bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in biochemical parameters related to atherosclerosis after Helicobacter pylori eradication
Authors: ANDO T. , MINAMI M. , ISHIGURO K. , MAEDA O. , WATANABE O. , MIZUNO T. , FUJITA T. , TAKAHASHI H. , NOSHIRO M. , GOTO H.
Published: July 2010

Background

Recent evidence suggests that Helicobacter pylori infection is involved in the pathogenesis of extra‐gastrointestinal diseases such as coronary heart disease.

Aim

To determine the association of H. pylori infection with biochemical parameters of atherosclerosis in the serum.

Methods

One hundred and fifty‐nine patients with H. pylori‐positive peptic ulcer (duodenal ulcer, n=89; gastric ulcer, n=70) receiving triple therapy were studied prospectively for up to 3 years for clinical parameters associated with inflammation and cardiovascular events. Blood was tested at the time of annual check‐up.

Results

Eradication was successful in 137 patients (86%), and body weight, body mass index (BMI) and TG levels increased gradually each year. No significant hanges were seen in plasma levels of total cholesterol, interleukin‐6 or interleukin‐8, whereas those of HDL‐C increased significantly, and those of C‐reactive protein, fibrinogen and LDL‐C decreased.

Conclusion

There is evidence for the possible implication of H. pylori infection in the etiology of cardiovascular events via its exacerbation of or influence on risk factors of atherogenesis.
Evaluation of the role of Helicobacter pylori as a promoter of gastric cancer from the viewpoint of structural chromosomal aberration
Authors: OHARA T. , KASANUKI J. , MORISHITA T. , YAMAMOTO N. , SHIBAHARA T. , SUZUKI H. , MASAOKA T. , NISHIZAWA T. , HIBI T.
Published: July 2010

Aim

To examine whether Helicobacter pylori induces structural chromosomal aberrations, such as loss of heterozygosity (LOH) and microsatellite instability (MSI) in the infected gastric mucosa.

Methods

Subjects were 13 patients with H. pylori‐positive and 9 with H. pylori‐negative gastric cancer and 20 patients with H. pylori‐positive and 4 patients with H. pylori‐negative chronic gastritis. Gastric mucosal tissues were endoscopically sampled from each subject. Each sample was checked for structural chromosomal aberrations (LOH and MSI) by PCR and microsatellite analysis, using a total of 31 primers corresponding to the regions containing the major genes of chromosomes 1q, 5q, 7q, 17p, 17q, 18q and 21q.

Results

All tissue samples obtained from cancer‐affected regions of the stomach had structural chromosomal aberrations (LOH or MSI), irrespective of H. pylori infection. The degree of structural chromosomal aberration was greater in poorly differentiated than well‐differentiated adenocarcinoma. In addition, structural chromosomal aberrations were also found in a few samples obtained from the chronic atrophic gastritis group, irrespective of H. pylori infection.

Conclusions

It seems unlikely that H. pylori serves as a direct promoter of gastric cancer, and H. pylori‐positive chronic gastritis may not always be a precancerous state.
Helicobacter pylori eradication and metachronous gastric cancer after endoscopic mucosal resection of early gastric cancer
Authors: NAKAGAWA S. , ASAKA M. , KATO M. , NAKAMURA T. , KATO C. , FUJIOKA T. , TATSUTA M. , KEIDA K. , TERAO S. , TAKAHASHI S. , UEMURA N. , KATO T. , AOYAMA N. , SAITO D. , SUZUKI M. , IMAMURA A. , SATO K. , MIWA H. , NOMURA H. , KAISE M. , OOHARA S. , KAWAI T. , URABE K. , SAKAKI N. , ITO S. , NODA Y. , YANAKA A. , KUSUGAMI K. , GOTO H. , FURUTA T. , FUJINO M. , KINJYOU F. , OOKUSA T.
Published: July 2010

Aim

To conduct a retrospective multicentre study at 31 medical centres in Japan, to investigate the association between the eradication of Helicobacter pylori and the development of new gastric cancer after endoscopic mucosal resection (EMR) for early gastric cancer.

Methods

Patients included those in whom early gastric cancer had been removed by EMR, and who had received follow‐up endoscopic treatment. All patients underwent follow‐up endoscopic treatment at least once a year after the initial EMR. The rate of new gastric cancer development was compared among those patients for whom H. pylori had been successfully eradicated and those with persistent H. pylori infection.

Results

The study included 2835 patients with a median follow‐up period of 2 years (range 0.5–12 years). Helicobacter pylori was eradicated in 356 patients (13%). Metachronous gastric cancers developed in eight (2%) patients among those who had been successfully treated for H. pylori, compared with 129 patients (5%) among those with persistent H. pylori infection (P = 0.021; OR = 0.42; 95% CI = 0.20–0.86).

Conclusion

Although longer term, prospective randomized controlled trials are needed to better estimate the extent and sustainability of possible benefits, this study suggests that the eradication of H. pylori may help reduce the incidence of metachronous gastric cancer.
Distribution comparison of depressed vs. non‐depressed early colorectal cancers
Authors: SAKAMOTO N. , TERAI T. , OHKUSA T. , ABE S. , BEPPU K. , KOBAYASHI O. , HIRAI S. , KONNO A. , NAMIHISA A. , OGIHARA T. , FUJII H. , MIWA H. , SATO N.
Published: July 2010

Background

Colorectal depressed tumours have a tendency to invade deeper mucosal layers and metastasize in the lymph nodes, despite their small size.

Aim

To investigate the clinical and endoscopic characteristics of depressed early colorectal cancers (intramucosal and submucosal adenocarcinoma) compared with non‐depressed early cancers.

Methods

Five hundred and seventy consecutive early colorectal cancers obtained through endoscopic resection or surgical operation were studied. Early cancers were endoscopically classified as either the depressed or non‐depressed type. The age and gender of the patients as well as the size and distribution of the cancers were compared between types. The tumour locations were classified into three groups: caecum to transverse colon (right colon), descending to sigmoid colon (left colon) and rectum.

Results

Patients were similar with respect to age and gender. The mean size of the depressed type was smaller than that of the non‐depressed type (mean 8.4 mm vs. 13.3 mm; P < 0.0001). The rate of occurrence of depressed type in the right colon was higher than that of non‐depressed type (49% vs. 23%) (P = 0.0006). Among the early cancers, the incidence of the depressed type in the right colon was higher than that in the left colon and rectum (15% in the right colon, 7% in the left colon and 4% in the rectum; P < 0.01).

Conclusions

Compared with non‐depressed early colorectal cancers, depressed cancers were smaller in size and more likely to be distributed in the right colon.
Helicobacter pylori eradication therapy modulates acidity and interleukin‐1β mRNA levels in un‐operated stomach and in remnant stomach after gastrectomy in gastric cancer patients
Authors: KATO S. , MATSUKURA N. , MATSUDA N. , TSUKADA K. , NAITO Z. , TAJIRI T.
Published: July 2010

Background

A number of studies have indicated that Helicobacter pylori eradication therapy helps prevent secondary cancers in the stomach.

Aim

To investigate the risk of secondary cancer in the residual stomach after gastrectomy by comparing molecular biomarkers from stomach mucosa biopsies and the pH of gastric juice between H. pylori patients with and without gastrectomy.

Methods

Conventional H. pylori eradication therapy was administered to 22 patients who had undergone gastrectomy and to 37 un‐operated patients. We measured pH levels of gastric juice, and collected stomach mucosa biopsy specimens by gastrointestinal fiberscopy. The mRNA expression levels of interleukin‐1β, interleukin‐8 and cyclo‐oxygenase 2 in the biopsy tissues were measured by real‐time polymerase chain reaction.

Results

Interleukin‐1β levels in the antrum of un‐operated H. pylori‐positive patients showed a reverse correlation with pH levels in the gastric lumen (correlation coefficient: −0.50, P = 0.007). After eradication, pH levels were strongly associated with interleukin‐1β mRNA levels, r = 0.83, P = 0.01, which, in the remnant stomach mucosa, decreased from 22.5 to 4.6 in the anastomosis and from 3.1 to 2.4 in the upper corpus, with a simultaneous and statistically significant decrease in pH.

Conclusions

Interleukin‐1β mRNA levels correlated with pH levels in the remnant stomach. This indicates that eradication therapy may contribute not only to a reduction in these cancer‐associated cytokines, but also to an improvement in the internal environment of the remnant stomach.
Twelve years’ progress in surgery for perforated gastric and duodenal ulcers: a retrospective study of indications for laparoscopic surgery, post‐operative course and the influence of Candida infection
Authors: NAKAMURA T. , YOSHIDA M. , OTANI Y. , KAMEYAMA K. , ISHIKAWA H. , KUMAI K. , KUBOTA T. , SAIKAWA Y. , KITAJIMA M.
Published: July 2010

Background

Twelve years has passed since we introduced laparoscopic surgery for gastroduodenal perforation.

Aim

To list problems and to investigate the feasibility of our clinical protocol for treatment of gastroduodenal ulcer perforation.

Methods

Case records of 62 patients and histology samples of 9 patients undergoing surgery for gastroduodenal perforation were retrospectively reviewed.

Results

Laparoscopic omental implantation is feasible for some cases of perforated peptic ulcer in patients who have either stenosis or massive perforations. In patients undergoing laparoscopic omental implantation, oral ingestion of water was started at 3.3 ± 0.5 post‐operative days. Helicobacter pylori was positive in 27 of 35 patients (77%). Of 22 cases in whom intraoperative ascitic culture was taken, Candida was positive in nine (41%), and in six of eight cases involving wound infection or intraperitoneal abscess. Histological examination of resected stomach revealed the fungi with hypha formation at the base of the ulcer in 44% of patients.

Conclusions

Laparoscopic omental implantation was more feasible than in the past. The possibility of Candida infection and subsequent abscess formation must be considered in patients with gastroduodenal ulcer perforation.
Review article: human pepsins – their multiplicity, function and role in reflux disease
Authors: ROBERTS N. B.
Published: July 2010

Human gastric juice contains a multiplicity of proteinases. These are classified as aspartic proteinases because of enzymic activity dependent on two oppositely placed aspartic acids in the active site region. At least seven zones of activity can be visualized by agar gel electrophoresis and a similar number of separate proteins resolved by high performance ion exchange chromatography.

The major enzyme secreted (up to 70% of the total) pepsin 3b is sensitive to the selective inhibitor pepstatin whereas gastricsin or pepsin 5 (20% of the total) is not. Minor enzymes including pepsin 1, which has an associated proteincarbohydrate complex attached is variable and can be <5% in normal and up to 20% of the total as in peptic ulcer patients.

The activity of these enzymes depends on the substrate and pH with significant digestion occurring up to pH 4.5. It has also been shown that these enzymes can bind to substrates like collagen up to pH 5.5.

In gastric secretion studies of patients with reflux oesophagitis the amount of pepsin and the profile of the enzymes in basal secretions, and that after pentagastrin stimulation, was found to be not different from healthy non‐refluxers.

Thus the problem with reflux is that gastric juice appears in the oesophagus, an area without any natural protection from proteolytic damage. The ability to reduce gastric secretion is therefore important in effective treatment. However, being able also to inhibit enzymic activity or protect substrates from damage using alginates offers considerable scope for future therapies.
Systematic review: infliximab therapy in ulcerative colitis
Authors: GISBERT J. P. , GONZÁLEZ‐LAMA Y. , MATÉ J.
Published: July 2010

Aim

To perform a systematic review and meta‐analysis on the efficacy and tolerance of infliximab in ulcerative colitis.

Methods

Selection of studies: evaluating efficacy of infliximab in ulcerative colitis. For the meta‐analysis, randomized clinical trials comparing infliximab vs. placebo/steroids. Search strategy: electronic and manual. Study quality: independently assessed by two reviewers. Data synthesis: meta‐analysis combining the odds ratios (OR).

Results

Thirty‐four studies (896 patients) evaluated infliximab therapy in UC, with heterogeneous results. Mean short‐term (2.3 weeks) response and remission with infliximab was 68% (95% CI 65–71%) and 40% (36–44%). Mean long‐term (8.9 months) response and remission was 53% (49–56%) and 39% (35–42%). Five randomized double‐blind studies compared infliximab with placebo, the meta‐analysis showing an advantage (P < 0.001) of infliximab in all endpoints (short‐/long‐term response/remission): ORs from 2.7 to 4.6, and number‐needed‐to‐treat (NNT) from 3 to 5. Similar infliximab response was calculated independently of the indication (steroid‐refractory/non‐steroid‐refractory) or the dose (5/10 mg/kg). Adverse effects were reported in 83% and 75% of the infliximab and placebo‐treated patients (OR = 1.52; 95% CI 1.03–2.24; number‐needed‐to‐harm (NNH) was 14).

Conclusion

Infliximab is more effective than placebo, with an NNT from 3 to 5, for the treatment of moderate‐to‐severe UC, achieving clinical remission in 40% of the patients at approximately 9 months of follow‐up. Further studies are necessary to confirm the long‐term efficacy of infliximab in ulcerative colitis.
Review article: steroid resistance in inflammatory bowel disease – mechanisms and therapeutic strategies
Authors: CREED T. J. , PROBERT C. S. J.
Published: July 2010

Background

Steroid resistance in inflammatory bowel disease presents a difficult clinical challenge. The advent of biological therapies coupled with an increasing understanding of the pathogenesis of inflammatory bowel disease has provided new therapeutic options.

Methods

We review the available literature of the mechanisms behind steroid resistance. In addition, we outline some of the options available for treating those patients who fail to respond adequately to glucocorticoids.

Results

Approximately 30% of patients prescribed glucocorticoids will not achieve clinical remission. Many such patients are offered immunosuppressive or, recently, biological agents. However, these agents are ineffective in a large proportion of patients. Immunosuppressive agents only bring 40–60% of patients into remission, and biological agents typically induce remission in just 40% of patients. In this review, the possible explanations for glucocorticoid resistance are discussed. Recent evidence suggests that in many patients it is mediated by interleukin‐2. Basiliximab, a biological agent that interrupts interleukin‐2 signalling, has shown significant benefit in early clinical studies.

Conclusions

Patients who fail to respond to steroid therapy should have alternative agents introduced in a timely fashion. Steroid refractory inflammatory bowel disease remains a difficult condition to treat, but new therapies and managements are emerging.
Review article: indeterminate colitis – definition, diagnosis and management
Authors: TREMAINE W. J.
Published: July 2010

Background

The term indeterminate colitis is imprecise and without a generally accepted definition. Nevertheless, it is a term that is commonly used by gastroenterologists, pathologists and surgeons.

Aim

To offer an opinion supported by published data, about the appropriate use of the term indeterminate colitis by addressing a series of questions.

Methods

A PubMed database search was performed using the keywords, ‘colitis’ and ‘inflammatory bowel disease’ each combined individually with the following adjectives: ‘indeterminate’, ‘unclassified’, ‘undefined’, ‘undiagnosed’ and ‘non‐specific’.

Results

There is no generally accepted definition of indeterminate colitis. All current applications of the term rely on exclusionary criteria and there is no confirmatory diagnostic test. Nevertheless, the diagnosis of indeterminate colitis appears to be durable in a subgroup of patients, suggesting that this group represents a unique phenotype.

Conclusions

Indeterminate colitis has expanded from a strictly defined, postcolectomy pathological diagnosis to become, in addition, a clinical diagnosis without generally accepted criteria. A diagnosis of indeterminate colitis should be qualified with descriptors for the diagnostic criteria applied.
Birth outcome in women treated with azathioprine or mercaptopurine during pregnancy: a Danish nationwide cohort study
Authors: LANGAGERGAARD V. , PEDERSEN L. , GISLUM M. , NØRGARD B. , SØRENSEN H. T.
Published: July 2010

Background

Data on birth outcome after exposure to azathioprine or mercaptopurine during pregnancy is sparse.

Aim

To examine the risk of adverse birth outcome among newborns of women exposed to azathioprine or mercaptopurine during pregnancy.

Methods

Data on drug use and births were obtained from Danish population registries. We included 76 exposed pregnancies in 69 women. Of these, we used 64 pregnancies exposed 30 days before conception or during the first trimester to examine the risk of congenital abnormalities, and 65 pregnancies exposed during the entire pregnancy to examine preterm birth and low birth weight at term. Their birth outcomes were compared with outcomes among women who did not fill prescriptions for azathioprine or mercaptopurine during pregnancy.

Results

Azathioprine‐ or mercaptopurine‐exposed women had a higher risk of adverse birth outcomes than unexposed controls. However, when the comparison was limited to newborns of women with the same types of underlying disease, relative risks for spontaneous and induced preterm birth, low birth weight at term, and congenital abnormalities were 1.1 (95% CI: 0.5–2.4), 4.0 (95% CI: 1.5–10.8), 1.7 (95% CI: 0.3–8.7) and 1.1 (95% CI: 0.5–2.9), respectively.

Conclusion

Our results suggest that adverse birth outcomes were caused by the underlying disease rather than by use of azathioprine or mercaptopurine.
Meta‐analysis: the effect of supplementation with probiotics on eradication rates and adverse events during Helicobacter pylori eradication therapy
Authors: TONG J. L. , RAN Z. H. , SHEN J. , ZHANG C. X. , XIAO S. D.
Published: July 2010

Background

Recent evidence found probiotics could inhibit Helicobacter pylori colonization from both in vitro and in vivo studies.

Aim

To systematically evaluate whether adding probiotics to anti‐H. pylori regimens could improve eradication rates and reduce side effects during anti‐H. pylori treatment.

Methods

Eligible articles were identified by searches of electronic databases. We included all randomized trials comparing probiotics supplementation to placebo or no treatment during anti‐H. pylori regimens. Statistical analysis was performed with Review Manager 4.2.8. Subanalysis/Sensitivity analysis was also performed.

Results

We identified 14 randomized trials (n = 1671). Pooled H. pylori eradication rates were 83.6% (95% CI = 80.5–86.7%) and 74.8% (95% CI = 71.1–78.5%) for patients with or without probiotics by intention‐to‐treat analysis, respectively, the odds ratio (OR) was 1.84 (95% CI = 1.34–2.54); the occurrence of total side effects were 24.7% (95% CI = 20.0–29.4%) and 38.5% (95% CI = 33.0–44.1%) for groups with or without probiotics, especially for diarrhoea, the summary OR was 0.44 (95% CI = 0.30–0.66).

Conclusions

Our review suggests that supplementation with probiotics could be effective in increasing eradication rates of anti‐H. pylori therapy, and could be considered helpful for patients with eradication failure. Furthermore, probiotics show a positive impact on H. pylori therapy‐related side effects.
Gastro‐oesophageal reflux disease in chronic laryngitis: prevalence and response to acid‐suppressive therapy
Authors: QUA C. S. , WONG C. H. , GOPALA K. , GOH K. L.
Published: July 2010

Background

Gastro‐oesophageal reflux is thought to cause chronic laryngitis through laryngopharyngeal reflux. Response of laryngitis to treatment with acid‐suppressive therapy supports this causal link.

Aim

To determine the prevalence of gastro‐oesophageal reflux disease in patients with chronic laryngitis and response to proton‐pump inhibitor therapy.

Methods

Patients with chronic laryngitis were recruited. The frequency and severity of reflux and laryngeal symptoms were scored and laryngitis graded by laryngoscopy. All patients underwent esophagogastroduodenoscopy and 24‐h ambulatory pH monitoring before receiving lansoprazole 30 mg b.d. for 8 weeks.

Results

The prevalence of gastro‐oesophageal reflux disease was 65.6% (21 of 32). Based on positive pH test, the prevalence was 25% (eight of 32). The change in laryngeal symptom score and laryngitis grade was significantly higher in GERD compared with non‐GERD patients (P = 0.010 for both). The proportion of patients with marked/moderate improvement in laryngeal symptoms were significantly higher in patients with reflux (14 of 21, 67%) compared to those without reflux (two of 11, 18%; P = 0.026).

Conclusions

The prevalence of gastro‐oesophageal reflux disease amongst our patients with chronic laryngitis was high. The response to treatment with proton‐pump inhibitors in patients with reflux disease compared to those without underlined the critical role of acid reflux in a subset of patients with chronic laryngitis.
Comparison of the effects of immediate‐release omeprazole oral suspension, delayed‐release lansoprazole capsules and delayed‐release esomeprazole capsules on nocturnal gastric acidity after bedtime dosing in patients with night‐time GERD symptoms
Authors: KATZ P. O. , KOCH F. K. , BALLARD E. D. , BAGIN R. G. , GAUTILLE T. C. , CHECANI G. C. , HOGAN D. L. , PRATHA V. S. V.
Published: July 2010

Background

Gastro‐oesophageal reflux disease (GERD) patients on proton pump inhibitors before breakfast or dinner have acid recovery at night. Bedtime immediate‐release omeprazole (IR‐OME) demonstrated better control of nocturnal pH than pantoprazole before dinner.

Aim

To compare repeated once daily bedtime dosing of IR‐OME, lansoprazole and esomeprazole on nocturnal gastric acidity.

Methods

Open‐label, randomized, crossover study enrolling 54 patients with nocturnal GERD symptoms comparing IR‐OME, lansoprazole and esomeprazole at steady state for nocturnal acid breakthrough (NAB), percentage of time with gastric pH > 4 and median gastric pH.

Results

Onset of nocturnal acid control with IR‐OME was rapid. During the first half of the night, percentage of time with gastric pH > 4 and median gastric pH were significantly higher after IR‐OME compared to esomeprazole or lansoprazole (P < 0.001, both comparisons). Over the 8‐h night‐time period, acid control with IR‐OME was significantly better than lansoprazole (P < 0.001), and comparable to esomeprazole. IR‐OME reduced NAB compared with esomeprazole and lansoprazole (61% vs. 92% and 92%; P < 0.001, both comparisons).

Conclusions

Bedtime IR‐OME provided more rapid control of night‐time gastric pH and decreased NAB compared with esomeprazole and lansoprazole. Nocturnal acid control with IR‐OME was superior to lansoprazole and comparable to esomeprazole. Bedtime dosing with IR‐OME may be effective for patients with night‐time heartburn.
Review article: glucagon‐like peptide 2 – current applications and future directions
Authors: WALLIS K. , WALTERS J. R. F. , FORBES A.
Published: July 2010

Background

Glucagon‐like peptide 2 (GLP‐2) is an important peptide growth factor secreted from the human intestine. The trophic properties of GLP‐2 are very specific to the gut where it is pivotal in the regulation of mucosal morphology, function and integrity.

Aims

This review details the current understanding of the molecular biology of GLP‐2, its mechanisms of action and physiological properties. A major focus is the discussion of recent clinical data evaluating the use of GLP‐2 as a therapeutic agent.

Methods

Relevant articles were identified using Medline searches and from the reference lists of key papers.

Results and Conclusions

In the treatment of short bowel syndrome, GLP‐2 has been shown to be highly effective in improving fluid absorption. In Crohn's disease, GLP‐2 is superior to placebo in the induction of remission. Early data also suggest that the effects of GLP‐2 on bone metabolism can provide a new treatment approach for patients with osteoporosis. In the future, the positive effects of GLP‐2 on intestinal barrier function, splanchnic perfusion and mucosal healing could be utilized to expand its therapeutic application to other causes of intestinal injury. However, important safety aspects need to be considered when using this potent growth‐promoting agent for a long term.
Meta‐analysis: Saccharomyces boulardii for treating acute diarrhoea in children
Authors: SZAJEWSKA H. , SKÓRKA A. , DYLAG M.
Published: July 2010

Background

Saccharomyces boulardii is a non‐pathogenic probiotic yeast considered useful against enteropathogens.

Aim

To assess the effectiveness of S. boulardii in treating acute infectious diarrhoea in children.

Methods

The following electronic databases were searched through August 2006 for studies relevant to acute infectious diarrhoea and S. boulardii: MEDLINE, EMBASE, CINAHL and The Cochrane Library; additional references were obtained from reviewed articles. Only randomized‐controlled trials were included.

Results

Five randomized‐controlled trials (619 participants) met the inclusion criteria. Combined data from four randomized‐controlled trials showed that S. boulardii significantly reduced the duration of diarrhoea compared with control. The pooled weighted mean difference was −1.1 days (95% CI: −1.3 to −0.8) with a fixed model and remained significant in a random effect model. Saccharomyces boulardii significantly reduced the risk of diarrhoea on days 3, 6 and 7. Also the risk of diarrhoea lasting >7 days was significantly reduced in the S. boulardii group vs. control group (1 RCT, n = 88, RR 0.25, 95% CI: 0.08–0.83; NNT 5, 95% CI: 3–20).

Conclusions

There exists a moderate clinical benefit of S. boulardii therapy in otherwise healthy infants and children with acute gastroenteritis, mainly a shorter duration of diarrhoea. However, these results should be interpreted with caution due to methodological limitations of the included studies.
The quantitative validation of non‐endoscopic disease activity indices in ulcerative colitis
Authors: HIGGINS P. D. R. , LEUNG J. , SCHWARTZ M. , MAPILI J. , WREN P. A. , ZIMMERMANN E. M.
Published: July 2010

Background

Ulcerative colitis disease activity indices have not been formally validated.

Aim

To analise quantitatively the psychometric and performance validity of two non‐endoscopic indices for ulcerative colitis, the Simple Clinical Colitis Activity Index and the Seo Index.

Methods

In 66 patients with ulcerative colitis, the measurement of disease activity was repeated with the two non‐endoscopic indices, St Mark's Index, and the Inflammatory Bowel Disease Questionnaire. Psychometric validity was evaluated by measuring the content, construct, criterion‐convergent and criterion‐predictive validity on a 0–1 scale. Performance validity was evaluated by measuring the reproducibility and responsiveness on a 0–1 scale.

Results

The Simple Clinical Colitis Activity Index had good to excellent psychometric and performance validity, while the Seo Index had moderate to excellent psychometric validity and moderate to good performance validity. The Simple Clinical Colitis Activity Index had weaknesses in content validity and in responsiveness. The Seo Index had weaknesses in content validity, construct validity and responsiveness.

Conclusions

These two non‐endoscopic indices for ulcerative colitis have good psychometric and performance validity, and are now the most rigorously validated disease activity indices for ulcerative colitis. The Simple Clinical Colitis Activity Index appears to have better overall validity. Quantitative evaluation identifies weaknesses in disease activity indices, and can lead to better disease activity indices for ulcerative colitis.
Efficacy and safety of thalidomide in children and young adults with intractable inflammatory bowel disease: long‐term results
Authors: LAZZERINI M. , MARTELOSSI S. , MARCHETTI F. , SCABAR A. , BRADASCHIA F. , RONFANI L. , VENTURA A.
Published: July 2010

Background

Anti‐tumour necrosis factor‐α antibodies are useful for the treatment of refractory Crohn's disease and ulcerative colitis. Thalidomide is another agent with tumour necrosis factor‐α suppressive properties.

Aim

To investigate the long‐term efficacy and safety of thalidomide in a group of children and young adults with refractory inflammatory bowel disease.

Methods

Twenty‐eight patients with refractory moderate‐severe inflammatory bowel disease (19 Crohn's disease, 9 ulcerative colitis) received thalidomide 1.5–2.5 mg/kg/day. Patients were assessed at baseline, at weeks 2, 4, 8 and 12, and then every 12 weeks by patient's diary, physical examinations, laboratory analyses and scoring on activity indexes. Primary outcomes were: (i) efficacy in inducing remission; and (ii) efficacy in maintaining remission.

Results

Remission was achieved with thalidomide in 21 of 28 (75%) patients (17 with Crohn's disease, 4 with ulcerative colitis). Mean duration of remission was 34.5 months. Sixteen of 20 (80%) patients suspended steroids. Reversible neuropathy occurred in seven of 28 (25%) patients, but only with cumulative doses over 28 g. Other side effects requiring thalidomide suspension were vertigo/somnolence (one of 28), and agitation/hallucinations (one of 28).

Conclusions

Thalidomide seems to be effective in inducing long‐term remission in children and adolescents with intractable inflammatory bowel disease. Neuropathy is the main adverse effect, but appears to be cumulative dose‐dependent, thus allowing long‐term remission before drug suspension.
Meta‐analysis: the efficacy of proton pump inhibitors for laryngeal symptoms attributed to gastro‐oesophageal reflux disease
Authors: GATTA L. , VAIRA D. , SORRENTI G. , ZUCCHINI S. , SAMA C. , VAKIL N.
Published: July 2010

Background

Many investigators have proposed an association between gastro‐oesophageal reflux disease and laryngo‐pharyngeal symptoms, suggesting that medical or surgical therapy for reflux may be useful.

Aim

To perform a meta‐analysis assessing the effectiveness of medical or surgical therapy for reflux disease in adult patients with laryngeal or pharyngeal symptoms presumed to be due to gastro‐oesophageal reflux disease.

Methods

Randomized controlled trials comparing medical or surgical treatments for gastro‐oesophageal reflux disease against placebo were identified by searching MEDLINE (1966–September 2005), EMBASE (1974–September 2005), the CCRCT (until September 2005) and abstracts from gastroenterology and ENT meetings. The relative risks of reporting symptomatic improvement or resolution of symptoms was evaluated using a random‐effects model.

Results

Five studies using high‐dose proton pump inhibitor as intervention met the inclusion criteria and were included in the meta‐analysis. No surgical studies met inclusion criteria. The pooled relative risk was 1.18 (95% confidence interval: 0.81–1.74). There was no heterogeneity between studies but evidence of significant publication bias. Sub‐group analysis performed evaluating Jadad scores and symptom type, did not change the relative risk.

Conclusions

Therapy with a high‐dose proton pump inhibitor is no more effective than placebo in producing symptomatic improvement or resolution of laryngo‐pharyngeal symptoms. Further studies are necessary to identify the characteristics of patients that may respond to proton pump inhibitor therapy.
Combined analysis of three crossover clinical pharmacology studies of effects of rabeprazole and esomeprazole on 24‐h intragastric pH in healthy volunteers
Authors: NORRIS V. , BAISLEY K. , DUNN K. , WARRINGTON S. , MOROCUTTI A.
Published: July 2010

Aim

To compare antisecretory effects of rabeprazole and esomeprazole after single and repeat dosing in Helicobacter pylori‐negative healthy volunteers.

Methods

Results were pooled from three smaller, open, crossover, randomized studies to obtain data from 80 subjects. The studies compared: (a) 5 days’ dosing of 20 mg rabeprazole and esomeprazole (n = 24); (b) single doses of rabeprazole 20 mg and esomeprazole 40 mg (n = 27) and (c) 5 days’ dosing of rabeprazole 10 mg and esomeprazole 20 mg (n = 29). Washout periods were ≥14 days. Intragastric pH was recorded continuously for 24 h on days 0, 1 and 5.

Results

Single doses of rabeprazole 20 mg maintained 24‐h intragastric pH >4 for longer than esomeprazole 20 mg (45% vs. 32%; P < 0.001); rabeprazole 20 mg and esomeprazole 40 mg were equivalent in their effects. After 5 days’ dosing, rabeprazole 20 mg maintained pH >4 for longer than esomeprazole 20 mg (62% vs. 56%; P = 0.046); the reverse was true for esomeprazole 20 mg vs. rabeprazole 10 mg (56% vs. 48%; P = 0.035). In general, intragastric pH AUC during 0–5 h after dosing was higher after esomeprazole than rabeprazole, whereas the reverse was true during the night.

Conclusions

The order of effects on 24‐h pH was: rabeprazole 10 mg ≤ esomeprazole 20 mg < rabeprazole 20 mg = esomeprazole 40 mg. Esomeprazole acts faster, whereas rabeprazole's effect lasts longer.
An open study of modafinil for the treatment of daytime somnolence and fatigue in primary biliary cirrhosis
Authors: JONES D. E. J. , NEWTON J. L.
Published: July 2010

Background

Fatigue is a debilitating symptom which frequently impairs the quality of life of patients with primary biliary cirrhosis (PBC). Although the mechanisms underpinning fatigue in PBC remain unclear, there is an emerging consensus that CNS mechanisms play a key role. It has recently been shown that there is a strong association between abnormalities in sleep regulation, in particular excessive daytime somnolence, and fatigue severity in PBC. The CNS‐acting drug modafinil has an established role in the treatment of excessive daytime somnolence in non‐liver disease states.

Aim

To explore, in an open label study, the responses of PBC patients suffering from significant daytime somnolence and associated fatigue to modafinil therapy.

Methods

All patients in the series (n = 21) underwent daytime somnolence assessment using the Epworth Sleepiness Scale and PBC symptom assessment using the PBC‐40, a multi‐domain, disease specific, psychometrically robust quality of life measure. Modafinil was started at a dose of 100 mg/day and was titrated according to tolerability and response. Patients underwent repeat Epworth Sleepiness Scale and PBC‐40 assessment after 2 months of treatment.

Results

Significant improvement was seen in Epworth Sleepiness Scale scores with modafinil therapy [15 ± 3 vs. 8 ± 6, P < 0.0005 (intention‐to‐treat analysis)]. An equally significant improvement in fatigue severity was also seen [PBC‐40 fatigue domain score (46 ± 6 vs. 34 ± 12, P < 0.0001) (intention‐to‐treat analysis)].

Conclusions

Open label modafinil therapy was associated, where tolerated by patients, with improvement in excessive daytime somnolence and associated fatigue in PBC. Further study in placebo‐controlled trials is warranted.
Chronic celecoxib users more often show regression of gastric intestinal metaplasia after Helicobacter pylori eradication
Authors: YANG H.‐B. , CHENG H.‐C. , SHEU B.‐S. , HUNG K.‐H. , LIOU M.‐F. , WU J.‐J.
Published: July 2010

Background and Aim

To test whether the chronic users of celecoxib, a selective cyclo‐oxygenase‐2 inhibitor, had less Helicobacter pylori‐related intestinal metaplasia or if such users’ intestinal metaplasia could be prone to disappear after H. pylori eradication.

Methods

The study enrolled 150 chronic celecoxib users and 216 non‐users who underwent pan‐endoscopy to detect H. pylori infection and its related intestinal metaplasia. One hundred and three H. pylori‐infected patients with intestinal metaplasia (43 chronic celecoxib users and 60 non‐users) received anti‐H. pylori therapy and completed the 12‐month follow‐up to survey the regression of intestinal metaplasia by mean intestinal metaplasia score.

Results

There were no differences in the prevalence of H. pylori‐related intestinal metaplasia between the chronic celecoxib users and controls (P > 0.05). On the 12th month of follow‐up, chronic celecoxib users had a lower mean intestinal metaplasia score (1.2 vs. 1.8, P < 0.005) and a higher regression rate of intestinal metaplasia (42% vs. 20%, P = 0.027) than non‐users.

Conclusions

With H. pylori infection, chronic celecoxib users still showed limited effects to decrease intestinal metaplasia. Nevertheless, celecoxib should be promising to assist H. pylori eradication for the control of gastric intestinal metaplasia and cancer risk.
Efficacy of tegaserod for functional constipation in Chinese subjects: a randomized double‐blind controlled trial in a single centre
Authors: ON CHAN A. O. , MO HUI W. , LEUNG G. , HU W. H. C. , LAM S. K. , WONG B. C. Y.
Published: July 2010

Background

Tegaserod has been shown to be effective in chronic constipation in Western population.

Aim

We investigated if tegaserod is equally effective in Chinese population.

Materials and methods

Two hundred and fifty patients were randomized to a double‐blinded 8‐week treatment of tegaserod 6 mg b.d. or placebo. Response during weeks 1–4 was defined as an increase in complete spontaneous bowel motion ≥1/week. Secondary efficacy included response during weeks 1–8, individual symptoms and scores, quality of life and global assessment of bowel habits and constipation.

Results

One hundred and nine patients from the treatment group and 107 from the placebo group completed the 8‐week treatment. Responder rates was 47.7% vs. 29% for the treatment and placebo groups (P = 0.005). The sustained complete spontaneous bowel motion rate was 29.4% vs. 15.7% in the two groups (P = 0.016). The response rates were higher than that reported previously in the Caucasian studies. There was improvement in the scores for stool form scale, bothersomeness of constipation, abdominal distension/bloating and satisfaction of bowel habit (P < 0.05). The mental score was higher in the treatment group (46.8 ± 9 vs. 43.6 ± 10,P = 0.01).

Conclusions

Tegaserod is effective in relieving chronic constipation in Chinese population. The efficacy observed may be higher than that in Western population.
Meta‐analysis: Helicobacter pylori eradication treatment efficacy in children
Authors: KHURANA R. , FISCHBACH L. , CHIBA N. , VAN ZANTEN S. V. , SHERMAN P. M. , GEORGE B. A. , GOODMAN K. J. , GOLD B. D.
Published: July 2010

Background  Several meta‐analyses assessing the efficacy of anti‐Helicobacter pylori treatment in adults have been published but a comparable meta‐analysis in children is lacking.

Aims  To summarize the efficacy of treatments aimed at eradicating H. pylori in children and to identify sources of variation in treatment efficacy across studies.

Methods  We searched Medline, reference lists from published study reports, and conference proceedings for anti‐H. pylori treatment trials in children. Weighted meta‐regression models were used to find sources of variation in efficacy.

Results  Eighty studies (127 treatment arms) with 4436 children were included. Overall, methodological quality of these studies was poor with small sample sizes and few randomized‐controlled trials. The efficacy of therapies varied across treatment arms, treatment duration, method of post‐treatment assessment and geographic location. Among the regimens tested, 2–6 weeks of nitroimidazole and amoxicillin, 1–2 weeks of clarithromycin, amoxicillin and a proton pump inhibitor, and 2 weeks of a macrolide, a nitroimidazole and a proton pump inhibitor or bismuth, amoxicillin and metronidazole were the most efficacious in developed countries.

Conclusions  Before worldwide treatment recommendations are given for eradication of H. pylori, additional well‐designed randomized placebo‐controlled paediatric trials are needed, especially in developing countries where both drug resistance and disease burden is high.
Dilated intercellular spaces and acid reflux at the distal and proximal oesophagus in patients with non‐erosive gastro‐oesophageal reflux disease
Authors: CAVIGLIA R. , RIBOLSI M. , GENTILE M. , RABITTI C. , EMERENZIANI S. , GUARINO M. P. L. , PETITTI T. , CICALA M.
Published: July 2010

Background  Acid exposure of proximal oesophagus and dilated intercellular space diameters of oesophageal epithelium are relevant in the perception of gastro‐oesophageal reflux.

Aim  To explain the relationship between gastro‐oesophageal reflux disease symptoms, acid exposure and intercellular space diameter along the oesophageal epithelium and to assess time‐related variability of intercellular space diameter.

Methods  Thirty‐three non‐erosive reflux disease (NERD), six erosive oesophagitis patients and 12 asymptomatic controls underwent oesophageal manometry and 24‐h dual‐channel oesophageal pH‐monitoring following endoscopy. Biopsies were taken 5 cm above the LES and 10 cm below the UES, at comparable levels, as pH sensors. A total of 100 intercellular space diameters per patient/control were measured blindly at transmission electron microscopy. In 15 patients, the investigation was repeated after 1 year.

Results  In all NERD patients, acid exposure was higher at mid‐proximal oesophagus (P < 0.01) and mean intercellular space diameters, at distal and mid‐proximal oesophagus, was three‐ and twofold higher (1.5 and 0.82 μm, respectively) compared with controls. Intra‐patient intercellular space diameter values were stable over time, not overlapping with those of controls.

Conclusions  Dilation of intercellular space diameter occurs along the distal and proximal oesophageal epithelium in NERD patients and could be responsible for the enhanced perception of proximal acid reflux. This finding appears to be time‐reproducible and to represent a sensitive, histopathological marker of NERD.
Thalidomide in luminal and fistulizing Crohn's disease resistant to standard therapies
Authors: PLAMONDON S. , NG S. C. , KAMM M. A.
Published: July 2010

Background  Thalidomide has been shown to be an effective treatment in Crohn's disease.

Aim  To assess the efficacy and tolerability of thalidomide in refractory Crohn's disease patients.

Methods  Twenty‐five patients were treated. Retrospective ‘estimated’ Crohn's Disease Activity Indices were assessed at baseline and at the end of follow‐up. Clinical response was defined as symptomatic improvement and a reduction in the ‘estimated’ Crohn's Disease Activity Index of >100 points, ≥50% reduction in draining fistulas or clinical improvement in perianal ulcers. Clinical remission was defined as symptom resolution and an ‘estimated’ Crohn's Disease Activity Index <150, complete fistula closure or complete ulcer healing.

Results  Six of eight patients treated for luminal disease responded to thalidomide at a median follow‐up of 12 months (three clinical responses, three clinical remissions). The median reduction in ‘estimated’ Crohn's Disease Activity Index was 212 points (P = 0.005). Nine of 11 patients with active fistulizing disease responded to thalidomide (six responses; three remissions). The four patients treated for both luminal and fistulizing disease had fistula response. Three of them had a response in luminal disease activity. One of two patients with ulcerating perianal disease responded. Twelve patients discontinued treatment because of adverse effects (three sedation; two abdominal pain; one leucopoenia; six neuropathy).

Conclusion  Thalidomide is an effective short‐ to medium‐term treatment in selected patients with refractory luminal and fistulizing Crohn's disease. Its long‐term use is limited by toxicity.
GI Epidemiology: nonalcoholic fatty liver disease
Authors: ANGULO P.
Published: July 2010

Background  Nonalcoholic fatty liver disease (NAFLD) is a common diagnosis in clinical practice. Insulin resistance and oxidative stress play an important role in NAFLD development and progression.

Aim  To review the data available on the epidemiology and natural history of NAFLD as well as the risk factors for its development and the areas where future research is necessary.

Results/Conclusions  NAFLD may affect individuals of any age range and race/ethnicity. NAFLD affects one in three adults and one in ten children/adolescents in the United States. Mortality in patients with NAFLD is significantly higher than in the general population of same age and gender with liver‐related complications being a common cause of death. Liver‐related morbidity and mortality in NAFLD occurs when the disease has progressed to advanced fibrosis and cirrhosis. Further studies are necessary to determine the impact of NAFLD on health‐related quality of life and resources utilization, and to the extent to which preventing the development of the metabolic syndrome would prevent NAFLD development and reduce liver‐related morbidity and mortality. Lifestyle intervention may improve NAFLD, but medications that increase insulin sensitivity and the antioxidant defenses in the liver deserve evaluation in carefully controlled trials.
Patients with irritable bowel syndrome or constipation have an increased risk for ischaemic colitis
Authors: SUH D.‐C. , KAHLER K. H. , CHOI I.‐S. , SHIN H. , KRALSTEIN J. , SHETZLINE M.
Published: July 2010

Aims

To estimate the relative risk for ischaemic colitis in patients with and without irritable bowel syndrome or constipation, and to evaluate the role of irritable bowel syndrome and constipation as confounders in the relationship between commonly used gastrointestinal medications and ischaemic colitis.

Methods

Patient cohorts were identified with the use of longitudinal MarketScan research databases from 1 January 1999 to 31 December 2002. Patients in each study cohort were matched 1:1 with comparable control patients using a propensity score. A Cox proportional hazards models were used to estimate relative risk for ischaemic colitis.

Results

The relative risk for ischaemic colitis was 3.17 and 2.78 times higher for patients with irritable bowel syndrome and constipation, respectively, than for those without these disorders. Patients who were taking an antispasmodic, a proton pump inhibitor, or an H2‐antagonist were at increased risk for ischaemic colitis [relative risk with 95% CI 2.73 (1.41–5.39), 2.00 (1.05–3.79), 2.75 (1.22–6.17) respectively]; however, when these results were adjusted for irritable bowel syndrome or constipation, the relative risks were attenuated and no longer statistically significant.

Conclusions

Patients with irritable bowel syndrome or constipation demonstrated a two‐ to threefold increased risk for ischaemic colitis. Moreover, irritable bowel syndrome and constipation strongly confounded the relationship between gastrointestinal drug use and the risk for ischaemic colitis, suggesting that etiologic studies of ischaemic colitis risk must account for the presence of irritable bowel syndrome or constipation.