A comparative dynamic study of the effectiveness of gastric cytoprotection by vitamin A, De-Nol, sucralfate and ulcer healing by pirenzepine in patients with chronic gastric ulcer (a multiclinical and randomized study)

The gastric cytoprotective effects of vitamin A, De-Nol and sucralfate were compared with the effectiveness of pirenzepine in healing ulcer in patients with chronic gastric ulcer. A total of 100 patients was randomized into different groups: the patients were treated with antacids, vitamin A (3 X 50.000 IU), De-Nol liquid (4 X 5 ml), sucralfate (4 X 1 g) or pirenzepine (3 X 50 mg). The treatment was continued for 4 weeks. At the beginning, 2 and 4 weeks after starting treatment the patients were subjected to endoscopy and the size of the ulcer was measured planimetrically. The ulcer-healing effect of De-Nol liquid was significantly better than that of the antacids (p less than 0.01). Ulcer size was reduced significantly in all groups (p less than 0.01), however, at the end of the study the gastric ulcers were smallest in the De-Nol treated group (p less than 0.001). The dynamics of ulcer healing in the second week was most favourable in the patients receiving vitamin A (p less than 0.01). The present data point to the cytoprotective effects of De-Nol liquid, vitamin A and sucralfate and to their ability of healing chronic gastric ulcers.     

Omeprazole and cimetidine in the treatment of ulcers of the body of the stomach: a double blind comparative trial. Danish Omeprazole Study Group.

OBJECTIVE--To see whether omeprazole was superior to cimetidine in healing ulcers of the body of the stomach. DESIGN--Double blind randomised parallel group study of omeprazole versus cimetidine for six weeks with assessment of healing at end of every second week. SETTING--Outpatient referrals in 11 centres in Denmark. PATIENTS--One hundred sixty one patients who satisfied the following criteria: age 18-79; one or more ulcers of body of stomach (that is, at or above the angulus) seen endoscopically within four days before study treatment; no H2 receptor antagonists taken within previous two weeks; no history of gastric surgery and no complications needing surgery; no concurrent treatment or disease that might confound assessment; oral contraception or an intrauterine device being used by women of childbearing age. INTERVENTIONS--Omeprazole 30 mg daily (one capsule in the morning) or cimetidine 1 g daily (one 200 mg tablet thrice daily, two tablets at bedtime) for six weeks. Inactive capsules and tablets provided so that all patients took same number of capsules and tablets daily. Compliance monitored by pill counts. END POINT--Endoscopic evidence of accelerated healing of type I gastric ulcers after four weeks of omeprazole. MEASUREMENTS AND MAIN RESULTS--Pain recorded on diary cards and patients assessed after two, four, and six weeks of treatment for clinical state and by endoscopy and biopsy and repeat laboratory tests. Twenty eight patients withdrawn during trial for violations of protocol. At two weeks healing rates were identical in the two treatment groups (omeprazole 41% (30/73 patients); cimetidine 41% (30/73]. At four weeks cumulative healing rates were 77% (53/69 patients) in the omeprazole treatment group and 58% (41/71) in the cimetidine treatment group (95% confidence interval of difference between groups 4% to 34%). By six weeks the cumulative healing rates in the two treatment groups differed by only 6% (60/68 patients (88%) given omeprazole; 53/65 (82%) given cimetidine). Log rank analysis with ulcer size used as covariable showed a significant difference in healing times in favour of omeprazole. There was no difference in the occurrence of pain relief between the two treatment groups. No serious clinical or biochemical side effects of treatment were noted. CONCLUSIONS--Omeprazole 30 mg daily accelerates healing of ulcers in the body of the stomach as compared with cimetidine 1 g daily. This effect is more pronounced in ulcers greater than 12 mm diameter.     

Controlled comparison of cimetidine and carbenoxolone sodium in gastric ulcer.

Fifty-four outpatients with endoscopically diagnosed benign gastric ulcer were allocated at random to treatment with either cimetidine 800 mg daily for six weeks or carbenoxolone sodium 300 mg daily for one week then 150 mg daily for five weeks. Ulcers were reassessed by endoscopy at the end of the trial. The endoscopist was unaware of the treatment and did not take part in the clinical care of the patients. Twenty-one of the 27 patients (78%) given cimetidine and 14 of the 27 (52%) given carbenoxolone had healed ulcers. Symptomatic response occurred earlier with cimetidine but was not significantly better. Unwanted effects were more common in the carbenoxolone group: 12 patients developed hypokalaemia, four of whom needed oral potassium supplements. The results suggest that histamine H2-receptor blockade is at least as effective as carbenoxolone sodium for benign gastric ulcer and produces fewer side effects.     

Combined treatment of advanced malignant melanoma with coumarin and cimetidine

Summary Immunostimulant therapy with coumarin and cimetidine was evaluated in 17 patients with advanced malignant melanoma. Induction therapy with coumarin 100 mg daily was given for 8 weeks, whereupon cimetidine 1000 mg daily was added. No patients had been previously treated with cytotoxic drugs, and all patients had a good performance status. In 16 patients progressive disease was observed, and only 1 patient experienced no change in condition, lasting 30 weeks. We conclude that treatment with this schedule of coumarin and cimetidine is without effect in advanced malignant melanoma.     

Gastro-protective effect of methanol extract of Ficus asperifolia bark on indomethacin-induced gastric ulcer in rats

The gastro-protective and antioxidant effects of methanol extract of Ficus asperifolia bark on indomethacin induced gastric ulcer were investigated in male rats. Thirty two male rats divided into 4 equal groups and were treated as follows: group1 (control), 0.5ml of 5% tween 80 (vehicle for the extract), groups 2 and 3, 100 and 500mg/kg of Ficus asperifolia extract respectively and group 4, cimetidine (100mg/kg). After two weeks of daily oral administration of vehicle, extract or cimetidine, gastric ulcer was induced in all rats with indomethacin (40 mg/kg, p.o). Gastric juice pH, gastric acid concentration, gastric ulcer score, percentage gastric ulcer inhibition, activity levels of superoxide dismutase (SOD), catalase and malondiadehyde (MDA) were determined. Ficus asperifolia extract significantly increased gastric pH (p.     

Prophylactic effect of cimetidine in duodenal ulcer disease.

Fifty-seven symptom-free patients with duodenal ulcer entered a double-blind trial to assess the prophylactic effect of cimetidine. Patients were randomly allocated to receive cimetidine 400 mg twice daily (29 patients) or placebo (28 patients). The trial was designed to imitate daily clinical practice, so duodenal ulcer disease was diagnosed by means of x-ray examination. Three patients from each group withdrew from the trial. All remaining patients continued to receive treatment for 12 months or until symptoms recurred. Three out of 26 patients suffered relapses during cimetidine treatment, compared with 20 out of 25 receiving placebo. No side effects were attributable to cimetidine. Long-term cimetidine treatment had no curative effect as relapses occurred soon after treatment was stopped. The estimated chance (cumulative remission rate +/- 2 SE) of remaining symptom-free 13 weeks after one year''s cimetidine treatment had been completed was 47 +/- 21%. Maintenance treatment with cimetidine is a suitable alternative to elective in surgery in patients with duodenal ulcer subjects frequent relapses. Further study is needed to establish the optimal duration and safety of prolonged cimetidine treatment.     

Cimetidine and stilbestrol treatment of peptic ulcer in menopausal women

Cimetidine in the daily dose of 1,000 mg was administered orally to menopausal women (group I) with peptic ulcer. The group II (n = 25) was given cimetidine (1,000 mg/24 hours) with stilboestrol in the daily dose of 1 mg. Healing of the ulcers was seen in 16 women of group I (72.7%) and in 23 women of group II (92.0%; p less than 0.05) following a 6-week treatment.     

Early results of the studies of the effect of cimetidine on selected parameters of humoral and cellular immunity in patients with peptic ulcer

The study aimed at evaluating an early effect of cimetidine on the blood IgG, IgA, IgM, number and functioning of T-cells in peripheral blood of patients with ulcerative disease. The study involved 27 patients (9 women and 8 men), aged between 27 and 70 years (mean 52.6 +/- 10.9 years). Nine of these patients suffered from the peptic ulcer and 8--from duodenal ulcer. Cell-mediated and humoral immunity were evaluated simultaneously in all patients prior to and after a 4-week treatment with cimetidine administered orally in the dose of 200 mg four times daily. Rosette test with theophylline and leukocyte migration test were used to assess cell-mediated immunity. It was found that cimetidine significantly increases blood serum IgG (p less than .01), the number of theophylline-resistant lymphocytes in TRFC-TR (P less than 0.01), and T-cell response to higher mitogen concentrations (PHA and Con-A) (p less than .005 and p less than .001, respectively).     

Therapeutic effect of cimetidine in patients undergoing haemodialysis.

Blood concentrations of cimetidine were measured and the therapeutic effect of the drug assessed patients undergoing maintenance haemodialysis. Thirteen patients were given a single oral 200-mg dose of cimetidine a mean of 2.7 hours before the start of dialysis. Dialysing for 6--12-6 m2 hours led to a mean fall of 71% in blood cimetidine concentration during haemodialysis. Nine patients with various upper gastrointestinal lesions diagnosed endoscopically were treated for up to six weeks with a reduced cimetidine dose of 200 mg 12-hourly; two patients received two courses of treatment. Repeat endoscopy after treatment disclosed satisfactory healing, and the drug did not accumulate. This lower dose regimen is recommended for patients receiving dialysis who develop upper gastrointestinal lesions for which a histamine H2-receptor antagonist is indicated.     

Comparison of cimetidine 800 mg once daily and 400 mg twice daily in acute duodenal ulceration.

A double blind trial was conducted in seven centres to evaluate the safety and efficacy of cimetidine 800 mg given at night compared with 400 mg given at breakfast and at bedtime. Altogether 197 patients with active duodenal ulcer confirmed by endoscopy entered the study, of whom 187 were eligible for analysis. After four weeks'' treatment the ulcer was healed in 76 of 91 patients (84%) receiving the once daily regimen and in 65 of the 96 patients (68%) receiving the twice daily regimen (p less than 0.05). Both dosage regimens were equally effective in reducing ulcer pain and consumption of antacids. Pain relief was considerable within the first two weeks, and most of the patients were free of symptoms by the end of treatment. No patients were withdrawn because of adverse events as these were few and mild, consistent with the proved safety profile of cimetidine. Cimetidine 800 mg given at night is as effective as 400 mg twice daily; the single dose regimen may improve patient compliance, thus facilitating treatment.     

Comparative Treatment of Helicobacter pylori–Positive Duodenal Ulcer Using Pantoprazole at Low and High Doses Versus Omeprazole in Triple Therapy

Background. Helicobacter pylori eradication has become the standard treatment for peptic ulcer disease. H. pylori –eradicating triple therapy with omeprazole plus two antibiotics has been used until recently; however, the efficacy of pantoprazole and antibiotics for H. pylori eradication has not been researched thoroughly until now. The aim of this randomized clinical trial was to verify the efficacy of triple oral therapy comparing the effects of pantoprazole using two different doses versus omeprazole twice daily in H. pylori eradication, in ulcer healing and relapses, and in gastritis improvement.
Materials and Methods. We enrolled 243 patients with H. pylori– positive duodenal ulcer and randomized them into three treatment groups: 84 patients (group Ome40) were assigned to receive omeprazole, 20 mg twice daily, plus amoxicillin, 1 gm twice daily, and clarithromycin, 500 mg twice daily for 10 days; 79 patients (group Pan40) were treated with pantoprazole, 40 mg daily, plus amoxicillin and clarithromycin at the same doses as those of group Ome40; and 80 patients (group Pan80) were treated with pantoprazole, 40 mg twice daily, plus amoxicillin and clarithromycin at the same doses as those of group Ome40.
Results. Ulcer healing was observed in 81 of 84 patients (96.4%) in group Ome40; in 66 of 79 patients (83.5%) in group Pan40; and in 77 of 80 patients (96.2%) in group Pan80. H. pylori was eradicated in 79 of 84 patients (94%) in group Ome40; in 63 of 79 patients (79.7%) in group Pan40; and in 75 of 80 patients (93.7%) in group Pan80.
Conclusions. We found that 10-day triple therapy with amoxicillin, clarithromycin, and either pantoprazole, 80 mg daily, or omeprazole, 40 mg daily, is highly effective in ulcer healing and is very well tolerated, achieving the 90% cure recommended for an ideal first-line anti– H. pylori positive duodenal ulcer treatment regimen.     

Cimetidine in patients with gastric ulcer: a multicentre controlled trial.

Forty-five adult outpatients with endoscopically confirmed gastric ulceration completed a double-blind trial of either cimetidine (1 g/day) or placebo. After six weeks 18 of the 23 patients receiving cimetidine showed complete ulcer healing compared with only six of the 22 patients receiving placebo. The cimetidine group also had fewer days with pain than the placebo group but the difference was not statistically significant. Cimetidine therefore seems to promote healing of gastric ulcers without severe side effects, although its effect on pain is less pronounced than in patients with duodenal ulcers.     

埃索美拉唑治疗幽门螺杆菌阳性十二指肠球部溃疡疗效观察

目的：比较埃索关拉唑与兰索拉唑、奥美拉唑三联疗法治疗幽门螺杆菌（Hp）阳性十二指肠球部渍疡疗效观察。方法：将84例Hp阳性的十二指肠球部溃疡随机分为三组。埃索美拉唑组（28例）：埃索美拉唑20mg＋阿莫西林1g＋呋喃唑酮100mg,每日2次,共7日,后服用埃索美拉唑20mg,每日一次,共21天;兰索拉唑组（28例）：兰索拉唑15mg＋阿莫西林1g＋呋喃唑酮100mg,每日2次,共7日,后服用兰索拉唑15mg,每日一次,共21天;奥美拉唑组（28例）：奥美拉唑20mg＋阿莫西林1g＋呋喃唑酮100mg,每日2次,共7日,后服用奥美拉唑20mg,每日一次,共21天。疗效结束4周后复查胃镜并检测Hp,观察腹痛缓解率、溃疡愈合率,Hp根治率及药物不良反应。结果：埃索美拉唑组、兰索拉唑组和奥关拉唑组溃疡愈合率分别为100％,85．7％,82．1％,HP根治率为85．7％,60．7％,64.3％,埃索美拉唑组溃疡愈合率及Hp根除率高于兰索拉唑组及奥美拉唑组,差异具有统计学意义（P〈0．05）。兰索拉唑组及奥美拉唑组溃疡愈合率及Hp根除率无明显差异（P〉0．05）。三组用药后不良反应少,具较好的安全性。结论：埃索关拉唑三联疗法治疗Hp阳性的消化性溃疡疗效优于兰索拉唑及奥美拉唑三联疗法,值得临床广泛应用。     

RAPID HEALING OF PEPTIC ULCERS IN PATIENTS RECEIVING FRESH CABBAGE JUICE

Thirteen patients with peptic ulcer were treated with fresh cabbage juice, which, experiments have indicated, contains an antipeptic ulcer factor. This factor (vitamin U) prevents the development of histamin-induced peptic ulcers in guinea pigs.The average crater healing time for seven of these patients who had duodenal ulcer was only 10.4 days, while the average time as reported in the literature, in 62 patients treated by standard therapy, was 37 days.The average crater healing time for six patients with gastric ulcer treated with cabbage juice was only 7.3 days, compared with 42 days, as reported in the literature, for six patients treated by standard therapy.The rapid healing of peptic ulcers observed radiologically and gastroscopically in 13 patients treated with fresh cabbage juice indicates that the anti-peptic ulcer dietary factor may play an important role in the genesis of peptic ulcer in man.     

Effects of melatonin and tryptophan on healing of gastric and duodenal ulcers with Helicobacter pylori infection in humans

Melatonin (MT) and its precursor L-tryptophan (TRP) are implicated in the protection of gastric mucosa against aspirin-induced lesions and in the acceleration of healing of idiopathic gastro-duodenal ulcers, but no information is available whether these agents are also effective in healing of gastroduodenal ulcers accompanied by Helicobacter pylori (H. pylori) infection. In this study three groups A, B and C, each including 7 H. pylori-positive patients with gastric ulcers and 7 H. pylori-positive patients with duodenal ulcers, aging 28-50 years, were randomly assigned for the treatment with omeprazole 20 mg twice daily combined with placebo (group A), MT administered in a dose of 5 mg twice daily (group B) or TRP applied in a dose of 250 mg twice daily (group C). All patients underwent routine endoscopy at day 0 during which the gastric mucosa was evaluated and gastric biopsies were taken for the presence of H. pylori and histopathological evaluation. The rate of ulcer healing was determined by gastroduodenoscopy at day 0, 7, 14 and 21 after the initiation of the therapy. Plasma MT, gastrin, ghrelin and leptin were measured by specific RIA. At day 21, all ulcers were healed in patients of groups B and C but only 3 out of 7 in group A of gastric ulcers and 3 out of 7 in duodenal ulcers. Initial plasma MT showed similar low levels in all three groups but it increased several folds above initial values in ulcer patients at day 7, 14 and 21. Plasma gastrin and leptin levels showed a significant rise over initial values in patients treated with omeprazole and placebo, MT or TRP while plasma ghrelin levels were not significantly affected by these treatments. We conclude that MT or TRP added to omeprazole treatment, significantly accelerates healing rate of H. pylori infected chronic gastroduodenal ulcers over that obtained with omeprazole alone and this likely depends upon the significant rise in plasma MT and possibly also in leptin levels, both hormones involved in the mechanism of gastroprotection and ulcer healing.     

Intermittent treatment of duodenal ulcer with cimetidine.

Intermittent treatment with short courses of cimetidine given only when symptoms recurred was assessed in patients with duodenal ulcer as an alternative to maintenance treatment. Their progress was followed up for up to 22 months. Gastroscopy was carried out in most attacks to confirm recurrence of the ulcer and subsequent healing. Out of 125 patients treated, 83 relapsed, of whom 21 defaulted. After retreatment 36 patients relapsed again. The pattern of relapse and remission for the group as a whole was similar after both courses of treatment, indicating an unchanged natural history. Nevertheless, wide variation occurred in individual patients, so that the pattern of relapse could not be predicted by the duration of the initial remission. Most patients had one or two or rarely three symptomatic relapses a year, which were rapidly treated successfully with cimetidine. Therefore, unless the necessity for long-term maintenance treatment is established, intermittent treatment provides an adequate alternative in most patients with duodenal ulcer.     

Serum concentration of prolactin, gastrin and glycocholic acid in patient with peptic ulcer treated with ranitidine

In 66 patients with peptic ulcer (11 with gastric ulcer, 55 with duodenal ulcer, 19 women, 47 men) the serum concentrations of prolactin, dehydrocholic acid and gastrin were determined. The studies were repeated after treatment with ranitidine: in 50 patients after three weeks and in 40 patients after another 30 days. During the first period ranitidine 2 x 150 mg was administered, while during the second period the dose was 1 x 150 mg. The results were compared with those obtained from 120 healthy subjects. Before starting the treatment prolactin levels were significantly higher than those in the control group. During the treatment a significant decrease of the levels was observed. Similar changes of prolactin concentrations were found in the group of 39 men with duodenal ulcer isolated from the studied patients, who were compared with a group of 50 healthy men. It was not found that the development of peptic ulcer and the treatment with ranitidine exerted and effect on the changes of gastrin and dehydrocholic acid concentrations.     

Phase I evaluation of coumarin (1,2-benzopyrone) and cimetidine in patients with advanced malignancies.

Fifty-four patients with advanced malignancies were treated on this phase I trial of coumarin and cimetidine. The dose of coumarin was escalated, with three patients treated at each dose level, while the cimetidine dose was held constant at 300 mg four times daily. Patients received coumarin alone as a single daily oral dose for 14 days; on day 15, cimetidine was added and both drugs were continued until progression of disease. This trial was initiated with patients receiving coumarin at 400 mg daily and closed at 7 g daily with four of five patients on this dose experiencing nausea and vomiting. Treatment was generally well tolerated over a wide range of coumarin doses. Symptomatic side effects were few, mild, and usually self limited. Side effects included insomnia, nausea, vomiting, diarrhea, and dizziness. Two patients withdrew from therapy because of daily nausea and vomiting. Typically, nausea, vomiting, and dizziness occurred 2.5-3 hours after a dose of coumarin. In most patients, these side effects abated spontaneously with continuation of therapy. There was no significant hematologic or renal toxicity. Hepatotoxicity occurred in only one patient and was manifested by asymptomatic abnormal elevations of serum hepatic transaminases. This toxicity was reversible upon interruption of therapy. Objective tumor regressions were observed in six patients with renal cell carcinoma. Responses occurred at coumarin doses ranging from 600 mg to 5 g daily. Coumarin is a relatively nontoxic, oral, outpatient therapy that warrants further investigations for the treatment of human malignancies. Because of its low toxicity, there is potential for combining coumarin with chemotherapeutic and/or biological agents in an attempt to improve on efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of interleukin-4 in down-regulation of endothelin-1 during gastric ulcer healing: effect of sucralfate.

BACKGROUND: The course of events associaed with healing gastric mucosal injury involves an orderly interplay between the array of signaling molecules that exert their influence on the processes leading to the restoration of the mucosal integrity. In this study, we investigated the effect of antiulcer agent, sucralfate, on the mucosal apoptotic processes during gastric ulcer healing by analyzing the expression of interleukin-4 (IL:4), endothelin-1 (ET-1), tumor necrosis factor-alpha (TNF-alpha), and the mucosal activity of capase-3, and constitutive (cNOS) and inducible nitric oxide synthase (NOS-2). METHODS: Rats with experimentally induced chronic gastric ulcers were administered twice daily for 14 days either sucralfate at 100 mg/kg or vehicle, and at different stages of treatment their stomachs were used for macroscopic and biochemical assessments. RESULTS: The ulcer onset was characterized by a massive epithelial apoptosis associated with a 33-fold increase in caspase-3 activity, 5.7-fold increase in TNF-alpha, 17.5-fold increase in NOS-2 and a 3.9-fold increase in ET-1, while the mucosal expression of cNOS activity showed a 7.6-fold drop and IL-4 expression fell by 37.2%. The healing was reflected in a rapid recovery in IL-4, and a decrease in apoptosis, caspase-3, TNF-alpha, ET-1 and NOS-2, and a slow recovery in cNOS activity, and the process was accelerated in the sucralfate-treated group. While in the absence of sucralfate the expression of IL-4 returned to that of the normal mucosa by the 7th day of healing and that of ET-1 and TNF-alpha by the 14th day, an accelerated ulcer healing with sucralfate treatment was associated with IL-4 recovery by the 4th day and that of ET-1 and TNF-alpha by the 10th day when the ulcer heated, while recovery in cNOS activity required 14 days. Yet, in both groups of animals the apoptotic DNA fragmentation rate, caspase-3 and the expression of NOS-2 activity remained significantly elevated even after the ulcer healed. CONCLUSIONS: The results suggest that a decrease in the mucosal expression of the regulatory cytokine IL-4 at the ulcer onset may well be a key factor causing dysregulation of ET-1 production, induction of TNF-alpha, and triggering the apoptotic events that affect the efficiency of mucosal repair process. We also show that accelerated ulcer healing by sucralfate may be the result of a rapid mucosal IL-4 generation that leads to the suppression of the mucosal apoptotic events.     

A new ulcer model, "unhealed gastric ulcers", induced by chronic treatment with indomethacin in rats with acetic acid ulcers.

The healing of experimental gastric ulcers induced in rats is consistently delayed upon chronic treatment with indomethacin. This study was designed to examine both the fate of such delayed ulcers and the effects of various antiulcer drugs on the delayed ulcers. Four-week treatment with indomethacin significantly delayed the healing of acetic acid ulcers. Such ulcers remained unhealed for up to 12 weeks after cessation of indomethacin treatment, and were thus designated as "unhealed ulcers". Two-week administration of sucralfate, cimetidine or omeprazole significantly reduced the ulcerated area, yet aluminum hydroxide had little or no effect. Four-week administration of sucralfate also extensively reduced the size of the "unhealed ulcers", yet aluminum hydroxide, cimetidine and omeprazole had an insignificant effect on "unhealed ulcers". In the 2 and 4 week sucralfate-treated group, the pH of the gastric contents was 4.0 vs. 1.7 and 4.5 vs. 2.1 in the control groups, respectively. Gastric acid secretion was extensively inhibited by cimetidine and omeprazole. It is concluded that prolonged indomethacin treatment results in the development of "unhealed ulcers" and that only sucralfate has a beneficial effect on such ulcers, irrespective of the length of the treatment.