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Acute upper gastrointestinal hemorrhage: Preliminary report of a randomized controlled trial comparing intravenous administration of ranitidine and omeprazole
A82
AGA ABSTRACTS
• THE EFFECT OF BOLUS VS C O N T I N U O U S FEEDING ON L O W E R ESOPHAGEAL SPHINCTER PRESSURE AND GASTROESOPHAGEAL REFLUX IN PERCUTANEOUS ENDOSCOPIC JEJUNOSTOMY PATIENTS. ~.J. DeMartino, M.L. Allen, A.J. D i M a r i n o R.M. Coben, C.P. Ruffini, Presbyterian Medical Center, U n i v e r s i t y of Pennsylvania, P h i l a d e l p h i a PA It has r e c e n t l y b e e n d e m o n s t r a t e d t h a t bolus feeding v i a a p e r c u t a n e o u s e n d o s c o p i c gastrostomy (PEG) t u b e s i g n i f i c a n t l y d e c r e a s e s lower esophageal s p h i n c t e r (LES) p r e s s u r e and results in increased g a s t r o e s o p h a g e a l r e f l u x (GER). The p u r p o s e of this study w a s to d e t e r m i n e if bolus or continuous f e e d i n g via a p e r c u t a n e o u s e n d o s c o p i c jejunostomy (PEJ) t u b e lowers LES p r e s s u r e or results in GER. six p a t i e n t s h a d t h e i r LES and esophageal p r e s s u r e s m o n i t o r e d w i t h a Dent sleeve catheter with side p o r t s 5 and i0 cm above the LES the day after PEJ placement. PEJ location in the jejunum was c o n f i r m e d f l u o r o s c o p i c a l l y just before m a n o m e try. A 15 m i n b a s e l i n e was collected, a 240 cc Jevity bolus f e e d i n g w a s given and m a n o m e t r i c r e c o r d i n g lasted one hr. Continuous feeding was then a d m i n i s t e r e d via a pump after a m i n i m u m two hr interval. M a n o m e t r i c r e c o r d i n g began after 30 min of c o n t i n u o u s f e e d i n g and lasted one hr. Four patients underwent scintigraphy during identical feeding c o n d i t i o n s to d e t e c t any GER. Lowest LES p r e s s u r e was m e a s u r e d every i0 sec unless that interval h a d e s o p h a g e a l c o n t r a c t i l e activity in w h i c h case that i n t e r v a l and an a d d i t i o n a l 30 sec interval w e r e e x c l u d e d from analysis. M e a n LES p r e s s u r e s (mmHg) are t a b u l a t e d b e l o w by time intervals. LES p r e s s u r e d u r i n g b a s e l i n e w a s 13.02 mmHg. Bolus Continuou~ I min 2 m i n 3 m i n 1 hr 1 min 2 min 3 m i n 1 hr 13.52 ii.ii 13.70 13.52 14.53 13.61 23.06 13.36 Contrary to g a s t r o s t o m y feeding neither bolus nor infusion f e e d i n g t h r o u g h a j e j u n o s t o m y site lowered LES pressure. S c i n t i g r a p h y r e v e a l e d no GER. PEJ feeding is a s a f e a l t e r n a t i v e to PEG feeding in p a t i e n t s s u s c e p t i b l e to GER.
• ACUTE UPPER GASTROINTESTINAL HEMORRHAGE : PREHMINARY REPORT OF A RANDOMIZED CONTROLLED TRIAL COMPARING INTRAVENOUS ADMINISTRATION OF RANITIDINE AND OMEPRAZOLE. D. Desor0z. P. Blanc. J.M. Bodes. Q.P. Pageaux. X.R. David, M. Vayrac, D. Larray, H. Midoel.. So.ice d'h6pato gestroent~ologie, H6pital Saint-Eloi, Montpetrmr, France Acute upper gastrointestinal bleeding is a serious complication of peptic ulcer disease. In such condition, the widely used Histamine H2 antagonists. have only small beneficial effects on surgery requirement or death rate, as shown by metaanalysls of the,-'apeutic trials. Omoprazole, a proton pump inhibitor, is highly effective for inhibiting gastdc acid secretion and for healing ~uodenal ulcers. The aim of the stu0'y was to compare the efficieecy of intravenous (IV) administration of high dose ranitidine and omeprazole in bleeding peptic ulcer. Patients and methed~. 76 patients with endoscopicaily proved peptic ulcer bleeding actively (oozing) or with recent signs of bleeding (visil0ie vessel, adherent clot) were randomized in two groups. The 38 patients of group I were given ranitidine : a 100 mg bolus Injection followed by continuous infusion of 400 mg/day for 3 days. The 38 patients of group II were given omeprazole : a 80 mg bolus injection followed by 40 mg IV every 8 hours for 3 days. A control endoscopy was done on Day 4. In patients with bleeding interruption, therapy was continued orally with 600 mg ranitidine or with 40 mg omeprazole per day. Patients were followed up to Day 15. Results. Both groups were comparable with regard to age, sex, cause of bleeding, hemorrhage severity and endoscopic findings. ON DAY 4 Persistent bleedino Reouirement of surof¢/ Death group I 10/38 6/38 3/38 NS NS NS group II 9/38 5/38 3/38 ON DAY 15 group I
Recurent blsedina Reouirement of suroery Death 3/28 1/28 7/38 NS NS NS group II 0/29 0/29 7/38 Conclusion : these preliminary data do not provide evidence for advantages of IV omeprazole over N ranitldine in patients with bleeding peptic ulcer.
GASTROENTEROLOGY, Vol. 108, No. 4
•
IMPAIRMENT IN HYDROPHOBICITY BY ACID AND PEPSLN AS THE POTENTIAL MECHANISM OF THE DAMAGE TO THE ESOPHAGEAL MUCOSA BY GASTROESOPHAGEAL REFLUXATE. J. DeResa, M. Marcinkiewiez, J. Sarnsiek, ILW. McCallum, University of V'wginia Health
Sciences Center, Charlottesville, VA. Among protective mechanisms operating within the mucus layer along the gastrointestinal tract, hydrophobicity seems to play a major role in the maintenance of the integrity of the epithelial compartment. Although the protective potential of hydrephobic structures and components within the gastric mucosa remains well established, their presence in the esophagus and response to intraluminal acid and pepsin, the major damaging factors in reflux esophagitis, remain unknown. Aims: 1) To study hydrophobicity of human e~phageal secretion collected during mucosal exposure to HCI and HCl/pcpe'in solutions and 2) To compare these results with corresponding values recorded during infusion of saline. Subjects & Methods: In 9 .a..a..a..a..a..asymptomatic volunteers (4F, 5M; mean age of 43, range 34-56) esophageal perfusian was conducted using our newly designed esophageal perfusion catheter (AJG;88:I081,1993). During an entire esophageal perfusion procedure (with NaC1, HCI and HC1/pepsin sulntious), collection of salivary secretion was carefully monitored to prevent contamination of esophageal secretion. In samples collected during each perfusion period, hydrophobicity was measured spnctrophotometrically using bis 8-anilino-l-naphtulenesulfunate (BIS-ANS) with excitation waveMngth fur the probe 385 nm and the emission range from 440-540 nm. The concentration of mucin (measured using periodic acid/Schiff me~odohigy) was adjusted to the same concentration of 100 pg/rni before assessment of hydrophobicity. Statistical analysis was performed using SigmaStat software for IBM PC. Results: Hydrophobicity of esophageal secretion elaborated under the impact of HCI (pH 2.1) declined significantly from its basal value of 222 *86 (pcrfusian with saline) to 67 =t=23 units; P<0.001. Luminal exposure to HCl/pepsin solution (.oH 2.1; concentration of pepsin 0.Smg/nd),,further impaired hydrophobic property of esophageal secretion to the value of 34 =t=l1 units, which was significantly lower than recorded during mucosal exposure to saline (P<0.001) and 49*/. lower than the corresponding. value . recorded . . during . .perfusion with t. HCI alone. In addition, we observed a sagnificant shift m the fluorescence e m ~ e n spectrum from 508 ---6.4 nm to 492 ~1.6 nm (P
• L A C T O F E R R I N I N H I B I T S T H E G R O W T H OF HELICOBACTER PYLOPd IN VITRO. E.I, DiM, J.H. Sema, and L.M. Lichtenberger. D e p a r t m e n t o f Physiology and Cell Biology, University o f Texas Medical School, Houston TX. Laetoferrin (LF), a glycoprotein found in mammalian milk, possesses antibacterial activity against a variety o f gram-negative bacteria. We tested LF for inhibitory activity against the gastritis and ulcer-causing bacteria Helicobacter pylori (liP). Bacteria were g r o w n in Brucella broth + 10% FCS under mieroaerophilic conditions at 37 ° C. Tubes were inoculated .with liP and cultured in medium with varying concentrations o f bovine LF for 5 days. To determine i f L F maintained any inhibitory activity after exposure to the degradative conditions in the st.omach, LF was incubated with pepsin at pH 2 for 4h at 37 ° C. This LF digest was then tested for inhibitory activity against HI'. At the end of the incubation period, cell growth was determined by reading turbidity at an O.D. o f 600nm. The results are expressed as percent o f cell number in control tubes after incubation (* p<0.05 versus 0 mg/ml). Cone. (mg/ml): 0 0.1..._33 0.5 ~ 2.0 LF 100~:2 88+3 * 85±1 * 36+6 * 14+0.3 * LF digest 100~2 944-8 944-5 92=t=3 87+5 Conclusions: Intact bovine LF can inhibit the growth o f HI', whereas a peptic digest o f LF is relatively inactive. Further investigations are warranted to determine whether ingestion o f dairy foods which are rich in LF, while concurrently suppressing acid secretion to block degradation o f LF, may provide anti-HP activity. (Funded by the National Dairy Promotion and Research Board and administered in cooperation with the National Dairy Council).
AGA ABSTRACTS
• THE EFFECT OF BOLUS VS C O N T I N U O U S FEEDING ON L O W E R ESOPHAGEAL SPHINCTER PRESSURE AND GASTROESOPHAGEAL REFLUX IN PERCUTANEOUS ENDOSCOPIC JEJUNOSTOMY PATIENTS. ~.J. DeMartino, M.L. Allen, A.J. D i M a r i n o R.M. Coben, C.P. Ruffini, Presbyterian Medical Center, U n i v e r s i t y of Pennsylvania, P h i l a d e l p h i a PA It has r e c e n t l y b e e n d e m o n s t r a t e d t h a t bolus feeding v i a a p e r c u t a n e o u s e n d o s c o p i c gastrostomy (PEG) t u b e s i g n i f i c a n t l y d e c r e a s e s lower esophageal s p h i n c t e r (LES) p r e s s u r e and results in increased g a s t r o e s o p h a g e a l r e f l u x (GER). The p u r p o s e of this study w a s to d e t e r m i n e if bolus or continuous f e e d i n g via a p e r c u t a n e o u s e n d o s c o p i c jejunostomy (PEJ) t u b e lowers LES p r e s s u r e or results in GER. six p a t i e n t s h a d t h e i r LES and esophageal p r e s s u r e s m o n i t o r e d w i t h a Dent sleeve catheter with side p o r t s 5 and i0 cm above the LES the day after PEJ placement. PEJ location in the jejunum was c o n f i r m e d f l u o r o s c o p i c a l l y just before m a n o m e try. A 15 m i n b a s e l i n e was collected, a 240 cc Jevity bolus f e e d i n g w a s given and m a n o m e t r i c r e c o r d i n g lasted one hr. Continuous feeding was then a d m i n i s t e r e d via a pump after a m i n i m u m two hr interval. M a n o m e t r i c r e c o r d i n g began after 30 min of c o n t i n u o u s f e e d i n g and lasted one hr. Four patients underwent scintigraphy during identical feeding c o n d i t i o n s to d e t e c t any GER. Lowest LES p r e s s u r e was m e a s u r e d every i0 sec unless that interval h a d e s o p h a g e a l c o n t r a c t i l e activity in w h i c h case that i n t e r v a l and an a d d i t i o n a l 30 sec interval w e r e e x c l u d e d from analysis. M e a n LES p r e s s u r e s (mmHg) are t a b u l a t e d b e l o w by time intervals. LES p r e s s u r e d u r i n g b a s e l i n e w a s 13.02 mmHg. Bolus Continuou~ I min 2 m i n 3 m i n 1 hr 1 min 2 min 3 m i n 1 hr 13.52 ii.ii 13.70 13.52 14.53 13.61 23.06 13.36 Contrary to g a s t r o s t o m y feeding neither bolus nor infusion f e e d i n g t h r o u g h a j e j u n o s t o m y site lowered LES pressure. S c i n t i g r a p h y r e v e a l e d no GER. PEJ feeding is a s a f e a l t e r n a t i v e to PEG feeding in p a t i e n t s s u s c e p t i b l e to GER.
• ACUTE UPPER GASTROINTESTINAL HEMORRHAGE : PREHMINARY REPORT OF A RANDOMIZED CONTROLLED TRIAL COMPARING INTRAVENOUS ADMINISTRATION OF RANITIDINE AND OMEPRAZOLE. D. Desor0z. P. Blanc. J.M. Bodes. Q.P. Pageaux. X.R. David, M. Vayrac, D. Larray, H. Midoel.. So.ice d'h6pato gestroent~ologie, H6pital Saint-Eloi, Montpetrmr, France Acute upper gastrointestinal bleeding is a serious complication of peptic ulcer disease. In such condition, the widely used Histamine H2 antagonists. have only small beneficial effects on surgery requirement or death rate, as shown by metaanalysls of the,-'apeutic trials. Omoprazole, a proton pump inhibitor, is highly effective for inhibiting gastdc acid secretion and for healing ~uodenal ulcers. The aim of the stu0'y was to compare the efficieecy of intravenous (IV) administration of high dose ranitidine and omeprazole in bleeding peptic ulcer. Patients and methed~. 76 patients with endoscopicaily proved peptic ulcer bleeding actively (oozing) or with recent signs of bleeding (visil0ie vessel, adherent clot) were randomized in two groups. The 38 patients of group I were given ranitidine : a 100 mg bolus Injection followed by continuous infusion of 400 mg/day for 3 days. The 38 patients of group II were given omeprazole : a 80 mg bolus injection followed by 40 mg IV every 8 hours for 3 days. A control endoscopy was done on Day 4. In patients with bleeding interruption, therapy was continued orally with 600 mg ranitidine or with 40 mg omeprazole per day. Patients were followed up to Day 15. Results. Both groups were comparable with regard to age, sex, cause of bleeding, hemorrhage severity and endoscopic findings. ON DAY 4 Persistent bleedino Reouirement of surof¢/ Death group I 10/38 6/38 3/38 NS NS NS group II 9/38 5/38 3/38 ON DAY 15 group I
Recurent blsedina Reouirement of suroery Death 3/28 1/28 7/38 NS NS NS group II 0/29 0/29 7/38 Conclusion : these preliminary data do not provide evidence for advantages of IV omeprazole over N ranitldine in patients with bleeding peptic ulcer.
GASTROENTEROLOGY, Vol. 108, No. 4
•
IMPAIRMENT IN HYDROPHOBICITY BY ACID AND PEPSLN AS THE POTENTIAL MECHANISM OF THE DAMAGE TO THE ESOPHAGEAL MUCOSA BY GASTROESOPHAGEAL REFLUXATE. J. DeResa, M. Marcinkiewiez, J. Sarnsiek, ILW. McCallum, University of V'wginia Health
Sciences Center, Charlottesville, VA. Among protective mechanisms operating within the mucus layer along the gastrointestinal tract, hydrophobicity seems to play a major role in the maintenance of the integrity of the epithelial compartment. Although the protective potential of hydrephobic structures and components within the gastric mucosa remains well established, their presence in the esophagus and response to intraluminal acid and pepsin, the major damaging factors in reflux esophagitis, remain unknown. Aims: 1) To study hydrophobicity of human e~phageal secretion collected during mucosal exposure to HCI and HCl/pcpe'in solutions and 2) To compare these results with corresponding values recorded during infusion of saline. Subjects & Methods: In 9 .a..a..a..a..a..asymptomatic volunteers (4F, 5M; mean age of 43, range 34-56) esophageal perfusian was conducted using our newly designed esophageal perfusion catheter (AJG;88:I081,1993). During an entire esophageal perfusion procedure (with NaC1, HCI and HC1/pepsin sulntious), collection of salivary secretion was carefully monitored to prevent contamination of esophageal secretion. In samples collected during each perfusion period, hydrophobicity was measured spnctrophotometrically using bis 8-anilino-l-naphtulenesulfunate (BIS-ANS) with excitation waveMngth fur the probe 385 nm and the emission range from 440-540 nm. The concentration of mucin (measured using periodic acid/Schiff me~odohigy) was adjusted to the same concentration of 100 pg/rni before assessment of hydrophobicity. Statistical analysis was performed using SigmaStat software for IBM PC. Results: Hydrophobicity of esophageal secretion elaborated under the impact of HCI (pH 2.1) declined significantly from its basal value of 222 *86 (pcrfusian with saline) to 67 =t=23 units; P<0.001. Luminal exposure to HCl/pepsin solution (.oH 2.1; concentration of pepsin 0.Smg/nd),,further impaired hydrophobic property of esophageal secretion to the value of 34 =t=l1 units, which was significantly lower than recorded during mucosal exposure to saline (P<0.001) and 49*/. lower than the corresponding. value . recorded . . during . .perfusion with t. HCI alone. In addition, we observed a sagnificant shift m the fluorescence e m ~ e n spectrum from 508 ---6.4 nm to 492 ~1.6 nm (P
• L A C T O F E R R I N I N H I B I T S T H E G R O W T H OF HELICOBACTER PYLOPd IN VITRO. E.I, DiM, J.H. Sema, and L.M. Lichtenberger. D e p a r t m e n t o f Physiology and Cell Biology, University o f Texas Medical School, Houston TX. Laetoferrin (LF), a glycoprotein found in mammalian milk, possesses antibacterial activity against a variety o f gram-negative bacteria. We tested LF for inhibitory activity against the gastritis and ulcer-causing bacteria Helicobacter pylori (liP). Bacteria were g r o w n in Brucella broth + 10% FCS under mieroaerophilic conditions at 37 ° C. Tubes were inoculated .with liP and cultured in medium with varying concentrations o f bovine LF for 5 days. To determine i f L F maintained any inhibitory activity after exposure to the degradative conditions in the st.omach, LF was incubated with pepsin at pH 2 for 4h at 37 ° C. This LF digest was then tested for inhibitory activity against HI'. At the end of the incubation period, cell growth was determined by reading turbidity at an O.D. o f 600nm. The results are expressed as percent o f cell number in control tubes after incubation (* p<0.05 versus 0 mg/ml). Cone. (mg/ml): 0 0.1..._33 0.5 ~ 2.0 LF 100~:2 88+3 * 85±1 * 36+6 * 14+0.3 * LF digest 100~2 944-8 944-5 92=t=3 87+5 Conclusions: Intact bovine LF can inhibit the growth o f HI', whereas a peptic digest o f LF is relatively inactive. Further investigations are warranted to determine whether ingestion o f dairy foods which are rich in LF, while concurrently suppressing acid secretion to block degradation o f LF, may provide anti-HP activity. (Funded by the National Dairy Promotion and Research Board and administered in cooperation with the National Dairy Council).