bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ropivacaine gel in active distal ulcerative colitis and proctitis—a pharmacokinetic and exploratory clinical study
Authors: ARLANDER E. , ÓST Å. , STÅHLBERGS D. , LÓFBERG R. 
Published: July 2010

SUMMARYBackground: Local anaesthetics have anti‐inflammatory effects as indicated by preclinical and explorative clinical data.Objective: To investigate the pharmacokinetics, tolerability and clinical efficacy of the new local anaesthetic ropivacaine in active distal ulcerative colitis.Methods: Twelve patients were openly given 200 mg ropivacaine gel rectally twice daily for 2 weeks in this open study.Results: Mean peak total plasma concentrations,Cmaxwere 1.37, 1.26, 1.03 and 0.99 mg/L on treatment days 1, 3, 7 and 14. The mean unbound plasma concentrations atCmaxwere 0.071, 0.058, 0.050 and 0.045 mg/L. The decrease inCmax(P< 0.01) as well as in the area under the plasma concentration‐time curve, AUC (P< 0.01), may be due to a decreased absorption but an increased metabolism cannot be excluded. The median time ofCmaxwas around 2 h and the mean terminal half‐life was around 2.7 h. Mucosal inflammation assessed endoscopically at the most severely affected site decreased after 2 weeks of treatment (P< 0.01: blinded) and there was also a trend towards histological improvement (P= 0.06). Clinical symptoms, including total number of stools, blood in stools and diarrhoea increased (P< 0.05) during the study. The treatment was, in general, well tolerated with few gastrointestinal complaints and there were no unequivocal signs of systemic effects.Conclusions: Ropivacaine given rectally as a gel, 200 mg twice daily does not accumulate over a 2‐week treatment period and carries a low risk for systemic adverse effects. The results suggest a therapeutic efficacy in active distal ulcerative colitis.
The effect of omeprazole on gastric juice viscosity, pH and bacterial counts
Authors: GODDARD A. F. , SPILLER R. C. 
Published: July 2010

SUMMARY Background: In vitro studies have shown that pH is an important determinant of mucus structure and function, but the relationshi P in vivo is unclear. Omeprazole increases intragastric pH and also allows bacterial overgrowth. In this study we have assessed the effect of omeprazole on gastric juice viscosity and examined the influence of pH and bacterial overgrowth on the resulting change. Methods: Gastric juice specific viscosity, pH and total bacterial counts were measured in nine healthy male volunteers before and after omeprazole 20 mg twice daily for 1 week. The effect of incubation at pH 2 and 7 was also determined. Viscosity changes were compared with changes in pH and bacterial counts. Results: Mean viscosity fell (P < 0.05) following treatment, though there was a wide range in viscosity both before and after treatment. The decrease was reproduced by incubation of pre‐treatment juice at pH 7 but not pH 2. The fall in viscosity was correlated (P < 0.05) with change in pH. Conclusion: Omeprazole decreases gastric juice, and hence gastric mucus, viscosity by increasing intragastric pH. This could be important if it allows improved penetration of antimicrobials to Helicobacter pylori within the mucus layer.
The effects of omeprazole and famotidine on mucin and PGE2 release in the rat stomach
Authors: YOSHIMURA K. , DELBARRE S. G. , KRAUS E. , BOLAND C. R. 
Published: July 2010

SUMMARY Background: Gastric antisecretory agents may inhibit the synthesis or secretion of gastric mucin during acid suppression, which would interfere with mucosal protection and limit the efficacy of the agents. Methods: Rats were dosed with famotidine, omeprazole, or buffer control for 4 weeks. Mucin synthesis, mucin histochemistry, mucin carbohydrate composition and prostaglandin E2 (PGE2) release were measured during and after drug treatment. Results: PGE2 release was maximally inhibited after 2 weeks of omeprazole or 4 weeks of famotidine. Total glycoprotein synthesis was inhibited at all times by omeprazole, but only after the cessation of dosing with famotidine. Sulphated glycoprotein synthesis was inhibited by both drugs at 2 weeks. PGE2 release and sulphated glycoprotein synthesis were restored to control values or more by the 5th day after the end of dosing, at which time total glycoprotein synthesis was significantly suppressed in both groups. Histologically, a reduction of PAS‐positive surface mucus was observed after 2 weeks of dosing in both groups. Both famotidine and omeprazole reduced the sialic acid content during and after treatment. Conclusions: These results suggest that long‐term anti‐secretory therapy also affects the production of factors involved in primary gastric mucosal defence, which should be considered in the assessment of response to treatment in clinical trials.
Helicobacter pylori infection induces accumulation of Vδ1 T cells via CCR2 upregulation
Authors: FUTAGAMI S. , HIRATSUKA T. , SHINDO T. , HAMAMOTO T. , UEKI N. , SUZUKI K. , KUSUNOKI M. , WADA K. , MIYAKE K. , OHASHI K. , GUDIS K. , TSUKUI T. , SAKAMOTO C. 
Published: July 2010

SummaryBackgroundWe investigated factors that impact γδ T‐cell phenotype accumulation in Helicobacter pylori‐infected gastric mucosa and peripheral blood.AimTo determine whether H. pylori infection induces accumulation of Vδ1 T cells via CC chemokine receptor 2 (CCR2) upregulation.MethodsMucosal biopsy samples from 22 H. pylori‐free and 75 H. pylori‐infected patients were classified into grades I–III gastritis groups as per our previous study. The number of γδ, Vδ1 and Vδ2 T cells was evaluated by immunostaining and then compared with counts in 17 patients after H. pylori eradication. TGF‐β, IFN‐γ and CCR2 mRNA expression levels in Vδ1 T cells stimulated by H. pylori component were also evaluated.Results γδ T‐cell count was significantly higher in grade III gastritis patients, who exhibited strong IgA and IgG responses to H. pylori urease, than in other groups. Vδ1 T cells were found dominantly residing in H. pylori‐infected gastric mucosa, whereas Vδ2 T cells were mainly found in peripheral blood. Vδ1 T‐cell count was significantly reduced after H. pylori eradication therapy. In in vitro studies, H. pylori component stimulation significantly upregulated both TGF‐β and IFN‐γ production in supernatant from stimulated Vδ1 T cells. Moreover, CCR2 mRNA expression in Vδ1 T cells stimulated with H. pylori components was significantly increased.ConclusionAccumulation of Vδ1 T cells may occur through the upregulation of CCR2 expression.
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

SummaryBackgroundRecent evidence suggests that Helicobacter pylori infection is involved in the pathogenesis of extra‐gastrointestinal diseases such as coronary heart disease.AimTo determine the association of H. pylori infection with biochemical parameters of atherosclerosis in the serum.MethodsOne 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.ResultsEradication 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.ConclusionThere 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

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

SummaryAimTo 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.MethodsPatients 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.ResultsThe 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).ConclusionAlthough 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

SummaryBackgroundColorectal depressed tumours have a tendency to invade deeper mucosal layers and metastasize in the lymph nodes, despite their small size.AimTo investigate the clinical and endoscopic characteristics of depressed early colorectal cancers (intramucosal and submucosal adenocarcinoma) compared with non‐depressed early cancers.MethodsFive 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.ResultsPatients 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).ConclusionsCompared 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

SummaryBackgroundA number of studies have indicated that Helicobacter pylori eradication therapy helps prevent secondary cancers in the stomach.AimTo 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.MethodsConventional 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.ResultsInterleukin‐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.ConclusionsInterleukin‐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

SummaryBackgroundTwelve years has passed since we introduced laparoscopic surgery for gastroduodenal perforation.AimTo list problems and to investigate the feasibility of our clinical protocol for treatment of gastroduodenal ulcer perforation.MethodsCase records of 62 patients and histology samples of 9 patients undergoing surgery for gastroduodenal perforation were retrospectively reviewed.ResultsLaparoscopic 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.ConclusionsLaparoscopic 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

SummaryHuman 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

SummaryAimTo 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).ResultsThirty‐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).ConclusionInfliximab 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

SummaryBackgroundSteroid 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.MethodsWe 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.ResultsApproximately 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.ConclusionsPatients 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

SummaryBackgroundThe 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.AimTo offer an opinion supported by published data, about the appropriate use of the term indeterminate colitis by addressing a series of questions.MethodsA 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’.ResultsThere 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.ConclusionsIndeterminate 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.