Twenty-Seventh Annual Meeting of the British Society of Gastroenterology

March 1967

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611

TWENTY -SEVENTH ANNUAL MEETING OF THE BRITISH SOCIETY OF GASTROENTEROLOGY The 27th Annual General Meeting of the British Society of Gastroenterology was held in London on November 3, 4, and 5, 1966, the president, Dr. F. Avery Jones (Central Middlesex, London) being in the chair. At the first session all papers dealt with various aspects of gastric function. Dr. B. 1. Hirschowitz (Birmingham, Alabama, U. S. A.) opened this section by discussing the effects of insulin on gastric secretion. He gave an introductory outline of the complex mechanisms which theoretically might be affected by the administration of insulin. Good evidence was presented that as far as the secretion of hydrochloric acid is concerned insulin exerts a dual effect: inhibition by the direct action of the insulin itself, and stimulation via the hypoglycemia induced by the insulin. The principal experimental findings in support of this hypothesis were, first, that increasing the dose of insulin by intravenous injection caused an increasingly exaggerated bimodal response, the stimulation of acid secretion being increasingly delayed, and second, that the injection of insulin could inhibit the acid response to the continuous intravenous infusion of histamine. A coincidental comment was that in the dog insulin appeared to cause a considerable degree of splenic contraction, believed to be a consequence of the direct effect of vagal stimulation on splenic capsule musculature. It was also noted that pepsin stimulation by hypoglycemia might continue during the period of acid inhibition. Dr. Hirschowitz then concentrated on the mechanism by which the insulin-induced inhibition of acid secretion might be mediated. He showed that a correction or prevention of altered blood sugar levels did not abolish the insulin inhibition. It could, on the other hand, be rapidly and completely reversed by the intravenous injection of potassium chloride or by rubidium, a biological substitute for potassium. The administration of other cations including sodium, calcium, or magnesium did

not in any way alter the inhibition. Likewise, glucose and glucagon were without effect. It would thus appear that the inhibitor effect of insulin on gastric acid secretion is the result of diversion of potassium ions from an intracellular mechanism in the parietal cell. A mathematical means of allowing for the inhibitor phase in the over-all response pattern to insulin was presented, and when suitable corrections were made in a senes of insulin dose-response curves it was found that the corrected values of acid output very closely paralleled the changes in blood sugar concentration. It was appropriate that there should follow an account of a clinical comparison between insulin and 2-deoxy-n-glucose (2DG) in the assessment of completeness of surgical vagotomy, since some of the pioneer work with 2DG had been done by Dr. B. 1. Hirschowitz. The comparison had been made by Mr. D. G. Thomas and Professor H. L. Duthie (Sheffield) in a series of 32 duodenal ulcer patients who underwent vagotomy with pyloroplasty. The insulin was given as a single intravenous injection, the dose being 20 units, and the 2DG was given as a lO-min infusion of a 25% solution, the total dose being 50 mg per kg. Eleven patients showed a totally negative response to both the insulin and the 2DG. Four patients classified as not responding to the insulin had a definite increase in acid concentration following the 2DG. Seventeen patients produced a positive insulin response, as judged by Hollander's criteria, at some time within the 2 hr following the insulin injection. However, the actual amount of the response and its time of onset varied substantially from patient to patient. In 5 patients the insulin response was positive within the 1st hr, but in 12 the positive response was not obtained until the 2nd hr following the insulin injection. In both subgroups the response to 2DG was greater in amount and almost invariably of earlier onset. In no instance was the 2DG

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response delayed until the 2nd hr following injection. There was thus evidence that the 2DG might more clearly discriminate between those with positive and negative responses. Of the patients tested, 90% displayed some sweating, hunger, and thirst, but the author's impression was that the severity of these symptoms was less than usually encountered after insulin. In 2 patients the symptoms were, however, severe enough to require treatment by the intravenous administration of 50% dextrose, which rapidly abolished them. In discussion of this paper it was generally agreed that the evidence was now good that 2DG acted by stimulating the vagi, although it was freely conceded that in view of its intracellular hypoglycemiclike action it was likely that it also might affect a variety of other cells in the central nervous and other systems. The occurrence of symptoms of mild hepatic damage was reported following the administration of 2DG to 2 patients. However, it was suggested that since general anesthesia followed within a few hours of these tests, one could not be certain that the signs of transient hepatic damage were of necessity related to the 2DG. It was generally felt that further careful assessment of the effects of 2DG was required before recommending its widespread use in the assessment of completeness of vagotomy. A study of plasma insulin levels in duodenal ulcer patients was presented by Drs. K. D. Buchanan, M. T. McKiddie, and W. G. Manderson (Glasgow). These authors examined the hypothesis that peptic ulcer patients might possess some abnormality of carbohydrate metabolism with a particular tendency toward hypoglycemia. They compared blood sugar concentration and plasma insulin levels concurrently following, on one occasion the oral administration of 50 g of glucose, and on a second occasion the intravenous infusion of 25 g of glucose. Fourteen patients with uncomplicated duodenal ulcer and 14 control subjects were studied. The duodenal ulcer patients showed more rapid increase in blood sugar and plasma insulin

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level following the oral glucose, but there was no significant difference in the pattern of either observation following the intravenous glucose. No significant correlation was found between the maximal acid responses and either the blood sugars or plasma insulin values. Two possible explanations for the apparent increase in rate of glucose absorption and increase in plasma insulin level following the oral glucose in the duodenal ulcer patients were (1) that the greater acid secretion in the ulcer patients might cause the liberation of increased amounts of secretin which in turn might affect insulin and perhaps even glucagon levels; or (2) that the changes simply reflected a faster gastric emptying rate in duodenal ulcer patients. In the discussion which followed, the second interpretation was favored. Drs. G. P. Crean, D. Hogg, and R. D. E. Rumsey (Edinburgh) presented the results of experiments in rats dealing with the question of whether duodenal obstruction might cause hyperplasia of the gastric mucosa. Different degrees of obstruction were produced by ligatures tied around the proximal duodenum, bougies being used to determine the final luminal cali~ ber. At intervals varying from 3 to 11 weeks the stomachs were removed, the amount of obstruction was reassessed, and measurements of gastric weight, mucosal volume, mucosal height, surface area, parietal cell population, and peptic cell population were made. Clear evidence of increases in all of these parameters apart from mucosal height was found in those with moderate outlet obstruction. Where no obstruction had been achieved no significant alteration in any of the parameters was found. Most of those animals in which excessive obstruction had been produced died of gastric perforation. Three that had survived this degree of obstruction were found to have very marked hyperplasia. Since there is a clearly defined border between the fundic gland area and pyloric antrum in the rat it was possible to make an accurate assessment of the antral-fundic ratio. This was found to be undisturbed by the hyperplasia even when this amounted

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to a 100 to 200% increase in gastric size. There was thus no evidence of a preferential increase in the antral mucosa in these obstruction experiments. The influence of sex hormones on gastric acid secretion had been investigated by Dr. J. H. Baron (Central Middlesex, London). It was first commented that human beings appeared to differ from experimental animals in that the male of the species produced on average 50% more gastric acid secretion than the female. In dogs there was no apparent sex difference in the gastric secretory responses. The gastric acid responses of male and female gray hounds with simple chronic gastric fistulas to intravenous infusion of histamine acid phosphate in doses ranging from 1 to 16 p..g per kg per min were compared. Once the initial secretory studies had been completed, orchidectomy or oophorectomy was performed and the dose-response curves were once more assessed. Following a further interval, stilbestrol, 1 to 2 mg per day, was administered orally to the males and testosterone propionate, 25 mg, was given intramuscularly twice a week to the females. The histamine responses were repeated once more. The only significant alteration in acid secretory response was found in the male dogs after 1 to 2 months of stilbestrol administration. However, on continuing the stilbestrol the secretory responses gradually returned to control values. Except for this finding there was no evidence that either castration or the chronic administration of the opposite sex hormone influenced secretory responses. There was likewise found to be no significant change in serum pepsinogen levels measured at intervals throughout these chronic experiments. The author extrapolated the findings to suggest that whatever the beneficial effect of stilbestrol in the treatment of male patients with chronic duodenal ulcer, it was not likely to be mediated via changes in gastric acid secretion. The following three papers were concerned with actions of the synthetic gastrin-like pentapeptide I.C.I. 50,123. Drs. A. M. Barrett and J. D. Fitzgerald (Phar-

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macology and Medical Departments, Imperial Chemical Industries, Limited) made some observations on the bioassay of stimulants of gastric secretion in the rat. The problems encountered in trying to develop a rapid, reproducible technique were discussed. Of particular importance was the anesthetic agent used, urethane appearing to interfere less with the responses than barbiturates or halothane. Marked differences in both the rate and size of response were found on giving the penta peptide and other stimulating fractions by intraperitoneal, subcutaneous, or intravenous routes. A Latin square technique had been found to be the most promising in the authors' hands. They had also developed a technique for simultaneously recording rectal motility at the time of measuring gastric responses in order to determine whether intestinal motility effects were apparent at doses which were likely to be physiological with regard to acid secretion. The study presented by Drs. J. J. Misiewicz, D. J. Holdstock, and Sheila L. Waller (Central Middlesex, London) also dealt with the gastrointestinal motility effects of the gastrin-like pentapeptide. Gastric motility was measured by open-ended tubes in the fundic area and the pyloric antrum. Sigmoid colon and rectal pressures were measured by air-filled balloons placed sigmoidoscopically at 20 and 10 cm from the anal margin. Radiotelemetering capsules were used to record ascending colon pressure changes. Radiological confirmation of all the recording devices was obtained at the beginning and end of each series of observations. The gastrin pentapeptide was given as a continuous, constant rate intravenous infusion, the doses varying from 0.01 to 0.1 p..g per kg per min. The gastric acid secretory responses to these doses were measured by aspiration on each occasion. The lower dose of pentapeptide resulted in near maximal secretory rates from the stomach, the increase to the larger dose resulting in only a small and sometimes insignificant further increase in output in the 17 patients studied. The only site at which definite evidence of increased motility was encountered was in the stom-

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ach, particularly in the pyloric antrum. Neither dose produced a significant alteration in the colonic or rectal motility patterns. The authors concluded that, at dose levels up to those required to produce virtually maximal acid response, the motor effects might well be limited to the stomach. Mr. 1. E. Gillespie and Mr. S. P. Master (Glasgow) presented experimental evidence from Heidenhain pouch dogs that large doses of gastrin pentapeptide, when given by rapid intravenous injection, could powerfully inhibit the pouch responses to the continuous intravenous infusion of histamine or to feeding. The pattern of inhibition was reproducible in degree and duration on repeating the single intravenous injections, with no evidence of "escape" from the inhibitor influence. It was possible to suppress completely the response to a meal by a series of timed single intravenous penta peptide injections. While the mechanism by which the inhibition was mediated is unknown, it appeared that it was not accompanied by measurable or observable side effects. The effect of histamine and gastrin II on intrinsic factor secretion in man had been studied by Drs. D. G. Weir, 1. J. Temperley, and D. Collery (Dublin). They had compared the acid and intrinsic factor outputs in the gastric juice in response to the continuous intravenous infusion of the two agents. Both produced a similar intrinsic factor secretion pattern, there being an initial peak followed by a lower steady state output. This was interpreted as showing an initial "wash out" phenomenon common to both stimuli. When the outputs during the 1st hr were compared with those of the 2nd hr a good correlation was found both for acid secretion and intrinsic factor production. Dose-response curves showed that maximal levels of both intrinsic factor and acid were obtained at 40 f1-g per kg per hr of histamine acid phosphate and 1 f1-g per kg per hr of gastrin II. Vagotomy with pyloroplasty in duodenal ulcer patients was found to reduce the intrinsic factor and acid responses to maximal stimulation by com-

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parable amounts, the effect on the maximal gastrin responses being less than that on the histamine responses. These various results all added strong support to the hypothesis that acid and intrinsic factor are produced by the same cell. In discussion it was suggested that in many respects the pattern of intrinsic factor outputs was similar to that of pepsinogen, and therefore that a protein-producing cell might be more likely to give rise to the intrinsic factor. However, it was also pointed out that there probably was a fairly constant relationship between pepsin-, mucus-, and acidsecreting cells within the stomach and that the hypothesis of a unicellular origin for hydrochloric acid and intrinsic factor still had very strong support. Mr. J. E. Black (Belfast) had sought to study possible physiological functions of the pyloric branch of the vagus nerve. This had clearly some relevance to the question of selective vagotomy in the surgical treatment of duodenal ulcer. Motility in the fundic gland area, the pyloric antrum, and the duodenum was monitored by miniature balloons introduced through gastric fistula cannulas in dogs. Insulin stimulation before and after various surgical pro~ cedures to preserve and then divide the pyloric nerve produced no evidence to suggest that this particular nerve had any influence on gastric or duodenal motility. Likewise there was no indication that the pyloric nerve influenced the response of a Heidenhain pouch to antral stimulation by a meal. Mr. J. Kilby (Bristol) had investigated the role of duodenal reflux in gastroduodenal disease. A fine tube with a weighted bag at the end of it was passed via the esophagus and stomach into the duodenum under radiological control. Suitably liquid barium was then injected by a hand syringe through the tube into the duodenal bulb. The authors found that in 20 normal subjects the pylorus was quite competent, there being no regurgitation of the radiopaque medium into the stomach. Thirtyfour duodenal ulcer patients were also studied, and in 14 of these the pyloric "sphincter" appeared competent. The re-

March 1967

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615

maining 20 patients demonstrated free re- derance of esophageal lesions. This was flux of the barium usually as a "squirt," particularly marked in males. The mean sometimes regurgitating as far proximally .duration of the celiac symptoms before the as the cardia. Those duodenal ulcer pa- diagnosis of gastrointestinal carcinoma was tients demonstrating incompetence at the almost 40 years, which once more made it gastroduodenal junction had on average a virtually certain that the malignant lelonger history of symptoms than those in sion was a result rather than a cause of whom this area was competent. The au- the celiac disorder. In no instance did mathors found free regurgitation almost in- lignant disease occur in the jejunum, at variably in all cases of benign gastric ulcer. which site the changes in the celiac synAlthough there was not a significant cor- drome are most pronounced. The increased relation, there was a general tendency for incidence of malignant disease, and espethe maximal acid responses to histamine cially esophageal carcinoma, was supported to be lower in those patients with free by evidence from other centers. regurgitation than in those with a comObservations on the digestion of protein petent "sphincter." It was hypothesized by human subjects were presented by Drs. that the reasons for the reduced acid se- M. Gay and C. W. Crane (Birmingham). cretion were (1) an alkalization of gastric In previous studies of protein absorption juice by the regurgitant alkaline liquid, the labeling of urinary ammonia and urea and (2) the accompanying damage to the and of peripheral venous blood urea was acid-secreting mucosa by the irritant duo- studied after the oral administration of denal juice. labeled yeast proteins. Absorption appeared On November 4, the first paper by Drs. to be rapid. However, the role of several O. D. Harris, W. T. Cooke, H. Thompson, factors such as (1) the rate of gastric and J. A. H. Waterhourse (Birmingham) emptying, (2) the rates of mixing of presented strong evidence that malignant labeled amino acids with urea in the body, disease, particularly lymphoma or gastro- (3) the rate of transfer of label to glutaintestinal carcinoma, was a significant mine, and (4) the rate of urinary excretion complication of adult celiac disease or idio- of ammonia and urea were not taken into pathic steatorrhea. A thorough review had account. In the experiments now reported been made of 202 patients in whom these problems had been overcome by (1) either .of the latter two diagnoses had injecting the labeled material directly into been confirmed. The mean duration of the small bowel by intubation, (2) cathesymptoms was 24.4 years and the mean terization of the hepatic veins (during period of follow-up after diagnosis was 8.2 cardiac catheterization), and (3) measuryears. Of the 77 patients in this series who ing the isotope content of both amino acids had died, full autopsy findings were avail- and urea concurrently in both hepatic able for 59. Fourteen had developed lym- venous and peripheral arterial or venous phomatous disease, 10 with the histologi- blood. Peak labeling of amino acids occal appearance of reticulum cell sarcoma curred within a few minutes and thereafter and 4 with typical Hodgkin's disease ap- there was a rapid decrease. Maximal labelpearances. The mean duration of the symp- ing of the urea occurred at about 5 min. toms before the diagnosis of lymphoma Maximal labeling of amino acids in hepatic was over 20 years. Since with treatment venous blood occurred much later, at 20 to the 5-year survival rate in reticulum cell 30 min, and, finally, maximal urea lasarcoma is approximately 20%, and in beling at 30 to 40 min. These findings sugHodgkin's disease approximately 35%, it gest that hydrolysis of the protein in the seemed only reasonable to conclude that small intestine is an important rate-dethe celiac symptoms had preceded the lym- termining factor in protein absorption and phoma rather than being a result of it. that split amino acids are immediately Thirteen patients in this series developed taken up in the portal blood. gastrointestinal carcinoma with a prep onThe value of measuring urinary indican

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excretion was discussed by Drs. G. Neale and S. Tabaqchali (Postgraduate Medical School, London). Since virtually all the indican excreted in the urine is derived from bacterial degradation, the quantitative estimate of urinary indican may be taken as an indirect assessment of the bacteriology of the intestinal tract. The authors measured the urinary indican excretion in 50 control subjects and in 172 patients with a variety of gastrointestinal disorders. A high degree of reproducibility was obtained in the controls. The highest values of urinary indican excretion were found in patients with the blind loop syndrome, and these levels were very similar to those in experimentally induced blind loops in rats. In a group of patients with malabsorption either from idiopathic steatorrhea or following small bowel resection, approximately 50% had elevated urinary indican levels. Low values were usually encountered in malabsorption from disaccharidase abnormality and in chronic pancreatitis. Apart from these diseases a good correlation was found between urinary indican excretion and fecal fat excretion. Antibiotic treatment in patients with the blind loop syndrome or with jejunal diverticulosis reduced the urinary indican loss in parallel with the fecal fat excretion and vitamin B12 malabsorption. All three findings were reversed on stopping the antibiotic treatment. In the discussion which followed, the suggestion was made that the urinary indican excretion was not elevated in pancreatic disease because of the deficiency of proteolytic enzymes and the consequent impaired ability to digest the bacteria. This was supported by some increase in urinary indican loss on giving pancreatic enzymes. Deficiency of y-macroglobulin was encountered in some patients with celiac disease by Drs. J. R. Hobbs and G. W. Hepner (The Royal Free Hospital, London). The most significant findings were with respect to the largest fraction-the yM-globulin. Fourteen of 52 patients with celiac disease studied showed lower than normal serum levels of this yM-globulin. Deficiencies of yA and yG were not so frequently en-

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countered. Treatment with a gluten-free diet in 8 patients restored the low yM levels to normal in 5. Those celiac patients with yM deficiencies did not show any clinical, biochemical, hematological, or histological features differing in any way from those patients with the disease but with normal yM levels. This would suggest that there is no very strong etiological relationship between the two findings, but raises the possibility that there may be some degree of lymphoreticular dysfunction in some patients with celiac disease. Dr. S. Tabaqchali and Professor C. C. Booth (Postgraduate Medical School, London) investigated the possible role of altered bile salt metabolism in the etiology of steatorrhea in the stagnant loop syndrome. Two possibilities were investigated: (1) that deconjugated bile salts might be directly toxic to the intestinal mucosa, and (2) that the unconjugated bile salts might be ineffective in aiding fat absorption. Analysis of juice removed from stagnant loops in patients had shown high levels of free bile acids, deoxycholic acid, and chenodeoxycholic acid. Different concentrations of these bile acids were tested for their ability to interfere with function in everted sacs of rat intestine. In the case of deoxycholic acid in a concentration equivalent to that encountered in the stagnant loop fluid, some diminution in glucose transport was encountered. However, feeding this bile acid to animals in the appropriate concentration did not cause steatorrhea. On comparison of the relative amounts of conjugated and unconjugated bile acids in the stagnant loop fluid it was observed that the proportion of conjugated acids was less than in controls and it was suggested that the conjugated bile acids might fall to levels below the critical micellar concentration, thus accounting for the impaired fat absorption. A detailed and comprehensive study of protein metabolism in a single patient with a long-standing intestinal blind loop syndrome was presented by Drs. E. A. Jones, A. Craigie, A. A. Tavill, G. Franglen, and V. M. Rosenoer (The Royal Free Hospital, London). The patient had 10 years pre-

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viously had an enteroenteric anastomosis performed for intestinal obstruction. He presented with gross malnutrition and, most significant among the biochemical abnormalities, a plasma albumin concentration of only 1.5 g per 100 ml. He had a high urinary indican excretion rate, and culture of the fluid from his loop grew a variety of enterobacteria, enterococci, lactobacilli, and bacteroides. Fecal nitrogen and fat excretion were also greater than normal. The rate of synthesis of various proteins was followed by the intravenous administration of HC-Iabeled sodium carbonate, a technique which introduces the label to the hepatic arginine pool and thus enables the tracing of the various newly formed plasma proteins. With this technique it was found that the synthesis rates both for albumin and fibrinogen were lower than normal. Antibiotic treatment, in the first instance with tetracycline and then with neomycin, in view of the persistence of tetracycline-resistant Escherichia coli, brought about a marked improvement in his clinical condition. The synthesis rates for both albumin and fibrinogen were increased, the fecal nitrogen and fat losses decreased, and the urinary indican excretion likewise was diminished. His serum albumin rose to 3.3 g per 100 ml. Oetailed analysis of the various plasma amino acids before and after antibiotic treatment showed that many of the essential amino acids which had been in lower than normal concentration were subsequently elevated to normal levels. The labeled urea clearance was more rapid before treatment than after treatment. It was postulated that the bacteria caused an excess deamination of the proteins, thereby releasing large quantities of ammonia which when absorbed were converted by the liver to urea. As a secondary consequence there were fewer protein amino acids available for small intestinal absorption. The possibility that bacterial toxins might also have interfered with the absorption mechanisms was thought unlikely, but could not be excluded. Drs. P. Smith, J. E. Middleton, T. Freeman, and R. Williams (Southampton

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and London) discussed the usefulness of the differential desferrioxamine test in the differential diagnosis of hemachromatosis from other disorders such as hemolytic states, infective hepatitis, and hepatic cirrhosis. A marker dose of 59Fe-ferrioxamine was given along with the desferrioxamine. High rates of elimination of the labeled iron were uniformly found in patients with hemachromatosis. Two of 5 patients with infective hepatitis showed high values, but these were less frequently encountered in chronic cirrhosis and in hemolytic disorders. There was a good correlation between the index of labeled iron elimination and the amount of iron in the liver biopsies in patients with hemachromatosis. In relatives of hemachromatosis patients known to have increased iron-binding capacity the results of the test were, however, normal and it seemed of limited usefulness in detecting those mildly affected by the disorder. The results of 253 ultrasonic scans of the liver were presented by Drs. C. F. McCarthy, P. Wells, F. Ross, K. T. Evans, and A. E. Read (Bristol). These workers used a simple technique of two-dimensional scanning, the probe being moved along either an intercostal or subcostal route, the latter showing some slight advantages over the former. The various problems in calibrating the machine and in excluding artifacts were discussed. It was apparent that minor technical abnormalities might result in highly abnormal patterns in the absence of disease. Cysts of the liver, as in polycystic disease, presented perhaps the easiest diagnostic challenge, all 7 of these patients being confidently diagnosed. With increasing experience the authors were able to distinguish metastatic deposits in the liver from a cirrhotic pattern with greater accuracy. In 35 of 41 cirrhotics examined, and 15 of 16 patients with metastatic disease in the liver, a correct diagnosis was reached by the ultrasonic scan, the diagnosis being subsequently checked by operation, or biopsy, or autopsy. It was claimed that metastases as small as 1 to 2 cm could be identified on a satisfactory scan. The main

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advantages of the procedure were that no injections or radioactive materials were required and that it caused no discomfort to the patient. The main disadvantage was that repeated calibrations were required for each examination. Drs. W. D. Stone, M. Gay, and C. W. Crane (Birmingham) produced evidence that patients with liver disease failed to detoxicate administered ammonia, primarily because of the impaired liver function rather than because of substantial shunting of the ammonia past the liver. 15N-labeled ammonium lactate was given to 4 patients with liver disease and to 2 normal subjects. The urinary excretion of labeled ammonia and urea was followed, a water diuresis having been induced. All the liver disease patients who were demonstrated to have portasystemic shunts excreated a proportion of the 15N-labeled ammonia in the 1st hr. The labeled urea excretion was greatest in those patients with the most marked biochemical indices of liver malfunction. There was also some correlation between these indices of hepatic damage and the amount of urinary ammonia loss. It was concluded that although both factors seemed to operate, the more important was probably the degree of liver disease. Dr. O. W. Hill (Central Middlesex, London) gave an account of the psychological assessment of a group of 13 patients with recurrent vomiting for which no organic cause could be demonstrated. From his detailed and careful study of these patients several recurring features clearly emerged. The first was the high incidence of conflict between the patient and the person or persons with whom he or she was living. In most of these cases, in spite of obvious open antagonism, the patient was unwilling to leave the situation because of a sense of adherence to duty. The early loss of a parent or another close relative was a frequent feature in those in whom vomiting had occurred in childhood. These factors were more frequently encountered in patients with psychogenic vomiting than in those with psychogenic abdominal pain. Dr. Hill felt that these patients often bene-

Vol. 52, No.3

fited from discussing the emotional problem openly with the psychiatrist and developing a somewhat dependent relationship with him. An occasional and useful temporary measure was chlorpromazine treatment. The effect on gastric acid secretion of perfusing the esophagus with acid solution was studied by Mr. G. R. Giles and Mr. C. G. Clark (Leeds). The experiments were prompted by the observation that while peptic ulcer could occur in the esophagus and in the duodenum, the effects of acid instillation in the latter were well known, whereas the effects of acidification of the lower end of the esophagus were unexplored. The esophagogastric junction was first defined by simple manometric methods, and the esophagus was perfused from a point 10 cm proximal to this junction. HCI, 0.1 Nand 0.01 N, was perfused in 12 normal subjects, 8 patients with duodenal ulcer, and 15 patients with hiatal hernia. Phenol red, 15%, was added to the perfusing solution as a marker. Gastric secretion was measured continuously both under basal conditions and while the patient was under the effect of the esophageal perfusions. Acid measurements were corrected for contamination by the perfusing solution when this occurred. In addition, in each case the maximal acid response was measured to the continuous intravenous infusion of histamine acid phosphate (0.04 mg per kg. per hr). In the normal subjects the perfusion of 0.1 N HCI slightly increased the volume of gastric secretion but had no effect on the acid output. Following the 0.01 N acid perfusion there was a slight increase in both volume and acid output. The 8 duodenal ulcer patients regularly showed increases in both volume and acid output, and 5 experienced heartburn during the test. The hiatal hernia patients were divided into those with heartburn, in whom both volume and acid were increased, and those without heartburn, in whom only the volume showed an increase. The hiatal hernia patients who did have heartburn gave acid responses to the esophageal perfusion which were proportionately nearer to maximal histamine

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619

responses than either the asymptomatic pressure. Following operation the pressure hiatal hernia or the duodenal ulcer pa- at the sphincter area was unchanged in 2 tients. The mechanism by which the gas- patients. In 8 there was a marked reductric acid response was stimulated on per- tion in pressure and in 1 no pressure change could be recorded at the gastroesophageal fusing the esophagus was unknown. Dr. D. A. W. Edwards (University Col- junction. Radiopaque clips were placed at lege Hospital, London) used a simple operation precisely at the diaphragmatic measurement of drinking time to assess hiatus and at the cardioesophageal juncvarious esophageal lesions. He measured tion. Postoperative X-rays showed that the the time taken for the subject to drink latter remained in a clearly subdiaphrag400 ml of water as quickly as possible in matic position in all but 1 of the pathe standing position. The time taken was tients. Of 9 showing no preoperative reflux generally faster for men than for women. on contrast radiography, 6 showed some Slow drinking times were generally en- reflux after operation. It was concluded, countered in achalasia of the cardia; dila- therefore, that the principal cause of tion only slightly improved the rate but esophageal reflux following vagotomy with cardiomyotomy almost invariably pro- pyloroplasty was impaired lower esophaduced a spectacular decrease in the drink- geal sphincter function consequent on the ing time. The measurement was usually vagal denervation. However, more pronormal in systemic sclerosis and peptic longed follow-up would be advisable to stricture of the esophagus. In carcinoma determine whether these changes persist of the middle and lower ends of the or are transient. esophagus, which had not yet obliterated Drs. C. W. O. Windsor and J. L. Collis the lumen, the drinking time was likewise (Birmingham) sought further information normal. It was underlined that this test in on the causes of anemia in hiatal hernia. no way assesses the ability of the esopha- Evidence of gastrointestinal blood loss gus to allow the passage of solid food. In was found in 59 of 400 consecutive paview of the considerable delay in the time tients undergoing operation for this contaken for untreated achalasics to swallow dition. In the paraesophageal type of lethe water it was suggested that in this dis- sion the incidence of anemia was 30%, ease the primary defect was not so much a whereas in the more common sliding type disor4er of peristalsis but rather an elastic of hernia the incidence was 11%. It was stricture which required a critical opening argued therefrom that reflux esophagitis pressure to allow the passage of intra- was not the sole cause of the bleeding. Peptic ulceration. and other possible luminal substances. The effect of subdiaphragmatic vagot- sources of blood loss, such as hemorrhoids omy on the function of the gastroesopha- and menorrhagia, were excluded by the geal sphincter was explored by Dr. D. A. appropriate examinations. The lack of corK. Woodward, Mr. J. A. Williams, and Dr. relation between the degree of anemia and M. Atkinson (Birmingham and Worces- the incidence of dysphagia was taken to inter). This study had been prompted by re- dicate that severe dietary lack was likeports of a high incidence of gastroesoph- wise not likely to be a contributing facageal reflux following vagotomy with tor. At operation particular attention was drainage procedure for chronic duodenal focused on the point where the stomach ulcer. A manometric and radiological crosses the edge of the right crus of the study had been made of the lower end diaphragm; 5 patients were found to have of the esophagus in 18 patients undergoing small gastric ulcers at this site. In another vagotomy with pyloroplasty. Before opera- group of 6 anemic patients 5 were found to tion it had been found that the intrave- have subserosal hemorrhages within the nous administration of 50 mg of Banthine same area. All those with anemia were reduced the pressure in the lower esopha- claimed to have been cured by the operageal region, and Mecholyl increased the tion to repair the hernial defect. It was

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therefore hypothesized that blood could be lost from gastric mucosa being abraded over this margin by respiratory and other movements. The susceptibility of gastric mucosa to aspirin-induced bleeding was investigated by Drs. D. N. Croft and P. H. N. Wood (West Middlesex, London). Evidence of bleeding amounting to more than 2 ml per day from the upper alimentary tract was encountered in 78% of 226 subjects following the repeated ingestion of aspirin. The stomachs of patients given repeated oral doses of soluble aspirin over 2 to 4 days prior to gastrectomy were found to contain numerous petechial hemorrhages and evidence of exfoliation of gastric cells. A group of 8 subjects who were known to lose less than 2 ml per day of upper gastrointestinal blood were further investigated. It was found that the rate of turnover of their gastric mucosal cells as measured indirectly by the output of deoxyribonucleic acid (DNA) in the gastric juice was significantly greater than a comparable group of patients in whom blood loss following aspirin ingestion was greater than 2 ml per day. Furthermore, the increase in DNA content of the gastric juice following aspirin ingestion was greater in those with the higher daily blood loss than in those with the relative resistance to bleeding. The authors interpreted their findings as suggesting that the more atrophic mucosa with a greater turnover rate of gastric cells was better able to resist the damaging effect of the aspirin than the relatively more slowly regenerating normal mucosa. The results of a 2-year trial of gastric cooling in the management of hematemesis were presented by Mr. J. B. McFarland and Mr. J. G. Gow (Liverpool). A simple apparatus circulating cooled water through a gastric-shaped balloon was employed. Patients admitted to both medical and surgical units of a large general hospital were randomly allocated to treatment with or without initial gastric cooling. In addition to this series, patients with severe complications rendering surgical treatment hazardous were accepted

Vol. 52, No.3

for elective treatment by gastric cooling. In the randomly allocated trial there was no difference in morbidity or mortality between the cooled series and the controls. The same amount of blood transfusion was required in each of the two groups. Analysis of a number of other clinical and hematological measurements showed that initial gastric cooling offered no advantage over conventional methods. Some support was given to the use of this method where serious complications might militate against operation. Mr. N. C. Tanner (Charing Cross Hospital, London) outlined his personal experience of 21 cases of organoaxial volvulus of the stomach encountered over the last 18 years. These patients required operation for relief of abdominal discomfort, excess belching, chest discomfort, and breathlessness. A technique was developed to allow the space previously occupied by the rotated stomach to be filled by the splenic and transverse colon. The gastrocolic omentum was first of all widely freed, the transverse colon being thereby mobilized so that it could be readily displaced into the subphrenic space. Thereafter a simple gastropexy fixing the lesser curvature to the ligamentum teres completed the operation. Clinical and radiological evidence of substantial relief in the majority of these patients was presented. A strong case for early surgery in the management of severe ulcerative colitis was made by Professor J. C. Goligher, Dr. F. T. De Dombal, Mr. N. G. Graham, and Dr. G. Watkinson (Leeds). The authors concentrated solely on the outcome of severe attacks of the disease. They first recorded their experience during the period 1952 to 1963, when total colectomy was undertaken only after fairly prolonged conservative management had failed to bring about some improvement. The overall mortality during this stage was 11.3% (4.8% in those medically treated and 20.0% in those undergoing operation). During the more recent 3-year period from 1964 to 1966 a comparable group of 81 patients in severe attacks was available for comparison. During this time total

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colectomy was undertaken in those over 60 years old within 3 to 4 days and in those under 60 years old within 5 to 6 days if there was obvious failure to respond to intensive medical measures. The mortality rate during this time fell to 1.3% (in those medically treated, no deaths; in those treated by surgery, 2.2%). In the first 10-year period the mortality rate in those over 60 years of age was approximately 50%, whereas in the more recent 3-year period no patient over this age died of a severe attack. These findings strongly suggest that early radical surgical treatment might have considerable advantages for patients with severe attacks of colitis which fail to respond rapidly to intensive conservative measures. The change in mortality was unlikely to be due to any change in surgical treatment or in the composition of the series with regard to age and other factors. The use of adrenocorticosteroid hormones was, again, unlikely to be an important factor, since the analysis showed that in the earlier series the mortality rate in those without steroids was 12.5% and those with steroids 11.9%, an insignificant difference. A review of eosinophilic granuloma of the gastrointestinal tract was given by Drs. P. R. Salmon and J. W. Paulley (Ipsw~ch). The pyloric antrum of the stomach and the ileum were the commonest sites and clinical presentation was usually as pyloric stenosis, intussusception, or with symptoms and signs suggestive of appendicitis. The detailed history and clinical findings in 3 patients were presented. In 1 there was a very strong family history of other allergic phenomena. The usual dramatic improvement on starting adrenocorticosteroid therapy in patients not subjected to operation was noted. The authors favored the hypothesis that the disorder was a manifestation of a systemic allergy rather than the other proposed explanations such as foreign body reaction, parasitic infection, or disturbance of estrogen-progesterone metabolism. An analysis of those patients with the celiac syndrome who failed to respond to

621

a gluten-free diet was presented by Drs. 1. J. Pink and B. Creamer (St. Thomas's Hospital, London). Fifty-four patients proved by jejunal biopsy to have the celiac syndrome were treated by gluten withdrawal. Of these, 17 showed poor or no response. Three different patterns of failure were observed. In the first there was histological evidence of very extensive disease which was probably irreversible; in these patients there was a rapid deterioration and fatal outcome. In the second group ill health persisted for protracted periods of time without any marked or early deterioration; evidence of pancreatic insufficiency was obtained in these patients. A third group showed an initial partial response but they failed to maintain good health; in some obvious dietary indiscretion would explain the course of events, but in 4 the reason for this pattern was unexplained. One patient unfortunately developed a lymphoma. The mortality rates in these three groups were 40, 66, and 20%, respectively, at 5 years. This compares unfavorably with a 2% 5-year mortality rate in those who do respond to the gluten-free diet. At the third session on November 5 the opening paper by Mr. A. G. Cox (Postgraduate Medical School, London) dealt with some of the effects of gastric surgery on nutrition. This study had been made at a peptic ulcer clinic in Glasgow, the information being obtained from a group of patients followed for not less than 8 years after a random allocation to either P6lya partial gastrectomy or vagotomy with gastrojejunostomy for chronic duodenal ulcer. It was first shown that the composition of the two operative groups with regard to height, operative weight, and age was comparable. Most of the observations showed very little difference between the two operative procedures. The mean weight gain in the vagotomy series had been 1.2 kg and there had been a mean weight loss in the P6lya gastrectomy series of 1.8 kg. This difference was not significant. The hemoglobin changes were very slightly and significantly different in favor of vagotomy. The serum iron and per-

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centage iron saturation were both marginally higher following vagotomy, and there would thus seem an indication that the P6lya partial gastrectomy patient would be more likely to develop an iron deficiency anemia. Serum vitamin B12 and serum folate levels were slightly higher in the vagotomy series but only in th(! case of the vitamin B12 was this a signifi·· cant difference. Serum alkaline phosphatase, plasma calcium, plasma phosphorus and metacarpal bone density measurements showed no difference between the two series. Analysis of the diets taken by the patients in the two groups by a dietitian showed no significant differences. In summary, there was little indication on nutritional or hematological grounds favoring one surgical procedure as opposed to the other. The question of vitamin E deficiency after gastric surgery was explored by Drs. M. S. Losowsky, P. J. Leonard, J. Kelleher (Leeds), and C. N. Pulvertaft (York). These workers argued that since there was good evidence of malabsorption of the other fat-soluble vitamins it might be possible that a deficiency of vitamin E would likewise arise after gastric surgery. Two measurements were made: the first, the direct plasma estimation of vitamin E concentration; and the second, an indirect measurement of vitamin E levels, namely, the ease of inducing hemolysis of red blood corpuscles on exposing them to hydrogen peroxide. Both measurements were made in 500 consecutive patients attending a gastric surgery follow-up clinic. Those undergoing the longest follow-up mainly comprised P6lya partial gastrectomies; those with the shortest follow-ups were usually vagotomy with drainage procedure. In the P6lya gastrectomy group there were 37% of patients with a low plasma vitamin E level, and in the vagotomy with drainage group the incidence was 31%. Eleven of these patients with evidence of vitamin E deficiency were studied in more detail. In 10 creatinuria was also present. All responded to treatment by pure a-tocopherol. No attempt has yet been made to correlate the symptoms or signs with the bio-

Vol. 52, No.3

chemical findings, but it was suggested that protracted vitamin E deficiency might be a factor in the muscle wasting which occasionally follows partial gastrectomy. This point, however, would require further specific investigation. Dr. D. M. Goldberg and Mr. A. D. Roy (Glasgow) recorded experiments dealing with the fate of pancreatic proteolytic enzymes in the human small intestine. Most of the observations had been made on patients with a total colectomy and ileostomy. On comparing ileostomy fluid with pancreatic juice it was clear that the trypsin was of identical nature in both juices. There was an indication, however, that chymotrypsin might exist in two separate forms. Incubation of the proteolytic enzymes with gastric juice maintained at a pH of not more than 3.0 for 2 hr brought about more than 90% inactivation of both enzymes. The trypsin was unaffected by acid alone at this pH, although approximately 30% inactivation of chymotrypsin was noted. Bile was without effect on either enzyme. When pure enzyme preparations were incubated with ileal contents there was found to be clear evidence of some binding of both enzymes by the solid portion of the ileal content. This was almost certainly protein binding. The feeding of enteric-coated capsules of the enzymes gave no evidence for any absorption of these substances from the small intestine. Preparation of mucosal cells from different segments of the alimentary tract showed some evidence of cellular absorption of both trypsin and chymotrypsin. Neomycin treatment did not appear to affect the recovery of either enzyme. The detailed histories of two families with a particularly high incidence of pancreatitis were presented by Dr. M. Carey and Professor O. Fitzgerald (Dublin). In one member of the first family there was also biochemical evidence of hyperparathyroidism. It is believed that this association had previously been reported on only one occasion. In the second family a strong association between pancreatitis, peptic ulcer, and diabetes mellitus was also noted.

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623

Drs. J. W. Freston, 1. A. D. Bouchier, assessed by the dietitian at frequent inand M. O'Grady (The Royal Free Hos- tervals throughout the period under obpital, London) presented studies on ex- servation. The high protein diet contained perimental cholelithiasis in rabbits. This on average 110 g of protein and 222 g of condition was induced by feeding the ani- carbohydrate. The high carbohydrate diet mals a 0.75% ,B-cholestanol diet. Control contained 67 g of protein and 350 g of animals, vagotomized, and sham-operated carbohydrate. Barium meal assessment of animals were fed comparable diets. In all ulcer healing was made at the end of the animals fed the diet for more than 2 6-month period on treatment. Two paweeks gallstones were found within the tients' ulcers perforated during the period gall bladder. Less than 5%, however, under observation; both were on treatment showed any histological evidence of an with estriol. At the conclusion of the trial inflammatory response. Periodic acid- it was found that those treated with either Schiff (PAS) -mucicarmine preparations estriol or with a high protein diet had on were made to identify mucus, and there average slightly fewer days of pain during was found to be an increase in mucus and treatment than those on either the dummy in goblet cells in the stone-containing tablets or on the high carbohydrate diet. gall bladders. The stones themselves were The differences, however, were not statisfound to contain appreciable quantities of tically significant. Radiological evidence of hexosamines. In the vagotomized rabbits healing was rarely obtained, only one ulthe size of the gall bladder was found to cer in the entire group being found to disbe larger than in those having a sham appear. It was admitted that these patients operation or in the controls. Stones were were all from a hospital referral series and encountered in the cystic duct more often, that those with lesser degrees of dyspepsia however, in the sham group than in the might have shown more evidence of revagotomized. The authors concluded that sponse to the various treatments. There the effects of vagotomy on the rabbit gall may not have been sufficiently marked difbladder under these experimental condi- ference in the constitution of the different tions were the enlargement of the gall blad- diets to make a significant difference in the der, the development of fewer stones, the rates of healing. Finally, it was observed less frequent occurrence of stones in the that the estrogenic potency of the prepaduct ~nd, in addition, less concentration of ration used in this trial differed from that bile. used in previous studies showing a more The results of a trial of estrogens and favorable response to this form of therapy. high protein and high carbohydrate diets A study of potassium secretion by the in the treatment of duodenal ulcer were rat colon was presented by Dr. C. J. Edpresented by Drs. A. M. Connell, J. monds (University College Hospital, LonFletcher, J. Howel Jones, M. J. S. Lang- don), starting with the observation that man, J. E. Lennard Jones, and F. Pygott the potassium content of colonic luminal (Central Middlesex Hospital, London). fluid is greater than that of the blood. The trial was designed to allow the si- Various mechanisms by which this increase multaneous comparison of both estrogen in intraluminal concentration might be obtreatment and the two diets. With respect tained were investigated. In the first into the estrogen treatment, patients were stance a study was made of the electrical randomly allocated in double blind fashion potential difference across the wall of the to treatment with estriol, 1 mg per day for colon. It was clearly demonstrated that 6 months, or a dummy treatment for the this potential difference was insufficient to same period of time. Of the 42 uncompli- account for the increase in fecal concencated duodenal ulcer patients in the trial 3 tration of potassium. A second possibility failed to complete the course. The various entertained was that increasing water absubgroups were comparable for age, length sorption from the colon might concenof history, and other features. Diets were trate the potassium within the lumen if the

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Vol. 52, No.8

colonic epithelium were relatively im- were mixed with a normal breakfast of permeable to potassium ions. This was in- eggs and porridge. The radioactivity in vestigated by perfusing isolated segments the stomach was then measured by scanof rat colon with isotonic solutions of dif- ning the upper abdomen at intervals. fering potassium concentration. It was From the first scan an outline contour found that greater potassium fluxes and map of the stomach was derived. The deincreasing intraluminal concentration of cay of radioactivity within this area was potassium occurred in the descending colon then followed. Two means of expressing than in the ascending segment. When the the emptying rate were used, the first being results of this study were compared with the radioactive half-life in the stomach observations of the electrical potential dif- area, the second being the square root of ference, there was a clear indication that the total emptying time. Results obtained the colonic mucosa actively secretes the with both methods were comparable, and the half-life was generally used. In 16 norpotassium ions into the lumen. Mr. D. M. Millar and Professor B. N. mal subjects the mean half-life was 68 Brooke (St. George's, London) described a min, in 25 patients with benign gastric ulmethod of serial portal venous sampling cer the mean was 69 min, in 27 patients in man and illustrated its use in the dem- with duodenal ulcer a more rapid mean onstration of macromolecular absorption figure of 56 min was obtained, while in 6 from the human colon. At operation an patients with pyloric stenosis from duointravenous cannula was introduced into denal ulcer the mean half-life was 82 the middle colic vein and passed so that min. The gastric emptying time as measthe tip lay at the junction with the portal ured by this technique was significantly vein. A good flow of portal venous blood more rapid in those with duodenal ulcer could thereby be obtained without collapse than in the normal subjects. Patients with of the vessel wall. By means of this tech- prepyloric ulcers did not show any differnique the absorption of large molecules ence in the rate of emptying from other from the colon at colectomy for ulcerative benign gastric ulcers, and 7 patients with colitis was measured. Solutions of poly- combined duodenal and gastric ulcers vinylpyrrolidone containing more than showed no evidence of delay in emptying. 90% of molecules having a molecular There was no correlation between the weight of more than 12,000 were intro- rate of emptying and the maximal acid reduced into the colon, and repeated sam- sponse of the various groups to the continplings of portal venous blood were ob- uous intravenous infusion of histamine. tained at short intervals thereafter. In Fourteen patients were also studied folthose patients operated upon for the lowing vagotomy with pyloroplasty (9 chronic form of ulcerative colitis both Finney and 5 Heineke-Mikulicz). The gassmall and large molecules were found to tric emptying times in both groups were pass from lumen into the portal blood, found to be virtually unchanged by the whereas in those patients with the acute operative procedure, those with a slow rate form of ulcerative colitis predominantly before operation continuing to have this large molecules were found to be ab- sort of pattern after operation. sorbed. Mr. R. P. Rosswick, Mr. R. D. StedeA standard meal labeled with radioac- ford, and Professor B. N. Brooke (St. tive chromium was used to assess the rate George's, London) employed a novel of gastric emptying in several groups of method for estimating gastric, small inpatients by Mr. G. H. Griffith, Mr. G. M. testinal, and total intestinal transit times. Owen, and Mr. R. Shields (Cardiff). These A small quantity of 1S11 was incorporated authors pointed out the difficulties of em- in an Araldite capsule which also contained ploying serial test meals, and meals con- two small lead pellets to make it radiotaining radiopaque substances. In the test paque. The amount of radiation emitted which they described 200 mc of chromium from this small capsule would have been

March 1967

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insufficient to cause mucosal damage even if it was retained in a fold of mucosa for several days. The pathway pursued by the capsule was followed at regular intervals by tracing with a portable sodium iodide scintillation counter. Localization of the capsule by this technique correlated satisfactorily with radiological checks on the position. Three groups of patients were studied: 10 controls without evidence of gastrointestinal disease, 6 patients with Crohn's disease, and 7 with ulcerative colitis. There was no obvious difference in the rate of progress of the capsule in the Crohn's disease patients when compared with controls. However, the ulcerative colitis patients showed some prolongation of gastric emptying time. Another method for measuring intestinal transit times was presented by Dr. J. M. Hinton (Middlesex Hospital, London). Pellets of barium-impregnated polythene varying in size from 3 to 5 mm in diameter were used as markers. The specific gravity of the pellets lay between 1 and 1.5. The usual technique was to give 25 pellets before breakfast. The stools were then collected in transparent plastic bags which were thereafter immediately sealed and radiographed, thus enabling a count of the pellets to be made. The transit time was expressed as that required for the passage of 80% of the ingested pellets. .various patterns of emptying in groups of normal subjects and in those with a variety of bowel disorders were presented. In all the normal subjects studied 80% of the markers had been passed by 7 days, but in patients with constipation it sometimes took 2 to 3 times as long for the same proportion of pellets to be passed. The meeting closed with a symposium, under the stimulating chairmanship of Professor Sheila Sherlock (Royal Free Hospital, London), on jaundice with special refer-

625

ence to biliary cirrhosis. This was a comprehensive review of several aspects of this rare but important disease which Professor Sherlock advocated should be named "chronic nonsuppurative destructive cirrhosis" rather than the more usual name of "primary biliary cirrhosis." Dr. L. J. Powell first summarized the recent advances in the understanding of bilirubin metabolism. Among the mechanisms discussed were the various sources of bile pigments, their transport in the blood, the mechanism of entry into the liver cell, the subsequent secretion into the bile, the role of enterohepatic circulation of bile pigments and, finally, the renal excretion. Dr. M. Thorpe presented fine illustrations of electron microscopy in this condition. Particularly striking were the changes in intercellular canaliculi, which were markedly diminished in biliary cirrhosis. A patient with the typical features of the disease was fully presented by Dr. Welton. The diagnostic features of importance to the pathological histologist were then discussed in detail by Dr. P. J. Scheuer. He stressed that wedge biopsies of liver were generally required, needle biopsies often proving insufficient. The destructive changes in bile ducts and the occurrence of round cell granulomas were clearly illustrated. Dr. D. Doniach gave a masterly account of the immunological status of patients with the disorder. Evidence that patients with chronic non suppurative destructive cirrhosis had deficient intestinal absorption of calcium was presented by Dr. C. D. Holdsworth. Professor Sherlock rounded off the symposium by discussing the various problems in differential diagnosis, treatment, and prognosis.

lain E. Gillespie, F.R.C.S. University of Glasgow Glasgow, Scotland

TRANSMISSION OF REFLEXES I agree with the criticism that Dr. James Christensen has made (this journal page 605) of our article in Amer. J. Physiol.

211: 634-642, 1966. It is certainly inappropriate to extrapolate these results to the intact unanesthetized animal and they