Studies on the expression of intestinal lactase in different individuals.

Sixty one duodenal biopsy specimens were examined for the expression of lactase at the level of enzyme activity, protein, and messenger RNA. Of the 51 samples with normal villous architecture, 39 were lactase persistent, 11 were nonpersistent (adult type hypolactasia), and one was of indeterminate status. All the lactase persistent individuals showed high mRNA and a high level of the lactase protein as detected by sodium dodecyl sulphate polyacrylamide gel electrophoresis. All the 11 non-persistent individuals tested showed a low level of lactase protein. Nine of the 10 samples tested showed low mRNA and one high mRNA. These results suggest that the lactase persistence polymorphism is controlled at the level of the expression of the lactase gene, though there may be some heterogeneity of the lactase non-persistence phenotype.

The effect of fasting on 24-hour intragastric acidity and plasma gastrin concentration.

Nine healthy subjects underwent two 24-h studies, either when fed six standard meals by mouth or when fasting. There was no significant difference in the median integrated 24-h intragastric acidity when fed or when fasting, 805 or 801 mmol.h/L, respectively. However, the median integrated 24-h plasma gastrin concentration was significantly higher when fed than when fasting, 284 pmol.h/L and 114 pmol.h/L, respectively (p less than 0.01). There appears to be a normal circadian rhythm for intragastric acidity: feeding appears to cause an acute decrease of intragastric acidity and to release gastrin, which in turn causes a compensatory rise of intragastric acidity. The results of this study suggest that the need to reinstate "normal" intragastric acidity is the drive to food-induced gastric acid secretion.

The timing of the evening meal affects the pattern of 24-hour intragastric acidity.

The object of the study was to examine the effect of varying the time of the evening meal on the pattern of 24-h intragastric acidity. Ten healthy subjects were studied; they ate regular meals throughout the day, but between 17.00 and 21.35 hours were separated into three groups. On three different days each group was fed the same dinner at either 17.15, 19.15, or 21.15 hours (early, standard or late). Variation in the evening meal's time caused significant changes in the pattern of acidity in the afternoon and evening, but did not affect 24-h intragastric acidity or nocturnal acidity. Integrated afternoon acidity (14.00 hours to dinner) was 69, 169 and 324 mmol.h/L when the subjects ate early, standard and late meals, respectively; evening acidity (dinner to midnight) was 235, 43 and 1 mmol.h/L with the three meals, respectively. The results suggest that, to control intragastric acidity, when the evening meal is eaten early (17.15 hours) dosing with an H2-antagonist should be after that meal, when eaten at the standard time (19.15 hours) dosing should be at bedtime, but when dinner is late (21.15 hours) the optimal regimen may involve dosing after lunch and also at bedtime.

Inappropriate hypergastrinaemia in asymptomatic healthy subjects infected with Helicobacter pylori.

An ELISA test determined serologically that eight of 95 apparently healthy men (aged 19-26 years) had an asymptomatic infection with Helicobacter pylori at the time of simultaneous measurement of 24 hour intragastric acidity and 24 hour plasma gastrin concentration. There was no significant difference in the median integrated 24 hour intragastric acidity between the H. pylori positive and H. pylori negative subjects (688 and 842 mmol/h/l; p = 0.271, respectively), whereas the median integrated 24 hour plasma gastrin concentration was significantly higher in the H pylori positive than in the H pylori negative subjects (389 and 198 pmol/h/l; p less than 0.001). Longterm hypergastrinaemia, associated with persistent H pylori infection, could be a cause of the increased parietal cell mass that is considered characteristic of duodenal ulcer patients.

Royal Free Hospital protocol for 24-hour intragastric acidity and plasma gastrin concentration.

The Royal Free Hospital protocol for simultaneous measurement of 24-hour intragastric acidity and plasma gastrin concentration is described in detail. The methods of analysing such data are discussed, with recommendations for a standard four-way analysis: median hourly 24-hour intragastric acidity or pH, or plasma gastrin concentration; integrated 24-hour intragastric acidity, or plasma gastrin concentration; analysis of integrated values according to meal-related intervals; and quantification of the percentage of time in a 24-hour period that intragastric pH is greater than 3.

Twenty four hour intragastric acidity and plasma gastrin concentration in healthy volunteers taking nizatidine 150 mg, nizatidine 300 mg, ranitidine 300 mg, or placebo at 21:00 h.

Nine healthy volunteers were studied on the seventh day of dosing at 21:00 h with nizatidine 150 mg (N 150), nizatidine 300 mg (N 300), ranitidine 300 mg (R 300), or placebo, given in a predetermined random order. The double-blind 24 hour studies, using the Royal Free Hospital standard protocol, simultaneously measured intragastric acidity and plasma gastrin concentration. Compared with placebo, subjects responded to dosing with each H2-antagonist by a significant decrease of 24 hour intragastric acidity (N 150-45%; N 300-49% R 300-56%; p less than 0.01) and a significant rise of plasma gastrin concentration (N 150 + 20%; N 300 + 27%; R 300 + 58%; p less than 0.01). All three drug regimens caused similar significant decreases of nocturnal acidity (N 150-72%; N 300-79%; R 300-85%; p less than 0.01) and increases of nocturnal plasma gastrin concentration (N 150 + 41%; N300 + 52%; R 300 + 80%; p less than 0.01). Dosing with ranitidine 300 mg at 21:00 h also caused a simultaneous significant decrease of morning acidity (-32%; p less than 0.05) with a significant increase of plasma gastrin concentration (+36%; p less than 0.05), but the antisecretory effects of nizatidine 150 or 300 mg at 21:00 h were only observed during the night, with no effect during the morning. No drug regimen had any effect on acidity or plasma gastrin in the afternoon or early evening.

Enprostil inhibits post-prandial gastrin release: a dose-response study.

In a double-blind placebo-controlled study in nine healthy volunteers, the effects of single doses of oral enprostil (8.75, 17.5, 35 and 70 micrograms), taken before a standard breakfast, were assessed on the post-prandial release of gastrin into the plasma. All doses of enprostil caused a significant dose-related decrease in median post-prandial plasma gastrin concentration (range from -29 to -44%). In the same subjects, two doses of 25 mg indomethacin caused a significant (38%) increase in median post-prandial plasma gastrin concentration.

The effects of famotidine, 40 mg at night, on 24-hour intragastric acidity and plasma gastrin concentration in healthy subjects.

The effects of 40 mg oral famotidine at 2115 h on 24-h intragastric acidity and plasma gastrin concentration were measured in a double-blind placebo-controlled study in 10 healthy subjects. The subjects were studied on the 7th day of treatment with either famotidine or placebo. Famotidine, 40 mg at night, caused a pulse of decreased intragastric acidity during the night, with a longer-lasting elevation of plasma gastrin concentration. However, in the latter part of the day there was complete recovery from the antisecretory effects of the drug, with normal intragastric acidity and normal concentrations of plasma gastrin.

Twenty-four-hour intragastric acidity and plasma gastrin concentration in healthy subjects and patients with duodenal or gastric ulcer, or pernicious anaemia.

Twenty-four-hour intragastric acidity and plasma gastrin concentration were measured in healthy subjects (n = 16), and patients with duodenal (n = 12) or gastric (n = 10) ulceration, or pernicious anaemia (n = 8). Median integrated 24-hour intragastric acidity was highest in duodenal ulcer patients and lowest in pernicious anaemia patients (1148 and 0 mmol.hour litre-1, respectively). Median integrated 24-hour plasma gastrin was highest in pernicious anaemia and lowest in the healthy subjects (9886 and 238 pmol.hour litre-1, respectively). Pernicious anaemia patients have unremitting hypergastrinaemia throughout the 24 hours. The results of this study not only provide a reference range of acidity and plasma gastrin in health and disease, but also will act as a baseline for future studies using antisecretory drugs.

Twenty-four-hour intragastric acidity and plasma gastrin concentration before and during treatment with either ranitidine or omeprazole.

Simultaneous 24-hour intragastric acidity and plasma gastrin concentrations were measured in 12 duodenal ulcer patients before and on the twenty-eighth day of treatment with either ranitidine 150 mg b.d. or omeprazole 20 mg o.m. Median integrated 24-hour intragastric acidity was decreased significantly from 1148 to 490 and 36 mmol.hour litre-1 during treatment with ranitidine and omeprazole, respectively, whilst median intragastric 24-hour plasma gastrin was raised significantly from 328 to 799 and 1519 pmol.hour litre-1 respectively. When the results of all 48 experiments were considered together, there was a significant inverse correlation between the 24-hour integrated values for intragastric acidity and plasma gastrin concentration. Both drugs caused a significant elevation of plasma gastrin throughout the 24 hours, although ranitidine had no effect on intragastric acidity from 1900 to 2200 hours. When compared with similar profiles of acidity and gastrin in pernicious-anaemia patients, the modest elevations of plasma gastrin observed in this study suggest that neither drug will be associated with clinically relevant enterochromaffin-like cell proliferation in duodenal ulcer patients.

Effect of oral famotidine on 24-hour intragastric acidity.

Twenty-four hour intragastric acidity was measured in nine volunteer subjects in a single-blind placebo-controlled cross-over study comparing the effects of famotidine with ranitidine. The volunteer subjects received famotidine (40 mg at night), famotidine (20 mg at night), ranitidine (300 mg at night) or placebo in a predetermined random order. Twenty-four hour intragastric acidity was measured after the seventh dose of each drug or placebo. Famotidine (20 mg), famotidine (40 mg) and ranitidine, all caused a significant decrease of intragastric nocturnal acidity when compared with placebo (P less than 0.01), with no effect during the daytime (P greater than 0.05). Treatment with all the drugs caused a significant rise of fasting plasma gastrin concentration compared with placebo (P less than 0.05).