bluuebunny/crossref_metadata_2025 huggingface dataset:
Responses of rat myocardial antioxidant defences and heat shock protein HSP72 induced by 12 and 24‐week treadmill training
Authors: Morán M. , Delgado J. , González B. , Manso R. , Megías A.
Published: December 2004

Aim:  The purpose of this study was to determine the effects of both a short (12 weeks) and a long‐term (24 weeks) endurance treadmill‐training programme on the levels of oxidative stress markers, the activity of the enzymatic antioxidants, and the content of the 72 kDa heat shock protein (HSP72) in rat myocardium.

Methods:  Thirty male Wistar rats were randomly assigned to exercise trained (n = 16) and sedentary (n = 14) groups. After 12 week of training, eight rats were killed while the remaining eight continued the training programme until 24 week.

Results:  Seven sedentary controls were killed together with each trained group. Levels of thiobarbituric acid‐reactive substances (TBARS), protein carbonyls, and total and oxidized glutathione (tGSH and GSSG) in myocardial homogenates were unchanged by training irrespective of the protocol duration. However, an increased content of the oxidative stress biomarkers was detected in hearts from both the 24‐week trained rats and their sedentary controls when compared with their corresponding 12‐week groups. The antioxidant enzymatic activities total and mitochondrial superoxide dismutase (tSOD and mtSOD, respectively), glutathione peroxidase (GPX) and glutathione reductase (GR), remained unchanged after the 12‐week training period whereas a significant increase in tSOD and mtSOD activities (18%, P < 0.05) was observed in heart homogenates of 24‐week trained animals as compared with their sedentary controls. HSP72 expression levels were not significantly modified after 12 week of training but a threefold increase was detected after 24 week (P < 0.05).

Conclusion:  These results demonstrate that a long‐term endurance training (24 weeks) induced discrete increases in antioxidant enzyme activities in rat myocardium and elicited a marked enhancement in HSP72 expression levels. However, a shorter training programme (12 weeks), was not effective in increasing heart antioxidant defences.
Evidence that the Na+‐K+ leak/pump ratio contributes to the difference in endurance between fast‐ and slow‐twitch muscles
Authors: Clausen T. , Overgaard K. , Nielsen O. B.
Published: December 2004

Aim:  Muscles containing predominantly fast‐twitch (type II) fibres [ext. dig. longus (EDL)] show considerably lower contractile endurance than muscles containing mainly slow‐twitch (type I) fibres (soleus). To assess whether differences in Na+‐K+ fluxes and excitability might contribute to this phenomenon, we compared excitation‐induced Na+‐K+ leaks, Na+ channels, Na+‐K+ pump capacity, force and compound action potentials (M‐waves) in rat EDL and soleus muscles.

Methods:  Isolated muscles were mounted for isometric contractions in Krebs–Ringer bicarbonate buffer and exposed to direct or indirect continuous or intermittent electrical stimulation. The time‐course of force decline and concomitant changes in Na+‐K+ exchange and M‐waves were recorded.

Results:  During continuous stimulation at 60–120 Hz, EDL showed around fivefold faster rate of force decline than soleus. This was associated with a faster loss of excitability as estimated from the area and amplitude of the M‐waves. The net uptake of Na+ and the release of K+ per action potential were respectively 6.5‐ and 6.6‐fold larger in EDL than in soleus, which may in part be due to the larger content of Na+ channels in EDL. During intermittent stimulation with 1 s 60 Hz pulse trains, EDL showed eightfold faster rate of force decline than soleus.

Conclusion:  The considerably lower contractile endurance of fast‐twitch compared with slow‐twitch muscles reflects differences in the rate of excitation‐induced loss of excitability. This is attributed to the much larger excitation‐induced Na+ influx and K+ efflux, leading to a faster rise in [K+]o in fast‐twitch muscles. This may only be partly compensated by the concomitant activation of the Na+‐K+ pumps, in particular in fibres showing large passive Na+‐K+ leaks or reduced content of Na+‐K+ pumps. Thus, endurance depends on the leak/pump ratio for Na+ and K+.
Impact of functional gastrointestinal disorders on health‐related quality of life: a population‐based case–control study
Authors: Halder S. L. S. , Locke G. R. , Talley N. J. , Fett S. L. , Zinsmeister A. R. , Melton L. J.
Published: December 2004

Background : The health‐related quality of life is impaired in patients with functional gastrointestinal disorders seen in referral centres.

Aim : To determine whether the health‐related quality of life is impaired in subjects with functional disorders in the community and whether any differences can be explained by psychological co‐morbidity.

Methods : In a population‐based, nested, case–control study, subjects reporting symptoms of either dyspepsia or irritable bowel syndrome and healthy controls were interviewed and completed a battery of psychological measures plus a validated, generic, health‐related quality of life measure (Medical Outcomes Study 36‐item short form health survey, SF‐36). The association between irritable bowel syndrome and dyspepsia and the physical and mental composite scores of SF‐36 were assessed with and without adjustment for psychological state.

Results : One hundred and twelve cases (30 dyspepsia, 39 irritable bowel syndrome, 32 dyspepsia and irritable bowel syndrome and 11 gastrointestinal symptoms but not dyspepsia or irritable bowel syndrome) and 110 controls were enrolled. In the unadjusted linear regression models, irritable bowel syndrome (but not dyspepsia) was negatively associated with the physical composite score (P < 0.05); in an adjusted model, the association between the physical health‐related quality of life and irritable bowel syndrome was explained by the Symptom Checklist‐90 somatization score alone. In unadjusted models, irritable bowel syndrome and dyspepsia were each negatively associated with the mental composite score (P < 0.05). The association between the mental health‐related quality of life and dyspepsia remained after adjusting for psychological covariates, but the association between this and irritable bowel syndrome was not significant after adjustment.

Conclusions : In the community, health‐related quality of life is impaired in subjects with irritable bowel syndrome and dyspepsia; however, much of this association can be explained by psychological factors.
Short‐term adverse effects of 5‐aminosalicylic acid agents in the treatment of ulcerative colitis
Authors: Loftus E. V. , Kane S. V. , Bjorkman D.
Published: December 2004

Aim: To determine whether there is a difference in short‐term adverse events in patients with ulcerative colitis treated with mesalazine, olsalazine or balsalazide.

Methods: MEDLINE was searched for articles published until 2002. Randomized trials of oral mesalazine, olsalazine or balsalazide for the treatment of active disease or the maintenance of remission were included. Outcomes of interest were the frequencies of patients experiencing adverse events and those withdrawn due to adverse events.

Results: Forty‐six trials were included. One study of mesalazine vs. sulfasalazine for active colitis showed significantly fewer patients with adverse events with mesalazine. Both balsalazide vs. sulfasalazine studies for active disease showed significantly fewer withdrawals with balsalazide. One trial of balsalazide vs. sulfasalazine for maintenance showed significantly fewer patients with adverse events with balsalazide. Otherwise, no significant differences in safety outcomes were noted.

Conclusion: All three 5‐aminosalicylic acid agents are safe in the short term. In mesalazine‐treated patients, the frequencies of adverse events or withdrawals due to adverse events were comparable with those in placebo‐treated patients and lower than those in sulfasalazine‐treated patients. Overall, adverse events or withdrawals were not significantly more frequent with olsalazine than with placebo or sulfasalazine. Adverse events and study withdrawals on balsalazide were less frequent than those on sulfasalazine.
Registered nurse‐administered propofol sedation for endoscopy
Authors: Chen S. C. , Rex D. K.
Published: December 2004

Propofol has several attractive properties that render it a potential alternative sedative agent for endoscopy. Compared with meperidine and midazolam, it has an ultra‐short onset of action, short plasma half‐life, short time to achieve sedation, faster time to recovery and discharge, and results in higher patient satisfaction. Shorter times to achieve sedation enhance efficiency in the endoscopy unit. Multiple studies have documented the safe administration of propofol by non‐anaesthesiologists. Administration by registered nurses is more cost‐effective than administration by anaesthesiologists. However, the administration of propofol by a registered nurse supervised only by the endoscopist is controversial because the drug has the potential to produce sudden and severe respiratory depression. More information is needed on how training nurses and endoscopists should proceed to give propofol, as well as the optimal level of monitoring to ensure the safety of nurse‐administered propofol.
A randomized controlled trial of calcium with vitamin D, alone or in combination with intravenous pamidronate, for the treatment of low bone mineral density associated with Crohn's disease
Authors: Bartram S. A. , Peaston R. T. , Rawlings D. J. , Francis R. M. , Thompson N. P.
Published: December 2004

Background : Osteoporosis is a common complication of Crohn's disease.

Aim : To study the effect on the bone mineral density of a bisphosphonate (pamidronate) given intravenously, in combination with oral calcium and vitamin D supplements, compared with oral calcium and vitamin D supplements alone.

Methods : Seventy‐four patients with Crohn's disease and low bone mineral density at the lumbar spine and/or hip were randomized to receive either a daily dose of 500 mg of calcium with 400 IU of vitamin D alone or in combination with four three‐monthly infusions of 30 mg of intravenous pamidronate over the course of 12 months. The main outcome measure was the change in bone mineral density at the lumbar spine and hip, measured by dual X‐ray absorptiometry, at baseline and 12 months.

Results : Both groups gained bone mineral density at the lumbar spine and hip after 12 months. There were significant (P < 0.05) changes in the pamidronate group, with gains of + 2.6%[95% confidence interval (CI), 1.4–3.0] at the spine and + 1.6% (95% CI, 0.6–2.5) at the hip, compared with gains of + 1.6% (95% CI, − 0.1–3.2) and + 0.9% (95% CI, − 0.4–2.1) at the spine and hip, respectively, in the group taking vitamin D and calcium supplements alone.

Conclusions : In patients with Crohn's disease and low bone mineral density, intravenous pamidronate significantly increases the bone mineral density at the lumbar spine and hip.
Patient‐led variable dosing with balsalazide as long‐term therapy for maintenance in ulcerative colitis: a 3‐year prospective observational study
Authors: Green J. R. B. , Swan C. H. J. , Gibson J. A. , Kerr G. D. , Swarbrick E. T. , Thornton P. C.
Published: December 2004

Background : The patient‐centred approach is new to the management of ulcerative colitis. To date, it has only been shown to be successful in a short‐term study.

Aim : To assess the feasibility, safety and efficacy of patient‐led dosing using balsalazide in the long‐term treatment of ulcerative colitis.

Methods : This was a 3‐year, two‐cohort, multi‐centre study: one cohort was in stable remission (52 patients) and the other was newly in remission (76 patients) from ulcerative colitis. Two 750‐mg balsalazide capsules were given twice daily for maintenance, increased by 750‐mg increments to a maximum of 6 g for up to 7 days depending on symptom severity. Clinical assessments were made every 12–14 weeks; laboratory assessments were made every 6 months.

Results : The average median daily dose of balsalazide was 3 g (range, 1.5–6 g). In the cohort with stable remission, 23 patients (44%) had relapsed by 3 years [median time to relapse, > 1095 days (36 months)]. In the cohort newly in remission, these values were 45 patients (59%) and 656 days (22 months), respectively. In the cohort with stable remission, the time since last relapse was significantly associated with relapse during the first year of treatment (P < 0.033).

Conclusions : Long‐term, patient‐led, maintenance treatment with balsalazide is well tolerated with a good safety profile and is effective for patients with ulcerative colitis.
Anti‐inflammatory effects of aloe vera gel in human colorectal mucosa in vitro
Authors: Langmead L. , Makins R. J. , Rampton D. S.
Published: December 2004

Background : Oral aloe vera gel is widely used by patients with inflammatory bowel disease and is under therapeutic evaluation for this condition.

Aim : To assess the effects of aloe vera in vitro on the production of reactive oxygen metabolites, eicosanoids and interleukin‐8, all of which may be pathogenic in inflammatory bowel disease.

Methods : The anti‐oxidant activity of aloe vera was assessed in two cell‐free, radical‐generating systems and by the chemiluminescence of incubated colorectal mucosal biopsies. Eicosanoid production by biopsies and interleukin‐8 release by CaCo2 epithelial cells in the presence of aloe vera were measured by enzyme‐linked immunosorbent assay.

Results : Aloe vera gel had a dose‐dependent inhibitory effect on reactive oxygen metabolite production; 50% inhibition occurred at 1 in 1000 dilution in the phycoerythrin assay and at 1 in 10–50 dilution with biopsies. Aloe vera inhibited the production of prostaglandin E2 by 30% at 1 in 50 dilution (P = 0.03), but had no effect on thromboxane B2 production. The release of interleukin‐8 by CaCo2 cells fell by 20% (P < 0.05) with aloe vera diluted at 1 in 100, but not at 1 in 10 or 1 in 1000 dilutions.

Conclusion : The anti‐inflammatory actions of aloe vera gel in vitro provide support for the proposal that it may have a therapeutic effect in inflammatory bowel disease.
Green tea and gastrointestinal cancer risk
Authors: Borrelli F. , Capasso R. , Russo A. , Ernst E.
Published: December 2004

Background : Gastrointestinal cancer is one of the leading causes of cancer mortality in the world. Therefore, numerous efforts are being made to find chemoprotective substances able to reduce its incidence. Amongst these, green tea, one of the most popular beverages world‐wide, has been reported to provide protective effects against gastrointestinal cancer.

Aim : To critically evaluate all epidemiological studies reporting an association between green tea consumption and a reduced risk of gastrointestinal cancer.

Methods : Epidemiological studies of green tea consumption in relation to gastrointestinal cancer or preneoplastic lesions were identified through computerized literature searches using the following databases: Medline (Pubmed), Embase, Amed, CISCOM, Phytobase and Cochrane Library. Only epidemiological studies indicating the type of tea (green tea) and the site of either cancer or precancerous lesions (stomach or intestine) were included. No language restrictions were imposed.

Results : Twenty‐one epidemiological investigations met our inclusion/exclusion criteria.

Conclusion : These studies seemed to suggest a protective effect of green tea on adenomatous polyps and chronic atrophic gastritis formations. By contrast, there was no clear epidemiological evidence to support the suggestion that green tea plays a role in the prevention of stomach and intestinal cancer.
Protein‐predominant meals inhibit the development of gastric tachyarrhythmia, nausea and the symptoms of motion sickness
Authors: Levine M. E. , Muth E. R. , Williamson M. J. , Stern R. M.
Published: December 2004

Background : Meal ingestion has been suggested to reduce susceptibility to the development of gastric tachyarrhythmia, the abnormal activity of the stomach that frequently accompanies nausea.

Aim : To determine the types of meal that are most effective in preventing the development of gastric tachyarrhythmia, nausea and the symptoms of motion sickness provoked by a rotating optokinetic drum.

Method : Participants received a carbohydrate beverage, a protein‐predominant beverage or nothing immediately before exposure to the rotating drum. Subjective symptoms of motion sickness and electrogastrograms were collected during a 6‐min baseline period and a subsequent 16‐min drum rotation period.

Results : Subjective symptoms of motion sickness scores were significantly more severe during the no‐meal condition than during either the protein or carbohydrate condition. Central, peripheral and, to some extent, gastrointestinal symptoms were more severe during the carbohydrate condition than during the protein condition. Gastric tachyarrhythmia increased significantly less from baseline to drum rotation during both the protein and carbohydrate conditions than during the no‐meal condition.

Conclusions : Liquid protein‐predominant meals were most effective in suppressing both the development of gastric tachyarrhythmia and the entire spectrum of motion sickness symptoms, including nausea.
The management of pelvic floor disorders
Authors: Cheung O. , Wald A.
Published: December 2004

Anorectal disorders, such as faecal incontinence, defecation difficulty and conditions associated with anorectal pain, are commonly encountered in the practices of gastroenterologists, urogynaecologists and colorectal surgeons. The evaluation of these disorders has been very much improved by the development and wider availability of diagnostic tests, such as manometry, endo‐anal ultrasound, static and dynamic pelvic magnetic resonance imaging and electromyography. After briefly reviewing the normal anatomy and physiology of the anorectum, the pathophysiology and diagnostic approaches to faecal incontinence, defecation disorders and functional anorectal pain are discussed. Until recently, the management of these disorders has been largely anecdotal. However, our therapeutic armamentarium has been expanded by pharmacological agents, such as nitrates, calcium channel blockers and botulinum toxin, as well as the development of novel techniques, such as sacral nerve stimulation. These and other pharmacological, behavioural and surgical approaches are reviewed with respect to the robustness of evidence to support their efficacy in patients with these disorders.
Metformin in the treatment of patients with non‐alcoholic steatohepatitis
Authors: Uygun A. , Kadayifci A. , Isik A. T. , Ozgurtas T. , Deveci S. , Tuzun A. , Yesilova Z. , Gulsen M. , Dagalp K.
Published: December 2004

Background : Increased insulin resistance is the major pathogenic mechanism in the development of non‐alcoholic steatohepatitis.

Aim : To investigate the therapeutic effect of metformin, a well‐known insulin‐sensitizing agent, in the treatment of non‐alcoholic steatohepatitis.

Methods : Thirty‐six patients with non‐alcoholic steatohepatitis were randomized into two groups. The first group was given lipid and calorie‐restricted dietary treatment alone, and the second group was given metformin 850 mg b.d. plus dietary treatment, for 6 months. The changes in biochemical, sonographic and histological parameters were compared.

Results : The mean serum alanine/aspartate aminotransferase, insulin and C‐peptide levels decreased and the index of insulin resistance improved significantly from baseline in the group given metformin. The mean changes in these parameters in the metformin group were significantly greater than those in the group given dietary treatment alone. Although more patients in the metformin group showed improvement in the necro‐inflammatory activity, compared with the group given dietary treatment alone, no significant differences in necro‐inflammatory activity or fibrosis were seen between the groups.

Conclusion : The data suggest that improvement of the insulin sensitivity with metformin may improve the liver disease in patients with non‐alcoholic steatohepatitis.
Transdermal hormone replacement therapy improves vertebral bone density in primary biliary cirrhosis: results of a 1‐year controlled trial
Authors: Pereira S. P. , O'Donohue J. , Moniz C. , Phillips M. G. , Abraha H. , Buxton‐Thomas M. , Williams R.
Published: December 2004

Background : Retrospective studies have suggested that hormone replacement therapy may reduce the rate of bone loss in primary biliary cirrhosis, but no controlled data are available.

Methods : Forty‐two post‐menopausal women with primary biliary cirrhosis were treated with calcium and vitamin D, either alone (n = 21) or together with transdermal hormone replacement therapy (n = 21). Bone densitometry was performed at baseline and at 1 year, and serum and urinary markers of bone turnover were measured at three‐monthly intervals.

Results : At entry, 17 patients (40%) had spinal or femoral osteopenia (T score − 1 to − 2.5) and nine (21%) had osteoporosis (T < − 2.5). In those given hormone replacement therapy, there was a significant decrease in the mean urinary deoxypyridinoline :creatinine ratios at 3 months (7.8 vs. 6.1 nm/mm creatinine for no hormone replacement therapy vs. hormone replacement therapy; P = 0.04) and a 48% reduction in urinary calcium excretion at 1 year (0.66 vs. 0.32 mm/mm creatinine; P = 0.01). Repeat bone densitometry at 1 year revealed a 2.25% increase in the hormone replacement therapy group (P = 0.02), compared with a non‐significant 0.87% decrease in L2–L4 bone mineral density in those not given hormone replacement therapy. Both treatment regimens were well tolerated, with no increase in cholestasis.

Conclusions : Compared with calcium and vitamin D alone, supplemental treatment with transdermal hormone replacement therapy for 1 year improved the vertebral bone density and urinary markers of bone turnover in post‐menopausal women with primary biliary cirrhosis.
DNA typing for Helicobacter pylori isolates from eradication‐failed patients: comparison of the isolates before and after therapy
Authors: Nada T. , Ando T. , Nobata K. , Tsuzuki T. , Minami M. , Ina K. , Iinuma Y. , Ichiyama S. , Ohta M. , El‐Omar E. , Kusugami K. , Goto H.
Published: December 2004

Background : Failure of Helicobacter pylori eradication occurs frequently despite use of multiple microbial agents.

Aim : We aimed to study differences between H. pylori strains isolated before and after eradication failure.

Methods : We treated 87 patients with peptic ulcer using triple therapy consisting of omeprazole plus combinations of clarithromycin, amoxicillin, or metronidazole. We studied the status of cagA, vacA, and iceA by PCR, and examined the differences in H. pylori isolates by pulsed‐field gel electrophoresis and arbitrary primer polymerase chain reaction. The minimum inhibitory concentration of clarithromycin, amoxicillin, or metronidazole was determined by an agar dilution method.

Results : Eradication therapy failed in 12 patients (14%); H. pylori isolates were obtained from all of these both before and after therapy. After eradication therapy, 10 patients were colonized with the same strain as before therapy, while the other two patients were colonized with different strains from those before therapy. In the former group, one isolate changed from metronidazole‐sensitive to ‐resistant, one changed from clarithromycin‐ and metronidazole‐sensitive to ‐resistant, and four were resistant to clarithromycin or metronidazole both before and after therapy. The other four isolates remained sensitive to clarithromycin and metronidazole after therapy. In the two patients who yielded apparently different isolates after therapy, they changed from clarithromycin‐ and metronidazole‐sensitive to ‐resistant.

Conclusion : Eradication of H. pylori by first‐line therapy is an important goal in the treatment of H. pylori‐positive peptic ulcer, and that appropriate antimicrobial sensitivity testing should be conducted in patients with eradication failure.
Elemental diet modulates the growth of Clostridium difficile in the gut flora
Authors: Iizuka M. , Itou H. , Konno S. , Chihara J. , Tobita M. , Oyamada H. , Toyoshima I. , Sasaki K. , Sato A. , Horie Y. , Watanabe S.
Published: December 2004

Background and aims : Tube feeding is regarded as a risk factor for Clostridium difficile‐associated diarrhoea. Recently, we reported that C. difficile toxin was frequently found in patients receiving an elemental diet. The present study was conducted to clarify whether elemental diets are associated with the growth of C. difficile in the gut flora.

Methods : C. difficile was cultured for 72 h in various concentrations of elemental diet containing 3% thioglycollate, and the growth rate or activity of C. difficile was evaluated by Gram stain or by measuring optical density at 560 nm. Faecal samples from 10 healthy adults were cultured in elemental diet + 3% thioglycollate. RNA was extracted from faeces with glass powder, which can eliminate PCR inhibitors, and mRNA of C. difficile toxin B was measured by reverse transcription PCR.

Results : Maximum OD560 value during culture in thioglycollate‐containing elemental diet was 2.4 times higher than that in thioglycollate alone (P = 0.0163). Viability of C. difficile was decreased in thioglycollate but not in thioglycollate‐containing elemental diet. Toxin B mRNA was detected in five faecal samples (50%) before culture and in all samples after culture.

Conclusions : Our results suggest that an elemental diet can modulate the growth of C. difficile in the gut flora.
Helicobacter pylori eradication treatment modulates epithelial cell proliferation and tissue content of hepatocyte growth factor in the gastric mucosa
Authors: Suzuki M. , Suzuki H. , Masaoka T. , Tanaka S. , Suzuki K. , Ishii H.
Published: December 2004

Background : Although Helicobacter pylori infection is now acknowledged as a major promoter of gastric cancer in humans, the carcinogenetic process of this effect has not been fully elucidated. Precancerous lesions such as intestinal metaplasia, enhanced proliferation of epithelial cells and elevated level of growth factors have been postulated to play a role.

Aim : To analyse a relationship between gastric mucosal proliferation, mucosal content of hepatocyte growth factor and prevalence of intestinal metaplasia before and after successful H. pylori eradication therapy.

Methods : We evaluated 25 H. pylori‐eradicated patients. At initial endoscopic examination, two biopsy tissue samples each were obtained from the antrum and great curvature of the corpus. Tissue content of hepatocyte growth factor and neutrophil myeloperoxidase were measured using an ELISA method, and histological assessment of intestinal metaplasia (haematoxylin and eosin) and proliferating cells (Ki‐67 immunostaining) was performed. The patients were treated with a 1‐week course of triple therapy. At 10 months after successful eradication, biochemical and histological assessments were repeated.

Results : Among all patients (n = 25), no intestinal metaplasia was detected in the corpus mucosa, but was observed in 10 patients (40%) in the antrum. This prevalence ratio was not changed after eradication. A slight decrease in HGF content was demonstrated in both sites, but the level of antral hepatocyte growth factor was significantly decreased in patients with intestinal metaplasia but not in those without. Proliferative index (Ki‐67 positive cells/epithelium) was decreased after eradication therapy in both sites. An increase in proliferative index was observed in the antrum with intestinal metaplasia compared with that without, which significantly decreased after eradication therapy.

Conclusions : H. pylori eradication therapy in the present study afforded an inhibitory effect on epithelial cell proliferation and on the mucosal content of HGF.
Helicobacter bilis infection in biliary tract cancer
Authors: Murata H. , Tsuji S. , Tsujii M. , Fu H. Y. , Tanimura H. , Tsujimoto M. , Matsuura N. , Kawano S. , Hori M.
Published: December 2004

Background:  Biliary tract cancer is a highly fatal disease with poor prognosis, but the aetiology is poorly understood.

Aim:  We aimed to identify Helicobacter bilis infection in the gallbladder in patients with biliary tract disease.

Methods:  Archival gallbladder specimens from 34 patients (14 males and 20 females) with an average age of 61.4 ± 12.2 years (mean ± SE) were retrieved, consisting of 11 cases of gallbladder cancer, three of bile duct cancer, 16 of cholecystolithiasis and four of pancreatic cancer. DNA was extracted and nested PCR using primers specific for 16S rRNA of H. bilis was performed.

Results : Amplification was observed in 3 of 11 gallbladder cancer cases (27.2%) and one of three cases with biliary duct cancer (33.3%). In total, four of 14 cases with biliary tract cancer were positive for H. bilis (28.6%). In addition, the presence of H. bilis was shown in two of 16 cases (12.5%) with cholecystolithiasis. Notably, although the number of cases examined was small, none of the four cases with pancreatic cancer showed the presence of H. bilis infection in the gallbladder without apparent abnormalities.

Conclusion:  H. bilis infection may play a role in biliary tract disease, particularly in biliary tract cancer.
Prevalence of symptomatic gastro‐oesophageal reflux disease in Japanese patients with peptic ulcer disease after eradication of Helicobacter pylori infection
Authors: Yamamori K. , Fujiwara Y. , Shiba M. , Watanabe T. , Tominaga K. , Oshitani N. , Matsumoto T. , Higuchi K. , Arakawa T.
Published: December 2004

Background : The association between cure of Helicobacter pylori infection and the development of gastro‐oesophageal reflux disease is controversial.

Aim : To examine the prevalence of symptomatic GERD (sGERD) in Japanese patients with peptic ulcer disease after successful eradication and identify associated factors affecting sGERD development.

Methods : We retrospectively examined 72 patients (40 gastric ulcer and 32 duodenal ulcer) with successful eradication. Associated factors such as age, gender, drinking and smoking habits, body mass index, presence of gastric atrophy and hiatal hernia were analysed.

Results : Seven (9.7%) of 72 peptic ulcer patients newly developed sGERD. There were no differences in mean age, gender, smoking habit, drinking habit, body mass index, or presence of gastric atrophy and hiatal hernia between the sGERD and non‐sGERD groups, while the proportion of subjects aged over 70 was significantly higher in the sGERD than the non‐sGERD group. Six of 40 patients with gastric ulcer newly developed sGERD while only one of 32 patients with duodenal ulcer developed it.

Conclusion : Approximately 10% of Japanese patients with peptic ulcer disease newly developed sGERD after cure of H. pylori infection. Age > 70 years was associated with development of sGERD. Eradication in patients in this age group should be carefully determined.
Impairment of gastrointestinal motility by nitrate administration: evaluation based on electrogastrographic changes and autonomic nerve activity
Authors: Nomura M. , Uehara K. , Harada K. , Uemura E. , Iga A. , Kawano T. , Nishikado A. , Saito K. , Nakaya Y. , Ito S.
Published: December 2004

Background : Nitrates decrease the tone of the lower oesophageal sphincter, and may thus induce gastro‐oesophageal reflux.

Aim : In the present study, we evaluated electrogastrographic changes and heart‐rate variability before and after the administration of nitrates.

Methods : In 15 patients with chest pain treated with nitrates, electrocardiography and percutaneous electrogastrography were performed before and after administration of nitrates. Autonomic nervous system function was evaluated by spectral analysis of heart‐rate variability and serial changes in low frequency and high frequency power, and the low frequency/high frequency ratio were compared. Electrogastrograms were analysed by obtaining peak power amplitudes and their dominant frequencies.

Results : After the administration of nitrates (isosorbide dinitrate), high frequency power, an index of parasympathetic nervous activity, was significantly decreased, whereas the low frequency/high frequency ratio, an index of sympathetic nervous activity, was significantly increased. The mean peak amplitude of the electrogastrogram significantly increased postprandially both before and after treatment. After isosorbide dinitrate treatment, however, mean peak amplitudes after a meal were significantly lower than those obtained before treatment. The mean dominant frequency of the electrogastrogram did not vary before and after treatment.

Conclusions : The present study suggests that nitrates inhibit gastrointestinal motility by decreasing autonomic nervous activity.
Diversity of vacA and cagA genes of Helicobacter pylori in Japanese children
Authors: Azuma T. , Kato S. , Zhou W. , Yamazaki S. , Yamakawa A. , Ohtani M. , Fujiwara S. , Minoura T. , Iinuma K. , Kato T.
Published: December 2004

Background : Helicobacter pylori infection is generally acquired in childhood and persists as an asymptomatic infection for decades in most infected individuals. Only a minority develops a clinical outcome even in childhood, such as peptic ulcer. It has been reported that H. pylori infection with the type I strain, which expresses the VacA and CagA antigen, is associated with peptic ulcer.

Aim : We examined the diversity of vacA and cagA genes in isolates obtained from Japanese paediatric patients with peptic ulcer or chronic gastritis to investigate the relationship between genetic diversity and clinical outcome.

Methods : The diversity of vacA and cagA genes was investigated by PCR and sequence analysis in 30 isolates obtained from Japanese paediatric patients with peptic ulcer (eight strains) or chronic gastritis (22 strains).

Results : All isolates from Japanese children were cagA‐positive strains. Twenty‐six strains (86.7%) had East Asian type CagA, and 4 (13.3%) had Western type CagA. The predominant vacA genotype was s1c/m1b (22/30, 73.3%). There was no significant association between the diversity of cagA and vacA genes and clinical outcome. All four children infected with Western CagA strain had a history of overseas travel or residence.

Conclusion : The predominant genotype of H. pylori in Japanese children is East Asian CagA and vacA s1c/m1b genotype, regardless of clinical outcome. Japanese H. pylori strains are homogeneously of the East Asian type; however, Western strains can be introduced into Japan concomitant with host movement from foreign countries in childhood.
Evaluation of treatment for gastro‐oesophageal reflux disease with a proton pump inhibitor, and relationship between gastro‐oesophageal reflux disease and Helicobacter pylori infection in Japan
Authors: Muramatsu A. , Azuma T. , Okajima T. , Ohtani M. , Dojo M. , Yamazaki Y. , Kuriyama M.
Published: December 2004

Background : Effective therapy for gastro‐oesophageal reflux disease (GERD) is associated with improvement in health‐related quality of life. It remains unclear whether Helicobacter pylori infection protects against GERD.

Aim : We evaluated the relationship between GERD and H. pylori, and whether the health‐related quality of life score improved after medical treatment.

Methods : We enrolled 151 outpatients with upper abdominal symptoms; 81 patients received omeprazole 20 mg/day for 2 weeks. Health‐related quality of life was assessed using the Gastrointestinal Symptom Rating Scale (GSRS) and the Psychological General Well‐Being (PGWB) index. H. pylori infection was diagnosed by serum antibody or endoscopy and the relationship between GERD and H. pylori was evaluated.

Results : In GERD patients, the mean GSRS score improved from 2.20 to 1.67 following treatment (P < 0.01). The mean GSRS reflux symptom score improved from 2.96 to 1.67 (P < 0.01). The mean PGWB score improved from 96.36 to 107.34 (P < 0.01). All scores in GERD patients significantly improved compared with non‐GERD patients. The H. pylori‐positive ratio was 66.15% in GERD patients and 65.21% in non‐GERD patients (P = 0.94).

Conclusions : Health‐related quality of life is useful for evaluation of proton pump inhibitor treatment in GERD. The presence of H. pylori was not associated with the prevalence of GERD.
Sex differences in mucosal response to Helicobacter pylori infection in the stomach and variations in interleukin‐8, COX‐2 and trefoil factor family 1 gene expression
Authors: Kato S. , Matsukura N. , Togashi A. , Masuda G. , Matsuda N. , Yamada N. , Naito Z. , Matsuhisa T. , Tajiri T.
Published: December 2004

Background : Gastric cancer incidence in men is almost double that in women. We investigated mucosal responses in the stomach against Helicobacter pylori (H. pylori) infections to elucidate the interindividual or sex‐related differences, which may in turn be associated with gastric cancer incidence, mucosal changes of stomach as measured by the Sydney System, and interleukin‐8, cyclooxygenase‐2 and trefoil factor family 1 (TFF1) gene expression.

Methods : An age‐, sex‐, H. pylori status‐ and disease‐matched case−control study was performed in 574 H. pylori‐positive and 225 H. pylori‐negative patients selected from 4125 patients with a diagnosis of benign disease of the stomach. Levels of acute and chronic inflammations, atrophy and intestinal metaplasia scored according to the Sydney System were compared by stomach site and by sex. Two biopsy specimens (antral and corpus gastric mucosa) from patients with benign gastric diseases (142 patients; 72 men, 70 women) were analysed for interleukin‐8, cyclooxygenase‐2 and TFF1 mRNA expression as measured by real‐time PCR.

Results : Inflammation and activity scores in antrum with H. pylori infection were higher in men, but scores declined according to age. Atrophy and intestinal metaplasia scores in corpus with H. pylori infection appeared more severe in men than in women, especially in older patients. In women, atrophy score increased with increasing age, particularly in postmenopausal H. pylori‐negative patients. Interleukin‐8 mRNA induction was detected in both antrum and corpus mucosa in H. pylori infection, but sex differences were not found. Response of cyclooxygenase‐2 mRNA expression against H. pylori infection in the mucosa was higher in men than women. In H. pylori‐negative patients, TFF1 mRNA levels in women were significantly higher than in men, and TFF1 mRNA was significantly lower in positive than negative women.

Conclusions : Sex differences in mucosal responses to H. pylori infection in the stomach may be correlated with sex differences in the incidence of stomach cancer.
Relationship between Helicobacter pylori infection and the prevalence, site and histological type of gastric cancer
Authors: Kato M. , Asaka M. , Shimizu Y. , Nobuta A. , Takeda H. , Sugiyama T. ,   the Members of the Multi‐Centre Study Group
Published: December 2004

Aim : To evaluate the relationship between Helicobacter pylori infection and gastric cancer in Japan.

Methods : This was a multicentre study conducted in various regions in Japan. A total of 6578 individuals as controls and 2503 with histologically confirmed gastric cancer were enrolled. H. pylori status was determined by enzyme‐linked immunosorbent assay (ELISA) for anti‐H. pylori immunoglobulin G (IgG).

Results : The prevalence of H. pylori infection in gastric cancer patients was markedly high in all age groups. In contrast, the rate increased with age among control subjects. The overall prevalence of H. pylori infection in control subjects was 50.2% (3300/6578) vs. 82.8% in gastric cancer patients (2072/2503) (OR = 2.47; 95% CI: 2.19–2.79). The prevalence of H. pylori in early gastric cancer was significantly higher than that in advanced gastric cancer (86.5% vs. 75.7%; OR = 2.06; 95% CI: 1.66–2.55). There were no significant differences in the prevalence of H. pylori between the intestinal and diffuse types of gastric cancer or among gastric cancer in antrum, body and cardia.

Conclusion : H. pylori infection is strongly associated with the development of gastric cancer. The difference in odds ratios among younger and older persons with gastric cancer likely reflects the decrease in prevalence of H. pylori in the population, and is more reflective of the actual risks associated with the infection.
Diagnostic value of culture, histology and PCR for Helicobacter pylori in the remnant stomach after surgery
Authors: Matsukura N. , Tajiri T. , Kato S. , Togashi A. , Masuda G. , Tokunaga A. , Yamada N.
Published: December 2004

Background : Diagnosis of Helicobacter pylori infection in the remnant stomach has not been established.

Aims : To investigate the diagnostic value of culture, histology, PCR and serum IgG against H. pylori (ELISA) with and without eradication therapy in the remnant stomach, compared with the unoperated stomach.

Methods : Biopsy samples for bacterial culture and histological diagnosis of H. pylori were taken from the stoma and upper corpus of the remnant stomach and gastric juice was used for PCR assay.

Results : Bacterial culture‐based diagnosis in the remnant stomach, sensitivity and specificity of culture were 95.1%, 100%; histology 89%, 92.3%; PCR 66%, 89.7%; and ELISA 100%, 50%, respectively, in cases without H. pylori eradication therapy. In assessment of the results of therapy for the remnant stomach, sensitivity and specificity of culture were 100%, 100%; histology 80%, 96.8%; PCR 80%, 91.7%; and ELISA 100%, 0%, respectively.

Conclusion : Bacterial culture had the highest diagnostic value in the remnant stomach as well as unoperated stomach. Sensitivity by histology and PCR was lower in the remnant stomach than the unoperated stomach, but specificity values were equal. Serum ELISA assay was not suitable for the remnant stomach.
Joint involvement in inflammatory bowel disease
Authors: De Vos M.
Published: December 2004

Peripheral involvement of the joints, including pauciarticular, asymmetrical, transitory and migrating synovitis and enthesiopathy, is observed in 10–20% of affected inflammatory bowel disease patients. Recurrence is common and frequently coincides with a flare‐up of intestinal disease. The true prevalence of axial involvement is less well established. Sacroiliitis is a hallmark of spondylitis, but is under‐reported due to its insidious onset and sometimes asymptomatic nature. Radiographic evidence of sacroiliitis is present in about 20–25% of patients. Ankylosing spondylitis, as defined by the Rome criteria, is present in 3–10% of inflammatory bowel disease patients, and is thought to have a different genetic predisposition in these patients compared with ‘classic’ ankylosing spondylitis: whereas the human leucocyte antigen B27 phenotype is present in 90% of patients with ‘classic’ ankylosing spondylitis, the prevalence decreases to only 30% in patients with ankylosing spondylitis secondary to Crohn's disease. Polymorphisms involving CARD15 appear to be a possible genetic trigger: 78% of patients with Crohn's disease and symptomatic or asymptomatic sacroiliitis carry at least one mutation, compared with only 48% of control Crohn's disease patients. Moreover, in other forms of spondyloarthropathy, a similar association has been reported: 42% of patients with spondyloarthropathy and associated asymptomatic chronic gut inflammation, who are considered likely to develop Crohn's disease and ankylosing spondylitis, are carriers of at least one CARD15 mutation, compared with only 7% of patients with normal histology. In addition to genetic markers, clinical features support the relationship between gut and joint pathophysiology. In cases of spondyloarthropathy, a very rapid, substantial and sustained improvement in symptoms has been reported following treatment with infliximab, suggesting an essential role for tumour necrosis factor‐α in spondyloarthropathy, similar to that observed in Crohn's disease.
The chemoprevention of colorectal carcinoma
Authors: Gasche C.
Published: December 2004

This review aims to provide an insight into some of the common pathways involved in the development of colorectal cancer — so‐called chromosomal instability and microsatellite instability. There is both clinical and molecular evidence to show that colorectal cancer development occurs over an extended period of time. Together with a knowledge of the molecular pathogenesis of colorectal cancer, this time window allows physicians to counteract cancer development, a strategy known as chemoprevention. In familial and sporadic colorectal cancer, aspirin, other nonsteroidal anti‐inflammatory drugs and cyclo‐oxygenase‐2 inhibitors have been tested for their ability to reduce polyp and cancer development in clinical studies. In inflammatory bowel disease‐related colorectal cancer, evidence from retrospective case–control studies shows that mesalazine (mesalamine) can reduce the development of dysplastic lesions or cancer. Although the mechanisms behind this are incompletely understood, general anti‐inflammatory, oxygen scavenger and some pro‐apoptotic and cyclo‐oxygenase inhibitory activities of mesalazine are thought to be involved. New molecular evidence points to a direct DNA stabilizing effect of mesalazine, resulting in a significant reduction of spontaneous microsatellite mutations.
The role of nutrition in the treatment of inflammatory bowel disease
Authors: Gassull M. A.
Published: December 2004

Nutrients may be involved in the modulation of the immune response through at least three different mechanisms. First, the intestinal ecosystem plays a pivotal role in the pathogenesis of inflammatory bowel disease, triggering the uncontrolled inflammatory response in genetically predisposed individuals. Nutrients, together with bacteria, are major components of, and can therefore influence, the intestinal environment. Second, as components of cell membranes, nutrients can mediate the expression of proteins involved in the immune response, such as cytokines, adhesion molecules and nitric oxide synthase. The composition of lipids in the cell membrane is modified by dietary changes and can influence cellular responses. Indeed, various epidemiological, experimental and clinical data suggest that the immune response may be sensitive to changes in dietary composition. Finally, suboptimal levels of micronutrients are often found in both children and adults with inflammatory bowel disease, although, with the exception of iron and folate, it is unusual to discover symptoms attributable to these deficits. However, subclinical deficits may have a pathophysiological significance, as they may favour the self‐perpetuation of the disease (due to defects in the mechanisms of tissue repair), cause defective defence against damage produced by oxygen free radicals and facilitate lipid peroxidation. These events can occur even in clinically inactive or mildly active disease, as well as in the development of dysplasia in the intestinal mucosa. Some dietary manipulations have been attempted as primary treatment for rheumatoid arthritis, and specially formulated diets for enteral nutrition have proved to be an effective treatment for Crohn's disease. Most trials, although lacking sufficient patient numbers, have demonstrated a role for dietary manipulation as primary therapy for inflammatory disease. Dietary lipids are one of the most active nutritional substrates modulating the immune response. Recently, it has been demonstrated that lipids may be a key factor explaining the therapeutic effect of clinical nutrition in Crohn's disease.