Duodenal Ulcer Healing Research Articles

Effect of Helicobacter pylori eradication on gastric metaplasia of the duodenum.

Helicobacter pylori associated duodenal ulcers occur in patches of gastric metaplasia. The pathogenesis of gastric metaplasia is unclear, but it has been produced in experimental animals by acute injury and has been shown to be present to a greater extent of H pylori positive subjects. This study aimed to discover if gastric metaplasia regressed with eradication of H pylori or healing of duodenal ulcers, or both. Thirty two duodenal ulcer patients with H pylori infection confirmed by biopsy urease test and by antral histological examination were studied. Patients were treated with triple therapy (deNol 240 mg twice daily, amoxycillin 500 mg three times daily, and metronidazole 400 mg three times daily) for two weeks after the first endoscopy and were subsequently re-endoscoped. Three duodenal bulb biopsy specimens were obtained per patient at each endoscopy. Biopsy sections were stained with haematoxylin and eosin to determine the severity of duodenitis, and with diastase periodic acid-Schiff/alcian blue to assess the extent of gastric metaplasia. Slides were assessed by two histopathologists unaware of treatment status. H pylori was eradicated in 63% of subjects and all ulcers were healed at follow up. The median extent of gastric metaplasia at the start of treatment and 6-18 months (median 10) after treatment was compared in the two groups. Gastric metaplasia declined in eradicators from 16% to 8% (p < 0.05) while in non-eradicators there was no significant change (25% initially and at follow up). A positive relation between extent of gastric metaplasia and duodenal inflammation score was present before treatment (r(s) = 0.74, p < 0.001) and was unchanged after treatment in the non-eradicator group (r(s) = 0.89, p < 0.001). In the eradicator group, however, the inflammation score had significantly declined (p < 0.02) and the close relation with gastric metaplasia was no longer present. These results suggest that H pylori itself is at least in part responsible for producing gastric metaplasia of the duodenum.

Optimizing acid suppression for treatment of acid-related diseases

Gastric acid is of central importance in the pathogenesis of duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease. Pharmacological reduction of acid secretion is, therefore, the mainstay of current treatment, but the optimal degree of acid suppression remains incompletely understood. This paper considers the ideal ways of assessing and reporting the pharmacological effectiveness of acid-inhibiting drugs and relating such data to clinical efficacy. Twenty-four-hour intragastric pH measurements are widely used for this purpose, although this technique cannot measure secretion quantitatively. Data on suppression of 24-hr intragastric acidity for groups of subjects have been successfully correlated with healing rates for duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease. Three primary determinants of healing have been derived from antisecretory data. These are the degree of suppression of acidity, the duration of suppression of acidity, and the duration of treatment. The order of importance of these determinants varies depending on the disease. Data on 24-hr intragastric acidity should be accompanied whenever possible by data on 24-hr plasma gastrin levels, as the relationship between suppression of acidity and a rise in gastrin varies widely between individuals. It is not possible to predict the plasma gastrin level from the intragastric pH or any other measurement of intragastric acidity. Comparative data sets in groups of subjects may provide useful information. Proton pump inhibitors produce a greater and longer-lasting degree of suppression of acidity than conventional doses of H2-receptor antagonists. For this reason, they are more effective in healing duodenal ulcer and gastric ulcer. However, in view of the importance of duration of treatment, healing rates with the H2-receptor antagonists approach those obtained with proton pump inhibitors if treatment is continued for a longer time. In gastroesophageal reflux disease in particular, although the optimal degree of acid suppression is not yet defined, the consistently superior performance of proton pump inhibitors demonstrates that increased suppression of acidity is clinically beneficial.

Sucralfate inHelicobacter pyloriEradication Strategies

Sucralfate monotherapy has been shown to suppress but not eradicate Helicobacter pylori. The combination of sucralfate with antibiotic(s) has been evaluated recently in the treatment of H. pylori-positive duodenal ulcer. The aim of this article is to review the efficacy of sucralfate-containing duotherapy and triple therapy in duodenal ulcer healing and H. pylori eradication rates. Reports on duotherapy and triple therapy including sucralfate as the mediating agent were analysed to assess the duodenal ulcer healing and H. pylori eradication rates. One study on duotherapy with sucralfate and amoxycillin achieved an ulcer healing rate of 86% and H. pylori eradication rate of 40%, which compared favourably with sucralfate monotherapy that resulted in duodenal ulcer healing and H. pylori eradication rates of 65% and 0% respectively. A total of six studies have examined triple therapy using sucralfate with two antibiotics. The duodenal ulcer healing rates were generally over 90% and the H. pylori eradication rates about 80% (range 59% to 100%). In one comparative study, the 4-week duodenal ulcer healing and H. pylori eradication rates of sucralfate-containing triple therapy were not distinguishable from those of omeprazole-containing triple therapy. It is concluded that sucralfate is an effective mediating agent for the eradication of H. pylori in patients with duodenal ulcer.

Molecular and cellular basis of ulcer healing.

The high ulcer recurrence rates after treatment with antacids or antisecretory drugs illustrate the need for direct treatment of GI ulcers by stimulating repair and healing mechanisms. The molecular regulators of ulcer healing include polyamines and growth factors such as EGF, TGF-beta, bFGF and PDGF. Oral treatment of rats with bFGF or PDGF accelerated the healing of chronic cysteamine-induced duodenal ulcers without decreasing gastric secretion. We found that sucralfate binds bFGF in vitro and in vivo, and the elevated local concentration of this growth factor may contribute to the ulcer healing properties of sucralfate. Parallel treatment with bFGF + sucralfate resulted in synergistic healing of chronic duodenal ulcers and chronic gastritis. Rapid changes in mucosal concentration of bFGF and EGF receptors during ulceration suggest that these peptides play a role in the natural history of GI ulcers. Thus, treatment based on molecular and cellular mechanisms of ulcer healing allows a direct and efficient ulcer therapy.

Closing Remarks H2-Receptor Antagonists andHelicobacter pyloriEradication

Background: To discuss the place of histamine H2-receptor antagonists in eradication therapy of Helicobacter pylori. Methods: Analysis of two papers in this supplement and the relevant literature. Results: Triple therapy comprising ranitidine and two antibiotics is effective in speeding up healing of duodenal ulcer and eradicating H. pylori from the stomach. Conclusion: Ranitidine is to be considered as a valuable and safe component of triple therapy against H. pylori in duodenal ulcer patients.

&lt;i&gt;Helicobacter pylori&lt;/i&gt;除菌が及ぼす十二指腸潰瘍治癒過程への影響

The effect of Helicobacter pylori (Hp) eradication on duodenal ulcer healing was studied in 24 patients with duodenal ulcer (16 males and 8 females, mean age : 41 years old) . Eradication was done with lansoprazole 30mg/day 6 weeks and amoxicillin 1,500mg/day 2 weeks. Hp infection was detected by serum Hp IgG antibody, rapid urease test, histological examination and 13C urea breath test. The follwing results was obtained. 1) Endoscopic findings at clearance : In total, S1 stage was 50% and S2 stage was 50%. S1 stage was 100% in Hp positive cases and S1 stage was 33% and S2 stage was 67% in Hp negative cases. 2) Endoscopic findings at eradication : S1 stage was 100% in Hp positive cases and S2 stage was 100% in Hp negative cases. From these results showed above, it is suggested that Hp eradication effect healing rate to S2 stage, also in relapsed cases. Because eradication rates was only 50%, however we must consider about the combination of medicine, duration of therapy and so on.

Clinical Evaluation of Lansoprazole in the Treatment of Peptic Ulcers

The clinical usefulness of lansoprazole in the healing of gastric and duodenal ulcers, the S 2 -stage shift rate (white scarring rate), and endoscopic healing rate with respect to degree of gastric mucosal atrophy were investigated. The subjects were 50 gastric ulcer and 37 duodenal ulcer patients. The endoscopic healing rate in patients with gastric ulcers after initial treatment with lansoprazole was 92% after 8 weeks. The S 2 -shift rate was 38% after 8 weeks. The 8-week healing rate in patients without atrophy was 100% and with atrophy was 92%, although the difference was not statistically significant. The S 2 -shift rate in patients without atrophy was 42% and in patients with atrophy was slightly lower, at 37%, although the difference was not statistically significant. The endoscopic healing rate in patients with duodenal ulcers was 93% after 6 weeks, and the S 2 -shift rate was 59%. It is firmly established that atrophic gastric mucosa shows a reduction in mucosal defense factors. However, lansoprazole achieved good endoscopic healing rates and S 2 -shift rates even in patients with gastric ulcers with atrophic background mucosa.

Treatment of nonsteroidal anti-inflammatory drug-associated gastric and duodenal damage. Efficacy of antisecretory drugs and mucosal protective compounds.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay of treatment for rheumatic diseases. However, a significant number of patients receiving these drugs experience upper gastrointestinal side effects, including physical injury to the gastroduodenal mucosa. This may range from clinically insignificant bleeding and minor erosive changes to deeper ulceration, with attendant risk of haemorrhage or perforation. The majority of the published literature concerning healing of NSAID-associated peptic ulcer with antisecretory drugs involves studies of the use of the H2-receptor antagonists, ranitidine and cimetidine. Peptic ulcers associated with NSAID use can be healed with these H2-receptor antagonists using the same doses as those used for healing of idiopathic gastric or duodenal ulceration. Most ulcers heal within 4-8 weeks in those patients who are able to discontinue their anti-inflammatory therapy. If the NSAID is continued, healing may be slightly delayed. At present, limited data only are available with respect to the use of the proton pump inhibitor, omeprazole, and no firm conclusions can be drawn regarding the use of the prostaglandin analogue, misoprostol, for the healing of NSAID-associated peptic ulceration.

Growth Factors: New ‘Endogenous Drugs’ for Ulcer Healing

The pathogenesis of gastroduodenal ulceration has been investigated mostly from the point of view of aggressive factors; the therapeutic interventions affected the healing process only indirectly. With the discovery of the potent healing capacity of growth factors, direct treatment of ulcers is now possible regardless of HCl and pepsin secretion. We review our recent data on how growth factors (e.g., bFGF, PDGF in comparison with EGF) can promote ulcer healing. Treatment of rats with bFGF, PDGF accelerated the healing of experimental chronic duodenal and gastric ulcers without suppressing gastric acid secretion and resulted in superior quality of ulcers healed. We also detected additive or synergistic action between bFGF and cimetidine or bFGF and sucralfate in the healing of chemically induced chronic duodenal ulcers and chronic erosive gastritis. We conclude that growth factors such as bFGF, PDGF can promote ulcer healing without the need to neutralize gastric secretion and may lead to a direct and efficient therapeutic regime.

The Current Role ofHelicobacter pyloriEradication in Clinical Practice

Helicobacter pylori is probably the commonest bacterial infection worldwide and is now accepted as the cause of chronic active type B gastritis. It is increasingly accepted as having a critical role in duodenal ulcer, where the prevalence of infection is 90 to 100%. More important is the dramatic reduction in duodenal ulcer recurrence after successful eradication of the organism to about 4% in a year compared to recurrences of up to 80% in those whose ulcers have been healed but in whom the infection persists. There is increasing evidence that what is now clear for duodenal ulcers may also hold true for patients with a gastric ulcer who are infected with H. pylori. Moreover, evidence is accumulating that the risk of a duodenal ulcer complication, such as, bleeding, is reduced following successful eradication of H. pylori. The treatment of duodenal ulcer patients with H. pylori eradication treatment has been advocated by an international working party who met first in Sydney at the 1990 World Congress and subsequently in Athens during the First European Gastroenterology Week. The most recent recommendation suggests that the infection should be treated in any duodenal ulcer patient after the first recurrence, and that a triple therapy regimen or a proton pump inhibitor combined with either amoxicillin or clarithromycin may be prescribed. The combination of a proton pump inhibitor and an antibiotic can eradicate H. pylori in over 80% of cases and simultaneously offers the advantage of rapid symptom relief and the highest rates of duodenal ulcer healing.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Sucralfate onHelicobacter pyloriand Severity of Gastritis in Patients with Duodenal Ulcer

Duodenal ulcer relapse rates have been reported to be lower following healing with sucralfate. The question arises whether this is related to an effect on Helicobacter pylori. In order to investigate this possibility, 43 patients with active duodenal ulcer were entered into a study. Endoscopy was performed at entry, following 6 weeks' treatment with sucralfate 1 g q.i.d., and at 4 and 12 weeks of post-documented healing. Antral and gastric corpus biopsies were taken for assessment of H. pylori status (CLOtest), density of infection, and severity of gastritis. In addition, 14C urea breath tests (UBT) were performed. Sucralfate therapy induced a significant decrease in the density of H. pylori infection, with a trend to improvement of the gastritis in the antrum, but not in the corpus. However, all patients remained CLOtest positive, and the overall gastric urease activity was unchanged following therapy. These effects did not appear to influence either initial duodenal ulcer healing or subsequent relapse rates. Sucralfate has a suppressive effect on H. pylori infection in the gastric antrum but the clinical relevance of this is uncertain.

Lansoprazole. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and its therapeutic efficacy in acid-related disorders.

Lansoprazole is a benzimidazole derivative that effectively decreases gastric acid secretion, regardless of the primary stimulus, via inhibition of gastric H+,K(+)-adenosine triphosphatase (ATPase). It provides effective symptom relief and healing of peptic ulcer and reflux oesophagitis after 4 to 8 weeks of therapy and appears to prevent recurrence of lesions when administered as maintenance therapy. When administered at therapeutic dosages, lansoprazole produced higher healing rates than ranitidine or famotidine in patients with duodenal and gastric ulcers. Lansoprazole heals duodenal ulcers more rapidly than ranitidine or famotidine. Relief of ulcer symptoms in lansoprazole recipients is at least equivalent to, and tends to be more rapid than, that in patients receiving histamine H2-receptor antagonists. In comparisons with omeprazole 20 mg/day, lansoprazole 30 mg/day produced duodenal ulcer healing more rapidly and reduced ulcer pain to a greater extent at 2 weeks, but overall healing rates were similar after 4 weeks of therapy. At therapeutic dosages, lansoprazole produces superior healing and symptom relief of reflux oesophagitis in comparison with ranitidine, and it tends to relieve heartburn more effectively than omeprazole, although both agents produce equivalent healing. Healing of peptic ulcers or reflux oesophagitis refractory to histamine H2-receptor antagonists occurs after 8 weeks in the majority of patients treated with lansoprazole, and lansoprazole and omeprazole demonstrate similar efficacy in patients with refractory peptic ulcers. In patients with Zollinger-Ellison syndrome, lansoprazole effectively controls mean basal gastric acid output. Lansoprazole is generally well tolerated in clinical trials. The incidence of adverse effects is similar to that of omeprazole, ranitidine and famotidine in comparative studies. Combination therapy with lansoprazole and antibacterial agents such as amoxicillin, tinidazole, roxithromycin and/or metronidazole appears to eradicate Helicobacter pylori in 22 to 80% of patients with this organism. Limited data also suggest that lansoprazole may have superior activity against H. pylori in comparison with omeprazole, although the clinical relevance of this preliminary finding requires further confirmation. Thus, lansoprazole may be considered as alternative to existing antisecretory agents available for the treatment of acid-related disorders, particularly because it may provide more rapid healing and relief of symptoms.

Sucralfate: the Bangkok review.

Sucralfate is a site-protective ulcer healing drug with a remarkable range of mechanisms of action. Recent studies highlight the capacity of sucralfate to bind basic fibroblast growth factor (bFGF) and deliver it in high concentration to the ulcer. Basic fibroblast growth factor stimulates the production of granulation tissue, angiogenesis and re-epithelization, thus improving the quality of ulcer healing. The effect of sucralfate in reducing parietal cell sensitivity may be another factor important in the lower relapse rate demonstrated after duodenal ulcer healing. Sucralfate has been demonstrated to be efficacious in healing both duodenal and gastric ulcers together with mild oesophagitis, and it is safe for both short-term use and maintenance. In stress ulcer prophylaxis it is as effective as acid suppression or neutralization and has the advantage of lesser rates of nosocomial pneumonia than are demonstrated with antacids or H2 antagonists. The potential advantages of sucralfate lie in the better quality of ulcer healing associated with longer duration of remission.

Improved duodenal ulcer healing with pantoprazole compared with ranitidine

Objective: To compare the efficacy and tolerability of pantoprazole 40 mg (once daily in the morning) with ranitidine 300 mg (once daily at bedtime) in duodenal ulcer healing. Design: Prospective multicentre, randomized, double-blind, parallel-group comparison. Patients: The study included 199 outpatients aged from 18 to 75 years, with endoscopically confirmed active duodenal ulcer disease. Methods: Endoscopy and standard laboratory assessments, including serum gastrin levels, were carried out at the beginning of the study, after 2 and, where applicable, after 4 weeks. Results: Of the patients, 182 (98 on pantoprazole, 84 on ranitidine), median age 39 years, completed the study

Current Status of Gastric Proton Pump Inhibitors in the Treatment of Acid-Peptic Disease

Proton pump inhibitors represent an important advance in the treatment of acid-peptic disease. Omeprazole, the prototype of the drug class, produces a profound and sustained degree of gastric acid suppression. Recent studies confirm earlier reports that omeprazole 20 mg/d is generally more effective than standard histamine2 receptor antagonist (H2RA) dosage regimens in treating duodenal ulcer (DU), gastric ulcer (GU), and erosive esophagitis. Omeprazole tends to accelerate DU and GU healing, especially during the first 2 weeks of treatment, and also accelerates mucosal healing in patients with all grades of esophagitis. Omeprazole is the drug of choice for treating patients with large or refractory ulcers, severe or refractory erosive esophagitis, Barrett's esophagus, and Zollinger-Ellison syndrome. Maintenance therapy with omeprazole seems to reduce ulcer recurrence and esophagitis, but optimal treatment regimens must be established. Dual therapy with omeprazole and amoxicillin shows encouraging results in eradicating Helicobacter pylori, reducing duodenal ulcer recurrence rates, and altering the natural history of peptic ulcer disease. Further studies are required to determine the efficacy of omeprazole in preventing nonsteroidal anti-inflammatory drug-induced ulcers and stress-related mucosal bleeding, and in treating upper gastrointestinal bleeding. Omeprazole is well-tolerated in the majority of patients receiving either short-term or long-term treatment. The type and frequency of adverse effects are similar to those reported with the H2RAs. There is no evidence to support genotoxicity or hypergastrinemia-induced enterochromaffin-like cell carcinoid of the stomach in patients receiving omeprazole treatment for more than 5 years. Omeprazole interacts selectively with hepatic P-450 and may potentially interact with phenytoin, warfarin, or diazepam. Pharmacoeconomic studies suggest that treatment with omeprazole provides a significant cost-savings over the H2RAs in patients with moderate to severe erosive esophagitis and possibly in patients with DU. Lansoprazole, a newly developed proton pump inhibitor, seems to offer no clear advantage over omeprazole.

Duodenal ulcer was healed solely by eradication of Helicobacter pylori

Source Citation Hosking SW, Ling TK, Chung SC, et al. Duodenal ulcer healing by eradication of Helicobacter pylori without anti-acid treatment: randomised controlled trial. Lancet. 1994 Feb 26;343:...

Ranitidine: a pharmacoeconomic evaluation of its use in acid-related disorders.

Ranitidine is a histamine H 2-receptor antagonist which, on the basis of its well established tolerability and efficacy profile, has been widely prescribed for the treatment of ulcer disease and mild to moderate reflux oesophagitis. However, the advent of more powerful gastric acid inhibitors (e.g. acid pump inhibitors) and the realisation of the role of Helicobactor pylori infection in duodenal ulcer disease could have considerable clinical and economic implications for the use of ranitidine (and other H 2-receptor antagonists). Simulation modelling studies based on current pricing policies in Europe predict that ranitidine-based treatment will be less cost effective than omeprazole in the short term healing of duodenal ulcer and reflux oesophagitis disease. During longer term treatment, omeprazole is expected to be the dominating strategy over ranitidine-based therapy in Europe and the US. However, the inherent limitations of modelling studies reinforce the need for randomised prospective trials, preferably conducted in a general practice setting and including a quality-of-life analysis. Of the currently accepted approaches for the long term management of recurrent duodenal ulcer disease, daily maintenance therapy with ranitidine has been shown to be more cost effective than intermittent treatment for up to 2 years in the US. The annual cost of providing continuous maintenance therapy with ranitidine 150 mg/day is higher than with cimetidine 400 mg/day, although the extra benefits include a reduced risk of pain and discomfort from an expected lower rate of ulcer recurrence with ranitidine. Simultaneous ulcer healing and eradication of H. pylori markedly reduces relapse rates and is likely to become the management strategy of choice in H. pylori-positive patients, particularly with the advent of more convenient, well tolerated and effective regimens. Moreover, widespread clinical acceptance of H. pylori eradication may yield substantial cost savings to society by reducing the overall need for long term antisecretory therapy. Nonetheless, maintenance therapy with histamine H 2-receptor antagonists remains indicated for patients at high risk of ulcer recurrence who are poorly responsive to or cannot tolerate H. pylori eradication regimens. In summary, the proven efficacy and tolerability of ranitidine will ensure its continued use in the treatment of many patients with duodenal ulcer and mild to moderate reflux oesophagitis. However, there is increasing clinical and economic data favouring the selection of omeprazole in patients with more severe symptoms of these diseases.(ABSTRACT TRUNCATED AT 400 WORDS)

Omeprazole. An update of its pharmacology and therapeutic use in acid-related disorders.

Omeprazole, a gastric acid pump inhibitor, dose-dependently controls gastric acid secretion: the drug has greater antisecretory activity than histamine H2-receptor antagonists. Omeprazole 20 to 40 mg/day is more effective than histamine H2-receptor antagonists in the short term treatment of duodenal ulcer, gastric ulcer and reflux oesophagitis. Available data suggest that omeprazole 10 to 40 mg/day is also more effective than ranitidine in the maintenance therapy of duodenal ulcer and reflux oesophagitis. The drug is also effective in patients with duodenal ulcer, gastric ulcer or reflux oesophagitis poorly responsive to histamine H2-receptor antagonists. The efficacy of omeprazole 20 mg/day appears to be similar to that of lansoprazole 30 mg/day in the short term treatment of duodenal ulcer, gastric ulcer and reflux oesophagitis. However, most available studies have been reported in abstract form only, and 2 of 3 studies in patients with duodenal ulcer have shown greater healing rates at 2 (but not 4) weeks with lansoprazole. Helicobacter pylori eradication decreases duodenal ulcer relapse rates and appears to be associated with improved duodenal ulcer healing rates. Evidence also suggests that H. pylori eradication is associated with reduced gastric ulcer relapse rates. Omeprazole monotherapy may suppress but does not eradicate H. pylori infection. Eradication rates with omeprazole 20 or 40 mg twice daily plus amoxicillin usually up to 2 g/day (3 g/day in a few studies) for 2 weeks appear to be similar to those of standard triple therapy (bismuth salt plus metronidazole, plus tetracycline or amoxicillin) or omeprazole plus clarithromycin, although eradication rates vary widely. Omeprazole plus amoxicillin appears to be better tolerated than triple therapy and represents a first-line treatment alternative in patients with H. pylori-associated peptic ulcer disease. Omeprazole plus amoxicillin plus metronidazole appears to be more effective than omeprazole plus amoxicillin in patients with metronidazole-sensitive H. pylori infection. Omeprazole remains a treatment of choice in patients with Zollinger-Ellison syndrome. The dosages should be adjusted according to individual response. However, relatively low dosages of 10 to 40 mg/day may be sufficient in some patients. The drug has also shown promise in the treatment of children with severe reflux oesophagitis, in patients with reflux oesophagitis and coexisting systemic sclerosis, and in the prevention of aspiration pneumonia. Evidence suggests that omeprazole is more effective than ranitidine in patients with nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage who continue to take NSAIDs, especially in patients with large gastric ulcers; however, completion of ongoing studies is required to verify this.(ABSTRACT TRUNCATED AT 400 WORDS)

Endoscopic assessment of blood flow in duodenal ulcers

The importance of blood flow in duodenal ulcer healing is unclear. Endoscopic reflectance spectrophotometry measures the index of oxygen saturation (ISO 2 ), which is significantly correlated with blood flow. In 97 consecutive patients who presented with duodenal ulcer bleeding, the difference in the index of oxygen saturation (δISO 2 : ulcer margin ISO 2 minus adjacent mucosa ISO 2 ) was determined during the initial endoscopic examination. Endoscopic examinations were repeated until the ulcers had healed (n = 86). Relative to the adjacent mucosa, 78% of the ulcer margins had increased blood flow (positive δISO 2 ) and 22% had decreased blood flow (negative δISO 2 ). Stepwise multi-linear regression analysis selected δISO 2 , ulcer size, and stigmata of recent hemorrhage as predictors of delayed healing. A significant negative linear correlation between δISO 2 and ulcer healing time (r = –0.35, p < 0.001, n = 86) was demonstrated. The scatter in the data precludes prediction of ulcer healing based on δISO 2 measurement in an individual patient. Multi-variate logistic regression analysis selected concurrent medical illness, duodenal deformity, frequent use of non-steroidal anti-inflammatory drugs, and stigmata of recent hemorrhage as factors significantly associated with delayed (longer than 5 weeks) ulcer healing. The results support the hypothesis that prognostic factors are identifiable at the time of ulcer diagnosis, even in patients who present with bleeding. Blood flow remains an equivocal factor that deserves to be re-studied taking multiple measurements around the ulcer and including a larger number of slow healers. (Gastrointest Endosc 1994;40:334-41.)

Accelerated healing of duodenal ulcers by oral administration of a mutein of basic fibroblast growth factor in rats

Background/Aims: Human basic fibroblast growth factor (bFGF) is an endothelial mitogen that stimulates angiogenesis and proliferation of other cells such as fibroblasts and smooth muscle cells. After this peptide was stabilized to acid and pepsin by site-specific mutagenesis, it was tested whether bFGF might accelerate the healing of experimental duodenal ulcers. Methods: This mutein peptide (bFGF-CS23) was administered orally in comparison with cimetidine to rats with chronic duodenal ulcers previously induced by cysteamine. Results: Oral bFGF-CS23 therapy maintained for 21 days at 100 ng/100 g twice daily resulted in (1) significant acceleration of healing of duodenal ulcers, i.e., reduction of mean ulcer area by 83% in the bFGF-CS23-treated rats compared with only 61% for cimetidine therapy and 40% for untreated controls; (2) complete healing with no residual ulcer in 62% of the bFGF-CS23-treated rats compared with only 7% of untreated rats; and (3) a ninefold increase in angiogenesis in the ulcer bed compared with untreated controls. A single dose of the bFGF-CS23 mutein had no effect on gastric output of hydrochloric acid or pepsin, but daily treatment for 2 or 3 weeks resulted in enhanced acid and pepsin outputs. Conclusions: Chronic duodenal ulcers can be healed rapidly by stimulating angiogenesis and other wound-healing processes in the ulcer bed without reduction of gastric acid.