Duodenal Ulcer Healing Research Articles

Restitution of frog gastric mucosa in vitro: Effect of basic fibroblast growth factor

Background: Rapid re-epithelialization after superficial gastric mucosal injury is caused by migration of persisting viable epithelial cells. Basic fibroblast growth factor (bFGF) has been reported to enhance the healing of experimental duodenal ulcer, but its mode of action is unclear. The present experiments examine whether an effect of bFGF on restitution might contribute to such healing. Methods: Paired halves of bullfrog fundic gastric mucosa in Ussing chambers were injured by luminal exposure to 1 mol/L NaCl for 10 minutes. Results: Luminal protamine or suramin, both known to interfere with endogenous bFGF, significantly inhibited electrophysiological recovery at neutral luminal pH (pHL). Luminal sucrose octasulfate, which prevents acid degradation of bFGF, and an exogenous, acid-resistant form of bFGF allowed electrophysiological recovery at a pHL of 3.0 that completely prevented restitution in control tissues. Electrophysiological recovery correlated well with morphological restitution. The presence of endogenous bFGF in normal and restituting bullfrog mucosa was confirmed by positive staining with a monoclonal antibody. Conclusions: It is concluded that rapid epithelial repair after surface injury is at least in part mediated by bFGF.

Evaluation of a variable dose ranitidine regimen in the treatment of duodenal ulcer disease

Objective: This double-blind, randomized, international, multicentre study was undertaken to determine the effect of a variable dose ranitidine regimen (300 mg four times daily for 7 days which was reduced to 300 mg at night for a further 21 days) on symptom relief and duodenal ulcer healing compared with the standard dose ranitidine regimen (300 mg at night for 28 days). Patients: The study included 223 patients with endoscopically-confirmed duodenal ulcers (ulcer diameter ≥ 5 mm). Results: After 2 weeks of treatment, complete ulcer healing was observed in 64 and 52% of patients for the variable dose and night-time regimens, respectively (P = 0.076). By 4 weeks, cumulative healing rates were 98 and 89%, respectively (P < 0.01)

Short report: effect of ranitidine on duodenal ulcer healing in patients with cirrhosis of the liver.

The effect of ranitidine (300 mg daily) on the healing of acute duodenal ulcer was investigated in patients with and without cirrhosis of the liver. Of the 109 patients who entered the study, two patients from each group were excluded. Healing rates after 4 and 8 weeks were significantly different between patients with cirrhosis and controls (4- and 8-week healing rates in cirrhotics and non-cirrhotics: 49 and 69%, and 71 and 91%, respectively). This study demonstrates that duodenal ulcer healing is delayed in patients with cirrhosis.

Treatment of acute duodenal and pyloric channel ulcers with sucralfate suspension (2 g/10 ml) twice daily

Objective: To evaluate the efficacy of a new formulation of sucralfate suspension in the healing of duodenal and/or pyloric ulcer in smoking and non-smoking patients. Design: A randomized, double-blind, placebo-controlled parallel group multicentre trial. Setting: Gastroenterology outpatient clinics. Patients: One hundred and eighty-four patients with duodenal or pyloric channel ulcers entered the study. Intervention: Patients were randomized to receive either sucralfate suspension 2 g (10 ml) twice daily or placebo suspension for up to 8 weeks. Main outcome measures: Symptomatic improvement and endoscopie healing was assessed at 2, 4 and 8 weeks. Results: Sucralfate suspension healed 64% of patients in 4 weeks compared with 44% healing on placebo (P = 0.008), and 74% of patients in 8 weeks compared with 55% on placebo (P = 0.009). Sucralfate achieved a therapeutic gain of 30% over placebo in non-smoking patients, but failed to achieve significantly greater overall healing rates than placebo in smokers. Conclusion: Sucralfate suspension 2 g twice a day is effective in healing duodenal ulcers in non-smoking patients.

Future prospects for proton pump inhibitors.

Future prospects for proton pump inhibitors depend on their efficacy and safety relative to H2-receptor antagonists, the therapeutic standard for acid peptic disorders. As safety concerns diminish, efficacy considerations become more important as these may pertain to cost effectiveness. Comparative, controlled trials show that omeprazole and lansoprazole are somewhat more effective than H2-blockers in healing duodenal and gastric ulcers, providing faster relief of symptoms. Relapse after cessation of therapy is similar between the two classes. The proton pump inhibitors are substantially more effective in healing lesions and relieving symptoms in patients with reflux oesophagitis, and are particularly effective in cases that have failed to heal after 12 weeks of treatment with H2-blockers. Relapse rates of oesophagitis are significantly less with prolonged treatment with omeprazole than ranitidine. A proton pump inhibitor combined with amoxicillin is less effective than triple therapy with antibiotics and bismuth in eradicating Helicobacter pylori infections, but is more convenient and associated with fewer side-effects. Efficacy might be improved by more optimal dosing regimens. Prospects for reversible proton pump inhibitors depend on the balance between their theoretical advantages and their acid inhibition profile which, at present, closely resembles that of H2-blockers.

Clinical efficacy of triple therapy in Helicobacter pylori-associated duodenal ulcer

Objective: To evaluate a triple treatment regimen of colloidal bismuth subcitrate (CBS), metronidazole and tetracycline in eradicating metronidazole resistant Helicobacter pylori in patients with duodenal ulcer and to assess interaction between metronidazole and tetracycline against H. pylori in vitro. Design: Eighty-nine patients with H. pylori infection and duodenal ulcer disease were treated with CBS 120 mg four times daily for 4 weeks, metronidazole 400 mg three times daily and tetracycline 500 mg three times daily for the first week. H. pylori was cultured and susceptibility to metronidazole and tetracycline assessed before and 4 weeks after treatment. In vitro interaction between metronidazole and tetracycline against H. pylori was evaluated with a checkerboard technique. Results: The triple therapy healed duodenal ulcer in 90.7% (59 out of 65) of patients with metronidazole sensitive strains and 79.2% (19 out of 24) of those with resistant strains (P > 0.05). H. pylori was eradicated in 92.3% (60 out of 65) of patients with metronidazole sensitive strains and in 62.5% (15 out of 24) with metronidazole resistant strains (P < 0.001). Healing of duodenal ulcer and improvement of antral inflammation was associated with eradication of the organism. Side effects were negligible. Synergism was observed against seven (30.4%) of 23 strains tested. Conclusions: The triple therapy with CBS, metronidazole and tetracycline for 1 week is effective in eradicating H. pylori. Resistance to metronidazole reduces, although not completely, the efficacy of triple therapy. Evaluation of in vitro interaction between antimicrobials may be helpful in chosing multiple chemotherapy for eradicating H. pylori.

Advances in the therapeutic uses of histamine H 2-receptor antagonists

The Hz-receptor antagonists are among the most widely prescribed of all drugs. By any standards, they have been an enormous therapeutic and commercial success and have become regarded as standard treatment for peptic ulceration in most countries. At present, there are four members of this class of drugs (cimetidine, ranitidine, famotidine and nizatidine) which are generally available. Others (e.g. roxatidine) have more limited availability. Although the molecular structures of these drugs differ, they have essentially similar pharmacology; all currently available Hz-receptor antagonists are competitive and reversible antagonists for histamine at the Hz receptor and are devoid of activity at the histamine Hi receptor. Although the Hz receptor is widely distributed in the body, the only known physiological action of histamine at this receptor is stimulation of acid secretion by parietal cells in the oxyntic mucosa of the stomach. Therefore, the principal pharmacological action of the Hz-receptor antagonist is inhibition of gastric acid secretion. Acid is of central importance in the pathogenesis of peptic ulceration and pharmacological, or less commonly surgical, reduction of acid secretion is widely used in the management of peptic ulceration. The Hz-receptor antagonists have been extensively studied in the treatment of duodenal ulcer and benign gastric ulcer. There are numerous published double-blind, endoscopically-controlled clinical trials which attest to the efficacy of these agents in healing duodenal and gastric ulcers. In addition, continuous maintenance treatment with Hz-receptor antagonists reduces ulcer relapse after healing, although such treatment is not appropriate or relevant to all patients (Howden, 1988). The clinical pharmacology and therapeutic applications of the Hz-receptor antagonists have been reviewed in detail elsewhere (Feldman and Burton, 1990a, 1990b; Howden and Hunt, 1991). Despite the enormous amount of attention that these drugs have attracted in the past, there continues to be a great deal of interest in new applications, new dosage schedules, adverse effects, drug interactions and complex issues of their human pharmacology, including ‘tolerance’ to continued use and possible rebound hypersecretion of acid after stopping treatment. It is the purpose of this chapter to critically review some of these areas in an attempt

Effect of triple therapy (antibiotics plus bismuth) on duodenal ulcer healing: A randomized controlled trial: Grahm DY, Lew GM, Evans DG, et al Ann Intern Med 115:266–269, 1991

Effect of triple therapy (antibiotics plus bismuth) on duodenal ulcer healing: A randomized controlled trial: Grahm DY, Lew GM, Evans DG, et al Ann Intern Med 115:266–269, 1991

Medical cover for 'The Open' golf championship.

A review of 10 years' provision of medical cover at a major golf championship is presented. The average consultation rate was approximately 1 in 200 of those attending of whom 3% required transfer to hospital, the majority to orthopaedic or general medical departments. Familiarity with acute resuscitation and musculoskeletal complaints is required of the medical attendants. The provision of physiotherapy and chiropody services is essential, especially for the participants' complaints, two-thirds of which affected the axial skeleton. Good communications and close liaison with the Chief Marshal, Police and Ambulance Services are vital.

Ulcer recurrence following duodenal ulcer healing with omeprazole, ranitidine, or placebo: A double-blind, multicenter, 6-month study. The Omeprazole Duodenal Ulcer Study Group

The present study determined whether the rate of relapse of duodenal ulcer was reduced after ulcer healing with omeprazole compared with ranitidine or placebo. It was made up of a double-blind, randomized, controlled multiple-center trial set within the United States. Patients were candidates if their duodenal or pyloric channel ulcer successfully healed in one of two large multicenter U.S. trials; one compared omeprazole, 20 mg once daily, before breakfast with ranitidine, 150 mg twice daily, and the other compared the same dose of omeprazole with placebo. Two hundred forty (73.8%) of the 325 patients with complete ulcer healing within 4 weeks of starting therapy who were eligible to enter the follow-up study were enrolled. There was no intervention. Endoscopic assessment of ulcer status was performed at 2, 4, and 6 months and whenever patients had symptoms thought to represent return of an ulcer. The lifetable relapse rates for duodenal ulcer according to initial ulcer therapy with omeprazole, ranitidine, or placebo were 76.7% [95% confidence interval (CI), 64%-89.3%], 59.8% (95% CI, 47.8-71.7%), and 50.4% (95% CI, 15.7%-85.2%), respectively. These rates were not statistically significantly different. Seventeen percent of recurrent ulcers occurred at a site different from that of the original ulcer. It is concluded that despite the more rapid rate of duodenal ulcer healing with omeprazole therapy, the rate of ulcer relapse appears similar and independent of whether ulcer healing was accelerated with omeprazole or ranitidine. (Gastroenterology 1992 Apr;102(4 Pt 1):1289-94)

Ulcer recurrence following duodenal ulcer healing with omeprazole, ranitidine, or placebo: A double-blind, multicenter, 6-month study

The present study determined whether the rate of relapse of duodenal ulcer was reduced after ulcer healing with omeprazole compared with ranitidine or placebo. It was made up of a double-blind, randomized, controlled multiple-center trial set within the United States. Patients were candidates if their duodenal or pyloric channel ulcer successfully healed in one of two large multicenter U.S. trials; one compared omeprazole, 20 mg once daily, before breakfast with ranitidine, 150 mg twice daily, and the other compared the same dose of omeprazole with placebo. Two hundred forty (73.8%) of the 325 patients with complete ulcer healing within 4 weeks of starting therapy who were eligible to enter the follow-up study were enrolled. There was no intervention. Endoscopic assessment of ulcer status was performed at 2, 4, and 6 months and whenever patients had symptoms thought to represent return of an ulcer. The lifetable relapse rates for duodenal ulcer according to initial ulcer therapy with omeprazole, ranitidine, or placebo were 76.7% [95% confidence interval (CI), 64%–89.3%], 59.8% (95% CI, 47.8–71.7%), and 50.4% (95% CI, 15.7%–85.2%), respectively. These rates were not statistically significantly different. Seventeen percent of recurrent ulcers occurred at a site different from that of the original ulcer. It is concluded that despite the more rapid rate of duodenal ulcer healing with omeprazole therapy, the rate of ulcer relapse appears similar and independent of whether ulcer healing was accelerated with omeprazole or ranitidine.

Eicosanoid synthesis in duodenal ulcer disease: decrease in leukotriene C4 by colloidal bismuth subcitrate.

The release of immunoreactive prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) from antral and duodenal mucosal biopsy specimens taken from 20 patients with duodenal ulcer disease was measured by radioimmunoassay before and four weeks after treatment with colloidal bismuth subcitrate. Gastroscopic and histological examination showed complete ulcer healing in 15/18 patients and duodenal histology looked normal (n = 15) or improved (n = 3): two patients failed to attend for a second endoscopy. Analysis of the supernatant from incubations of biopsy tissue in vitro showed that unstimulated antral release of PGE2 was significantly more than that from the duodenal mucosa (p less than 0.05), whereas basal release of LTC4 was significantly lower from antral biopsy specimens (p less than 0.05). Subsequent incubation of specimens with calcium ionophore A23187 caused an increase in LTC4 but not in PGE2 generation. The ability of antral and duodenal mucosa to form ionophore mediated LTC4 in patients with duodenal ulcer disease was significantly greater (p less than 0.05; p less than 0.01 respectively) than that of normal gastroduodenal mucosa. After colloidal bismuth subcitrate treatment, basal synthesis of PGE2 was unchanged in duodenal and antral specimens. In contrast, basal duodenal LTC4 was reduced (p less than 0.05), and the capacity for ionophore mediated duodenal LTC4 formation was substantially and significantly reduced after treatment (p less than 0.001). These results indicate that after therapeutic healing of duodenal ulcer (accompanied by clearance of inflammatory cell infiltrate), there is a reduced ability of duodenal mucosa to generate proinflammatory peptidoleukotrienes.

Short report: short-term triple therapy for H. pylori-associated duodenal ulcer disease.

Thirty consecutive patients with endoscopically proven duodenal ulceration who had Helicobacter pylori infection on culture and histology, were treated with tripotassium dicitrato bismuthate (1 tablet q.d.s., 400 mg metronidazole t.d.s. and 500 mg tetracycline t.d.s. for one week, followed by the bismuth salt for a further 3 weeks. All patients were endoscoped at entry and 4 weeks after cessation of treatment, to check for ulcer healing and H. pylori eradication. Two antral biopsies were taken at each endoscopy for histological and microbiological evidence of H. pylori infection. Complete healing of duodenal ulcers was observed in 27/30 patients (90%). Gastritis improved or completely resolved in 26 patients. Eradication of H. pylori was achieved in 27 patients. Of the three patients who failed to heal, two were H. pylori-positive at follow-up and one was H. pylori-negative.

Effect of Duodenal Ulcer Healing Induced by Omeprazole and Ranitidine on the Generation of Gastroduodenal Eicosanoids, Platelet-Activating Factor, Pepsinogen A, and Gastrin in Duodenal Ulcer Patients

The effect of duodenal ulcer healing induced by omeprazole on gastroduodenal generation of eicosanoids, platelet-activating factor (PAF), pepsinogen A, and gastrin was evaluated. Sixty patients with endoscopically proven duodenal ulcer were randomized to receive 20 mg omperazole once daily or 300 mg ranitidine at bedtime for 2 weeks. Patients whose ulcers did not heal were treated for an additional 2 weeks. Endoscopic biopsy specimens and serum samples were obtained before and after treatment. There was no significant difference in the healing rate between the two treatment modalities. At 2 weeks healing rates were 60% and 56% in the omperazole and ranitidine groups, respectively, whereas at 4 weeks the respective healing rates were 96% and 86%. Ulcer healing induced by omeprazole and ranitidine was not accompanied by significant changes in mucosal leukotriene B4 or C4 generation. Mucosal PAF significantly decreased in patients treated with omeprazole for 4 weeks. In omperazole-treated patients there was a trend towards increase in mucosal prostaglandin E2 generation which was significant in the fundus after 4 weeks of treatment. After 2 weeks of omeprazole treatment, serum gastrin and pepsinogen A levels almost doubled when compared with their pretreatment levels. In conclusion, duodenal ulcer healing with 20 mg omeprazole daily is not superior to healing rates with 300 mg ranitidine at bedtime after both 2 and 4 weeks of treatment. In omeprazole-treated subjects ulcer healing was accompanied by a significant decrease in mucosal PAF generation and increased levels of serum gastrin and pepsinogen A.

Sulphydryl-containing agents: a new approach to the problem of refractory peptic ulceration.

Refractory peptic ulceration is the term applied to those gastric and duodenal ulcers which remain unhealed despite active treatment for at least 3 months. Sulphydryl-containing agents stimulate the formation of gastrointestinal mucus, bind the oxygen-derived free radicals that mediate tissue damage and play an important role in protein synthesis. This is the first report which suggests that these agents stimulate the healing of refractory gastric and duodenal ulceration without any adverse events.

Effects of FRG-8813, a new-type histamine H2-receptor antagonist, on the healing of gastric and duodenal ulcer in rats and spontaneously ulcerative mice

We examined the anti-ulcer effects of FRG-8813, a new-type histamine H2-receptor antagonist, in chronic ulcer models of rats and mice (W/WV). FRG-8813, given orally twice a day for 7 days, accelerated the healing of gastric or duodenal ulcer induced by acetic acid injection or application at the non-antisecretory doses (0.3 approximately 3 mg/kg). Administration of FRG-8813 to rats with ulcers increased the amounts of mucus in the gastric mucosa. These actions of FRG-8813 were more potent than those of famotidine or cimetidine. In W/WV mice, several ulcers spontaneously developed on gastric mucosa during the 8 weeks after the birth. The ulcers were aggravated by several unknown factors after the ulcer generation in W/WV mice. The aggravation of ulcers was inhibited by the 4-week administration of FRG-8813 with diet at the dose of 1 or 10 mg/kg/day, but was not inhibited by cimetidine at the dose of 100 mg/kg/day. From these results, we suggest that FRG-8813 is able to accelerate the healing of ulcers by antisecretory plus increasing actions on the integrity of the gastric mucosal defense mechanisms; therefore FRG-8813 is expected to be a useful drug for the treatment of gastric or duodenal ulcers in humans.

Role of sucralfate in peptic disease.

Sucralfate, a basic aluminum salt of sucrose, was the first successful drug with a major cytoprotective mechanism of action. It binds bile acids and pepsin and adheres to both ulcerated and nonulcerated mucosa. Sucralfate stimulates the synthesis and release of gastric mucosal prostaglandins as well as bicarbonate and the epidermal growth factor which stimulates healing. Sucralfate is the safest drug available today in the treatment of dyspeptic symptoms and compared to ranitidine and cimetidine it has the following characteristics. (2) The short-term healing of duodenal ulcers is the same for sucralfate, cimetidine and ranitidine. (3) Sucralfate-treated patients have a lower recurrence rate of duodenal ulceration after healing when compared with cimetidine and the recurrence rate is not connected with the presence or absence of Campylobacter pylori.

Misoprostol in the treatment of duodenal ulcers in the people's Republic of China: A comparative, double-blind, multicenter study

In recent years, it has become mandatory for many pharmaceutical companies to conduct country-specific clinical studies which are needed for obtaining regulatory approvals for their drugs. Such studies are important to delineate possible racial or environmental (lifestyle) differences which could not have been predicted from data obtained in other populations. A double-blind, randomized, double-dummy, multiclinic, comparative trial examined the tolerance and efficacy of misoprostol (200 μg QID) and cimetidine (200 mg QID) for the treatment of duodenal ulcers in the People's Republic of China. The trial characteristics and monitoring complied with the standards in the United States of America and the People's Republic of China. Two hundred consenting outpatients of either sex, aged 18–75 years, who had duodenal ulcers (not less than 0.3 cm in longest diameter and not more than 2 ulcers) were enrolled. Endoscopy, physical examination, and laboratory assessments wereperformed on entry and after 4 weeks of treatment. The effects of the treatment on ulcer healing, dyspeptic symptoms, tolerance, and adverse drug reactions were determined. Both treatment groups were well matched for demographic characteristics and disease severity at entry to the study. Misoprostol showed equal efficacy to cimetidine in inducing ulcer healing (60.7% vs. 67.9% for misoprostol and cimetidine, respectively, P > 0.05) and resolving dyspeptic pain. The extent of duodenal ulcer healing achieved by misoprostol in this study is essentially similar to the ulcer healing rates noted in many other worldwide studies, indicating the absence of racial differences in response to misoprostol. The adverse effects observed for misoprostol and cimetidine were also very similar. Both drugs were very well tolerated; however, slightly more patients experienced transient diarrhea with misoprostol (6.4%) than with cimetidine (3.8%). In conclusion, this trial supports the world- wide efficacy and tolerance of misoprostol for the treatment of duodenal ulcers and indi- cates the absence of racial influences on the safety and efficacy of misoprostol. © 1992 Wiley-Liss, Inc.

Evaluation of Peptic Ulcer Healing with a Highly Magnifying Endoscope

Gastric and duodenal ulcer healing and scarring were evaluated with a highly magnifying endoscope. The appearance of scar was classified into three types: Sa, with a depression at the center; Sb, with a pattern of regenerated mucosa reaching the center; and Sc, with a uniform pattern throughout. The relationship between regenerative mucosal patterns and histologic findings of biopsy specimens was investigated in 58 patients with gastric ulcer. Mucosal regeneration was sufficient in 26.7% of patients with Sa pattern, 79.2% of patients with Sb pattern, and 100% with Sc pattern. From prospective endoscopic follow-up observations, the relationship between endoscopic findings of ulcer scars and ulcer relapses was investigated in 80 patients with gastric ulcer and 56 patients with duodenal ulcer. As a result, patients who completed the cycle of ulcer healing from Sa pattern through Sb to Sc patterns had rarely relapse. In contrast, patients with a Sa pattern of mucosal scar showed a high rate of recurrence: 88.8% for gastric ulcer, and 88.0% for duodenal ulcer. Our method of evaluation of gastric and duodenal ulcer healing with a highly magnifying endoscope may have important prognostic and therapeutic implications. It may indicate a population of patients (with Sa scarring pattern) with a high risk of ulcer recurrence and therefore requiring prolonged prophylactic treatment.

Morphologic and Ultrastructural Effects of Maalox TC on Human Gastric and Duodenal Mucosa

Prostaglandins (PGs) and aluminum-containing antacids (Al.AAs) are effective in preventing gastric and duodenal lesions induced by neutralizing agents. The efficacy of Al.AAs is thought to be due to neutralizing properties and to stimulation of endogenous PGs synthesis. Liquid Maalox has the same effect as cimetidine 400 mg on postprandial duodenal acid load. In numerous prospective studies, Al.AAs have been shown to be as effective as cimetidine in the short-term treatment of duodenal ulcer (DU). Maalox TC at a dosage of 3 tablets b.i.d. provides an effective method for preventing DU relapse. Its effect is similar to that of nighttime cimetidine. Meta-analysis of prospective trials suggests that Al.AAs prevent stress ulcers more effectively than does cimetidine. It has been suggested that Al.AA acts by inducing surface epithelial cell disruption. Al-induced mucosal protection could be caused by a stimulated release of endogenous PGs, induced by Al microcrystal penetration of cells. In a recent study, we showed that small amounts of Al were absorbed by human gastric mucosa and accumulated in lysosomes; however, we did not observe any histological or ultrastructural lesions of the gastric mucosa. Prostaglandins (enprostil, misoprostol, and rioprostil) are as effective as cimetidine, but less effective than ranitidine, in healing DU. Enprostil and rioprostil have been shown to be as effective as ranitidine in treating gastric ulcer (GU). Moreover, enprostil inhibits postprandial gastrin release, whereas H2-blockers increase gastrin levels. Coadministration of misoprostol with aspirin is highly effective in healing aspirin-induced gastroduodenal lesions. Moreover, cotreatment with misoprostol was associated with a marked decrease in GU in patients with osteoarthritis receiving NSAIDs chronically.(ABSTRACT TRUNCATED AT 250 WORDS)