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`Gut, 1989, 30, 573-578
`
`Comparison of gastric body and antral pH: a 24 hour
`ambulatory study in healthy volunteers
`
`G McLAUCHLAN, G M FULLARTON, G P CREAN, AND K E L McCOLL
`From the University Department of Medicine, Western Infirmary, Glasgow and Gastrointestinal Centre,
`Southern General Hospital, Glasgow
`
`SUMMARY Simultaneous ambulatory records of gastric antral and body pH were made over 24
`hours in nine healthy volunteers by means of endoscopically positioned and anchored glass
`electrodes. Intragastric pH was temporarily raised after the endoscopy with the median pH value 30
`minutes after the procedure being 3.9 (range 1 5-70) for the antrum and 4.1 (range 1 5-70) for the
`body. Daytime pH (median pH value between 1200 h and 2300 h) was lower in the antrum
`(median=1.9, range 16-2.6) than in the body (median=2.7, range 1.8-45) (p<0O05) and this was
`because of the rise in pH on eating being less marked in the antrum than in the body. The median
`peak pH recorded during the evening meal was only 4.1 (range 24-642) in the antrum compared
`with 6.3 (range 4.4-6.7) in the body (p<001). Preprandial pH (median value over the hour prior to
`the evening meal) was similar in the antrum (median= 1 9, range 1 2-25) and body (median= 1 9,
`range 1.3-28). Night-time pH (median pH value between 2300 h and 0500 h) in six subjects
`remained low and was similar in the antrum (median= 14, range 12-1.7) and body (median=13,
`range 11-1-7). In two subjects, however, there were episodes of raised night-time pH which were
`more marked in the antrum than in the body. Antral biopsies showed gastritis in four of the nine
`normal volunteers, which in three was associated with the presence of campylobacter-like
`organisms. This study shows the significant regional variations in day and night-time intragastric
`pH.
`
`Over the past decade there has been a dramatic
`increase in the use of ambulatory pH monitoring of
`the upper gastrointestinal tract (GIT) for research
`purposes and as an aid to diagnosis. Previously, most
`studies of intragastric pH depended on the analysis of
`aspirated gastric juice and had several shortcomings.
`Gastric aspiration may invoke duodenogastric reflux
`or stimulate acid secretion' and may be difficult after
`a solid meal or during the night when little juice is
`present in the stomach.3 The use of in situ pH
`electrodes overcomes these problems and also allows
`the monitoring of pH in specific regions of the
`stomach rather than just giving a mean intragastric
`value. Because of the problems of maintaining the
`position of electrodes within the stomach, little is
`
`known about regional variations in intragastric pH
`under conditions of normal daily living.4 Using a
`technique developed to allow accurate localisation of
`electrodes within the upper gastrointestinal tract
`(GIT), we have monitored simultaneously the pH of
`the body and antrum of the stomach over a 24 h
`period in nine healthy volunteers.
`
`Methods
`
`SU BJ ECTS
`Four male and five female healthy volunteers ranging
`in age from 20-56 years were studied. None had any
`gastrointestinal tract (GIT) symptoms or history of
`gastrointestinal problems. Four of the subjects were
`smokers (numbers 1, 2, 8, and 9).
`
`Address for correspondence: Dr Kenneth E L McColl. University Department
`of Medicine, Western Infirmary, Glasgow G 11 6NT.
`Accepted for publication 20) Octoher 1988.
`
`EXPERIMENTAL DESIGN
`The volunteers were admitted to our investigational
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`574
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`unit for the 24 hours of the study. At approximately
`0900 h, and with the subjects fasted since the
`previous evening, two combined glass electrodes
`(Radiometer GK2802C) were positioned endo-
`scopically with one anchored to the antral mucosa
`and the other 10 cm proximal in the body of the
`stomach. On withdrawal of the endoscope the elec-
`trodes were connected to a Digitrapper Mark II Gold
`(Synectics) solid state instrument which records the
`pH from each electrode every four seconds. On
`recovery from the sedation, the subjects were fully
`ambulatory and the pH recordings continued until
`the following morning. They consumed the normal
`hospital meals consisting of breakfast (taken one
`hour after the endoscopy), mid-morning tea and
`biscuit, lunch, mid-afternoon coffee and biscuit,
`dinner, and evening snack. They went to bed
`between 22 00 h and 23 0() h and rose between 06 00 h
`and 07 00 h. At the end of the 24 h recording period
`the electrodes were withdrawn, with the fixation clips
`still attached, by traction on the leads.
`
`ENDOSCOPIC PROCLDURE
`The technique of anchoring the electrodes in position
`endoscopically has been comprehensively described
`in a previous publication.' The two electrodes are
`attached to each other by Micropore tape so that one
`is 10 cm distal to the other and two short loops of
`nylon thread are attached to the distal electrode. The
`electrodes are then passed orogastrically alongside a
`wide channel endoscope (Olympus ITIO) and the
`distal electrode secured in the antrum by clipping
`both nylon loops to the mucosa using a clip fixing
`device (Olympus HX-2L). At the time of the endo-
`scopy a biopsy of the antrum was taken for histo-
`logical
`examination.
`subjects
`All
`received
`Midazolam (Hypnovel) 4 mg iv immediately before
`endoscopy.
`The electrodes were calibrated in buffers of pH
`7-01 (Synectics 5001) and pH 1-07 (Synectics 5002) at
`the start and end of each recording. The clip fixing
`device and the electrodes were sterilized by immer-
`sion in 2% glutaraldehyde for one hour.
`
`pH ANALIYSIS
`The data from the Digitrapper were stored on an
`Amstrad PC 1512 microcomputer. Detailed analysis
`was done of daytime and night-time pH. Daytime pH
`was taken as 12(00 h-23 00 h as the period before
`1200 h was affected by the endoscopic procedure.
`Night-time pH was taken as 23 00 h-O5 00 h so that it
`included only that time when patients were recum-
`bent in bed. The pH changes associated with the
`evening meal and with the endoscopy were analysed
`in greater detail. The Gastrosoft software package
`(Synectics) was used to obtain median pH values for
`
`M7 cLauichlaln, FiLllarton, Crean, and Mc( oll
`
`each individual over the different time periods
`studied.
`Statistical
`significance
`differences
`of
`between the values for the antrum and body was
`assessed using the Wilcoxon's signed-rank test for
`paired data.
`
`HIS 0 LLOGY
`The gastric biopsies were examined in a single
`blind fashion using haematoxylin and cosin stain.
`Campylobacter-like organisms were identified by the
`fast cresyl violet stain.
`Each subject gave written informed consent to the
`study which was approved by the Southern General
`Hospital Ethical Committee.
`
`Results
`
`In each subject the electrodes were confirmed to have
`remained firmly anchored in place by observing
`transient resistance to dislodgement on removal of
`the electrodes and by the presence of fresh blood
`and tissue in the retrieved clips. The drift of the
`electrodes over the 24 h recording period was
`negligible with the end calibration values always
`being within 0( 15 pH units of the initial values.
`Malfunction of the recording equipment prevented
`analysis of the daytime pH in one subject and of the
`night-time pH in another subject.
`
`pH IMMEDIAITII.Y AFTER ENDOSCOPY
`The pH of the antrum and body was higher immedi-
`ately after the endoscopy compared with other
`fasting periods. Thirty minutes after the placement
`procedure, the antral pH ranged from 1 5-7-0
`(median=3.9) and body pH from 1-5-7-0 (median=
`4.1). In contrast, preprandial antral pH (median pH
`value for each individual over the hour before the
`evening meal) ranged from 1-2-2 5 (median= 1.9)
`and preprandial body pH from 1 3-2-8 (median= 1.9)
`(Table 1). After the endoscopy, the median time for
`the pH to return to preprandial values was 54 minutes
`(range 0-I 10) for the antrum and 57 minutes (range
`0-120) for the body. There was no significant
`difference between the pH readings in the antrum
`and body after endoscopy. The pH tracing of subject
`no 3 illustrating the effect of the endoscopy is shown
`in Figure 1.
`
`DAYTIME pH
`In seven of the eight subjects, the daytime pH - that
`is, median pH value between 1200 h and 2300 h,
`which included prandial and postprandial periods
`was lower in the antrum than in the body (Table 2).
`The median daytime pH of the eight subjects was 2 7
`(range 18-4X5) for the body compared with 1.9
`(range 16-2 6) for the antrum (p<005). Likewise,
`
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`Comparison ofgastric body and antralpH: a 24 hour ambulatory study in healthy volunteers
`
`575
`
`Table 1
`
`Effect ofevening meal on the pH ofthe gastric body and antrum
`
`Subject no
`
`Preprandial
`pHt
`
`Delay in pH
`rise after starting
`meal
`
`Time to reach peak
`pH after starting
`meal (min)
`
`Peak pH during
`meal
`
`Time to return to
`basal pH after starting
`meal (min)
`
`1
`
`2
`
`3
`
`Body
`Antrum
`Body
`Antrum
`Body
`Antrum
`Body
`Antrum
`Body
`Antrum
`Body
`Antrum
`Body
`Antrum
`Body
`Antrum
`Median values Body
`Antrum
`
`4
`
`5
`
`6
`
`7
`
`8
`
`2-2
`2-0
`2-8
`2-5
`1-4
`1-9
`1-4
`1.5
`2-1
`2-1
`2-2
`2-2
`1-8
`1-6
`1-3
`1-2
`1-9
`1-9
`
`45 (sec)
`30 (min)
`16 (sec)
`11 (min)
`8 (sec)
`1 (min)
`240 (sec)
`6 (min)
`60 (sec)
`6 (min)
`16 (sec)
`9 (min)
`16 (sec)
`6 (min)
`50 (sec)
`2 (min)
`30 (sec)
`6 (min)*
`
`21
`45
`12
`28
`24
`43
`20
`40
`7
`13
`16
`53
`8
`30
`6
`34
`14
`37*
`
`4.4
`2.4
`6-6
`4-5
`6-4
`4-1
`6-6
`4-2
`6-2
`4-5
`6-7
`6-2
`4-4
`2-4
`4 4
`3-0
`6-3
`4 1'
`
`210
`210
`63
`86
`95
`126
`127
`136
`121
`201
`130
`94
`120
`126
`45
`37
`120
`126
`
`*Significantly greater than body with p=0-01; 'Significantly less than body with p<0-01; tPreprandial pH represents the median value over
`the hour before the evening meal.
`
`E c
`
`1ii
`
`Time (h)
`Twenty four hour ambulatory simultaneous pH recordings ofgastric antrum and body in subject number 3. This
`Fig. 1
`shows the increased pH after the endoscopy and the fact that eating increases body pH more than antral pH. In contrast,
`episodes ofincreased nocturnal pH are more pronounced in the antrum than in the body.
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`576
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`McLauchlan, Fullarton, Crean, and McColl
`
`Table 2
`
`Daytime and nighlt-time pH ofgastric body and antrum
`
`Suibject nio
`
`Mediani pH
`
`%pH<3
`
`Median pH
`
`%pH<3
`
`Mediati pH
`
`%poH<3
`
`Daytime (12 00 h-23 00 h)
`
`Night-time (23 00 h-OS 00 h)
`
`Day+night (12 00 0-0)500 h)
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`Median values
`
`3-2
`22
`2-5
`2-4
`2-0
`1-8
`1.8
`1-9
`3-1
`2-6
`3-0
`2-0
`1.9
`1-7
`4*5
`1-6
`
`-
`
`-
`
`Body
`Antrum
`Body
`Antrum
`Body
`Antrum
`Body
`Antrum
`Body
`Antrum
`Body
`Antrum
`Body
`Antrum
`Body
`Antrum
`1-3
`Body
`1-3
`Antrum
`2 7
`1-4
`Body
`59
`Antrum
`1.9*
`90+
`1-5
`*Significantly less than body with p<00(5; 'Significantly greater than body with p<0O05.
`
`1-6
`1.5
`1.7
`1-7
`2-0
`3-2
`1.3
`1-5
`3-6
`4-4
`1
`1
`1.2
`1-1
`182
`
`46
`92
`27
`95
`81
`83
`79
`77
`56
`64
`63
`89
`87
`1K)
`39
`96
`
`-
`
`-
`
`100
`97
`88
`89
`89
`60
`1(K)
`98
`46
`34
`100
`1(H)
`100
`4
`
`-
`
`100
`100
`1(X)
`93*
`
`2-7
`18
`2-3
`2 2
`2(0
`22
`1-6
`1-6
`3.2
`3-1
`1-6
`1-7
`1.7
`16
`
`-
`
`2-0
`1-8
`
`65
`94
`48
`91
`84
`75
`87
`85
`53
`53
`70
`93
`93
`94
`
`-
`
`70
`91
`
`the percentage daytime pH<3 was higher for the
`antrum (median=90%) than for the body (median=
`59%) (p<O-05).
`More detailed analysis showed that the difference
`in daytime pH between the body and antrum was not
`caused by differences in the preprandial pH but in the
`pH response to meals. The preprandial pH (median
`value over the hour before starting the evening meal)
`of the eight subjects ranged from 1-3 to 2-8 (median=
`1.9) for the body which was similar to the values for
`the antrum (range, 1-2-2-5; median=1.9) (Table 1).
`On commencing to eat, the antral pH was later than
`the body pH in starting to rise and also in reaching its
`peak pH (Table 1). The median time for the body pH
`to begin to rise after starting the evening meal was 30
`seconds (range 8-60 seconds) compared with six
`minutes (range two to 30 minutes) for the antrum
`(p=0.01), and the median time for the body to reach
`its peak prandial pH was 14 minutes (range six to 24
`minutes) compared with 37 minutes (range 13-53
`minutes) for the antrum (p=0.01). The two regions
`of the stomach also differed with respect to the peak
`pH achieved during the evening meal. The peak pH
`values for the body ranged from 4-4-67 (median=
`6.3) and for the antrum 2-4-6-2 (median=4.1)
`(p<0-01). The time for the pH to return to prepran-
`dial levels after starting the evening meal was similar
`
`in the body (median= 120 minutes) and antrum
`(median= 126 minutes). The pH tracing of subject no
`7 illustrating the differing pH response of the body
`and antrum on eating is shown in Figure 2.
`
`NIGHT-TIME pH
`The night-time pH (median value between 2300 h
`and 0500 h) of the individual subjects varied from
`1.2-44 (median= 1.5) for the antrum and was similar
`for the body (range 1-1-3.6, median=1.4). There
`were clear differences, however, in the night-time pH
`between the eight individuals. In six the night-time
`pH showed little, if any, fluctuation with the pH of
`the body being less than 3 for more than 88% of the
`time and the pH of the antrum being less than 3 for
`more than 84% of the time (Table 2). Two of the
`female subjects (numbers 3 and 5) showed a different
`pattern having well defined episodes of raised antral
`and body pH throughout the night. On each of
`the occasions, the rise in pH was evident in both
`electrodes although usually more marked and pro-
`longed in the antral electrode (Fig. 1). The duration
`of the episodes of raised pH recorded by the antrum
`electrodes in these two patients varied from 40-90
`minutes and the peak pH reached during the episodes
`varied from 3-5-7. The episodes of raised pH were
`more pronounced in patient number 5 who was the
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`Comparison ofgastric body and antral pH: a 24 houir amblulatory studv in healthy volunteers
`
`577
`
`pH
`
`Meal
`
`0
`
`E
`
`4
`
`2
`
`V
`
`-- -''-
`
`Discussion
`The first unexpected finding from this study was that
`intragastric pH when measured using in situ glass
`electrodes, is markedly increased after upper gastro-
`intestinal endoscopy and may reach neutral values.
`The reason for this is not clear. Midazolam, which
`was the only premedication used, is not known to
`interfere with gastric secretion or motility. The high
`pH readings could be related to the aspiration of the
`gastric juice and insufflation of air during the endo-
`scopic examination. In addition, retching during the
`endoscopy is likely to cause duodenogastric reflux of
`alkaline juices. Whatever the explanation, the obser-
`vations should be borne in mind if pH readings are
`taken for diagnostic or research purposes at endo-
`scopy as they do not reflect normal fasting gastric
`values. Because of the effect of the endoscopic
`procedure, detailed analysis of our data was started
`at 12 00 h, three hours after the procedure.
`The premeal daytime pH was similar in the antrum
`and body but the rise in pH with eating was more
`immediate and more marked in the body. Though
`there has been no previous study of regional varia-
`tions in gastric pH using fixed electrode position,
`Fimmel et al monitored body and antral pH in four
`using
`healthy
`positioned
`electrodes
`volunteers
`fluoroscopically.6 They found also that the pH of
`the two regions was similar during fasting and that
`eating resulted in a more marked rise in pH in the
`body than in the antrum. Intragastric pH rises on
`eating because of the buffering effect of the food
`exceeding the meal stimulated increase in acid secre-
`tion. As the latter does not peak until 60-90 minutes
`after starting to eat,' the rise in intragastric pH is most
`pronounced shortly after starting to eat when the
`buffering effect of the food predominates. In the
`in gastric body pH was
`present study the rise
`maximum 14 minutes after starting to eat, and then
`fell even though gastric emptying of a solid meal does
`not usually begin until 27 minutes after starting the
`meal.' This subsequent fall in pH can be explained
`by the increasing acid output overwhelming the
`buffering capacity of the food. Our finding that the
`rise in pH was later and less inthe antrum compared
`with the body can be explained by previous scinti-
`graphic observations that a solid meal is initially
`concentrated in the body and then 'fed' into the
`antrum.' By the time the food reaches the antrum its
`buffering effect will be largely overcome by the
`increasing acid secretion. In addition the slower rate
`of delivery of the food into the antrum will minimise
`its buffering effect. The differences in gastric body
`and antral pH observed after the solid meal are
`consistent with the observation made by Eyerly and
`Breuhaus 50 years ago that the stomach acts more
`like a hopper than a churn.'
`
`.
`
`.
`
`l
`
`.
`
`.
`
`1700
`
`1
`
`sz1
`1900
`Time (h)
`Fig. 2
`Effect of evening meal on the pH of the gastric
`antrum and body in subject number 7 whiose tracings are
`representative ofthe subjects studied.
`
`oldest patient studied (56 years) than in patient
`number 3 who was the second oldest (45 years).
`
`DAYTIME AND NIGHT-TIME pH COMBINED
`When the median pH values were calculated for each
`individual for the entire daytime and night-time
`period (1200 h-O5 00 h) there was no significant
`difference between the body and antrum, the values
`ranging from 16-3 2 (median=2.0) for the former
`and 16-3.1 (median= 1.8) for the latter (Table 2).
`
`ANTRAL BIOPSIES
`The histology of the antral biopsies was normal in five
`of the subjects but in four (nos 2, 3, 5, and 9) there
`was evidence of chronic superficial gastritis with
`infiltration of lymphocytes and plasma cells in the
`lamina propria. Campylobacter-like organisms were
`present in three (nos 2, 3, and 9) of these four
`subjects with gastritis. Both of the subjects with
`periods of raised night-time pH had gastritis and in
`subject number 5 who had the most pronounced
`episodes of raised night-time pH the gastritis was not
`associated with Campylobacter-like organisms.
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`McLauchlan, Fullarton, Crean, and McColl
`
`The night-time pH in most of the subjects was low
`and showed little fluctuation consistent with the
`fasting state. In the two oldest subjects studied,
`however, the pH rose considerably for variable
`periods of time throughout the night. The fact that
`the distal electrode was secured in the antrum and
`also that the rise in pH affected both electrodes
`means that the changes could not be explained by
`displacement of the electrode into the duodenum or
`oesophagus. Interestingly, the rise in pH in the
`antrum was usually more marked than that in the
`more proximal body electrode, this pattern being
`opposite to that occurring after a meal. These obser-
`vations would be consistent with the rises in gastric
`pH being the result of duodenogastric reflux of
`alkaline juices. Fimmel et al studied 24 h intragastric
`pH using a single unfixed electrode in normal volun-
`teers and noted similar periods of elevated pH in a
`proportion of their subjects which they also attrib-
`uted to duodenogastric reflux.5 Previous studies have
`showed duodenogastric reflux in healthy volunteers
`both in the fasting state and after meals.1"-'4
`In spite of the fact that all our patients were
`asymptomatic healthy volunteers, four ofthe nine
`antral biopsies showed evidence of gastritis and in
`three of these Campylobacter-like organisms were
`also identified. This is consistent with the study by
`Jones et al which demonstrated circulating antibodies
`to Campylobacter in 16-49% of healthy volunteers.'5
`A high correlation exists between the antibody and
`the presence of the bacterium and gastritis in antral
`biopsies.'6 Duodenogastric reflux has been suggested
`as a cause of gastritis'7-'9 and in this study the two
`subjects with episodes of raised nocturnal gastric pH
`both had evidence of gastritis. In the subject with the
`most marked episodes of raised nocturnal pH, the
`gastritis was not associated with Campylobacter.
`By showing differences in the pH of the antrum
`and body of the stomach during the day and night this
`study emphasises the fact that intragastric pH is not a
`single entity.
`
`The authors wish to acknowledge the helpful advice
`of Dr Michael Lucas, Department of Physiology,
`University of Glasgow, in the preparation of this
`manuscript.
`
`References
`
`1 Eyerly JB. Comparative pH values within the stomach,
`pylorus and duodenum in antacid therapy. Am J Dig Dis
`1940; 7: 431-4.
`2 Schlotthauer B, Noller HG. Ergebnisverfalschungen bei
`
`gastritis:
`
`der Magenuntersuchung, bedingt durch die Schlauch-
`technik. Munchner Med Wochenschr 1964; 17: 785-9.
`3 Levin E, Kirsner JB, Palmer WL, Butler C. The
`variability and periodicity of the nocturnal gastric secre-
`tion in normal individuals. Gastroenterology 1948; 10:
`939-51.
`4 Emde C, Garner A, Blum AL. Technical aspects of
`intraluminal pH-metry in man: current status and
`recommendations. Gut 1987; 28: 1177-88.
`5 McLauchlan G, Buchanan NMM, Crean GP, McColl
`KEL. An endoscopic procedure for accurate localisa-
`tion of intraluminal pH electrodes. Endoscopy 1987; 19:
`124-6.
`6 Fimmel CJ, Etienne A, Gilluffo T, et al. Long-term
`ambulatory gastric pH monitoring: validation of a new
`method and effect of H2-antagonists. Gastroenterology
`1985; 88: 1842-51.
`7 Bauerfeind P, Cilluffo T, Fimmel CJ, et
`al. Die
`Schweiz
`Langzeit-pH-Metrie.
`intragastrale
`Med
`Wochenschr 1985; 115: 1630-41.
`8 Fordtran JS, Walsh JH. Gastric acid secretion rate and
`buffering content of the stomach after eating. J Clin
`Invest 1973; 52: 645-57.
`9 Robinson PH, Clarke M, Barrett J. Determination of
`delayed gastric emptying in anorexia nervosa and
`bulimia nervosa. Gut 1988; 29: 458-64.
`10 Eyerly JB, Breuhaus HC. A method of measuring
`acidity and protein digestion within the human stomach.
`Am J Dig Dis 1939; 6: 187-92.
`11 Muller-Lissner SA, Fimmel CJ, Sonnenberg A, et al.
`Novel approach to quantify duodenogastric reflux in
`healthy volunteers and in patients with type 1 gastric
`ulcer. Gut 1983; 24: 510-8.
`12 Keane FB, Dimagno EP, Malagelada JR. Duodenogas-
`tric reflux in humans: its relationship to fasting antro-
`duodenal motility and gastric, pancreatic, and biliary
`secretion. Gastroenterology 1981; 81: 726-31.
`13 Heading RC. Duodenogastric reflux. Gut 1983; 24:
`507-9.
`14 Hostein J, Bost R, Faure H, Lachet B, Fournet J.
`Valeur diagnostique de la pHmetrie gastrique au cours
`du reflux duodeno-gastrique. Gastroenterol Clin Biol
`1987; 11: 206-11.
`15 Jones DM, Eldridge J, Fox AJ, Sethi P, Whorwell PJ.
`Antibody to the gastric campylobacter-like organism
`('Campylobacter pyloridis') - clinical correlations and
`distribution in the normal population. J Med Microbiol
`1986; 22: 57-62.
`16 Jones DM, Lessells AM, Eldridge J. Campylobacter-
`like organisms on the gastric mucosa: culture, histo-
`logical and serological studies. J Clin Pathol 1984; 37:
`1002-6.
`17 O'Connor HJ, Wyatt JI, Dixon MF, Axon ATR.
`Campylobacter like organisms and reflux gastritis. J Clin
`Pathol 1986; 39: 531-4.
`18 Niemela S, Karttunen T, Heikkila J, Lehtola J.
`Characteristics of reflux gastritis. Scand J Gastroenterol
`1987; 22: 349-54.
`19 Ritchie
`Alkaline
`IJP.
`reflux
`reappraisal. Gut 1984; 25: 975-87.
`
`a
`
`critical
`
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