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A disposable probe to measure the esophageal acid burden
A250
AGA ABSTRACTS
@ EFFICACY AND TOLERANCE OF PANTOPRAZOLE 40MG VS 80MG IN
PATIENTS WITH REFLUX OESOPHAGITIS - A MULTICENTRE STUDY 'C van Rensburo 1, P Honiball2, H Grundling 3, J van Zyl 3, Spies 2, G De V_os2, F El.off2, J Lo_uw4, A Cariem 4, A Simjee% S SegalS, J Botha b, I Marks4, I Theron/, T Bethke/. Depts. o~ Medicine & G~stroenterolog,y, Univ~.rsities of Stellenbosc~ 1, Pretoria% BJ,oemfontein°,Cape Town'*, NataW and Witwatersrand ~ and ./ Byk Gulden . Pantoprazole (Pz) is a new H +K + , -ATPase inhibitor. AIM: To compare the efficacy and tolerance of Pz 40 mg versus Pz 80 mg taken orally in the morning in patients with moderate to severe reflux oesophagitis (RO). PATIENTS AND METHODS: 192 outpatients (intention-to-treat; 97 on 40mg and 95 on 80rag) of both sexes with endoscopically confirmed RO (stag e II or III Savary/Miller classification) were entered. The primary evaluation criterion was end0scopically confirmed complet e healing of the RO. Improvement in typical reflux symptoms and other gastrointestinal symptoms, as well as drug tolerability and safety were recorded. Healing rates after 4 and 8 weeks were analysed using the Cochran/ManteI-Haenszel method. RESULTS: 86/97 patients entered into the40 mg Pz group and 87/95 in the 80 mg Pz group completed the study as per protocol. Nineteen patients were excluded from the protocol-correct analysis due to protocol violations (Pz 40rag 11, Pz 80rag 8). The healing rates after 4 weeks were 78% in the 40 mggroup and 72% in the 80 mg group. The cumulative healing rates after 8 w,eeks were 95% and 94%, respectively (p >0.05. Cochran/ManteI-Haenszel}, and time until healing of RO comparable in both groups. Differences between doses were also not significant in an intention-to-treat analysis. Both dosing schedules were well tolerated and the patients experienced remarkable symptom relief. No adverse events could definitely be ascribed to the trial medication, furthermore there were no changes in laboratory values of clinical significance. CONCLUSION: The 40 mg Pz dosage is comparable to the 80 mg dosage in RO; both in efficacy and tolerability.
• T H E E F F E C T O F E R A D I C A T I O N OF H E L I C O B ~ C T E R PYLORI (Hp) ON S Y M P T O M S OF N O N - U L C E R D Y S P E P S I A (NUD): A R A N D O M I Z E D D O U B L E - B L I N D P L A C E B O C O N T R O L L E D TRIAL. S V e l d h u y z e n v a n Zanten, D Malatjalian, R Tanton, D Leddin, R H Hunt, W B l a n c h a r d et al. D a l h o u s i e and MoMaster, Halifax, H a m i l t o n Canada~ H p m a y p l a y a r o l e in N U D b u t to d a t e t r e a t m e n t trials have suffered frommethodologic flaws. W e ~ r e v i o u s l y v a l i d a t e d a s y m p t o m score for u s e as o u t c o m e m e a s u r e (J C l i n E p i d e m i o l 1 9 9 3 ; 4 6 : 2 7 3 ) in N U D studies. I n t h i s s t u d y H p - p o s i t i v e p a t i e n t s (N=53) suffering from N U D w e r e r a n d o m i z e d to t r i p l e t h e r a p y [bismuth s u b s a l i c y l a t e (BSS) 302mg qid, a m o x y c i l l i n 5 0 0 m g tid, m e t r o n i d a z o l e 500mg tid] or i d e n t i c a l l o o k i n g placebo. Placebo was e s p e c i a l l y m a d e up for BSS. P a t i e n t s s y m p t o m score w e r e t a k e n a n d e n d o s c o p y p e r f o r m e d (biopsies t a k e n for c u l t u r e a n d h i s t o l o g y from a n t r u m a n d body) at baseline, 6 w e e k s (visit 2) and 6 m o n t h s (visit 3). If p a t i e n t s c o n t i n u e d to be H p - p o s i t i v e t h e y were actively treated and again reviewed 6 weeks later (visit 4) Results: four p a t i e n t s (two a c t i v e t w o on placebo) d r o p p e d out of study b e f o r e v i s i t 2. H p was eradicated in 26 of 27 (96%) p a t i e n t s in a c t i v e g r o u p a n d 1 of 22 (5%) of p l a c e b o group. A l t h o u g h s y m p t o m s d i d improve t h r o u g h o u t t h e study there w e r e no s i g n i f i c a n t d i f f e r e n c e s at v i s i t 2,3, or 4 in o u t c o m e s (measured on 7 - p o i n t scales) :global assessment, eight upper GI-symptoms (eg e p i g a s t r i c pain, belching, p o s t p r a n d i a l bloating) and o v e r a l l q u a l i t y of life b e t w e e n t r e a t m e n t groups. It h a s b e e n s u g g e s t e d t h a t it m a y t a k e longer for symptoms to improve following eradication, b u t no c o n t i n u o u s improvement in s y m p t o m s e v e r i t y o v e r t i m e w a s found b e t w e e n v i s i t 2 and v i s i t 3 in H p e r a d i c a t e d patients. The study did have 80% power to detect a two point d i f f e r e n c e on t h e s e v e n p o i n t s y m p t o m score scales t h a t w e r e used. Conclusion: e r a d i c a t i o n of Hp d o e s not improve N U D - s y m p t o m s w h e n c o m p a r e d to placebo.
GASTROENTEROLOGY, Vol. 108, No. 4
O A DISPOSABLE,PROBE TO MEASUIiE,TRE ESOPHAGEAL ACIqDoSURDEN. G. V a n t r a p p e n t a / 5 ) J. Janssens t a ) , G. Huyberechts t ), R. V~nn Overstraeten" ". (a) Center for Gastroenterological Research, KULeuven; (b) Interuniversity Micro Electronics Center (IMEC), Leuven, Belgium. There is increaslng evidence that the acid burden imposed upon the esophageal mucosa is t h e main cause of symptoms and lesions in GERD. The acid burden is determined by the duration of acid exposure and the acidity of the refluant during a given time period. The aim of this study was to develop a disposable probe that allows to measure the acid burden in a minimally invasive and inexpensive way. The probe consists of a matrix of an inert electrical conductive compound embedded in a polymer matrix which shows pH-dependent degradation resulting in the release of the electrical conductive material. The probe resistance is measured before and after the acid exposure period. The figure summarizes the in-vitro results. The sensor response is defined as the relative change in probe conductivity measured in 0.9~0 saline solution before and after immersion of the probe in test solutions of various pH values. The sensor response of similar probes after identical immersion periods of different pH values is plotted versus pH. It shows that the sensor response is small for pM values above 4 and increases with increasing acidity below pH 4- The effect of the duration of acid exposure on the sensor response depends upon layer thickness and composition.
g' "or 0
.
.
1
2
.
.
3
.
4
.
5
6
7
pH-
Conclusion: This probe (12/2/0.7 mm) can be anchored in the esophagus by means of a tiny wire. As the patient does not have to wear any recording apparatus he/she can carry o u t his/her daily routine without restriction. This will allow studies on the magnitude and the pathological role of the acid burden in a population of primary care patients.
• EFFECT OF CURING HELICOBACTER PYLORI (HP) INFECTION ON INTRAGASTRIC pH DURING OMEPRAZOLE TREATMENT. *D Arn~trong, +JP IdstrOm, oj Labenz, )M Sto~e, G Dorta, G BOrsch, AL Blum. GI Units, CHUV, Lausanne, Switzerland, McMaster University, Ontario, Canada, °Etisabeth Hospital, Essen, Germany; +Clinical Pharmacology, Amra H~ssle, Sweden; ! Iustitute of Pathology, Bayreuth, Germany. We have previously shown that tntrngas~c pH during omeprazole (OME) therapy was higher in Hp positivethan in Hp negative subjects, but the two groups had similar spontaneous acidity. Our aim was to investigatethe effect of coring tip infection on gaslxic pH, particularly during OME administration. Methbds: lip infection was diagnosed in otherwise healthy subjects (Hp+ve) by I3C urea breath test, serology (ELISA), Rapid Urease Test and Warthin Statyy stain in endoscopic gastric biopsies. 24-hour pH-recordings, before and after a one-week course of OME, 20rag once daily, were performed, using a glass pH electrode 5 cm below the cardia and repeated 4 weeks after Cure (Hp-ve). Results: Cure was achieved with amoxycillin 2xlg + OME 2x60mg daily in 5 subjects, and with amoxycillin 2xlg + clarithromycin 2x500mg + OME 2x40mg daily for 14 days in 13 subjects. Cure of lip infection was associated with lower gastritis scores in corpus and antrum, and with lower plasma gastrin levels (p<0.01). OME-induced fall in [H+] activity (raM) was calculated as ((10"P H without OME)-(10-P H with OMED. Table shows median (95% CI) pH values with and without OME, and OME-indaced fall in [H+] for the 24-hour period (241,), meal- (M), non-meal day- (D) and night- (N) related periods before and 4 weeks after cure of Hp infection (*p<0.01 vs Hp+ve. Wilcoxon's paired data test). pH without OME pH with OME OME induced fall in [I-I+]] Hp+ve Hg-ve lip+re Hp-ve Hp+ve Hg-ve I 24 h 1.3 1.2 5.4 3.6* 54.6 51.5 [ (1.2-1,4) (1.0-1.3) (4.3-6.0) (2.1-4.4) (38-69) (29-69) I M 1.6 1.4 4.9 4.3* 31.8 35.4 ] (1.3-1.8) (1.3-1.9) (4.5-5.7) (3.5-4.5) (18-50) (17-59) / D 1.2 1.2 5.0 3.9* 70.8 61.0 / (0.9-1.3) (1.0-1.5) (3.6-6.5) (2.0-4.2) (45-77) (29-93) / N 1.3 1.1 6.1 3.2* 48.2 52.0 / (1.2-1.6) (1.0-1.4) (4.1-6.8) (1.6-2.0) (28-69) (25-86) / Conclusions: Cure of lip infection did not affect spontaneous gas~c pH values. In contrast. OME treatment led to much higher pH values before than after cure. However. OME produced similar falls in H+ activity before and after core. We hypothesize that the apparently higher effectiveness of OME in the ~esence of Hp infection is due to base production (bicarbonate, ammonia, tertiary amines) induced by lip infection and not to a direct interaction between lip and OME.
Supported by a grant from Astra Hdssle, Sweden.
AGA ABSTRACTS
@ EFFICACY AND TOLERANCE OF PANTOPRAZOLE 40MG VS 80MG IN
PATIENTS WITH REFLUX OESOPHAGITIS - A MULTICENTRE STUDY 'C van Rensburo 1, P Honiball2, H Grundling 3, J van Zyl 3, Spies 2, G De V_os2, F El.off2, J Lo_uw4, A Cariem 4, A Simjee% S SegalS, J Botha b, I Marks4, I Theron/, T Bethke/. Depts. o~ Medicine & G~stroenterolog,y, Univ~.rsities of Stellenbosc~ 1, Pretoria% BJ,oemfontein°,Cape Town'*, NataW and Witwatersrand ~ and ./ Byk Gulden . Pantoprazole (Pz) is a new H +K + , -ATPase inhibitor. AIM: To compare the efficacy and tolerance of Pz 40 mg versus Pz 80 mg taken orally in the morning in patients with moderate to severe reflux oesophagitis (RO). PATIENTS AND METHODS: 192 outpatients (intention-to-treat; 97 on 40mg and 95 on 80rag) of both sexes with endoscopically confirmed RO (stag e II or III Savary/Miller classification) were entered. The primary evaluation criterion was end0scopically confirmed complet e healing of the RO. Improvement in typical reflux symptoms and other gastrointestinal symptoms, as well as drug tolerability and safety were recorded. Healing rates after 4 and 8 weeks were analysed using the Cochran/ManteI-Haenszel method. RESULTS: 86/97 patients entered into the40 mg Pz group and 87/95 in the 80 mg Pz group completed the study as per protocol. Nineteen patients were excluded from the protocol-correct analysis due to protocol violations (Pz 40rag 11, Pz 80rag 8). The healing rates after 4 weeks were 78% in the 40 mggroup and 72% in the 80 mg group. The cumulative healing rates after 8 w,eeks were 95% and 94%, respectively (p >0.05. Cochran/ManteI-Haenszel}, and time until healing of RO comparable in both groups. Differences between doses were also not significant in an intention-to-treat analysis. Both dosing schedules were well tolerated and the patients experienced remarkable symptom relief. No adverse events could definitely be ascribed to the trial medication, furthermore there were no changes in laboratory values of clinical significance. CONCLUSION: The 40 mg Pz dosage is comparable to the 80 mg dosage in RO; both in efficacy and tolerability.
• T H E E F F E C T O F E R A D I C A T I O N OF H E L I C O B ~ C T E R PYLORI (Hp) ON S Y M P T O M S OF N O N - U L C E R D Y S P E P S I A (NUD): A R A N D O M I Z E D D O U B L E - B L I N D P L A C E B O C O N T R O L L E D TRIAL. S V e l d h u y z e n v a n Zanten, D Malatjalian, R Tanton, D Leddin, R H Hunt, W B l a n c h a r d et al. D a l h o u s i e and MoMaster, Halifax, H a m i l t o n Canada~ H p m a y p l a y a r o l e in N U D b u t to d a t e t r e a t m e n t trials have suffered frommethodologic flaws. W e ~ r e v i o u s l y v a l i d a t e d a s y m p t o m score for u s e as o u t c o m e m e a s u r e (J C l i n E p i d e m i o l 1 9 9 3 ; 4 6 : 2 7 3 ) in N U D studies. I n t h i s s t u d y H p - p o s i t i v e p a t i e n t s (N=53) suffering from N U D w e r e r a n d o m i z e d to t r i p l e t h e r a p y [bismuth s u b s a l i c y l a t e (BSS) 302mg qid, a m o x y c i l l i n 5 0 0 m g tid, m e t r o n i d a z o l e 500mg tid] or i d e n t i c a l l o o k i n g placebo. Placebo was e s p e c i a l l y m a d e up for BSS. P a t i e n t s s y m p t o m score w e r e t a k e n a n d e n d o s c o p y p e r f o r m e d (biopsies t a k e n for c u l t u r e a n d h i s t o l o g y from a n t r u m a n d body) at baseline, 6 w e e k s (visit 2) and 6 m o n t h s (visit 3). If p a t i e n t s c o n t i n u e d to be H p - p o s i t i v e t h e y were actively treated and again reviewed 6 weeks later (visit 4) Results: four p a t i e n t s (two a c t i v e t w o on placebo) d r o p p e d out of study b e f o r e v i s i t 2. H p was eradicated in 26 of 27 (96%) p a t i e n t s in a c t i v e g r o u p a n d 1 of 22 (5%) of p l a c e b o group. A l t h o u g h s y m p t o m s d i d improve t h r o u g h o u t t h e study there w e r e no s i g n i f i c a n t d i f f e r e n c e s at v i s i t 2,3, or 4 in o u t c o m e s (measured on 7 - p o i n t scales) :global assessment, eight upper GI-symptoms (eg e p i g a s t r i c pain, belching, p o s t p r a n d i a l bloating) and o v e r a l l q u a l i t y of life b e t w e e n t r e a t m e n t groups. It h a s b e e n s u g g e s t e d t h a t it m a y t a k e longer for symptoms to improve following eradication, b u t no c o n t i n u o u s improvement in s y m p t o m s e v e r i t y o v e r t i m e w a s found b e t w e e n v i s i t 2 and v i s i t 3 in H p e r a d i c a t e d patients. The study did have 80% power to detect a two point d i f f e r e n c e on t h e s e v e n p o i n t s y m p t o m score scales t h a t w e r e used. Conclusion: e r a d i c a t i o n of Hp d o e s not improve N U D - s y m p t o m s w h e n c o m p a r e d to placebo.
GASTROENTEROLOGY, Vol. 108, No. 4
O A DISPOSABLE,PROBE TO MEASUIiE,TRE ESOPHAGEAL ACIqDoSURDEN. G. V a n t r a p p e n t a / 5 ) J. Janssens t a ) , G. Huyberechts t ), R. V~nn Overstraeten" ". (a) Center for Gastroenterological Research, KULeuven; (b) Interuniversity Micro Electronics Center (IMEC), Leuven, Belgium. There is increaslng evidence that the acid burden imposed upon the esophageal mucosa is t h e main cause of symptoms and lesions in GERD. The acid burden is determined by the duration of acid exposure and the acidity of the refluant during a given time period. The aim of this study was to develop a disposable probe that allows to measure the acid burden in a minimally invasive and inexpensive way. The probe consists of a matrix of an inert electrical conductive compound embedded in a polymer matrix which shows pH-dependent degradation resulting in the release of the electrical conductive material. The probe resistance is measured before and after the acid exposure period. The figure summarizes the in-vitro results. The sensor response is defined as the relative change in probe conductivity measured in 0.9~0 saline solution before and after immersion of the probe in test solutions of various pH values. The sensor response of similar probes after identical immersion periods of different pH values is plotted versus pH. It shows that the sensor response is small for pM values above 4 and increases with increasing acidity below pH 4- The effect of the duration of acid exposure on the sensor response depends upon layer thickness and composition.
g' "or 0
.
.
1
2
.
.
3
.
4
.
5
6
7
pH-
Conclusion: This probe (12/2/0.7 mm) can be anchored in the esophagus by means of a tiny wire. As the patient does not have to wear any recording apparatus he/she can carry o u t his/her daily routine without restriction. This will allow studies on the magnitude and the pathological role of the acid burden in a population of primary care patients.
• EFFECT OF CURING HELICOBACTER PYLORI (HP) INFECTION ON INTRAGASTRIC pH DURING OMEPRAZOLE TREATMENT. *D Arn~trong, +JP IdstrOm, oj Labenz, )M Sto~e, G Dorta, G BOrsch, AL Blum. GI Units, CHUV, Lausanne, Switzerland, McMaster University, Ontario, Canada, °Etisabeth Hospital, Essen, Germany; +Clinical Pharmacology, Amra H~ssle, Sweden; ! Iustitute of Pathology, Bayreuth, Germany. We have previously shown that tntrngas~c pH during omeprazole (OME) therapy was higher in Hp positivethan in Hp negative subjects, but the two groups had similar spontaneous acidity. Our aim was to investigatethe effect of coring tip infection on gaslxic pH, particularly during OME administration. Methbds: lip infection was diagnosed in otherwise healthy subjects (Hp+ve) by I3C urea breath test, serology (ELISA), Rapid Urease Test and Warthin Statyy stain in endoscopic gastric biopsies. 24-hour pH-recordings, before and after a one-week course of OME, 20rag once daily, were performed, using a glass pH electrode 5 cm below the cardia and repeated 4 weeks after Cure (Hp-ve). Results: Cure was achieved with amoxycillin 2xlg + OME 2x60mg daily in 5 subjects, and with amoxycillin 2xlg + clarithromycin 2x500mg + OME 2x40mg daily for 14 days in 13 subjects. Cure of lip infection was associated with lower gastritis scores in corpus and antrum, and with lower plasma gastrin levels (p<0.01). OME-induced fall in [H+] activity (raM) was calculated as ((10"P H without OME)-(10-P H with OMED. Table shows median (95% CI) pH values with and without OME, and OME-indaced fall in [H+] for the 24-hour period (241,), meal- (M), non-meal day- (D) and night- (N) related periods before and 4 weeks after cure of Hp infection (*p<0.01 vs Hp+ve. Wilcoxon's paired data test). pH without OME pH with OME OME induced fall in [I-I+]] Hp+ve Hg-ve lip+re Hp-ve Hp+ve Hg-ve I 24 h 1.3 1.2 5.4 3.6* 54.6 51.5 [ (1.2-1,4) (1.0-1.3) (4.3-6.0) (2.1-4.4) (38-69) (29-69) I M 1.6 1.4 4.9 4.3* 31.8 35.4 ] (1.3-1.8) (1.3-1.9) (4.5-5.7) (3.5-4.5) (18-50) (17-59) / D 1.2 1.2 5.0 3.9* 70.8 61.0 / (0.9-1.3) (1.0-1.5) (3.6-6.5) (2.0-4.2) (45-77) (29-93) / N 1.3 1.1 6.1 3.2* 48.2 52.0 / (1.2-1.6) (1.0-1.4) (4.1-6.8) (1.6-2.0) (28-69) (25-86) / Conclusions: Cure of lip infection did not affect spontaneous gas~c pH values. In contrast. OME treatment led to much higher pH values before than after cure. However. OME produced similar falls in H+ activity before and after core. We hypothesize that the apparently higher effectiveness of OME in the ~esence of Hp infection is due to base production (bicarbonate, ammonia, tertiary amines) induced by lip infection and not to a direct interaction between lip and OME.
Supported by a grant from Astra Hdssle, Sweden.