Protective Effect of Famotidine, Omeprazole, and Melatonin Against Acetylsalicylic Acid-Induced Gastric Damage in Rats

It has been reported that both omeprazole and famotidine have a protective effect against gastric mucosal damage induced by acetylsalicylic acid (ASA) and other nonsteroidal antiinflammatory drugs. Since active oxygen species and lipid peroxidation were reported to play a role in the pathogenesis induced by ASA, we aimed to study if omeprazole and famotidine have any antioxidant effect by comparing their protective effect with that of melatonin, an effective antioxidant and free radical scavenger. Mucosal damage was evaluated by macroscopic examination, histological analysis and by measurement of lipid peroxidation (LPO), glutathione (GSH), and myeloperoxidase (MPO) activity. Omeprazole (20 mol/kg per os), famotidine (3 mg/kg per os), and melatonin (10 mg/kg intraperitoneally) significantly prevented gastric ulcerogenesis induced by ASA (200 mg/kg per os) and decreased the ulcer index. Gastric LPO and MPO activity that were increased significantly by ASA were decreased after treatment with omeprazole, famotidine, and melatonin. ASA treatment decreased significantly the gastric GSH levels, and pretreatment with omeprazole, famotidine, or melatonin increased it significantly. Famotidine and omeprazole decreased the gastric acidity, which was increased by ASA, whereas melatonin had no effect on this parameter. These findings suggest that active oxygene species and LPO have an important role in the pathogenesis of gastric mucosal damage induced by ASA and that both famotidine and omeprazole may be protective against this damage, although they were not as efficient as melatonin as an antioxidant. On the other hand, the antisecretory effect of omeprazole and famotidine may also be contributing to their antiulcer effect.     

Can famotidine and omeprazole be combined on a once-daily basis?

OBJECTIVE: Prompt and long-standing acid control following once-daily administration of antisecretory drugs is desirable. The objective of this study was to determine whether co-administration of a well-characterized H2-receptor antagonist, famotidine, can be combined with the proton-pump inhibitor omeprazole. MATERIAL AND METHODS: Intragastric 24-h pH-metry was performed in healthy, Helicobacter pylori-negative volunteers on day 1 and after 8 days of daily administration of 20 mg omeprazole, 10 mg famotidine, or a combination of these in a three-way crossover design. RESULTS: A combination of famotidine and omeprazole raised the gastric pH level to >4 in less than 1 h. The percentage of daytime with pH > 4 on day 1 was significantly higher with the combination of omeprazole and famotidine (median: 37%) than that with omeprazole alone (22%; p < 0.05). On day 8, daytime intragastric pH > 4 following treatment with omeprazole (median: 55%) or a combination of omeprazole and famotidine (61%) was superior (p < 0.05) to that with famotidine (21%). On day 1 treatment with both famotidine and the combination (famotidine and omeprazole) showed a significantly shorter time to reach a pH of 4 (medians: 93 and 63 min, respectively) compared with treatment with omeprazole alone (173 min; p < 0.05). CONCLUSIONS: Compared with treatment with omeprazole alone, on day 1 famotidine and omeprazole in combination improved the duration of and time to reach intragastric pH > 4. With regard to duration with pH > 4, the combination therapy was superior to famotidine alone on day 8. The rapid acid control with an H2-receptor antagonist may be combined with the long-lasting antisecretory effect of a proton-pump inhibitor.     

Omeprazole enhances efficacy of triple therapy in eradicating Helicobacter pylori.

Triple therapy has been recommended as the most effective treatment for Helicobacter pylori eradication. Despite achieving a comparatively high eradication result, however, around 10% of patients still fail to be cured. Omeprazole can enhance efficacy of single and double antibiotic protocols and is particularly effective when combined with clarithromycin and a nitroimidazole. This study examined the effect of combining triple therapy with omeprazole. A prospective, randomised, unblinded, single centre trial was carried out on consecutive patients with symptoms of dyspepsia and H pylori infection confirmed by rapid urease test, microbiological culture, and histological assessment. Patients were given a five times/day, 12 day course of colloidal bismuth subcitrate chewable tablets (108 mg), tetracycline HCl (250 mg), and metronidazole (200 mg) with either 20 mg omeprazole twice daily (triple therapy+omeprazole) or 40 mg famotidine (triple therapy+famotidine) at night. Compliance and side effects were determined using a standard questionnaire form. One hundred and twenty five of 165 triple therapy+omeprazole patients and 124 of 171 triple therapy+famotidine patients returned for rebiopsy four weeks after completion of treatment. Significantly more triple therapy+omeprazole patients achieved eradication 122 of 125 (97.6%) as assessed by negative urease test, culture, and histological assessment, when compared with 110 of 124 (89%) triple therapy+famotidine patients (p = 0.006; chi 2). There were 30 triple therapy+omeprazole (24%) and 26 triple therapy+famotidine (21%) patients with de novo metronidazole resistant H pylori included in the study. Side effects were mild and infrequent and were comparable in both groups, although pain in duodenal ulcer, gastric ulcer, and oesophagitis patients seemed to subside earlier in those taking omeprazole. Compliance (>95% of drugs taken) was achieved by 98% of patients of both groups. A 12 days regimen of triple therapy with omeprazole is more effective in achieving H pylori eradication than is triple therapy plus famotidine. Use of 20 mg omeprazole twice daily rather than 40 mg famotidine with a 12 day, low dose triple therapy enhances eradication to over 97% whether the H pylori is metronidazole sensitive or resistant.     

Dysregulation of gastric H,K-ATPase by cigarette smoke extract

AIM： To test whether the expression and activity of H,K-ATPase in parietal cells would be affected by cigarette smoke extract.
METHODS： Extracts of cigarette smoke were administered into mice by gastric gavage （5 mg/kg body weight/day） for 3 d or in drinking water for 7 or 14 d. For the latter, each day a mouse consumed 5 mL water containing extracts of two cigarettes, on average. Control littermate mice received only vehicle. To compare the amount of H,K-ATPase in control and smoke-treated mice, the stomach was processed for Western blotting and immunohistochemical analysis using monoclonal antibodies specific for α- or β-subunits of H,K-ATPase. The p-nitrophenylphospatase activity assay was used as a measurement for K-dependent H,K-ATPase activity.
RESULTS： Probed transblots showed an increase in the amount of H,K-ATPase in smoke-treated mice which was confirmed by immunohistochemistry and was found to be due to increased amounts of protein per parietal cell rather than an increased parietal cell number. The increase in the amount of H,K-ATPase was associated with an enhancement of its enzymatic activity. K-dependent activity in control and smoketreated mice was significantly different （respectively, 0.12 μmol/mg vs 0.27μmol/mg per minute, P 〈 0.05）.
CONCLUSION： Administration of cigarette smoke extract is associated with an increase in the amount and activity of H,K-ATPase and hence, smokers are susceptible to development of peptic ulcer.     

The effects of rabeprazole on parietal cells and enterochromaffin-like cells in rats: a comparison with omeprazole

Background. We investigated the effects of rabe-prazole compared with those of omeprazole on enterochromaffin-like cells and parietal cells in rats. Methods. Rabeprazole or omeprazole was administered for 7 days by intraperitoneal injection (100 mg/kg or 20 mg/kg once a day) and the serum gastrin concentration, the antral density of G cells and D cells, fundic histamine content, fundic H⁺, K⁺-ATPase mRNA level, and parietal cell morphology were determined. Results. Both rabeprazole and omeprazole inhibited gastric acid secretion and increased the intragastric pH to over 6.5, as well as causing a marked increase in the serum gastrin concentration. The serum gastrin level was lower with rabeprazole treatment than with omeprazole treatment at both doses. Also, the antral G-cell density was higher with omeprazole than with rabeprazole, while the increase in both the histamine content and the H⁺, K⁺-ATPase mRNA level in the fundic mucosa was higher with omeprazole treatment at both doses, with the difference being significant at 100 mg/kg. Ultrastructural examination indicated that the stimulation of parietal cells by omeprazole was stronger than that by rabeprazole. Conclusions. Rabeprazole treatment does not drive enterochromaffin-like cells and parietal cells as strongly as omeprazole treatment despite its potent acid suppressive effect, suggesting that it represents a new generation of proton pump inhibitors. Received: March 16, 2001 / Accepted: August 10, 2001     

Recombinant human granulocyte colony-stimulating factor reduces colonic epithelial cell apoptosis and ameliorates murine dextran sulfate sodium-induced colitis

Objective. Prompt and long-standing acid control following once-daily administration of antisecretory drugs is desirable. The objective of this study was to determine whether co-administration of a well-characterized H₂-receptor antagonist, famotidine, can be combined with the proton-pump inhibitor omeprazole. Material and methods. Intragastric 24-h pH-metry was performed in healthy, Helicobacter pylori-negative volunteers on day 1 and after 8 days of daily administration of 20 mg omeprazole, 10 mg famotidine, or a combination of these in a three-way crossover design. Results. A combination of famotidine and omeprazole raised the gastric pH level to >4 in less than 1 h. The percentage of daytime with pH?>?4 on day 1 was significantly higher with the combination of omeprazole and famotidine (median: 37%) than that with omeprazole alone (22%; p?0.05). On day 8, daytime intragastric pH?>?4 following treatment with omeprazole (median: 55%) or a combination of omeprazole and famotidine (61%) was superior (p?0.05) to that with famotidine (21%). On day 1 treatment with both famotidine and the combination (famotidine and omeprazole) showed a significantly shorter time to reach a pH of 4 (medians: 93 and 63 min, respectively) compared with treatment with omeprazole alone (173 min; p?0.05). Conclusions. Compared with treatment with omeprazole alone, on day 1 famotidine and omeprazole in combination improved the duration of and time to reach intragastric pH?>?4. With regard to duration with pH?>?4, the combination therapy was superior to famotidine alone on day 8. The rapid acid control with an H₂-receptor antagonist may be combined with the long-lasting antisecretory effect of a proton-pump inhibitor.     

The comparative effects of single intravenous doses of omeprazole and famotidine on intragastric pH

Background The ideal medication for the treatment of acid-related diseases, for example, hemorrhagic ulcers and stress-related gastric bleeding, should have a rapid onset of action to promote hemostasis and alleviate symptoms. The aim of our study was to investigate the inhibitory effects on gastric acid secretion after single intravenous administrations of omeprazole 20mg and famotidine 20mg.Methods Ten healthy Helicobacter pylori-negative male subjects participated in this randomized, double-masked, two-way crossover study. Intragastric pH was monitored continuously for 4h after a single intravenous administration of omeprazole 20mg and after a single intravenous administration of famotidine 20mg. The administration of the two agents was separated by a 7-day washout period.Results In all ten subjects, the length of time that intragastric pH remained over 3, during the 0- to 3- and 0- to 4-h study periods, was greater after famotidine treatment than after treatment with omeprazole, and famotidine increased the average pH during the 0 to 3- and 0 to 4-h study periods significantly more than omeprazole did. During the 4-h study period, famotidine provided a longer duration of pH of more than 2, 3, 3.5, 4, 5, 6, and 7, compared to omeprazole.Conclusions In Helicobacter pylori-negative healthy male subjects, an intravenous dose of 20mg famotidine increased intragastric pH more rapidly than intravenous omeprazole 20mg.     

Inhibitory Potency of Twice-a-Day Omeprazole on Gastric Acidity Is Enhanced by Eradication of H. pylori in Duodenal Ulcer Patients

The gastric pH-elevating effect of proton pump inhibitors such as omeprazole has been reported to be greater in the presence than in the absence of an H. pylori infection. It is unknown if this effect persists when a higher dose of omeprazole is taken. We undertook both 24-hr pH-metry and 24-hr aspiration studies in 12 H. pylori-positive patients with a history of duodenal ulcer (DU); (1) when not on omeprazole; (2) when on omeprazole 20 mg twice a day for 8 days; (3) two months after eradication of H. pylori and when not on omeprazole; and (4) after eradication of H. pylori and when on omeprazole twice a day. Eradication of H. pylori in DU results in lower mean and median pH; decreased percent pH q 3/ 4, and greater median H⁺ after breakfast, after lunch, and overnight; and omeprazole appears to have less of a pH-elevating effect in the absence than in the presence of an H. pylori infection. The fall in gastric juice NH₃ concentration as a result of eradicating H. pylori partially explained the lower pH-elevating effect of omeprazole. The variation in acid inhibitory effect of omeprazole after as compared with before eradication of H. pylori could not be explained by differences; (1) in gastric juice concentrations of IL-1, IL-8, IL-13, or epidermal growth factor; (2) in the fasting or fed total concentration of gastric juice bile acids; (3) in the fasting concentrations or area under-the-curve (AUC) of the gastric H⁺ concentrations in response to food; or (4) in the pharmacokinetics of omeprazole. The difference in H⁺ AUC without omeprazole minus with omeprazole was actually greater when compared after versus before eradication of H. pylori. Thus, in DU the pH-elevating potency of omeprazole taken twice a day is greater in the presence than in the absence of an H. pylori infection.     

Comparison of the effect of omeprazole--a substituted benzimidazole--and ranitidine--a potent H2-receptor antagonist--on histamine-induced gastric acid secretion and the ultrastructure of canine parietal cells

Gastric acid secretion and mucosal biopsy findings in canine stomach were evaluated after administration of omeprazole or ranitidine with and without histamine stimulation. Pretreatment with omeprazole (1 mg/kg) or ranitidine (0.5 mg/kg) almost completely prevented subsequent stimulation of acid secretion by histamine (40 micrograms/kg-h). Only ranitidine pretreatment, however, prevented post-histamine morphological transformation of parietal cells into the active state after histamine. Omeprazole pretreatment did not prevent the development of canaliculi and the reduction in the number of tubulovesicles in parietal cells after histamine. This canalicular expansion was, however, only partial with microvilli tightly packed together. Injection of omeprazole or ranitidine during half maximal stimulation by histamine effectively inhibited gastric acid secretion both in gastric fistulas (GF) and Heidenhain pouches (HP), and transformed the morphology of parietal cells into the resting state. In addition, omeprazole treatment with and without histamine stimulation increased the number of parietal cells with condensed mitochondria. This study demonstrates that omeprazole and ranitidine, while both potent inhibitors of gastric acid secretion, affect the parietal cell ultrastructure in different ways. Omeprazole does not prevent the formation of canaliculi in histamine-stimulated cells. This underscores the relative value of morphometrical studies of parietal cells.     

Role of Gastrin/CCK-B Receptor in the Regulation of Gastric Acid Secretion in Rat

The aim of this study was to investigate whethergastrin regulates morphological changes andalpha-subunit gene expression in parietal cells throughthe gastrin/CCK-B receptor on enterochromaffin-likecells by histamine release. Treatment with 100 mg/kgof YM022, a potent and selective gastrin/CCK-B receptorantagonist, for one week in rats did not alter mRNAlevels of histidine decarboxylase or H⁺,K-ATPase. However, parietal cell morphology predominantlychanged to the resting form, although the serum gastrinconcentration was significantly increased. Additionaltreatment with YM022 and oral omeprazole, 100 mg/kg, for one week markedly suppressed theincreases of mRNA levels of histidine decarboxylase andH⁺, K-ATPase and completely blocked themorphological transformation of the parietal cells to astimulated form induced by treatment with omeprazolealone. This indicates that the morphologicaltransformation of parietal cells to an activated formwith a subsequent increase in H⁺, K-ATPasesynthesis caused by hypergastrinemia is mediated by increasedhistidine decarboxylase gene expression inenterochromaffin-like cells via gastrin/CCK-Breceptors.     

Famotidine versus omeprazole, in combination with amoxycillin and tinidazole, for eradication of Helicobacter pylori infection

BACKGROUND: Eradication regimens combining two antibiotics with a proton pump inhibitor have been studied intensively. In contrast, only a few studies have focused on the possible role of H2-receptor antagonists in eradication therapy. The mechanism involved in the synergy between antibiotics and proton pump inhibitors is still controversial. OBJECTIVES: To compare the results of two triple-therapy regimens, different only in the antisecretory drugs used, in patients with Helicobacter pylori infection, and to assess the impact of primary resistance to metronidazole on treatment outcome. METHODS: A total of 120 patients with peptic ulcer and non-ulcer dyspepsia were randomly assigned to a 2-week course of either: famotidine 40 mg twice a day, amoxycillin 1 g twice a day and tinidazole 500 mg twice a day (FAT group; n = 60); or omeprazole 20 mg twice a day, amoxycillin 1 g twice a day and tinidazole 500 mg twice a day (OAT group; n = 60). Upper endoscopy was performed prior to treatment and at least 4 weeks after completion of treatment and discontinuation of the antisecretory therapy. H. pylori status was assessed by a biopsy urease test, histology and culture. RESULTS: In the intention-to-treat analysis, eradication of H. pylori was achieved in 48 of the 60 patients (80%; 95% confidence interval: 70-90%) in the FAT group, compared to 50 of the 60 patients (83.3%; 95% confidence interval: 74-93%) in the OAT group. In the per protocol analysis, eradication therapy was achieved in 48 out of 53 patients (90.6%; 95% confidence interval: 83-98%) treated with FAT and 50 out of 57 patients (87.7%; 95% confidence interval: 79-96%) treated with OAT (not significant). The primary metronidazole resistance was present in 28.8% of strains. Overall, per protocol eradication rates in strains resistant and susceptible to metronidazole were 83.3% and 91.3% respectively (P > 0.05). CONCLUSIONS: Two-week courses of either high-dose famotidine or omeprazole, both combined with amoxycillin and tinidazole, are equally effective for eradication of H. pylori infection. In a 2-week triple therapy, metronidazole resistance has no significant impact on eradication rates.     

Influence of the stimulation state of the parietal cells on the inhibitory effect of omeprazole on gastric acid secretion in dogs

The relationship between the stimulation state of the parietal cells and the gastric antisecretory properties of omeprazole has been evaluated in dogs with gastric fistulas maximally stimulated with pentagastrin. Intravenous administration of omeprazole (5 mumol/kg) 4 h before the start of stimulation with pentagastrin inhibited the acid response by 71%. This inhibition was prevented when omeprazole was given during an infusion of somatostatin at a dose that completely inhibited acid secretion. When given 18 h before stimulation with pentagastrin, omeprazole inhibited the acid response by 50%. This inhibitory effect was almost completely suppressed when omeprazole was administered during an infusion of somatostatin or after the administration of cimetidine, and was increased when omeprazole was given during an infusion of pentagastrin. These data indicate that the inhibitory effect of omeprazole given by rapid intravenous injection is related to the activity of the parietal cells at the moment of administration of the drug. They suggest that, in the intact animal as well as in the isolated gastric glands, the uptake of omeprazole by the parietal cells is related to the stimulation state of these cells.     

Cardiovascular effects of omeprazole and famotidine.

In a randomized, placebo-controlled, double-blind, crossover comparison, 12 patients with congestive heart failure (New York Heart Association class II) and dyspeptic complaints were treated orally for 1 week each with placebo, 40 mg omeprazole daily, and 40 mg famotidine daily. Non-invasive haemodynamic measurements were taken on the last day of treatment. Although omeprazole did not alter cardiac performance in impedance cardiography and mechanocardiography, the administration of famotidine led to a significant fall in stroke volume and cardiac output as compared with placebo (both p less than 0.05). Thus, omeprazole did not exert any relevant cardiovascular effects, in contrast to the H2-receptor antagonist famotidine.     

The effect of omeprazole on ultrastructural changes in gastric parietal cells

This study was designed to compare the effects of omeprazole and cimetidine on ultrastructural changes in parietal cells of guinea pigs during histamine stimulation. Both omeprazole and cimetidine remarkably inhibited acid secretion induced by histamine stimulation. Omeprazole, however, failed to prevent the morphological transition of parietal cells to an active stage during histamine stimulation, in contrast to cimetidine which inhibited the morphological transition. In addition, it was noticed that administration of omeprazole caused vacuolation in approximately 27% of all parietal cells. This phenomenon was not seen in control animals with histamine stimulation alone and only very rarely in cimetidine treated animals. Ultrastructural findings suggested that vacuoles originated in secretory canaliculi of parietal cells. These results may be the key to explain the difference of the inhibitory mechanism between omeprazole which acts on the final step of intracellular process (so-called proton pump) and cimetidine which acts on the H2-receptor site of plasma membrane.     

Comparison of adjuvant therapies by an H2-receptor antagonist and a proton pump inhibitor after endoscopic treatment in hemostatic management of bleeding gastroduodenal ulcers

Aim: Upper gastrointestinal bleeding is often associated with a higher risk of serious blood loss. Both H2‐receptor antagonists and proton pump inhibitors are commonly given intravenously for endoscopic hemostatic therapies. We compared the effects of a H2‐receptor antagonist (famotidine) and a proton pump inhibitor (omeprazole) injected during the early phase (the first 3 days) on cessation of bleeding and prevention of its recurrence in patients who underwent endoscopic therapy for gastroduodenal ulcer bleeding. Methods: Consecutive patients who were hospitalized at our clinic with bleeding gastroduodenal ulcers and underwent endoscopic therapy were randomly assigned to receive injections of famotidine, omeprazole, or both. Injection of acid suppressants was switched on the fourth day to the oral administration of omeprazole continued for 8 weeks. Results: Over a 25‐month period, 116 patients were enrolled. The overall success rate for endoscopic hemostasis was 115/116 (99.1%). The success rate of hemostasis and prevention of recurrent ulcer bleeding by type of acid suppressant following endoscopic hemostasis was 39/40 (97.5%) for Group 1 (3‐day omeprazole administration), 35/37 (94.6%) for Group 2 (3‐day famotidine administration), and 38/39 (97.4%) for Group 3 (1‐day famotidine and then 2‐day omeprazole administration), yielding an overall rate of 112/116 (96.6%). No significant difference in the hemostatic effect was observed among the groups. There were also no differences in the duration of hospital days and the number of fasting days between the three groups. Conclusion: Famotidine and omeprazole injected during the early phase of a bleeding ulcer may have similar effects to an adjuvant therapy for preventing rebleeding from endoscopically treated upper gastrointestinal bleeding in Japanese patients.     

Stimulation of gastric acid secretion increases mucosal blood flow in immediate vicinity of parietal cells in baboons

In acute experiments carried out in 27 baboons under general anesthesia, the regional gastric mucosal and muscle layer blood flow and gastric acid secretion were measured during 4 hr. Baboons were allocated to each of the following six groups: control, gastric acid stimulation with histamine 40 g/kg/hr intravenous, inhibition of basal or stimulated acid secretion with either ranitidine 50 mg intravenous or omeprazole 1 g/kg/hr. There were no significant cardiovascular alterations during the experiments. Histamine stimulation produced a concomitant rise in acid secretion and increase in blood flow only to the mucosal layer of the parietal-cell-bearing area of the stomach. Neither the underlying muscle layer nor the non-parietal-cell-bearing fundic or antral mucosa took part in this response, suggesting that a mechanism controlling blood flow is present in close proximity to the parietal cells. It was also established that the increase in blood flow occurs in response to parietal cell activity and not as a result of the action of histamine on the vascular system. Suppression of both basal and stimulated acid secretion did not cause a fall of mucosal blood flow below basal levels in any part of the stomach, indicating that drugs that inhibit parietal cell activity can be used in conditions where gastric mucosal ischemia should be avoided.Supported by South African Medical Research Council and Swiss National Foundation grant 3.846.0.83.     

Peptic ulcer disease in a patient with ankylosing spondylitis receiving a conventional nonsteroidal anti-inflammatory drug

BACKGROUND: A 42-year-old man with a 10-year history of HLA-B27-positive ankylosing spondylitis presented with upper abdominal pain and nausea after receiving oral ketoprofen 200 mg/day. His gastrointestinal symptoms did not improve with the addition of ranitidine 150 mg twice daily. He had previously responded well to conventional nonsteroidal anti-inflammatory drugs. INVESTIGATIONS: Physical examination, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, radiography, laboratory tests, upper gastrointestinal endoscopy, histopathologic examination and culture of biopsy specimens. DIAGNOSIS: Helicobacter pylori-positive duodenal ulcer. TREATMENT: For eradication of H. pylori: omeprazole 20 mg twice daily, clarithromycin 500 mg twice daily and amoxicillin 1 g twice daily for 1 week. For ankylosing spondylitis: diclofenac 150 mg/day in combination with omeprazole 20 mg/day for 2 months.     

Efficacy of famotidine 20 mg twice a day versus 40 mg twice a day in the treatment of erosive or ulcerative reflux esophagitis

Two different doses of famotidine (20 mg twice a day versus 40 mg twice a day) were evaluated in a double-blind, randomized multicenter study in 474 symptomatic patients with erosive ulcerative reflux esophagitis. A total of 238 patients were treated with famotidine 20 mg and 236 patients with 40 mg at breakfast and dinnertime. Relief of symptoms was significant in all patients after six and 12 weeks and not different in both treatment groups. Overall endoscopic healing was significantly better in the famotidine 40 mg twice a day group compared with 20 mg twice a day at week 6 (58% versus 43%;P<0.05) and at week 12 (76% versus 67%;P<0.05). Extending treatment to 24 weeks with 40 mg of famotidine twice a day in those patients not healed after 12 weeks did not result in further symptom relief or in significantly better overall healing. The differences in efficacy of these two doses were more pronounced with increasing severity of esophagitis. Analyzed by grade of esophagitis at entrance, healing was significantly better with famotidine 40 mg twice a day at week 6 for grade II, at week 12 for grades III and IV, and at week 24 for grade IV esophagitis. The results show that in the treatment of erosive/ ulcerative reflux patients famotidine 40 mg twice a day is more effective and achieves faster healing than famotidine 20 mg twice a day.for the Dutch Esophagitis Study Group.Participating physicians: P. Batenburg, J. Beker, J. Bellaar Spruijt, L. van Bergeijk, J. Bergmann, W. Bode, J. de Boer, H. Boot, G. Dorrepaal, J. Douma, J. Drapers, J. Ferwerda, H. Festen, A. Geraedts, J. Götz, E. van der Hoek, R. van Hogezand, J. Juttmann, M. Kloppenburg, F. Lalisang, W. Lesterhuis, D. van der Linde, G. van der Linden, J. van Maanen, J. Minkema, C. Mulder, I. van Munster, J. Nadorp, G. Nelis, J. Nicolai, R. Ouwendijk, D. Overbosch, A. van der Putten, J. Raats, F. Schuitemaker, J. Sindram, G. Slagboom, P. Snel, P. Stijnen, J. Thies, J. Thijs, H. Tuynman, B. Uyterlinde, J. ten Veen, K. te Velde, M. Vidakovic-Vukic, F. Vismans, A. Vogten, G. Vosmaer, P. de Vries, H. Walinga, S. van der Werf, I. Wesdorp, B. Westerveld, A. Wolff, R. Ypma.This study was supported by a grant from Merck Sharp & Dohme, The Netherlands.This study was presented in part at the annual meeting of the American Gastroenterology Association, May 1991 (Gastroenterology 100:63A, 1991).     

Helicobacter pylori infection: Is sequential therapy superior to standard triple therapy? A single-centre Italian study in treatment-naive and non-treatment-naive patients

BACKGROUND:

Clarithromycin resistance has decreased the eradication rates of Helicobacter pylori.

AIMS:

To determine whether a 10-day course of sequential therapy (ST) is more effective at eradicating H pylori infection than triple therapy (TT) in the first or second line, and to assess side effects and compliance with therapy.

METHODS:

One hundred sixty treatment-naive and 40 non-treatment-naive patients who were positive for H pylori infection by ¹³C-urea breath test or endoscopy were enrolled. Eighty of 160 patients underwent TT, while 80 of 160 underwent ST with omeprazole (20 mg) plus amoxicillin (1 g) twice/day for five days, followed by omeprazole (20 mg) with tinidazole (500 mg) twice/day and clarithromycin (500 mg) twice/day for five consecutive days. H pylori eradication was evaluated by ¹³C-urea breath test no sooner than four weeks after the end of treatment.

RESULTS:

Eradication was achieved in 59 of 80 treatment-naive patients treated with TT (74%), in 74 of 80 patients treated with ST (93%), and in 38 of 40 non-treatment-naive patients (95%). Eradication rates in treatment-naive patients with ST were statistically significantly higher than TT (92.5% versus 73.7%; P=0.0015; OR 4.39 [95% CI 1.66 to 11.58]). Mild adverse effects were reported for both regimens.

CONCLUSIONS:

ST appears to be a well-tolerated, promising therapy; however, randomized controlled trials with larger and more diverse sample populations are needed before it can be recommended as a first-line treatment.     

Effects of cimetidine and omeprazole on angiogenesis in granulation tissue of acetic acid-induced gastric ulcers in rats.

We investigated the effects of cimetidine and omeprazole on angiogenesis in granulation tissue and on the healing of gastric ulcers induced by acetic acid in rats. Either cimetidine (50 or 100 mg/kg) or omeprazole (10 or 20 mg/kg) was orally administered once daily for 9 consecutive days from the day following ulcer production. The ulcer index on the 10th and 30th days after ulcer production, and the extent of angiogenesis on the 10th day were examined. Cimetidine dose-dependently decreased the extent of angiogenesis on the 10th day, whereas the ulcer index on the 10th days was not significantly different between cimetidine-treated and control rats. The ulcer index of the groups treated with cimetidine during the initial 9-day period was increased compared with the control group on the 30th day. In contrast, oral omeprazole did not affect angiogenesis on the 10th day and decreased the ulcer index on both the 10th and 30th days. These results suggest that oral cimetidine may inhibit angiogenesis in ulcer granulation tissue possibly via the blocking of histamine H2 receptors and this may be one cause of delayed ulcer healing.