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See articles on pages 209 and 214 In 1637 Rene Descartes wrote “The soul by which I am, what I am, is entirely distinct from my body and even if the body were not, the soul would not cease to be what it is”.1 Descartes was thus reflecting on the longstanding conundrum of relationships between body and soul which have continued to this day and are equally mirrored in our views on diseases of the gastrointestinal tract. The fathers of gastroenterology clearly recognised the relationships between the brain and gut. In his classic studies of the control of gastric secretion conducted on his subject Tom with a permanent gastric fistula,2 Stuart Wolf found that emotional state affected secretion and that mucosal blood flow, measured by a simple thermistor, altered in parallel.3 Similar relationships between rectal mucosal blood flow and psychological state were also reported by Almy.4 In his now classic “hoax” experiment, he induced anxiety in a “volunteer” by pretending to identify an abnormality during sigmoidoscopy. This induced a marked change in colonic motor activity and a change in mucosal colour. In the last half century however the onset of an era of objectivity has influenced how we view gastrointestinal symptoms. Quite rightly …

Gastric secretion and fasting plasma gastrin levels were investigated in 26 patients with bilharzial hepatic fibrosis and 26 controls. The groups did not differ in their basal secretion. When stimulated by intravenous infusion of histamine the maximal acid output in patients with bilharzial hepatic fibrosis was significantly less than in the control group. This was unlikely to be a result of neutralisation by reflux of alkaline duodenal contents as the volumes of reflux were not different from control subjects, but was compatible with a true reduction in gastric secretion as assessed by two-component hypothesis. Neither the lowered gastric acidity nor the liver damage in patients with bilharzial hepatic fibrosis correlated with circulating gastrin. The fasting levels of plasma gastrin in these patients were not different from controls. As in other liver diseases the cause of diminished gastric secretion remains unclear.

Gastric secretory response to insulin-induced hypoglycaemia was stuided in 21 subjects following vagotomy and a drainage procedure for duodenal ulcer. Eighteen subjects had one early test, ie, within one month of operation, and at least one late test, ie, six months or more after operation. Seven subjects had at least two late tests. When the insulin test results were expressed in terms of their Hollander status,there was as much variability with time as expected from previous reports. However, when results were expressed in terms of new criteria, decribed in the previous paper, the insulin status of postvagotomy patients remained constant with time.

Revue de l'etat actuel des connaissances sur le role protecteur des secretions gastriques contre l'infection venant de l'ingestion de bacteries ou parasites. Consequences de l'hypochlorhydrie et de l'achlorhydrie

In 19 subjects (four controls, one gastric ulcer and 14 duodenal ulcer) maximal gastric secretion was evoked with histamine 0.13 mumol/kg/h (0.04 mg/kg/h) for two to two and a half hours. A slow intravenous bolus dose of 200 mg cimetidine was given at the beginning of the last hour. Gastric secretion was measured before and after cimetidine administration and expressed both as mean acid output (mmol H+/h) and 'pyloric loss and duodenogastric reflux corrected' volume (Vg, ml/h). Mean reduction by acid output was 86%; mean reduction by corrected volume (Vg) was only 64%. The discrepancy, which is significant (p less than 0.01), is caused by a marked increase in duodenogastric reflux after cimetidine.

Upper gastrointestinal function in response to a mixed nutrient meal was evaluated in hyperthyroid patients, both before and after therapy, and in healthy controls. Gastric secretion, gastric emptying, and pancreatic secretion were all normal and normally integrated postprandially in the hyperthyroid patients. Bile acid output was reduced (P less than 0.05) in this group of patients relative to healthy controls. Duodenal bile acid concentrations, however, were above the critical micellar concentration in most of the hyperthyroid patients, and the bile acid output and concentration remained unchanged in all patients three months after treatment. After radioactive iodine therapy, when gastrointestinal symptoms were returning toward normal, a small but statistically significant increase in gastric secretion was observed. However, gastric emptying and pancreatic secretion, like biliary secretion, remained unchanged. Abnormalities responsible for the diarrhoea and steatorrhoea in hyperthyroidism appear to reside primarily distal to the duodenum. However, reduced bile acid output may be a contributory factor in some patients.

We studied 29 patients who had gastric secretion tests after a vagotomy for duodenal ulcer. There were 14 patients who developed a recurrent duodenal ulcer during the follow-up period and 15 patients who remained free from recurrence. Insulin-stimulated gastric secretion increased with time in the recurrent ulcer group, but not in the group with a satisfactory outcome. On the basis of our results, post-vagotomy patients could be divided into three groups. The first group had a high secretion immediately after the operation and it remained high. The risk of recurrent ulcer in that group was about 50%. The second group had an initially low secretion which increased with time, and the risk of recurrent ulcer in that group was the same as for the first group. The third group had an early low secretion which did not increase with time and the risk of recurrence in this group was less than 5%.

The relationship of gastric secretion in response to a single injection of insulin and in response to a histamine infusion, in unoperated patients with duodenal ulcer was studied before and after vagotomy. The secretion in response to insulin was significantly less than that in response to histamine. The ratio was about 0.7 before vagotomy, and about 0.4 after vagotomy irrespective of the adequacy of vagotomy. Highly significant correlations were obtained between the responses to the two stimuli, both in the unoperated group and in the whole postoperative group as well as in the inadequate vagotomy group, but not in patients after adequate vagotomy. Thus, the proportional differences between individuals in response to insulin were substantially the same as the proportional differences in response to histamine. The algebraic excess of histamine- over insulin-stimulated secretion before vagotomy did not differ from the value after vagotomy. Histamine-stimulated secretion after adequate vagotomy approximated to, but after inadequate vagotomy was greater than the preoperative algebraic excess of histamine- over insulin-stimulated secretion. These results are consistent with a new model of acetylcholine/histamine-receptor relationships. A certain proportion of the parietal cells are insensitive to the vagus but sensitive to histamine; and those sensitive to the vagus are also sensitive to histamine, but only when their vagal innervation is intact.

Because of inherent and inseparable variables, studies of the effect of smoking on gastric secretion and motility have proved inconclusive. The only firm conclusions to be drawn from the work reviewed are that the prognosis of both gastric and duodenal ulcers is made worse by regular smoking and that the healing and response of gastric ulcers to medical treatment is impaired. The mechanisms through which these effects are produced are unknown. It is not even certain that nicotine is the chief noxious agent in tobacco. Careful statistical and epidemiological studies have yielded such facts as exist and this approach seems the most promising one for future studies.

No significant difference has been detected in the acid gastric secretion of cats obtained by vagal stimulation before and after pancreatectomy.

On the basis that the most repeatable measurement of acid output of the stomach is the peak half hour after an augmented dose of histamine, the author suggests a modification of the Kay test, including titration of the gastric juice to neutrality and measurement of the chloride concentration. The aspiration tube was sited fluoroscopically. It is suggested that the ;peak half hour' should be substituted for the period 15-45 minutes after administration of histamine. This modification is supported by the presented data. It should be noted, however, that the titration technique has also been modified. The ranges of basal and maximum gastric secretion (volume, acidity, acid output, parietal and non-parietal components) in 20 normal males and 20 normal females are presented and analysed for differences of age and sex. Both basal and maximum (histamine stimulated) gastric secretion declined with age, more so in women than in men. ;Maximum' gastric secretion was greater in men than in women, especially in older subjects.

lcirculation. Increased gastric production ofammonia incirrhosis didnotaffect acidoutputsignificantly, andthereduced responsetohistamine was not duetoincreased serum histaminase activity. Since a significant relationship was demonstrated between hypokalaemia andhyposecretion, andsince theoutputofgastric juice appeared more greatly reduced involumethanacidconcentrations, thepossibility ofarelationship between gastric hyposecretion anddisorders ofwaterandelectrolyte metabolism isconsidered. Fewclinical studies ofgastric secretory function in thepresence ofhepatic disease havebeenreported, andtheresults oftenappearinconsistent with experimental data. Inanimals, increased production ofacid results fromcholestasis (Silen, Skillman, Hein, andHarper, 1962), hepatocellular injury (Hein, Silen. Skillman, andHarper, 1963), orthecreation ofaportal-systemic collateral circulation (Gregory, 1958). Although these circumstances arepertinent, together orseparately, inhumanswithcirrhosis, qualitative (Wang,1936;Bockus, 1963)and quantitative studies (Ostrow, Timmerman, andGray, 1960) indicate adiminution ingastric secretion with this disease. Nevertheless, increased acid production might beanticipated ifthere isagreater incidence ofpeptic ulcer withcirrhosis (Swisher, Baker, and Bennett, 1955), especially after portacaval anastomosis (Bendett, Fritz, andDonaldson, 1963) andif haemorrhage fromoesophageal varices isattributable toacid-peptic reflux (Chiles, Baggenstoss, Butt, andOlsen, 1953; Liebowitz, 1961). Theprimary purpose ofthepresent investigation wastherefore acomparison ofgastric secretion in control individuals andinpatients withcirrhosis, bothunderbasalcircumstances andfollowing stimulation, thelatter byanaugmented doseof histamine orpeptone broth. Simultaneously, factors whichmightinfluence gastric secretion inthe 'This investigation wassupported inpartbyresearch grant AM-06908 fromtheNational Institutes ofHealth, Public HealthService. 2EliLilly travelling fellow. presence ofcirrhosis werestudied also, including hepatic function, thepresence ofaportal-systemic collateral circulation, thecontent ofelectrolytes and ammoniaingastric juice, thehistology ofthe stomach, andtherelationship ofsecretory responses after histamine injection toserumhistaminase activity. MATERIAL

Glucagon suppresses gastric acid secretion in normal subjects and in ulcer patients. It has no inhibitory effect while the stomach is under maximal histamine stimulation. The mechanism of action is discussed, and experiments are described which indicate that glucagon is unlikely to be of value in the treatment of peptic ulcer.

There is considerable evidence that the adrenocortical steroids potentiate both human and canine gastric secretion. In this study, the action of the adrenocortical inhibitor, SU 4885, has been observed in dogs having separated pouches of the stomach. No effect was noted on the secretory responses to meat, histamine, or mecothane when the drug was given by single intravenous injection. However, the 24-hour output of acid was inhibited when the drug was given orally for a period of 10 to 14 days. While this effect may be due to the ability of the drug to inhibit adrenocortical function, there is no positive supporting evidence.

This paper reports a follow-up of 91 healthy men who had a histamine gastric function test performed 28 years ago and relates the original gastric function test to the subsequent development of duodenal ulceration.

The spontaneous output of pepsin was not found to be significantly reduced in this study of patients who had had a vagotomy.

By a statistical study using the Kay augmented histamine test it has been shown that performing a gastrojejunostomy has no fundamental effect on gastric secretion and that the post-operative differences are due entirely to reflux and/or loss through the stoma.

In the study to be described confirmation of the findings of Giles, Clark, and Buchan (1968) that the presence of acid in the lower oesophagus may stimulate gastric secretion has been sought. Also the influence of hiatal repair on the response to acid has been examined. The presence of acid in the lower oesophagus stimulates gastric secretion in man. The response to acid perfusion is greater in symptomatic hiatus hernia patients than in controls. Basal and perfusion outputs are lower in hiatus hernia patients with oesophagitis than in those without inflammatory change. Hiatal repair diminishes the gastric response in both groups; this effect is particularly marked in patients with oesophagitis.

Increasing suppression of gastric secretion by anticholinergic drugs is accompanied by a rising mucus concentration; the actual output of mucus shows little change despite a marked reduction in the secretory volume. The problems involved in the estimation of mucus secretion and the importance of the above findings in relation to the therapeutic use of anticholinergic drugs in peptic ulceration are discussed.

The work of Glass has suggested that glandular mucoprotein and mucoproteose can be isolated by a fractional precipitation method from gastric secretion. These studies have failed to confirm this hypothesis and point out a fallacy of the original technique used.

The effect of intraduodenal acid on pentagastrin-stimulated gastric secretion has been investigated in 12 normal subjects and 23 patients with chronic duodenal ulceration. Plasma secretin levels were monitored during each test using a highly sensitive radioimmunoassay. Significant inhibition of gastric secretion occurred in the normal subjects and duodenal ulcer patients. A significant rise in plasma secretin was observed in both groups after intraduodenal acid though there was a complete lack of correlation between the magnitude of the secretin response and the degree of gastric inhibition. Ten subjects received intraduodenal acid and a subsequent intravenous infusion of exogenous secretin (0.125-0.25 units/kg over six minutes). Gastric inhibition occurred after the acid instillation but not after secretin infusion despite plasma secretin levels greatly in excess of those produced by intraduodenal acid. These results suggest that release of secretin by itself cannot explain the gastric inhibitory response to intraduodenal acid in man.

The inhibitory effect of ranitidine and cimetidine on pentagastrin stimulated volume, acid and pepsin secretion has been studied in eight healthy volunteers. Both compounds inhibit all measured components of gastric secretion in a dose dependent manner. On a molar basis ranitidine is on average 11.14 times for volume, 13.04 times for acid, and 9.74 times for pepsin secretion more potent than cimetidine as measured by the ID50-values.

The effect of sodium taurocholate instillation on the stimulated stomachs of patients with duodenal ulceration has been investigated. Instillation into the stomach of sodium taurocholate significantly reduced pentagastrin stimulated volume and outputs of both acid and sodium, with no change in the calculated volume of duodenogastric reflux. These observations are not consistent with the back-diffusion theory, but suggest direct parietal cell inhibition of gastric secretion by sodium taurocholate.

A second commercially prepared secretin has been found to inhibit the acid secreted by Heidenhain pouches in dogs in response to a meal but not to histamine. This inhibition is not affected by pancreatectomy.

The effects of metoclopramide on gastric emptying and gastric secretion have been assessed in man using the double sampling test meal. Metoclopramide increases the rate of emptying of the stomach. The magnitude of the effect is directly related to the initial emptying time. Metoclopramide has no effect on the acid response to a water test meal.

The gastric secretory response to insulin is mediated predominantly by the vagus. The associated hypoglycaemia stress response is mediated by the sympathetic nervous system. Inhibition of the sympathetic response by simultaneous alpha and beta receptor blockade was studied in five healthy young adults. No appreciable modification of gastric secretory output resulted.

The existence of more than one gastric pepsin has been reported by many authors. Herriott, Desreux, and Northrop (1940) separated two proteolytic fractions from human gastric juice by salt-fractionation methods, and similar results were described by Baker (1951) and Taylor (1959b). Using moving boundary electrophoresis, Kushner, Rapp, and Burtin (1964), Merten, Schramm, Grassmann, and Hannig (1952), and Taylor (1959a) have all identified two or more different proteolytic components in both swine and human gastric juice. Ryle and Porter (1959), Tang, Wolf, Caputto, and Trucco (1959) and Seijffers, Segal, and Miller (1963), using ion-exchange chromatography, have also isolated at least two different proteases in human gastric secretion. The two proteases most commonly isolated both digested proteins with two pH maxima, one near 2-0 the other around 3-5 (Taylor, 1959a). The third pepsin found by some authors was found by Tang and by Ryle to have a singlepH at 3.0. This, however, was only a minor component of gastric juice and was only occasionally found. There is good evidence therefore that two pepsins, and sometimes three, are present in human gastric juice. Furthermore, Taylor (1959b) has shown that these pepsins are obtainable from different parts of the stomach. Using material obtained at necropsy, he showed that one pepsin could be extracted from the fundic mucosa and the other from the pyloric mucosa. The fundic pepsin digested proteins with pH maxima at 2.2 and 3 5; the pyloric had more acidic peaks on thepH-activity curve at 1P7 and 3*1. Peptic activity/pH curves drawn in the present work have shown at some time or another five peaks of peptic activity below pH 4-5. However, three of these peaks occurred very rarely, and attention has been focused on the two peaks that were most frequently seen, namely, pH 1.8 and pH 2.2. This paper therefore first attempts to associate stimuli with the appearance of these peaks, and then to examine the occurrence of these pepsins in different conditions of the stomach in health and disease. METHOD

Marked decreases in 24-hour Heidenhain pouch secretion, lasting from nine to 18 days, were observed in five mongrel bitches during periods of naturally occurring oestrus. Neither oophorectomy nor control celiotomy caused significant change in Heidenhain pouch secretion in bitches who were not experiencing oestrus. The oral administration of diethyl stilboestrol, in doses ranging between 5 mg and 70 mg per day, had no clear-cut effect on Heidenhain pouch secretion.

In a woman with diarrhoea and the Zollinger-Ellison pattern of gastric secretion, the secretion of fluid and bicarbonate into the duodenum in response to secretin was found to be significantly greater than in controls. No pancreatic tumour was found at operation. The pancreas was, however, larger than normal. The patient did not show symptoms of peptic ulcer disease until vagotomy and pyloroplasty had been performed. A capacity to secrete large amounts of bicarbonate was believed to be the explanation of why she was able to tolerate great amounts of acid.