Gut 1995; 36: 539-543

Effect of Helicobacter pylorn status on intragastricpH during treatment with omeprazole

E F Verdu', D Armstrong, R Fraser, F Viani, J-P Idstrom, C Cederberg, A L Blum

Division ofGastroenterology,CHUV, Lausanne,SwitzerlandE F VerdIR FraserF VianiA L Blum

Division ofGastroenterology,McMaster University,Hamilton, OntarioL8N 325, CanadaD Armstrong

Division of ClinicalPharmacology, AstraHfissle AB, Molndal,SwedenJ-P IdstromC Cederberg

Correspondence to:Dr E Verdu6, CHUV(Ancienne CliniqueInfantile), Division deGastro-enterologie, CH-1011 Lausanne, Switzerland.

Accepted for publication15 July 1994

AbstractTo test the hypothesis that Helicobacterpylon1 infection is associated with adecreased intragastric acidity duringomeprazole therapy, ambulatory 24 hourdual point gastric pH recordings wereperformed in 18 H pyloni positive and 14H pylori negative subjects. There was afour to six week washout period betweenthe two pH recordings made in eachsubject after one week courses of placeboor omeprazole, 20 mg daily. Duringplacebo, median 24 hour pH values werenot different in the corpus (H pylori posi-tive=1.5, negative=1-4; p=0*9) or antrum(H pyloni positive= 13, negative= 12;p=0 1). However, during omeprazoletreatment, median 24 hour pH valueswere higher in H pylori positive subjects,both in the corpus (H pylori posi-tive=5 5, negative=4*0; p=0.001) andantrum (H pylorn positive=5.5, nega-tive=3.5; p=0.0004). During placebotreatment, the only difference between thetwo groups was a higher later nocturnalpH in the antrum in the H pylorn positivegroup. During omeprazole treatment,gastric pH was higher both in the corpusand in the antrum in the Hpylon positivegroup for all periods, except for mealtimein the corpus. These data indicate thatomeprazole produces a greater decreasein gastric acidity in subjects with Hpyloninfection than in those who are H pylonnegative. It is not, however, knownwhether there is a causal relationshipbetween H pylorn infection and increasedomeprazole efficacy.(Gut 1995; 36: 539-543)

Keywords: Acid inhibition, Helicobacter pylori,omeprazole, intragastric pH-metry.

Omeprazole has been shown to have bothdirect1 and indirect23 effects on Helicobacterpylori, but it is not known whether infection withthe organism may itself influence gastric acidityduring omeprazole therapy. It has been reportedthat during treatment with omeprazole, theintragastric pH is higher in patients with duo-denal ulceration than in healthy controls.4 5 It isunclear whether this reduction in gastric acidityis observable in all subjects with H pylori infec-tion, or whether it is confined to a subset ofpatients who develop peptic ulceration. If theincreased susceptibility to omeprazole is relatedsolely to Hpylori infection then Hpyloni negativesubjects and H pylori positive subjects withoutulceration should show different degrees of acid

suppression in response to an equal dose ofomeprazole.To test the hypothesis that Hpylori infection

is associated with decreased intragastric acidityduring treatment with omeprazole, we haveconducted gastric pH-metry in H pylori posi-tive individuals and compared the pH datawith those obtained previously in 14 H pylorinegative individuals.

Methods

SUBJECTSFourteen H pylon negative healthy subjects(seven men and seven women, age range:22-46 years) and 18 H pylori positive subjects(1 1 men and seven women, age range: 22-45years) were studied. Students and employeesof a university hospital who had volunteeredfor an H pylori screening programme were alsoinvited to participate in the present study.H pylori status was determined using the 13Curea breath test performed before enrolmentand confirmed serologically by a specificELISA technique (Roche), in the H pyloripositive group.None of the subjects had a history of gastro-

intestinal disease or other illnesses. At the timeof enrolment, all were asymptomatic and weretaking no medication except the oral contra-ceptive pill or paracetamol. Subjects wereexcluded if they had a history of alcohol ordrug abuse. Smokers were not excluded fromthe study, but they were asked not to smokeduring pH-metry.

All subjects gave written, informed consent,and the study was conducted according to theDeclaration of Helsinki. The protocol wasapproved by the local ethical committee.

PROTOCOL

Treatment planSubjects received a one week course ofomeprazole (20 mg once daily) and a one weekcourse of placebo. The H pylori negativesubjects received placebo and omeprazoletreatment sequentially, following a single blinddesign. The H pylori positive subjects weretreated in a randomised, cross over, doubleblind fashion. Washout periods lasted four tosix weeks between treatments.

24 hourpH-metryAt the end of each one week treatment period,24 hour intragastric pH-metry was performedusing a standard protocol. Subjects arrived at

539

on June 14, 2020 by guest. Protected by copyright.

http://gut.bmj.com

/G

ut: first published as 10.1136/gut.36.4.539 on 1 April 1995. D

ownloaded from

Verdui, Armstrong, Frazer, Viani, Idstrdm, Cederberg, Blum

50

0)

0~~~~~~

-~~~~~~~~E

0 cc C. c

o~~~~W E

omeprazole treatment, after placebo and after washout periods offour to six weeks. Thebroken line shows normnal cut off value for excess d 13C02 per mil,. horizontal bars showmedian values. Four transiently negative breath tests were observed during omeprazoletreatment and one was observed during placebo administration. All subjects had a positiveresult after washout periods.

the laboratory at 08:00 hours after anovernight fast. The pH measuring assemblywas passed through an anaesthetised nostriland positioned fluoroscopically, so that theproximal pH electrode was located in thecorpus, 5 cm from the cardia, and the secondelectrode was located in the antrum. 7.5 cmdistally. Recordings started at 08:30 andstandard meals, prepared in the hospital., wereprovided for all subjects.6 After the supervisedingestion of the study medication at 08:45,subjects returned home with instructions to eatbreakfast at 09:15, lunch at 13:00, and supperat 19:00. At the start of the recording., subjectswere provided with two litres of water to beconsumed during the study., but other bever-ages were not allowed. Subjects retired to bedat 22:00 and arose at 06:00 to return to thelaboratory by 08: 15. The position of theassembly was checked before removal at 08:30.Subjects were instructed to use the eventmarker on the data logger to mark the start andend of each meal, the times at which theyretired to bed and got up., and the occurrenceof any other important event.

EquipmentIntragastric pH measurements were performedusing two combined glass pH electrodes(GK2801C, Radiometer, Copenhagen, Den-mark). The electrodes were covered by asilicon rubber tube (OD/ID 3.0 mm/2.5 mm)with one electrode at the tip and the othersituated at 7.5 cm proximally. The electrodeswere connected to a 512 kbyte memory datalogger (LZ-105, Kaufhiold, Berlin., Germany),in which electrode potentials were stored with-out prior processing. The pH electrodes werecalibrated before and after each recording,usLingstnar ufe solutionsAofpH 1 nC9 andn7.38 at room temperature (S 1368 and S 1356,

Radiometer, Copenhagen, Denmark). At theend of each recording, data were transferred toa computer (Atari-Mega-ST4, Atari Sunny-vale, Ca, USA) running under the OS-9 oper-ating system (Microware, Des Moines, IA,USA), and were transformed to pH valuesafter correction for buffer temperature and 24hour pH electrode drift. Data were transferredto a computer disk for later analysis andstorage.

13C urea breath testIn all subjects, breath tests were performedbefore enrolment. In subjects found to beH pylori positive, additional breath tests wereconducted before and after each treatmentweek. Two breath samples were obtainedbefore and 30 minutes after administration of100 mg of 13C urea mixed in 100 ml orangejuice.7 The ratio 13C02/12C02 was measuredby mass spectrometry; the ratio in the 30minute sample was subtracted from that in thebaseline breath sample and compared with areference value.8 Results were expressed asexcess delta 13C02 per thousand (133C02 permil), and a value of >5 was considered as apositive result.

DATA ANALYSIS AND STATISTICAL EVALUATIONAs in previous studies9 we predefined thefollowing time intervals; entire recording(0830-0830), mealtime periods (0915-1115,1300-1500, 1900-2100), night-time (2200-0600), and the remaining combined non-mealdaytime period. The overall night-time periodwas divided into early (22:00-02:00) and late(02:00-06:00) night-time; individual medianpH values for each period of interest wereobtained for statistical analysis. Summary 24hour pH curves for each individual wereobtained by calculating consecutive 1 minutemedian pH values resulting in 1440 datapoints; group curves are presented as meansfor H pylori positive and H pylori negativegroups.The Mann-Whitney U test was used to

compare median pH values between groupsand the Wilcoxon rank test for paired data wasused to compare pH values within each group.

Multiple comparisons between breath testvalues at enrolment, after treatments, and afterwashout periods were performed using theFriedman test, followed by Wilcoxon-Wilcox.

ResultsFourteen H pylori negative subjects completedthe study and no adverse events attributable toomeprazole were detected. Seventeen H pyloripositive subjects completed the study. Datafrom one H pylori positive subject wereexcluded when the subject was found to beachlorhydric (median 24 hour pH of 6-2during administration of placebo). A secondsubject was withdrawn during omeprazoletreatment and replaced, because of the devel-opment of high transaminase activities whichreturned to normal after stopping treatment.

540

on June 14, 2020 by guest. Protected by copyright.

http://gut.bmj.com

/G

ut: first published as 10.1136/gut.36.4.539 on 1 April 1995. D

ownloaded from

Helicobacter pylori and omeprazole efficacy

Q

Q

0830 2030

Time

Figure 2: Placebo mean pH curves for the corpus (upper), and antrum (lower) 24 hozrecordings in H pylori positive subjects (heavy line) andH pylori negative subjects (tline). Similar median 24 hour gastric pH values were observed in both groups, in thecorpus (p=0 9) and in the antrum (p= 0 1).

13C UREA BREATH TEST AND SEROLOGYThe median a 13C02 per mil did not chafter the placebo treatment period compwith the values obtained at enrolment;subject had a negative breath test after pla(but it became positive after the was]period. The median a 13C02 per millower after omeprazole treatment periodat enrolment (p<OOl) or after pla(p<OO1), but the effect was transient andthe washout period the breath tests were apositive in the four subjects whose breathhad become negative after omeprazole (Fi

All subjects who had a positive breathalso had a positive serology. Transi4negative breath tests were also associatedpositive serology, although serological titrithese four cases were lower than tobtained during enrolment (data not sho

TABLE I Median pH values (95% CI) in the corpus for the entire 24 hour recordingfor other time periods during the placebo and omeprazole treatment phases in Helicobpylori positive (HP+ve) and negative (HP-ve) subjects

Placebo Omeprazole

Time HP+ve HP-ve HP+ve HP-ve

24 Hours 1-5 (1-3-1-7) 1-4 (1-2-2-0) 5-5 (455-56) 4-0 (24(p=0.9 p=0.001

Mealtime 2.3 (2 1-3.0) 2.0 (16-2.9) 5.6 (5 1-5 6) 5.2 (4.1p=0.1 p=0 2

Daytime 1.3 (1.2-1.7) 1-4 (1.2-2.1) 5-4 (4 1-5 6) 2.9 (2.1p=0 5 p=0o00l

Night-time 1 1 (0.9-1.8) 1.1 (1 0-1 8) 4 7 (3 2-5.2) 1 9 (1 <p=03 p=0007

Early night-time 1.0 (0.9-1.2) 0o9 (0.7-1.3) 2.7 (2 1-4.4) 14(14p=0 4 p=0-008

Late night-time 1.4 (1.2-3.1) 1.2 (1 0-1 3) 6 5 (4 2-7.0) 2.1 (1 Ep=0 07 p=0 0007

INTRAGASTRIC pH-METRYDuring placebo administration, the mean 24hour pH curves were similar in the two groupsin both the antrum and corpus, apart from asomewhat higher later nocturnal pH in Hpyloripositive subjects (Fig 2). Similarly, the median24 hour pH values in the two groups were notdifferent and nor were the mealtime, non-mealdaytime, and nocturnal median pH values.However, the late nocturnal median pH valueswere higher in the H pylori positive subjects in

0830 the antrum (p=0 03) but not in the corpus(p=007) (Tables I and II).During omeprazole administration, the

mean 24 hour pH curves in both the antrumand corpus were clearly higher in the H pyloripositive than in the negative subjects, through-out the entire recording period (Fig 3). Themedian 24 hour pH values were higher in theH pylori positive group as were the mediannon-meal daytime and nocturnal pH values;the mealtime pH values were higher in Hpyloripositive subjects in the antrum but not in thecorpus (Tables I and II).

Discussion0830 During omeprazole treatment, the median 24

hour pH values in the Hpylori positive subjectswr were appreciably higher than in the H pylorihin negative subjects. The difference was evident

during the entire recording, except for meal-time periods, but was most noticeable duringthe nocturnal part of the recording. In con-trast, during placebo treatment, the median24 hour pH values did not differ between the

ange two groups and the 24 hour pH profiles weretared similar.one Previous studies have suggested thatcebo omeprazole might produce a greater fall inhout gastric acidity in duodenal ulcer patients thanwas in healthy subjects,4 5 but it was not possible tothan say whether this was a result of the presumedcebo H pylori infection or whether it was associatedafter rather with an ulcer diathesis in these patients.igain The results of the present study suggest that ittests may be the Hpylori infection, and not the ulcerg 1). diathesis, which is associated with the greatertest susceptibility to omeprazole.

ently It seems likely that the H pylori relatedwith accentuation of omeprazole induced gastrices in hypoacidity is prolonged since this interactionhose would be consistent with the efficacy of ome-twn). prazole noted in duodenal ulcer patients.4 5

However, it is not clear whether this inter-and action will persist after eradication ofH pylori,acter and, if it does persist, how long it will be

evident. At present, the mechanisms underly-ing the interaction between H pylori andomeprazole are unknown and it is, therefore,difficult to predict the possible consequences.

6-4-6) It is possible that the presence of H pylori and1-5.8) its subsequent suppression or eradication in

patients with reflux oesophagitis (a disease1-4 3) unrelated to H pylon) may change the thera-3-2.5) peutic efficacy of a given dose of omeprazole. If0-1 9) the H pylori related effect is dependent on the

presence and concentration ofH pylori in the3-5.4) gastric mucosa, it is also possible that the sup-

pression of H pylorn in patients with peptic

541

on June 14, 2020 by guest. Protected by copyright.

http://gut.bmj.com

/G

ut: first published as 10.1136/gut.36.4.539 on 1 April 1995. D

ownloaded from

Verdui, Armstrong, Frazer, Viani, Idstrom, Cederberg, Blum

TABLE II Median pH values (95% CI) in the antrum for the entire 24 hour recordingandfor other time periods during the placebo and omeprazole treatment phases inHelicobacter pylon positive (HP+ve) and negative (HP-ve) subjects

Placebo Omeprazole

Time HP+ve HP-ve HP+ve HP-ve

24Hours 13(1.1-23) 12(1.1-14) 55(45-57) 35(20-42)p=O 1 p=0.0004

Mealtime 1.5 (1.3-2.2) 1.4 (11-1 5) 5.5 (46-5.5) 4.4 (20A48)p=03 p=0.003

Daytime 1.2 (0 9-1 9) 1.2 (10-1 4) 5.6 (44-5.7) 2.8 (1 6-40)p=0-6 p=00003

Night-time 1.5 (14-3 3) 1.2 (10-1-4) 5.8 (3 9-5.9) 2.5 (14-36)p=007 p=0.003

Early night-time 1 1 (1 0-1 6) 1 0 (0 9-1 1) 2.8 (16-4-3) 1.6 (11-21)p=O-O9 p=0-001

Late night-time 4-1 (2.7-48) 1-4 (11-16) 6.8 (60-7.0) 4-3 (1.8-61)p=003 p=0O002

ulcer disease who are pretreated with ome-prazole may alter the efficacy of eradicationregimens which require the concomitantadministration of an antisecretory agent.The mechanisms responsible for the

enhanced effect of omeprazole on intragastricpH in the H pylori positive subjects areunclear. It may be that H pylori has only anindirect effect on the efficacy of omeprazole,related to the development of an immune cellinfiltrate and gastritis. Mononuclear cells pro-duce factors which liberate gastrin10 and stim-ulate acid secretion by histamine release fromenterochromaffin-like cells." 12 It is, there-fore, possible that gastritis is responsible forthe decreased antral somatostatin13-16 and in-creased plasma gastrin17-22 seen in H pyloriinfection. The resulting parietal cell stimula-tion would decrease the intracanalicular pH23leading either to increased transformation ofomeprazole into the active sulphenamideform, or to increased availability of proton

Q

Q.

0830 2030 0830

TimeFigure 3: MeanpH curves for the corpus (upper) and antrum (lower) 24 hour recordingsin H pylon positive subjects (heavy line) and H pylon negative subjects (thin line) duringomeprazole therapy. Gastric acidity was decreased to a much greater extent by omeprazolein H pylon positive subjects (corpus: p= 0 001; antrum: p= 0 0004) than in H pylorinegative subjects.

pumps susceptible to the activated omepra-zole.

It has been reported that H pylori densitydecreases in the antrum and increases in thecorpus after four weeks of omeprazoletherapy.24 25 Theoretically, this could increasethe exposure of parietal cells to a variety of sub-stances released by H pylori which can inhibitacid secretion in vitro.26 27 However, thesubjects in the present study received omepra-zole at a lower dose for only one week and itis unknown whether this would, in fact, beadequate to produce the reported redistribu-tion of H pylori within the stomach and a con-sequent improvement of the gastritis sufficientto affect gastric acidity. The fact that the 13Curea breath test became transiently negative inonly a minority of subjects (Fig 1), suggeststhat the decreased acidity was not due to aneffect of omeprazole on H pyloni density.Confirmation of this supposition would, how-ever, require gastric pH studies earlier andlater during the course of omeprazole therapywith endoscopic biopsies from the antrum andcorpus to monitor changes in H pylori densityand mucosal inflammation.The daytime intragastric pH profiles found

during placebo administration in both groupsare similar and consistent with the pH curvesrecorded in healthy subjects in previousstudies.28 The nocturnal pH increases inH pylori positive subjects appear an exag-geration of the pattern observed in H pylorinegative subjects. We have previously shownthat although nocturnal alkalinisation may bepartly caused by duodenogastric reflux, otherpossibilities, such as mucosal wedging of theantral electrode, must also be considered.9 Themore noticeable peaks in pH found in theH pylori positive group could be explained byan effect of the organism on gastric motility,leading to more rapid gastric emptying of acidor to increased reflux. However, no clearrelationship has been established betweenH pylori infection and altered gastrointestinalmotility.29-32 Acid hyposecretion, as a result ofeither mucosal atrophy33 or direct inhibition ofacid production induced by H pylori infection,is another possible explanation for the highernocturnal pH found in H pylori positivesubjects during omeprazole treatment. It isunlikely that any of the H pylori positivesubjects in this study had gastric mucosalatrophy, since they were, in general, young,and the pH curves during placebo administra-tion showed no evidence of hypoacidity. Onthe other hand, acid secretory inhibitors pro-duced by H pylori have been investigated onlyin vitro26 27 34 and their clinical relevance is notknown.Ammonia and carbamate produced by

H pylori and the consequent neutralisation ofsecreted gastric acid35 36 may also be respon-sible for the increased gastric pH observedduring omeprazole administration in H pyloripositive subjects. Studies investigating thispossible mechanism will probably require pro-longed monitoring of intragastric ammonia.

Although indirect, the current studysuggests an important interaction between

542

on June 14, 2020 by guest. Protected by copyright.

http://gut.bmj.com

/G

ut: first published as 10.1136/gut.36.4.539 on 1 April 1995. D

ownloaded from

Helicobacter pylori and omeprazole efficacy 543

omeprazole and H pylori status. Directevidence will require the investigation ofH pylori positive subjects tested before andafter eradication. As the effects of H pyloriinfection on gastric feedback mechanisms,such as gastrin, may be long lasting,22 37 suchstudies should allow sufficient time afterH pylori eradication for healing of associatedgastritis, which may itself modify gastricacidity.

In conclusion, H pylori infected subjectshave a higher intragastric pH during treatmentwith omeprazole than H pylori negativesubjects, although there is no differencebetween the two groups with regard to gastricacidity in the absence of omeprazole. Furtherstudies are required to determine whether theincreased susceptibility to omeprazole is a con-sequence, directly or indirectly, of H pyloriinfection or whether the increased omeprazoleefficacy and H pylori infection are co-pheno-mena associated with another underlyingabnormality.Supported by Swiss National Fund 32-36349.92.

1 Mauch F, Malfertheiner P, Bode G. Identification of anATPase-system of Helicobacter pylori and its affection bybenzimidazoles. Acta Gastroenterol Belg 1993; 56: A53.

2 Michetti P, Corthesy-Theulaz I, Porta N, Racine L,Kraehenbuhl J-P, Blum AL. T84 human intersticial cellmonolayers as a model to study adhesion and intra-epithelial penetration of Helicobacter pylori. ActaGastroenterol Belg 1993; 56: A116.

3 Rune S. Helicobacter pylori, peptic ulcer disease and inhibi-tion of gastric acid secretion. Digestion 1992; 51: 11-6.

4 Cederberg C, Thomson ABR, Mahachai V, Westin JA,Kirdeikis P, Fisher D, et ad. Effects of oral omeprazole on24-hour intragastric acidity in duodenal ulcer patients.Gastroenterology 1992; 103: 913-8.

5 Cederberg C, Rohss K, Lundborg P, Olbe L. Effect of oncedaily intravenous and oral omeprazole on 24-hour intra-gastric acidity in healthy subjects. Scand Jf Gastroenterol1993; 28: 179-84.

6 Margalith D, Duroux P, Bauerfeind P, Emde C, Koelz H-R,Biollaz J, et al. Famotidine should be taken with supper:the effect of drug-meal interactions on gastric acidityand plasma famotidine levels. European Journal ofGastroenterology and Hepatology 1991; 3: 405-12.

7 Logan RP, Polson RJ, Misiewicz JJ, Rao G, Karim NQ,Newell D, et al. Simplified single sample "Carbon ureabreath test for Helicobacter pylori: comparison withhistology, culture, and ELISA serology. Gut 1991; 32:1461-4.

8 Klein PD. Clinical applications of 13CO2 measurements.Federation Proceedings 1982; 41: 2698-701.

9 Verdui E, Fraser R, Armstrong D, Murphy G, Blum AL.Duodenogastric reflux (DGR) monitoring: is gastricpH-metry adequate? Gastroenterology 1993; 104: A218.

10 Calam J, Golodner EH, Walsh JH, Soll AH. Mononuclearcells, but not H pylori, release gastrin from culturedG-cells via diffusible factors. Gut 1993; S3: W1 1.

11 Andersson K, Mattsson H, Larsson H. The role of gastricmucosal histamine in acid secretion in experimentallyinduced lesions in rats. Digestion 1990; 46: 1-9.

12 Tari A, Yamamoto G, Sumii K, Sumii M, Takehara Y,Haruma K, et al. Role of histamine2 receptor in increasedexpression of rat gastric H+-K+-ATPase cs-subunitinduced by omeprazole. Am_Physiol 1993; 265: G752-8.

13 Karnik PS, Monahan SJ, Wolfe MM. Inhibition of gastringene expression by somatostatin. Jf Clin Invest 1989; 83:367-72.

14 Kaneko H, Nakada K, Mitsuma T, Uchida K, Furusawa A,Maeda Y, Morise K. Helicobacter pylori infection inducesa decrease in immunoreactive-somatostatin concentra-tions of human stomach. Dig Dis Sci 1992; 37: 409-16.

15 Lamers CBHW. Gastric secretory abnormalities in duo-denal ulcer: primary or secondary to Helicobacter pyloriinfection? ScandJ3 Gastroenterol 1992; 27: 99-103.

16 Moss SF, Legon S, Bishop AE, Polak JM, Calam J. Effect ofHelicobacter pylori on gastric somatostatin in duodenalulcer disease. Lancet 1992; 340: 930-2.

17 Queiroz DMM, Mendes EN, Rocha GA, Moura SB,Resende LMH, Barbosa AJA, et al. Effect ofHelicobacter pylori eradication on antral gastrin - andsomatostatin - immunoreactive cell density and gastrinand somatostatin concentrations. Scand J Gastroenterol1993; 28: 858-64.

18 Brady III CE, Hadfield TL, Hyatt JR, Utts SJ. Acidsecretion and serum gastrin levels in individuals withCampylobacter pylori. Gastroenterology 1988; 94: 923-7.

19 Levi S, Beardshall K, Haddad G, Playford R, Ghosh P,Calam J. Campylobacter pylori and duodenal ulcers: Thegastrin link. Lancet 1989; 27: 1167-8.

20 McColl KEL, Fullarton GM, El Nujumi AM, MacDonaldAM, Brown IL, Hilditch TE. Lowered gastrin and gastricacidity after eradication of Campylobacter pylori induodenal ulcer. Lancet 1989; 26: 499-500.

21 Smith JTL, Pounder RE, Nwokolo CU, Lanzon-Miller S,Evans DG, Graham DY, et al. Inappropriate hyper-gastrinaemia in asymptomatic healthy subjects infectedwith Helicobacter pylori. Gut 1990; 31: 522-5.

22 El Omar E, Penman I, Dorrian CA, Ardill JES, McCollKEL. Eradicating Helicobacter pylori infection lowersgastrin mediated acid secretion by two thirds in patientswith duodenal ulcer. Gut 1993; 34: 1060-5.

23 Helander HF, Fryklund J, Wallmark B. Structure andfunction of isolated gastric glands. Gastroenterology 1987;92: A1431.

24 Labenz J, Gyenes E, Ruhl GH, B6rsch G. Amoxicillin-omeprazole for eradication of Helicobacter pylori. In:Pajares JM, Pefta AS, Malfertheiner P, eds. Helicobacterpylori and gastroduodenal pathology. Berlin/Heidelberg:Springer-Verlag, 1993: 342-6.

25 Logan RPH, Walker MM, Gummett PA, Misiewicz JJ,Baron JH. The effect of omeprazole on Helicobacterpylori infection. Hepatogastroenterology 1994; 41: A94.

26 Beil W, Birkholz C. Inhibition of H+/K+ ATPase by fattyacids produced by Helicobacter pylori. Gastroenterology1993; 104: A41.

27 Danon SJ, Lee A, Larsson H. Acid inhibitory factors ofHelicobacter pylori fact or artefact? Gastroenterology 1993;104: A688.

28 Cilluffo T, Armstrong D, Castiglione F, Emde C, GaleazziR, Gonvers J-J, Blum AL. Reproducibility of ambulatorygastric pH recordings in the corpus and antrum Effect offood, time, and electrode position. Scand Jf Gastroenterol1990; 25: 1076-83.

29 Prakash C, Marshal BJ, Plankey MW, Guerrant R,McCallum RW. Gastric emptying of solids in patientswith Campylobacter pylori gastritis. Am J Gastroenterol1987; 82: A53.

30 Wegener M, Borsh G, Schaffstein J, Schulz-Flake C, MaiU, Leverkus F. Are dyspeptic symptoms in patients withCampylobacter pylori-associated type B gastritis linked todelayed gastric emptying? Am Jf Gastroenterol 1988; 83:737-40.

31 Waldron B, Smith D, Campbell FC. Gastroparesis,acid secretion and Helicobacter pylori colonisation infunctional dyspepsia. Gut 1993; S4: T175.

32 Pieramico 0, Ditschuneit H, Malfertheiner P.Gastrointestinal motility in patients with non-ulcerdyspepsia: a role for Helicobacter pylori infection?Am J Gastroenterol 1993; 88: 364-8.

33 Katelaris PH, Seow F, Lin BPC, Napoli J, Ngu MC, JonesDB. Effect of age, Helicobacter pylori infection, andgastritis with atrophy on serum gastrin and gastric acidsecretion in healthy men. Gut 1993; 34: 1032-7.

34 Vargas M, Lee A, Fox JG, Cave DR. Inhibition of acidsecretion from parietal cells by non-human-infectingHelicobacter species: a factor in colonization of gastricmucosa? Infect Immun 1991; 59: 3694-9.

35 Triebling AT, Korsten MA, Dlugosz JW, Paronetto F,Lieber Ch. Severity of Helicobacter-induced gastric injurycorrelates with gastric juice ammonia. Dig Dis Sci 1991;36: 1089-6.

36 Mobley HLT, Hausinger RP. Microbial ureases: signifi-cance, regulation, and molecular characterization.Microbiol Rev 1989; 53: 85-108.

37 McColl KEL, Fullarton GM, Chittajalu R, El Nujumi AM,MacDonald AMI, Dahill SW, et al. Plasma gastrin, day-time intragastric pH, and nocturnal acid output beforeand at 1 and 7 months after eradication of Helicobacterpylori in duodenal ulcer subjects. Scand J Gastroenterol1991; 26: 339-46.

on June 14, 2020 by guest. Protected by copyright.

http://gut.bmj.com

/G

ut: first published as 10.1136/gut.36.4.539 on 1 April 1995. D

ownloaded from