A prospective randomized trial of vagotomy in chronic duodenal ulceration: 4-year follow-up.

A total of 153 patients (124 male and 29 female) with uncomplicated chronic duodenal ulceration were studied in a prospective, randomized trial of proximal gastric vagotomy (PGV) and truncal vagotomy and pyloroplasty (TVP), conducted in four Manchester hospitals. Of these, 137 patients have now been followed up for 2.5 to 5.5 (mean 4.1) yr. There have been 15 (21 per cent) recurrent ulcers following PGV compared with 5 (7.5 per cent) after TVP (P less than 0.05). A satisfactory functional result was obtained in 82 per cent of patients after TVP compared with 73 per cent following PGV and there was little difference between the groups with regard to the incidence of dumping, heartburn and vomiting. There was significantly more diarrhoea following TVP (13 per cent) compared to PGV (1.4 per cent) but this represented only a minor clinical problem.

Randomized trial of elective highly selective or truncal vagotomy in chronic duodenal ulceration.

Between 1973 and 1976, 153 patients (124 men, 29 women) with uncomplicated, chronic, duodenal ulcer were entered into a prospective randomized trial of highly selective vagotomy (HSV) or truncal vagotomy and pyloroplasty (TVP). The study was conducted in four Manchester hospitals and the operations were performed by consultants or chief registrars. The follow-up was conducted by personal interview using a standardized questionnaire. The medical gastroenterologist did not know which type of operation the patient had had. The patients who had symptoms were referred back to the surgeon who performed the operation. The clinical laboratory and follow-up data were analysed by computer. There were no operative deaths. Three patients died from unrelated causes, 13 were lost to follow-up; 137 (89.5%) were followed up for a mean of 4.1 years (range from 2.5 to 5.5 years). A modified Visick grading was used to assess the results of surgery. The outcome was good in 82% after TVP and 73% after HSV. This difference and those in the incidences of early or late postprandial dumping, bilious vomiting, weight loss, anemia and heartburn were not significant. Diarrhea was more frequent after TVP (13.4%) than after HSV (1.4%); although the difference was significant (p less than 0.025), this complaint did not present a serious clinical problem. Ulcers recurred in 15 (21.4%) patients following HSV and in 5 (7.5%) after TVP; this difference was statistically significant (p less than 0.05).

Effect of urogastrone on gastric secretion and serum gastrin concentration in patients with duodenal ulceration.

A one-hour infusion of 0.25 micrograms/kg urogastrone administered to seven patients with duodenal ulceration resulted in significant reduction of basal acid secretion (p less than 0.05) but was without significant effect on basal pepsin and intrinsic factor secretion or on serum gastrin concentration. In another group of five patients with duodenal ulceration a one-hour infusion of urogastrone was given on five successive days. On day 1 and 5 urogastrone was administered after establishing a plateau response to intravenous pentagastrin 1.2 micrograms/kg/h. A mean reduction of 65% in acid output during the urogastrtone infusion was seen on day 1 and this was maintained during the next hour. On day 5 the pentagastrin-stimulated acid output was less than on day 1 and a further significant decrease was noted after urogastrone. Pepsin and intrinsic factor output were also significantly inhibited. There was no change in fasting serum gastrin or urogastrone concentration.

Long-term therapy with carbenoxolone in the prevention of recurrence of gastric ulcer. Natural history and evolution of important side-effects and measures to avoid them.

Between 1970 and 1979, 140 patients aged between 19 and 84 years with endoscopically confirmed gastric ulcer (GU), were treated with Biogastrone in reducing doses for 6 months. They received a daily dose of 300 mg for one week, 150 mg for 5 weeks, 100 mg for 6 weeks and 50 mg for the remainder of the 6 months. All the patients were reviewed at 2, 4, 6, 8, 12, 16, 20, 32, and 38 weeks and thereafter every 3 months or earlier in the event of significant dyspepsia. The anticipated recurrence rate of GU of approximately 42% at 2 years (3) was nearly halved to 26.7% over a median follow-up of 36 months in 140 cases completing the full six months course of treatment. The incidence of side effects was as follows: (i) A weight gain of 3.5 kg or more was seen in 23% of the patients at 2 weeks; this effect was maintained through the 6 month period. (ii) Oedema was noted in 14% of the patients at 2 weeks but declined to a 2% incidence by the end of the study. (iii) Elevated diastolic blood pressure in 14--18% of patients below 60 years and 20--27% patients above 60 years of age was noted throughout the study period. A high proportion of patients (38%) receiving other therapy had hypertension prior to the trial period; Carbenoxolone treatment had little further effect on blood pressure in these patients. (iv) Hypokalaemia was noted in the early stages of treatment especially in those over 60 years (43%). The incidence declined with the reduction in dosage through the 6 month treatment period. All side effects were successfully treated by diuretics and potassium supplements.

Cimetidine and gastric cancer.

Three patients with dyspeptic symptoms who were being treated with the H2-receptor blocking drug, cimetidine, were later found to have gastric carcinoma. It was not possible to determine whether the association was fortuitous, whether the drug had masked the neoplastic change, or whether it was involved in some other way. Repeated clinical and endoscopic evaluation is essential in patients on this treatment for any length of time.

A prospective randomized trial of vagotomy in chronic duodenal ulceration.

In a prospective, randomized trial, 76 patients with duodenal ulceration treated by truncal vagotomy and pyloroplasty were compared with 77 patients who underwent highly selective vagotomy. A total of 149 patients was followed up for from 1 to 4 years, the average follow-up period being 2.6 years. There was no operative mortality and no significant difference in postoperative morbidity between the two groups. The incidence of recurrent ulceration was greater after highly selective vagotomy, but this difference was not statistically significant. The clinical results were comparable in each group, and although the incidence of diarrhoea and dumping was greater after vagotomy and pyloroplasty, this difference was not statistically significant.

Comparison of an intragastric method of estimating acid output with the pentagastrin test in normal and duodenal ulcer subjects.

Using Fordtran's technique but substituting the meat extract Oxo for the steak meal we investigated gastric acid secretion in eight control subjects and nine patients with chronic duodenal ulcer. Intragastric titration was performed using a double lumen tube measuring the pH in the stomach every three minutes and adjusting it to 5.5 throughout the test by infusing 0.3-M sodium bicarbonate. On a separate day a pentagastrin test was performed using a conventional gastric aspiration technique. In the eight control subjects the mean acid output after pentagastrin was 13.7 +/- 2.1 (SEM) mmol/h, whereas the mean hourly acid output measured by intragastric titration was 20.1 +/- 3.1. The greater response to Oxo than to pentagastrin in the controls (deltaAO = + 46%) was significant (P less than 0.01). This is in contrast with our duodenal ulcer patients whose mean hourly acid outputs were 22.7 +/- 4.4 and 23.0 +/- 4.4 mmol/h in response to pentagastrin and Oxo respectively (r = 0.95). The findings, while clearly at variance with those of Fordtran and Walsh (1973), are more in keeping with the concept of increased endogenous secretory drive in duodenal ulcer patients compared to normal subjects.

Failure of oral bromocriptine to affect hypergastrinemia in two patients with the Zollinger-Ellison syndrome.

Bromocriptine was administered to 2 subjects with gastrin-secreting tumors of the pancreas. The absorption of the drug was confirmed by a rise in growth hormone levels but no change in the elevated serum gastrin levels were observed. Bromocriptine does not appear to affect gastrin hypersecretion in the way that it influences the hypersecretion of pituitary hormones.

Gastro--oesophageal reflux in late pregnancy.

Lower oesophageal sphincter pressure and fasting plasma gastrin and progesterone were measured in 31 women in the last trimester of pregnancy and in 10 healthy female control subjects. Eighteen of the pregnant women suffered from heartburn but 13 did not. All of the control subjects and 10 women from each of the two pregnant groups were tested for gastro--oesophageal reflux by direct measurement of intraluminal pH. The mean barrier pressure of the lower oesophageal sphincter was lower in both groups of pregnant women than in the controls (P less than 0-05) and the mean barrier pressure of the women with heartburn was lower than that of the pregnant women without heartburn, though this difference did not reach statistical significance. Eight of 10 of the pregnant women with heartburn had moderate or severe reflux, and3 of 10 of the pregnant women without heartburn also had moderate or severe reflux. Most women who reflux have heartburn, nevertheless, some asymptomatic women also reflux, and therefore all pregnant women must be considerered at risk from Mendelson's syndrome if subjected to a general anaesthetic for an emergency obstetric procedure.

Effects of oral calcium gluconate on gastric acid secretion and serum gastrin concentration in man.

A single oral dose of 4-46 mmol calcium gluconate at pH 5-6 was administered intragastrically to 15 male volunteers without gastrointestinal disease. There was a significant rise in acid output from 30-90 minutes after the calcium was given compared with the basal hourly collection. The serum gastrin level 30 minutes after calcium administration was significantly raised, but no correlation could be demonstrated between the acid and gastrin responses. Serum calcium levels were unchanged throughout. An equimolar dose of magnesium sulphate had no such effects. This study suggests that the intragastric administration of calcium results in independent release of gastric acid and gastrin from the gastric mucosa.

Experimental hypergastrinaemia in the dog.

In order to investigate chronic hypergastrinaemia in dogs, studies with various excluded antrum preparations were performed. Gastric secretion was collected from denervated fundic pouches and gastrin levels were measured pre- and postoperatively by radioimmunoassay. In some samples the gastrins were separated according to their molecular size. Distinct hypergastrinaemia and acid hypersecretion developed in dogs where the antrum was excluded by a mucosal septum. Gastrin levels rose to 349 +/- 64 pg/ml (normal 76 +/- 19 pg/ml). Analysis of the gastrin pattern showed a predominance of smaller gastrin components. Although there was marked hypersecretion in most of the dogs with hypergastrinaemia, no close correlation was evident between these parameters. Some of the dogs with hypergastrinaemia developed anastomotic ulcers.

Effect of urogastrone on gastric secretion and plasma gastrin levels in normal subjects.

Purified human urogastrone was given by intravenous infusion to 12 normal volunteer subjects and measurements made of gastric acid, pepsin and intrinsic factor secretion, and of plasma gastrin concentration. Clinical, haematological, and biochemical screening tests were made throughout the period of study. Urogastrone inhibited acid and intrinsic factor secretion whether stimulated by pentagastrin, histamine, or insulin, but had a much less marked effect on gastric pepsin output. Plasma gastrin levels did not alter significantly. Limited dose-response studies showed that 0-25 mug urogastrone kg--1 hr--1 resulted in inhibition of acid output of 80% and was not associated with clinical side-effects. No significant alteration in any of the haematological or biochemical measurements was observed in any of the subjects.

Effect of urogastrone in the Zollinger-Ellison syndrome.

The effects of human urogastrone (0-25 mug. per kg. per hour intravenously) in four male patients with proven Zollinger-Ellison syndrome (z.e.s.) and in four healthy control subjects have been studied. After urogastrone in z.e.s. patients gastric acid volume and concentration decreased and basal acid output was reduced by 50-82%; the concentrations of intrinsic factor and pepsin in gastric juice increased by 60-300%; and peak plasma-gastrin concentration increased by 127-164% of basal concentration. A significant negative correlation between increase in plasma-gastrin concentration and decrease in acid output was observed (r=-0-72, P less than 0-01). Ulcer pain was relieved 30-60 minutes after the beginning of urogastrone infusion. These results suggest that urogastrone can inhibit the endogenously stimulated acid hypersecretion in z.e.s.

Immunoradiometric assay for ferritin in human serum.

A sensitive, specific and precise immunoradiometric assay for ferritin has been developed. Ferritin was measured in the serum of 160 hospital controls, 101 females (118 +/- 9 mug/l) and 59 males (189 +/- 16 mug/l). This difference was statistically significant. In 28 patients with untreated iron deficiency anaemia, serum ferritin concentration (6.1 +/- 0.7 mug/l) was significantly lower than in the controls, but it was within the normal range in 14 cases of polycythaemia vera treated by repeated phlebotomy. In 4 patients with primary haemachromatosis (2884 +/- 56 mug/l), 25 with secondary iron overload states (5702 +/- 1235 mug/l) and 8 with haemolytic anaemia (1612 +/- 605 mug/l), serum ferritin levels were markedly elevated. In 14 cases of transfusional siderosis there was a highly significant correlation between serum ferritin concentration and units of blood transfused. A circadian rhythm in serum ferritin concentration was observed in 7 healthy subjects.