Gut 1995; 37: 17-22

Relations between upper abdominal symptomsand gastric distension abnormalities in dysmotilitylike functional dyspepsia and after vagotomy

L E A Troncon, D G Thompson, N K Ahluwalia, J Barlow, L Heggie

AbstractPostprandial bloating and fullness arecommonly found both in dysmotility likefunctional dyspepsia, and after vagotomybut the relation between gastric accom-modation and symptom production hasnot been investigated. Intragastric pres-sure levels and symptoms developedduring controlled distension of the gastricfundus were recorded in nine patientswith functional dyspepsia, in sevenpatients after truncal vagotomy, and in 11healthy volunteers. The procedure wasrepeated after ingestion of a liquidnutrient meal (250 ml; 250 kcal). Gastrictone, expressed as the average value ofpressure over the distension period waslower in controls (median: 11-3 mm Hg)than in either the dyspeptic patients(median: 16.48 mm Hg) or postvagotomypatients (median: 19.12mm Hg) (p<0.05).Meal ingestion reduced gastric tone incontrols, but no significant changeoccurred in either the dyspepsia or thepostvagotomy patients. Volumes at whichdiscomfort was elicited by distensionduring fasting were lower both in dys-peptic patients (median: 210 ml) and inpostvagotomy patients (median: 180 ml)than in healthy volunteers (median: 660ml) (p<0.05). Discomfort thresholds wereunaffected by meal ingestion. Theseresults suggest that a disturbance ofgastric relaxation may be related tosymptom development in dysmotility likefunctional dyspepsia, while similaritiesbetween dyspeptic patients and post-vagotomy patients suggest that theimpaired gastric accommodation infunctional dyspepsia may be due to anunderlying vagal defect.(Gut 1995; 37: 17-22)

Keywords: gastric distension, dyspepsia, vagotomy,postprandial bloating.

Functional dyspepsia, also known as chronicidiopathic dyspepsia, is a common conditiondefined by upper abdominal symptoms thatare not explained by any structural abnor-mality on conventional investigation.1Functional dyspepsia is now conventionallysubdivided into ulcer like, reflux like, and dys-motility like groups2 according to symptomsexperienced. Symptoms in patients with dys-motility like dyspepsia include epigastric dis-comfort or pain, upper abdominal bloating,

early satiety, belching, nausea, and vomiting.2These symptoms often occur in clusters andare characteristically associated with foodingestion.

Several studies have suggested an associa-tion between the symptoms of dysmotility likedyspepsia and abnormalities of upper gastroin-testinal motility, including abnormal gastricmyoelectric activity,3 antral dysmotility,4delayed gastric emptying,4 5 and disturbancesof duodenal and jejunal motor activity.67Nevertheless, these dysfunctions cannot fullyexplain the symptoms, because almost half thepatients show no detectable abnormality ofgastric manometric activity or gastricemptying8 and no correlation exists betweensymptom severity and those functionalabnormalities that are found.5 9A similar symptom pattern to that charac-

terising dysmotility like dyspepsia (particularlypostprandial bloating), is commonly foundin patients after bilateral truncal vagotomyl°in whom defective relaxation of the gastricfundus occurs in response to distension.1 1This similarity of symptom character, raisesthe possibility that a disturbance of thegastric accommodation process in responseto food, might be common to the two condi-tions.

In a previous study12 we assessed gastricaccommodation mechanisms in normal sub-jects by determining intragastric pressure-volume relations during controlled gastricdistension, both under fasting conditions andafter meal ingestion, and showed that foodincreased gastric accommodation.

In this paper, we report a study designed tocompare the relations between symptoms andgastric responses to distension, in patients withdysmotility like functional dyspepsia and inpatients with similar upper abdominalsymptoms after bilateral truncal vagotomy.

Methods

SUBJECTSNine patients with dysmotility like functionaldyspepsia (five male and four female; medianage: 40 years; range: 22-54), seven postvago-tomy patients (six male and one female;median age: 45 years; range: 31-74), and 11healthy asymptomatic volunteers (six male andfive female; median age: 25 years; range:22-44) participated in the study after givinginformed consent. The protocol for the studyhad been previously approved by the SalfordHealth Authority ethics committee.

Department ofMedicine, UniversityofManchester MedicalSchool, Hope Hospital,SalfordL E A TronconD G ThompsonN K AhluwaliaJ BarlowL Heggie

Correspondence to:Dr D G Thompson,Department of Medicine,Hope Hospital, Eccles OldRoad, Salford M6 8HD.

Accepted for publication1 November 1994

17

Troncon, Thompson, Ahluwalia, Barlow, Heggie

Functional dyspepsia patientsAll the patients with functional dyspepsia hadbeen referred to our centre because of chronic,severe, upper abdominal symptoms, particu-larly bloating, related to meals. All had sufferedfrom their symptoms for at least one year andregarded themselves as being seriously dis-abled. None had evidence of a peptic ulcer,previous gastric surgery or any systemic diseaseknown to affect gastrointestinal motility.Common laboratory tests, upper digestive tractendoscopy, barium meal examination, andabdominal ultrasonography were normal in all.

Postvagotomy patientsAll postvagotomy patients had been referred forassessment of postprandial symptoms. All hadbeen submitted to bilateral truncal vagotomy andpyloroplasty for peptic ulcer three to 18 years(median: 10 years) before the study. All sufferedfrom severe postprandial bloating, which hadstarted soon after the surgery and which hadcaused them to reduce the size of their meals. Inaddition, three had dumping syndrome and threeothers had postprandial diarrhoea.

All drugs were stopped for at least 72 hoursbefore the study in all patients.

Healthy volunteersVolunteers were recruited from the medicalpersonnel and student population of theUniversity of Manchester. All were symptomfree at the time of study and none gave ahistory of either digestive tract or systemicdisease, or previous abdominal surgery.

STUDY DESIGNGastric accommodation was assessed bothduring fasting and after the ingestion of astandard meal, by serial measurement of intra-gastric pressure during stepwise fundaldistension using an ultrathin polyethylene bag(capacity 1200 ml), mounted on a 14 Frenchgauge polyvinyl catheter (RT 20 N, PennineHealth Care Products, Derby, UK). Details ofthe methodology have been previously pub-lished.'2 The catheter bag assembly was intro-duced through the mouth into the gastric fundusand the proximal end of the catheter wasconnected to a strain gauge transducercalibrated against a commercial electronicdigital manometer (DPI 700, Druck, Grosby,Leicestershire, UK), capable of measuring intra-bag pressure in the range 0 to 64 mm Hg with amaximum inherent error of 0.25 mm Hg. Ateach distension volume, a series of 12 consecu-tive readings of intrabag pressure were taken atfive second intervals and averaged to give a meanvalue for intragastric pressure. Inflation of thebag in the air showed no increase in intrabagpressure until at least 1200 ml was introduced.

PROTOCOL

Bag insertionAll subjects were studied in the morning after

an overnight fast while reclining comfortably ina semirecumbent position in a quiet room.Firstly, the bag was folded upon the gastrictube, swallowed, and advanced until sited inthe body of the stomach. The bag was thenunfolded by inflation with 400 ml of air andthe tube was gently withdrawn until resistanceof the bag against the lower oesophagealsphincter was felt. The catheter was thenreinserted 2 cm to ensure that the proximalend of the bag was clear of the gastro-oesophageal junction, the bag fully deflated,and the catheter fixed to the cheek withadhesive tape.

Fasting inflationsAfter a 10 minute rest period, the bag was pro-gressively inflated in 30 ml increments at oneminute intervals until the maximal toleratedvolume was reached.

In previous studies with this technique it wasfound that the first distension of the stomachinduced a variable degree of gastric relaxation,after which the pressure-volume relationsremained constant during all subsequent fast-ing distensions.12 In this study, therefore, asecond inflation was performed immediatelyafter the first, and the data from this secondinflation were used to construct the fastinggastric pressure-volume curve.

Post-meal inflationAt the end of the fasting study, the bag wasdeflated and the subject was allowed to rest for10 minutes before drinking 250 ml of a liquidmixed nutrient meal (Fortison, Cow and Gate,Trowbridge, composition: 1.0 kcallml; carbo-hydrate: 12.0%; protein: 4.0%; lipid: 4.0O/o).Five minutes after the end of meal ingestion,another graded gastric distension was per-formed to the maximal tolerated volume.

ASSESSMENT OF SENSATIONS ELICITED BYGASTRIC DISTENSIONAt every 150 ml of gastric distension, subjectswere asked to report their sensations. Subjectswere specifically instructed to report the firsttime they felt uncomfortable. Gastric disten-sion was stopped at the maximally toleratedvolume, which corresponded either to thesensation of painful discomfort or to thedevelopment of nausea. Throughout the study,the subjects were kept unaware of the volumein the bag.

DATA ANALYSISPressures recorded during each distensionwere plotted against the corresponding bagvolumes for each subject studied. From theseintragastric pressure-volume curves the follow-ing parameters were derived.

Gastric tone , an index of tone was obtainedby adding all the values of intragastric pressureobtained from the inflations between 30 ml tothe maximally tolerated volume and dividingthis value by the number of inflation steps.

18

19Abdominal symptoms and gastric distension abnormalities in dyspepsia

Figure 1: Pressure-volumerelations (median values)for three series of controlledgastric distension (O=first,fasting, A =second, fasting,and 0 third, after ameal) in 11 controlsubjects, nine dysmotilitylike functional dyspepticpatients, and sevenpostvagotomy patients.

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Figure 2: Individual valuesof intragastric pressureduring gastric distension infasting conditions and aftermeal ingestion in 1 1 controlsubjects, nine dysmotilitylike functional dyspepticpatients, and sevenpostvagotomy patients.

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Volume at the onset of discomfort - the volumeof inflation at which the sensation of dis-comfort was first reported.

Pressure at the onset of discomfort - the intra-gastric pressure recorded at the onset ofdiscomfort.Maximal tolerated volume - the volume of

inflation at which distension was stopped.Pressure at the limit of tolerance - the intra-

gastric pressure recorded at the maximaltolerated volume.

STATISTICAL ANALYSISTo avoid the assumption of a normal distribu-tion of the data, the results are expressed asmedian and range of distribution. Non-parametric tests were used for the statisticalanalysis'3; for comparisons between the threegroups we used the Mann-Whitney U test.Paired data regarding fasting versus fed resultswere analysed by the Wilcoxon's signed rankmatched paired test. Differences were taken tobe biologically relevant for values of p of lessthan 005.

Results

PRESSURE:VOLUME CHARACTERISTICSFigure 1 shows the intragastric pressurevolume relations during the three gastricdistensions in the three groups of subjects.

10 300 450 600 Fasting studiesGastric tone - Fig 2 presents the data for the

Volume (ml) three subject groups. Values for controlsranged from 8.0 to 206 mm Hg (median: 11.3mm Hg) and were significantly lower than

tiffness - as in previous studies'2 this those for either the functional dyspepsiai as the slope of the log transformed patients or the postvagotomy patients. Valuespressure-volume curves, calculated obtained in dyspeptic patients and postvago-egression. For convenience, values tomy patients were similar, however (p<0.20).ed X 105. Gastric stiffness - data for the slopes of theensation - to assess the sensations intragastric pressure-volume curves rangeddistension the following parameters from 43-115 mm Hg/30 ml in controlsd. (median: 78 mm Hg/30 ml). Values obtained

in functional dyspepsia patients (median: 75mm Hg/30 ml; range: 41-192 mm Hg/30 ml)were similar (p>0 10). In the postvagotomy

Dyspepsia Postvagotomy group, values ranged 46-113 mm Hg/30 ml(median: 60.5 mm Hg/30 ml) and were againsimilar to both the control and dyspeptic

n,n.1n n,n.1n groups (p>005).

tiFasting Fed Fasting Fed

After mealGastric tone - data are again shown in Fig 2.

In the control group, postprandial gastric tonewas lower than during fasting. In contrast, noconsistent reduction in tone occurred in eitherthe functional dyspepsia, or the postvagotomy,patients (p>0. 10).

Gastric stiffness - was reduced by food incontrol subjects. Slope values ranged from28.0 to 92-2 mm Hg/30 ml (median: 602 mmHg/30 ml) and were consistently lower than inthose found during fasting (p<005). Infunctional dyspepsia patients, slope values

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Troncon, Thompson, Ahluwalia, Barlow, Heggie

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*p<0-05 vcontrolsFigure 3: Volume (median and interquartilewithin the intragastric bag at the onset of, anmaximal tolerated, discomfort in fasting condafter meal ingestion in 1 1 control subjects (C)dysmotility like functional dyspeptic patientsseven postvagotomy patients (PV).

were also reduced by meal ingepostprandial values (median: 43.5ml; range: 21 0-114.0 mm Hg/30were lower than fasting values (pcontrast, postvagotomy patientschange in stiffness after meal ingevalues (median: 64.0 mm Hg/3030-0-16.0 mm Hg/30 ml) remaininthose recorded during fasting (p>0

SENSORY RESPONSES TO DISTENSION

FastingVolume at onset of discomfort - in

group, the inflation volume at the ccomfort was 660 ml (media510-990). Discomfort was elicitevolumes both in the dyspepti(median: 210 ml) and in the pogroup (median: 180 ml) (p<0 05)

Pressure at onset of discomfort - tawithin the bag at the onset of discsimilar in all three subject groups (]Maximum tolerated volume - wa

controls (660 ml (range: 540-901dyspeptic patients (median: 525390-750), but both were higher (p<in postvagotomy patients (mediairange: 210-660) (Fig 3).

Pressure at the limit of tolerance -in all groups (Fig 4).

fort After mealVolume at onset of discomfort - the volume at

Fed which discomfort was first reported in thenormal subjects (median: 615 ml; range330-850) was similar to fasting values (Fig 3).In the functional dyspepsia group, volumes

T (median: 240 ml; range: 120-660) were alsosimilar to fasting and were again consistentlylower (p<0 05) than those recorded in the

* normal subjects. Values in the postvagotomyj patients were also similar to fasting and lower

(p<0.05) than those seen in the normalr W | subjects.C FD PV Pressure at the onset of discomfort - was

reduced by meal ingestion (Fig 4) in thecontrol subjects and the functional dyspepsia

volume group. In contrast, values were not differentFed from fasting (median: 17.9 mm Hg; range:

106-2 1 7) in the postvagotomy group.Maximum tolerated volume and pressure -

neither the maximum tolerated distension. ; volumes nor the pressures were changed by

1i food in any of the groups studied.

DiscussionThe results of this study show that patientswith dysmotility like functional dyspepsia show

IF~wv abnormally raised proximal gastric tone afterC FD PV meal ingestion, and an increased sensitivity to

distension, suggesting that a disturbance ingastric relaxation may be related to the

interval) symptoms.id at the Gastric relaxation is a property of theltions and proximal stomach in response both to disten-

(ED), and sion and to nutrient ingestion,'4 mediated atleast in part by an inhibitory non-adrenergic,non-cholinergic vagal pathway.'4 15

stion, with While an impairment in gastric relaxationmm Hg/30 after food has previously been suspected to beml), which associated with postprandial symptoms in<0.05). In patients with functional dyspepsia,' threeshowed no recent studies aiming at assessing intragastricstion, slope pressure-volume relations in dyspeptic patientsml; range: have failed to show any abnormality.'6-18 It

ig similar to does not seem that methodological differences05). could account for the discrepancy between

these previously reported results and our owndata because the techniques used for assessingpressure-volume relations seem to be similar inall studies. The most probable explanationtherefore seems to lie in patient selection, we

the control studied a more homogeneous subgroup of)nset of dis- dyspeptic patients, including only those within) (range dysmotility like symptoms and excluding thosed at lower with other dyspeptic symptom patterns, whichic patients were included by others and which mightistvagotomy have reduced the possibility of showing an

(Fig 3). abnormality.he pressure After bilateral truncal vagotomy in dogs, an.omfort was impaired gastric relaxatory response to intra-Fig 4). intestinal nutrient15 and to feeding'9 has beens similar in seen, showing that the relaxation is vagally0)), and in mediated. Our study seems now to confirmml; range: this abnormality in humans. It is of further-C0 02) than interest to note that the abnormalities in then: 440 ml; dyspeptic patients resemble closely those

found in postvagotomy patients suggestingwas similar perhaps a common aetiology for the develop-

ment of symptoms in the two conditions. Our

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Abdominal symptoms and gastric distension abnormalities in dyspepsia

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Figure 4: Pressure (median and interquartile interval) within intragastric bag at the onsetof, and at the maximal tolerated, discomfort duringfasting and after meal ingestion in 11control subjects, nine dysmotility like functional dyspeptic patients, and seven postvagotomypatients. Abbreviations as in Fig 3.

work thus not only supports the concept that,in humans, intact vagal pathways are of majorimportance in the mediation of gastric relax-atory response to distension and to food, butalso suggests that a neural defect may partici-pate in the production of gastric tone abnor-malities in functional dyspepsia although itremains uncertain where precisely in thepathway such a defect might occur.

Our method of estimating gastric tone byaveraging intragastric pressures measuredduring distension probably includes compo-nents of both basal tone and the relaxatoryresponse to distension. In the fasted state,gastric tone seems to be the consequence of a

balance between excitatory cholinergic'4 andnon-adrenergic, non-cholinergic inhibitoryvagal efferents, the second entailing nitricoxide release.20

It seems unlikely that the increased fastinggastric tone in dyspeptic patients is caused bycholinergic hyperactivity because measure-

ments of vagally mediated gastric acid secre-

tion21 and pancreatic polypeptide release22 infunctional dyspepsia are normal. It seems moreprobable therefore that the increased fastingtone is the result of defective neural inhibitorypathways. These defects do not necessarilyimply damage to the vagus nerve trunks,

however, as the destruction of intramuralganglia and intrinsic nerve fibres of thestomach also impairs gastric accommodationto a similar degree to vagotomy.23The postvagotomy patients, showed normal

gastric wall stiffness in the fasted state, but,unlike controls and dyspeptic patients, failed toshow a reduction in stiffness after meal inges-tion. This is unlikely to be explained simply byan abnormality of the passive viscoelasticproperties of the stomach, which it has beensuggested, exists after vagotomy,24 as gastricstiffness reflects more than the passive elasticcharacteristics of the stomach, being changedby meal ingestion'2 as well as by intragastriclipids and osmolytes.25

Both the dyspepsia and postvagotomypatients reported the onset of discomfort at anabnormally low volume both under fastingconditions and after meal ingestion although itis important to note that the intragastric pres-sure at which discomfort was triggered wassimilar to that in the normal subjects. Previousexperimental work in humans26 has suggestedthat epigastric fullness and abdominal dis-comfort may be elicited either by excessivedistension of a relaxed stomach or by thedevelopment of increased gastric muscle tone.As intramural tension can be expressed as afunction of both gastric wall stretch (which isrelated to intragastric volume) and gastric tone(which is related to intragastric pressure),12 itfollows that if intragastric pressure is similar,and the volume is less, then the discomfortmust be the result of either changedmechanoreceptor sensitivity or increased tonein the gastric wall. As our data show that in thefasted stomach tone is increased in bothpatient groups studied, this seems to be themost plausible explanation for the increaseddiscomfort and is thus consistent with the viewthat a failure of the stomach to relax inresponse to meal ingestion is the cause of post-prandial bloating, not only in postvagotomypatients but also in dysmotility like dyspepsia.

After vagotomy, defective postprandialgastric relaxatory responses and increasedintragastric pressure probably contribute to theaccelerated initial phase of gastric emptyingknown to occur in the condition.27 This con-trasts, however, with the reports of eithernormal9 or delayed4 5 gastric emptying in func-tional dyspepsia. We have, however, recentlydescribed abnormal intragastric distribution ofingested food in dysmotility like dyspepticpatients and found an increased transfer ofintraluminal contents from the fundus to theantrum even when overall gastric emptyingwas normal.28 The results of this study nowsuggest that the cause of such intragastric foodmaldistribution may be impaired fundalrelaxation.

In conclusion, our results show that dys-motility like functional dyspepsia patients withpostprandial bloating symptoms show, defec-tive gastric accommodation both to distensionand to food, and a lower threshold for theonset of abdominal discomfort. These results,which parallel those found in a group ofpostvagotomy patients with similar symptoms

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suggest a common underlying neural defect ofvagally mediated pathways. The precise natureof this defect in the dyspeptic patients remainsto be determined, however.The authors are indebted to Mrs J Young for the assistance inpreparing the manuscript. Part of this study was presented atthe American Gastroenterological Meeting held in SanFrancisco, 1992 and appeared in abstract form inGastroenterology 1992; 102: A528.Dr Troncon was the recipient of a fellowship grant from a

covenant between the University of Sao Paulo, Brazil and theInteramerican Development Bank.

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