Eradication of Helicobacter pylori and prevention of recurrence of duodenal ulcer: a randomized, double-blind, multi-centre trial of omeprazole with or without clarithromycin.

BACKGROUND: Antimicrobial treatment for Helicobacter pylori eradication is currently recommended for all patients with duodenal ulcer disease, but consensus on the best treatment is lacking. METHODS: Patients with active duodenal ulcer and H. pylori were enrolled in a double-blind, randomized, placebo-controlled multi-centre study. Patients received omeprazole 40 mg daily for 28 days and either clarithromycin 500 mg t.d.s. or placebo t.d.s. for the first 14 days. Patients underwent endoscopy before starting treatment, at 2 weeks, immediately after stopping treatment if unhealed at 2 weeks, and at 1, 6 and 12 months after the end of treatment, or at the recurrence of symptoms. Eradication of H. pylori, duodenal ulcer healing and ulcer recurrence were measured. RESULTS: One-hundred and fifty-four patients were recruited and randomized to omeprazole plus clarithromycin (n = 74) or to omeprazole plus placebo (n = 80). One month after treatment, H. pylori was eradicated in 57 of 69 (83%; 95% CI: 72-91%) patients receiving omeprazole plus clarithromycin, compared with 1 of 75 (1%; 95% CI: 0-7%) receiving omeprazole alone (P < 0.001). In patients receiving omeprazole plus clarithromycin the ulcer healed at 2 weeks in 83% (95% CI: 71-91%) and at 4 weeks in 100% (95% CI: 95-100%), compared with 77% (95% CI: 66-86%) and 97% (95% CI: 91-100%) in those given omeprazole plus placebo (N.S.). Ulcers recurred at 12 months in 6% (95% CI: 1-16%) of patients given omeprazole plus clarithromycin, compared with 76% (95% CI: 63-86%) of patients given omeprazole plus placebo (P < 0.001). The incidence of side-effects was similar in both treatment groups (38% with clarithromycin dual therapy and 29% with omeprazole plus placebo; P = 0.304). Ninety per cent of patients took at least 90% of their prescribed medication. CONCLUSIONS: Omeprazole plus clarithromycin dual therapy eradicated H. pylori in 83% of patients with duodenal ulcer and significantly decreased 12-month recurrence from 76% to 6%.

Enprostil, a prostaglandin E2 analogue, in the treatment of duodenal ulcer; a multicentre comparison with cimetidine.

In a multicentre trial, 120 patients with endoscopically diagnosed duodenal ulcer were randomly allocated to treatment with either 35 micrograms enprostil b.d. or 400 mg cimetidine b.d. for up to 6 weeks on a double-blind basis. After 6 weeks, 82% (42/51) of enprostil-treated patients and 92% (44/48) of cimetidine-treated patients were healed. Corresponding healing figures on an intention-to-treat basis were 70% and 76%. No significant differences were detected between treatments with respect to healing rates or symptom control at any time. Side-effects were reported by 14 patients taking enprostil and 17 patients taking cimetidine; none were serious but they resulted in withdrawal of one and two patients respectively. Enprostil was found to be similar in efficacy and tolerance to cimetidine.

Instability of N-nitroso compounds in gastric juice and preliminary results from analyses of fresh samples by using an improved analytical method.

Using an improved method for determination of total N-nitroso compounds (NOC), we examined the stability of those compounds in fresh gastric juice samples during storage and the effects of the addition of 2% sulphamic acid on NOC concentration in 212 samples. The NOC levels in fresh samples decreased very rapidly at -20 degrees C, especially during the first 24 hours of storage (P < 0.01), and nitrite concentration also showed a decreasing trend during storage. The addition of sulphamic acid significantly reduced NOC levels from 1.97 +/- 0.21 to 1.10 +/- 0.12 mumol/l (mean +/- SE, P < 0.01), especially in samples of initially high pH. However, in some individual samples (16.5%) the NOC levels actually increased by 14.1% (P < 0.01). The results from analysis of NOC in 212 fresh samples in relation to pH demonstrated two significantly higher peaks of NOC concentrations at intragastric pH ranges 1.1 to 2.99 (P < 0.05) and 6.0 to 7.9 (P < 0.01). There was a significant relationship between nitrite level and intragastric pH (r = 0.480, P < 0.01), the nitrite concentration increasing dramatically when the pH exceeded 6.0. The present study suggest that a major proportion of the unidentified NOC formed through intragastric nitrosation is labile NOC; if the true concentration of NOC is to be determined it is therefore essential to analyse fresh gastric juice samples directly after collection and without pretreatment. It will also be necessary to characterize those labile NOC in order to study further the mechanism of endogenous N-nitrosation in man and its relation to human carcinogenesis.

Changing pattern of oesophageal cancer in a general hospital in the UK.

Reports in the literature indicate that there is a change in the pattern of oesophageal cancer. This prompted us to retrospectively examine 15 years of endoscopy records in this district general hospital to identify all patients with oesophageal cancer and to determine whether data from our area were similar to other reported series. Examination of 22,789 consecutive endoscopy records identified 199 oesophageal cancer cases. Overall 50% of these were adenocarcinomas, an even higher percentage than that reported in series based on cancer registry information. The number of squamous cell carcinomas in females was noted to be rising and this was associated with an increase in the age of female patients. Female patients were also significantly older than males. The cancer origins tended to be lower in the oesophagus in males than in females. These results support a rise in the percentage of oesophageal adenocarcinomas. Absolute numbers of cancers detected rose over the 15-year study, but this was in direct proportion to the number of endoscopies carried out annually and probably reflects an increased usage of endoscopy services during the period of study.

The relationship between gastric mucosal changes and nitrate intake via drinking water in a high-risk population for gastric cancer in Moping county, China.

There are conflicting reports on whether nitrate intake is related to gastric carcinogenesis. In this laboratory/field study from a high-risk area for gastric cancer, we analysed 178 samples of drinking water for nitrate and nitrite, and examined the relationship between gastric mucosal lesions (including gastric cancer) and quality of different types of drinking water and nitrate intake via water. The results showed that the nitrate content in the local drinking water was generally very high, with a mean of 109.6 mg/l (range 4.4-497.2 mg/l). There were significant differences in the nitrate content in drinking water from different wells in qualitatively different types of water. The histological changes were closely related to the quality of drinking water and its nitrate content. The results suggest that nitrate in drinking water probably plays an important role in gastric carcinogenesis and that in future aetiological studies of gastric cancer should include more information on well depth, the presence of public or private wells and nitrate content of water.

Effects of fruit juices, processed vegetable juice, orange peel and green tea on endogenous formation of N-nitrosoproline in subjects from a high-risk area for gastric cancer in Moping County, China.

The effects of four fruit juices, processed vegetable juice, orange peel, green tea and low dose vitamin C on endogenous N-nitrosation in 86 subjects from a high-risk area for gastric cancer in Moping County, China were studied using urinary excretion of N-nitrosoproline (NPRO) as an indicator. After ingestion of 300 mg L-proline, urinary excretion of NPRO was significantly increased from a baseline of 2.5 +/- 1.6 micrograms/day to 8.7 +/- 6.2 micrograms/day. (P < 0.001). Vitamin C (75 mg) administration significantly reduced NPRO formation (62.3%, P < 0.002) although NPRO excretion remained higher than the baseline level (4.2 +/- 1.3 vs 2.2 +/- 1.2 micrograms/day, P < 0.001). Intake of fruit juices and green tea extracts (containing 75 mg vitamin C) or of orange peel powder (containing 3 mg vitamin C) together with 300 mg L-proline inhibited NPRO formation effectively to the baseline level or to levels significantly lower than the baseline level (P < 0.05-0.005). A processed juice of a number of vegetables (300 ml) significantly catalysed endogenous nitrosation (14.7 +/- 11.8 vs 9.4 +/- 4.7 micrograms/day, P < 0.05). Endogenous N-nitrosation was unaffected by the presence of intragastric lesions. The present study shows that endogenous nitrosation in this population is profoundly affected by environmental factors and that inhibitors, such as vitamin C, alpha-tocopherol and other non-nutritive compounds in the foods do inhibit endogenous nitrosation either synergistically or in an additive manner. The significance of fruits and vegetables in prevention of human cancers is discussed.

Hypothesis on the relationship between gastric cancer and intragastric nitrosation: N-nitrosamines in gastric juice of subjects from a high-risk area for gastric cancer and the inhibition of N-nitrosamine formation by fruit juices.

The concentration of N-nitrosamines (NNA) in gastric juice was determined as an indicator of intragastric N-nitrosation in 85 subjects from a high-risk area for gastric cancer (GC) to examine the relationship between N-nitroso compounds (NOC), pH and intragastric lesions under strictly controlled conditions. Mean gastric pH in subjects with GC or dysplasia (Group GD, 5.0 +/- 2.7) was higher than that from subjects with intestinal metaplasia (Group IM, 3.8 +/- 2.1, p = 0.068) and significantly higher than in those with normal mucosa or superficial gastritis (Group NS, 2.6 +/- 1.9, p < 0.001). No significant difference (p > 0.1) was found in total NNA concentrations between the three groups (GD 1.81 +/- 1.05 micrograms/l, IM 1.46 +/- 0.79 micrograms/l, NS 1.56 +/- 1.38 micrograms/l). However, two obvious peaks of nitrosation were observed at pH ranges of < 2.0 and 5.5-7.5. These observations were confirmed by using the N-nitrosoproline test in the same subjects under the same conditions (r = 0.772, p < 0.05). These results indicate that intragastric nitrosation can occur in both acidic and nearly neutral conditions. The first peak is related to acid-catalysed nitrosation (ACN) and the second is related to biologically catalysed nitrosation (BCN). According to these and other published results the hypothesis that there are two basic mechanisms, ACN and BCN, for intragastric N-nitrosation in humans is explored. Gastric carcinogenesis in high-risk areas is more likely to be related to intragastric NOC formed by ACN, compared to low-risk areas where it is more likely to be related to intragastric NOC formed by BCN. Fruit juices and orange peel significantly inhibited intragastric nitrosation by both ACN and BCN.

An initial comparison of nine centres registering patients with the UK National Barrett's Oesophagus Registry (UKBOR).

Initial data from the first nine hospitals registering at least 50 patients each with UKBOR were analysed. This involved 2102 Barrett's oesophagus (BO) cases (M1261:F841), mean 234 patients per centre (range 73-636) and M:F ratio 1.5 (range 1.1-2.3). There was an equal geographical distribution of the hospitals, three each in the north of the country (N), Midlands (Mid) and the south of the country (S). The catchment populations varied from 145,000 to 450,000. The M:F ratio for N, Mid and S was 1.6, 1.3, 1.7, respectively. The mean age at diagnosis in males was 62.0 years (range 53.2-66.3) and in females 67.6 years (range 59.3-73.4), with little geographical variation. The age distribution varied somewhat between the centres; the peak age for males being 40-49 years in one northern hospital, 60-69 years in seven others and 70-79 years in one hospital. For females it was 60-69 years and 70-79 years in each of four hospitals, and 80-89 years in one. The BO diagnosis rate in the under 50s was fairly constant; F mean 14% (range 0-23%); M (eight centres) mean 23% (range 16-27%). However, in one northern centre it was much higher (43%). Information on patients with a diagnosis of oesophageal adenocarcinoma (AC) was available from seven centres. A total of 59 AC were diagnosed (M44:F15, ratio 2.9). The overall mean rate of AC in BO was 3.6% (range 0.5-7.5%). Minor variations in BO patient characteristics may have been due to the hospitals' different policies on diagnostic and reporting criteria. However, the much higher percentage of men under age 50 in the one N centre may reflect a genuine difference in diet and lifestyle, or possibly genetic susceptibility.

Effects of high dose vitamin C treatment on Helicobacter pylori infection and total vitamin C concentration in gastric juice.

Low gastric juice total vitamin C concentration in the presence of Helicobacter pylori (H. pylori) infection probably plays a role in gastric carcinogenesis. In vitro vitamin C has been shown to inhibit the growth of H. pylori. The aims of this study were to determine the effect of high dose vitamin C administration on H. pylori infection and on gastric juice total vitamin C concentration in patients with H. pylori related chronic gastritis. Sixty patients with dyspeptic symptoms and proven chronic gastritis and H. pylori infection, who were undergoing routine endoscopy, entered the study after giving informed consent. They were randomly coded into two treatment groups. Group 1 (controls, n = 28) were treated with antacids for 4 weeks and Group 2 (n = 32) received vitamin C 5g daily also for 4 weeks. Nine patients did not complete the study and were excluded. Plasma and gastric juice total vitamin C levels were measured at baseline, at the end of 4 weeks treatment and again 4 weeks after treatment cessation. In the control group H. pylori infection remained unchanged in all 24 patients throughout as did the mean gastric juice total vitamin C concentration. However, in the vitamin C treated group eight of 27 patients (30%) who completed the treatment course the H. pylori infection was eradicated (P = 0.01). In these patients the mean gastric juice total vitamin C concentration rose significantly from 7.2 +/- 1.6 micrograms/ml after 4 weeks treatment (P < M 0.001) and 19.8 micrograms/ml 4 weeks after treatment was discontinued (P < 0.001). In the remaining 19 patients with persistent H. pylori infection, the mean gastric juice total vitamin C concentration rose less than in those with successful H. pylori eradication; 6.3 +/- 1.7 micrograms/ml before treatment, 10.8 +/- 1.5 micrograms/ml after 4 weeks treatment (P < 0.05) and a return to pre-treatment levels (7.1 +/- 2.7 micrograms/ml) 4 weeks after vitamin C intake stopped. There were no side effects of vitamin C treatment. This study has shown that 4 weeks daily high dose vitamin C treatment in H. pylori infected patients with chronic gastritis resulted in apparent H. pylori eradication in 30% of those treated. In those patients there was also a highly significant rise in gastric juice total vitamin C concentration which persisted for at least 4 weeks after the treatment ceased. A significant, though less marked, gastric juice total vitamin C concentration increase was observed during vitamin C treatment even in subjects with persistent H. pylori infection, though this was not maintained after treatment ended. The mechanism whereby vitamin C treatment appeared to result in H. pylori eradication is unclear. Further confirmatory studies are indicated.

Controlled trial of a carbenoxolone/alginate antacid combination in reflux oesophagitis.

A double-blind controlled trial was carried out in 37 patients with oesophagitis, confirmed endoscopically and histologically, to compare the efficacy of treatment with a carbenoxolone/alginate antaacid combination with that of the alginate antacid compound used alone. The total daily dosage of carbenoxolone was 100 mg. During the 8-week-period of the trial patients were seen every 2 weeks and endoscoped at 4 and 8 weeks. Response to treatment was assessed symptomatically and endoscopically using 6-point grading scales, and multiple oesophageal biopsies were taken at each endoscopy. The addition of carbenoxolone to the alginate antacid compound was shown to enhance symptomatic relief and to increase healing of oesophagitis and oesophageal ulceration significantly. No serious side-effects were reported in either group. Although there were a number of biochemical or clinical abnormalities recorded, none required any alteration in treatment.

A single centre's 20 years' experience of columnar-lined (Barrett's) oesophagus diagnosis.

BACKGROUND: The pattern of oesophageal carcinoma type has been changing for some time in a number of countries, with adenocarcinoma becoming more frequent OBJECTIVE: To investigate the prevalence of columnar-lined (Barrett's) oesophagus and oesophageal adenocarcinoma in Barrett's oesophagus during a 20-year period in a single centre. METHODS: All upper gastrointestinal endoscopy and histology reports for the period January 1977 to December 1996 inclusive were reviewed. Data were analysed from patients who had histologically proven Barrett's oesophagus. The data were analysed as a single cohort and in five-year bands according to the date of diagnosis. RESULTS: Of 44,721 endoscopies, 636 Barrett's oesophagus cases were diagnosed; 508 (323 males 185 females; M:F ratio 1.7) were histologically proven. The frequency of Barrett's oesophagus detection increased steadily from 0.2% to 1.6% of all endoscopies per five-year band. The M:F ratio and the mean ages at diagnosis (61 years, range 60-63 for males and 69 years, range 68-79 for females) remained constant throughout. Barrett's oesophagus was diagnosed at a younger age in males (peak 60-69 years) compared to females (peak 70-79 years). The male oesophageal adenocarcinoma incidence (11.1%) was almost twice that in females (6.5%). In the majority (81%), the initial diagnosis of oesophageal adenocarcinoma and Barrett's oesophagus was made concurrently. CONCLUSIONS: The increasing Barrett's oesophagus frequency may reflect an increasing incidence or recognition of this condition or both. Barrett's oesophagus males are more likely to develop oesophageal adenocarcinoma than females.

Treatment of Helicobacter pylori infection.

Helicobacter pylori infection is now recognised as the major cause of chronic active gastritis and peptic ulcer disease and eradication of the infection will prevent recurrence of the majority of such ulcers. A large number of different treatment combinations have been tried, but 100% H pylori eradication has not been achieved due to the use of wrong drug combinations or dosages, non-compliance and development of primary or acquired bacterial resistant strains. However, consistent 95-96% H pylori eradication can now be achieved with triple therapy employing a high-dose proton pump inhibitor twice daily together with any two of the following drugs: nitroimidazole, clarithromycin, or amoxycillin in appropriate dosages taken two to three times daily and all concurrently for one week. The problem of resistant bacterial strains has to be addressed, as this development is one of the consequences of failed eradication treatment.

Susceptibilities of drugs to nitrosation under standardized chemical conditions.

Of 22 drugs with either a N,N-dimethylamino, N,N-diethylamino or N-morpholino group in the molecule, eight were converted to volatile N-nitrosamines by nitrosative cleavage in reactions of nitrite and drug in a molar ratio of 4:1 at pH 3. Under standardized conditions yields were greatest with aminopyrine and minocycline which contains two N,N-dimethylamino groups in the molecule. Oxytetracycline, chlortetracycline, tetracycline, promethazine, chlorpromazine, imipramine and disulfiram gave much lower yields and amitriptyline, clomiphene, clomipramine, dextropropoxyphene, diphenhydramine, disopyramide, erythromycin, mepyramine, methapyrilene, penicillin G procaine salt, procaine, tamoxifen, trimeprazine and tripelennamine yielded no detectable levels of volatile N-nitrosamines. Nitrosation products of 57 drugs were also examined by a group selective procedure estimating both volatile and non-volatile N-nitroso compounds. Virtually all of the yield obtained from aminopyrine or minocycline could be accounted for by N-nitrosodimethylamine (NDMA). However, compounds yielding excess N-nitrosamines compared to NDMA were obtained from the other three tetracyclines, presumably as a result of the cleavage of a methyl group from the N,N-dimethylamino substituent to form desmethyl-N-nitroso compounds. In general, the drugs giving the highest yields of N-nitroso compounds were those containing secondary rather than tertiary amino groups. A considerable range of susceptibilities towards nitrous acid was observed overall; ten drugs containing a secondary or tertiary amino- or amido- or hydrazido - group did not react with nitrous acid to form N-nitroso compounds.

Susceptibilities of drugs to nitrosation under simulated gastric conditions.

Drugs of differing structures and pharmacological actions have been incubated at 37 degrees C and pH 2.0 under conditions simulating those within the normal fasting stomach. The nitrite concentration (25 microM) was kept as constant as possible for 3 hr in an attempt to mimic its in vivo replenishment from the saliva. The extents of N-nitrosation varied widely, but were less than those observed by Gillatt et al. (Fd Chem. Toxic. 1984, 22, 269) using the WHO Nitrosation Assay Procedure, in which the initial nitrite concentration is 40 mM, 1600 times greater, and the pH (3.0) is close to the optimum for the N-nitrosation of secondary amines. The highest yield of N-nitroso compound was obtained with the benzathine salt of penicillin G whereas some drugs, including hydrochlorothiazide and chlorthalidone, produced no detectable N-nitroso derivative. The degree of N-nitrosation was consistently reduced when the initial nitrite concentration of 25 microM was not replenished during the incubations, underlining the importance of simulating the continuous supply of nitrite from the saliva. In all instances, the reactions of the drugs with nitrous acid were inhibited and, in most cases, completely prevented by the presence of ascorbic acid (125 mg).

Pyrogastrone treatment of peptic oesophagitis: analysis of 104 patients treated during a 3 1/2-year period.

A retrospective analysis was carried out in 104 patients with peptic oesophagitis treated with Pyrogastrone (carbenoxolone with alginate-antacid) during a 3 1/2-year period. There wer 3 treatment groups: one had Pyrogastrone alone, another pyrogastrone with metoclopramide and in the third, both agents were given together with cimetidine. Highly significant symptomatic improvement was achieved in 85% of 96 patients treated between 4 and 8 weeks and equally significant endoscopic healing was noted in 76% of 55 patients for the same period. Best results were seen in those given Pyrogastrone alone; the concurrent use of metoclopramide and cimetidine did not enhance healing or symptom relief. 40% of patients received multiple courses, 22% were treated for at least six months and 16% for one year or longer continuously; 3 patients for over 3 years. The only noteworthy side effects were due to the tablet flavour and chewing property. These results confirm clinical trial experience that Pyrogastrone is highly effective in healing peptic esophagitis.

Carbenoxolone interactions in man--preliminary report.

Carbenoxolone is a potent ulcer-healing drug which is extensively bound to plasma proteins and therefore has the potential for displacement interaction. However, carbenoxolone has been shown to be bound to human serum albumin in vitro at a different class of binding site to many other drugs and does not potentiate the pharmacological activity of warfarin, tolbutamide, chlorpropamide or phenytoin in the rat. In the present study four volunteers each received a single 100 mg dose of Biogastrone and the plasma half-life of carbenoxolone was determined. The procedure was repeated with a concurrent dose of either warfarin 10 mg, tolbutamide 500 mg, chlorpropamide 250 mg or phenytoin 100 mg. Chlorpropamide appeared to delay the absorption of carbenoxolone but no effects were observed with the other drugs. The study with concomitant chlorpropamide treatment was repeated with 6 gastric ulcer patients on an established Biogastrone regimen. In these patients the delayed absorption of carbenoxolone was confirmed although no changes in the glucose-lowering activity of chlorpropamide were evident. Further investigations into this findings are in progress.

Prevalence of Campylobacter pylori in duodenal and gastric mucosa--relationship to inflammation.

Endoscopic biopsies from 310 patients were studied for the presence of Campylobacter pylori (Cp). In the first group of 150 patients duodenal and antral biopsies were obtained and in the second (160 patients) biopsies were taken from various sites in the stomach including the antrum, incisura, body and fundus. In the duodenum there was a strong association with active inflammation and the presence of gastric metaplasia. Cp were never seen in the normal duodenum. In the stomach Cp presence was associated with gastritis irrespective of severity and site, but was absent in areas showing intestinal metaplasia. Cp were seen in histologically normal biopsies from all areas of the stomach but were significantly more common in normal fundal than normal antral mucosa.

An enzyme-linked immunosorbent assay for the serodiagnosis of Campylobacter pylori-associated gastritis.

An ELISA system, using an acid extractable cell surface C. pylori antigen, has been used to detect anti-C. pylori antibodies in 176 endoscoped patients. The antibody concentration was related to histological diagnosis and colonisation with Campylobacter-like organisms. The criteria for sero-positivity was determined from the median antibody concentration in a group of 368 non-endoscoped control patients. The specificity and sensitivity of the sero-diagnostic assay for histological gastritis in antral biopsies was 83.0% and 95.6% respectively. The positive (79.3%) and negative predictive values (94.3%) indicate that such a sero-diagnostic assay could be used to screen patients prior to endoscopy.

The influence of amiloride on the therapeutic and metabolic effects of carbenoxolone in patients with gastric ulcer. A double-blind controlled trial.

Patients with benign gastric ulcer were treated for four weeks with carbenoxolone sodium as Biogastrone tablets 100 mg three times a day, and if the ulcers were not healed at 4 weeks treatment was continued for a further 4 weeks. Fifty two patients entered the trial, and 12 were withdrawn. In 17 patients who were randomly allotted double-blind additional dummy tablets 16 of their ulcer healed completely endoscopically, whereas of the 23 patients given additional amiloride 5 mg three times a day only 14 ulcers healed, a significant reduction in ulcer healing. The clinical (weight gain and oedema) and metabolic (hypertension, hypokalaemia and hypernatraemia) side-effects were reduced by the active amiloride therapy, but serum carbenoxolone levels were not affected. Thus the potassium-retaining diuretic amiloride, like the aldosterone antagonist spironolactone, markedly reduces both the ulcer-healing and the metabolic side-effects of carbenoxolone sodium, and should not be used together with it in the treatment of peptic ulcer.

Carbenoxolone (duogastrone) and cimetidine in the treatment of duodenal ulcer--a therapeutic trial.

A double-blind, double-dummy trial to compare carbenoxolone (Duogastrone) with cimetidine has been carried out in patients with duodenal ulcer. Sixty patients completed the six week trial period, 31 patients were treated with carbenoxolone and 29 with cimetidine. Both groups were comparable with respect to age, sex, smoking habits and alcohol intake. There were no significant differences between groups during the trial period with respect to symptomatic relief and antacid consumption. Endoscopy after six weeks of therapy showed healing in 61% of patients receiving carbenoxolone and 72% in those receiving cimetidine, a difference which is not significant. No serious side-effects occurred with either drug.