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The occurrence of peptic ulcer increased rapidly in all Western countries from the 19th to the 20th century, attributed to a possible epidemic of Helicobacter pylori, a new pathogenic strain, or a change in host susceptibility. The early trends in hospital admissions for peptic ulcer and dyspepsia in London and New York during the 19th century are reviewed to test these hypotheses.

Objectives: Mortality data of peptic ulcer are mostly national and limited to the 20th century. The New York City data from 1804 have therefore been examined by both year of death and year of birth (cohort analysis), to consider whether the increases and subsequent decreases in deaths from gastric, followed by duodenal ulcer, can be attributed to Helicobacter pylori., Methods: The annual mortality reports of New York City described gastric ulcer from 1838 and duodenal ulcer from 1931. The age-specific death rates per 100,000 population were calculated in 10-yr periods both by year of death and by year of birth for each disease according to age and sex., Results: For gastric ulcer the period-of-death-age contours from the 1850s to the 1990s showed an increase to a mid-19th century plateau, but the cohort-age contours revealed a peak mortality for those born in the 1870s. Women born between about 1770 and 1880 showed a faster increase in mortality. For duodenal ulcer the period of birth contours showed a decline from a peak for those born in the 1880s and 1890s, with no sex difference., Conclusions: This urban study with data regarding deaths from gastric ulcer registered from 1838 and in those born from the 1770s, revealed by cohort analysis a peak in the 1870s, and for duodenal ulcer in the 1880s, comparable to national data worldwide. These time changes in fatalities are compatible with a change in the environment of children born in these decades, as, for example infection by a pathogenic strain of H. pylori.

Indigestion and heartburn have been described for thousands of years, but it was only in the 16th century that the disease peptic ulcer was established by autopsy. At first, only gastric ulcers were identified. In the 18th century, duodenal ulcers, most of which were fatal cases after perforation or hemorrhage, were seen. In the 19th century, when autopsy became a common, even routine, hospital procedure, uncomplicated acute and chronic ulcers were found and then correlated with symptoms. Thus, our current clinical understanding dates from the 1820s, by which time peptic ulcers were being reported in the U.S. It is unclear why gastric ulcers were not diagnosed at The Mount Sinai Hospital until 1873 and duodenal ulcers until 1885. However, after that time both conditions were diagnosed frequently, and they rapidly became common and were treated medically and surgically.

Gastric spiral organisms were first described in man in 1939 and identified as Helicobacter pylori causing peptic ulcers in the early 1980s. Surgical specimens of gastric resections from 1939 showed H. pylori to be present. Full-thickness sections of gastric mucosa from gastric specimens from the eighteenth-century Hunterian Collection at The Royal College of Surgeons of England were examined by histology for the presence of H. pylori. Four gastric ulcers and a section from an oesophageal varix showed remarkable preservation of the overall architecture, but surface autolysis did not allow identification of the bacteria. However, the presence of lymphoid aggregates in the Hunterian specimens suggests that H. pylori may have been present before autolysis.

Objective: To determine whether eradication of Helicobacter pylori infection reduces recurrence of benign gastric ulceration., Design: Randomised, double blind, controlled study. Patients were randomised in a 1:2 ratio to either omeprazole 40 mg once daily for eight weeks or the same treatment plus amoxycillin 750 mg twice daily for weeks 7 and 8. A 12 month untreated follow up ensued., Setting: Teaching and district general hospitals between 1991 and 1994., Subjects: 107 patients with benign gastric ulcer associated with H pylori., Main Outcome Measures: Endoscopically confirmed relapse with gastric ulcer (analysed with life table methods), H pylori eradication, and healing of gastric ulcers (Mantel-Haenszel test)., Results: 172 patients were enrolled. Malignancy was diagnosed in 19; 24 were not infected with H pylori; four withdrew because of adverse events; and 18 failed to attend for start of treatment, leaving 107 patients eligible for analysis (35 omeprazole alone; 72 omeprazole plus amoxycillin). In the omeprazole/amoxycillin group 93% (67/72; 95% confidence interval 84% to 98%) of gastric ulcers healed and 83% (29/35; 66% to 94%) in the omeprazole group (P = 0.103). Eradication of H pylori was 58% (42/72; 46% to 70%) and 6% (2/35; 1% to 19%) (P < 0.001) and relapse after treatment was 22% (16/72) and 49% (17/35) (life table analysis, P < 0.001), in the two groups, respectively. The recurrence rates were 7% (3/44) after successful H pylori eradication and 48% (30/63) in those who continued to be infected (P < 0.001)., Conclusions: Eradication of H pylori reduces relapse with gastric ulcer over one year. Eradication rates achieved with this regimen, however, are too low for it to be recommended for routine use.

Ammonia, released in the gastric mucosa by the action of Helicobacter pylori urease on transuded plasma urea, curtails the biosynthesis of mucus and/or causes the mucus to be disassembled at the mucosal surface. These changes facilitate colonisation by H pylori and may promote gastric ulcer formation.

Neither basal nor peak acid output changed significantly after treatment for four weeks with carbenoxolone sodium as Biogastrone tablets in patients with gastric ulcer or Duogastrone capsules in patients with duodenal ulcer.

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.

Basal and pentagastrin stimulated gastric secretion was measured in seven patients with duodenal, and six with gastric ulcers before and after four weeks' treatment with colloidal bismuth subcitrate (as De-Nol), one tablet four times a day. Each duodenal and all but one of the gastric ulcers healed. After De-Nol there were no significant changes in basal, or pentagastrin stimulated volume, acid output, or primary parietal component. There were marked decreases in basal (duodenal ulcer -25%; gastric ulcer -16%) and pentagastrin stimulated total pepsin outputs, (duodenal ulcer -42%, gastric ulcer -36%). There were insignificant decreases in basal output of mucus, but postpentagastrin stimulated mucus output was significantly inhibited (p less than 0.05) in patients with duodenal (-16%) and with gastric ulcer (-27%). The drop in gastric proteolysis after De-Nol is unlikely to be because of the healing of the ulcers and is more likely to be because of the drug. The ulcer healing efficacy of De-Nol may be related to this decline in the proteolytic action of gastric juice, but is unlikely to be because of a quantitative change in mucus, or in acid secretion.

A single-blind study of 339 patients in 19 centres compared the efficacy and tolerance of ranitidine in treating endoscopically confirmed gastric ulcers. Ranitidine (150 mg twice daily) was compared with cimetidine (1 g daily in divided doses) over 4 weeks, followed by a second 4-week treatment for any patient whose ulcer was not healed. In 292 patients who completed the study, endoscopy showed healing in 69% of patients receiving ranitidine and 59% receiving cimetidine after 4 weeks, and 90% and 88%, respectively, by 8 weeks. These results were not significantly different, and, similarly, healing rates for different ulcer sites did not differ. There were no serious adverse drug reactions during the study. Ranitidine is an effective and safe treatment for healing gastric ulcers, with a tendency to produce a faster healing rate than cimetidine during the first 4 weeks of treatment.

Antacids prove ready if only temporary relief of the symptoms of ulcers. Physicians have been able to increase the rate of healing of gastric ulcers by advising patients to stop smoking and then either admit them to hospital for bed-rest, or use carbenoxolone sodium as an outpatient therapy. The early trials of some other drugs have shown increase in rate of healing of gastric ulcer, but there is no medical treatment which will prevent the high recurrence rate of benign gastric ulcer. The limited data indicate that adequate medical reduction in acid secretion and enhancement of mucosal resistance may benefit patients with duodenal ulcer.

The absorption of carbenoxolone sodium has been studied in 15 patients with gastric ulcer and eight patients with duodenal ulcer treated for four weeks. Blood levels of carbenoxolone showed a log distribution, varied markedly between patients, and were significantly higher after Biogastrone tablets (300 mg/day) than after Duogastrone capsules (200 mg/day). Serum carbenoxolone levels were similar in patients taking Biogastrone tablets before or after meals, and in patients taking Biogastrone tablets or Duogastrone capsules with or without antacids following chronic administration. Serum carbenoxolone levels were similar in patients whose gastric ulcers had or had not healed after four weeks' treatment. Serum carbenoxolone was significantly higher in patients who developed oedema, and was significantly correlated with age and with fall in plasma potassium. Carbenoxolone may exert its metabolic effects systemically, but its ulcer-healing effects topically; additional studies are needed to test this hypothesis.