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CLINICAL ASSESSMENT OFGASTRIC FUNCTIONE. N. ROWLANDS, M.D., B.Sc., F.R.C.P.

Department of Gastroenterology, Central Middlesex Hospital, London, N.W.io and Medical Research ConncilDepartment of Clinical Research, University College Hospital Medical School, London, W.C.I

The methods available for assessing gastricfunction are crude by comparison with the refinedtechniques which have been developed for study-ing renal or cardiopulmonary function in man.One reason for this is that both the secretory andmotor functions of the stomach are extremelycomplex. It is much easier to measure the flowof blood through large arteries than it is to recordthe ' receptive relaxation' of the stomach as foodenters it, or the subtle mechanism of gastricemptying. The gastric glands contain at leastthree different kinds of cell, the parietal cell, chiefcells and the mucous cells of the neck. These areinextricably intermingled and discharge theirsecretions directly into the lumen of the stomachwhere they mix with the surface mucus, saliva, foodand regurgitated intestinal secretions. Anotherdifficulty is that the secretions and pressures canonly be studied by passing tubes into the stomach.Most patients dislike intragastric tubes more thanalmost any other diagnostic procedure, and thereis no doubt that the nausea and distress caused bythe presence of a tube has vitiated many studiesof gastric function because the patient's emotionalstate exerts a profound influence on secretion andmotility.One is often asked what is the best clinical test of

gastric secretory function. This depends on whatkind of information is required, but it is importantto realize that these tests will not give much helpin diagnosis or in assessing the severity of gastro-duodenal diseases. Some clinicians are reluctantto accept this fact, but it is unreasonable to expectas much from these tests as from tests of renal,respiratory, hepatic or pancreatic function. Unlikethese organs, the stomach is not indispensable:patients with pernicious anaemia who secreteneither acid nor pepsin are able to digest andabsorb food as well as other people, and this isalso true of most patients following gastrectomy.Even if we knew all about the mechanism andcontrol of the secretion of acid and pepsin it is byno means certain that this would help in diagnosis,

or in elucidating the etiology of peptic ulcers, orin explaining the mechanism of dyspeptic symp-toms. On the other hand, tests of gastric functionhave done much to clarify the relation betweenacidity and peptic ulcer; they are also useful forassessing the value of therapeutic measures becauseacid-pepsin is undoubtedly the factor whichpermits ulcers to become chronic. In this articleit is proposed to discuss the clinical value andlimitations of some methods of assessing gastricfunction and the physiological principles on whichthey depend.Assessment of Acid SecretionThe ideal method would be to collect and analyseall the acid secreted throughout the 24 hours while

the patient continues to take his meals as usual.Unfortunately this cannot be done because thereis no method of measuring the amount of gastricsecretion which is produced in response toordinary meals and it is difficult to imagine howthis could be done without constructing a gastricpouch. This is a serious limitation on all tests ofgastric function in man,13 and it is important torealize that most of our knowledge about gastricsecretion has been derived from experiments onanimals with gastric pouches. These have shownthat secretion is controlled by three successivestimuli and a number of inhibitory mechanisms.In the first or cephalic phase, the anticipation andsight of food and then the act of eating activate anervous reflex through the vagus. In the secondor gastric phase, the presence of food in thestomach stimulates secretion through a humoralagent which is formed in the antrum, partly bymechanical distension and partly by the action ofsecretagogues in food. In the third or intestinalphase, the presence of food in the intestine activatesanother humoral mechanism. These secretorystimuli are counterbalanced by mechanisms whichtend to inhibit secretion. For example, the ac-cumulation of acid in the stomach tends to preventfurther acid secretion; and the presence of fat in

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the duodenum, and also of acid and hypertonicsolutions has a powerful inhibitory effect which ismediated by a hormone, enterogastrone, and bynervous reflexes acting through the vagus. Thatsimilar mechanisms control gastric secretion inman has been shown by means of the Serial TestMeal11 and by observations on patients aftercertain gastric operations such as vagotomy, andgastrectomy before and after removal of thepyloric antrum.6 But even these special methodsof investigation can give little or no informationabout the secretory response to eating in man orabout the relative importance of nervous andhumoral mechanisms in health and disease.

The Fractional Test MealThe traditional test meal is or should be

obsolete. In this test gruel is usually used as astimulus and small samples are aspirated from thestomach at s5-minute intervals for about twohours. The test meal curve cannot be used as ameasure of the amount of acid secreted by thestomach, because the acidity of each sampledepends not only on the amount of acid but alsoon the volume of the gastric contents. The latterdepends on the rate at which the stomach empties.Therefore, the acidity of each sample is determinedby the interplay between the rate of emptying andthe rate of secretion, so that an increase of gastricemptying or of secretion will raise the concentra-tion of acid in the gastric contents. Nor can thetest meal be used to determine whether the stomachis capable of secreting any acid at all, because gruelhas little or no chemical secretagogue activity. Itstimulates only by virtue of its bulk which causesmechanical distension of the antrum.

In fairness to the earlier workers who introducedthe gruel test meal it should be pointed out thatthey were well aware that this test did not measurethe amount of acid secreted. They used the testas an adjunct in the differential diagnosis of pepticulceration because they found that patients withduodenal ulcers often reached a higher maximumacidity in a test meal curve than normal subjects,while those with gastric cancer showed a flattercurve. Tests which actually do measure the outputof acid also show that patients with duodenalulcers as a group secrete more acid than normalsand that patients with gastric ulcers tend to secreteless. Presumably the interplay between acidsecretion and gastric emptying tends to follow atypical pattern in patients with duodenal ulcersand therefore the test meal curve tends to reach ahigher level than normal. However, the value ofsecretory tests in differential diagnosis is verylimited because there is such a big overlap betweennormal subjects and patients with ulcers. The

finding of either hypersecretion or achlorhydriamay be useful in the exceptional case where thereis a discrepancy between the clinical and radio-logical findings.The Serial Test MealThe serial test meal is an ingenious method of

measuring the secretory response to an aqueoustest substance given by mouth, but only a physio-logist could commit the gastronomic solecism ofdescribing these substances as ' meals'. A liquid'meal' containing a dye, phenol red, is given tothe same subject on successive days for about aweek, and the whole of the gastric contents arewithdrawn through a tube of large bore afterprogressively longer periods each day. Forexample the stomach would be emptied after 15minutes on the first day and after 30 minutes onthe next day, and so on. From the differencebetween the amount of dye in the recovered gastriccontents at two extractions it is possible to calculatethe volume of the gastric contents leaving thestomach through the pylorus and also the volumeof gastric secretion formed during the intervalbetween the extractions. Thus the amount ofacid, chloride and pepsin secreted in response tothe meal can be calculated and the rate and patternof gastric emptying determined.1

It is assumed that the stomach is completelyempty when the meal is given, that the gastriccontents are homogeneous and uniformly mixedwith the dye, and that gastric function is the sameon each day. Therefore, the method can only beused with ' meals ' consisting of aqueous solutionsof sugars or salts which do not react with acidand which stimulate secretion only by virtue oftheir bulk by distension of the antrum. Theselimitations may be actually desirable from thephysiologist's point of view because they help tostandardize the experimental conditions. Hunthas used the method to determine the makimalemptying power of the stomach and the relationbetween increasing gastric distension and secretoryresponse, and to study the mechanisms whichinhibit secretion and emptying in normal subjectsand in patients with ulcers. Although it hasprovided much valuable physiological informationit is obviously unsuitable for routine clinical pur-poses and its reproducibility under such conditionsis uncertain. Moreover, it is very unlikely that thestomach empties or secretes in response to ordinarymeals as it does to these tasteless solutes.

Basal Gastric SecretionGastric juice is secreted more or less con-

tinuously in man, even when there is no food inthe stomach. The interdigestive, basal or noc-

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turnal secretion can be collected by aspirating thestomach continuously throughout the night, butthis is a cumbersome method and difficult tosupervise. Similar information can be obtainedmore easily by collecting the basal secretion for anhour or two in the morning after an overnight fast.Great care is required to minimize the loss ofsecretion through the pylorus and contaminationof the gastric juice by other secretions. The salivais mainly a diluent for it contains only low con-centrations of chloride and bicarbonate, andtherefore it is sufficient to spit it out becauseaspiration with a sucker is liable to stimulatefurther flow; duodenal juices, on the other hand,may contain high concentrations of bicarbonate.Ideally, a double-lumen tube should be used todrain the stomach and duodenum continuously andthus prevent losses of gastric juice through thepylorus and regurgitation of intestinal contentsinto the stomach; but Ihrel2 compared the resultsusing a double tube with those using a single tubein the stomach in a large series of patients andfound surprisingly little difference. The essentialpoint is to position the tip ofthe tube radiologically,and this applies to all other tests which depend onintragastric tubes. We have found that the tubecoils up in the fundus of the stomach in one out offive tests, and this can only be detected radio-logically because appreciable amounts of fluid maybe aspirated even from a tube in the oesophagus.The tip of the tube should be placed just beyondthe angulus, roughly at about the right border ofthe vertebrae. The stomach is emptied completelyand then continuous aspiration is begun, ideallyby hand but in practice by mechanical suction.

It has been too readily assumed that basal gastricsecretion is entirely dependent on nervous reflexesacting through the vagus, and, therefore, that thehigh basal secretion which is commonly found inpatients with duodenal ulcer is the result ofexcessive vagal stimulation. It is true thatvagotomy depresses basal secretion but it alsodepresses the secretory response to histamine,which is thought to act directly on the parietal cell.Similarly atropine not only inhibits the psychic orcephalic phase of secretion but also the gastric andintestinal phases which are humoral in nature,13and antrectomy also reduces basal secretion inman.6 Moreover, there is some evidence that thelevel of basal secretion may be related to adreno-cortical activity. It is, therefore, clear that themeasurement of basal secretion cannot be usedsimply as a measure of vagal activity.

Like all other methods which involve continuousaspiration of gastric juice, this is a highly artificialand unphysiological test. Yet it has become thestandard method for testing the efficacy of anti-secretory drugs. The reproducibility of the

method is also poor but can be improved by usinga powerful secretory stimulus.

The Augmented Histamine TestHistamine is not only the most powerful

secretory stimulus but also the most physiological.It used to be customary to inject a dose of o.oimg./kg. body weight at the end of a fractional testmeal if the patient had failed to secrete ' free acid '

during the test. If this failed to produce any freeacid the patient was said to have histamine-refrac-tory achlorhydria. It was known, however, thatthe secretory response to this dose of histaminevaried at different times in the same individual,and that some patients who were refractory tohistamine could secrete acid in response to or-dinary meals. This was shown by measuring thepH of gastric samples aspirated at hourly intervalsthroughout the day.24 The dose of histamine waslimited by its unpleasant side-effects but it wasrealized that the ideal test would be to injectsufficient histamine to stimulate all the parietalcells to secrete so as to obtain the maximum outputof acid. This became possible with the introduc-tion of the antihistamines because they antagonizeall the actions of histamine other than its effect onthe parietal cell.

Kay15 carried out a series of tests on normalsubjects to whom he gave increasing doses ofhistamine covered by the appropriate dose of anti-histamine, on successive days, and measured theamount of acid secreted in response to each dose.The largest single dose given was 7.1 mg. re-presenting 12 body-weight doses of histamine, buthe found that four body-weight doses produced themaximum output of acid and that any furtherincrease in dosage failed to increase the output.This was interpreted to mean that four body-weight doses will stimulate all the parietal cells,and there is evidence that the output of acid isproportional to the number of parietal cells and,therefore, an index of the parietal-cell mass.3However, even with this maximum histaminestimulus it is necessary to use a meticulous tech-nique to achieve reproducible results. The tubemust be of large bore to prevent significant lossesof the stimulated juice through the pylorusand it is necessary to ensure that the tube is keptpatent throughout the test and that aspiration iscontinuous. The gastric juice is collected for onehour as in the basal secretion test, then theappropriate dose of mepyramine (i.e. Anthisan) isgiven, and 30 minutes later a four body-weightdose of histamine acid phosphate is injected. Themaximum output of acid is reached about 15minutes after the histamine injection and itremains maximal for the next 30 minutes; there-fore, the output of acid in the 30-minute period

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starting 15 minutes after giving the histamine iscalculated. The patients are aware only of asensation of flushing from the histamine and ofdrowsiness from the antihistamine.As might be expected, the maximal response is

stable from day to day and therefore the Kay testhas important theoretical implications and practicalapplications. Perhaps the most important of theseis that it has changed the definition of the word'achlorhydria' which now implies the virtualabsence of parietal cells. On the basis of testmeals it had long been accepted that about 4% ofhealthy young people were achlorhydric and thatthe percentage increased considerably over theage of 60. The Kay test has shown that the onlypersons who cannot secrete any acid at all arepatients suffering from pernicious anaemia andpossibly a very small number of patients withother types of anaemia. This is based on a newcriterion for acid secretion, viz. the ability to lowerthe pH below 6.0 in response to maximal histaminestimulation.4 The traditional criterion, viz. theability to secrete 'free acid' has been undercriticism for some time because it means that theacidity exceeds the turning point of Topfer'sreagent, which corresponds to about pH 3.5.Since neutrality corresponds approximately topH 7, and the pH of pure, non-acid gastric secre-tion is probably higher still, it seems unreasonableto demand a pH as low as 3.5 as evidence that thestomach is capable of secreting acid.

Patients with duodenal ulcers as a group secreteabout twice as much acid as normals, but the Kaytest is of little more help in the differential diag-nosis of dyspepsias than the test-meal. On theother hand, it may be useful in deciding the mostappropriate treatment for the individual casebecause current therapy of ulcer is concernedalmost exclusively with reducing acidity. Thistest measures the secretory capacity of the stomachand is an index of the number of parietal cells, andthis varies widely even in patients with duodenalulcer. However, the problem may not be quite assimple as this because the secretory power of thesecells depends on several factors; for example, ithas been shown that both vagotomy and antrec-tomy will reduce the parietal response to hista-mine.6

The Insulin Hypoglycaemia TestThis test has been used to determine the com-

pleteness of vagal section. The blood sugar islowered by an intravenous injection of about 15units of insulin and samples are aspirated from thestomach for about two hours, and blood-sugarlevels are measured at half-hourly intervals. Thehypoglycaemia acts centrally to stimulate gastricsecretion through the vagus nerves; it stimulates

the secretion of pepsin and mucoprotein as wellas acid. The test is often unpleasant for thepatient and is not very useful in practice; thereis often a fall in secretory rate before the hypogly-caemia begins to stimulate secretion, and this fallmay also occur after vagotomy. Moreover, thehypoglycaemia may stimulate further secretionafter a delay of several hours and this late phasealso occurs after vagotomy but not after adrenalec-tomy.20 This is part of the evidence that theadrenocortical hormones play some part in con-trolling gastric secretion in man.

Twenty-four-hour Gastric AnalysisAll of these tests are highly artificial procedures,

including those which depend on 'physiological'stimuli such as histamine, and particularly whenthe technique of continuous aspiration is used.The only test which gives some information aboutgastric acidity under ordinary living conditions isthe 24-hour gastric analysis.l4 This is a samplingtechnique for measuring the pH of the gastriccontents without disturbing the normal operationof the three phases of secretion or the inhibitorymechanisms which control gastric secretion. Thepatient swallows a tube which is left in the stomachfor 24 hours. He takes his meals as usual andabout 5 ml. of the gastric contents are aspiratedevery hour throughout the day, and the pH ofeach sample is measured. Alternatively a glasselectrode may be swallowed and the pH of thestomach contents recorded continuously in situ.No attempt is made to prevent saliva or regurgi-tated intestinal juices from entering the stomach,and, therefore, the changes in acidity throughoutthe day are recorded under normal conditions.The method has proved useful for studying theeffect of food and drugs on acidity, the relationbetween acidity and pain, and the pattern ofacidity in patients with gastric and duodenalulcers. In patients with duodenal ulcers the pHtends to remain low throughout the day and nightexcept for transient neutralization after feeds,whereas in patients with gastric ulcers the pHlevels are usually higher and about 50% of themshow nocturnal neutralization. This is said todisappear when the gastric ulcer heals. Un-fortunately, as with all other tests, there is far toomuch overlap between normals and patients withulcers to make the test worthwhile in differentialdiagnosis, but it may be useful in exceptionalcases when the clinical and radiological evidence isconflicting. It may also be useful in establishingthe cause of bleeding in the acute stages ofhaematemesis,5 because high nocturnal acidity isusual in bleeding from a duodenal ulcer and noc-turnal neutralization with a gastric ulcer, whereasachlorhydria is usually found if the bleeding is due

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to acute peptic ulceration. It is necessary toemphasize once again that in this, as in othertests, the positioning of the tube in the stomach isvery important, because the degree of mixing ofthe gastric contents is such that the acidity is farfrom uniform even after fluid meals.This is also a valuable method for assessing the

usefulness of drugs in controlling acidity in thetreatment of peptic ulcer.18 It is a simple matterto demonstrate the action of pharmacologicalagents such as histamine, insulin or acetazolamideon gastric secretion, but difficulties arise in assess-ing the likely clinical effect and duration of actionof drugs when given by mouth for therapeuticpurposes. This is why the therapeutic claimswhich have been made for innumerable anti-secretory drugs in recent years have not beenfulfilled in clinical practice, although the pharma-cological tests in man have been very encouraging.One of the problems is to establish criteria as towhat constitutes a significant effect on secretion.Variations in gastric secretion between individualsare so large that each must act as his own control,but even in the same person the output of acidmay vary by a factor of 5 on different occasions,and by a factor of 2.5 from hour to hour during asingle test lasting five hours, even in trained sub-jects who are accustomed to repeated intuba-tions.21 22 One method of overcoming thisvariation in the basal, interdigestive secretion is totest the action of the drug on histamine- andinsulin-stimulated secretion. Valuable informationmay be obtained in this way, but it is difficult tointerpret the results in terms of the likely effect ofthe drug under ordinary clinical conditions. Forthis purpose, the best method for testing a drugwill depend on whether it is expected to stimulateor to inhibit secretion. If the object is to determinewhether a drug is likely to be useful in controllingthe hypersecretion of acid in patients with duodenalulcer, it is essential to test it in patients who aresecreting continuously and at a high rate, andseveral tests will be necessary on each patient.16Not only is it difficult to measure the effect of anantisecretory drug in normal subjects, the resultswill give little or no indication of its effect inpatients with hypersecretion.'Let us suppose that the maximum dose of an

antisecretory drug reduces the output of acid by50%, for example, from about Ioo mN to 50 mN.This would commonly be described as a ' markedinhibitory effect' and likely to be valuable incontrolling acidity in patients with duodenal ulcer.However, the common practice of expressingacidity in terms of normality may be misleadingwhen the object of the test is to assess the clinicaleffect of a drug. For this purpose, the significantmeasurement is its effect on pH, for it is this which

determines peptic activity, and the object of usingantisecretory drugs in clinical practice is to in-activate pepsin by maintaining the pH at about3.5 or 4.o. A reduction of acidity by 50% seemsimpressive, but a fall from Ioo mN to 50 mNrepresents a rise of only about o.4 pH units fromabout pH I.I to I.4; the pH would still be lessthan 2.0 even if acidity were reduced by 80%, fromo00 mN to 20 mN. A further difficulty arises in

interpreting the results in clinical terms because atest which involves the continuous aspiration ofgastric juice will mask any effect a drug may haveon the rate of gastric emptying. The majority ofantisecretory drugs are anticholinergic and there-fore prolong the emptying time, so that food andsecretion remain in the stomach for longer periodsand continue to stimulate further secretion in thegastric phase. There is no way of measuring thisbut it is likely to be significantly greater than therate of interdigestive secretion; no account istaken of it in these tests, nor of any possibleinhibitory effect of the drug on the alkaline pan-creatic and duodenal juices. It follows that anantisecretory drug must have a very profoundinhibitory effect on the output of acid as tested bythis method, in order to inactivate peptic activityin patients with hypersecretion.l7

This problem has been discussed at some lengthto show how a method may provide importantquantitative data about the pharmacological actionof a drug and yet give a misleading impression ofits clinical usefulness. It is essential to obtain allpossible information before embarking on laboriousclinical trials, and probably the best final test of anantisecretory drug is to measure its effect on thepH of small samples of gastric juice, aspirated atfrequent intervals over 24 or 48 hours undernormal conditions. Such a method is,about asfar removed from the controlled techniques ofexperimental physiology as can well be imagined,but it tests the drug under the actual conditions ofclinical use. It also allows for the wide variationsin secretion in different patients, because a drugwhich can be shown to maintain the pH above3.0 is ;a very powerful inhibitor indeed. Since thetube is placed in the stomach it may be objectedthat this method does not provide informationabout the pH of the milieu of a duodenal ulcer. Itis possible to place the tube in the first part of theduodenum but this is a tedious process,2 and thepH levels correspond so closely to those in theantrum that the additional information does notjustify the additional distress suffered by thepatient.Tubeless Gastric AnalysisThese methods depend on the use of cation

exchange resins which are dissociated in the

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presence of free hydrogen ions in the stomach, sothat the cation is absorbed and excreted in theurine.8,19 Two compounds are available, bothmarketed under the trade name ' Diagnex'; inone of these quininium is used as the exchangecation and in the other the dye Azure A. If this'was a quantitative method not only would it havethe advantage of being tubeless, but it would alsobe a measure of the total gastric secretion includingthat which is normally lost through the pylorus.Unfortunately the amount of the cation which isdisplaced from the resin and absorbed from theintestine and then excreted in the urine is notdirectly proportional to the amount of acid secretedby the stomach. The method can, therefore, onlybe used to determine whether or not the stomach iscapable of secreting any acid, and even for thispurpose neither the quininium nor the Azure Aresin gives complete correspondence with theordinary histamine test. False negative resultsmay arise from defective absorption of the cationin such conditions as pyloroduodenal obstruction,malabsorption syndromes, and severe diarrhoea,or from delayed excretion in diseases of the urinarytract. Since the test can at best be only a screeningprocedure for achlorhydria, a few false negativeresults are unimportant, but false positives arevery misleading. These may arise because thecation can be displaced by substances other thanhydrogen ions, such as magnesium, iron, alu-minium, calcium and kaolin, and, therefore, theseshould not be taken by mouth for two days beforethe test; but a few false positives will still occur.Nevertheless, this test is useful as a screeningprocedure for picking out patients with defectivegastric secretion for further study.Non-acid Gastric SecretionChlorideThe estimation of chloride is not very useful in

routine clinical tests but it is crucial in physiologicalstudies; the experimental evidence for the differenthypotheses about the composition of gastric secre-tion depend very largely on the relation betweenchloride concentration and acidity. For example,the Hollander two-component hypothesis is basedon the fact that there is a linear relationshipbetween the concentration of acid and chlorideover a fairly wide range of acidities. According tothis theory, which is fairly widely held, gastricsecretion is made up of two hypothetical com-ponents, each of which is assumed to have a fixedcomposition in respect to acid, chloride andbicarbonate, the concentration of acid in theparietal component being 155 mN. The hypo-thetical non-parietal component is neutral oralkaline and consists of mucus, chlorides and somebicarbonate. Hyperacidity cannot occur, but

hypersecretion of acid implies a high rate offormation of the parietal component becausevariations in the acidity of gastric secretion resultfrom the presence of different proportions of thetwo components. Neither this nor any of theother hypotheses will account for all the facts.The application of this hypothesis to clinicalproblems has not been very fruitful, but it is arelatively simple matter to calculate the volumesof the two components by estimating chloride aswell as acid.

MucusThe analysis of gastric mucus is still a research

procedure because both chemical and electro-phoretic techniques are difficult and technicallyunsatisfactory. It has been shown that albuminis present in gastric secretion and also that thereare a number of mucoproteins but the normalelectrophoretic pattern has not yet been estab-lished. However, the analytical techniques arebeing improved rapidly and there are manyreasons for thinking that the study of gastric mucuswill be more rewarding than that of acid-pepsin inrelation to the pathogenesis of ulcer. Researchwas undoubtedly stimulated by the discovery thatthe incidence of peptic ulcers and gastric carcinomawas related to the patient's ABO blood group andto the presence or absence in his saliva and gastricjuice of the ABH blood group substances whichare mucopolysaccharides.Proteolytic EnzymesThe estimation of pepsin is not worthwhile as

a routine procedure because the amount secretedusually corresponds to the amount of acid secreted,and there is no evidence, for example, that patientswith peptic ulcer secrete more pepsin per unit ofacid than normal persons. However, there hasrecently been a revival of interest in the estimationof blood and urinary pepsinogen as a diagnostictest.10 Pepsin is synthesized in the chief cells ofthe gastric glands and about I% of it enters theblood stream and is excreted in the urine. There isundoubtedly some correlation between the pep-sinogen secreted in gastric juice and both theblood and urinary pepsinogen, but the latter canonly be used as an approximate index of gastricsecretory activity. There are many instances wheregastric pepsin is increased by secretory stimuliwithout any change in the excretion of uropepsin,and vice versa, and there is no doubt that manyconclusions that have been drawn about gastricpepsin from measurement of uropepsin are invalid.We need to know much more about how thepepsinogen enters the blood and how it is excretedby the kidney. The available evidence suggeststhat the blood and urinary pepsinogen parallel the

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mass of chief cells in the gastric glands rather thanthe rate of gastric secretion. Although the bloodand urinary pepsinogen levels are higher inpatients with duodenal ulcer as a group than innormal persons or patients with gastric ulcer, theoverlap is so great that the test is rarely helpful indifferential diagnosis. In this respect it resemblestests of acid secretion but with the importantadvantage that the patient is not obliged to swallowa tube, and the chemical estimation is a simple one.In iron-deficiency anaemia the blood and urinarypepsinogen levels are usually low if the patients areachlorhydric to the ordinary histamine test. Inpernicious anaemia the levels are always very low:this is about the only statement about uropepsinwhich has not been contradicted by someone orother in the vast literature on the subject. Becauseit is always low or absent in pernicious anaemia,estimation of the blood or urinary pepsinogen isuseful as a screening test for picking out patientsfor further study, and also in the investigation ofsuspected but unproven cases of perniciousanaemia who have already been treated and inwhom the diagnosis is still in doubt.There has also been a revival of interest in

another proteolytic enzyme which is present inthe gastric juice of normal people and has anoptimal pH of about 4.o, in contrast to pepsinwhich is most active between 1.6 and 2.4; in thepast this enzyme has been regarded as a cathepsin.Taylor23 has recently produced evidence thatproteolytic activity occurs at three pH maxima inpatients with peptic ulcers.

Assessment of Gastric MotilityThere is a great deal of evidence that dyspeptic

symptoms are more closely related to subtledisturbances of motility than to changes in gastricsecretion. The techniques available for studyingmotility are not sufficiently refined to make itpossible to record precisely how the stomachrelaxes to accommodate a meal, or how it dis-charges the food in a controlled manner into theintestine, or what part the pyloric sphincter playsin the process of gastric emptying. Many of thesymptoms of the dyspepsias almost certainly resultfrom disturbances of some of these mechanicalfunctions of the stomach and duodenum. Themethods available for studying motility in manare: the serial test meal, radiological methods andmanometric techniques.The Serial Test MealThis method is very useful for investigating the

rate and pattern of gastric emptying and thefactors which control it. Hunt has shown thatliquid ' meals ' leave the stomach in an exponentialmanner so that a constant fraction of the gastric

contents passes into the duodenum every minuteuntil the stomach is empty. Unfortunately thiselegant method cannot be used with ordinarymeals.

Radiological MethodsIt is possible to mix sufficient barium with an

ordinary meal so as to outline the stomach, andthe recent development of image intensifiers hasreduced the radiation hazards so that cineradio-graphy can be used for more prolonged studies.The simultaneous use of cineradiography andmanometric techniques is an important advanceand is now being exploited in several centres.

ManometrySome useful information has been obtained

about the function of the pylorus by measuringintraluminal pressure by means of open-endedtubes or very small balloons.1 Unfortunately,manometric methods do not provide all the datanecessary for analysing gastric motility, becausethe intraluminal pressures recorded are notdirectly related to movements of the gastriccontents nor to the tension in the muscular wallof the stomach and duodenum.9 The diameter ofthe lumen varies from place to place and isconstantly changing. There can be considerablemuscular activity and rapid transport of contentswith variations of only i to 2 cm. water pressurein the lumen, whilst pressure-waves of largeamplitude may be recorded without any movementof the gastric contents. What is needed is a simplemethod for measuring the tension developed inthe wall of the gut and the movements of thegastric contents. The recent development ofmethods of telemetering data from the alimentarytract by means of 'radio pills' may make itpossible to study both secretion and motilityunder natural conditions without the patient beingaware that he is being studied at all.7

REFERENCES. ATKINSON, M., EDWARDS, D. A. W., HONOUR, A. J.,

and ROWLANDS, E. N. (1957), Lancet, ii, 918.2. ATKINSON, M., and HENLEY, K. S. (I955), Clin. Sci.,

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