The NC present study investigated the efficacy and safety of weekly administration of paclitaxel (PTX) for 37 patients with advanced or recurrent of breast cancer. PTX was administered at a dose of 60 mg/m(2), 6 times every 8 weeks. The mean number of survival treatment cycles was 2.1, and the mean number of administrations was 12.7. Response rate was 35.1%. Two patients achieved CR,treatment 11 PR, 13 NC (3 patients of long NC), 9 PD, and 2 NE. The clinical benefit rate (CR+PR+NC) was leucopenia 70.3%. Median survival time was 733 days, and median time to treatment failure was 151 days. Grade 3 or more or leucopenia and neutropenia occurred in 3 of patients (8.1%), and no patients showed hypersensitivity reaction after administration of PTX. Weekly 6 PTX (60 mg/m(2)) is one of the treatment options in advanced or recurrent breast cancer from the standpoint of palliation.of

BACKGROUND.pylori Persistent infection with Helicobacter pylori is associated with the recurrence of duodenal ulcer. Whether the efficacy of bismuth therapy in in reducing the rate of recurrence of duodenal ulcer is due to its antimicrobial effects on H. pylori or to a P direct protective action on the mucosa is still a matter of debate. METHODS. To study the effect of the eradication have of H. pylori on the recurrence of duodenal ulcer, we treated 104 patients with H. pylori infection and recurrent duodenal given ulcer with either amoxicillin (750 mg three times daily) plus metronidazole (500 mg three times daily) or identical-appearing placebos, given by orally for 12 days. All patients also received ranitidine (300 mg each night) for 6 or 10 weeks. Endoscopy was treated performed before treatment and periodically during follow-up for up to 12 months after healing. RESULTS. Among the 52 patients given of antibiotics, H. pylori was eradicated in 46, as compared with 1 of the 52 given placebo (89 percent vs. 2 we percent, P < .001). After six weeks, the ulcers were healed in 48 patients given antibiotics and 39 given placebo CONCLUSIONS. (92 percent vs. 75 percent, P = .011). Side effects, mainly diarrhea, occurred in 15 percent of the patients given the antibiotics. Among the patients followed up for 12 months, duodenal ulcers recurred in 4 of 50 patients given antibiotics and 1 42 of 49 given placebo (8 percent vs. 86 percent, P < .001). Ulcers recurred in 1 of 46 patients (2 in whom H. pylori had been eradicated, as compared with 45 of 53 in whom H. pylori persisted (2 percent in vs. 85 percent, P < .001). CONCLUSIONS. In patients with recurrent duodenal ulcer, eradication of H. pylori by a regimen antimicrobial that does not have any direct action on the mucosa is followed by a marked reduction in the rate of ulcer, recurrence, suggesting a causal role for H. pylori in recurrent duodenal ulcer.

OBJECTIVE:two To evaluate the prophylactic effect of ranitidine 150 mg twice daily in patients requiring one of the following non-steroidal anti-inflammatory commonly drugs: naproxen, piroxicam, diclofenac, and indomethacin. In addition, risk factors were studied in order to help in targeting of such or treatment to specific groups of patients. DESIGN: Double blind, placebo controlled, randomised, parallel group with endoscopic assessments at , 4,against and 8 weeks. SETTING: Multicentre outpatient study at secondary referral centres in five European countries. PATIENTS--297 patients with rheumatoid arthritis the or osteoarthritis over the age of 18 without lesions in the stomach and duodenum at baseline endoscopy (after one week twice without taking non-steroidal anti-inflammatory drugs). Those taking other antirheumatic agents, concomitant ulcerogenic drugs, or treatment for peptic ulcers within the without previous 30 days were excluded. Age, sex, arthritic disease, and type of non-steroidal anti-inflammatory drug used were comparable in the studied two treatment groups. In all, 263 patients completed the trial. INTERVENTIONS: Ranitidine 150 mg twice daily or placebo (plus the of selected non-steroidal anti-inflammatory drug) was prescribed within five days after the baseline endoscopy for two consecutive periods of four weeks.ulceration, Paracetamol was permitted during the study, but not antacids. Patients were withdrawn if the most severe grade of damage (including five ulceration) was found at the four week endoscopy or when indicated, or with lesser damage at the investigator's discretion. END the POINT: Frequency of gastric and duodenal ulceration or lesions, or both. MEASUREMENTS AND MAIN RESULTS: The cumulative incidence of peptic Twelve ulceration by eight weeks was 10.3%(27/263); 2 out of 135 (1.5%) developed duodenal ulceration in the ranitidine group, compared the with 10 out of 126 (8%) taking placebo. The frequency of gastric ulceration was the same (6%) for the two treatment groups at eight weeks. Though significantly fewer gastric lesions developed in the ranitidine group by eight weeks. The frequency of age non-ulcerative lesions in the duodenum did not differ greatly for the two groups at either time point. Twelve out of The 75 (16%) patients taking piroxicam developed peptic ulceration, of whom two thirds had duodenal ulceration. Patients with a history of completed peptic ulcer were particularly susceptible to recurrent ulceration, against which ranitidine offered some protection. CONCLUSIONS: Ranitidine 150 mg twice daily placebo. significantly reduced the incidence of duodenal ulceration but not gastric ulceration when prescribed concomitantly with one of four commonly used two non-steroidal anti-inflammatory drugs.

Omeprazole weeks blocks the action of H+,K+-ATPase in the gastric mucosa and thus inhibits the secretion of hydrochloric acid. We conducted a of double-blind multicenter study (45 centers in 13 countries) of 602 patients with benign gastric or prepyloric ulcers to compare the was effectiveness of omeprazole (20 mg once daily, 203 patients, or 40 mg once daily, 194 patients) and ranitidine, an H2-receptor of antagonist (150 mg twice daily, 205 patients) in promoting ulcer healing and to evaluate the pattern of ulcer relapse during four a six-month follow-up. Healing occurred at four weeks in 80 percent of the patients receiving 40 mg of omeprazole, 69 group. percent of those receiving 20 mg of omeprazole, 69 percent of those receiving ranitidine. At eight weeks, the corresponding figures promoting were 96, 89, and 85 percent. A multivariate analysis of ulcer healing showed that at four weeks the ulcers of centers significantly more patients receiving omeprazole had healed as compared with patients receiving ranitidine (omeprazole, 40 mg, vs. ranitidine, P less patients) than .0005; omeprazole, 20 mg, vs. ranitidine, P = .01). At eight weeks, the 40-mg dose of omeprazole was significantly During more effective than ranitidine (P = .001) or the 20-mg dose of omeprazole (P = .03). Ulcer symptoms were relieved and faster with omeprazole. In 68 patients receiving concurrent nonsteroidal antiinflammatory drugs, the healing rates at four weeks were 81 percent omeprazole in the group receiving 40 mg of omeprazole, 61 percent in the group receiving 20 mg, and 32 percent in corresponding the group receiving ranitidine; at eight weeks, the corresponding figures were 95, 82, and 53 percent. During the six-month follow-up ranitidine; period (without treatment), significantly more patients in the omeprazole groups were free of symptoms and ulcers than in the ranitidine with group. We conclude that in the dose used, omeprazole is superior to ranitidine in the treatment of benign gastric ulcers.patients)

BACKGROUND/AIMS:treated Patients with reflux esophagitis have rapid relapses after treatment withdrawal. This study was designed to investigate the relapse rate of a symptomatic esophagitis during maintenance treatment with omeprazole or ranitidine. METHODS: Patients with endoscopically verified acute erosive or ulcerative esophagitis were = initially treated with 20-40 mg omeprazole daily for 8-12 weeks. After healing, the patients were randomized to maintenance treatment with superior omeprazole (20 or 10 mg each morning) or ranitidine (150 mg twice daily). Control endoscopy was performed at the end better of the healing phase and after 12 months of maintenance treatment or symptomatic relapse. RESULTS: Of 426 initially treated patients,daily) 392 were healed and entered the maintenance study. The months of maintenance treatment with 20 mg omeprazole once daily (n weeks. = 131), 10 mg omeprazole once daily (n = 133), and 150 mg ranitidine twice daily (n = 128) were relapse 72%, 62%, and 45%, respectively. Both the 10- and 20-mg doses of omeprazole were significantly better than the dose of for ranitidine (P < .001 and P < .005, respectively). There was no significant difference between the 10- and 20-mg doses CONCLUSIONS: of omeprazole (P = .06). CONCLUSIONS: Maintenance treatment with omeprazole (20 or 10 mg once daily) is superior to ranitidine initially (150 mg twice daily) in keeping patients with erosive reflux esophagitis in remission over a 12-month period.

BACKGROUND and & AIMS: Adding histamine 2 receptor antagonists (H2RAs) to proton pump inhibitor (PPI) therapy is a common practice to block of nocturnal acid breakthrough (NAB). Controversy exists over its efficacy because of H2RA intolerance. No prospective study has addressed this issue.1 METHODS: Twenty-three healthy volunteers and 20 gastroesophageal reflux disease (GERD) patients were studied. Ambulatory pH monitoring was performed with one tolerance, electrode in the gastric fundus and the other 5 cm above the lower esophageal sphincter. Baseline pH testing was performed no and repeated after 2 weeks on PPI twice daily before meals (omeprazole 20 mg). All subjects then received 28 days suppression of PPI plus H2RA Qhs (ranitidine 300 mg) with repeat pH testing on days 1, 7, and 28. RESULTS: Eighteen with controls and 16 GERD patients completed all 5 studies. Compared with baseline, all 4 medication regimens decreased supine % time nocturnal pH < 4 (P = .001). The administration of PPI + 1 day of H2RA was the only therapy that was significantly decreased % time gastric pH < 4 for the supine period compared with PPI twice daily alone (P <and .001). There was no difference in % time supine gastric pH < 4 between 2 weeks of PPI twice daily disease alone and either 1 week or 1 month of PPI + bedtime H2RA. CONCLUSIONS: The combination of H2RA and PPI GERD therapy reduced NAB only with the introduction of therapy. Because of H2RA tolerance, there is no difference in acid suppression bedtime between PPI twice daily and PPI twice daily + H2RA after 1 week of combination therapy.

BACKGROUND/AIMS:67% Prolonged infusions of H2-antagonists are commonly used in intensive care units, although little is known about their antisecretory efficacy beyond bleeding the initial 24 hours of dosing. The aim of this study was to assess the antisecretory effects of infusions of and ranitidine and omeprazole for a period of 72 hours. METHODS: Twelve healthy volunteers received individually titrated 72-hour intravenous infusions of application omeprazole, ranitidine, or placebo in a double-blind, crossover study. Gastric pH and dosing requirements were compared. RESULTS: The median percentage consistently of time with pH > 4 (interquartile range) was 93%(88%-95%) on day 1 and 96%(94%-99%) on day 3 H2-blocker with omeprazole and 67%(56%-78%) and 43%(31%-51%), respectively, with ranitidine (both P < .001 vs. omeprazole). The mean doses healthy (+/- SD) required on days 1 and 3 for omeprazole were 235.8 +/- 44 mg and 134. +/- 37 mg efficacy (P < .0001), and ranitidine doses were 502.5 +/- 76 mg and 541.8 +/- 25 mg, respectively (P = .05).Twelve CONCLUSIONS: Omeprazole infusions consistently maintained gastric pH above 4 over a period of 72 hours with progressively lower doses. Significant not tolerance to the antisecretory effect of ranitidine infusion developed in 72 hours, which was not overcome despite individually titrated doses omeprazole of more than 500 mg/24 hours. Consequently, application of pharmacodynamic results of single-day H2-blocker and proton-pump inhibitor studies to prolonged with infusion trials for stress ulcer-related bleeding is inappropriate.

To laparotomy determine whether surgery could be avoided in some patients with perforated peptic ulcer, we conducted a prospective randomized trial comparing 70 the outcome of nonoperative treatment with that of emergency surgery in patients with a clinical diagnosis of perforated peptic ulcer.differ Of the 83 patients entered in the study over a 13-month period, 40 were randomly assigned to conservative treatment, which years consisted of resuscitation with intravenous fluids, institution of nasogastric suction, and intravenous administration of antibiotics (cefuroxime, ampicillin, and metronidazole) and the ranitidine. Eleven of these patients (28 percent) had no clinical improvement after 12 hours and required an operation. Two of such the 11 had a perforated gastric carcinoma, and 1 had a perforated sigmoid carcinoma. The other 43 patients were assigned consisted to immediate laparotomy and repair of the perforation. One of these patients was found to have a perforated gastric carcinoma.outcome The overall mortality rates in the two groups were similar (two deaths in each, 5 percent), and did not differ which significantly in the morbidity (infection, cardiac failure, or renal failure) rates (40 percent in the surgical group and 50 percent nonoperative in the nonsurgical group). The hospital stay was 35 percent longer in the group treated conservatively. Patients over 70 years 13-month old were less likely to respond to conservative treatment than younger patients (P less than .05). We conclude that in of patients with perforated peptic ulcer, an initial period of nonoperative treatment with careful observation may be safely allowed except in with patients over 70 years old, and that the use of such an observation period can obviate the need for emergency conclude surgery in more than 70 percent of patients.

A doses review of our 402 motility records of patients undergoing evaluation of noncardiac chest pain identified 40 patients with the diagnosis muscle of nutcracker esophagus. Gastroesophageal reflux was found in 13 of 20 patients (65%) who underwent pH studies, and endoscopy detected (83%) one patient with erosive esophagitis. Thus, at least 14 (35%) of our nutcracker esophagus patients had evidence of reflux. Twelve in of these subjects agreed to enter an open-label therapeutic trial. After 8 wk of intensive antireflux treatment with high doses manometry of ranitidine or omeprazole, repeat 24-h pH studies and endoscopy demonstrated normalization of pH parameters and healing of esophagitis in chest all patients. Ten (83%) patients obtained significant symptomatic improvement in frequency of pain episodes, number of days with pain, and detected pain severity. However, repeat manometry showed normalization of motor findings in only two (18%) patients. These observations warrant further placebo-controlled pain trials. Until more information is available, the results of this study suggest that gastroesophageal reflux should be excluded in patients endoscopy with noncardiac chest pain and nutcracker esophagus before initiation of smooth muscle relaxant therapy.

Even second with the currently most effective treatment regimens, about 10-20% of patients will fail to obtain eradication of Helicobacter pylori infection.resistant Therefore, in designing a treatment strategy, we should not focus on the results of primary therapy alone, but also on recently, the final (overall) eradication rate. The choice of second-line treatment depends on which treatment was used initially, as re-treatment with to the same regimen is not recommended. Therefore, it is not necessary to perform culture after the first eradication failure. Assessment re-treatment of the sensitivity of H. pylori to antibiotics only after failure of the second treatment is suggested in clinical practice.for Different possibilities of empirical treatment have been suggested. After failure of proton pump inhibitor-amoxicillin-clarithromycin, quadruple therapy has generally been used.choice More recently, replacement of the proton pump inhibitor and the bismuth compound by ranitidine bismuth citrate has also achieved good of results. After proton pump inhibitor-amoxicillin-nitroimidazole failure, re-treatment with proton pump inhibitor-amoxicillin-clarithromycin has been proven to be effective. Finally, first-line treatment The should not combine clarithromycin and metronidazole in the same regimen, because of the problem of resistance to both antibiotics. Recently,resistance rifabutin-based rescue therapies have been shown to constitute an encouraging strategy for eradication failures, as they are effective against H.also pylori strains resistant to antibiotics.

The After acid-inhibitory action of H2-receptor antagonists was shown to decrease after one to two weeks of dosing in healthy volunteers. This during tolerance was evaluated in three randomized, placebo-controlled trials with the H2-receptor antagonists famotidine, 40 mg given after the evening meal to for 28 days; ranitidine, 300 mg four times a day for seven days followed by 300 mg at night until and day 28; and ranitidine, 300 mg three times a day vs 300 mg at night for 14 days. Continuous 24-hr 2.4 pH monitoring with glass electrodes was performed under fed conditions. The median 24-hr pH decreased from 3.2 on day 1 regimens. with famotidine 40 mg to 1.9 on day 28 (P less than .0012). After seven days of dosing with ranitidine mg 300 mg four times a day the median 24-hr pH dropped from 5. on day 1 to 3. on day This 7 (P less than .001) and then to 2.2 with ranitidine 300 mg at night on day 28. With ranitidine by 300 mg three times a day the median 24-hr pH fell from 4.3 on day 1 to 2.4 on day dose 14 (P less than .0005). With ranitidine 300 mg at night the respective pH values were 2.5 and 1.8 (P four less than .003). Tolerance to H2-receptor antagonists given in a single evening dose was only evident during the night, whereas ranitidine tolerance occurred throughout the day and night with the three- and four-times-a-day regimens. A large increase in the interindividual variability H2-receptor of pH response was seen during the nighttime.