molecular mechanisms.

Methods

Human oesophageal epithelial cells were stimulated with unconjugated bile acids, conjugated bile acids and inflammatory cytokines. Protein and mRNA of interleukin‐8 were measured by enzyme‐linked immunosorbent assay and quantitative real‐time polymerase chain reaction, respectively. In addition, we examined protein kinases and transcription factors involved in interleukin‐8 synthetic pathways using protein kinase inhibitors and luciferase expression vectors, respectively.

Results

Unconjugated bile acids induced interleukin‐8 production from human oesophageal epithelial cells stronger than conjugated bile acids. However, conjugated bile acids in acidic media resulted in remarkable increase of interleukin‐8 production compared with those in neutral‐pH media. Mutation of the binding site of NF‐kB, AP‐1 and NF‐IL6 abrogated the induction of luciferase activities by 100%, 70% and 30%, respectively. Inhibitor of protein kinase A, protein kinase C or p38 mitogen‐activated protein kinase attenuated the production of interleukin‐8 by cholic acid.

Conclusions

These results indicate that bile acids induce interleukin‐8 expression from oesophageal epithelial cells mainly via the activation of NF‐kB as well as AP‐1.
Gene expression clusters of a lipopolysaccharide‐stimulated pathway in peripheral blood monocytes of Japanese patients with Crohn's disease
Authors: NAITO Y. , TAKAGI T. , MIZUSHIMA K. , UETA M. , KINOSHITA S. , HANDA O. , KOKURA S. , ICHIKAWA H. , YOSHIDA N. , YOSHIKAWA T.
Published: July 2010

Background

Recent reports support the notion that patients with Crohn's disease have a dysregulated innate immune response to endogenous flora.

Aim

To reveal the distinct gene expression clusters of a lipopolysaccharide‐stimulated pathway in the peripheral blood monocytes of Japanese patients with Crohn's disease.

Materials and methods

Total RNA was extracted from peripheral blood monocytes of four patients in the remission stage of Crohn's disease as well as four controls, and gene expression profiles before and after lipopolysaccharide stimulation were investigated using a high‐density oligonucleotide probe array. To focus on innate immunity, the expression of genes to be studied was narrowed down to 118 probe sets which were selected using the following keywords: lipopolysaccharide, toll, myd and tir along with a software of NetAffx Analysis Center.

Results

Using hierarchical clustering analysis, we picked up to 44 and 36 probe sets for which expression had decreased before and after lipopolysaccharide stimulation, respectively, in patients with Crohn's disease compared with healthy volunteers. The expression of TLR5, 7, MyD88, SIGIRR, and Tollip was decreased both before and after lipopolysaccharide stimulation in patients with Crohn's disease.

Conclusion

We found several interesting clusters in monocytes before and after stimulation with lipopolysaccharide. These genes may have been responsible for the immunological differences between the Crohn's disease and control patients.
Inadequate dietary intake but not renal tubular acidosis is associated with bone demineralization in primary biliary cirrhosis
Authors: ALLOCCA M. , CROSIGNANI A. , GRITTI A. , BENETTI A. , ZUIN M. , PODDA M. , BATTEZZATI P. M.
Published: July 2010

Background

Metabolic bone disease associated with primary biliary cirrhosis (PBC) is inadequately characterized. Renal tubular acidosis (RTA) may lead to bone loss through chronic mobilization of skeletal calcium salts to buffer increased acid load.

Aim

To evaluate the prevalence of RTA in PBC and establish the relationships among bone mineral density (BMD), renal function and nutritional status.

Methods

We enrolled 69 female patients with compensated PBC and 35 control patients with chronic hepatitis C. RTA was searched in all patients, and 24‐h dietary recalls were collected at enrolment. BMD was measured by dual‐energy X‐ray absorptiometry at the femur neck, lumbar spine and radius ultradistalis sites.

Results

No patients received a diagnosis of RTA. BMD values (Z‐scores) showed only little deviation from normal population with no difference between PBC and controls. Osteopoenic PBC patients (T‐score < 1) showed significantly lower daily phosphorus intake [median: 672 (288–1374) vs. 921 (253–1923) mg/day; P = 0.037], with a trend towards lower caloric intake than their nonosteopoenic counterparts.

Conclusions

Renal tubular acidosis is uncommon in compensated PBC. Cholestasis is not associated with an increased risk of bone demineralization. Inadequate dietary intake may be a preventable factor contributing to bone loss in PBC.
Systematic review: Helicobacter pylori eradication for the prevention of gastric cancer
Authors: FUCCIO L. , ZAGARI R. M. , MINARDI M. E. , BAZZOLI F.
Published: July 2010

Background

Helicobacter pylori is recognized as one of the most significant risk factors for gastric cancer, and H. pylori eradication has been proposed as a possible primary chemo‐preventive strategy to reduce gastric cancer incidence.

Aim

To evaluate the available evidence on the efficacy of H. pylori eradication in the prevention of gastric cancer.

Methods

Epidemiological, observational and interventional studies, as well as decisional models, were taken into account in this review.

Results

Large‐scale epidemiological studies clearly link H. pylori infection with non‐cardia gastric cancer. Current evidence suggests that, in a subpopulation of treated subjects, H. pylori eradication prevents the progression of preneoplastic lesions. Studies that have attempted to evaluate the effect of H. pylori eradication on the incidence of gastric cancer have not provided definitive answers. H. pylori eradication seems to reduce the incidence of gastric cancer in patients without baseline precancerous gastric lesions. Decisional models suggest that H. pylori screening could be cost‐effective, but there is not yet sufficient evidence to support the setting up of a general screening programme.

Conclusion

Helicobacter pylori eradication is a plausible intervention for gastric cancer prevention; however, it seems to be relevant in only a subset of subjects.
Review article: fructose malabsorption and the bigger picture
Authors: GIBSON P. R. , NEWNHAM E. , BARRETT J. S. , SHEPHERD S. J. , MUIR J. G.
Published: July 2010

Fructose is found widely in the diet as a free hexose, as the disaccharide, sucrose and in a polymerized form (fructans). Free fructose has limited absorption in the small intestine, with up to one half of the population unable to completely absorb a load of 25 g. Average daily intake of fructose varies from 11 to 54 g around the world. Fructans are not hydrolysed or absorbed in the small intestine.

The physiological consequences of their malabsorption include increasing osmotic load, providing substrate for rapid bacterial fermentation, changing gastrointestinal motility, promoting mucosal biofilm and altering the profile of bacteria. These effects are additive with other short‐chain poorly absorbed carbohydrates such as sorbitol.

The clinical significance of these events depends upon the response of the bowel to such changes; they have a higher chance of inducing symptoms in patients with functional gut disorders than asymptomatic subjects. Restricting dietary intake of free fructose and/or fructans may have durable symptomatic benefits in a high proportion of patients with functional gut disorders, but high quality evidence is lacking.

It is proposed that confusion over the clinical relevance of fructose malabsorption may be reduced by regarding it not as an abnormality but as a physiological process offering an opportunity to improve functional gastrointestinal symptoms by dietary change.
Pharmacodynamic effects of single doses of rabeprazole 20 mg and pantoprazole 40 mg in patients with GERD and nocturnal heartburn
Authors: WARRINGTON S. , BAISLEY K. , LEE D. , LOMAX K. , DELEMOS B. , BOYCE M. , MOROCUTTI A.
Published: July 2010

Background

Rabeprazole and pantoprazole are both used for symptomatic treatment of gastro‐oesophageal reflux disease (GERD). Speed and duration of acid suppression and intensity of effect after a single dose may be important pharmacodynamic properties in clinical use.

Aim

To compare antisecretory effects of single doses of rabeprazole and pantoprazole in patients with GERD and a history of nocturnal heartburn.

Methods

An open‐label, randomized, two‐way crossover, clinical pharmacology study was conducted. Twenty‐nine Helicobacter pylori‐negative GERD patients (17 men, mean age 44 years), with a history of nocturnal heartburn (mean frequency 4.7 episodes/week), received a single dose of rabeprazole 20 mg or pantoprazole 40 mg, with a 14‐day ‘washout’. Intragastric pH was recorded continuously from 24 h before to 24 h after dosing.

Results

Mean area under the intragastric pH–time curve (AUC) was significantly higher after dosing with rabeprazole 20 mg than with pantoprazole 40 mg in all time intervals analysed, including night (P ≤ 0.02). Mean percentage time with pH > 3 and >4 was significantly greater after rabeprazole than pantoprazole in all time intervals (P ≤ 0.004).

Conclusion

In GERD patients with nocturnal heartburn, a single oral dose of rabeprazole 20 mg increased intragastric pH more than pantoprazole 40 mg did throughout the 24 h after dosing.