Do Japanese and Swedish peptic ulcer patients respond differently to Helicobacter pylori eradication therapies and what are their histological features?

BACKGROUND: As a consequence of gastric histological differences, Japanese and Swedish peptic ulcer (PU) patients may respond differently to Helicobacter pylori eradication therapies. METHODS: The study was single-blind and compared four eradication therapies in Japanese and Swedish patients with healed gastric (GU) or duodenal (DU) ulcer. Swedish patients received either (a) omeprazole+clarithromycin (OC, where O = 20 mg, C = 500 mg) for 2 weeks, or triple therapy with (b) omeprazole + amoxicillin + clarithromycin (OAC-L where O = 20mg, A = 1 g, C = 250 mg); (c) OAC-H (where O = 20 mg, A-1 g, C-500 mg); or (d) omeprazole + metronidazole + clarithromycin (OMC, where O = 20 mg, M = 400 mg, C = 250 mg) for 1 week. Antibiotic doses were weight-adjusted downwards in Japanese patients. H. pylori was assessed using the urea breath test (UBT), histology and culture pre-entry, with UBT being repeated 4 and 8 weeks after stopping treatment. Histology and culture were repeated if the UBT was positive post-therapy. RESULTS: Recruitment included 120 patients from Japan (43 GU, 61 DU, 16 GU+DU) and 120 from Sweden (119 DU, 1 GU+DU). There were 26 exclusions from a FAS analysis due to H. pylori negativity (14), no drug administration (7) or no data after visit 1 (5). Eradication rates (FAS) from Japan were (a) 63%, (b) 93%, (c) 96% or (d) 96%, and for Sweden (a) 92%, (b) 86%, (c) 93% or (d) 96%. Dual therapy was less effective in patients with gastric atrophy associated with GU disease. Tolerability was good in all treatment groups, with no serious adverse events. CONCLUSION: Triple therapies were safe and effective for H. pylori eradication in Japanese and Swedish peptic ulcer patients. Dual therapy was significantly less effective in the Japanese patients, half of whom had a history of GU and more abnormal histology than in the Swedish patients, all of whom had DU.

Comparison of gastric histology among Swedish and Japanese patients with peptic ulcer and Helicobacter pylori infection.

BACKGROUND: The natural course of Helicobacter pylori gastritis may vary between different ethnic groups. Gastric histopathology and the occurrence of H. pylori organisms in the stomach were investigated in healed duodenal (DU) and gastric (GU) ulcer patients recruited in Sweden (S) and Japan (J) in an identical trial. METHODS: In 203 patients (JGU = 39, JDU = 55, SDU = 109), various morphological gastritis variables and H. pylori were assessed from biopsy specimens obtained using a specific sampling protocol and interpreted according to guidelines of the updated Sydney grading system. RESULTS: The ratio of GU:DU was observed to be very different between the recruited Japanese (39:55) and Swedish (0:109) patients. A comparison of data from SDU and JDU showed that the prevalence of H. pylori infection and the antral predominant gastritis demonstrated by both SDU and JDU were essentially identical. A comparison of data from JDU and JGU demonstrated a greater prevalence of H. pylori infection in the antrum, but not corpus, of JDU compared to JGU patients. The prevalence of atrophy and intestinal metaplasia was higher in both the antrum and corpus of JGU compared to JDU in all patients. CONCLUSIONS: The site specified biopsy methodology and standardized interpretation criteria utilized in this study clearly show that the histotopographic profile of Swedish and Japanese DU patients is essentially the same.

Comparison of Gastric Histology Among Swedish and Japanese Patients with Peptic Ulcer and <emph type="2">Helicobacter pylori</emph> Infection.

BACKGROUND: The natural course of Helicobacter pylori gastritis may vary between different ethnic groups. Gastric histopathology and the occurrence of H. pylori organisms in the stomach were investigated in healed duodenal (DU) and gastric (GU) ulcer patients recruited in Sweden (S) and Japan (J) in an identical trial. METHODS: In 203 patients (JGU = 39, JDU = 55, SDU = 109), various morphological gastritis variables and H. pylori were assessed from biopsy specimens obtained using a specific sampling protocol and interpreted according to guidelines of the updated Sydney grading system. RESULTS: The ratio of GU:DU was observed to be very different between the recruited Japanese (39:55) and Swedish (0:109) patients. A comparison of data from SDU and JDU showed that the prevalence of H. pylori infection and the antral predominant gastritis demonstrated by both SDU and JDU were essentially identical. A comparison of data from JDU and JGU demonstrated a greater prevalence of H. pylori infection in the antrum, but not corpus, of JDU compared to JGU patients. The prevalence of atrophy and intestinal metaplasia was higher in both the antrum and corpus of JGU compared to JDU in all patients. CONCLUSIONS: The site specified biopsy methodology and standardized interpretation criteria utilized in this study clearly show that the histotopographic profile of Swedish and Japanese DU patients is essentially the same.

Effect of budesonide enema on remission and relapse rate in distal ulcerative colitis and proctitis.

BACKGROUND: Glucocorticosteroid enemas are equally effective as 5-ASA enemas in the treatment of active distal ulcerative colitis (UC). With the introduction of budesonide, the risk of systemic side effects may be reduced. We investigated whether budesonide enema, 2 mg/100 ml, administered twice daily (b.i.d.) could increase the remission rate in comparison with the once daily (o.d.) standard regimen. Furthermore, we evaluated whether 2 mg budesonide enema, given twice weekly, could have a relapse preventing effect. METHODS: 149 patients with active distal UC were treated in a controlled, double-blind multicentre study with two parallel groups: placebo enema in the morning and budesonide enema in the evening (i.e. 2 mg/day) or budesonide enema b.i.d. (i.e. 4 mg/day) until remission (absence of clinical symptoms and endoscopic healing) or at most 8 weeks. Patients in remission were randomized to either budesonide enema or placebo enema twice weekly for 24 weeks or until relapse. RESULTS: The remission rates at 4 weeks were 33% for o.d. and 41% for b.i.d. regimens (NS) and correspondingly 51% and 54% at 8 weeks (NS). The b.i.d. group had an increased frequency of impaired adrenal function, 32% versus 4.8% (P = 0.001). The relapse rates during maintenance treatment with budesonide enema and placebo were 15% versus 24% after 8 weeks, 31% versus 27% after 16 weeks and 41% versus 51% after 24 weeks (NS). CONCLUSION: Budesonide enema 2 mg o.d. appears to be the optimal dosage in active distal UC. We could not show that budesonide enema twice weekly is sufficient to maintain remission.

Dose finding study of mosapride in functional dyspepsia: a placebo-controlled, randomized study.

BACKGROUND: Prokinetic agents have shown variable efficacy in the treatment of functional dyspepsia. Mosapride is a new prokinetic 5-hydroxytryptamine-4 agonistic agent. AIM: To evaluate the efficacy of three dosage regimens of mosapride compared with placebo in the treatment of functional dyspepsia. METHODS: Patients were randomly allocated to treatment with placebo or mosapride (5 mg b.d., 10 mg b.d. or 7.5 mg t.d.s.) in a double-blind, prospective, multicentre, multinational study. The change in symptom severity score from an untreated baseline week to the sixth week of treatment was used to compare treatment efficacy. RESULTS: There were 141, 140, 143 and 142 patients valid for evaluation in the intention-to-treat population in the placebo, mosapride 5 mg b.d., mosapride 10 mg b.d. and mosapride 7.5 mg t.d.s. groups, respectively. The mean changes in the overall dyspeptic symptom score were - 0.90, - 0.94, - 0.88 and - 0.89, respectively, and the proportions of patients feeling better at the end of the treatment period were 60%, 59%, 59% and 61%, respectively. No statistically significant difference was seen. CONCLUSIONS: Treatment of functional dyspepsia with mosapride was not superior to placebo. The result raises the question of whether treatment with prokinetic agents is appropriate for functional dyspepsia.

[Celiac disease can be associated with severe neurological symptoms. Analysis of gliadin antibodies should be considered in suspected cases]. / Celiaki kan vara förenad med allvarliga neurologiska symtom. Gliadinantikroppsanalys bör övervägas i oklara fall.

Celiac disease can be associated with a wide spectrum of neurological and psychiatric symptoms (cerebellar ataxia, neuromuscular manifestations, epilepsy, dementia), even in the absence of malabsorption or gastrointestinal symptoms. The case of a 72-year-old man with a rapidly progressive, lethal encephalopathy secondary to celiac disease is reported, together with a review of documented neurological symptoms in celiac disease. The aetiology of these neurological symptoms is unknown, although immunological mechanisms are suspected.

The HOMER Study: the effect of increasing the dose of metronidazole when given with omeprazole and amoxicillin to cure Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori eradication with omeprazole, amoxycillin, and metronidazole is both effective and inexpensive. However, eradication rates with different dosages and dosing vary, and data on the impact of resistance are sparse. In this study, three different dosages of omeprazole, amoxycillin, and metronidazole were compared, and the influence of metronidazole resistance on eradication was assessed. METHODS: Patients (n = 394) with a positive H. pylori screening test result and endoscopy-proven duodenal ulcer in the past were enrolled into a multicenter study performed in four European countries and Canada. After baseline endoscopy, patients were randomly assigned to treatment for 1 week with either omeprazole, 20 mg twice daily, plus amoxycillin, 1,000 mg twice daily, plus metronidazole, 400 mg twice daily (low M); or omeprazole, 40 mg once daily, plus amoxycillin, 500 mg three times daily, plus metronidazole, 400 mg three times daily (medium M); or omeprazole, 20 mg twice daily, plus amoxycillin, 1,000 mg twice daily, plus metronidazole, 800 mg twice daily (high M). H. pylori status at entry was assessed by a 13C urea breath test and a culture. Eradication was defined as two negative 13C-urea breath test results 4 and 8 weeks after therapy. Susceptibility testing using the agar dilution method was performed at entry and in patients with persistent infection after therapy. RESULTS: The eradication rates, in terms of intention to treat (ITT) (population n = 379) (and 95% confidence interval [CI]) were as follows: low M 76% (68%, 84%), medium M 76% (68%, 84%), and high M 83% (75%, 89%). By per-protocol analysis (population n = 348), the corresponding eradication rates were: low M 81%, medium M 80%, and high M 85%. No H. pylori strains were found to be resistant to amoxycillin. Prestudy resistance of H. pylori strains to metronidazole was found in 72 of 348 (21%) of the cultures at entry (range, 10%-39% in the five countries). The overall eradication rate in prestudy metronidazole-susceptible strains was 232 of 266 (87%) and, for resistant strains, it was 41 of 70 (57%; p <.001). Within each group, the results were as follows (susceptible/resistant): low M, 85%/54%; medium M, 86%/50%; and high M, 90%/75%. There were no statistically significant differences among the treatment groups. 23 strains susceptible to metronidazole before treatment were recultured after therapy failed; 20 of these had now developed resistance. CONCLUSIONS: H. pylori eradication rates were similar (approximately 80%) with all three regimens. Metronidazole resistance reduced efficacy; increasing the dose of metronidazole appeared not to overcome the problem or significantly improve the outcome. Treatment failure was generally associated with either prestudy or acquired metronidazole resistance. These findings are of importance when attempting H. pylori eradication in communities with high levels of metronidazole resistance.

The MACH2 study: role of omeprazole in eradication of Helicobacter pylori with 1-week triple therapies.

BACKGROUND & AIMS: The role of omeprazole in triple therapy and the impact of Helicobacter pylori resistance on treatment outcome are not established. This study investigated the role of omeprazole and influence of primary H. pylori resistance on eradication and development of secondary resistance. METHODS: Patients (n = 539) with a history of duodenal ulcer and a positive H. pylori screening test result were randomized into 4 groups. OAC group received 20 mg omeprazole, 1000 mg amoxicillin, and 500 mg clarithromycin; OMC group received 20 mg omeprazole, 400 mg metronidazole, and 250 mg clarithromycin; and AC (amoxicillin, 1000 mg, and clarithromycin, 500 mg) and MC (metronidazole, 400 mg, and clarithromycin, 250 mg) groups received no omeprazole. All doses were administered twice daily for 1 week. H. pylori status was assessed before and after therapy by 13C-urea breath test. Susceptibility testing was performed at entry and in patients with persistent infection after therapy. RESULTS: Eradication (intention to treat [n = 514]/per protocol [n = 449]) was 94%/95% for OAC, 26%/25% for AC (P < 0.001), 87%/91% for OMC, and 69%/72% for MC (P < 0.001). Primary resistance was 27% for metronidazole, 3% for clarithromycin, and 0% for amoxicillin. Eradication in primary metronidazole-susceptible/-resistant strains was 95%/76% for OMC and 86%/43% for MC. Secondary metronidazole and clarithromycin resistance each developed in 12 patients: 8 treated with omeprazole and 16 without omeprazole. CONCLUSIONS: Addition of omeprazole achieves high eradication rates, reduces the impact of primary resistance, and may decrease the risk of secondary resistance compared with regimens containing only two antibiotics.