Long-term prevention of erosive or ulcerative gastro-oesophageal reflux disease relapse with rabeprazole 10 or 20 mg vs. placebo: results of a 5-year study in the United States.

BACKGROUND: Erosive gastro-oesophageal reflux disease (GERD) is a chronic condition requiring long-term maintenance treatment. However, few trials of proton pump inhibitors in maintaining healing of erosive or ulcerative GERD are conducted for longer than 1 year. AIM: To compare the efficacy and safety of 10- and 20-mg rabeprazole with placebo in the 5-year maintenance of healing in patients previously diagnosed with erosive/ulcerative GERD healed in an acute efficacy trial. METHODS: Patients (N = 497) were randomized to receive once-daily doses of 10- or 20-mg rabeprazole or placebo. The primary efficacy measure was endoscopically documented absence of oesophageal erosions or ulcerations. RESULTS: After 5 years, relapse rates in both rabeprazole groups were significantly lower than with placebo (rabeprazole 20 mg, 11%; 10 mg, 23%; placebo, 63%; P < 0.001 for rabeprazole vs. placebo; P = 0.005 for rabeprazole 20 mg vs. 10 mg). Both rabeprazole doses were significantly superior to placebo in preventing relapse of heartburn frequency and improving patient quality of life. Analyses of adverse events, biopsy findings and laboratory values showed no evidence of clinically significant effects. CONCLUSIONS: Five-year maintenance therapy with rabeprazole is effective in preventing relapse of erosive or ulcerative GERD and is well tolerated.

Rabeprazole for the prevention of recurrent erosive or ulcerative gastro-oesophageal reflux disease. Rabeprazole Study Group.

OBJECTIVES: To evaluate the efficacy and tolerability of rabeprazole 10 mg and 20 mg versus placebo for the prevention of endoscopically demonstrable relapse in patients previously diagnosed with erosive or ulcerative gastro-oesophageal reflux disease (GORD) who had no oesophageal erosions or ulcerations at study entry. The study also assessed the effectiveness of rabeprazole in preventing GORD symptom recurrence and reductions in quality of life. DESIGN/METHODS: The trial used a multicentre, randomized, double-blind, parallel-group design and enrolled 288 male and female outpatients of > or =18 years of age. Patients were assigned to treatment with either rabeprazole 10 mg or 20 mg once daily in the morning (QAM) or placebo and followed for 52 weeks. RESULTS: Both rabeprazole doses were significantly more effective than placebo in preventing endoscopically demonstrable GORD relapse (P<0.001 versus placebo). The cumulative relapse rate for rabeprazole 10 mg at week 52 was 23%; for rabeprazole 20 mg, 14%; and for placebo, 71%. Both rabeprazole doses were also significantly superior to placebo in preventing relapse of heartburn frequency (P<0.001 for all comparisons between rabeprazole and placebo), with no significant differences between the two doses. Rabeprazole was also significantly more effective than placebo in preventing relapse of day-and night-time heartburn severity, maintaining overall patient well-being, and reducing antacid use. Both rabeprazole doses were well tolerated; most treatment-emergent adverse events were mild or moderate. There were no clinically significant changes in clinical laboratory values, thyroid function tests, vital signs, or electrocardiograms. CONCLUSION: Once-daily treatment with rabeprazole 10 mg or 20 mg is effective and well tolerated in preventing relapse of erosive or ulcerative GORD and associated symptoms and maintaining quality of life.

[Column extraction analysis in pharmacology and toxicology (author's transl)]. / Säulenextraktionsanalyse in Pharmakologie und Toxikologie.

The extraction of lipophilic compounds from body fluids is preferably performed with a new procedure, the Extrelut-column extraction. The aqueous solution is applied onto the column and remains as the stationary phase on the porous support material. On elution with organic solvents lipophilic substances are extracted from the aqueous phase into the eluent. The method offers several advantages: No formation of emulsions, saving of solvents, high recovery rates and purer extracts than are obtained using conventional extraction. Three examples of application are described: A barbiturate determination from blood and serum, which is highly simplified compared with the conventional extraction. The isolation of basic compounds from blood using extraction and simultaneous purification by means of coupled extraction and absorption columns. A thin-layer chromatographic screening procedure for drugs in urine including column extraction.

Segmental tuberculosis of the colon diagnosed by colonoscopy.

Segmental tuberculosis of the colon is a rare clinical entity. In the absence of pulmonary or ileocecal involvement, colonic tuberculosis may be difficult to differentiate from neoplasm or Crohn's disease by symptomatic and radiological means. Colonoscopy and biopsy can, however, establish the diagnosis and prevent operative intervention, as indicated in the present report. A patient with a radiologically demonstrated strictured lesion of the sigmoid colon was found at colonoscopy to have several hemorrhagic transverse ulcers ranging in diameter between 1-4.5 cm. Multiple target colonoscopic biopsies, specifically from the ulcer beds, revealed necrotizing granulomas and acid-fast bacilli. Antituberculous chemotherapy produced remarkable symptomatic, radiographic and endoscopic improvements and averted exploratory laparotomy for the establishment of the diagnosis. This case report points out the importance of colonoscopic biopsy as a useful diagnostic modality in this disease.

Staphylococcal micrococcins. II. Isolation, purification and identification.

Seven strains belonging to the Micrococcaceae family and excreting substances with antibiotic activity, were grown in submerged cultures on technical scale for isolation, purification and identification of biologically active compounds. Two basic substances were isolated and classified to the micrococcin antibiotics family. The naturally occurring mixture of micrococcin M1 and M3 was called micrococcin M. This antibiotic has the formula C48H50O11N12S6 and a molecular weight of about 1160, melting point 221--224 degrees C, and optical rotation [a]20/D = + 66.6. Other antibiotically active substances produced by seven investigated strains were identified as micrococcin M or as separate compounds. Comparison with previously described micrococcin and micrococcin P has been made.

Evaluation of column extraction: a new procedure for the analysis of drugs in body fluids.

A method is described for the extraction of drugs from body fluids, whereby liquid-liquid extraction is replaced by liquid-solid elution. The aqueous sample is absorbed on a column filled with dry supporting material. By elution with organic solvents lipophilic substances are extracted from the water phase which remains on the column. The eluate containing the drugs is free of emulsions. For optimal extraction any pH value and a variety of solvents can be used. Column extraction of urine, serum and blood is easily performed and gives high recovery rates, which are superior to conventional extraction. Thin layer chromatography of drugs following conventional XAD-2 and column extraction, demonstrates identical qualitative results, but shows higher purity of the column extracts. The sensitivity of detection is enhanced.

Thin layer chromatographic screening for methaqualone, phenothiazines, opiates and benzodiazepines.

A method is described which permits the simultaneous detection of methaqualone, phenothiazines, opiates and benzodiazepines in urine. Its diagnostic application is discussed. After cleavage of conjugates with hydrochloric acid, the substances are extracted and identified by thin-layer chromatography. In most cases analysis can be carried out using 2 solvent systems, phenothiazines, methaqualone and opiates being visualised using a three stage spray sequence. Since phenothiazines can interfere with the detection of methaqualone, a specific eluant is used to ensure reliable detection of the latter. Methaqualone can be positively identified by its characteristic metabolite pattern, whereas phenothiazines can only be detected as a group.

The effect of stirring of the luminal solution on the protection of the rat intestinal mucosa during ischemic injury.

Segments of rat ileum made ischemic for 15 min by occlusion of their mesenteric vessels were intraluminally perfused at slow and rapid rates with Krebs buffer containing O2, O2 + glucose or nitrogen. Mucosal leucine influx was measured at the end of the ischemic period. O2 and O2 with glucose provided protection against the ischemic injury, particularly when the stirring of the luminal solution was increased. Rapid perfusion in the absence of oxygen or glucose also protected the intestine probably by rinsing the ischemic gut of noxious agents.

Rabeprazole is superior to ranitidine in the management of active duodenal ulcer disease: results of a double-blind, randomized North American study.

OBJECTIVE: The primary purpose of this study was to compare the efficacy and tolerability of rabeprazole versus ranitidine in the treatment of patients with active duodenal ulcer disease. METHODS: This multicenter, double-blind, randomized, parallel-group study enrolled 376 patients. Patients were randomly assigned to receive rabeprazole 20 mg administered once daily in the morning (q.a.m.) with matching ranitidine placebo twice daily (b.i.d.) (n = 188), or ranitidine 150 mg b.i.d. with matching rabeprazole placebo q.a.m. (n = 188). Three visits were scheduled: wk 0 (baseline; days -3 to -1), wk 2 (day 15+/-3 days), and wk 4 (day 29+/-3 days). The primary efficacy response variable was defined as complete regeneration of the mucosa at the site of all ulcers identified during the study. Secondary efficacy variables included patients' ratings of frequency and severity of ulcer pain, frequency of antacid use, and improvement of overall physical well-being. Tolerability was evaluated with analyses of adverse events, laboratory evaluations, fasting serum gastrin levels, vital signs, body weight, and electrocardiograms. RESULTS: Up to 4 wk of treatment with rabeprazole 20 mg q.a.m. produced significantly greater healing rates, compared to treatment with ranitidine 150 mg b.i.d. (83% vs 73%; p = 0.017). Significant differences between treatment groups were also observed for secondary efficacy indices. At wk 2, rabeprazole was more likely than ranitidine to produce complete resolution of duodenal ulcer pain (39% vs 25%; p = 0.006), improvement in duodenal ulcer nighttime pain severity (76% vs 65%; p = 0.044), and improvement in overall well-being (55% vs 41%; p = 0.009). At wk 4, the proportion of patients with normalization of overall well-being was significantly higher in the rabeprazole group than in the ranitidine group (45% vs 29%; p = 0.003). Rabeprazole was safe and well tolerated in this study. CONCLUSIONS: In patients with active duodenal ulcer disease, rabeprazole 20 mg q.a.m. is superior to ranitidine 150 mg b.i.d. in healing, resolving ulcer pain frequency, improving nighttime pain severity, and improving overall well-being. Rabeprazole is an effective and well-tolerated alternative treatment for patients with active duodenal ulcer disease.

Filiform polyposis of the colon presenting as massive hemorrhage: an uncommon complication of Crohn's disease.

A case of localized filiform polyposis of the colon is presented. This lesion was part of a more generalized inflammatory bowel disease with clinicopathological features indicative of Crohn's disease. An unusual feature of this case was profuse rectal bleeding, initially from a solitary sigmoid ulcer and later from the area of filiform polyposis. A step by step clinicopathological follow-up emphasizing the development of filiform polyps is provided.

An alternative non-macrolide, non-imidazole treatment regimen for curing Helicobacter pylori and duodenal ulcers: ranitidine bismuth citrate plus amoxicillin. The RBC H. pylori Study Group.

BACKGROUND: Because patients who fail to be cured of H. pylori infection following macrolide or imidazole therapy are difficult to treat, there is a clear need for a reasonably effective and simple second-line treatment regimen. The purpose of these two studies was to evaluate the efficacy of ranitidine bismuth citrate (RBC) plus amoxicillin for the cure of H. pylori infection and for healing duodenal ulcers and preventing ulcer relapse. MATERIALS AND METHODS: Two identically designed randomized, double-blind, double-dummy studies were conducted in patients with an H. pylori-associated duodenal ulcer. Patients were treated with either RBC 400 mg bid for 4 weeks plus amoxicillin 500 mg qid for 2 weeks, RBC 400 mg bid for 4 weeks and placebo qid for 2 weeks, placebo bid for 4 weeks and amoxicillin 500 mg qid for 2 weeks, or placebo bid for 4 weeks and placebo qid for 2 weeks. Patients with healed ulcers after 4 weeks of treatment were eligible for entry into a 24-week observation phase for the assessment of H. pylori status (culture, histology, and CLOtest) and ulcer relapse. RESULTS: A total of 229 patients with confirmed H. pylori infection at baseline were evaluated. Of these, 132 whose ulcers had healed entered the 24-week posttreatment observation phase. The combination of RBC plus amoxicillin resulted in higher H. pylori cure rates (55%) and higher duodenal ulcer healing (74%) than did either treatment alone. All treatment were well tolerated. CONCLUSIONS: The combination of ranitidine bismuth citrate plus amoxicillin cures H. pylori infection in more than half of the patients treated. This treatment regimen shows promise as the basis for future non-macrolide, non-imidazole triple therapy regimens for curing H. pylori infection. Such regimens may be appropriate second-line treatment for patients who are resistant to or who are unable to tolerate macrolide- or imidazole-containing therapies.

Efficacy and safety of esomeprazole compared with omeprazole in GERD patients with erosive esophagitis: a randomized controlled trial.

OBJECTIVE: In patients with gastroesophageal reflux disease (GERD), esomeprazole, the S-isomer of omeprazole, has demonstrated pharmacological and clinical benefits beyond those seen with the racemic parent compound. This study was designed to further evaluate the efficacy and tolerability of esomeprazole relative to that of omeprazole in healing erosive esophagitis and resolving accompanying symptoms of GERD. METHODS: Esomeprazole 40 mg was compared with omeprazole 20 mg once daily in 2425 patients with erosive esophagitis (Helicobacter pylori negative by serology) in an 8-wk, multicenter, randomized, double-blind, parallel-group study conducted in 163 centers throughout the US. The primary efficacy endpoint was the proportion of patients with healed esophagitis at wk 8. Secondary endpoints were the proportion of patients healed at wk 4, resolution of heartburn at wk 4, time to first resolution and sustained resolution of heartburn, and proportion of heartburn-free days and nights. Safety and tolerability were also assessed. RESULTS: Significantly more patients were healed with esomeprazole versus omeprazole at wk 8 (93.7% vs 84.2%, p < 0.001; life table estimates, intention-to-treat analysis). Healing rates at wk 4 were 81.7% and 68.7%, respectively. Esomeprazole was superior to omeprazole for all secondary measures and had a similar safety profile. The most common adverse events in both treatment groups were headache, diarrhea, and nausea. CONCLUSIONS: Esomeprazole demonstrates significantly greater efficacy than omeprazole in the treatment of GERD patients with erosive esophagitis. The tolerability and safety of esomeprazole are comparable to that of omeprazole. (Am