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Background In EMBRACA, talazoparib prolonged progression-free survival versus chemotherapy (hazard ratio [HR] 0.542 [95% confidence interval (CI) 0.413-0.711]; P Patients and methods This randomized phase III trial enrolled patients with gBRCA1/2-mutated HER2-negative ABC. Patients received talazoparib or physician's choice of chemotherapy. OS was analyzed using stratified HR and log-rank test and prespecified rank-preserving structural failure time model to account for subsequent treatments. Results A total of 431 patients were entered in a randomized study (287 talazoparib/144 chemotherapy) with 412 patients treated (286 talazoparib/126 chemotherapy). By 30 September 2019, 216 deaths (75.3%) occurred for talazoparib and 108 (75.0%) chemotherapy; median follow-up was 44.9 and 36.8 months, respectively. HR for OS with talazoparib versus chemotherapy was 0.848 (95% CI 0.670-1.073; P = 0.17); median (95% CI) 19.3 months (16.6-22.5 months) versus 19.5 months (17.4-22.4 months). Kaplan–Meier survival percentages (95% CI) for talazoparib versus chemotherapy: month 12, 71% (66% to 76%)/74% (66% to 81%); month 24, 42% (36% to 47%)/38% (30% to 47%); month 36, 27% (22% to 33%)/21% (14% to 29%). Most patients received subsequent treatments: for talazoparib and chemotherapy, 46.3%/41.7% received platinum and 4.5%/32.6% received a poly(ADP-ribose) polymerase (PARP) inhibitor, respectively. Adjusting for subsequent PARP and/or platinum use, HR for OS was 0.756 (95% bootstrap CI 0.503-1.029). Grade 3-4 adverse events occurred in 69.6% (talazoparib) and 64.3% (chemotherapy) patients, consistent with previous reports. Extended follow-up showed significant overall improvement and delay in time to definitive clinically meaningful deterioration in global health status/quality of life and breast symptoms favoring talazoparib versus chemotherapy (P Conclusions In gBRCA1/2-mutated HER2-negative ABC, talazoparib did not significantly improve OS over chemotherapy; subsequent treatments may have impacted analysis. Safety was consistent with previous observations. PRO continued to favor talazoparib.

Resume Introduction La peau est l’organe le plus frequemment atteint par la maladie des emboles de cristaux de cholesterol (MECC) qui peut parfois se manifester initialement uniquement par des symptomes dermatologiques. Nous rapportons l’observation d’une MECC associee a une erythrodermie a l’origine d’un diagnostic errone de syndrome d’hypersensibilite medicamenteuse (HM). Observation Une femme de 66 ans presentait une erythrodermie a la suite de l’introduction d’allopurinol quelques mois plus tot. On notait une degradation recente de la fonction renale avec une creatininemie a 523 μmol/L et une hypereosinophilie (HE) a 5666/mm3. Les criteres n’etaient finalement pas suffisants pour retenir le diagnostic d’HM. En examinant les anciennes numerations il etait constate une HE fluctuante remontant a plus de 10 mois avant l’introduction d’allopurinol. La biopsie renale permettait de diagnostiquer une MECC. Conclusion Nous rapportons une presentation evocatrice d’une HM dans une MECC, dont les symptomes cliniques sont lies a l’HE et non pas aux emboles.

We aimed to increase pathologic complete response (pCR) in patients with invasive breast cancer by adding preoperative capecitabine to docetaxel following 5‐fluorouracil, epirubicin, cyclophosphamide (FEC) (with trastuzumab for patients with HER2‐positive disease) and to evaluate 5‐year disease‐free survival (DFS) associated with this preoperative regimen. Chemotherapy included four cycles of FEC100 (5‐fluorouracil 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2 IV on Day 1 every 21 days) followed by 4 21‐day cycles of docetaxel (35 mg/m2 days 1 and 8) concurrently with capecitabine (825 mg/m2 orally twice daily for 14 days followed by 7 days off) (wTX). For HER2‐positive patients, treatment was modified by decreasing epirubicin to 75 mg/m2 and adding trastuzumab (H) in standard doses (FEC75‐H →wTX‐H). The study objective was to achieve a pCR rate in the breast and axillary lymph nodes of 37% in patients with HER2‐negative breast cancer and of 67% in patients with HER2‐positive breast cancer treated with preoperative trastuzumab. A total of 186 patients were enrolled on study. In an intent‐to‐treat analysis, the pCR rate was 31% (37/118, 95% CI: 24–40%) in the HER2‐negative patients, 24% (15/62, 95% CI: 14–37%) in ER‐positive/HER2‐negative patients, 39% (22/56, 95% CI: 27–53%) in the ER‐negative/HER2‐negative patients, and 46% (29/63, 95% CI: 34–48%) in the HER2‐positive patients. The pCR rate in the 40 trastuzumab‐treated patients was 53% (21/40, 95% CI: 38–67%). Grade 3 and 4 adverse events included neutropenia, leukopenia, diarrhea, and hand‐foot skin reactions. One trastuzumab‐treated patient developed grade 3 cardiotoxicity, and 4 others experienced grade 1–2 decrements in left ventricular function; all five patients’ cardiac function returned to their baseline upon completion of trastuzumab. At 5 years, disease‐free survival was 70% in the HER2‐negative population (78% in ER‐positive/HER2‐negative and 62% in the ER‐negative/HER2‐negative patients) and 80% in the HER2‐positive patients (87% in the trastuzumab‐treated HER2‐positive patients). At 5 years, overall survival was 80% in the HER2‐negative population (88% in ER‐positive/HER2‐negative and 71% in the ER‐negative/HER2‐negative patients) and 86% in the HER2‐positive patients (94.5% in the trastuzumab‐treated HER2‐positive patients). FEC100 (FEC75 with trastuzumab) followed by weekly docetaxel plus capecitabine, with or without trastuzumab is a safe, effective preoperative cytotoxic regimen. However, the addition of capecitabine to docetaxel following FEC, with or without trastuzumab, did not increase pCR rates nor 5‐year DFS over the rates that have been reported with standard preoperative doxorubicin/cyclophosphamide (AC) followed by paclitaxel, with or without trastuzumab. Therefore, the use of capecitabine as part of preoperative chemotherapy is not recommended.

Purpose: We conducted a randomized phase III study to determine whether patients with early breast cancer would benefit from the addition of capecitabine (X) to a standard regimen of doxorubicin (A) plus cyclophosphamide (C) followed by docetaxel (T). Experimental Design: Treatment comprised eight cycles of AC→T (T dose: 100 mg/m2 on day 1) or AC→XT (X dose: 825 mg/m2 twice daily, days 1–14; T dose: 75 mg/m2 on day 1). The primary endpoint was 5-year disease-free survival (DFS). Results: Of 2,611 women, 1,304 were randomly assigned to receive AC→T and 1,307 to receive AC→XT. After a median follow-up of 5 years, the study failed to meet its primary endpoint [HR, 0.84; 95% confidence interval (CI), 0.67–1.05; P = 0.125]. A significant improvement in overall survival, a secondary endpoint, was seen with AC→XT versus AC→T (HR, 0.68; 95% CI, 0.51–0.92; P = 0.011). There were no unexpected adverse events. Of patients with estrogen receptor (ER)–positive/HER2-negative disease, 70% of whom were node-positive, 26% and 59% had tumors with a centrally assessed Ki-67 score of Conclusions: The very low event rate in patients with ER-positive, low Ki-67 cancers, regardless of nodal status, strongly suggests that these patients should not be enrolled in adjuvant trials that assess 5-year DFS rates and that central Ki-67 analyses can identify these patients. Clin Cancer Res; 21(19); 4305–11. ©2015 AACR.

This study describes the validation of a computer program for automated analysis of ambulatory 24-hour two-channel esophageal manometry. The program's ability to characterize contractions and to calculate their duration and amplitude was validated against manual evaluation. An independent reference standard for the identification and classification of contractions was established by submitting representative recordings to a group of 14 experts in upper gastrointestinal motility; the program's ability to identify and classify contractions was then validated against the majority verdict of the experts. The results show an excellent correlation between the manual and computer evaluations of both contraction amplitude (p = 0.9957) and duration (p = 0.8241). The concordance between the experts was also excellent: 97 (72%) of 135 pressure events were classified identically by 12 or more experts. Computer-aided manometry analysis (CAMA) had a sensitivity of 98.9% and a specificity of 93.5% for the detection of contractions, with sensitivities of 94.7% and 84.4% and specificities of 94.9% and 94.2% for the classification of propagated and nonpropagated contractions, respectively.

The effectiveness of a single, morning oral dose of 40 mg omeprazole or a twice daily oral dose of 150 mg ranitidine was compared in a randomized endoscopically controlled double-blind trial at 37 clinics in Austria, Germany and Switzerland. A total of 178 out-patients in stages I-IVa (after Savary and Miller) were entered into the trial: 78 in stage I, 60 in stage II, 27 in stage III, and in 13 in stage IVa. As early as at the end of the third treatment week there was a significantly higher rate of complete healing or reduction into a lower stage with omeprazole than ranitidine (85% vs 67%; P less than 0.02). After six treatment weeks, healing tendency after omeprazole compared with ranitidine was 85% vs 45% (P less than 0.04). Omeprazole also brought earlier improvement in symptoms. The difference was statistically significant for heartburn (pyrosis): P less than 0.01. Both drugs were equally well tolerated and there were no clinically significant side-effects. This is the first demonstration that the ATPase inhibitor omeprazole is superior to the H2-receptor antagonist ranitidine in the treatment of reflux oesophagitis.

134 outpatients with acute benign gastric ulcer confirmed by endoscopic biopsy received either 1 g sucralfate suspension four times daily or one 150 mg ranitidine tablet twice daily for six to 12 weeks in a multicentre therapy study (double-blind study according to the double-dummy technique). After six to 12 weeks, respectively, 56% and 82% of the ulcers had healed in the sucralfate group. The rates of healing in the ranitidine group were 72% and 88%, respectively. The differences in the rates of healing between sucralfate and ranitidine were not statistically significant. Ranitidine was superior to the sucralfate suspension in corpus ulcer. In the distally located ulcers, the two kinds of treatment were equivalent. There were no appreciable differences between the medications with regard to antacid consumption and compliance. Gastric pain was influenced better by ranitidine than by sucralfate.

In a multi-centre double-blind (double-dummy) trial the effectiveness of low-dose antacid gel (6 X 12 ml/d; neutralisation capacity 120 mmol) was compared with that of a standard dose of cimetidine (1 g/d) in the curative treatment of gastric ulcer. Antacid gel was given to 65 patients, cimetidine to 60. Diagnosis was confirmed by endoscopic biopsy, which was also employed in a serial follow-up. After 4 weeks antacid gel and cimetidine produced cures in 43% and 52%, respectively; after 8 weeks 76% and 89%, respectively, the difference between the two methods not being statistically significant. There was also no statistically significant difference with regard to ulcer pain. In one case each in the antacid and cimetidine groups, the treatment had to be stopped because of side effects. Diarrhoea was more common on cimetidine than on antacid gel. It is concluded that both low-dose antacids gels and cimetidine are suitable in the treatment of gastric ulcers.

SUMMARY Analysis of clinical data obtained in a double-blind randomized study, which compared liquid antacid (neutralizing capacity 120 mmol per day) with 1 g cimetidine in the treatment of 125 patients with gastric ulcer, revealed that, before starting treatment 71 % of the patients complained of epigastric pain, approximately 50% of bloating, and approximately 30 % of nausea, heartburn, constipation or vomiting. Epigastric pain before treatment was significantly more frequent in patients with large ulcers (P < 0.05) and in patients with ulcers unhealed after 4 weeks of therapy (P < 0.05). This finding was the result of a highly significant correlation between diurnal epigastric pain and ulcer size and delayed healing (P < 0.005). Nocturnal pain did not correlate with prognosis. In contrast to this correlation between pain before therapy and healing, the disappearance of epigastric pain with therapy did not signify ulcer healing. Only 14 (38%) of the 37 patients with healed ulcer were free from pain after the 4 weeks of therapy, whereas 25 (49%) of the 52 patients with persistent ulcers had no pain at this time. Placebo pain tablets relieved ulcer pain effectively in more than 85% of the patients, irrespective of whether the ulcer was healing or not. The other symptoms (bloating, nausea, heartburn, constipation or vomiting) were also alleviated by 4 weeks of therapy but no correlation was found with ulcer size or prognosis. The loss of the prognostic significance of ulcer pain is probably due to a complex interaction of the trial schedule on the patient's level of consciousness. The highly effective placebo pain tablets and improvement of symptoms, which are unlikely to be due to gastric ulcer symptoms that are also unlikely to be affected by a decrease in gastric acidity such as bloating and constipation), suggest that ulcer treatment in a controlled trial changes pain perception. We conclude that treatment trials have effects that go beyond the rates of healing.

Helicobacter pylori infection, a highly prevalent pathogen, is a major cause of chronic gastritis and peptic ulcer and a risk factor for gastric malignancies. Antibiotics-based H. pylori eradication treatment is 90% effective. However, it is expensive and causes side effects and antibiotic resistance. Probiotics could present a low-cost, large-scale alternative solution to prevent or decrease H. pylori colonization. A literature search of the MEDLINE database (1966-2006) has been performed selecting all in vitro, animal, and human fully published English-language studies dealing with H. pylori and probiotics. Probiotics had an in vitro inhibitory effect on H. pylori. Animal studies demonstrated that probiotic treatment is effective in reducing H. pylori-associated gastric inflammation. Seven of 9 human studies showed an improvement of H. pylori gastritis and decrease in H. pylori density after administration of probiotics. The addition of probiotics to standard antibiotic treatment improved H. pylori eradication rates (81% vs. 71%, with combination treatment vs. H. pylori-eradication treatment alone; chi(2)test: P=0.03). Probiotic treatment reduced H. pylori therapy-associated side effects (incidence of side effects: 23% vs. 46%, with combination therapy vs. H. pylori-eradication treatment alone; chi(2)test: P=0.04). No study could demonstrate the eradication of H. pylori infection by probiotic treatment. So long-term intake of products containing probiotic strains of probiotics may have a favorable effect on H. pylori infection in humans, particularly by reducing the risk of developing disorders associated with high degrees of gastric inflammation.

Purpose We conducted a multicenter phase II trial to determine the efficacy/safety of capecitabine and weekly paclitaxel, a combination with preclinical evidence of synergy, in patients with metastatic breast cancer (MBC) previously treated with a taxane. Patients and Methods Eligibility criteria included measurable MBC, history of every-3-week taxane therapy (adjuvant or for MBC), and no previous taxane on a weekly basis, capecitabine, or infusional 5-fluorouracil. Patients received capecitabine 825 mg/m2 per dose orally twice daily (1650 mg/m2 per day) on days 1–14 and weekly paclitaxel 80 mg/m2 intravenously on days 1 and 8, followed by a 1-week rest period (every-3-week cycle) until progression or intolerable toxicity. Fifty-four women were treated, most with previous every-3-week taxane exposure as adjuvant therapy (n = 43) rather than for MBC (n = 11). The median number of delivered cycles was 7, with dose modifications in 30 patients. The intent-to-treat objective response rate (primary study endpoint) was 59% (95% confidence interval, 46%–72%), including 7 complete and 25 partial responses. Results Three patients had stable disease for ≥ 6 months, for a clinical benefit rate of 65% (95% confidence interval, 51%–76%). Median objective response duration, time to progression, and overall survival were 8.1 months, 8.4 months, and 21.6 months, respectively. Grade 3/4 treatment-related adverse events consisted of neutropenia (13%), anemia (2%), hand-foot skin reaction (20%), fatigue (7%), diarrhea (4%), nausea/vomiting (4%), and pain (2%). No patients developed grade 3/4 neuropathy. Conclusion Capecitabine and weekly paclitaxel were highly active with acceptable tolerability in patients with MBC previously treated with a taxane, consistent with our recently published experience in taxane-naive women with MBC.

The aim of this study was to assess whether the taking of an additional biopsy from the incisura angularis increases the chance of detecting maximal degrees of atrophy and intestinal metaplasia (IM) in patients with Helicobacter pylori gastritis and functional dyspepsia. At entry into a randomised trial, biopsies were taken from 328 patients (mean age 48 years), two from both the gastric antrum and corpus, and one from the incisura angularis, and comparative grading of gastritis variables was carried out. Biopsy material from the gastric antrum, corpus, and the incisura angularis revealed no notable differences in atrophy or an incidence of IM and mucosa-associated lymphatic tissue. However, when the incisura biopsies were classified histologically, 58% contained antral mucosa (AM), 18% corpus mucosa (CM), and 24% intermediate zone mucosa. AM at the incisura was associated with considerably more severe gastritis in both the incisura and antrum (14% atrophy, 20% IM) than in CM of incisura (2% atrophy, 6% IM). Corpus atrophy and IM were rare in the AM group and absent from the CM group. Incisura angularis biopsy in patients with H. pylori gastritis and functional dyspepsia does give additional information regarding the severity of gastritis expected in the corpus and antrum. Antral-type mucosa in the incisura angularis region seems to indicate an increased risk for the development of atrophy and/or IM. (c) 2006 Elsevier GmbH. All rights reserved.

The current guidelines of the German Society for Digestive Diseases (DGVS) endoscopy recommends for patients representing with reflux symptoms. In daily routine as well as in Guidelines from other countries and international guidelines, however, a symptom-based strategy for the management of patients with reflux disease is favoured. Since either strategies is dependent on specific clinical findings, neither can be recommended. The preference for one or the other strategy depends on the prevalence of so-called alarm symptoms, risk factors for a reflux carcinoma or Barrett's metaplasia, demographic factors, e. g., age and gender, patient's wish and initial response to empirical therapy with proton pump inhibitors (PPI). However, most patients with characteristic reflux symptoms without any alarm symptoms and/or other risk factors can be safely managed with a symptom-based strategy in acute and long-term care.

Summary To evaluate therapies available for the treatment of irritable bowel syndrome, and provide consensus recommendations for their use, a total of 51 double-blind clinical trials using bulking agents, prokinetics, antispasmodics, alosetron, tegaserod and antidepressants were selected. The quality of studies was assessed using 5-point scale. Meta-analyses were performed on all studies, and on ‘high-quality studies’. The efficacy of fibre in the global irritable bowel syndrome symptoms relief (OR: 1.9; 95% CI:1.5–2.4) was lost after exclusion of low-quality trials (OR: 1.4; 95% CI: 1.0–2.0, P = 0.06). When excluding the low-quality trials, an improvement of global irritable bowel syndrome symptoms with all antispasmodics (OR: 2.1; 95% CI:1.8–2.9) was maintained only for octylonium bromide, but on the basis of only two studies. Antidepressants were effective (OR: 2.6, 95% CI: 1.9–3.5), even after exclusion of low-quality studies (OR: 1.9, 95% CI: 1.3–2.7). Alosetron (OR: 2.2; 95% CI: 1.9–2.6) and tegaserod (OR: 1.4; 95% CI: 1.2–1.5) showed a significant effect in women. We recommend the use of tegaserod for women with irritable bowel syndrome with constipation and alosetron for women with severe irritable bowel syndrome with diarrhoea. Antidepressants can be beneficial for irritable bowel syndrome with diarrhoea patients with severe symptoms. Loperamide can be recommended in painless diarrhoea. Evidence is weak to recommend the use of bulking agents in the treatment of irritable bowel syndrome with constipation.

Gastro-oesophageal reflux disease and non-erosive reflux disease are chronic, highly prevalent conditions requiring long-term treatment that is both effective and practical. On-demand therapy with a proton pump inhibitor may meet that need. It is becoming a mainstay of long-term treatment because it reduces the risk of over- and under-treatment, is cost-effective and user friendly. Epidemiological and clinical observations speak also in its favour. However, for the anticipated benefits of on-demand therapy to accrue in clinical practice, on-demand treatment algorithms are required. These algorithms must specify the initial evaluation and treatment of candidates, and follow-up protocols for an on-demand strategy. Our group has developed such algorithms, which are presented here.

Summary Background : Compliance studies have shown that patients with reflux symptoms generally take their medication only when experiencing these symptoms. Aim : To evaluate the efficacy of on-demand rabeprazole maintenance therapy in patients with non-erosive reflux disease. Methods : This multicentre, randomized, double-blind, placebo-controlled, withdrawal study compared 6 months of on-demand treatment with rabeprazole 10 mg vs. placebo. Adults with a history of reflux symptoms, a negative endoscopy, and ≥3 days of moderate to very severe heartburn in the 7 days before enrolment (N = 535) entered 4 weeks of open-label, acute treatment with rabeprazole 10 mg once daily. Patients with complete symptom relief then entered the on-demand phase. The primary end-point was discontinuation due to lack of heartburn control during the on-demand phase. Results : Eighty-three percent (432 of 523) of patients reported complete symptom relief at the end of the acute phase. During on-demand treatment, rates of discontinuation because of inadequate heartburn control were 20% (28 of 139) for placebo vs. 6% (16 of 279) for rabeprazole (P

Summary Background : Lactobacillus johnsonii (Lj1) had an in vitro and in vivo inhibitory effect on Helicobacter pylori. Fermented milk containing Lj1 (LC1), coadministered with antibiotics had a favourable effect on H. pylori gastritis. Aim : Evaluate the effect of LC1 intake without antibiotics on H. pylori gastritis. Methods : Fifty H. pylori positive healthy volunteers were randomised in a double-blind study to LC1 or placebo. Gastric biopsies from the antrum and corpus were obtained before, and after 3 and 16 weeks of treatment, for histology and quantitative cultures. Results : Severity and activity of antral gastritis was reduced after 16-week LC1 intake (pretreatment and 16-week inflammatory cell score: 6.0 ± 0.8 vs. 5.3 ± 0.1; P = 0.04). H. pylori density decreased in the antrum after LC1 intake (3-week: 4.4 ± 0.6; 16-week: 4.3 ± 0.5 log10 colony forming units (cfu) vs. pretreatment 4.5 ± 0.4 log10 cfu; P = 0.04, respectively). Mucus thickness increased after 16 weeks of LC1 consumption (change of mucus thickness with LC1 and placebo in the antrum: 0.6 ± 1.3 vs. -0.2 ± 1.0, P = 0.01; in the corpus: 0.3 ± 1.1 vs. -0.6 ± 1.5, P = 0.03). Conclusion : LC1 intake had a favourable, albeit weak, effect on H. pylori associated gastritis, particularly in the antrum. Regular ingestion of fermented milk containing L. johnsonii may reduce the risk of developing disorders associated with high degrees of gastric inflammation and mucus depletion.

Background: Acid test meals may improve the accuracy of the 13 C urea breath test (UBT). This has been attributed to changes in gastric emptying rather than to the effects of gastric pH on Helicobacter pylori urease. Aims: To determine whether enhancement of 13 CO 2 excretion in the UBT in H pylori infected volunteers by acidification of a test meal is due to a delay in gastric emptying. Methods: Urease activity in vitro was measured in intact bacteria and in bacterial homogenates. Urease activity in vivo was assessed by means of the UBT. Eleven H pylori infected subjects underwent UBTs with neutral Ensure (pH 7.0), acidified Ensure (pH 3.0), and apple juice (pH 3.0). Gastric emptying was assessed by 13 C sodium acetate breath test. Results: From pH 7 to pH 3, the in vitro urease activity of intact bacteria increased sixfold. In contrast, urease activity of bacterial homogenates was inactivated by low pH. In vivo, urease activity, as measured by the UBT 20 minutes after meal ingestion, was higher with apple juice (δ 13 CO 2 =21.1; p=0.03) and acidified Ensure (δ 13 CO 2 =25.5; p=0.01) than with neutral Ensure (δ 13 CO 2 =12.5). Gastric emptying was faster with apple juice (T max =36.7 (8) minutes) but not with acidified Ensure (T max =63.3 (5) minutes; p=0.06) than with neutral Ensure (T max =65.0 (3) minutes; p=0.04). Conclusions: The higher UBT found with acidified compared with neutral test meals was independent of the emptying rates of the test meals but may have been due to medium acidity dependent activation of intra-bacterial urease in intact H pylori .

Summary Background: Rapid and consistent acid suppression on the first day of dosing may be important in treating acid-related disorders. Aim: To compare the antisecretory activity and onset of action of single doses of rabeprazole, lansoprazole, pantoprazole, omeprazole capsule, omeprazole multiple unit pellet system (MUPS) tablet and placebo in healthy Helicobacter pylori-negative subjects. Methods: This cross-over, double-blind, randomized study was performed in 18 H. pylori-negative subjects. Twenty-four-hour intragastric pH monitoring was performed on the day of treatment (once-daily dose of rabeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg, omeprazole capsule 20 mg, omeprazole MUPS tablet 20 mg or placebo). Results: The intragastric pH (3.4) and time at pH > 4 during the 24 h post-dose (8.0 h) were significantly greater with rabeprazole than with lansoprazole, pantoprazole, omeprazole capsule, omeprazole MUPS tablet or placebo (P ≤ 0.04 for rabeprazole vs. the others). Daytime and night-time pH values were higher with rabeprazole and lansoprazole than with pantoprazole, omeprazole capsule and omeprazole MUPS tablet (P ≤ 0.04). Conclusion: Rabeprazole was the most potent acid inhibitor of all the proton pump inhibitors tested during the first day of dosing.

Aim: To determine whether pre-treatment antibody response to Helicobacter pylori virulence factors predicts eradication success and symptom relief 12 months after triple therapy in non-ulcer dyspep ...

Background: Previous studies on the treatment of Helicobacter pylori infection in functional dyspepsia have shown little, if any, effect on dyspeptic symptoms. However, whether such treatment might be of benefit in patients resistant to acid inhibitors has not been formally tested. Aim: The present study investigated the effect of H pylori treatment in patients with functional dyspepsia resistant to conventional treatment. Patients: A total of 181 H pylori positive patients with chronic functional dyspepsia who had not responded to a one week antacid run-in and two week double blind antisecretory or placebo treatment were included. Methods: Patients were randomised to two weeks of treatment with omeprazole 40 mg twice daily combined with amoxicillin 1 g twice daily or omeprazole 20 mg once daily alone. The primary outcome variable (“response”) was defined as no need for further therapy or investigations for dyspeptic symptoms 4–6 months after treatment. Results: H pylori infection was healed in 10% of patients after omeprazole and in 52% after omeprazole plus amoxicillin. The respective “response” rates were 66% and 62% (NS). H pylori treatment and cure of H pylori infection had no effect on complete resolution of all dyspeptic symptoms, individual symptoms, or various aspects of quality of life. Conclusion: In functional dyspepsia, H pylori treatment and cure of H pylori are no more effective for symptoms over six months than short term acid inhibition. These results do not support treatment of H pylori in functional dyspepsia.

To assess the effect of a late-evening, high-fat meal on nocturnal supine gastro-oesophageal reflux, eight healthy volunteers (aged 20 to 38 years) underwent two ambulatory oesophageal pH-metry recordings, the first after a standardized light meal at 1930 h and the second after a high-fat meal including peppermint and chocolate, at 2130 h. Between 2300 and 0700 h, when subjects were supine, the median acid exposure time (percentage recording with pH less than 4) increased from 0.0\% (range, 0.0-6.8\%) after the standardized meal to 7.9\% (0.0-17.8\%) after the high-fat meal (p = 0.031). Similarly, the median number of reflux episodes increased from 0 (0 to 11) after the standardized meal to 7 (0 to 26) after the high-fat meal (p = 0.031). Reflux occurred after both meals, but, in general, persistent nocturnal reflux was observed only after the high-fat meal. Thus, the analysis of oesophageal pH recordings should consider the effects of meal composition and timing on oesophageal acid exposure.

Currently, one of the most important unresolved questions concerning Helicobacter pylori is whether eradication of the organism leads to a sustained improvement in symptoms in patients diagnosed with functional (non-ulcer) dyspepsia. Recently, two very similar studies, the ORCHID and OCAY studies, have been completed and the combined results of these two multicentre, multinational, randomised, double blind, controlled clinical trials are reviewed.

Background: Rabeprazole has a faster onset of antisecretory action than omeprazole, and it is of interest to determine whether this translates into faster symptom relief in patients with gastro-oesophageal reflux disease. Aims: To assess the relief from heartburn after 3 days of treatment with standard-dose rabeprazole or high-dose omeprazole (primary end-point). Secondary end-points included the decrease in score for other symptoms of gastro-oesophageal reflux disease, healing rates and quantification of antacid use. Methods: Patients with endoscopically confirmed erosive oesophagitis were randomized to receive 4 weeks of double-blind treatment with rabeprazole (20 mg) or omeprazole (40 mg). Patients who were not healed after 4 weeks received a further 4 weeks of treatment. Results: Two hundred and seventy-four patients were screened, 251 patients were randomized and 230 patients completed the trial. The numbers of patients with relief from heartburn on day 4 were similar in the two groups (84% for rabeprazole; 95% confidence interval, 76–90%; 83% for omeprazole; 95% confidence interval, 75–89%). There were no significant differences between the treatments in the relief from other gastro-oesophageal reflux disease symptoms or in healing rates. The number of reports of severe heartburn during the first 3 days was higher in the omeprazole group (daytime heartburn: 4.7% for rabeprazole vs. 10.3% for omeprazole, P=0.005; night-time heartburn: 4.7% for rabeprazole vs. 9.8% for omeprazole, P=0.01; statistical comparisons defined post hoc). Conclusions: Standard-dose rabeprazole was as effective as high-dose omeprazole in relieving symptoms by day 4 of treatment and in healing oesophageal lesions, but had a faster onset of action in patients with severe heartburn. This suggests that the improved pharmacological properties of rabeprazole translate into a clinically relevant advantage.

Background: Peptic ulcer bleeding remains a disease with considerable morbidity and mortality. Epinephrine is the most widely used endoscopic injection agent, but bleeding recurs in 20% of high-risk cases. Fibrin glue might be an ideal injection agent, based on its physiologic properties, despite its demanding injection technique and high cost. The aim of this study was to determine whether the injection of fibrin glue in combination with epinephrine improves outcome for patients at high risk of recurrent bleeding. Methods: Patients were prospectively randomized to injection of epinephrine alone (n = 70) or epinephrine plus fibrin glue (n = 65). Endoscopy was repeated daily until the ulcer base was clean. All patients were treated with high-dose omeprazole. Results: Initial hemostasis was 100% in both groups. There was no significant overall difference in rates of recurrent bleeding (24.3% and 21.5%, respectively, for epinephrine and epinephrine plus fibrin). When patients were stratified according to Forrest criteria, no significant difference could be found, although there was a trend toward less recurrent bleeding after fibrin injection of actively bleeding ulcers. There was no significant difference in the proportions of patients who required surgery (10% and 6%, respectively, for epinephrine and epinephrine plus fibrin). Mortality was the same (3%) in each group. Conclusions: Adding fibrin glue to epinephrine for injection treatment of bleeding peptic ulcers does not improve outcome. Fibrin glue might be of some value in selected cases. (Gastrointest Endosc 2002;55:348-53.)

The classical treatment of neoplastic lesions is surgical resection. Improved detection of early lesions has offered new therapeutic strategies. Thus, for the last 20 years it has been increasingly attempted to undertake endoscopic resection of such tumors. While there is no doubt that morbidity and mortality are lower than after surgery, it was assumed that the long-term prognosis is not as good as with surgery. Surprisingly, however, the 5-year survival rates are excellent. Therefore, in local mucosal lesions of colon, stomach, and esophagus, endoscopic removal has become standard treatment. In Barrett’s esophagus, the treatment modality it is still discussed controversially, despite encouraging results. Since we are yet not able to completely eliminate the premalignant specialized intestinal epithelium of the esophagus, it is still uncertain whether eradication of the malignant or dysplastic lesion is sufficient.

Background: Conventional techniques for measuring gastric acidity have demonstrated the decrease in gastric acidity produced by proton pump inhibitors (PPI); however, such techniques do not detect transient or localized pH changes which may modify the intragastric environment without affecting the therapeutic efficacy of PPIs. Aim: To investigate local and temporal variations in intragastric pH and to test the hypothesis that omeprazole produces prolonged, generalized gastric anacidity (pH >6). Methods: A single-blind study was conducted with triple-point 24-hour gastric pH-metry on days 7, 14 and 21 in 14 healthy, Helicobacter pylori-negative volunteers (7 M; 20–46 years) who received placebo for 7 days, followed by omeprazole 20 mg daily for 14 days. Results: Omeprazole increased the median 24-hour pH significantly in the distal corpus (placebo: 1.3 (95% CI 1.1 to 1.6); omeprazole week 1: 4.0 (2.6–5.0); omeprazole week 2: 4.0 (2.8–4.6)) and at all other gastric recording sites (p < 0.01). At both corpus sites, nocturnal pH was lower and mealtime pH was higher than the non-meal daytime pH during placebo and both omeprazole administration periods; in the antrum, however, the major difference noted was that meal-time pH was higher than non-meal daytime pH. Antral pH was lower during meals and higher at night than proximal corpus pH. During placebo, gastric pH >6.0 was observed at 1 site only for 1.7% (median; 95% CI 0.4–3.3%), at 2 sites simultaneously for 0.24% (0.0–1.0%) and at 3 sites for 0.0% (0.0–0.28%), respectively, of the recording periods; during the second week of omeprazole, the equivalent results were 7.7% (1.4–14.0%), 4.9% (0.21–15.7%) and 4.7% (0.0–9.9%), respectively. Conclusions: Omeprazole, 20 mg daily, does not produce gastric anacidity despite significant increases in median 24-hour pH values. The time-, meal- and site-related variations in gastric pH observed under normal physiological conditions are seen to persist, with prolonged periods of low pH throughout the stomach and preservation of the normal, meal-related rise and nocturnal fall in gastric pH during omeprazole administration.

Background Oral capecitabine was evaluated in terms of overall response rate, safety, and tolerability as first-line therapy in women aged > or = 55 years with advanced/metastatic breast cancer. Patients and methods Ninety-five patients were randomized (2:1) to either intermittent oral capecitabine 1,255 mg/m2 twice daily (two weeks' treatment followed by a one-week rest period) or intravenous CMF (cyclophosphamide. methotrexate, 5-fluorouracil [5-FU]) administered every three weeks. Results The overall response rate in the capecitabine group was 30% (95% confidence interval (95% CI): 19%-43%), including three complete responses (5%). The response rate observed in the CMF group was 16% (95% CI: 5%-33%), with no complete responses. Median time to disease progression was 4.1 months with capecitabine and 3.0 months with CME. Survival was similar in the two treatment groups (median 19.6 months with capecitabine. 17.2 months with CMF). The safety profiles were different for capecitabine and CMF. However, both regimens were generally well tolerated and treatment interruption and/or dose modification was effective in managing toxicities associated with capecitabine. Alopecia and myelosuppression were rare in patients receiving capecitabine while diarrhea and hand-foot syndrome were more common. Treatment interruption and/or individual dose adjustment of capecitabine was required in 34% of patients and was generally effective in managing adverse events. Treatment was stopped owing to toxicity in 16% of patients in the capecitabine arm. The incidence of deaths during or within 28 days of stopping study treatment was 8% and 6% in the capecitabine and CMF arms, respectively. Conclusions An oral, twice-daily regimen of capecitabine is effective and well tolerated when used as first-line chemotherapy in older patients (> or = 55 years) with advanced/metastatic breast cancer, and is suitable for outpatient therapy.

31 cases of non-fulminant hepatitis A complicated by acute renal insufficiency are reported in the literature. Two-thirds of those patients needed dialysis, usually when depending on the severity of their hyperbilirubinemia. This report concerns the first published case of non-fulminant cholestatic hepatitis A complicated by acute renal insufficiency in which a spontaneous remission of renal function occurred without need for dialysis despite a very severe hyperbilirubinemia.

Objective The supernatant of Lactobacillus johnsonii La1 culture was shown to be bactericidal and to have a partial, acid-independent suppressive effect on Helicobacter pylori in humans. The aim of the present study was to investigate the effect of L. johnsonii La1 -acidified milk (LC-1) on H. pylori infection. Design and methods Fifty-three volunteers infected with H. pylori as determined by positive 13 C-urea breath test and positive serology were randomized to receive either LC-1 or a placebo 180 ml twice a day for 3 weeks. All subjects also received clarithromycin 500 mg bid during the last two weeks of acidified milk therapy. Oesophagogastroduodenoscopy and biopsies were performed at inclusion and repeated 4-8 weeks after the end of the treatment. H. pylori infection was confirmed by urease test and histology. H. pylori density and inflammation were scored using a modified Sydney classification. Results LC-1 ingestion induced a decrease in H. pylori density in the antrum (P= 0.02) and the corpus (P= 0.04). LC-1 also reduced inflammation and gastritis activity in the antrum (P = 0.02 and P = 0.01, respectively) and of activity in the corpus (P=0.02). Clarithromycin eradicated H. pylori in 26% of the subjects; LC-1 did not improve the antibiotic effect. Conclusion These results suggest that H. pylori infection and gastritis can be down-regulated by LC-1.

BACKGROUND Capecitabine is an oral, tumor-targeted fluoropyrimidine carbamate with high activity in metastatic breast carcinoma and in paclitaxel-pretreated metastatic breast carcinoma. METHODS The current multicenter, Phase II trial assessed the efficacy and safety of intermittent oral capecitabine, 1255 mg/m2 twice daily (2 weeks of treatment followed by a 1-week rest period), in patients with metastatic breast carcinoma in whom prior taxane therapy had failed. All patients had failed treatment or had disease that was refractory to two or three previous chemotherapy regimens, one of which contained a taxane. Nearly all patients (96%) also had received prior anthracycline chemotherapy. Seventy-five patients were recruited at 5 centers, 74 of whom received treatment. RESULTS The overall response rate was 26%, with response rates of 27% and 20%, respectively, in the subgroups of patients previously pretreated with paclitaxel (n = 47) or docetaxel (n = 27). The median survival was 12.2 months, the median duration of response was 8.3 months, and the median time to disease progression was 3.2 months. The most common treatment-related adverse events (all grades) were hand-foot syndrome (62%), diarrhea (58%), nausea (55%), emesis (37%), and stomatitis (34%). However, the majority were mild to moderate in intensity and only three patients experienced Grade 4 (according to the National Cancer Institute of Canada Common Toxicity criteria) adverse events. The only Grade 3 treatment-related adverse events reported in ≥ 10% of the patients were hand-foot syndrome (22%), diarrhea (16%), and stomatitis (12%). Myelosuppression and alopecia were rare, and there were no reported treatment-related deaths. CONCLUSIONS The results of the current study demonstrate that capecitabine is an effective and well tolerated treatment in patients with taxane-refractory or taxane-failing metastatic breast carcinoma. In addition, it is a convenient, orally administered drug, which makes it an attractive agent for use in outpatient treatment. Cancer 2001;92:1759–68. © 2001 American Cancer Society.

Diurnal variations in the pattern of esophageal motility and acidity were studied in 14 healthy volunteers. Data from a two-channel manometry and one-channel pH-metry recording were stored in a portable 1-MByte, solid-state data logger for subsequent computerised analysis. Comparison of predefined nighttime, mealtime and nonmeal daytime periods showed that propagated contractions predominated during mealtimes (56\% of all contractions) and nonmeal daytime periods (53.5\% of contractions) and that their propagation velocity (2.98 cm/sec) was at its lowest and the AUC of all contractions (134.6 hectoPascal.sec) at its greatest during mealtime periods. During the night, propagated contractions (0.136/min) and simultaneous contractions (0.025/min) were significantly less frequent than during both meal (1.31/min and 0.172/min, respectively) and nonmeal daytimes (0.665/min and 0.133/min, respectively), whereas the nocturnal segmental contraction frequency (0.181/min) was not significantly lower than the nonmeal daytime contraction frequency (0.243/min). Median reflux time was in the normal range (1.2\%), although two subjects had prolonged reflux times (9.5\% and 14.5\%). In conclusion, all subjects showed similar patterns of diurnal esophageal contractory activity determined partly by meal intake and partly by a characteristic clustering of nocturnal contractions that could not be explained by episodes of nocturnal gastroesophageal reflux. It may, therefore, be speculated that nocturnal contraction clusters are associated with rhythmic phenomena such as MMC or specific sleep stages.

Background & Aims: Intestinal contractions are triggered by electric activity of pacemaker cells within the smooth muscle. However, the precise spatial organization of the pacemaker system is unknown. We directly assessed the spatiotemporal organization of pacemakers by video image analysis combined with manometry and electromyography. Methods: Isolated segments of rat ileum were perfused arterially with oxygenated fluorocarbon solution and luminally with saline. Luminal end pressures, extracellular electric activity, and images of the intestine were recorded simultaneously. Tetrodotoxin, N G -nitro-L-arginine methyl ester (L-NAME), L-arginine, and eserine were administered arterially. Results: Myogenic contractions originated in discrete areas (dominant pacemakers) and propagated faster in aboral than in oral direction. Dominant pacemakers were distributed along the intestine at regular intervals. The preparations were mostly driven by 1 pacemaker at the time, but 2 or 3 pacemakers with different frequencies could be active simultaneously. Tetrodotoxin decreased aboral propagation velocity and revealed multiple regularly spaced pacemaker areas. Eserine increased, whereas L-arginine decreased, their frequency. After L-NAME, pacemaker activity increased and isolated pacemakers with higher frequency appeared. Conclusions: Nonneural pacemakers in rat ileum are functionally organized not as a continuous system but show a segmental arrangement, spatially and temporally modulated by neural activity. GASTROENTEROLOGY 2000;119:386-394

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with gastrointestinal mucosal damage. Omeprazole prevents the formation, and accelerates the healing, of NSAID-induced ulcers. Aim: To test whether omeprazole accelerates healing of standardized gastroduodenal lesions in the presence of diclofenac. Methods: In a double-blind, double-dummy, placebo-controlled, crossover study, 12 healthy volunteers received consecutive, 2-week courses of omeprazole (40 mg o.d.) and placebo, in random order, with an intervening, 4-week washout period; diclofenac (50 mg t.d.s.), was given for the second week of each course. Five endoscopies were performed, one at the outset and the others before and after each course of diclofenac. Biopsies were taken from the endoscopically normal mucosa of the corpus, antrum and duodenum and also from any new mucosal lesion that developed after diclofenac. The sites of biopsies taken before each course of diclofenac were evaluated endoscopically after each course to assess the extent of healing according to a predetermined healing score scale. Results: The healing scores observed after administration of placebo/diclofenac (median=0; range 0–6) and after omeprazole/diclofenac (median=0; range 0–6; P=0.17) did not differ. Small gastroduodenal lesions developed de novo in six subjects during placebo/diclofenac and in seven during omeprazole/diclofenac. Focal chemical gastropathy was observed only in close proximity to macroscopic lesions. Conclusions: In healthy subjects, omeprazole does not accelerate the healing of pre-existing mucosal lesions or prevent the development of small diclofenac-induced mucosal lesions.

Omeprazole produces a higher intragastric pH during Helicobacter pylori (H. pylori) infection than after cure. We tested the hypothesis that this difference is due to the production of ammonia by H. pylori.Gastric acidity and acid output (AO) were measured overnight in 12 subjects, with and without omeprazole, before and 1 and 6 months after cure of H. pylori infection. Gastric ammonia ([NH3]), total bile acid ([TBA]) and protein concentrations and plasma omeprazole levels were measured.During omeprazole, median AO were 0.0 mmol/h before, 0.86 mmol/h (p = 0.003 vs before cure) at 1 month, and 0.34 mmol/h (p = 0.02) at 6 months after cure; median NH3 output was 0.17 mmol/h before, 0.03 mmol/h (p = 0.002) at 1 month, and 0.02 mmol/h (p = 0.005) at 6 months after cure. AO and NH3 output were similar 1 and 6 months after cure. When corrected for [NH3], AO and gastric pH curves were similar before and after cure. Omeprazole plasma levels increased after cure and gastric [TBA] were unchanged.The higher pH observed before cure of H. pylori during omeprazole administration is attributable, in large part, to ammonia production. Other acid-neutralizing substances and changes in acid secretion may also be important, but duodenogastric reflux and omeprazole pharmacokinetics are not involved.

Correa's hypothesis proposes that gastric carcinogenesis is due to atrophic gastritis and hypochlorhydria which permit gastric bacterial colonization, the reduction of dietary nitrates to nitrites and the formation of potentially carcinogenic N-nitroso compounds (NOCs).To test the hypothesis that omeprazole-induced hypochlorhydria is associated with increased intra-gastric concentrations of nitrate-reducing bacteria (NRB), nitrites and NOCs.Single-blind study in healthy volunteers.Fourteen healthy subjects (seven female, mean age 24 years), free of Helicobacter pylori infection, received a one-week course of placebo followed by a two-week course of omeprazole, 20 mg daily.Fasted gastric samples, aspirated using a sterile double-lumen nasogastric tube at the end of the 1 st week (placebo) and the 2nd and 3rd weeks (omeprazole), were cultured aerobically and anaerobically; gastric pH and intra-gastric concentrations of nitrates, nitrites and NOCs were also determined.After weeks 1, 2 and 3, the intra-gastric concentrations of nitrate-reducing bacteria exceeded 10(5) colony-forming units (c.f.u.)/ml in 3, 7 and 9 subjects, respectively (P0.05). A gastric pH greater than 4.0 was associated with increased NRB (P0.05); however, neither increased gastric pH nor increased NRB, alone or in combination, was associated with increased intra-gastric concentrations of nitrites or NOCs (P0.05).A two-week increase in gastric pH in healthy, H. pylori-negative subjects was associated with increased intra-gastric concentrations of nitrate-reducing bacteria but not of nitrites or N-nitroso compounds. These data suggest that reduced gastric acid secretion is not a necessary precursor to the formation of carcinogenic N-nitroso compounds and that other mechanisms should be invoked to explain gastric carcinogenesis.

Background & Aims: Oral immunization with Helicobacter pylori urease can cure Helicobacter infection in animals. As a step toward therapeutic immunization in humans, the safety and immunogenicity of oral immunization with recombinant H. pylori urease were tested in H. pylori –infected adults. Methods: Twenty-six H. pylori –infected volunteers were randomized in a double-blind study to four weekly oral doses of 180, 60, or 20 mg of urease with 5 μg heat-labile enterotoxin of Escherichia coli (LT), LT alone, or placebo. Side effects and immune responses were evaluated weekly after immunization, and gastric biopsy specimens were obtained after 1 month and 6 months for histology and quantitative cultures. Results: Diarrhea was noted in 16 of 24 (66%) of the volunteers who completed the study. Antiurease serum immunoglobulin A titers increased 1.58-fold ± 0.37-fold and 3.66-fold ± 1.5-fold (mean ± SEM) after immunization with 60 and 180 mg urease, respectively, whereas no change occurred in the placebo ± LT groups ( P = 0.005). Circulating antiurease immunoglobulin A–producing cells increased in volunteers exposed to urease compared with placebo (38.9 ± 13.6/10 6 vs. 5.4 ± 3.1; P = 0.018). Eradication of H. pylori infection was not observed, but urease immunization induced a significant decrease in gastric H. pylori density. Conclusions: H. pylori urease with LT is well tolerated and immunogenic in H. pylori –infected individuals. An improved vaccine formulation may induce curative immunity. GASTROENTEROLOGY 1999;116:804-812

Background: Omeprazole produces a higher intragastric pH in the presence of Helicobacter pylori infection than after cure. Aim: To investigate whether this effect also occurs with pumaprazole (BY841), a reversible proton pump antagonist which, in contrast to omeprazole, does not require activation in the acid compartment of the parietal cell. Methods: In a randomized, crossover, double-blind study, 24-h intragastric pH was measured in 13 H. pylori-positive subjects before and after a 1-week course of omeprazole (20 mg o.d.) or of pumaprazole (100 mg b.d.). The studies were repeated after the infection was cured. Results: In the absence of drug administration, the median 24-h pH values before cure (median 2.0, 90% CI: 1.2–3.2) did not differ from those after cure (median 1.5, 90% CI: 1.3–2.2; P = 0.115). The 24-h pH values were higher before cure of the infection than after during both pumaprazole (6.0, 4.8–6.7 vs. 4.3, 2.6–5.7; P = 0.002) and omeprazole (5.8, 4.0–6.2 vs. 3.6, 2.8–5; P = 0.004). Both before and after cure, there were no significant differences between the two drugs with respect to acid inhibition over the 24-h period. The median decrease in acid inhibition after cure of the infection (calculated as the difference in H+ activity in mmol/L) during pumaprazole (median 0.05, 90% CI: 6 × 10–4– 2.3) was no different from that during omeprazole (median 0.2, 90% CI: 3 × 10–3–1.5; P = 0.6). Conclusions: Both before and after cure of H. pylori infection, pumaprazole raised the intragastric pH over a 24-h period to a similar degree as omeprazole. H. pylori infection similarly augments the pH-increasing effect of both drugs. This effect is related to H. pylori infection and not to an increased activation of acid inhibitory agents in the parietal cell compartment.

Helicobacter pylori colonises the gastric mucosa, but can also be found within the oral cavity. The presence of H. pylori was monitored in the oral cavity of 22 patients with duodenal ulcer, before and after antibiotic treatment and of 24 hospital employees who were or were not professionally exposed to H. pylori. Gastric infection was determined by breath test. Bacteria in the oral cavity were detected by nested PCR of samples containing saliva and dental plaque, using primers specific for 16S rRNA and ureC genes. Before treatment, 9 out of 22 infected ulcer patients harbored H. pylori in their oral cavity. Bacteria disappeared from the oral cavity of 3 of 7 cured patients. Twelve of 17 exposed subjects harbored H. pylori in their oral cavity, while no bacteria could be detected in the mouths of the 7 nonexposed subjects. Presence of bacteria in the oral cavity reflects handling of contaminants; it does not correlate with gastric infection and does not seem to promote it.

Background It is uncertain whether treatment of Helicobacter pylori infection relieves symptoms in patients with nonulcer, or functional, dyspepsia. Methods We conducted a double-blind, multicenter trial of patients with H. pylori infection and dyspeptic symptoms (moderate-to-very-severe pain and discomfort centered in the upper abdomen). Patients were excluded if they had a history of peptic ulcer disease or gastroesophageal reflux disease and had abnormal findings on upper endoscopy. Patients were randomly assigned to seven days of treatment with 20 mg of omeprazole twice daily, 1000 mg of amoxicillin twice daily, and 500 mg of clarithromycin twice daily or with omeprazole alone and then followed up for one year. Treatment success was defined as the absence of dyspeptic symptoms or the presence of minimal symptoms on any of the 7 days preceding the 12-month visit. Results Twenty of the 348 patients were excluded after randomization because they were not infected with H. pylori, were not treated, or had ...

This chapter reviews the evidence for a link between functional dyspepsia and Helicobacter pylori infection from three angles. In the section on pathophysiology, we evaluate how H. pylori could theoretically produce dyspeptic symptoms: many mechanisms can be proposed. In the discussion on epidemiology, we evaluate possible associations between the occurrence of symptoms and infection. Here, many studies claiming a coincidence or chronological sequence of infection and symptoms are criticized because of their poor design. In the section on the improvement of functional dyspepsia by the treatment of H. pylori infection, the conclusion is reached that if such an effect occurs at all—which is unlikely—it is very weak. The controversy on the link between H. pylori infection and functional dyspepsia is presently ongoing. Some authors are still trying to save an elegant concept that once looked so plausible but now has the facts against it.

Background.~ Helicobacter pylori (H. pylori) produces large amounts of ammonia. Based on higher readings obtained with an ammonia-sensitive electrode when compared to a specific enzymatic assay, it has been claimed that H. pylori also produces potentially toxic volatile amines. Method. We measured ammonia concentrations (NH3) in gastric aspirates from 11 H. pylori positive subjects (22–40 y, 6~ m), using an ammonia electrode sensitive to ammonia and amines, and an enzymatic assay specific for ammonia. Continuous aspiration was performed overnight and 220 aspirates were analyzed before and 6~weeks after cure of H. pylori. Gastric samples were diluted 1:3 (before cure) and 1:1 (after cure) according to dilution curves constructed prior to the assays. Results. Median (95% CI) NH3 detected by the elec-trode/enzymatic assay were 4.34~m m[4.12–4.61]/4.50~m m [4.28–4.68] (p~>~.05) before cure and 0.54~m m[0.42–0.60]/0.73~m m[0.71–0.81] after cure (p~>~.05). Intra-class correlation coefficient between the two methods was 0.91 before cure and 0.90 after cure (p~

BACKGROUND: In healthy subjects, continuous infusions of high dose ranitidine and omeprazole produce high intragastric pH values. AIM: To test the hypothesis that both drugs also maintain high intragastric pH values in patients with bleeding ulcers. PATIENTS AND METHODS: In two parallel studies, 20 patients with bleeding duodenal ulcers and 20 patients with bleeding gastric ulcers were randomly assigned to receive either ranitidine (0.25 mg/kg/hour after a bolus of 50 mg) or omeprazole (8 mg/hour after a bolus of 80 mg) for 24 hours. Intragastric pH was continuously recorded with a glass electrode placed 5 cm below the cardia. RESULTS: Both drugs rapidly raised the intragastric pH above 6. During the second 12 hour period, however, the percentage of time spent below a pH of 6 was 0.15% with omeprazole and 20.1% with ranitidine (p = 0.0015) in patients with duodenal ulcer; in patients with gastric ulcer it was 0.1% with omeprazole and 46.1% with ranitidine (p = 0.002). CONCLUSIONS: Primed infusions of omeprazole after a bolus produced consistently high intragastric pH values in patients with bleeding peptic ulcers, whereas primed infusions with ranitidine were less effective during the second half of a 24 hour treatment course. This loss of effectiveness may be due to tolerance.

PURPOSE Paclitaxel is a highly active single agent in the treatment of breast cancer. However, its optimal incorporation into combination regimens awaits definition. In this phase II study, we added paclitaxel, administered by 1-hour infusion, to a previously described combination regimen that included mitoxantrone, fluorouracil (5-FU), and high-dose leucovorin (NFL). PATIENTS AND METHODS Forty-six patients with metastatic breast cancer received the following regimen as first- or second-line treatment: paclitaxel 135 mg/m2 by 1-hour intravenous (i.v.) infusion on day 1, mitoxantrone 10 mg/m2 by i.v. bolus on day 1, 5-FU 350 mg2/m by i.v. bolus on days 1, 2, and 3, and leucovorin 300 mg i.v. over 30 to 60 minutes immediately preceding 5-FU on days 1, 2, and 3. Courses were administered at 3-week intervals for a total of eight courses in responding patients. RESULTS Twenty-three of 45 assessable patients (51%) had major responses. Previous chemotherapy, and in particular previous treatment with doxorubicin, did not affect response rate. The median response duration was 7.5 months. Myelosuppression was moderately severe, with 76% of courses resulting in grade 3 or 4 leukopenia. Hospitalization for treatment of fever during neutropenia was required in 13% of courses, and two patients died as a result of sepsis. Two patients developed severe congestive heart failure after a large cumulative anthracycline dose. CONCLUSION This combination regimen was active as first- or second-line therapy for metastatic breast cancer, although its activity compared with other combination regimens or with paclitaxel alone is unclear. Myelosuppression was more severe than anticipated based on previous results with the NFL regimen or with paclitaxel administered at this dose and schedule as a single agent. The infrequent development of cardiotoxicity in these patients suggests that the paclitaxel/mitoxantrone combination may not share the problems previously reported with the paclitaxel/doxorubicin combination.

BACKGROUND & AIMS: Omeprazole is less effective in healthy subjects than in patients with duodenal ulcers. The aim of this study was to determine whether Helicobacter pylori augments the pH-increasing effect of omeprazole in patients with duodenal ulcers. METHODS: In 16 patients with duodenal ulcers, baseline intragastric acidity was measured before and 4-6 weeks after the cure of H. pylori infection. In 17 patients with duodenal ulcers, 24-hour pH metry was performed during treatment with 20 mg omeprazole once daily before as well as after eradication of H. pylori. Intragastric acidity was measured using a glass electrode placed 5 cm below the cardia. H. pylori infection was assessed by [13C] urea breath test, culture, histology, and rapid urease test. RESULTS: H. pylori eradication resulted in marked decrease of the pH-increasing effect of omeprazole (24-hour median gastric pH, 5.5 vs. 3.0; P