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Introduction Resistance to clarithromycin and fluoroquinolones is increasing in many countries. We aimed to assess the efficacy of a tailored PCR-guided triple therapy versus an empirical triple therapy in the treatment of H. pylori infection. Patients and methods French multicenter prospective open-label randomized study to assess H. pylori and resistance to clarithromycin and levofloxacin with GenoType HelicoDR® test. Patients of the control group were treated with empirical therapy of proton pump inhibitor (PPI), amoxicillin, and clarithromycin for 7 days. Patients of the experimental group with clarithromycin-susceptible strains, clarithromycin-resistant/levofloxacin-susceptible strains, and with clarithromycin-resistant/levofloxacin-resistant strains received tailored therapy of PPI, amoxicillin, and clarithromycin for 7 days, PPI, amoxicillin, and levofloxacin for 10 days, and PPI, amoxicillin, and metronidazole for 14 days, respectively. H. pylori eradication was assessed by 13C urea breath test at least 28 days after the end of treatment. Results We included 526 patients: 260 (49.4%) were randomly assigned to empirical triple therapy and 266 (50.6%) to tailored therapy. Clarithromycin and levofloxacin resistances were 23.3% and 12.8%, respectively. Follow-up urea breath test was available for 415 (78.9%) patients. Tailored therapy was superior to empirical therapy in terms of eradication (85.5% vs. 73.1%, RR = 1.85, 95%CI [1.25–2.78], p = 0.003). Findings were consistent in the susceptibility analysis using multiple imputation (RR = 1.61, 95%CI [1.14–2.27], P = 0.003) and per-protocol analysis (RR = 1.89, 95%CI [0.25–2.78], p = 0.003). Conclusion In a country with a high level of clarithromycin resistance, tailored PCR-guided therapy was superior to empirical triple therapy for H. pylori eradication ( https://www.ClinicalTrials.gov : NCT01168063 ).

Summary Background There is no consensus on the standard treatment of gastric mucosa-associated lymphoid tissue (MALT) lymphoma for Helicobacter pylori-negative patients and for patients with persistent disease despite H. pylori eradication. Aim To evaluate the comparative efficacy and safety of alkylating agents and rituximab alone or in combination. Methods In this monocentric retrospective study, which included 106 patients who had not been previously treated with anti-cancer agents, we evaluated the efficacy and safety of oral alkylating agents monotherapy (n = 48), rituximab monotherapy (n = 28) and the therapy combining both drugs (n = 30). Evaluations were performed at weeks 6 (W6), 25 (W25), and 52 (W52) and after 2 years (W104). Results After a median follow-up period of 4.9 years (range 0.4–17.2 years), complete remission and overall response were significantly higher in patients in the combination therapy group at W104 (92% and 100% respectively) compared with patients treated with alkylating agents alone (66% and 68%) and rituximab alone (64% and 73%). The 5-year progression-free survival probabilities were 68%, 70% and 89% in patients treated with alkylating agents alone, rituximab alone and combination therapy respectively. Haematological adverse events were reported in 32 (30%) patients (mostly grade 1) and were more frequent in the two groups receiving alkylating agents (P = 0.05 and P

Resume Les recommandations recentes concernant la prise en charge therapeutique de l’infection par Helicobacter pylori, emanant des conferences de consensus europeennes, nord-americaines et pacifico-asiatiques, tendent a elargir les indications du traitement d’eradication : patients a risque de complication ulcereuse qui vont etre mis sous anti-inflammatoires non steroidiens ; patients sous aspirine a faible dose ayant eu une complication hemorragique ; patients dyspeptiques non investigues de moins de 45 ans sans signes d’alarme ; patients sous inhibiteur de la pompe a protons (IPP) au long cours ; anemie ferriprive inexpliquee ; purpura thrombopenique idiopathique. En ce qui concerne la prevention du cancer gastrique distal, l’eradication est recommandee apres resection gastrique pour cancer, en cas de gastrite atrophique et chez les apparentes au premier degre d’un patient atteint de cancer gastrique. Le traitement de premiere intention recommande en France est la tritherapie amoxicilline-clarithromycine-IPP, permettant une eradication dans environ 70 % des cas. En cas d’echec, le plus souvent du a l’existence d’une resistance a la clarithromycine, il est recommande de remplacer cet antibiotique par le metronidazole. Un antibiogramme est necessaire apres deux echecs. Mais, etant donne que la prevalence de la resistance primaire a la clarithromycine est de presque 20 % en France, la pratique d’un test de sensibilite a la clarithromycine avant tout traitement pourrait etre une approche plus judicieuse, qu’il faut evaluer. Deux autres antibiotiques peuvent etre associes a l’amoxicilline et aux IPP : une fluoroquinolone, la levofloxacine et un derive de la rifampicine, la rifabutine.

Nonsteroidal anti-inflammatory drugs (NSAIDs), other than aspirin, are to some extent metabolized by cytochrome P450 2C9 (CYP2C9). The CYP2C9 359Leu (CYP2C9*3) loss-of-function allele could be a risk factor for acute upper gastrointestinal bleeding (AUGIB) related to the use of NSAIDs other than aspirin. To test this hypothesis, we performed a prospective, multicenter, case-case study in patients hospitalized for AUGIB related to the use of NSAIDs. A total of 131 patients had been treated with aspirin and 57 patients had been treated with an NSAID other than aspirin (non-ASP). In the aspirin group, 12 patients (9.2%) had the CYP2C9 359Leu allele as compared with 19 (33.3%) in the non-ASP group (odds ratio (OR) = 5.0; 95% confidence interval 2.2-11.1, P < 0.0001). In a multivariate analysis, CYP2C9 359Leu remained associated with the non-ASP group (OR = 7.2 (2.6-20.3), P = 0.0002) even though 40% of these patients were under treatment with antiulcer drugs at the time of admission. Therefore the results of the study support the hypothesis that the CYP2C9 359Leu allele is a robust risk factor for AUGIB related to the use of NSAIDs other than aspirin.

Le lymphome gastrique du MALT (mucosa associated lymphoid tissue) est un lymphome B caracterise par une infiltration tumorale de la muqueuse gastrique par des petits lymphocytes caracteristiques du MALT. Le diagnostic histologique difficile necessite des pathologistes entraines. Il peut regresser apres eradication de l’infection a Helicobacter pylori. Le traitement des malades non repondeurs n’est pas consensuel: radiotherapie, chimiotherapie, immunotherapie ± chimiotherapie sont en evaluation. Le risque de cancer gastrique metachrone impose un suivi endoscopique au long cours.

Summary Background : The treatment of acid-related symptoms requires rapid and consistent acid suppression, especially with on-demand regimens. Aim : To compare the antisecretory activity of low-dose rabeprazole and omeprazole in healthy, Helicobacter pylori-negative subjects. Methods : In this randomized, double-blind, placebo-controlled, three-way crossover study, 27 volunteers were given rabeprazole 10 mg, omeprazole 10 mg, or placebo once daily for 7 days with a 10–14-day washout between treatments. Intragastric pH was monitored for 24-h on days 1 and 7 of each treatment. Results : Median gastric pH was significantly higher with rabeprazole than with omeprazole or placebo: day 1: 2.3, 1.4 and 1.3, respectively (P = 0.0056, rabeprazole vs. omeprazole; P

Ethanol undergoes gastric first pass metabolism by alcohol dehydrogenase (ADH). We have shown that cimetidine and famotidine both cause competitive inhibition of human gastric ADH in vitro. However, in a randomized 4-way cross-over study in 12 healthy subjects a 7-day course of treatment with cimetidine (800 mg day-1), ranitidine (300 mg day-1) or famotidine (40 mg day-1), did not modify the pharmacokinetics of ethanol given as a post-prandial 0.3 g kg-1 dose. We conclude that gastric mucosal concentrations of histamine H2-receptor blockers achieved after oral dosing are probably too low to cause significant inhibition of gastric ADH in vivo.

A specific technique for detection of pulmonary aspiration during the perioperative period is lacking. In this study, we developed a scintigraphic method for its diagnosis. Technetium 99m sulphur colloid was given orally 2 h before an i.v. infusion of propofol in patients undergoing elective colonoscopy. During the procedure, patients were spontaneously breathing 100% oxygen via a face mask. After recovery from anaesthesia, patients had a chest scinti-scan. As a control group, 10 healthy men were studied. The lung scan was considered positive if any tracer activity greater than background level was detected in the lung field. Among 96 patients studied, three patients had a positive chest scinti-scan. One of the three patients developed pneumonia while the other two remained asymptomatic. In none of the control asymptomatic group was tracer detected in the chest. We suggest that this technique is specific and can be used as a tool to assess the risk of pulmonary aspiration during different anaesthetic procedures.

This is the first reported case of a histologically-proved mediastinal metastatic site of a transitional cell carcinoma of the bladder.A 61-year-old woman who had undergone a total cystectomy 3 years earlier for transitional cell carcinoma was hospitalized for dysphagia. Endoscopy showed impassable stenosis beginning 25 cm below the dental arch, without any developing endoluminal lesion. Histologic analysis of the biopsy samples identified transitional cell carcinoma infiltration of the muscularis and deep mucosa of the esophagus.Three years after a diagnosis of bladder cancer, invasion of the paraesophageal lymph nodes was accompanied by infiltration of the esophageal muscularis and contiguous mucosa. Esophageal stenoses by carcinomatous mediastinitis are rare; when they occur, it is usually secondary to breast cancer. They are generally treated endoscopically, which entails a risk of perforation.

The treatment of acid-related symptoms requires rapid and consistent acid suppression, especially with on-demand regimens.To compare the antisecretory activity of low-dose rabeprazole and omeprazole in healthy, Helicobacter pylori-negative subjects.In this randomized, double-blind, placebo-controlled, three-way crossover study, 27 volunteers were given rabeprazole 10 mg, omeprazole 10 mg, or placebo once daily for 7 days with a 10-14-day washout between treatments. Intragastric pH was monitored for 24-h on days 1 and 7 of each treatment.Median gastric pH was significantly higher with rabeprazole than with omeprazole or placebo: day 1: 2.3, 1.4 and 1.3, respectively (P = 0.0056, rabeprazole vs. omeprazole; P0.0001, rabeprazole vs. placebo); day 7: 3.7, 2.2 and 1.3, respectively (P = 0.0016 rabeprazole vs. omeprazole; P0.0001, rabeprazole vs. placebo). Time with gastric pH above 4 was significantly higher with rabeprazole than with omeprazole: day 1, 5.8 h vs. 3.7 h, respectively (P0.02); day 7, 10.5 h vs. 4.6 h, respectively (P = 0.0008).Rabeprazole 10 mg provides more rapid acid inhibition compared with omeprazole 10 mg. After 7 days, the time with pH above 4 is more than doubled with rabeprazole 10 mg vs. omeprazole 10 mg.

To compare the efficacy of different regimens in patients in whom previous Helicobacter pylori eradication therapy has failed.In this study named StratHegy patients (n=287) were randomized to receive one of three empirical triple therapy regimens or a strategy based on antibiotic susceptibility. The empirical regimens were omeprazole, 20 mg b.d., plus amoxicillin, 1000 mg b.d., and clarithromycin, 500 mg b.d., for 7 days (OAC7), clarithromycin, 500 mg b.d., for 14 days (OAC14) or metronidazole, 500 mg b.d., for 14 days (OAM14). In the susceptibility-based strategy, patients with clarithromycin-susceptible strains received OAC14, whilst the others received OAM14. The 13C-urea breath test was performed before randomization and 4-5 weeks after eradication therapy.In the intention-to-treat analysis, the eradication rates for empirical therapies were as follows: OAC7, 47.4% (27/57); OAC14, 34.5% (20/58); OAM14, 63.2% (36/57); it was 74.3% (84/113) for the susceptibility-based treatment (P0.01 when compared with OAC7 and OAC14). In patients receiving clarithromycin, the eradication rates were 80% for clarithromycin-susceptible strains and 16% for clarithromycin-resistant strains; in patients receiving OAM14, the eradication rates were 81% for metronidazole-susceptible strains and 59% for metronidazole-resistant strains.Eradication rates of approximately 75% can be achieved with second-line triple therapy based on antibiotic susceptibility testing. If susceptibility testing is not available, OAM14 is an appropriate alternative.

The efficacy of infliximab in ulcerative colitis (UC) and indeterminate colitis has been poorly assessed and preliminary results are conflicting.The records of 30 patients treated with infliximab for ulcerative colitis (n=19) or indeterminate colitis (n=11) were reviewed. Infliximab was given because of steroid resistance (n=18), dependence (n=5) or intolerance (n=7); five patients had failed on cyclosporin; 19 patients had a severe flare-up.Median duration of follow-up was 10 months. In 28 patients with active disease, the response rate was 75% at day 7, with 43% having a complete remission, and 50% at month 1, with 32% having a complete remission. Among the 22 responders, the probability of relapse was 73% at month 6. The probability of complete remission without steroids, taking into account the re-treatment for relapse (n=11), was 57% (95% confidence interval (CI): 45% to 69%) at month 6. The probability of colectomy was 33% (95% CI: 23% to 43%) at month 12. In indeterminate colitis, response rate was only 50% at day 7 and 30% at month 1. Concomitant use of antimetabolite agents was associated with better results.Infliximab was able to induce a rapid response in some patients with UC or indeterminate colitis refractory to conventional treatment. Long-term results were less favourable, with frequent relapses, and about one-third of the patients required a colectomy.

Helicobacter pylori resistance to clarithromycin is relatively frequent in France and is assumed to be the main cause of failure of the proton pump inhibitor-amoxicillin-clarithromycin (proton pump inhibitor-AC) therapy, which is the first-line regimen in France.To determine the respective effects of clarithromycin primary and secondary resistances on efficacy of the proton pump inhibitor-AC regimen and to determine whether failures are associated with persistence of the same strain or with emergence of a new one.A total of 123 H. pylori-infected patients were treated for 7 days with omeprazole 20 mg b.d., amoxicillin 1 g b.d., and clarithromycin 500 mg b.d. Eradication was assessed by breath test in 102 patients. Minimal inhibitory concentrations of clarithromycin were determined by E-test. Strain genotyping was performed by random amplified polymorphic DNA.The pre-treatment and post-treatment prevalences of clarithromycin resistance were 19% (23 out of 123) and 69% (nine out of 13), respectively. The rates of eradication were 68% (69 out of 102), 79% (67 out of 85), and 12% (two out of 17) for all, susceptible and resistant strains, respectively. The post-treatment isolate was available for six patients with a susceptible pre-treatment isolate and a persistent infection. Resistance emerged in two patients and was associated with persistence of the pre-treatment strain in one and with selection of a new strain in the other.In our hospital, failures of the proton pump inhibitor-AC therapy are related to both clarithromycin primary and secondary resistances, but the emergence of secondary resistance does not explain all of the failures in the initial clarithromycin-susceptible group. In that group a new strain can emerge after failure.

There is increasing evidence that some organ-specific and generalized autoimmune diseases in humans might be related to a breakdown of oral tolerance. We explored this hypothesis in human primary glomerulonephritides. We prospectively counted intraepithelial T lymphocytes in the duodenal mucosa (as a marker of rupture of oral tolerance), together with IgA1 and IgA2 mucosal plasma cells, in patients with primary glomerulonephritides.We investigated eight adults with immune-complex glomerulopathy (membranous nephropathy+membranoproliferative glomerulonephritis), 16 adults with an idiopathic nephrotic syndrome, and 25 adults with IgA nephropathy. Patients with glomerulonephritides were compared to two control groups: group 1 consisted of nine healthy adults; group 2 comprised five adults with coeliac disease before dietary gluten withdrawal or during a clinical relapse related to gluten ingestion. (The latter disease is associated with increased numbers of intraepithelial T lymphocytes, and a breakdown of oral tolerance to gliadins is involved in the pathogenesis of coeliac disease). Duodenal fibroscopy was performed under neuroleptanalgesia. Four to six endoscopic biopsy specimens were taken from the second duodenum. Intraepithelial T lymphocytes were blindly counted on paraffin sections stained with haematein-eosin-saffron (HES), within the epithelium of a villus in a zone with at least 100 cells. Mucosal IgA1 and IgA2 plasma cells were blindly counted in a mucosal tissue unit by using specific mouse monoclonal antibodies directed against IgA1 and IgA2, with alkaline phosphatase anti-alkaline phosphatase (APAAP) revelation. As values were not normally distributed, we used non-parametric analysis of variance with the Kruskal-Wallis test, and compared median values by using the non-parametric Mann-Whitney test.Intraepithelial T lymphocytes were significantly more abundant in patients with primary glomerulonephritides and coeliac disease than in healthy controls (P0.0001 in the Kruskal-Wallis test): healthy controls, median 11 (range 4.65-16); immune complex glomerulopathy, 27.45*** (15-93); idiopathic nephrotic syndrome, 16.5** (9-26.5); IgA nephropathy, 26.10*** (11.3-47.5); coeliac disease, 55*** (20-80) (*P0.05; **P0.01; ***P0.005, Mann-Whitney test). No difference was found in the number of duodenal IgA1 and IgA2 plasma cells between controls and patients with primary glomerulonephritides. IgA1 and IgA2 plasma cells were increased in patients with coeliac disease.The significant increase in intestinal intraepithelial T lymphocytes in primary glomerulonephritides suggests a pathophysiological role of oral tolerance breakdown.

Proton pump inhibitors are the most potent pharmacologic inhibitors of gastric acid secretion currently available, and have proven effective in the treatment of gastro-oesophageal reflux disease (GERD). The object of this study was to compare the efficacy and tolerability of a new proton pump inhibitor, rabeprazole at two different dosages, with that of omeprazole in the healing of erosive GERD.Rabeprazole 20 mg once daily (QD) and 10 mg twice daily (BID) were compared with omeprazole 20 mg QD in a double-blind, multicentre, parallel group study involving 310 patients with erosive GERD. The primary efficacy endpoint was oesophageal mucosal healing determined by endoscopy. Secondary endpoints included reduction in symptoms and improvements in quality-of-life scores.The healing rates between both rabeprazole groups and the omeprazole group were equivalent in both the per-protocol and intent-to-treat populations. In the per-protocol population, rabeprazole 20 mg was noted to have a numerical trend toward more rapid daytime heartburn relief. However, by 4 and 8 weeks of treatment, no significant differences were found between groups for secondary endpoints, adverse events, or laboratory abnormalities including elevation of serum gastrin levels.Rabeprazole 20 mg in two different dosing schedules is as effective as omeprazole 20 mg QD with regard to efficacy and tolerability in patients with erosive GERD.

Esomeprazole is the first proton pump inhibitor to be developed as an optical isomer for the treatment of acid-related diseases.Four hundred and forty eight duodenal ulcer patients with Helicobacter pylori infection, confirmed by 13C-urea breath test (UBT), and no current ulcer, were randomised to double-blind treatment with esomeprazole 20 mg twice daily (b.d.) (n=224) or omeprazole 20 mg b.d. (n=224), in combination with amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. for 1 week (EAC and OAC, respectively). A negative UBT at both 4 and 8 weeks after completing therapy indicated successful H. pylori eradication.Intention-to-treat (ITT) analysis comprised 400 patients (EAC, n=204; OAC, n=196) and per protocol (PP) analysis 377 patients (EAC, n=192; OAC, n=185). Eradication rates (95% confidence intervals) for ITT and PP populations were: EAC, 90% (85-94%) and 91% (86-94%); OAC, 88% (82-92%) and 91% (86-95%). Between-group differences in eradication rates were not statistically significant. Both regimens were well tolerated, with an adverse event profile and frequency typical of proton pump inhibitor plus antibiotic combination therapy.Esomeprazole-based triple therapy for 1 week is highly effective in eradicating H. pylori infection in duodenal ulcer disease, offers comparable efficacy to omeprazole-based therapy, and is well tolerated.

Direct or indirect methods are available to diagnose Helicobacter pylori infection. Direct assessment with histopathology, culture, rapide urease test, amplification of gene sequences requires the collection of biopsy samples via an endoscope. Culture is the gold standard, but histopathology is commonly used in clinical practice. Serology, 13C-urea breath test and detection of antigens in stools are indirect methods. In clinical practice, direct assessment is required for the initial diagnosis as only patients with endoscopic lesions need H. pylori eradication. Among indirect methods, serology should be used only in epidemiologic studies. Urea breath test and detection of antigens in stools are the most appropriate methods to assess eradication.

The products released by Helicobacter pylori (H. pylori) in the gastric antral and duodenal mucosa may be involved in mucosal ulceration by stimulating the local formation of cytotoxic factors such as nitric oxide (NO), superoxide or peroxynitrite. The present study investigates the ability of purified H. pylori lipopolysaccharide (LPS) to induce nitric oxide synthase (iNOS) in rat duodenal epithelial cells following in vivo challenge and its interaction with superoxide in promoting cellular damage and apoptosis. H. pylori LPS (0.75-3 mg kg(-1) i.v. or 3-12 mg kg(-1) p.o.) induced a dose - dependent expression of iNOS activity after 5 h in the duodenal epithelial cells, determined by [(14)C] arginine conversion to citrulline. The epithelial cell viability, as assessed by Trypan Blue exclusion and MTT conversion, was reduced 5 h after challenge with H. pylori LPS, while the incidence of apoptosis was increased. The iNOS activity and reduction in cell viability following H. pylori LPS challenge i.v. was inhibited by the selective iNOS inhibitor, 1400 W (0.2-5 mg kg(-1) i.v.). Concurrent administration of superoxide dismutase conjugated with polyethylene glycol (250 - 500 i.u. kg(-1), i.v.), which did not modify the cellular iNOS activity, reduced the epithelial cell damage provoked by i.v. H. pylori LPS, and abolished the increased incidence of apoptosis. These results suggest that expression of iNOS following challenge with H. pylori LPS provokes duodenal epithelial cell injury and apoptosis by a process involving superoxide, implicating peroxynitrite involvement. These events may contribute to the pathogenic mechanisms of H. pylori in promoting peptic ulcer disease.

Skin abnormalities are the most common manifestations in patients with systemic sclerosis but many other organs can be involved. We report here the case of a 61 year-old-man in whom small bowel involvement was the initial presentation of limited systemic sclerosis. The clinical features consisted of recurrent small bowel obstruction without any organic lesion. The patient responded well to erythromycin (125 mg thrice a day before meals) and octreotide (50 microg subcutaneously at bedtime) with complete symptom relief. This permitted recovery of nutritional autonomy for two years. This observation shows that, in patients with intestinal pseudo-obstruction, systemic sclerosis should be considered. The long-term administration of octreotide and erythromycin can be effective in treating small bowel dysmotility in such patients.

Esophageal involvement in Crohn's disease is uncommon. We report here a case with pre-eminent esophageal symptoms and numerous tuberculoid granulomas at histopathological examination. This is an opportunity to review the differential diagnoses and to describe the clinical, endoscopic and histopathological features of this localisation.

Triple therapy based upon omeprazole, amoxycillin and clarithromycin for 7 days is the reference treatment used in France for the eradication of Helicobacter pylori. However, optimal dosages of omeprazole and clarithromycin have not been determined.To compare four eradication regimens using this treatment in patients with non-ulcer dyspepsia.Two hundred and seventy-four patients with symptoms of dyspepsia, normal upper GI endoscopy and a positive urease test were included in the study. A 13C-urea breath test (UBT) was obtained before and 6 weeks after treatment. Patients were randomized to one of the following 7-day regimens: 20 mg omeprazole o.m. plus amoxycillin 1000 mg b.d. plus clarithromycin 250 mg b.d. (O20AC500) or 20 mg omeprazole o.m. plus amoxycillin 1000 mg b.d. plus clarithromycin 500 mg b.d. (O20AC1000) or 20 mg omeprazole b.d. plus amoxycillin 1000 mg b.d. plus clarithromycin 250 mg b.d. (O40AC500) or 20 mg omeprazole b.d. plus amoxycillin 1000 mg b.d. plus clarithromycin 500 mg b.d. (O40AC1000). Compliance was assessed by returned tablet counts. Eradication was defined as conversion from positive 13C-UBT at entry to negative 13C-UBT 6 weeks after cessation of therapy.Two hundred and fifty-eight patients were included in the intention-to-treat (ITT) analysis. From the least to the most effective regimen, eradication rates were: O20AC1000: 60.0% (95% CI: 47.6-72.4), O20AC500: 64.1% (52.3-75.8), O40AC1000: 64.2% (52.7-75.7), O40AC500: 74.6% (64.2-85.0) (N.S.). Overall compliance was good in 92% of patients. The most frequent adverse events were diarrhoea and taste impairment, occurring mainly in the high-dose clarithromycin groups.Eradication rates obtained in this study were lower than those expected on the basis of previously reported studies. This study supports the use of a double dose of omeprazole, although the difference between groups was non-significant, but provides no argument in favour of a high dose of clarithromycin.

Gastric bicarbonate secretion might be modified in portal hypertension as a consequence of the intramucosal increase in prostaglandins and nitric oxide content. Therefore, we studied gastric bicarbonate secretion in control and portal hypertensive rats and investigated the role of prostaglandins and nitric oxide. Basal gastric bicarbonate secretion was studied in rats, using a gastric pH back-titration technique, two weeks after partial portal vein ligation or a sham operation. The effects of the following drugs were investigated: the prostaglandin synthase inhibitor indomethacin (5 mg/kg intravenously), prostaglandin (PGE2) (1 mg/kg intravenously), the nitric oxide synthase inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME, 5 mg/kg intravenously) and N(G)-monomethyl-L-arginine (L-NMMA, 50 mg/kg intravenously), and the nitric oxide donor nitroprusside (5 mmol/liter in the gastric perfusate). Plasma leakage in the gastric wall was also measured after Evans blue dye injection in portal hypertensive and sham-operated rats pretreated by indomethacin (5 mg/kg, intravenously) and L-NAME (5 mg/kg, intravenously). Basal bicarbonate secretion was significantly increased in portal hypertensive rats as compared to controls. After indomethacin, the bicarbonate secretion was significantly reduced to a similar level in both groups. PGE2 increased bicarbonate secretion significantly more in portal hypertensive rats than in sham-operated rats. The NO synthase inhibitor L-NMMA significantly increased bicarbonate secretion in portal hypertensive rats only, while the other inhibitor, L-NAME, increased it significantly more in portal hypertensive than in the sham-operated rats. Plasma leakage in portal hypertensive rats, which was increased in the basal condition as compared to control, was further enhanced by indomethacin but not by L-NAME pretreatment. The nitric oxide donor significantly reduced bicarbonate secretion in portal hypertensive rats to reach a similar level as in sham-operated rats. Basal gastric bicarbonate secretion is increased in portal hypertensive rats. This could be due to an enhanced prostaglandin mucosal level. Nitric oxide, which reduces bicarbonate secretion, may contribute to limiting prostaglandin-induced bicarbonate overproduction.

Resume Introduction Il s’agit du premier cas rapporte de localisation mediastinale d’un carcinome transitionnel de vessie prouve par l’examen histologique. Observation Une femme de 61 ans, ayant eu 3 ans auparavant une cystectomie totale pour carcinome a cellules transitionnelles, a ete hospitalisee pour dysphagie. Une fibroscopie a montre une stenose infranchissable debutant a 25 cm des arcades dentaires sans lesion bourgeonnante endoluminale. L’analyse histologique des prelevements biopsiques a conclu a un carcinome transitionnel infiltrant la musculeuse et la partie profonde de la muqueuse œsophagienne. Discussion Trois ans apres le diagnostic d’un cancer de vessie, un envahissement des ganglions peri-œsophagiens s’est accompagne d’une infiltration de la musculeuse et de la muqueuse œsophagienne par contiguite. Les stenoses œsophagiennes par mediastinite carcinomateuse sont rares. Elles surviennent habituellement en cas de cancer du sein. Leur traitement est en general endoscopique, avec risque de perforation.

Circulating IgA class anti-endomysium and anti-reticulin antibodies are reliable serological markers for the diagnosis of coeliac disease. The aim of this study was to evaluate their diagnostic sensitivity and specificity, and their prevalence in a group of coeliac adults taking a gluten-free diet followed in Ile-de-France.One hundred and forty-five sera from 134 patients were examined for IgA and IgG anti-endomysium and anti-reticulin antibodies by indirect immunofluorescence. Sixty-eight patients were confirmed coeliacs; 8 patients with noncoeliac (unresponsive to a gluten-free diet) duodenal villous atrophy and 58 patients with no villous atrophy served as controls.In active coeliac disease, the sensitivity of anti-endomysium and anti-reticulin antibodies was 88% and 50%, respectively. Their specificity was 100%: they were never detected in case of noncoeliac villous atrophy. Under a strict gluten-free diet, their prevalence was 7% and 0%, respectively.In the studied population, the diagnosis accuracy of IgA anti-endomysium antibodies confirms their usefulness in screening and follow-up of coeliac disease. The absence of anti-endomysium and anti-reticulin antibodies in those cases with noncoeliac villous atrophy suggests that in the latter, different immunopathologic mechanisms, as compared with coeliac disease, are concerned.

Par rapport a l’omeprazole 10 mg, le rabeprazole 10 mg au premier jour de traitement, entraine un controle plus rapide et plus puissant de la secretion acide gastrique diurne et nocturne. De plus, le taux de sujets repondeurs au rabeprazole 10 mg est 2 fois plus important qu’avec l’omeprazole 10 mg.

The gastrojet, a closed loop pH feedback infusion pump capable of maintaining intragastric pH at a target value by infusing H2 blockers at variable rates, was used to assess factors influencing the quantity of famotidine required to maintain intragastric pH above 4 for 24 hours in 34 fed patients with duodenal ulcers. The following factors were considered: sex, age, duration of the disease, previous bleeding, previous poor response to H2 blockers (ulcer unhealed at six weeks, or recurrence within three months during maintenance treatment), activity of the ulcer disease, smoking habits, cirrhosis. The patients had taken no antisecretory drugs for the 15 days before the study. Two standardised meals were given during the study period (from 1000 to 1000). Fifty ml of famotidine (4 mg/ml) was loaded into infusion bags and the pump was programmed to deliver the drug intravenously at 11 rates varying from 0 to 40 microliters/min. The target pH was 4. Mean famotidine use was 111 mg (range 33 to 200), the 23 hour median pH was 5.3, and the mean time during which pH was above 4 was 75.4%. There was a negative correlation (p < 0.001) between famotidine delivery and the inhibition of gastric acidity. Statistical analysis showed that only cirrhosis significantly influenced drug delivery, median pH, and the time during which pH was above 4. Mean drug delivery in the cirrhotic and non-cirrhotic patients was 135 v 97 mg (p < 0.04), 23 hour median pH was 4.7 v 5.6 (p < 0.01), and the mean time at pH > 4 was 65.9 v 81.6% (p < 0.01). There were large interindividual variations in famotidine requirements, but not only cirrhosis was predictive of dose requirement. These results suggest that the appropriate amount of famotidine to treat duodenal ulcer in cirrhotic patients is probably higher than the usually recommended dose.

We report a case of a 32-year-old man admitted for massive rectal bleeding related to a solitary diverticulum of the right colon. A superior mesenteric angiogram performed in emergency indicated the site of bleeding, but the correct diagnosis was only established at the histologic examination of the right colon that was surgically resected.

Patients with cirrhosis often have gastric mucosal lesions associated with portal hypertension. Microvascular changes due to portal hypertension may cause mucosal ischaemia. The decrease in intramucosal pH is used as an index of this condition. In this study we compared the gastric intramucosal pH in patients with cirrhosis and portal hypertension and in control group.Estimates of pH were calculated using the Henderson-Hasselbalch equation, assuming that measured concentrations of CO2 in the gastric lumen (pCO2) and of HCO3- in arterial blood represented intramucosal CO2 and intramucosal HCO3- concentrations, respectively. Tonometer measurements of intragastric CO2, validated in vitro, were made in patients treated by famotidine (10 mg.h-1 continuous infusion) to suppress gastric acid secretion and minimize CO2 production from luminal gastric bicarbonate. Intramucosal pH was determined in 19 control patients (mean age: 50.2 years) and in 25 patients with cirrhosis and portal hypertensive gastropathy (mean age: 54.2 years). In the patients with cirrhosis the severity of mucosal and parietal abnormalities induced by portal hypertension were graded according to endoscopic score from 0 to 9 and endoscopic ultrasonography score from 0 to 3.The mean endoscopic and ultrasonographic scores were 5.0 and 1.8 respectively. The median gastric intramucosal pH of patients with cirrhosis (7.42; range: 7.36 to 7.53) was similar to that of the controls (7.42; range: 7.33-7.51). A positive correlation was found between intramucosal pH and severity of portal hypertensive gastropathy, in the antrum, but not in the fundus.These findings do not support the hypothesis that gastric mucosal lesions are the consequence of ischaemia in patients with cirrhosis.

Frequency and severity of digestive adverse events due to NSAIDs are not similarly estimated by rheumatologists and gastroenterologists. A recent meta-analysis showed that NSAIDs users were at approximately three times greater relative risk for developing serious adverse gastrointestinal events than nonusers. Additional risk factors included age greater than 60 years, previous history of gastrointestinal events and concomitant corticosteroid use. Serious adverse gastrointestinal events are rare and preventive treatments cannot be evaluated with prospective trials. Therefore, the model of acute lesions induced by a 7 days treatment with NSAIDs is used. Most of patients given NSAIDs for a few days have gastric lesions (erosions or submucosal hemorrhage) which do not cause symptoms and spontaneously disappear despite the treatment continues. Evaluation of severity of lesions at day 7 after starting treatment proved to be adequate to compare gastrotoxicity of different NSAIDs and to assess efficiency of gastroprotection drugs. This model is appropriate to evaluate the protective effect of diacerheine.

To study the specificity of gut hyperpermeability in primary glomerulonephritis, we investigated intestinal permeability by means of 51Cr-EDTA testing in 20 healthy individuals and in 30 patients with Immunoglobulin A nephropathy (IgA GN), 25 with idiopathic nephrotic syndrome (INS) and 20 with immune complex glomerulonephritis (IC-GN; membranous+membranoproliferative glomerulonephritis). Gut permeability was statistically increased in each patient group versus the controls [controls: 2% (0.4-3.9); IgA GN: 3.25% (0.7-17.70); INS: 3.71% (0.82-10); IC-GN: 3.40% (0.30-16); results are median (range); p0.005, nonparametric Mann-Whitney test]. An increase in intestinal permeability exceeding the upper limit of control values (95th percentile) was observed in 36% of IgA GN, 60% of INS and 50% of IC-GN patients. We conclude that intestinal permeability is frequently increased in primary glomerulonephritis and may also be increased in types of glomerulonephritis other than IgA GN.

The prevalence and the pathogenesis of gallstones in patients with chronic pancreatitis have never been studied prospectively. The aim of this study was to evaluate prospectively the prevalence of gallstones with ultrasonography and to look for markers of pigment or cholesterol stone formation in gallbladder bile. Ultrasonography was performed in 39 patients and detected gallstones in 7 patients and sludge in 3. Common bile duct and intrahepatic bile duct dilatation were observed in 16 and 13 patients, respectively. Liver biopsies were obtained in 31 patients and cirrhosis was found in 4. There were calcium bilirubinate granules in 7 of the 27 bile samples examined. Cholesterol crystals were not found in any case. The nucleation time (median: 21 days) was higher in patients with chronic pancreatitis than in patients with cholesterol stones (median: 2 days) (P0.001) but was not different from nucleation time in patients either free of stones (median: 21 days) or with pigment stones (median: 21 days). The cholesterol saturation index was similar in patients with chronic pancreatitis and in controls. The 2 patients with chronic pancreatitis who underwent cholecystectomy had pigment stones. Calcium bilirubinate granules were more frequent in patients with intrahepatic bile ducts dilatation (P0.02). In conclusion, this study demonstrates a high prevalence of cholelithiasis in chronic pancreatitis patients. Pigment stone formation could be favored by cholestasis.